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100 Technology Offers stemming from EU Biotechnology RTD results
KI-NA-20-603-EN-C
Innovation is fed by research. Poor exploitation of research results is a European
weakness which holds back the innovation process. In an attempt to remedy this,
the European Union’s Fifth Research Framework Programme specified, for the first
time, that a Technological Implementation Plan (TIP) should be delivered as a part
of the final report of all research contracts. It was an effort to support the spirit of
entrepreneurship and to sensitize European scientists towards intellectual property and ownership of research results. This booklet contains 100 technology offers
deriving from biotechnology projects supported since 1994 under the last three EU
Research Framework Programmes, and selected on the basis of the TIPs and with
the help of scientific officers of the European Commission at DG Research. The
booklet’s objective is to raise interest among Europeans to create new successful
partnerships. Industrial participation is an important factor in EU translational
research. Exploitation is a key to innovation.
EUR 20603
GENERAL INFORMATION
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EUR 20603
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EUR 20603 —100 Technology Offers stemming from EU biotechnology RTD results
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EUROPEAN COMMISSION
100 Technology Offers stemming from
EU Biotechnology RTD results
Editors
K.Torbjörn Ingemansson
Miomir Knezevic
Directorate-General for Research
2005
Life sciences, genomics and biotechnology for Health
EUR 20603
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P re fa ce
European competitiveness, research and innovation
are all interlinked. Europe has a reputation for being
very strong in research but weak in exploiting
research results. We urgently need to improve our
performance in transforming research into innovative
products and services.
What measures can we take to do this?
We rightly emphasise promoting knowledge transfer
and the use of research results. For the Seventh
Research Framework Programme, we are proposing
dedicated actions in all thematic areas to better communicate research results and make them widely
available to companies, particularly small and medium
sized enterprises that could exploit them.
We also aim to foster industrial participation in European research projects, notably by way of Technology Platforms and Joint Technology Initiatives. Here
we intend to make maximum use of research results so
that Europe keeps or gains technological leadership.
Under the Seventh Research Framework Programme
“Industry-academia partnerships” mobility scheme
should also increase knowledge sharing and transfer.
We would also like to make European scientists more aware of issues of intellectual property rights and
ownership of research results. This means supporting the spirit of entrepreneurship in research.
The Commission will define EU guidelines to improve knowledge transfer between research organisations and business.
The technology offers presented in this publication offer the reader an insight into the wealth of technology which already today stems from EU research projects. I believe that these examples provide an
excellent encouragement for European researchers to pursue their efforts in exploiting research results.
Janez Potočnik
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Table of contents
Ta b l e o f co n te n t s
Introduction
11
Biopharmaceuticals
19
1.
2.
20
3.
4.
5.
6.
7.
Large scale manufacture of mAb in protein free media
Improved strategy for the design of chemically defined media for
the production of biopharmaceuticals. Establishement of cell banks under
protein-free cryopreservation conditions
Antibiotic Biosynthesis Enzymes
Drug Development by Genome Based Technologies
Improved production process for the manufacturing of vaccines
ET-743 (Yondelis) a new chemical entity with potential in cancer treatment
Non-ribosomal Peptide synthesis
24
28
30
32
36
40
Food Biotechnology
43
1.
2.
3.
4.
5.
44
48
50
52
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
Evaluation/validation of novel biosensors in real environmental and food samples
Adapted in vitro digestion model
Rapid test systems for microorganisms in food, beverages and environment
Electrical biochip arrays
Microarrays for detection of gene expression in muscle; genes associated
with meat quality
Hydroxynitrile lyases for industrial Enantioselective Synthesis
Procedures for genetic mapping and marker identification in pigs including
microsatellite AFLP targeting method.
Diagnostic DNA fingerprinting for use in meat quality control and product
specification verification systems
Food grade, genetically modified Lactococcus lactis starter strain that produces
butter-aroma component at high levels, for the production of
improved, highly aromatic fermented diary drinks
A pig diversity database
Utilisation of fiber preparations to enhance probiotic viability and stability
during freeze-drying and in foods
Biotechnology of Extremophiles
Apparatus for expanding of food pieces by means of microwaves and high
turbulent air
Development of molecular diagnostic tools for the detection of bacteria
Continuous Membrane Mediated Cheese Process
Construction of non-GMO lactic acid bacteria with the capacity to produce
dairy products with increased vitamin B2 content
Immunomodulating characteristics of Lactobacillus fermentum strains
Switching the mode of metabolism in baker’s yeast, Saccharomyces cerevisiae,
from fermentation to respiration
Devise genetic test for excess glycogen content in pig muscle
54
58
60
64
68
72
76
78
80
82
84
88
90
94
98
7
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100 Technology Offers stemming from EU biotechnology RTD results
Technology
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
8
NMR structures of membrane proteins, complexes and lipid assemblies;
A dedicated wide-bore ultra high field MAS NMR spectrometer for biological
research
Phage display of Peptide/MHC complexes
Multibarrier for the in situ treatment of groundwater contaminated by mixed
pollutants
Liquid gallium cooled rotating, anode X-ray generator for x-ray diffraction
applications
Information system for registration, storing and communicating information
on immunisations
GeneminingTM of a diversity of thermostable amylolytic enzymes
Portable on site analytical systems based on fully electrical biochips
Robust biosensors for pollutants
STREPTOMYCES
Relationship between ABA and sugar sensing
Embryo sac specific genes for the generation of female sterility and the induction
of parthenogenesis/autonomous endosperm development
Bioremediation technology for removal of mercury from aqueous waste streams
On-line analysis of mercury by sequential injection stripping analysis (SISA)
using a chemically modified electrode
Industrial exploitation of gas/solid technology for the production of natural
esters for the food and fragrance industry
Guidelines for design and implementation of a sustainable biological remediation
system based on substrate injection and groundwater circulation
Cliniporator™
Ultraflat surface for AFM; AFM for biomolecules
Biosynthesis and Biodegradation of Biosilica (Silica Nanobiotechnology)
A novel multiplex high accuracy automated DNA Sequencer with high
throughput of 500 kilobases per day
Programmable restriction enzyme
A dedicated wide-bore ultra-high-field MAS NMR spectrometer, probes,
accessories, software and sample preparation methods for biological MAS NMR
and Imaging research
Modification of cellular stress responses for improved protein production in
filamentous fungi
Change in material chemistry induces cell attachment for low adhesion
materials
Tissue scaffolds and stents: Fabrication of a nanofeatured surface on the inside
wall of a tube.
Embossing and casting nanoscale pattern into soft materials
Ultra-high adhesion nanofeatured surfaces
Ultra-low adhesion nanofeatured surfaces
Thermostable enzymes of industrial interest from Sulfolobus and genetic
systems for their overexpression in Sulfolobus
RemaLog Xray
101
102
106
108
112
114
118
122
124
126
130
132
136
138
142
148
152
154
156
158
160
162
166
170
172
174
176
178
180
182
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Introduction
Plant Biotechnology
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Rhizoremediation of pollutants
GIQS Backbone - inter enterprise data warehousing for quality management in
food chains
RPE, a gene involved in plant response to nematodes
Biochemical markers for dormancy break in potato tubers
Method for enhancing the content of sulphur compounds in plants
Extraction process of pectin from potatoes, with low residual starch
New mapping populations, molecular markers and genes from maize
DDRT-PCR protocols for potato gene cloning.
A porous-matrix sensor to measure the matric potential of soil water
Real-time PCR for analysis of gene/transcript copy numbers
Identification of pathogenicity-related secretions from root knot and cyst
nematodes
MAX4 gene patent
New genetic promoters from maize
Know-how and data about molecular genetic diversity in a genebank collection
of lettuce
AtSERK1 transgenic Arabidopsis plants
185
186
188
190
194
198
202
204
208
212
214
216
220
222
226
228
Biomedical technology – therapy
231
1.
2.
232
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
Improvement of Bacillus strains for production of secreted proteins
Peptides mimicking Vibrio Cholerae O 139 Capsular Polysaccharide and their
use to elicit protective immune response
Animal ventilator for small animals fully MRI compatible
Anti-bacterial (MRSA) drug series (the xf drugs)
DiscoveryBASE Screening workflow for target protein identification
Novel antibacterial drug candidates based on toxin-antitoxin modules
Screening strategy of microbes involving genetic and chemical fingerpriting as
well as bioactivity profile determination
Development of procedures for plasma processing flat substrates to produce
micrometric patterns using physical masks
Use of parvovirus-like particles as vaccine vectors
Enzyme-mediated serial cultivation of anchorage-dependend cells
Assays to screen for inhibitors of FtsA interactions, a protein vital for bacterial
proliferation
Development of receptors to optimally retarget human T cells to MHC-restricted
tumor or viral antigens
CIM® monolithic chromatographic supports - enabling technology for analysis
and purification of novel biotherapeuticals
Microfluidic networks on surface plasmon resonance chips
Integrated technology for efficient therapeutic retrovirus production based on
modular cell lines
Protocols for Cliniporator™ use in tumors, skin, liver, muscle
High and stable recombinant virus production by recombinase mediated
targeting of hot-spot chromosomal integration sites
234
238
240
242
246
250
252
254
258
260
262
268
272
276
278
280
9
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100 Technology Offers stemming from EU biotechnology RTD results
18.
19.
20.
21.
Genetically redirected effector lymphocytes for adoptive immunotherapy
of cancer
Combinatorial fungal PKS enzymes for novel polyketides
Bioartificial liver, Immortalised human liver cell line
Bioactive peptides- Fluorescent Analogues for rapid binding and function screening
Biomedical technology – diagnostic
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Diagnostic test and means for the identification of bacterial pathogens
causing pneumonia
Demonstration of the superior sensitivity of lung densitometry on multi-slice
CT images for the assessment of progression of emphysema as compared to
conventional lung function tests in a multi-centre study
MELVIR - Diagnosis of melanoma
Test kits, antibody/DNA, database, training, patent
Use of a human skin explant model for the testing of novel cell lines, drugs etc.
in the modulation of alloreactivity. Cell line and DNA bank for genetic
assessment in transplantation
Sequencing of Heparan Sulphate
Development of Medical X-ray digital System
Development and validation of a DNA-chip technology for the assessment of
the bacteriological quality of bathing and drinking water
A new diagnostic tool to identify micro and nanosized inorganic foreign bodies
inside pathological tissues, food and environment
Genotyping of parasites in breakthrough cases in RTS,S/AS02 and Control
groups in The Gambia, 1999 and in the Mozambique Phase II efficacy study,
2003-2004
282
284
286
288
291
292
296
300
302
304
306
310
312
314
316
Index
319
Index of the Owners of technology
Index of the contact persons
Index of application domains
320
322
324
10
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Introduction
I n t ro d u c t i o n
Industrial participation in EU funded
B i o te ch n o l o g y R e s e a rch f ro m F r a m e w o r k
P ro g r a m m e s 4 to 6
K . To r b j ö r n I n g e m a n s s o n * , M i o m i r K n e ze v i c ,
A l f re d o A g u i l a r
*Corresponding author: [email protected]
Affiliation: K. Torbjörn Ingemansson and Miomir Knezevic are with the Biotechnology and Applied
Genomics unit in the Directorate of Health Research at DG RTD. Alfredo Aguilar, Head of Unit, for
Biotechnology and Applied Genomics, now for community cooperation activities in the directorate International Cooperation.
Abstract – Innovation is fed by research. Poor exploitation of research results is a European weakness which holds back the innovation process. In an attempt to remedy this, the European
Union’s Fifth Research Framework Programme specified, for the first time, that a Technological Implementation Plan (TIP) should be delivered as a part of the final report of all
research contracts. It was an effort to support the spirit of entrepreneurship and to sensitize European scientists towards intellectual property and ownership of research results.
This booklet contains 100 technology offers deriving from biotechnology projects supported since 1994 under the last three EU Research Framework Programmes, and selected on the basis of the TIPs and with the help of scientific officers of the European Commission at DG Research. The booklet’s objective is to raise interest among Europeans to
create new successful partnerships. Industrial participation is an important factor in EU
translational research. Exploitation is a key to innovation.
11
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100 Technology Offers stemming from EU biotechnology RTD results
European Union funded Biotechnology RTD
European Union (EU) Research, Technological development and Demonstration (RTD) funding brings
together public and private organisations across Europe to perform collaborative and multidisciplinary
research, so called translational research. Industrial participation is an important factor to support the
treaty which states the objective of EU RTD funding; “fostering better exploitation of the industrial
potential of policies of innovation, research and technological development” (ref. 1). EU RTD funding
evolved from minor action programmes in the beginning of the eighties, to the research Framework
Programmes (FP) of several 10 of billions proposed for FP7.
The last three Framework programmes, from 1994 to 2006, have funded Biotechnology research
mainly through the BIOTECH programme II (FP4 1994-1998), the Cell Factory key action, KA3
(FP5 1998-2002) and the Biotechnology and Applied Genomics part of the Health priority in FP6
(2002-2006) (See figure 1 and glossary).
Figure 1: Evolution of EU-funded Biotechnology programmes
in FP4, FP5 and FP6.
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Introduction
European Union role
The work of the Directorate General for Research is driven by a combination of policy objectives and
innovative research topics. The programme structure and research topics are discussed and announced
with a political and research community consent. Proposals are selected by peer review process according to specific evaluation criteria (ref. 2) and a specific database of evaluators originating from around
the world (ref. 3). A large majority of the evaluators is highly satisfied with the EU evaluation process
and even regarding it better than in their own countries (ref. 4). The “quality stamp” of being selected
for funding in the EU programmes is highly regarded in the scientific community. Together with the last
years’ development of financial controls in establishing EU research contracts, according to the model
contract, a new tool, a “due diligence test” has been developed. The declaration “EC money is easy
money”, in consideration of time-to-contract and the influence on the contracted work, e.g. flexibility
and decision power, is becoming a reality in the European research community for translational
(applied) research. The simplification of the funding process, which was always asked for, is primarily
sought for the application procedure. The primary reason for the long maturation of this subject is that
EU is establishing research contracts and not grants. There are pros and cons with this procedure but as
discussed above, the investment community looks positively on the “research contract procedure” as
due diligence is an important factor when to be funded by investors.
Public funding (public money) plays an important role as a part of the research investment community
(See figure 2). The “journey” is long for an innovative project to go through all the phases; seeding,
Figure 2: The important role of public funding in the journey of an innovative idea to the stock market.
Risk sharing and money demand are major driving forces.
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100 Technology Offers stemming from EU biotechnology RTD results
start-up, growth, expansion to finally reach the stock market. There are several opportunity windows
for different types of funding from the investment community; founders, business angels, public bodies, venture capital, banks, etc. The whole process is driven by 2 main forces: Risk sharing and Money
demand. During the “journey” sharing of the risk is essential. Risk is high in the seeding and the startup part of the journey. The important role of public funding, such as EU, is to satisfy the money demand
which at these stages is still low. Public funding can also push technology development, either by supporting an emerging technology or to catalyze a technology shift from an old to a new one. Some of the
technology offers presented in this publication are examples of this process.
In an enabling technology, such as biotechnology, it was early realised that stakeholders all over Europe
were needed to understand to be able to apply this new technology and its entire offspring successfully.
The European taxpayer needed to be explained its benefits and possibilities.
The situation was complex; the public’s knowledge of genomics and the “genomic revolution”, measured by several “Eurobarometer” studies (ref. 5), was low but the industrial interest was high. The
industrial interest was clearly seen in the BIOTECH programmes where industrial participation was
closely monitored.
Industrial participation – the key to exploitation
The majority of participants in EU Biotechnology research contracts are from academia or private/commercial research institutes. The percentage of industrial partners, from small and medium sized (SME)
to large companies, was in the framework programmes FP4 and FP5 about 17-18%, whereof 7-8% from
large industries. In the ongoing FP6, in the part Biotechnology and Applied Genomics, the industrial
participation is now after 3 calls increasing to almost 25% (See figure 3 and ref. 6). Very interesting is
the participation from large industry which continues to be at 7-8%. The increase is clearly due to the
strong participation of SMEs.
The reason is that not only EC services has made a special effort during FP6 to attract and inform SMEs
but also that several member states put in place special supportive measures for SMEs. An important
political signal came also from the European Parliament when they put a target of 15% of the budget
for FP6 to support SMEs due to their important role in the innovation process.
For an SME, with an innovative idea, public funding can be of beneficial support through the early
stages of development. Important is that the project is close to its core business as EU funding has to be
matched by 50% with its own capital. There are mainly two financial benefits with EU funding. It is
high risk money and no demand for investment return and secondly, there is no associated influence on
the management of the company, because it is not equity financing. In FP6 an increased interest from
SMEs to coordinate EU research projects has been noticed. Coordination costs are fully funded up to
7% of the EU financial contribution.
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Introduction
Figure 3: Industrial participation in Biotech research in FP4, FP5 and 3 calls in FP6.
European Union innovation process
Industrial partners are important to reach exploitation considering the innovation “wheel”
(see figure 4). Europe’s knowledge base is well-known around the world and Europeans are among the
most cited ones through excellent dissemination in high standard scientific reviewed journals. The
European weakness is the exploitation of research results and industrial partners can have a tremendous
impact on the outcome of a project such as financial and scientific management, knowledge and experience how to manage intellectual property, e.g. setting up consortium agreements. The major reason for
this low exploitation of research results could probably be found in the culture part of the innovation
“wheel”, e.g. education at Master level and university level in entrepreneurship and its related topics.
Large industrial partners can have several objectives to participate in EU funded projects but the
participation of SMEs is straightforward. They participate or coordinate only a project which is close
to their “core business”, for economical reasons, i.e. the funding scheme of 50% meaning they invest
50% of their own resources. This results in an efficient and effective project. The most exploitation oriented projects are Demonstration projects (ref. 7). A special effort was made in FP4 when demonstration proposals were evaluated in cooperation with the European Patent Office (EPO), which performed
a novelty check on the proposals. This approach was very useful during the evaluation process. In FP6,
clinical trials, are usually run as demonstration parts of a project.
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100 Technology Offers stemming from EU biotechnology RTD results
Exploitation of research results usually happen several years from the closure of a project. The technology
offers presented in this publication are mainly originating from FP4 and FP5 projects. Several technology
offers have been sold during the preparation of this publication, which is very encouraging for European
research. Especially results obtained from projects close to the market, e.g. demonstration projects. It is difficult to give a figure but estimated about 5% of the projects originally interested in publishing an offer
decided not to due to change of ownership. Several different exploitation “journeys” had been discovered
during the preparation of this publication. In conclusion it all depends on the entrepreneurs; their culture,
their personal background knowledge, their type of organisation they were working in before, their country of origin, regional political regime and policy regarding start-ups. Clear is that EU funding is highly
appreciated due to that the projects are; multidisciplinary (different scientific disciplines work together) and
risk sharing (50% financial contribution has to come from other sources). Specifically in projects that are
built upon a “core technology”. The Multidisciplinarity was natural in the early BIOTECH programs and
is now developing further in the emerging nano-biotechnology area. The risk sharing is most obvious in
problem-oriented projects where several partners together contribute to the core technology from their
own niches. To be able to add 50% of EU financial contribution to a research project is always beneficial.
Figure 4: Innovation “wheel” – Knowledge base, Culture, Commercialisation and its co-factors.
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Introduction
Foresight and predictions
The backbone for biotechnology is advances which can be made on the basis of genetic information of
all living material. Exploitation of this genetic information has yet only started. But other interesting
areas of research are evolving and need attention, e.g. nanotechnology. New technology platforms are
set up, some are new, some are based on the old ones (ref. 8). Funding policies will change but the
exploitation of genetic information and consequently the development of biotechnology as a tool has
just started. The term biotechnology and its direct funding by EU as a technology, got branched out
from FP5 (1998) and will probably in the future programmes be treated as a tool applicable in many different areas of research where the genomic revolution will affect our future lifes, e.g. genetic testing,
individualized medicines and foods. “Biotechnology is dead – Long live biotechnology”!
List of Figures:
1. Evolution of EU-funded Biotechnology programmes in FP4, FP5 and FP6 .
2. The important role of public funding in the journey of an innovative idea to the stock market. Risk
sharing and money demand are two main forces.
3. Industrial participation in Biotech research in FP4, FP5 and 3 calls in FP6.
4. Innovation “wheel” – Knowledge base, Culture, Commercialisation and its co-factors.
List of References:
1. Consolidated version of the treaty establishing the European Community.
Official Journal: 21-12-2002 C325/33
2. Guidelines on proposal evaluation and selection procedures; www.cordis.lu/fp6
3. EU Framework Programme Experts; www.cordis.lu/experts/fp6_candidature.htm
4. Peer review evaluation of proposals in the biotechnology programme of the European Union.
A. Aguilar, T. Ingemansson, S. Hogan, E. Magnien, Research Evaluation, Dec. 1998, 141-146.
5. Europeans and Biotechnology 2002. Eurobarometer 58.0. www.europa.eu.int
6. A case study on Biotechnology and Applied Genomics. T. Ingemansson, M. Knezevic A. Aguilar.
Eurobiotech News 2004, 5:3, 28 and 30.
7. An opportunity for exploitation of research in biomedical engineering: The EC Life Sciences
Demonstration Projects. O. Le Dour and I. Norstedt, Technology and Health Care 6, 1998,
237-243.
8. Industrial platforms – a unique feature of the European Commissionęs biotechnology R&D programme. A. Aguilar, T. Ingemansson, S. Hogan, E. Magnien. Trends in Biotechnology, September
1998 (Vol 16), 365-368.
Glossary
EU RTD Framework programme 5 structure of the Quality of Life and management of living resources part:
• Key action 1 (KA 1) Food, Nutrition and Health
• Key action 2 (KA 2) Control of Infectious Diseases
• Key action 3 (KA 3) The Cell Factory
• Key action 4 (KA 4) Environment and Health
• Key action 5 (KA 5) Sustainable Agriculture, Fisheries and Forestry, and Integrated Development of
Rural Areas including Mountain Areas
• Key action 6 (KA 6) The Ageing Population and Disabilities
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© Photodisc inc, 1993
Biopharmaceuticals
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
1 . L a rg e s ca l e m a n u fa c t u re o f m A b
i n p ro te i n f re e m e d i a
P
Title of result:
H
Large Scale Manufacture of mAb in protein free media
Ownership: Polymun Scientific, Immunobiologische Forschung GmbH
A
R
T EC H N O LO GY D E S C R I PT I O N
M
Abstract of the technology:
A
C
E
U
T
Human monoclonal antibodies have been produced in recombinant CHO-cells. A novel protein-free
culture and production medium has been established and the results compared with serum supplemented medium. The novel protein-free medium exhibited at least comparable productivities and stabilities
in repeated de-batch systems as well as in continuous perfused fluidized bed reactors. The overall productivities of antibody secretion was higher in the fed-batch production system. The mAbs C2F5 and
C2G12 were produced in clinical grade purities and tested in phase I human clinical trials. The antibodies were safe and did not show any adverse effect. We would demonstrate that we have now a complete
technology platform including cost effective protein-free media for large scale manufacture of CHOcell recombinant antibodies. We offer this technology platform to Polymun customers on a non-exclusive basis.
I
C
Detailed description of the technology:
A
L
S
Recombinant CHO-cells producing human monoclonalantibodies have been adapted from serum supplemented medium to a protein-free medium. Reproducable adaptation protocols have been established
which can be applied to any other CHO cells. A complete serum and protein free cell banking system
has also been established which now allows the establishment of an entire manufacturing process on
protein-free media. Long term stability tests in laboratory scale cultures, production tests in repeated
fed-batch (500l Scale) as well as long term continuous perfusion (more than 3 months) in fluidized bed
reactors have shown stability of antibody secretion. In fed-batch culture up to 600g antibody/m3 were
accumulated whereas in the continuous perfused system up to 100g/m3 were achieved. Two human
monoclonal antibodies, C2G12 and C2F5 respectively were produced for human clinical trials. Both
antibodies were well tolerated. Nevertheless the serum half lifes (beta-clearence time) were different.
C2G12 had an average half life of 12 days whereas C2F5 had only 5 days. Since both antibodies have
identical constant region genes (lgG1 kappa) we conclude that the different half live are depending on
their different variable regions. We have now a complete technology package for the production of
human mAbs in rec. CHO cells in protein-free media. We are using this technology for Polymun’s own
products and also offer this technology package on a non-exclusive base to Polymun’s customers.
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S
41cq77_one_hundred
C
I
T
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Results of demonstration trials available. A complete technology package
for production of mAbs in rec. CHO-cells in protein-free media is offered
to Polymun customers
A
L
Current stage of development of the technology:
E
Patents granted
Partnership/other contractual agreements
C
Patents applied for but not yet granted
Exclusive rights
License agreement reached
U
Intellectual Property Rights
21
M
R
A
H
P
O
I
Polymun is offering proprietary technology platform to potential partners who
are interested to develop their antibodies for clinical application and industrial
manufacture, from the genes to product launch. The technology platform can
also be applied to develop other glyco-proteins of interest. Polymun will continue the development of the antibodies C2G12, C2F5 and an additional proprietary antibody, C4E10 for immunotherapy of HIV-1 in adults and in HIV1 positive pregnant women (the anti HIV-1 antibodies). Polymun is codeveloping two glycoproteins (other than mAbs) with a major European Pharmaceutical company using proprietary technology platform (- the CHO-GP).
Polymun is further negotiating a strategic partnership with a public European
Bio-TechStart Up. Polymun’s partnership must be treated confidential.
- The potential applications of these project results are:
1. A cost effective manufacture of CHO cell recomb. Antibodies for human
application,
2. Also other CHO-cell recombinant glycoproteins can be produced on the
base of Polymun’s proprietary protein-free technology platform,
3. Speed of product development is accelerated.
- The users of the project results are Polymun and Polymun’s customers in the
co-development of CHO rec. –glycoproteins.
- The main innovative benefits are,
1. Cots effective and safer production,
2. Unlimited production scale.
- Analyses of the market sector: the majority of novel biopharmaceuticals
(IND’s are monoclonal antibodies. A market analysis is not available.
B
Innovative Aspects
Main advantage
A
Exploitation potential
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
O
P
H
Organisation/Firm
Polymun Scientific, Immunobiologische
Forschung GmbH
Title:
First Name:
Surname:
Prof Dr
Hermann
Katinger
Address:
Phone:
Fax:
E-mail:
+43 1360066203
+43 13697615
[email protected]
Nussdorfer Lände 11
A-1190 Vienna, Austria
A
Organisation Type: University
R
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
M
A
A P P L I C AT I O N D O M A I N S
C
E
U
T
I
C
A
L
S
22
Agriculture
Plant
Food
Feed
Dairy
Pharmaceutical
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
P
H
A
R
M
A
C
E
U
T
I
C
A
L
S
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B
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100 Technology Offers stemming from EU biotechnology RTD results
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I
O
P
H
2 . I m p ro v e d s t r a te g y f o r t h e d e s i g n o f
ch e m i ca l l y d e f i n e d m e d i a f o r
t h e p ro d u c t i o n o f b i o p h a r m a ce u t i ca l s .
E s ta b l i s h e m e n t o f ce l l b a n k s u n d e r
p ro te i n - f re e c r yo p re s e r v a t i o n co n d i t i o n s
A
Title of result:
R
M
Improved strategy for the design of chemically defined media for the production of biopharmaceuticals. Establishment of cell banks under protein-free cryopreservation conditions
A
Ownership: Milteny Biotec GmbH
C
T EC H N O LO GY D E S C R I PT I O N
E
Abstract of the technology:
U
T
I
C
A
L
This result represents a method for the design and optimization of chemically defined cell culture media
used for the production of biopharmaceuticals with mammalian cell cultures. The design of chemically
defined cell culture media that are free of any components of animal or human origin is an important
prerequisite for the establishment of processes of a high biosafety standard for the manufacturing of
biopharmaceuticals. The described method provides a reliable strategy for the design and optimization
of these cell culture media. During the project it proved to be applicable to various cell lines and
processes. A safe source for the cell material is a critical requirement for the production of biopharmaceuticals with mammalian cell lines. A reliable strategy for cryopreservation of producer cell lines using
defined cryopreservation conditions which are not dependent on any components of animal or human
origin. This enables the establishment of cell banks of very high quality and biosafety standards as
sources of cell material for the manufacturing of biopharmaceuticals with mammalian cell cultures.
S
Detailed description of the technology:
An improved strategy for the design of chemically defined cell culture media that are free of any components of animal or human origin. It considers the specific needs of the producer cell line as well as
those of the given process. The first step of the strategy is the adaptation of the producer cell line to one
of the protein-free SMIF media. The media of the SMIF medium line have been proven to be applicable for many cell lines of industrial relevance such as CHO, BHK, MDCK and others. After the successful adaptation the producer cell line will grow under protein-free cultivation conditions. During the
adaptation phase, cultivation parameters that are critical for the given process (like for example productivity or product integrity) must be monitored. On the basis of these data the basal protein-free medium is then supplemented with chemically defined components to improve the performance of the culture with respect to the process requirements. The new medium formulation is then tested under
process conditions with the critical parameters monitored again. This procedure is an iterative process
24
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A
C
I
T
U
E
will be repeatedly performed until the critical parameters reach the values required for the given process.
In the end the application of this strategy results in a formulation for a chemically defined medium that
is free of any components of animal or human origin while being optimized to meet the specific needs
of the given producer cell line and manufacturing process. Result 2 consists of an optimized method for
cryopreservation and revitalization of mammalian cell lines using protein-free cryopreservation media
that are free of any components of animal or human origin. The method comprises optimized protocols
for 1. The transfer of the cells to the cryopreservation media and freezing of the cells and 2. Thawing of
the cells and theeir transfer to chemically defined culture media. During the project the method has
proven its applicability to various producer cell lines (BHK, CHO, MDCK). The method provides a
reliable strategy for the cryopreservation of mammalian cell lines using chemically defined cryopreservation media and thus enables the establishment of safe sources of cell material for the production of
biopharmaceuticals with mammalian cell cultures.
L
S
41cq77_one_hundred
M
R
A
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Results of demonstration trials available. The result is currently applied by
several users of the SMIF media line to optimize the medium for their specific cultivation purposes. Cell banking under protein-free cryopreservation
conditions is used as a standard procedure by GBF.
A
C
Current stage of development of the technology:
P
25
O
Secret know-how: strategy for the optimization of chemically defined cell culture media – strategy for the adaptation of cell lines to growth in protein-free
cell culture media – optimized protocols for cryopreservation and revitalisation
of mammalian cell lines.
I
Comments:
Patents granted
Partnership/other contractual agreements
B
Patents applied for but not yet granted
Exclusive rights
License agreement reached
H
Intellectual Property Rights
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
Exploitation potential
O
Innovative Aspects
Main advantage
P
H
A
R
M
A
C
E
Exploitable result of interest for third parties. The main potential application
for this result is an improvement of process development for the manufacturing of biopharmaceuticals with mammalian cell cultures. Potential users of the
result are process developers or manufacturers of biopharmaceuticals. The main
innovative features and benefits are : 1. The result provides a reliable way to
defined cultivation conditions that are free of any components of animal or
human origin, 2. The chemically defined conditions can be established with
respect to the demands of the producer cell line and the requirements of the
process, 3. A higher level of biosafety is achieved. A market analysis is not available. The main potential application of this result is an improved establishment
of cell banks under chemically defined cryopreservaton conditions, free of any
components of animal or human origin. Potential users of the result are process
developers, establishers of cell banks or manufacturers of biopharmaceuticals.
Innovative features and benefits are: 1. The result provides a method for the
establishment of reliable sources of cell material for the manufacturing of biopharmaceuticals, 2. Cryopreservation of mammalian cell lines is possible under
defined conditions free of any components of animal or human origin, 3. Application of the result enables a higher level of biosafety for cell banks.
U
T
I
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
C
A
Organisation/Firm
Milteny Biotec GmbH
L
Address:
S
Niederlassung Teterow,
Robert Koch-Str.1, 17 166 Teterow,
Germany
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Dr
Roland
Wagner
Phone:
Fax:
E-mail:
+49 3996 158 260
+49 3996 1580 222
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
26
Agriculture
Plant
Food
Feed
Dairy
Pharmaceutical
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
P
H
A
R
M
A
C
E
U
T
I
C
A
L
S
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100 Technology Offers stemming from EU biotechnology RTD results
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I
3. Antibiotic Biosynthesis Enzymes
O
Title of result:
P
Antibiotic Biosynthesis Enzymes
H
Ownership: University of Oxford
A
T EC H N O LO GY D E S C R I PT I O N
R
Abstract of the technology:
M
New enzymes for making β-lactam antibiotics or precursors for their production.
A
Detailed description of the technology:
C
E
Enzymes for the production of monocylic and bicyclic β-lactams have been identified and characterised
by biochemical and structural analyses. Mutant versions of the enzymes can be used for preparing commercially important antibiotics.
U
Current stage of development of the technology:
T
I
C
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
A
Intellectual Property Rights
L
S
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
Exploitation potential
Innovative Aspects
Main advantage
28
New/more efficient routes to β-lactam antibiotics.
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L
S
41cq77_one_hundred
A
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Title:
First Name:
Surname:
Address:
Phone: +44 1865 275625
Fax:
+44 1865 285002
E-mail: [email protected]
Industry
Research Institute
Start-up company
I
Other
U
Organisation Type: University
T
Chemistry Research Laboratory,
Mansfield Road, Oxford OX1 3TA,
United Kingdom
Professor
Christopher
Schofield
C
Organisation/Firm
University of Oxford,
Organic Chemistry Department
50-249 employees
250-500 employees
>500 employees
E
Organisation size: < 50 employees
A
R
M
A
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
H
P
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Pharmaceutical
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
C
A P P L I C AT I O N D O M A I N S
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100 Technology Offers stemming from EU biotechnology RTD results
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I
O
4. Drug Development by Genome Based
Te ch n o l o g i e s
P
Title of result:
H
Drug Development by Genome Based Technologies
Ownership: Combinature Biopharm AG
A
R
T EC H N O LO GY D E S C R I PT I O N
M
Abstract of the technology:
A
C
At Combinature Biopharm, optimised genetic engineering technologies have been developed which
represent convenient tools for the targeted derivatization of even complex natural products that would
otherwise be difficult to obtain. These novel analogs (mainly antibiotics) are evaluated internally and
represent the starting materials for our drug development programs.
E
U
Detailed description of the technology:
T
I
C
A
L
S
There is an urgent medical need for new drugs, since development pipelines are drying up and resistance to antibiotics and other chemotherapeutic agents is becoming an increasingly frequent problem. In
the past natural product played the most significant role in the discovery and development as a source
for commercially successful drugs. The unmatched chemical diversity and complexity is the main reason for the success of natural product derived compounds over their counterparts obtained by pure
chemical synthesis. Despite these facts, natural product research is currently going through a phase of
reduced interest, as big pharmaceutical companies in particular have downgraded or even stopped this
kind of research. Reasons for this development might be that natural products are often synthesized in
low amounts and mixtures, the rediscovery of known compounds and the challenge of natural product
derivatization using chemical means. The use of modern Genome-based technologies, established in the
past few years, offer the opportunity to increase the attractiveness of natural products as a source for
drug leads. Genome-based screening technologies have been established at Combinature to provide fast
access to the enormous genetic potential of Actinomycetes, soil bacteria known to represent one of the
most important sources for bioactive metabolites. The application of PCR screening technologies using
genetic marker (“Genome Mining”), like halogenase genes, allowed the identification of both previously unknown producer of valuable drug candidates and novel enzymes which con be used for compound
modification. This screening technology opens the door for a systematic reevaluation of strain collections to preselect those strains harbouring the genetic potential to synthesize valuable known or novel
compounds. Genetic engineering technologies comprising diverse technologies also known as “combinatorial biosynthesis”, “pathway engineering”, “precursor directed biosynthesis” and “heterologous
expression” will help to overcome further undesired aspects of natural products, the difficulty in derivatizing complex structures and the qualitative and quantitative improvement of the production.
30
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A
Combinature Biopharm established and applies these genome based technologies, such as genome based
screening and genetic engineering, for the discovery and development of important drugs.
L
S
41cq77_one_hundred
I
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
U
T
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
C
Current stage of development of the technology:
C
Patents granted
Partnership/other contractual agreements
A
Patents applied for but not yet granted
Exclusive rights
License agreement reached
E
Intellectual Property Rights
Genome based technologies can be applied to overcome the problems of
targeted derivatization of even complex natural compounds.
H
A
R
Innovative Aspects
Main advantage
M
Exploitation potential
P
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Robert-Roessle-Str. 10
D-13125 Berlin, Germany
Organisation Type: University
Organisation size: < 50 employees
Industry
Phone:
Fax:
E-mail:
+49 30 9489 4050
+49 30 9489 4051
[email protected]
Research Institute
50-249 employees
O
Dr.
Stefan
Pelzer
Start-up company
250-500 employees
I
Address:
Title:
First Name:
Surname:
B
Organisation/Firm
Combinature Biopharm AG
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Pharmaceutical
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Drug Development
31
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
5 . I m p ro v e d p ro d u c t i o n p ro ce s s f o r
t h e m a n u fa c t u r i n g o f v a cc i n e s
P
Title of result:
H
Improved production process for the manufacturing of vaccines
Ownership: Chiron Behring GmbH & Co KG
A
R
T EC H N O LO GY D E S C R I PT I O N
M
Abstract of the technology:
A
C
E
U
T
I
C
A
L
S
Within the framework of this EU project, the feasibility of an industrial mammalian cell culture process
with protein free fermentation media was demonstrated. We targeted on the influenza vaccine production derived from permanent MDCK suspension culture. Initially infections viruses are produced,
which are afterwards inactivated and splitted to a sub-unit. One dose consists of a trivalent vaccine. In
order to switch over from protein or serum containing production media (which were long time ‘state
of the art’) to a protein free medium fermentation process, there are lots of parameters that have to be
checked. The target cell line has to grow sufficiently in that particular medium (similar growth rate and
absolute cell concentration). The immunogenicity and quality of the desired product has to be evaluated and shown to be not different from protein containing medium product. The purification of that
product has to be proven efficiently and easy. The reason for replacing the fermentation medium to protein-free, in a commercial production process is that we postulate the following issues of real importance in the near future. Price: we calculated an enormous economic saving during fermentation process:
1 liter conventinal production medium (protein containing) ~15$ US
1 liter protein-free medium SMIF CB ~2,5$ US, if we assume the media cost to 40 % in the overall production costs, this would be an enormous saving.
Regulatory acceptance: easier due to the fact that the final product is free from adventitious agents and
animal derived components. Also the labor intensive work for quality control is clearly reduced,
because all medium containing ingredients are chemically defined and do not differ from one production batch to the other.
Compliance: if additional compounds in traditional media correlate with impurities in the final product
(BSA,bovine products, or stabilizer) the more compliant we expect our vaccine produced without these
substances.
Detailed description of the technology:
The fermentation results (product yield, primary product recovering steps) under protein-free medium
conditions were almost comparable to the protein-containing flu cell culture process and proven up to
the 100 liter scale. Cell propagation has to be performed until now in a chemically defined medium
which is similar in the basic formulation to SMIF medium and is also animal component free. Virus production standard protocols had to be modified in order to optimise the conditions in cell preparation
prior to infection. First batches with different stains were purified according to the standard protocol
and regarded as feasible. Product quality and stability is similar to the protein-containing process.
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A
C
Immunogenicity tests in a mice test system performed with vaccine produced with SMIF or with protein-containing medium showed a comparable product quality. These vaccines proved to be superior to
egg derived vaccine.
L
S
41cq77_one_hundred
T
U
E
C
A
M
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Results of clinical phase III trials available. Production plant studies at 2500
liter scale have been performed in clinical phase III. High strain specific antibody titres were observed in the immunised people. Various field strains
have been taken into account for trivalent vaccines. Purification of those
viruses have been checked according to international specification for
human vaccines. Produced material was checked according to international
standards in clinical studies. Scale up to 2500 liter manufacturing scale was
succesful.
I
Current stage of development of the technology:
Intellectual Property Rights
Innovative Aspects
Main advantage
R
A
H
O
Exploitation potential
P
System for the production of immunological and therapeutic products from
animal cell culture. WO 97/37000 and 97/37001. Patents filed in US. Patents
pending in Europe.
Chiron Behring will exploit all results in this project concerning the European
market and US market alone. Collaborations to Asian and ROW countries are
already initiated. Chiron Behring searches expertise collaboration in the virology and purification field. The partner should come from the field of applied
research and should have experience in the propagation of influenza and other
virus (replication and budding of viral particles and cell systems, avoiding of
defective interfering particles). Furthermore, expertise in immunogenic characterisation of purified antigen is highly welcomed (epitop mapping, glycosylation pattern, lectin blotting). In addition new techniques in the separation of
viral particles from cellular supernatants is one of our main objectives. The
partner interested should deal with modern separation techniques (field flow
fractionation, affinity chromatography, DNA-protein interaction, etc.). We
also seek partners that are involved in the field of evaluation of permanent cell
derived vaccines (key aspects as e.g. tumorgenicity testings).
33
I
Comments:
Patents granted
Partnership/other contractual agreements
B
Patents applied for but not yet granted
Exclusive rights
License agreement reached
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
New ways for the proudction of vaccines are in the target line of all biological
manufactures. For a long-time it is the aim of the pharmaceutics industry to
produce economic, ecologic, safe and efficient drugs. Former ways to produce
for example flu vaccines involved embryonated hen eggs. This needed million
of eggs, which produced a lot of biological and infectious waste (chicken
embryos), and were also not an ethical way of production. In the future there
will be a huge market for flu vaccines due to increasing vaccination acceptance
levels. In case of a pandemic a technology is needed that will have the power to
built up sufficient doses for protection. This would fit to Chirons slogan: “Protecting life right from the start”. The production of drugs with permanent cell
lines, is an innovative safe way. Drugs are produced in a biological environment
under controlled conditions. The production of human vaccines with this technology is possible. MDCK cells are a potential production system for many
whole virus systems. But Chiron Behring demands for this technology: All raw
materials that finally get into the drug should be unquestionable. The medium
used for cell propagation should be screened in order to be adventitious agent
free. Especially regarding human or animal viruses or prion particles it is necessary to identify the origin of material and have a certificate of suitability. The
approach “cultivating in protein-free medium” introduced here, also combined
with a reduction of contamination risks. Raw materials of animal origin are
excluded. We have evaluated parameters so far, that our product should fulfil
the prerequisites for clinical studies and should have the potential to become an
innovative product of high quality and biosafety.
O
P
H
A
R
M
A
C
E
U
T
I
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
C
A
Organisation/Firm
Chiron Behring GmbH & Co KG
L
Address:
S
Emil v. Behringstrasse 76
D-35041 Marburg, Germany
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Dr
Jürgen
Vorlop
Phone:
Fax:
E-mail:
+49 6421 394188
+49 6421 392738
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
34
Agriculture
Plant
Food
Feed
Dairy
Pharmaceutical
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
P
H
A
R
M
A
C
E
U
T
I
C
A
L
S
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I
O
6 . E T- 74 3 ( Yo n d e l i s ) a n e w ch e m i ca l e n t i t y
w i t h p o te n t i a l i n ca n ce r t re a t m e n t
P
Title of result:
H
ET-743 (Yondelis) a new chemical entity with potential in cancer treatment.
Ownership: PharmaMar S.A.U.
A
R
T EC H N O LO GY D E S C R I PT I O N
M
Abstract of the technology:
A
C
E
U
T
I
The primary objective of this EU Project was to identify cancer agents for certain deadly tumours using
small marine animals. European researchers has been using chemical agents extracted from a type of
Caribbean sea squirt, named Ecteinascidia turbinata, to treat some tumours. The breakthrough findings
have been published in the Marine Drugs journal. The project, has helped to establish trials in 24 EU
centres across seven European countries. The project, aimed to test the chemicals in treating sarcomas,
a rare tumour that kills about 3,900 Europeans each year. Patients with sarcomas tend only to live
between six to 12 months once diagnosed, depending on how the cancer spreads across the body.
Although sarcomas respond to chemotherapy, which shrinks the tumour’s growth, a cure has not yet
been found. However, the discovery of the alkaloid chemical, Ecteinascidin-743 (ET-743), is a breakthrough for medical science. The chemical is used as a chemotherapeutic agent and has shown promising results in patients where other treatments have failed. It has enormous potential for treating a range
of cancers, including breast cancer.
C
A
Detailed description of the technology:
L
S
The identification and development of new anticancer entities with activity in clinical settings where the
available therapies have a little impact in the outcome of patients is one of the most important priorities
in therapeutic medicine. The potential of the nature and specifically of the marine ecosystem in the
acquisition of anticancer drugs is being revamped: ET-743 (Yondelis) a new chemical entity discovered
in the tunicate E. turbinata is a representative example of a new class of chemical entity with potential
in cancer treatment. This demonstration project has attempted to characterize the therapeutic impact of
ET-743 in different conditions where there is a lack of available therapies or settings in which there is a
need to incorporate new agents in addition to conventional therapies. The proposed frame of intervention of this demonstration project has included a number of conditions that harbour a dismal prognosis and lead to a high number of deaths/calendar year in the EU. A total of 167 EU patients have been
entered into the program that included a network of 24 EU centres belonging to seven different countries. The contribution of this program to the development of ET-743 has been significant: The data
generated in sarcoma represents the first generation of activity with a new drug in the past 25 years. In
fact, experts in sarcoma consider ET-743 the third component of the therapeutic armamentarium in sarcoma, the characterization of activity in this demonstration program also led to the implementation of
a compassionate program that has provided access to a new active experimental drug to EU citizens thus
leading to significant social benefit. The evidence generated has supported the implementation of fur-
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A
C
I
T
U
ther studies in less pre-treated patients, both with ET as single agent or in combination, and to the activation of a clinical program in paediatric sarcomas. The early data generated in this program also led to
obtaining the orphan drug designation by the EMEA and to the construction of a pooled analysis for
registration purposes. The indicative results generated in women bearing advanced pre-treated breast
cancer have been the platform for additional studies in combination with other active drugs thus comparative studies vs conventional therapies can be rationally planned in the future. ET-743 has failed to
demonstrate activity in renal cancer and melanoma; such evidence has been generated with a rather limited cohort of patients thus exposing a low number of individuals to an experimental drug, an important ethical matter in experimental medicine.
L
S
41cq77_one_hundred
Current stage of development of the technology:
A
C
E
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : in clinical trials Fase II-Fase III
R
Patents granted
Partnership/other contractual agreements
A
Patents applied for but not yet granted
Exclusive rights
License agreement reached
M
Intellectual Property Rights
37
P
O
I
The EU funding helped to carry out trials for Yondelis in the 24 EU centres
across the seven countries. Some 167 patients are participating in the trials to
test the chemical’s effectiveness against soft-tissue sarcomas. Data from these
trials has already proved significant in developing the chemical. Yondelis may
also be tested against other tumour types such as breast cancer, which kills
130 000 EU citizens a year. It may also be tested in combination with other
treatments. The Europe-wide testing will allow further co-operation and teamwork between key European research centres. The funding provided a vital
boost in helping to accelerate the drug development process and get it to market, to make it available to patients sooner.
B
Innovative Aspects
Main advantage
H
Exploitation potential
41cq77_one_hundred
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
O
P
Organisation/Firm
PharmaMar S.A.U.
H
Address:
A
Avda. de los Reyes, 1,
P. Industrial. La Mina Norte
28770 Colmenar Viejo
(Madrid – Spain)
R
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Dr.
José
Jimeno
Phone:
Fax:
E-mail:
+34/91.846.60.00
+34/91.846.60.01
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
M
A
A P P L I C AT I O N D O M A I N S
C
E
U
T
I
C
A
L
S
38
Agriculture
Plant
Food
Feed
Dairy
Pharmaceutical
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
P
H
A
R
M
A
C
E
U
T
I
C
A
L
S
Pagina 39
O
12:54
I
04-11-2005
B
41cq77_one_hundred
39
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
7. N o n - r i b o s o m a l Pe p t i d e s y n t h e s i s
O
Title of result:
P
Non-ribosomal Peptide synthesis
H
Ownership: Philipps University Marburg
A
T EC H N O LO GY D E S C R I PT I O N
R
Abstract of the technology:
M
A
C
E
U
T
The ability to synthesize small bioactive peptides nonribosomally that find application in modern medicine is widely spread among microorganisms. As broad as the spectrum of biological activities is the
structural diversity of these peptides that are mostly cyclic or branched cyclic in nature, containing
unnatural amino acids, small heterocyclic rings and other unusual modification in the peptide backbone.
These peptides are synthesized from simple building blocks by multimodular enzymes, the so-called
nonribosomal peptide synthetases (NRPSs). Each cycle of chain elongation is carried out by a dedicated NRPS-module that harbors all catalytic units referred to as domains, necessary for substrate activation, covalent binding, and optional modification as well as peptide-bond formation. A terminal domain
(thioesterase or cyclase) releases the full-length linear or cyclic peptide and defines its shape in terms of
region- and stereo-selectivity. Recent biochemical, genetic and structural studies have unveiled the key
principles of nonribosomal peptide synthesis allowing the use of NRPS potential for combinatorial
biosynthesis.
I
C
Detailed description of the technology:
A
Chemoenzymatic approach to new macrocyclic peptide antibiotics.
Module and domain swaping to generate new NRPS-templates.
Post/synthetic modifications to generate structural diversity.
L
S
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
40
Patents granted
Partnership/other contractual agreements
04-11-2005
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L
S
41cq77_one_hundred
FB-Chemie-Biochemie, Meerwein
Str. 35032 Marburg, Germany
Industry
Research Institute
Start-up company
I
+49/6421/282/5715
+49/6421/282/2191
[email protected]
Other
U
Organisation Type: University
Phone:
Fax:
E-mail:
T
Address:
Professor Dr.
Mohamed
Marahiel
C
Title:
First Name:
Surname:
Organisation/Firm
Philipps University Marburg
A
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
50-249 employees
250-500 employees
>500 employees
E
Organisation size: < 50 employees
A
R
M
A
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Glycopeptide, antibiotics
H
P
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
C
A P P L I C AT I O N D O M A I N S
41
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Food
Biotechnology
© Valio Gefilus Product Family, Finland, 2005.
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
O
D
1 . Ev a l u a t i o n / v a l i d a t i o n o f n o v e l
b i o s e n s o rs i n re a l e n v i ro n m e n ta l a n d
food samples
Title of result:
B
I
Construction of novel chemical sensors, biosensors and immunosensors with improved
characteristics of sensitivity, stability and selectivity for the rapid detection of environmental pollutants and food contaminants in real samples. The biosensors that were
developed will be used in the future in food safety and control.
O
Ownership: UNIVERSITY OF ATHENS
T
T EC H N O LO GY D E S C R I PT I O N
E
C
Abstract of the technology:
H
N
O
L
Develop new approaches and novel devices to monitor and therefore prevent chemical contamination
in environment and foods. Some significant achievements were that novel biosensors for environmental pollutants such as pesticides, stimulating agents, PAHs, bacteria, pathogens, and other environmental pollutants were constructed and evaluated/ validated. Work was focused on flow injection systems
for the detection of organophosphorus and carbamate insecticides. Other significant work included validation, testing of amperometric enzyme biosensors based on dendrimer layers in fruit and vegetable
juices. The monitoring the fermentation of wine was another application of the devices of the present
project. A novel simple device for the rapid detection of doping materials was also developed.
O
Detailed description of the technology:
G
Y
The targets were:
1. Examination of microfluidics and chip sampling.
2. Examination of real time for mobile platforms of sensors.
3. Examine array technologies.
4. Study matrix effects.
5. Explore manufacturing practices.
A commercialization and scale-up production of biosensors will soon follow the evaluation/ validation
that was made during the last 24 months of the project. During the project, there was a free flow of creative ideas concerning the use of biosensors based on diverse biological recognition element, alternative
operating formats, and innovative signal transducers for applications in real environmental and food
samples.
44
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Y
41cq77_one_hundred
L
O
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
O
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
G
Current stage of development of the technology:
H
Patents granted
Partnership/other contractual agreements
C
Patents applied for but not yet granted
Exclusive rights
License agreement reached
N
Intellectual Property Rights
45
T
O
I
B
D
O
O
Main advantages
The experimental studies were focused on development of biosensors for the
rapid detection of species in a single mode (one-shot sensors) or for the continuous monitoring of analytes using flow injection analysis. The analytes included a wide range of species in real environmental and food samples such as pesticides in fruits, vegetables, waters and in foods, heavy metals in waters and
other environmental samples, species in wines and monitoring its fermentation,
polycyclic aromatic hydrocarbons (PAHs) and PCBs in atmospheric air and
other environmental samples. The studies also included an evaluation/ validation of the biosensors of the present project. Standardization procedures
included comparison with Official Methods of Analysis of the Association of
Official Analytical Chemists (AOAC) and these were mainly chromatographic techniques. There was no need for sample preparation or pre-treatment when
using our biosensing devices.
This close collaboration between European scientists had a result the transfer
of theoretical and applied scientific knowledge between participating centers
resulting in the construction and future commercialization of small sized
biosensing devices to detect rapidly pollutants at low cost and that are portable
for in field applications. The results obtained with the devices of the present
project were correlated with HPLC techniques (liquid chromatography-mass
spectrometry (LC-MS) measurements of the samples) with good agreement.
After the validation of the devices with chromatographic methods, it was concluded that the biosensors could be used as an alternative mode of detection to
the costly time consuming chromatographic procedures.
F
Innovative Aspects
E
Exploitation potential
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
O
D
Organisation/Firm
University of Athens
Address:
B
Chemistry Department
Panepistimiopolis-Kouponia
15771-Athens, Greece
Organisation Type: University
Industry
Title:
First Name:
Surname:
Prof.
Dimitrios
Nikolelis
Phone:
Fax:
E-mail:
++302107274577
++302107274754
[email protected]
Research Institute
Start-up company
Other
I
Organisation size: < 50 employees
50-249 employees
250-500 employees
>500 employees
O
T
A P P L I C AT I O N D O M A I N S
E
C
H
N
O
L
O
G
Y
46
Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
D
B
I
O
T
E
C
H
N
O
L
O
G
Y
Pagina 47
O
12:54
O
04-11-2005
F
41cq77_one_hundred
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
2 . A d a p te d i n v i t ro d i g e s t i o n m o d e l
O
Title of result:
D
Adapted in vitro digestion model
Ownership: Institute of Food Research
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
T
E
In vitro model of human digestion used to perform simulated gastric and duodenal digestions on potentially allergenic proteins and foods containing these proteins, adapted from the IFR in vitro biochemical digestion model. Resistance to digestion is one of the properties of a novel protein or target transgene which is considered in the allergenic risk assessment which has to be performed as part of a novel
foods safety assessment. Consequently the in vitor digestion model has an application in this area.
C
Detailed description of the technology:
H
N
O
L
O
G
Y
The model comprises of two distinct environments - the gastric and duodenal. The gastric model applies
a low acidity to the test meal/ sample. The degree of dilution and mixing is controlled to mimic that
found within the fundus of the stomach. Lipid is added where appropriate as a phospholipid-stabilised
oil emulsion system of controlled particle size (~10µm). The concentration of lipid can be varied from
0.2%w/w and 20% w/w (reflecting the concentration within the stomach after a low and high fat meal).
Where lipid is not required phospholipid is added as a solution of single-shelled liposomes. Pepsins and
a fungal analogue of gastric lipase are added to initiate protein hydrolysis and to achieve 10% (by
weight) hydrolysis of the lipid prior to delivery to the duodenal environment. After two hours incubation at 37°C the pH is rapidly titrated to 6.5 to mimic emptying into the duodenum. Biosurfactants are
added (a mix of various bile salts and phospholipids) of the same form and concentration as those secreted in the bile during digestion in vivo. Porcine pancreatic lipase, colipase, trypsin and chymotrypsin are
added to facilitate lipolysis and proteolysis. Temperature and pH are held constantly at 37°C and pH6.5
respectively. The digestion is allowed to proceed at these conditions for a further 15 minutes. Throughout the digestion process samples can be withdrawn for analysis at any time and, if required and
analysed to assess degree of protein degradation.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
48
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
04-11-2005
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Y
41cq77_one_hundred
G
Intellectual Property Rights
O
Patents granted
Partnership/other contractual agreements
H
The model represents a significant advance on previous in vitro systems by the
incorporation of the most recent descriptions of the multiphase and dynamic
nature of digestion and it also allows protein degradation and fragmentation
profiles to be determined during digestion. Comparison of the model with
human gastric and duodenal aspirates has shown semi-quantitative agreement
for the digestion of model meals containing potentially allergenic proteins.
B
I
O
T
E
Innovative Aspects /
Main advantages
C
Exploitation potential
N
O
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Dr
Martin
Wickham
Phone:
Fax:
E-mail:
+44 (0)1603 255000
+44 (0)1603 507723
[email protected]
O
Title:
First Name:
Surname:
Address:
Norwich Research Park
Colney Lane
Norwich NR4 7UA – UK
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
F
O
Organisation/Firm
Institute of Food Research
D
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
49
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
O
3 . R a p i d te s t s y s te m s f o r m i c ro o rg a n i s m s i n
f o o d , b e v e r a g e s a n d e n v i ro n m e n t
D
Title of result:
Rapid test systems for microorganisms in food, beverages and environment
Ownership: Scanbec Oy
B
I
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
T
E
C
H
One of the major activity fields of the young biotech company Scanbec Oy is the development of new
nucleic acid based analytical tools in connection with food, industrial, pharma-biotechnological and
environmental applications. Thereby Scanbec is opening up new solutions for the application of the
electrical biochip technology. The technology named FastScan is based on an enzyme-linked hybridization assay with an electrical signal read-out. The FastScan technology can be used for a fast and cultivation-independent detection and quantification of microorganisms and their activities by means of RNA,
DNA or protein based methods and provides a reliable and easy analysis in routine microbial diagnostics for many different applications.
N
O
Detailed description of the technology:
L
O
G
Y
Electrical biochips represent a new and alternative technology platform for many applications of DNA
and protein chips. The analytical system “FastScan” developed by Scanbec GmbH is a powerful system
for the detection and quantification of microorganisms based on a hybridization assay with electrical
signal read out using electrical biochip technology and provides a reliable and easy analysis in routine
microbial diagnostics with the following applications:
• detection and identification of Legionella in aquatic environments
• detection of food-spoiling and food-pathogenic microorganisms
• detection of obligate beer-spoiling microbes and quality check of brewers yeast
• detection of spoilage bacteria and yeasts in non-alcoholic beverages
The detection principle is based on a sandwich hybridization system with capture probes immobilized
on mobile carriers (paramagnetic beads) and Digoxigenin labelled detection probes, both specifically
hybridizing to the RNA or DNA target of interest. The detection is performed by an enzymatic reaction of the Anti-DIG-Alkaline-Phosphatase coupled to the detection probe and liberating molecules,
which are redox recycled at the electrodes on the chip and yielding current responses, which are measured by a sensitive multi channel potentiostat performing quantitative multi channel readout. The used
biochips made in silicon chip technology are based on interdigitated ultramicroelectrode arrays. The
probes necessary for the detection are not immobilized directly on the chip surface but are transported
to the chip by paramagnetic beads. By exchanging the beads and the corresponding detection probes
attached to them various analyses based on the detection of DNA and RNA target molecules can be carried out with the same chip.
50
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Y
41cq77_one_hundred
L
O
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
O
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
G
Current stage of development of the technology:
H
Patents granted
Partnership/other contractual agreements
C
Patents applied for but not yet granted
Exclusive rights
License agreement reached
N
Intellectual Property Rights
PhD
Antje
Breitenstein
Phone:
Fax:
E-mail:
+358-44-2986962
+358-8-5532389
[email protected]
T
O
O
Title:
First Name:
Surname:
Address:
PL 19; FIN-90571 Oulu; Finland
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
F
O
Organisation/Firm
Scanbec Oy
D
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
I
In contrast to conventional microbial detection methods performed especially
in food diagnostics, the use of the FastScan technology is of great advantage
since it is highly sensitive, flexible as well as considerably less time-consuming
(analysis time is reduced from several days to a few hours. Due to the fact that
the analytical device is comparably small it can be used for on-site measurements. Additionally, time consuming and laborious sample preparation and
labeling procedures as it is needed for biochips with optical read-out are not
required.
B
Innovative Aspects
Main advantage
E
Exploitation potential
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
51
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
4 . E l e c t r i ca l b i o ch i p a r r a y s
O
Title of result:
D
Electrical biochip arrays
Ownership: Fraunhofer Institute for Silicon Technology
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
Electrical biochip arrays are manufactured employing standard semiconductor technology; they enable
highly sensitive and selective detection procedures.
T
E
Detailed description of the technology:
C
H
Sub-µm sized biosensing electrochemical transducers are made in advanced silicon technology and produced in an industrial semiconductor line, procedures of capture immobilisation for the detection of
DNA and RNA as well as for proteins and haptens are established. The integration with microfluidic
components and highly sensitive electronics build the basis of smart portable analytical systems
N
Current stage of development of the technology:
O
L
O
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
G
Intellectual Property Rights
Y
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
Exploitation potential
Innovative Aspects
Main advantage
52
World wide no comparable technology as yet.
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G
Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Address:
Phone:
Fax:
E-mail:
+48 (4821) 17-4221
+48 (4821) 17-4250
[email protected]
L
O
Dr.
Rainer
Hintsche
N
Fraunhoferstr. 1, 25524 Itzehoe,
Germany
Title:
First Name:
Surname:
O
Organisation/Firm
Fraunhofer Institute for Silicon Technology
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
I
O
T
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
B
D
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
O
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
F
E
A P P L I C AT I O N D O M A I N S
53
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
O
D
5 . M i c ro a r r a y s f o r d e te c t i o n o f g e n e
e x p re s s i o n i n m u s c l e ; g e n e s a s s o c i a te d
with meat quality
Title of result:
B
1. Microarrays for detection of gene expression in muscle
2. Genes associated with meat quality
I
Ownership: Sygen International plc.
O
T EC H N O LO GY D E S C R I PT I O N
T
Abstract of the technology:
E
C
H
N
O
Eight SSH cDNA libraries and a normalized library have been made from pig muscle. PCR products
amplified from the libraries have been spotted on to glass slides to construct a microarray which has
been successfully used for the identification of differentially expressed genes associated with meat quality in pig muscle. These libraries and array resources could be a useful tool for future meat quality studies in pig (the focus of our experiments) as well as more general studies of muscle biology and gene
expression. The microarrays have been used to identify differentially expressed genes in muscles that
differ for meat quality traits. Characterization of these genes and identification of SNPs has shown that
some of these genes are associated with meat quality. Selection of such DNA markers in breeding stock
is already being used to add value to the meat industry by improving meat quality traits.
L
Detailed description of the technology:
O
G
Y
8 cDNA SSH libraries have been constructed to obtain contrasts between different phenotypes of interest and to enrich for genes that are differentially expressed between these phenotypes:
SSH library 1 + 2 contrast between the two most diverse breeds (based on phenotypic data generated in
the project)
SSH library 3 + 4 contrast between muscle types - Longissimus Dorsi vs. Semimembranosus
SSH library 5 + 6 contrast between high and low Meat Quality (based on pH and colour score)
SSH library 7 + 8 contract of high and low Stress (based on index of pre-slaughter urinary cortisol and
adrenaline levels).
The libraries have been quality checked for a low level of sequence redundancy. A full-length cDNA
library with an average insert size of 1.4kb has also been produced from mRNA from LD and SM
pooled from 5 different pig breeds. Microarrays have been constructed using 7056 purified PCR products representing a non-redundant subset of the cDNA clones from the above SSH libraries, spotted in
triplicate onto amino saline glass slides. These libraries and microarrays are key resources for the study
of pig muscle gene expression and have potential application for other studies of muscle gene expression. More than 300 separate meat quality, carcass, biochemical and sensory related traits have been
recorded on a total of 500 pigs representing 5 different breeds. Muscle samples showing greatest variation in these traits have been utilized in microarrying experiments to identify differentially expressed
genes related to sensory & texture related traits, intra-muscular fat, pH & drip loss, and loin percent54
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L
O
age. Some of these genes have been further characterized, and following SNP identification, have been
converted to DNA markers associated with meat quality. Typical additive allele substitution effects of
useful markers are in the range of 0.2 and 0.6 standard deviations of a phenotypic unit. These DNA
markers are available for incorporation into pig breeding programs for improvement of meat quality
traits in breeding stock or for differentiation of slaughter pigs at the commercial level.
G
Y
41cq77_one_hundred
H
C
E
T
O
I
B
D
O
O
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : There are two aspects to the technology described: microarrays and DNA
markers. These two components are at different stages of development and
can be used independently of each other.
1. Array resources:
The libraries and microarrays described are fully tested and have already
been used for the discovery of differentially expressed genes in pig muscle.
These are ready for exploitation in further research on muscle gene expression and meat quality.
2. DNA markers
The process of DNA marker development involves gene discovery via
microarray experiments, discovery of genetic variation in the identified gene
(SNP discovery) and association of that variation (SNP) with the trait of
interest.
Following our microarray experiments, differentially expressed genes are at
different stages of development. Some are under going further confirmation
work, some are in SNP discovery phase, others are in the SNP association
phase whilst some have been fully validated as DNA markers that are associated with meat quality.
N
Current stage of development of the technology:
Intellectual Property Rights
Patents granted
Partnership/other contractual agreements
F
Patents applied for but not yet granted
Exclusive rights
License agreement reached
55
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
Exploitation potential
O
Innovative Aspects
Main advantage
D
B
I
O
T
1. Array resources:
These arrays and cDNA libraries provide a new resource for studying gene
expression in pig muscle and an alternative to oligonucleotide arrays that are
not yet fully developed or widely available for the pig. They are ready for
exploitation in further research on muscle gene expression and meat quality
with Sygen and its project partners or by other interested parties.
2. DNA markers
Sygen has already signed commercial exploitation deals, involving use of DNA
markers for meat quality traits, with several third parties. These deals followed
successful trials that demonstrated significant improvements in quality for meat
processors which can be directly translated into commercial and financial
added value. Sygen is interested in working with 3rd parties to demonstrate
and commercially exploit the value both of existing DNA markers and the
newly discovered DNA markers from this project that relate to meat quality.
E
C
H
N
O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
L
Title:
First Name:
Surname:
Organisation/Firm
Sygen International plc.
O
Address:
G
Y
2, Kingston Business Park,
Kingston Bagpuize,
Oxfordshire, OX13 5FE,
United Kingdom
Organisation Type: University
Organisation size: < 50 employees
Dr.
Graham
Plastow
Phone:
+44 1865 8222 75
Fax:
+44 1865 8201 87
E-mail:
[email protected]
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
56
Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
D
B
I
O
T
E
C
H
N
O
L
O
G
Y
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12:54
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100 Technology Offers stemming from EU biotechnology RTD results
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O
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6 . H y d rox y n i t r i l e l y a s e s f o r i n d u s t r i a l
E n a n t i o s e l e c t i v e Sy n t h e s i s
D
Title of result:
Hydroxynitrile lyase for industrial enantioselective synthesis
Ownership: University of Stuttgart
B
I
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
T
E
(R)- as well as (S)-cyanohydrins are obtained highly stereoselective in the reactions of aldehydes and
ketones, respectively, with HCN in presence of hydroxynitrile lyases as biocatalyst. The reactions are
performed in organic solvents or a two-phase system.
C
Detailed description of the technology:
H
N
Current stage of development of the technology:
O
L
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
O
Intellectual Property Rights
G
Y
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Exploitation potential
Innovative Aspects
Main advantage
58
Patents granted
Partnership/other contractual agreements
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Y
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CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation Type: University
Research Institute
50-249 employees
O
L
0049-711-685-4268
0049-711-685-4269
[email protected]
Start-up company
250-500 employees
Other
>500 employees
E
C
Organisation size: < 50 employees
Industry
Phone:
Fax:
E-mail:
O
University of Stuttgart
Institute of Organic Chemistry
Pfaffenwaldring 55
D-70569 Stuttgart - Germany
N
Address:
Prof
Franz
Effenberger
H
Title:
First Name:
Surname:
Organisation/Firm
University of Stuttgart
I
O
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
B
D
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
O
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
F
T
A P P L I C AT I O N D O M A I N S
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100 Technology Offers stemming from EU biotechnology RTD results
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7. P ro ce d u re s f o r g e n e t i c m a p p i n g a n d
m a r ke r i d e n t i f i ca t i o n i n p i g s i n c l u d i n g
m i c ro s a te l l i te A F L P ta rg e t i n g m e t h o d .
Title of result:
B
I
Procedures for genetic mapping and marker identification in pigs including microsatellite AFLP targeting method. Construction of genetic maps and identification of QTL in
non-pig farmed species.
Ownership: Keygene nv
O
T
T EC H N O LO GY D E S C R I PT I O N
E
Abstract of the technology:
C
H
N
O
L
O
G
Y
Procedures have been established to construct genetic (linkage) maps using large numbers (up to 2000)
ALFP markers, or a combination of AFLP markers and microsatellite markers in pigs. These procedures take into account the complexities that result from the pedigree structure that is common in farm
animals such as pigs, where marker information originates from multiple families. Regarding the AFLP
markers, procedures have been developed to determine zygosity with high confidence and to identify
markers which have linkage to multiple chromosomes, thereby complicating the mapping procedure.
Framework markers may be needed to establish linkage groups, depending on the number of informative meisoses. A microsatellite targeting method was developed, capable of amplifying scorable
microsatellites in pigs. A number of primer combinations were identified yielding one, and occasionally more than one, microsatellite-containing fragment (microsatellite marker). This method may be useful to generate framework markers for genetic mapping and to integrate genetic maps constructed using
different pedigrees. These procedures take into account the complexities that result from the pedigree
structures commonly encountered in these species, where marker information typically originates from
multiple families. The procedures involve deriving zygosity of AFLP markers (co-dominant scoring)
with high confidence and identification (elimination) of markers which complicate the mapping procedure. Framework markers may be needed to establish linkage groups, depending on the pedigree structure and the available number of co-informative meisoses. Methods have been established to identify
AFLP markers for monogenic traits and QUL using the combination of bulked segregant analysis and
AFLP typing. This approach does not require a pedigree structure and can be used without prior
sequence information. These advantages, together with the high multiplex capacity of the AFLP technology, make this procedure attractive for use in farm animal species, for example in commercial breeding populations.
Detailed description of the technology:
The result is a procedure which will be followed to construct genetic maps in pigs. It involves the determination of zygosity of animals at AFLP markers, the verification of inheritance patterns of markers
from parents to offspring, the grouping of markers (AFLP and other) into linkage groups, and the
ordering of markers on the chromosomes. The result is a genetic map. The result further includes a pro60
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cedure to amplify and visualise, without any prior sequence information, polymorphism at microsatellites at anonymous positions in the genome. This result strengthens the AFLP technology further and
may facilitate the construction of genetic maps. The result further include a powerful method to identify AFLP markers associated with monogenic or polygenic traits using a combination of bulked segregant analysis and the AFLP technology.
G
Y
41cq77_one_hundred
H
C
E
T
O
I
B
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : The procedure for genetic mapping has been established using the pig pedigrees included in the project (PiGMaP pedigrees). It is reasonable to assume
that the procedure has general utility in other pig pedigrees. The microsatellite-AFLP targeting technique has been developed using a subset of pigs
from the PiGMaP pedigrees. The results suggest the method can be applied
to other pedigrees as well. Application to farm animals and fish: Genetic
maps of AFLP markers or combinations of AFLP markers and other marker types such as microsatellites can be constructed u sing farm animal pedigrees. Bulked segregant analysis in combination with the AFLP technology
can be used to identify AFLP markers for important traits in a highly efficient way without the need for a pedigree structure.
N
Current stage of development of the technology:
Intellectual Property Rights
D
Patents granted
Partnership/other contractual agreements
The AFLP technology is covered by international patent applications filed by
Keygene nv. AFLP is a trademark. The procedures for genetic mapping in pigs
will be treated as trade secret. A patent application may be filed for the
microsatellite targeting method, pending further research and depending upon
the outcome of a patent search.
61
F
Comments:
O
O
Patents applied for but not yet granted
Exclusive rights
License agreement reached
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O
Exploitation potential
O
Innovative Aspects
Main advantage
D
B
I
O
T
E
C
H
N
O
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G
Y
62
The procedures for genetic mapping will be exploited through Keygene’s
Molekular Marker Services (MMS) business unit. Keygene MMS performs contract research for third parties. The ability to construct genetic maps using
AFLP markers in livestock species will be included among the services Keygene
MMS offers. The microsatellite-targeting method will be exploited through
Keygene’s MMS for use in animal and possibly also plant species. However,
further research is needed to establish the potential of the method in full. The
role of the partner will be to provide sample materials to be used for AFLP typing with the aim to construct genetic maps or to identify AFLP markers associated with traits of interest to the partner. The role of Keygene will be to carry
out AFLP typing, construct the genetic maps and/or to identify AFLP markers associated with the trait(s) of interest to the partner. The applications of
AFLP technology in farm animal genetics include identification of genetic
markers for use in marker-assisted selection. This can be achieved without the
need for specific pedigrees and without prior sequence information. The construction of (high density) genetic maps results in placing these markers on particular chromosomes or chromosome regions, which may provide information
about the number of loci(QTL) controlling the trait and suggest candidate
genes based on comparative maps. This technology can be applied to any
species and is there fore also of interest to the farm animal and fish breeding
industry. The main benefits of this technology are the low cost in comparison
with alternative marker systems as a result of the high multiplex ratio of the
AFLP technology. Other advantages include the fact hat no prior sequence
information is needed and that large numbers of genetic markers that can be
generated.
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Y
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CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Address:
Phone:
Fax:
E-mail:
+31 317 466866
+31 317 424939
[email protected]
L
O
Dr
Michiel
van Eijk
N
Agrobusiness Park 90
NL-6700AE , The Netherlands
Title:
First Name:
Surname:
O
Organisation/Firm
Keygene nv
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
I
O
T
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
B
D
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
O
Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
F
E
A P P L I C AT I O N D O M A I N S
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100 Technology Offers stemming from EU biotechnology RTD results
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O
O
D
8. Diagnostic DNA fingerprinting for use
i n m e a t q u a l i t y co n t ro l a n d p ro d u c t
s p e c i f i ca t i o n v e r i f i ca t i o n s y s te m s
Title of result:
B
Diagnostic DNA fingerprinting for use in meat quality control and product specification
verification systems.
I
Ownership: PIC Group (Sygen International)
O
T EC H N O LO GY D E S C R I PT I O N
T
Abstract of the technology:
E
C
H
N
O
L
O
AFLP was used in this project in partnership with Keygene NV to locate candidate markers for commercially important traits in pigs. Subsequently a number of different approaches have been used to
identify diagnostic DNA markers that can be used in marker assisted selection for the development of
new products. These include among others markers explaining variation in appetite and growth, backfat, susceptibility to scrotal hernia, litter size, reproductive longevity and resistance to e. coli F18. Markers have been identified which are closely linked to genes and QTL of interest and in some cases they
are likely to be causative polymorphisms. A marker closely linked to the dominant white locus was
identified using AFLP and was then converted to a simple PCR based test for high throughput routine
genotyping. This test was then used to fix the preferred allele in a new breeding line in turn speeding up
the development of a new parent female product for use by pig producers who wish to produce white
slaughter pigs. A number of other markers were then identified that could be used to more accurately
select for white slaughter pigs. Markers have also been developed for confirmation of breed and these
markers can also be used as part of traceability systems (that have also been developed).
G
Detailed description of the technology:
Y
The result is a process for marker assisted selection, for product differentiation or for traceability, where
these tools are an enhancement of selective breeding for pig production or for improving the production and traceability of pork. Application is achieved through a number of existing technology platforms, primarily using PCR. As the number of markers which are available increases then new technologies will be required to exploit these results effectively (e.g. high density genotyping systems such
as DNA chips or other detection platforms).
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O
N
H
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Applied research. Application in pig breeding, for selection of parent animals or for application in traceability. The technology can be provided
through breeding stock or be used to select or verify genetic inputs. In some
situations it may be useful to demonstrate their value in specific systems as
part of introduction of this technology.
O
G
Current stage of development of the technology:
E
Markers are covered by patent applications or granted patents and are available
for licensed use.
O
Comments:
Patents granted
Partnership/other contractual agreements
T
Patents applied for but not yet granted
Exclusive rights
License agreement reached
C
Intellectual Property Rights
65
B
D
O
O
Two main applications are the improvement of the quality and consistency of
pork products, and, as a quality control program, verifying meat quality or origin specifications. A range of DNA markers has been developed. These can be
used in marker-assisted selection to increase the accuracy and speed of genetic
improvement (breeding). Those that are associated with key meat quality and
sensory traits are able to be used by abattoir and meat processing organizations
to specify meat quality traits that they want their suppliers to adhere to. The
meat quality traits that the DNA markers are associated with include pH, intramuscular fat, drip loss, and color, as well as a range of sensory and texture (eating quality) traits. Additional sets of DNA markers are also available allowing
the abattoir and meat processing organizations to verify if the product received
from their suppliers is in fact according to their genetic specifications. The
DNA markers that are available may have a simple role (breed verification,
where this is might be a product specification) or a more complex multiplex of
DNA markers capable of being used very cost-effectively in traceability and
origin verification programmes.
F
Innovative Aspects
Main advantage
I
Exploitation potential
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O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
O
D
Organisation/Firm
PIC Group (Sygen International)
Address:
B
2 Kingston Business Park,
Kingston Bagpuize, Oxon,
OX13 5FE, United Kingdom
I
Organisation Type: University
O
Organisation size: < 50 employees
Title:
First Name:
Surname:
Dr
Graham
Plastow
Phone:
Fax:
E-mail:
+44 1865 822200
+44 1865 820187
[email protected]
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
T
A P P L I C AT I O N D O M A I N S
E
C
H
N
O
L
O
G
Y
66
Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
D
B
I
O
T
E
C
H
N
O
L
O
G
Y
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100 Technology Offers stemming from EU biotechnology RTD results
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D
9 . Fo o d g r a d e , g e n e t i ca l l y m o d i f i e d
L a c to co cc u s l a c t i s s ta r te r s t r a i n t h a t
p ro d u ce s b u t te r - a ro m a a t h i g h l e v e l s ,
f o r t h e p ro d u c t i o n o f i m p ro v e d , h i g h l y
a ro m a t i c f e r m e n te d d i a r y d r i n k s
B
Title of result:
I
O
Food grade, genetically modified Lactococcus lactis starter strain that produces diacetyl
(butter-aroma component) at high levels, for the production of improved, highly
aromatic fermented dairy drinks.
T
Ownership: CSK Food Enrichment
E
T EC H N O LO GY D E S C R I PT I O N
C
H
Abstract of the technology:
N
O
L
O
G
Y
NIZO food research has produced two food-grade prototype Lactococcus lactis subsp. Cremoris
starter strains that efficiently produce the flavour compound diacetyl under (semi-) aertobic conditions.
Importantly in terms of application possibilities it should be noted that the diacetyl producing strain is
the product of self-cloning strategies. Moreover, the strain expresses desired attributes with respect to
their use in milk-fermentation, including proteolytic activity and the ability to ferment the milk-sugar
lactose. The genetically modified strains could be shown to display high-level stability, both at the
genetic and the metabolic level under industrially relevant conditions. CSK food enrichment has evaluated the industrial applicability and functionality of the prototype modified starter strain of Lactococcus lactis produced by NIZO food research. Milk fermentation appeared to lead to rapid acidification
and good diacetyl production levels, when the modified strain was used as an adjunct starter. Fermentation conditions were optimised and it was shown that the eventual diacetyl level produced can be controlled efficiently by the inoculum ratio (starter culture relative to modified adjunct starter), combined
with the level of aeration. In conclusion the diacetyl producing starter variant strain displays promising
characteristics that can provide a novel approach to generate more aromatic buttermilk-like products
using ‘simple’ fermentation conditions.
Detailed description of the technology:
In order to create prototype starter strains that produce high amounts of diacetyl during fermentation
a co-factor engineering apporach was taken in which the redox balance (NADH over NAD+ ratio) in
the cell is disturbed by high level productio nof the lactococcal NADH-oxidase enzyme, using the nisin
inducible expression (NICE) system. This plasmid-borne characteristic was combined with the foodgrade selection arker system based on the lacF gene combined with a second lactococcal plasmid that
encodes the enzymes involved in lactose fermentiation, but lacks the lacF encoding gene. These two
plasmids were introduced into a L. lactis MG1363 derivative harboring a deletion in its chromosomal
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L
O
N
H
C
E
I
B
D
O
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Prototype/demonstrator available for testing – Results of demonstration trials available. The diacetyl-starter strain of Lactococcus is completely foodgrade and is the product of self-cloning strategies. Its functionality has been
proven in terms of stability under industrially relevant conditions, its capacity to generate high levels of diacetyl in the eventual fermented product. For
application in fermented dairy drink production, the system has been tested
in depth. However, for other specific applications (other (non)-dairy products) the performance of the system has not yet been optimised, and might
thus require additional R&D input.
O
Current stage of development of the technology:
O
T
aldB gene, which is the desired background for efficient diacetyl production using the co-factor engineering strategy. The resulting food-grade strain is therefore able to ferment lactose, proteolytically
active and was shown to produce high levels of diacetyl under laboratory conditions, when grown aerobically. Semi-industrial milk fermentation shave focussed on utilisation of the modified, diacetyl forming strain as an adjunct starter in combination with an industrial starter strain. The two strains were
inoculated in milk in various ratios and fermentation was continued until no further acidification was
observed. Under anaerobic or micro-aerobic conditions only traces of diacetyl could be detected, and a
significant increase in diacetyl production was measured when (mild- to vigorous-) aeration was administered during fermentation. More detailed optimisations of the fermentation conditions have shown
that the eventual diacetyl level produced can be controlled efficiently by the inoculum ratio, combined
with the level of aeration. Overall the conditions used during these fermentations are clearly compatible with industrial fermentation processes and are therefore expected to be directly translatable to
industrial scale production processes. The food-grade, genetically modified diacetyl producing strain
generates a highly successful approach to create more aromatic fermented dairy products, and is especially suitable for the application in the production of fermented dairy drinks, like buttermilk.
G
Y
41cq77_one_hundred
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Comments:
F
Intellectual Property Rights
Patents granted
Partnership/other contractual agreements
NIZO patent holder: EP-0355036; werkwijze voor the selecteren en stabiel
handhaven van recombinant DNA in melkzuurbacterien.
NIZO patent holder: EP-0712935; werkwijze voor het reguleren fan de genexpressie in melkzuurbacterien.
69
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F
O
Exploitation potential
O
Innovative Aspects
Main advantage
D
B
I
O
T
E
C
H
N
O
L
O
G
Y
70
The commercialisation of the prototype starter culture includes production and
distribution of fermented products, marketing and processing of legislatory
aspects related to the application of genetically modified bacteria in food fermentations. A partner interested in the production and sales of the product that
can be generated by the starter strain produced, can obtain high-quality starter
culture concentrate from CSK food enrichment. Applications of the modified
starter strain should initially be discussed with this partner. Potential partners
can utilise the technology developed and the starter culture produced in industrial scale food-fermentations. The concept has been well developed for the fermentation of milk, leading to highly aromatic fermented products that are certainly attractive to market as more tasteful, more aromatic etc. With respect to
the fact that genetic modification has been used to construct the prototype
starter culture in this project it has to be noted that the strains produced are the
product of self-cloning and thus do not contain any ‘foreign’ DNA and are for
that reason classified as lowest level of genetically modified organisms. The
starter culture is available for industrial research evaluation and for application.
Eventual interested parties will have to negotiate licence agreements with the
patent holder NIZO food research for the commercial application of two of the
genetic tools used in the system that is applied. CSK food enrichment is the
partner that can take care of the starter production at an industrially relevant
scale and is the primary partner to approach for requests or questions related to
application of the technologies developed. Within the current consortium, no
specific activity is undertaken to market the prototype starter cultures recognized as deliverables of this project. This attitude is caused by the consumer
resistance towards food products that contain genetically modified organisms
or products derived thereof. The starter cultures produced can be applied in the
production of more aromatic fermented food-products, generating a more
interesting end-product for the consumer in terms of flavour. The end-users for
these starters can come obviously from the dairy industry, but might also be
found within other sectors of the food-industry that deals with fermentation of
raw, natural products like vegetables, meats etc. The main innovative features
are that through a simple fermentation process, higher levels of a high value
metabolite can be generated that bring novel or improved flavour characteristics to a product. In the current market where consumers are interested in novel
products having improved or altered taste-profiles, the products that can be
generated through application of these starter cultures can be very fruitful, provided that the issues surrounding application of genetically modified organisms
in foods is solved.
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Y
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CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Pallasweg 1, PO Box 225
NL-8901 BA Leeuwarden,
The Netherlands
Phone:
Fax:
E-mail:
+31 58 2844242
+31 58 2844210
[email protected]
L
O
Dr
Aart
van Boven
N
Address:
Title:
First Name:
Surname:
O
Organisation/Firm
CSK Food Enrichment
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
I
O
T
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
B
D
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
O
Agriculture
Plant
Food
Feed
Pharma
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
F
E
A P P L I C AT I O N D O M A I N S
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
1 0 . A p i g d i v e rs i t y d a ta b a s e
O
Title of result:
D
A pig diversity database
Ownership: Roslin Institute
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
T
E
C
The Roslin Institute was chosen as the ultimate data repository site. A database has been mounted on
the Roslin webserver and the data collected during the project were made available to the participants
at http://projects.roslin.ac.uk/pigbiodiv/. The objective of the project was to evaluate the European pig
diversity at DNA level. The study covered 70 breeds originating from 15 countries, including a sample
of European wild pig and one Chinese breed. The data collected will soon be made publicly available
and should provide guidance in setting action plans for managing biological diversity within each country, along the recommendations of the Rio Convention. Commercial opportunities for breeding companies or breeders’ associations may also be envisioned.
H
N
Detailed description of the technology:
O
L
O
G
Y
In addition to the Chinese Meishan breed and a sample of European wild pig, 68 European domestic
breeds (or lines) were sampled. These 68 populations belonged to 3 categories of breeds, namely local
breeds (29), national varieties of international breeds (18) and commercial lines (21). DNA was extracted from about 50 pigs from each population, and use was made of 2 genetic markers for evaluating
diversity, namely microsatellites and amplification of fragment length polymorphism (AFLP). Free
access to the project design (participant, breeds, markers) is currently allowed, whereas access to the
genotypes identified is restricted to the participants until publication of the main scientific results. The
data collected cover as substantial part of the world pig genetic resources, and nearly half a million datapoints were generated during the project. The information gathered is thus probably rather unique in
the field of genetic diversity study in farm animals
Current stage of development of the technology:
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Results of demonstration trials available.
The database is fully operational.
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73
H
C
E
T
O
I
B
D
Main advantage
The feasibility of downloading export forms from the Roslin database directly
into standard available softwares was demonstrated during the preparation of
the final report by INRA. This procedure will continue to be applied in preparing the scientific articles which were outline during the last project meeting in
Roslin, 25-26 September 2000. An important milestone is the “post-final”
meeting to be held in Cordoba, 7-9 November 2002, during which a more
detailed programme of publications will be discussed. For longer term plans,
one should refer to the new project PibbioDiv2.
The data stored at Roslin offer opportunities for comparisons with similar
genotyping results obtained in various laboratories across the world, using
either microsatellites or AFLP. In particular, comparability of microsatellite
allele sizes across laboratories using different sequencers is ensured through the
information provided on reference DNAs. The critical evaluation of livestock
genetic resources and conservation of pig populations are important factors in
enabling the European agriculture and food industries to respond to future
changes in consumer needs. One of the main outcome of the PigBioDiv project was the possibility to quantify the relative contributions of a large number
of European pig breeds to this species genetic diversity. The data collected
should provide guidance for managing genetic diversity within European countries, along the recommendations of the Rio convention, and in keeping with
the aims of the FAO Global Programme for Management of Farm Animal
Genetic Resources. Commercial opportunities may also be envisioned, since
the project has included a significant component aimed at quantifying diversity of major international breeds and commercial lines where the level of diversity is expected to be relatively small. This result of PigBiodiv may also be seen
as the accomplishment of the “strong technology transfer element of the programme, as manifested by the databases set-up on Internet”, which was listed
as one important objective of this demonstration project.
O
Innovative Aspects
O
Exploitation potential
N
O
L
O
Patents granted
Partnership/other contractual agreements
F
Patents applied for but not yet granted
Exclusive rights
License agreement reached
G
Intellectual Property Rights
41cq77_one_hundred
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
O
D
Organisation/Firm
Roslin Institute
Address:
B
Roslin Midlothian
EH29 9PS Scotland UK
Organisation Type: University
Industry
Title:
First Name:
Surname:
Mr
Chris
Haley
Phone:
Fax:
E-mail:
+ 44 3 5274200
+44 3 4400434
[email protected]
Research Institute
Start-up company
Other
I
Organisation size: < 50 employees
50-249 employees
250-500 employees
>500 employees
O
T
A P P L I C AT I O N D O M A I N S
E
C
H
N
O
L
O
G
Y
74
Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
D
B
I
O
T
E
C
H
N
O
L
O
G
Y
Pagina 75
O
12:54
O
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F
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75
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
O
D
1 1 . U t i l i s a t i o n o f f i b e r p re p a r a t i o n s to
e n h a n ce p ro b i o t i c v i a b i l i t y a n d
s ta b i l i t y d u r i n g f re e ze - d r y i n g a n d
in foods
B
Title of result:
I
Utilisation of fiber preparations to enhance probiotic viability and stability during
freeze-drying and in foods.
O
Ownership: VTT Biotechnology
T
T EC H N O LO GY D E S C R I PT I O N
E
Abstract of the technology:
C
H
N
O
Selected fiber preparations have potential in technological applications in protecting probiotic viability
and stability during processing and storage in food matrices. An oat fiber carrier protected fresh cells
during storage in low pH juice, whereas polydextrose-type of products proved to be promising freezedrying carriers for probiotic cells (good stability in powdery from an also when incorporated into cereals). These results indicate that it is possible to develop probiotic-fiber pairs where the fiber helps to
maintain the viability and stability of the probiotic. However, these functions seem to be at least partially application dependent (e.g. depending on the composition, pH, and water activity of the probiotic product).
L
O
Detailed description of the technology:
G
Y
Specific fibers can be used as technological aiding agents to improve the viability and stability of probiotics in different applications. The type of fiber, the way it is formulated and the probiotic strain and
food matrix of interest all affect the protective capability of fibers, thus technology is applicationdependent.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
76
Patents granted
Partnership/other contractual agreements
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Y
41cq77_one_hundred
O
L
Utilising fibers and prebiotics in the protection of probiotics enables the development of healthier foods with better quality (i.e. better viability and stability
of the probiotic strain).
B
I
O
T
E
C
H
N
O
Innovative Aspects
Main advantage
G
Exploitation potential
Dr.
Maria
Saarela
Phone:
Fax:
E-mail:
+358-20-722 4466
+358-20-7227072
[email protected]
O
Title:
First Name:
Surname:
Address:
P.O. Box 1500, 02044 VTT, Finland
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
F
O
Organisation/Firm
VTT Biotechnology
D
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
77
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
1 2 . B i o te ch n o l o g y o f E x t re m o p h i l e s
O
Title of result:
D
Biotechnology of Extremophiles
Ownership: Hamburg University of Technology
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
Extremophiles and their enzymes (extremozymes) for the sustainable production of chemicals, biopolymers, materials, and fuels from renewable resources.
T
E
Detailed description of the technology:
C
H
N
O
L
O
G
Y
Extremophiles are unique microorganisms that are adapted to survive in ecological niches such as high
or low temperatures, extremes of pH, high salt concentrations and high pressure. These extremophiles
are applicable in various fields including detergent, textile, paper, food, feed, pharmaceutical and chemical industries. The cell components of extremophilic archaea and bacteria are unique and provide a
valuable source for new biocatalysts and compounds. Their biological systems and enzymes can even
function at temperatures between -5 and 130°C, at pH values between 0 and 12, at salt concentrations
up to 35%, in the presence of organic solvents and at high pressure (1000 bar). Biocatalysts from
extremophiles basically allow the use of enzymes in industrial processes even under harsh conditions
under which conventional proteins would completely denature. The extreme stability of their enzymes
and membranes, and the synthesis of unique organic compounds and polymers make extremophilic
microorganisms interesting candidates for basic and applied research. Furthermore, biocatalysts from
extremophiles show important environmental benefits because they are biodegradable, specific, show
improved use of raw materials and minimise pollutant emissions and reduce energy consumption while
simultaneously improving quality and purity of products, e.g. optically pure compounds. This technology will play a key role especially for the sustainable production of chemicals, biopolymers, materials
and fuels from renewable resources.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
78
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
04-11-2005
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41cq77_one_hundred
G
Intellectual Property Rights
O
Patents granted
Partnership/other contractual agreements
O
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Exploitation potential
B
I
O
T
E
C
H
N
Innovative Aspects
Main advantage
D
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Kasernenstr. 12, 21073 Hamburg
Organisation Type: University
Organisation size: < 50 employees
Industry
Phone:
Fax:
E-mail:
+ 49 40 42878 3117
+ 49 40 42878 2582
[email protected]
Research Institute
50-249 employees
O
Prof. Dr. Dr. h.c.
Garabed
Antranikian
Start-up company
250-500 employees
O
Address:
Title:
First Name:
Surname:
F
Organisation/Firm
Institute of Technical Microbiology
Hamburg University of Technology
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
79
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
O
13 . Apparatus for expanding of food pieces by
means of microwaves and high turbulent air
D
Title of result:
Apparatus for expanding of food pieces by means of microwaves and high turbulent air
Ownership: Wageningen University and Research
B
I
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
T
E
C
A new expansion process was developed combining high-turbulent air treatment with microwave technology. The key concept of the technology and build prototype is that a fast evaporation at the product
surface can be accomplished applying turbulent air contact and a fast internal evaporation applying
microwaves. The combination of heating technologies gives the possibility to make expanded products
in a minimal processing time avoiding high product temperatures.
H
Detailed description of the technology:
N
O
L
O
G
Y
The result is a new process for expanding vegetable materials. With the new process unique products
can be obtained due to the combined fast surface and volumetric heating leading to homogeneous
expanded product. The manufactured prototype of 7-20 kg/h can easily be scaled up to industrial units
of 500 kg/h. Different applications for the new puffing process were successfully developed: expansion
of vegetables for soups, sauces etc., expansion of fruits for muesli, yoghurt, milk etc., puffing of grain
products and pulses for cattle feed, pasteurisation of spices with maintainance of ethereal oils, expansion of starch based snacks to fatfree snacks with adjustable roasting level and roasting of cocoa beans
etc. The microwave technology applied in the prototype is tailor-made developed with specialised software calculation and simulation of the electric field distribution within the cavity. The high turbulentair technology applied for surface expansion is patented by Torftech Ltd., UK. The result of this project a new expansion technology based on simultaneous surface and volumetric expansion gives the possibility to produce unique products not possible with any other expansion technique. Quality can be
kept high due to reduced thermal burden and short processing times.
Application areas for the newly developed technology:
- expansion of vegetables to highly homogeneous porous products for soups, sauces etc.
- expansion of fruits to highly homogeneous porous products for muesli, yoghurt, milk etc.
- puffing of grain products and pulses for cattle feed
- pasteurisation of spices with maintainance of ethereal oils
- expansion of starch based snacks to fatfree snacks with adjustable roasting level
- roasting of cocoa beans etc.
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41cq77_one_hundred
G
Current stage of development of the technology:
O
L
O
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Prototype based on extension of proven Torbed equipment.
Intellectual Property Rights
N
T
D
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
O
The new developed technology showed the following benefits:
- application of lower air temperatures leading to reduced surface heating,
improved colour and possibility to treat temperature sensitive products like
fruits and certain herbs
- possibility of expanding larger products homogeneously due to combined
surface and volumetric treatment
- shorter processing times leading to a higher nutritional content of the product
- no need for after-drying, final moisture content can be reached with the new
puffing technology
I
Innovative Aspects
Main advantage
E
Exploitation potential
C
The prototype is available for testing and via colloboration of the SME's of the
consortium a combined industrial unit will be manufactured
B
Comments:
Patents granted
Partnership/other contractual agreements
H
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Title:
First Name:
Surname:
Drs.
Erik
Esveld
Address:
Phone:
Fax:
E-mail:
+31.317.475129
+31.317.475347
[email protected]
PO.Box 17, 6700 AA
Wageningen, the Netherlands
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
F
O
O
Organisation/Firm
Agrotechnology and Food Innovations
Wageningen University and Research
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
81
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
O
14. Development of molecular diagnostic
to o l s f o r t h e d e te c t i o n o f b a c te r i a
D
Title of result:
Development of molecular diagnostic tools for the detection of bacteria
Ownership: Ribo Technologies BV
B
I
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
T
E
C
Microscreen is specialized in the development of molecular diagnostic test for the detection and identification of bacteria from various sources. Products of Microscreen are developed according to the latest
molecular (DNA) technology and are produced under the highest quality standard (ISO 9001:2000).
The tests are very sensitive, rapid (< 4 hours), reliable and can be used for high throughput screening. It
is foreseen that within 5 to 10 years DNA-tests will replace a substantial part of the current conventional culturing methods.
H
N
Detailed description of the technology:
O
L
O
G
Y
The detection of whole-bacterial cells via the labelling of specific nucleic acids with fluorescently
labelled oligonucleotide probes is called fluorescence in situ hybridization (FISH). FISH requires no
cultivation and cells can be fixed before analysis. The FISH assay is a culture-independent technique and
has been proven to be a reliable and validated method for the enumeration of whole bacterial cells in
mixed populations. FISH probes have different applications; Quality control of Food/Feed products,
efficacy control for the application of the probiotic/prebiotics. Pathogen detection. For Microscreen the
FISH technology belongs to the core of the company. A patent position has been obtained on this technique and the company is already supplying the gut microflora research market with FISH tests. A logical step is expansion of these efforts in other markets. Currently Microscreen is investigating high
through put application of the FISH technique using an automated microscope, flowcytometry and/or
filter cytometry. FISH probes can be used for application on these machines in a routine setting. QPCR
is a method to quantitatively detect low amounts of bacteria in different matrices. Microscreen has
developed a test for the quantitative detection of Mycobacterium paratuberculosis in fecal samples from
cows (ParaScan). ParaTBC results in Johne’s disease in cattle. This disease results in considerable losses
with regards to milk production and meat production. Breeding programs are installed focussed on the
prevention and reduction of Johne’s disease . The ParaScan can be instrumental in these breeding programs. Microscreen has developed the SalScan, a qPCR test for the detection of Salmonella bacteria.
This test was developed to be used in the food and feed industry. The food and feed market has much
need for such a test. For each customer an application study is necessary, each customer has a different
matrix in which the Salmonella bacteria must be detected. Each matrix requires a special sample preparation procedure. After a successful introduction with one customer others will follow. LisScan, TocScan, BacScan, CampScan These are relatively new tests for the detection of Listeria, Total count of bacteria, Bacillus group 1 and Campylobacter species. These tests are in various stages of readiness. Expect-
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O
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
N
Development phase
Tested, available for demonstration
Already on the market
L
Current stage of development of the technology:
O
ed finalisation of the tests is mid 2005. Also these test will find wide application in the food and feed
industry. The market requires more and more automated total system solutions capable of detecting
more than one target. This approach is currently investigated by Microscreen.
G
Y
41cq77_one_hundred
H
Intellectual Property Rights
C
Patents granted
Partnership/other contractual agreements
E
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Dr.
Michel
van der Rest
Phone:
Fax:
E-mail:
+31 50 31 66 787
+31 50 31 66 797
[email protected]
O
Title:
First Name:
Surname:
Address:
L.J.Zielstraweg 1
9713 GX Groningen
The Netherlands
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
F
O
Organisation/Firm
Ribo Technologies BV
D
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
I
The food and feed market has much need for molecular testing. The following
figures demonstrate the enormous market size for diagnostic testing in the food
and feed market: 2003 to 2008 An increase in the number of tests from 1.1 billion 1.5 billion (+36%). Traditional testing will grow form 0.90 billion to 1.00
billion (+11%). Molecular diagnostics wil grow from 0.23 billion to 0.46 billion
(+100%) The market value will increase from ($) 3.2 billion to 4.9 billion
(+53%) Source: Frost & Sullivan. Also evident is that most of the growth in this
market will be driven by rapid test systems involving FISH and qPCR.
B
Innovative Aspects
Main advantage
O
T
Exploitation potential
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
83
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
O
1 5 . Co n t i n u o u s Me m b r a n e Me d i a te d C h e e s e
P ro ce s s
D
Title of result:
Continuous Membrane Mediated Cheese Process
Ownership: Agrotechnology & Food Innovations b.v.
B
I
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
T
E
C
H
N
O
L
O
G
Y
A cheese production system is developed based on membrane technology. The goal of using membrane
technology is to improve the quality of cheese compared to cheese produced with increased yield, that
has less accepted texture and taste than traditionally produced cheese. The total process comprises the
following units:
- ultrafiltration unit to concentrate milk;
- enzyme membrane reactor to destabilise milk using immobilised chymosin;
- heat exchanger for controlled coagulation;
- curd drainage in moulds.
These units can operate independently when separated by buffer tanks. This makes the total process
flexible and suitable to produce different types of cheese with a standard configuration. The main innovation of the result is the implementation of an enzyme membrane reactor in which chymosin is immobilized and does not end up in the final cheese. Parallel to the flow of the milk along the enzyme there
is the possibility to add or remove specific components to or from the milk through the membrane. For
this principle a new spiral wound membrane module is developed in which recycling of a solution along
the permeate side is possible. Immobilization of enzyme is not common in the dairy industry but can
be efficient in the demonstrated system when enzyme release is minimal. The final system was demonstrated to produce continuously a cheese with slightly increased yield but with a quality much closer to
traditional cheese compared to other membrane mediated cheeses. Two pilot plants were installed at the
location of two end-users: Mevgal, Greece, and Lactalis, France. In each pilot a 6 m2 membrane reactor
was installed with the intention to produce 75 kg cheese per day. Cheese production with a prototype
set-up was successful, however, mainly due to immobilisation problems, the demonstration on pilot
scale was not that successful. The main problem was the scale-up of the enzyme membrane reactor.
Optimisation finally resulted in some successful trials at Mevgal, but within the project length Lactalis
did not manage to duplicate this. One of the problems that also had to be overcome was microbial contamination. Further demonstration and/or research is desired to overcome the last problems. The
potential of this process is that membrane technology makes traditional cheese processing more flexible, also, when used in combination with traditional cheese processing steps. Extension of the membrane reactor technique with other enzymes allow milk components modification without any enzyme
ending up in the milk, unless wanted.
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41cq77_one_hundred
G
Detailed description of the technology:
H
C
E
T
O
I
B
D
O
Each process step contributes to the final quality of the cheese, but each process step can be changed
easily to produce a different type of cheese.
O
Ad a). Standardized milk is fed to an ultrafiltration unit and concentrated with a factor two to three.
This preconcentration of the milk gives a better control of the texture in the heat exchanger. The concentrated milk must be pasteurized afterwards before it can be fed to the enzyme membrane reactor
(EMR).
Ad b). The enzyme membrane reactor consists of a newly developed spiral wound membrane module
in which on the feed side chymosin is immobilized. Milk passing allong the membrane surface will be
destabilized, but coagulation of milk inside the module must be prevented. On the permeate side of the
membrane module a nutrient solution is circulated to add or remove specific components to or from the
milk. To realize this the configuration of the traditional spiral wound module had to be altered by plugging the inner permeate tube in the middle and putting baffles on the permeate side for maximum contact of the solution with the membrane. The entrance and outlet of the module are on the two different
sides of the plug on the inner permeate tube.
Ad c). The heat exchanger is installed behind the EMR for controlled coagulation of the milk. Inside the
heat exchanger the rate of coagulation, the temperature and the residence time of the curd can be controlled. The destabilized milk flows through a stainless steel tube in the heat exchanger. The diameter of
the tube determines the rate of heating of the curd and the shear on the wall. Shear stress should be as
low as possible to prevent concentration because of pressure drop.
Ad d). The curd flowing out of the heat exchanger is collected in a mould to remove whey and give the
curd the shape of the final cheese.
N
O
L
O
The result can be divided in four different parts:
a) Concentration of milk;
b) Enzyme membrane reactor for milk destabilisation with immobilised chymosin;
c) Heat exchanger for controlled coagulation;
d) Curd concentration with moulds.
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
F
Current stage of development of the technology:
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
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O
Exploitation potential
O
Innovative Aspects
Main advantage
D
The innovative aspect of the MEMCHEEP project is the use of a membrane
reactor in cheese processing, allowing regular enzymatic treatment without the
enzyme ending up in the final product. Especially for enzymatic modifications
of milk components, a membrane reactor offers much potential.
B
I
O
T
E
C
H
N
O
L
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
O
Organisation/Firm
Agrotechnology & Food Innovations b.v.
Dr
Charon
Zondervan
Phone:
Fax:
E-mail:
31-317-475337
31-317-475347
[email protected]
G
Title:
First Name:
Surname:
Address:
Y
PO Box 17, 6700 AA
Wageningen, The Netherlands
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
86
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
D
B
I
O
T
E
C
H
N
O
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Y
Pagina 87
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100 Technology Offers stemming from EU biotechnology RTD results
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O
O
D
1 6 . Construction of non-GMO lactic acid
bacteria with the capacity to produce
dairy products with increased vitamin B2
content
B
Title of result:
I
Construction of non-GMO lactic acid bacteria with the capacity to produce dairy
products with increased vitamin B2 content.
O
Ownership: University College Cork
T
T EC H N O LO GY D E S C R I PT I O N
E
Abstract of the technology:
C
H
N
This technology exploits the natural capabilities of certain bacteria to produce vitamins. In this case lactic acid bacteria were used to select non-GMO variants with an intrinsic capacity to overproduce vitamin B2 (riboflavin) in their growth medium. Such variants can readily be obtained from a variety of different lactic acid bacteria and may be used for in situ vitamin production of dairy products with
enhanced vitamin B2 content.
O
Detailed description of the technology:
L
O
G
Y
Bacteria possess many biosynthetic pathways, including those that lead to the production of various B
vitamins. The ability of bacteria to produce vitamins has been exploited and the described technology
offer extends the application of vitamin production in situ in food and dairy products. For this purpose,
certain lactic acid bacteria which had been shown to possess the biosynthetic pathway to produce vitamin B2 (riboflavin) were exposed to a toxic vitamin B2 analog. This allowed the isolation of a number
of spontaneous and stable variants that overproduced vitamin B2 and that secreted this vitamin into the
growth medium. Animal depletion models showed that products derived from such bacteria can indeed
restore a vitamin B2 deficiency and demonstrate the potential of bacteria that have been used in the production of fermented foods for thousands of years can be used as an in situ delivery system for B2 vitamin. The technology is in principle suitable for other B vitamins as well, provided that the bacterium in
question possesses the biosynthetic pathway for the vitamin. Further detailed information can be
obtained by reading the following literature:
LeBlanc, J.G., Burgess, C., Sesma, F., Savoy de Giori, G. and D. van Sinderen. (2005) Improvement of the
Riboflavin Status of Rats by Ingestion of Milk Fermented by Lactococcus lactis. J. Dairy Sc. 88: 3435-3442
Le Blanc, J. G., Burgess, C., Sesma, F., Savoy de Giori, G. and D. van Sinderen. (2005) Riboflavin overproducing Lactococcus lactis strains are capable of improving the riboflavin status in deficient rats. Brit.
J. Nutr. 2: 262-267.
Burgess, C., O’ Connell-Motherway, M., Sybesma, W., Hugenholtz, J., and D. van Sinderen. (2004)
Riboflavin production in Lactococcus lactis: potential for in situ production of vitamin-enriched foods?
Appl. Environ. Microbiol., 70: 5769-5777.
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41cq77_one_hundred
L
O
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
O
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
G
Current stage of development of the technology:
H
C
Since vitamin B2 overproduction has been described in literature for other bacteria not used ion food production, the technology is currently not covered by
a patent.
T
Comments:
Patents granted
Partnership/other contractual agreements
E
Patents applied for but not yet granted
Exclusive rights
License agreement reached
N
Intellectual Property Rights
I
The technical know-how to generate vitamin B2 overproducers is available
from existing literature, the novelty of the above described technology lies in
the application of producing the vitamin in situ in the food product. Moreover,
a similar strategy may in principle be applied for other B vitamins.
B
Innovative Aspects
Main advantage
O
Exploitation potential
Dr
Douwe
Van Sinderen
Phone:
Fax:
E-mail:
+ 353 21 4901365
+ 353 21 4903101
[email protected]
O
Title:
First Name:
Surname:
Address:
University College Cork,
Department of Microbiology,
Western Road, Cork, Ireland
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
F
O
Organisation/Firm
University College Cork
D
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
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O
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1 7. I m m u n o m o d u l a t i n g ch a r a c te r i s t i c s o f
L a c to b a c i l l u s f e r m e n t u m s t r a i n s
D
Title of result:
Immunomodulating characteristics of Lactobacillus fermentum strains
Ownership: Probiomics Ltd
B
I
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
T
E
C
H
N
O
The aim of the LABVAC program within FP4 was to utilize Lactobacillus strains as delivery vehicles
for oral vaccines and to identify strains with enhanced adjuvant capacity. Within this program, the adhesion of various Lactobacillus strains to the immuno sampling sites of the small intestine, namely the Peyers Patches, was investigated and it was shown that some strains had a greater affinity for these sites than
the others and that adhesion correlated with an enhanced adjuvant activity. These aspects have been
extended to examine the Lactobacillus strains when used without vaccine antigens and a Lactobacillus
fermentum strain with high affinity for the Peyers Patches has been identified and shown to have a range
of clinical benefits in trials as well as shown to have immunomodulating activity. Studies continue to
explore the mechanisms of function in terms of the intestinal microbes and the immune responses triggered. Partnerships are sought to develop applications of these findings to food and OTC pharmaceuticals as well as basic mechanistic studies to lead to an understanding of function and to pave the way
for future product development.
L
O
Detailed description of the technology:
G
Y
Probiotics. Their role in immunomodulation and extraintestinal conditions as well as intestinal disturbances. Probiotics can have antimicrobial activity and can modulate the immune system. When functioning in the intestine, many health benefits can be achieved. It is now apparent that the entire body
benefits from good intestinal health and specific probiotics can play a beneficial role in a vast range of
conditions outside of the intestine at most mucosal sites. Probiotics are oral preparations of live
microbes, generally Lactobacillus and Bifidobacterium strains, that excert a beneficial effect on the host
by exerting an antagonistic activity against disease causing bacteria an/or by immunomodulation. In
recent years it has been recognised that not all Lactobacillus and Bifidobacterium strains are the same
and that a new generation of probiotic strains is emerging. These new probiotic strains of Lactobacillus
are well characterised and shown in scientifically valid clinical trials to be effective for particular applications. Some specific probiotic strains have been shown to colonise the intestine and reduce levels of
harmful bacteria and have been shown to effectively reduce the symptoms of a range of gastrointestinal
conditions. The colonisation of the intestine can be enhanced if the probiotic strain can attach to the
intestinal mucosa. This attachment has been shown to enhance immunomodulation by the probiotic
strain and in fact one probiotic strain, Lactobacillus fermentum PCCTTM has been shown in laboratory
studies to specifically attach to the immunosampling site of the intestine, namely the Peyers Patches.
Furthermore, modulation of the intestinal microbes can influence conditions outside the intestine.
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L
O
N
H
C
Potentially harmful bacteria can produce metabolites that can pass trough the intestinal mucosa. For
example, endotoxins produced by some of the intestinal microbes can pass the intestinal mucosa and
lead to endotoxaemia and liver damage. Probiotics that help maintain or re-establish beneficial microbes
in the intestine; may therefore play a role in reducing the severity of a number of conditions not identified as disturbances of the intestine but rather have been shown to be linked in some way to the intestinal microbes eg autism and chronic fatigue syndrome. As the list of potential applications of probiotics increases, it could raise concerns that a single preparartion can not be effective against such a wide
range of applications. However, by understanding that the probiotic strains may have the capacity to
modulate both the intestinal microbes and the immune system, including both protective antibodies and
antibodies linked to allergic responses, as well as cytokines which can down-regulate inflammation, a
wide range of conditions could potentially be targeted with probiotics and influenced by intestinal
health.
G
Y
41cq77_one_hundred
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T
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
I
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
E
Current stage of development of the technology:
Intellectual Property Rights
Patents granted
Partnership/other contractual agreements
B
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Innovative Aspects
Main advantage
The particular strains of Lactobacillus fermentum has been trademarked as
PCC® and has an extensive scientific dossier supported by numerous clinical
trials addressing gastrointestinal health and immunoregulation. The whole
organism is currently being commercialised in Australasia while the mechanistic studies which provide insight in functional aspects support the product
develop programme.
91
F
Exploitation potential
O
O
D
Comments:
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O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
O
D
Organisation/Firm
Probiomics Ltd
Address:
B
Australian Technology Park
1 Central Ave, Eveleigh, NSW 1430,
Australia
Organisation Type: University
Industry
Title:
First Name:
Surname:
A/Prof.
Patricia
Conway
Phone:
Fax:
E-mail:
+612 9202 4526
+612 9209 4256
[email protected]
Research Institute
Start-up company
Other SME
I
Organisation size: < 50 employees
50-249 employees
250-500 employees
>500 employees
O
T
A P P L I C AT I O N D O M A I N S
E
C
H
N
O
L
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Y
92
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Probiotics
D
B
I
O
T
E
C
H
N
O
L
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Y
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100 Technology Offers stemming from EU biotechnology RTD results
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1 8 . S w i t ch i n g t h e m o d e o f m e ta b o l i s m i n
b a ke r ’ s y e a s t , S a cch a ro m y ce s
ce re v i s i a e , f ro m f e r m e n ta t i o n
to re s p i r a t i o n
B
Title of result:
I
Switching the mode of metabolism in baker’s yeast, Saccharomyces cerevisiae, from
fermentation to respiration.
O
Ownership: Gothia Yeast Solutions AB
T
T EC H N O LO GY D E S C R I PT I O N
E
Abstract of the technology:
C
H
N
O
Relevant natural hexose transporters in yeast were deleted and replaced by an artificial chimeric hexose
transporter composed of parts of Hxt1 and Hxt7. In the presence of high sugar concentrations such
constructs produce negligible amounts of ethanol, and other by-products, while the growth rate is
maintained as high as 70-85% of wild type levels depending on the strain background. Even more relevant for the potential use of such strains for production of heterlogous proteins and also of low alcohol beverages is that the biomass yield increased up to 50% in mutants compared to their parental
strains. The new strains offer improved product yields in processes with simplified process control.
L
Detailed description of the technology:
O
G
Y
For many years, the construction of a S. cerevisiae strain that does not produce ethanol even at high
sugar concentrations has been a goal for the scientific community. In the field of biotechnology, ethanol
formation is often undesirable as it lowers the yield of biomass. This is a serious drawback when using
S. cerevisiae as a host for the production of, e.g. heterologous proteins and other high-value products.
Traditionally, in industrial applications different kinds of process control has been implemented in order
to keep the sugar concentration low and thereby prevent ethanol formation. However, this is costly and
a strain offering the possibility to avoid sophisticated control schemes would be of great benefit to
industrial biotechnology. Until now all efforts to make non-ethanol producing S. cerevisiae strains suitable for biotechnological applications have failed. Previous attempts have generated strains with only a
minor decrease in ethanol production and/or a very low growth rate making them unsuitable as production organisms. The recently described respiratory Saccharomyces cerevisiae KOY.TM6*P strain is
to our knowledge the first reported strain of S. cerevisiae (a second strain has recently been transformed
accordingly; see below), which almost completely redirects the flux of glucose from ethanol fermentation to respiration even at high external glucose concentrations (OTTERSTEDT K., LARSSON C.,
BILL R., STĀHLBERG A., BOLES E., HOHMANN S., GUSTAFSSON L. (2004) Switching the
mode of metabolism in the yeast Saccharomyces cerevisiae. EMBO Reports. 5:532-537; ELBING K.,
LARSSON C., BILL R.M., ALBERS E., SNOEP J.L., BOLES E., HOHMANN S., GUSTAFSSON
L. (2004) Role of hexose transport in control of glycolytic flux in Saccharomyces cerevisiae. Appl. Envi-
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ronment. Microbiol. 70: 5323-5330; ELBING K., STĀHLBERG A., HOHMANN S., GUSTAFSSON
L. (2004) Transcriptional responses to glucose at different glycolytic rates in Saccharomyces cerevisiae.
Eur. J. Biochem. 271: 4855-4864). In the KOY.TM6*P strain, portions of the genes encoding the predominant hexose transporter proteins, Hxt1 and Hxt7, were fused within the regions encoding their
transmembrane (TM) domains 6. The resulting chimeric gene, TM6*, encoded a chimera composed of
the amino-terminal half of Hxt1 and the carboxy-terminal half of Hxt7. It was subsequently integrated
into the genome of an hxt null strain. In a subsequent study (HENRICSSON C., DE JESUS
FERREIRA MC., HEDFALK K., ELBING K., LARSSON C., BILL RM., NORBECK J.,
HOHMANN S., GUSTAFSSON L., (2005) Engineering of a Novel Saccharomyces cerevisiae Wine
Strain with a Respiratory Phenotype at High External Glucose Concentrations. Appl. Environment.
Microbiol. In press.) we have demonstrated the transferability of this respiratory phenotype to the V5
hxt1-7∆ strain, a derivative of a strain used in enology. We also show by using this mutant that it is not
necessary to transform a complete hxt null strain with the TM6* construct to obtain a non-ethanol producing phenotype. The resulting V5.TM6*P strain, obtained by transformation of the V5 hxt1-7∆ strain
with the TM6* chimeric gene produced only minor amounts of ethanol when cultured on external glucose concentrations as high as 5%. Despite the fact that the glucose flux was reduced to 30% in the
V5.TM6*P strain compared with that of its parental strain, the V5.TM6*P strain produced biomass at a
specific rate as high as 85% of the V5 wild type strain. Even more relevant for the potential use of such
a strain for production of heterlogous proteins and also of low alcohol beverages is that the biomass
yield increased by 50% in the mutant compared to its parental strain.
G
Y
41cq77_one_hundred
D
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
O
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
B
Current stage of development of the technology:
Intellectual Property Rights
O
Patents granted
Partnership/other contractual agreements
F
Patents applied for but not yet granted
Exclusive rights
License agreement reached
95
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100 Technology Offers stemming from EU biotechnology RTD results
F
O
Exploitation potential
O
Innovative Aspects
Main advantage
D
B
I
O
Gothia Yeast Solutions offers Saccharomyces cerevisiae strains, TM6*, as a
production platform in various areas of biotechnology. The main advantage of
such strains is that they maintain a fully respiratory metabolism also at high
sugar concentrations while the growth rate is still as high as 70%-855 of the
wild-type levels. Strain with such characteristics have not been available before
and they offer the possibility of acquiring a high biomass yield and no formation of ethanol without using a controlled sugar feed. The TM6* strains characteristics are valuable for production of, e.g. heterologous proteins including
membrane proteins. General features of using S. cerevisiae as production host
are its ease of cultivation but also its GRAS status, which makes the purification procedure less rigid. Another area where the TM6* characteristics would
be of great advantage is in the production of low or non-alcoholic beverages.
T
E
C
H
N
O
L
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
O
Title:
First Name:
Surname:
Organisation/Firm
Gothia Yeast Solutions AB
Professor
Lena
Gustafsson
G
Address:
Y
Address:
Terassgatan 7
411 33 Göteborg , Sweden
Organisation Type: University
Organisation size: < 50 employees
Phone: 46 31 773 2597
Fax:
46 31 773 2599
E-mail: [email protected]
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
96
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
D
B
I
O
T
E
C
H
N
O
L
O
G
Y
Pagina 97
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12:54
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100 Technology Offers stemming from EU biotechnology RTD results
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O
O
1 9 . D e v i s e g e n e t i c te s t f o r e xce s s g l y co g e n
co n te n t i n p i g m u s c l e
D
Title of result:
Devise genetic test for excess glycogen content in pig muscle
Ownership: Swedish University of Agricultural Sciences
B
I
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
T
E
C
A SNP haplotype was identified that shows complete association with the RN-mutation. Further analysis of the chromosomal region showing complete association to the RN locus revealed the causative
gene and the causative mutation, a missense mutation (R200Q) in the PRKAG3 gene. A diagnostic test
based on the pyrosequencing method has been established and is currently applied in several Hampshire
populations.
H
Detailed description of the technology:
N
O
L
O
G
The use of SNP haplotype analysis for analysing the RN region in pigs. Five SNPs from the RN region
were identified. The SNPs occur both in coding sequences and in random genomic DNA isolated from
BACs maping to the RN region. Three SNPs were used to screen a random sample of about 100 purebred Hampshire which have been typed for RN status using glycogen measurement. Two alleles occur
at the RN locus, the recessive rn+ allele associated with normal glycogen values and the dominant RNallele associated with high glycogen values. A SNP haplotype was identified that show complete association with the RN- mutation. Further analysis of the chromosomal region showing complete association to the RN locus revealed the causative gene and the causative mutation, a missense mutation
(R200Q) in the PRKAG3 gene. A diagnostic test based on the pyrosequencing method has been established and is currently applied in several Hampshire populations.
Y
Current stage of development of the technology:
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : results of demonstration trials available
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41cq77_one_hundred
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Intellectual Property Rights
O
O
Patent: PCT/FR00/02500 Variants of the gamma chain of AMPK, DNA
sequences encoding the same, and uses thereof.
B
I
O
T
E
C
H
N
Comments:
Patents granted
Partnership/other contractual agreements
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Prof
Leif
Andersson
Phone:
Fax:
E-mail:
+4618 4714 904
+4618 4714 833
[email protected]
O
Title:
First Name:
Surname:
Address:
Uppsala Biomedical Center
S-75124 Uppsala, Sweden
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
F
O
Organisation/Firm
Swedish University of Agricultural Sciences
D
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
99
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Te c h n o l o g y
© stockbyte, 2000
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100 Technology Offers stemming from EU biotechnology RTD results
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E
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N
1 . N M R s t r u c t u re s o f m e m b r a n e p ro te i n s ,
co m p l e x e s a n d l i p i d a s s e m b l i e s ;
A d e d i ca te d w i d e - b o re u l t r a h i g h f i e l d
M A S N M R s p e c t ro m e te r f o r b i o l o g i ca l
re s e a rch
O
Title of result:
L
750 MHZ wide bore NMR spectrometer, probes and accessories for microimaging
O
Ownership: Bruker BioSpin GmbH
G
T EC H N O LO GY D E S C R I PT I O N
Y
Abstract of the technology:
A new ultra high field and wide bore NMR spectrometer operating at 17.6 Tesla (750 MHz proton resonance frequency) i.e. a system based on a newly developed highly homogeneous superconducting
magnet system with 89mm room temperature bore has been developed. The increase of field strength
combined with the large access bore facilitate higher sensitivity and dispersion, essential for biological
solid state NMR, including magic angle spinning (MAS), and for magnetic resoance microscopy (microimaging). New improved pulse programming and pulse sequence execution capabilities were developed
for this system as required particularly for the intended solid state experiments. A new generation of
flat-coil solid state NMR probes and of triple resonance NMR probes, optimized for protein analysis
at ultra high magnetic field at variable temperatures was realized. Furthermore, micro-imaging facilites
for applications involving small objects up to 30 mm diameter at ultra high field have been developed
and implemented for applications involving small animal models (mice, fish, chicken embryos) e.g. to
resolve the relationship between the genetic program and biological functionality. Since the system
operates at highest magnetic field strength available for a wide bore configuration with imaging capabilities, it is the most powerful magnetic resonance microscope in the world. Furthermore, it represents
the state of the art in the field of solid state NMR in the context of material and biological sciences. The
system does not rely on any additional technology and is fully self-sustained. All these new products
have immediately been made commercially available. Several orders for the new spectrometer have
already been received. The groundbreaking results obtained during the demonstration project have in
addition resulted in a dramatic increase in further scientific research in biological solid state NMR and
in addition in a large interest in the new probe technologies for common solids NMR spectrometers and
in high field solid state NMR spectrometers in general.
Detailed description of the technology:
A new ultra high field 750MHz wide bore NMR spectrometer and significant accessories have been
developed as products and represent the state-of-the-art. It represents the first ultra-high field NMR
spectrometer which has been built. Previous highest field reached for a wide bore magnet was 600MHz
or 14T. It's main part has been the 17.6 Tesla wide bore 89mm rtb magnet system. The magnet was been
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Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
Exploitation potential
Innovative Aspects
Main advantage
Marketing started as soon as the demonstrator was ready for measurements.
The exploitation is successfully in progress, 6 system orders for the
AVANCE750WB were already received till the mid of 2003. The typical application is in structural genomics, high resolution NMR imaging of animals and
materials science such as in Nanotechnology, and we already experience a
strong interest in the new technology.
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designed and constructed within the time frame planned on the first attempt and meets or exceeds the
project plan specifications i.e. in respect to magnetic field strength, field homogeneity, and magnetic
drift rate (<3Hz/h). The system electronics and acquisition software of the state-of-the-art high field
AVANCE spectrometers were further developed to meet the requirements for solid state NMR for the
AVANCE750 'wide bore' as defined in the project.
- New improved pulse programming and pulse sequence execution capabilities (very fast phase shifts)
were realised by hardware improvements in the pulse sequence generation and by improved acquisition control software. Applications programs were implemented for common and the new pulse
sequences.
- Higher stability, linear amplitude control over >90dB, and over a broadbanded frequency range of 30325MHz at kilowatt rf output power level were achieved by new transistorized high power amplifiers.
- A new generation of double resonance and triple resonance solid state NMR probes was developed
with flat coil and MAS versions, optimized for operation at ultra high magnetic field. The rotor diameters for the MAS probes includes 2,5mm, 4mm and 7mm with spinning speeds of up to 15 and
35KHz and VT ranges starting from below -100°C going up to over +100°C.
- A new microimaging probe for 1H imaging at 750MHz was developed for small objects/animals up
to 30 mm diameter. Pulse sequences for applications involving small animal models (e.g., chicken
embryos and mice) were implemented.
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CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
C
H
Organisation/Firm
Bruker BioSpin GmbH
N
Address:
Silberstreifen,
D-76287 Rheinstetten, Germany
Title:
First Name:
Surname:
Dr.
Gerd
Wolff
Phone:
Fax:
E-mail:
+49 (721) 5161-151
+49 (721) 5161-297
[email protected]
O
Organisation Type: University
L
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
O
G
A P P L I C AT I O N D O M A I N S
Y
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Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
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2 . P h a g e d i s p l a y o f Pe p t i d e / M H C co m p l e x e s
C
Title of result:
H
Phage display of Peptide/MHC complexes
N
Ownership: Université Pitié-Salpétrière
O
T EC H N O LO GY D E S C R I PT I O N
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Abstract of the technology:
O
G
Y
Characterizing peptide (P) epitopes targeted by Major Histocompatibility Complex (MHC)-restricted
T cells of unknown specificity would have broad implications. During the course of this work we have
validated an original strategy based on the utilization of a phage displayed library of P/MHC complexes. We show that soluble MHC molecules associate with peptides presented by a phage, thereby resulting in the formation of multivalent P/MHC phages. As proof of concept, we have used this strategy to
select mimotopes of T cell epitopes presented by murine MHC. This strategy opens up new perspectives for antigen discovery and the manipulation of T cell responses. Our next goal is to characterize
mimotopes and epitopes targeted by human T cells of unknown specificity (such as T cells infiltrating
human tumors).
Detailed description of the technology:
Complex formation is stabilized by the interaction of the soluble partner (MHC) with two components,
P and ß2-microglobulin (ß2m), both of which are covalently linked to the phage. The association step
between P and MHC is accomplished by incubating phage presenting peptides in the presence of a high
concentration of soluble MHC. During this incubation step, peptides presented by the phage are able
to displace peptide associated with soluble MHC. Exchange is favored by the fact that peptides
endowed with a high affinity for H-2Kb are not included in the preparation of the soluble H-2Kb dimers
that we used. For the construction of the libraries, we randomized six positions in the sequence of the
wild type peptide OVA while respecting the anchor positions of H-2Kb. Clones are selected within the
phage libraries according to their ability to bind targets of interest (Antibody, Soluble TCR or T cell).
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
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Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
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Intellectual Property Rights
O
Patents granted
Partnership/other contractual agreements
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E
Main advantage
First description of peptide libraries presented on the surface of bacteriophages
in the context of class I MHC.
Determination of the idiotypic specificity of a T-lymphocyte using classical
methods remains a laborious undertaking without guarantee of success. The
procedure described here has a low cost and screening is performed within a
few days.
H
Innovative Aspects
C
Exploitation potential
N
O
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Title:
First Name:
Surname:
Organisation/Firm
Université Pitié-Salpétrière
Address:
Unité Inserm 543, Cervi
Centre Hospitalo-Universitaire
Pitié-Salpétrière
83 Bvd. De L’hopital
75013 Paris, France
Organisation Type: University
Organisation size: < 50 employees
Industry
Phone:
Fax:
E-mail:
MD. Ph.D
Guy
Gorochov
33 1 42 17 75 07
33 1 42 17 74 90
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Antigen discovery
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100 Technology Offers stemming from EU biotechnology RTD results
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Title of result:
O
MULTIBARRIER for the in situ treatment of groundwater contaminated by mixed pollutants
L
Ownership: Flemish institute for technological research, Vito
O
T EC H N O LO GY D E S C R I PT I O N
E
3 . M u l t i b a r r i e r f o r t h e i n s i t u t re a t m e n t
o f g ro u n d w a te r co n ta m i n a te d b y m i x e d
p o l l u ta n t s
C
G
Abstract of the technology:
Y
The developed MULTIBARRIER is a Permeable Reactive Barrier based on the combination of different physical (e;g. adsorption), chemical (e.g. reduction, oxidation) and biological (e.g. biodegradation,
bioprecipitation) processes. In the PRB several carrier materials are used. The carrier materials carry
bacterial biofilms and can play a role in the detoxification process. The development was based on the
combination of the processes and materials and their compatibility. In the presented system a groundwater mixture based on BTEX, VOCLs and heavy metals (Zn, As) could completely be treated (biodegraded or precipitated). Every combination of pollutants needs a tailor made MULTIBARRIER
concept. The partners understand the mechanisms in a way that successful combinations of materials
and bacteria can lead to the full treatment of the groundwater. The MULTIBARRIER system can be
applied for treatment of groundwater contaminated by the leachates from landfills or contaminated by
complex industrial megasites (e.g. gasmanufacturing plants).
Detailed description of the technology:
In order to remediate contaminated groundwater, many techniques have been developed and applied.
However, although groundwater is often polluted with complex mixtures of different chemicals, most
remediation techniques only deal with one or a few pollutant types. Sanitation of groundwater polluted with mixtures of hazardous compounds has received wrongly less attention and remains a problem.
A combination of different existing technologies may be a solution, but one should consider (I) the
impact of one remediation technique on another one and (II) the influence of co-contaminants on the
removal efficiency of the processes. The study focuses on MULTIBARRIERs, i.e. permeable reactive
barriers in which different pollutant removal processes (biological and physicochemical processes) are
combined to treat in situ groundwater containing mixed pollutants. Different MULTIBARRIER concepts to treat groundwater were designed, evaluated and compared. One of the objectives of the study
was to answer the question whether the removal processes should be applied one after the other
(sequential MULTIBARRIER), or whether a combination of different processes in one zone (mixed
MULTIBARRIER) is also possible. The latter may require more optimisation but the installation is
expected to be less complex and less expensive. Another important question concerns the choice of the
terminal electron acceptors (TEA) for the biological process.
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In the future MULTIBARRIER concepts for treating complex mixed pollutions, such as groundwater
polluted with leachate, will be developed and tested.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
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In a first stage of this work, lab-scale batch and column tests were set-up to evaluate several sequential
and mixed MULTIBARRIERS. A model pollutant mixture was defined consisting of (i) the heavy metals zinc (5 mg/l) and arsenate (0.2 mg/l), (ii) the chlorinated ethenes PCE (2 mg/l) and TCE (5 mg/l),
and (iii) the aromatic hydrocarbons benzene, toluene and m-xylene (BTX, 2 mg/l each). The investigated pollutant removal processes were reductive dehalogenation of the chlorinated aromatic hydrocarbons (CAHs) with zero valent iron, sorption/reduction of the metals and biodegradation of BTmX and
also someCAHs. In the biobarrier oxygen, nitrate, sulfate as well as iron were tested as terminal electron acceptor (TEA). As oxygen and nitrate are known to have a negative influence on the performance
of zerovalent iron, only sequential MULTIBARRIERS (Fe0 + BIO) were tested with these TEAs. In all
concepts, the sorption part was considered mainly as a pollishing step. In one column set-up the Fe(III)
generated during corrosion of the zerovalent iron was present as only TEA. Both mixed and sequential MULTIBARRIER configuration showed to be suitable for sanitation of mixed groundwater polution. Indications were found for an impoved removal in mixed systems. In all tested MULTIBARRIER
concepts chlorinated ethenes and heavy metal removal was observed when zerovalent iron was present,
except in the columns where Fe(III)EDTA was added as TEA. Biodegradation of BTmX was observed
under aerobic, denitrifying and iron reducing conditions, but to a much lesser extend when sulfate was
present as TEA. In a second stage of this work, a partially mixed MULTIBARRIER was installed on
pilot scale in a container system (5m x 2.4 m x 2.4 m) in which an aquifer is simulated. The tested
MULTIBARRIER consists of a mixed Fe0+BIO zone followed by an anaerobic BIO-zone and a sorption zone. Iron (III) originating from the corrosion of the zerovalent iron was selected as TEA. Besides
monitoring of the chemical composition of the goundwater and the field parameters, in situ mesocosm
socks and molecular techniques like PCR-DGGE are being used to monitor changes in the microbial
population in the different zone.
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Exploitation potential
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Innovative Aspects
H
N
Main advantage
O
The MULTIBARRIER allows that passive in situ groundwater treatment systems can be applied to treat complex mixtures of pollutants (need normally different techniques). The concept must always be tailor made in function of the
application.
The MULTIBARRIER replaces a train of techniques by one integrated, tailor
made, system. This makes risk management of (mega)sites, polluted by complex mixtures of pollutants (even organics and inorganics) feasible and much
cheaper compared to other techniques.
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CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
Flemish institute for technological research, Vito
Address:
Boeretang 200
B 2400 – Mol, Belgium
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Dr.
Ludo
Diels
Phone:
Fax:
E-mail:
00 32 14 33 69 24
00 32 14 32 65 86
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
110
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
H
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O
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Y
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100 Technology Offers stemming from EU biotechnology RTD results
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4 . Liquid Gallium Cooled Rotating,
Anode X-ray Diffraction Application
H
Title of result:
N
Liquid Gallium Cooled Rotating Anode X-Ray Generator for X-ray Diffraction Applications
Ownership: General High Voltage Industries Ltd.
O
L
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
G
Y
A novel type of X-ray generator which is practically service-free.
The main application will be determinations of the structure of proteins (i. e. Sturctural Genomics) but
also material research.
Detailed description of the technology:
Novel type of X-ray generator is close to the demonstration phase.
1. 12 kWatt HV generator including a microprocessor based controller for automatic operation and
diagnosis
2. A rotating anode, the heart of the system, which constitutes the novelty of the design: a layer of liquid Gallium/Indium is the heat transfer and hearing components.
3. A novel type of cathode excels by a proven extremely long lifetime.
4. A special type of focusing optics to concentrate the X-rays on the protein crystal.
The main goal of the project is a service-free automatic x-ray generator which delivers higher intensities
by a higher cooling effiency and by focusing of the X-rays This enables the collection of higher resolution data in a shorter time.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
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Partnership/other contractual agreements
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Exploitation potential
The special design of this new generator has following advantages:
Main advantage
- No rotating feed-through of axis prone to air leakage
- No mechanical bearings: hydrostatic bearing based on liquid metal lubrication
- Very long lasting cathode (5 years) instead of only one month for presently
used Tungsten filaments.
- Practically free of service under continuous running conditions.
- Higher maximum power: 13 kWatt instead of 5kWatt of conventional
instruments.
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E
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N
O
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Innovative Aspects
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
General High Voltage Industries Ltd.
Address:
New Road, Highley, Bridgnorth,
Shropshire WV16 6NN, U.K.
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Dr.
Jules
Hendrix
Phone:
Fax:
E-mail:
+44 (1746) 862 555
+44 (1746) 862 666
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Molecular Biology
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100 Technology Offers stemming from EU biotechnology RTD results
T
H
N
Title of result:
O
Information system program for registration, storing and communicating information on
immunisations
L
Ownership: Swedish Institute for Infectious Disease Control
O
T EC H N O LO GY D E S C R I PT I O N
E
5 . I n f o r m a t i o n s y s te m p ro g r a m f o r
re g i s t r a t i o n , s to r i n g a n d co m m u n i ca t i n g
information on immunisations
C
G
Abstract of the technology:
Y
A web-based information system program for registration, storing and communicating information on
immunisations. The system, which was developed and field tested in the EUSAFEAC project, is
designed to provide a life long record of all immunisations administered to an individual, to facilitate
follow-up of immunisation programs and to facilitate management of information by providers of
health care. It could be used as a module in a medical records system or as a stand alone system for
immunisation programs. The system is designed for use at district, regional or national levels. Functions
in the system include:
• Planning of immunisations
• Call of vaccinees
• Registration of vaccinations
• Printing of immunisation certificate
• Statistics on immunisations
• Documentation and reporting of adverse event following immunisation
• Regulation of data access depending on assignment
• Logging for documentation of use of data
The system is available in Swedish and English versions and has a function for translation into other languages.
Detailed description of the technology:
Svevac is built using a multi-tiered web based architecture with the aim of making a database independent application with good scalability, maintainability, performance and a sound component based structure. The tiers used in the system are presentation, business logic, helpers, persistence control and database. The presentation tier separates the presentation code and user interface from business logic in
order to make the architecture more modular and easier to maintain. The business tier performs all calculations and decision-making. The helpers tier handles security, access control, and resource and localization management. All data base access is performed in one tier which is in it's turn used by the persistence control layer to map all persistent objects to the database. All the components are built using
an interface approach, making them easy to replace with other components implementing the same
interfaces. Since Svevac is a web-based application, the users must have web browsers as client front
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ends. The application is developed and tested for Internet Explorer 5.5 and higher, Netscape 6 and
Mozilla 1.0. Client script must be enabled. In order to get full functionality on pages that access external information Adobe Acrobat Reader (version needed depends on the external material’s current version) is required. All functions in the application are adapted for a screen resolution of at minimum
800x600 pixels, but a higher resolution is recommended, in order to avoid scrolling. All user interface
design is separated from code using the code-behind technique available in Microsoft.Net. All layout
specific formatting is as far as possible located in separate style sheets. The client code is written using
ECMA/Javascript. The server programming is in C# using Microsoft.NET framework v1.1 and the
database management system is Microsoft SQL Server 2000. Note that no stored procedures are used
to maintain database independent design. All communications with the database goes via the database
mappings/persistence layer and is dispatched to the component that in it’s turn handles architecture
independent database communication. The web server used is the Microsoft IIS5 under Windows 2000
(Server). In order to be able to use a load balancing and build a web farm, the Windows version must be
Advanced Server or higher. IIS should be secured using the IIS-lockdown utility and the system should
be updated with the latest critical updates and service packs. The communication between client and
server requires at least an ISDN (64/128 kbps) connection in order to get acceptable response times, but
ADSL (>512 kbps) is recommended.
All communication from the business logic and the user interface code behind goes through the database persistence layer, which in its turn calls the database communication layer. The persistence layer
performs the mapping of tables, keys and relations in the database to classes that can be used as objects
directly. All calls to the database are made in a transparent way to the client (programmer), which simplifies development, minimizes the task of creating queries to get data from the database and centralizes
all code to access the database. In order to get better performance, specialized SQL-queries can be
authored by programmers, and used for more efficient calculations and manipulations. The custom
queries are stored with the object they belong to in the persistence component to centralize maintenance
of the application. This way, developers can get both ease of use and performance. The database communication components allows access to multiple types of database engines and adapt transaction handling, type marshalling and other database specific traits transparently to the clients. A framework for
translations is used in which the persistence component uses the translation component without this
affecting any other components and tiers. Thus the translation is transparent to developers concerned
with other aspects of the application than the database tier. The framework allows for single persistence
objects to return different strings depending on the selected culture.
The communication with the web-server is secured using a SSL certificate to encrypt information and
thereby prevent information disclosure to third part, ensure data integrity and provide authenticity. To
prevent sensitive information to be disclosed from the clients, the browsers are instructed not to cache
(save information to memory or disc) pages with sensitive data on them. This is only a recommendation,
so there is no way to guarantee that the browser honours this. To guarantee that no caching is made on the
clients disc a setting in the browser (ideally disallowing caching of content transmitted over an encrypted
channel) should be made. All access to the information system is regulated using a password and role based
login schema. The users only gain access to the information that their current active role permits. Administrators can administrate users that have lower access than themselves, this enables the system to have
local administrators with administrative privileges on their own unit or in a region. After 45 minutes of
inactivity the user is automatically logged out, the time limit can be changed by altering the session time
out and should be set at as small amount as possible to increase risk of users forgetting to log out when
leaving their session unattended and thereby risk that unauthorized use occur. This should of course not
be done in such a fashion that usability of the application is severely impaired. The centralized storage of
G
Y
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data in one central database makes it easy to perform back up and restore on the system in case of system
malfunction. Also the problems with concurrent access are kept at a minimum because all concurrency
handling can be made at central places, in the database component and in the database manager itself. A
programme version with Public Key Infrastructure (PKI) is currently being field-tested.
The language module in the system is capable of handling multiple languages and character encodings.
It cooperates with the persistence layer and the database components and provides them with a language/locale aware way to get data from the database and mapping the requests to the correct resource
for the active language. Microsoft ASP.NET by default handles requests and responses using UTF8
(Unicode) and therefore the application can handle the majority of all character sets commonly used.
L
Current stage of development of the technology:
O
G
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Y
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
Swedish Institute for Infectious Disease Control
Address:
S:t Larsområdet, Byggn 10
221 85 LUND
SWEDEN
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Dr
Harald
Heijbel
Phone:
Fax:
E-mail:
+46 46 188035
+46 46 188041
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
Exploitation potential
A P P L I C AT I O N D O M A I N S
116
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Information System
H
N
O
L
O
G
Y
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6 . G e n e m i n i n g T M o f a d i v e rs i t y o f
t h e r m o s ta b l e a m y l o l y t i c e n z y m e s
H
Title of result:
N
GeneminingTM of a diversity of thermostable amylolytic enzymes
Ownership: Prokaria Ltd
O
L
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
G
Y
A proprietary genetic screening methodology based on PCR was developed using primers designed on
the bases of conserved regions defined by multiple alignments. Only 4 well conserved amino acids are
needed. The method was used on DNA from biomass samples as well as strains with good results for
starch degrading and starch modifying enzymes. About 1000 amylase-type genes were isolated and partially sequenced. They represent 174 genes coding for amylolitic enzymes, of which 169 belong to family 13. 137 genes are not found in databases (<98% identity) and therefore, regarded as new. Now 33
genes of the amylase family 13 are expressed, 27 novel enzymes were partially characterized, thereof, 13
enzymes have been fully characterized.
Detailed description of the technology:
This method is particularly good for screening for enzymes that are difficult to assay for in high through
put fashion. DNA from biomass or strains is screened by PCR and the obtained fragments are then
sequenced. The sequences is evaluated to avoid replication and known genes. Selected candidates are
chosen on the basis of novelty and on the basis of sequence characteristics known to relate to the
enzyme activities desired. This involves obtaining the complete gene from the sample by gene walking.
A major advantage of this approach is that the gene is already cloned and expressed relatively early and
the work has been spent on novel genes identified by conserved sequence characteristics.
The following table shows the key enzymes and genes that were discoverd in the program and are now
available for testing or further developement with interested parties.
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H
N
O
L
O
G
Expressed
10
2
1
4
1
3
1
1
4
E
C
4
2
7
33
T
Alpha amylasese
Alpha-glucosidase
Amylo-pullulanase
Branching enzyme
Cyclodextrin glucosyl transferase
Cyclomaltodextrinase
Unspecified glycosyl hydrolase (starch)
Glycosyl transferase
Maltogeneic amylase
Maltodextrin glucosyltransferse
Neopulllanase
Debranching enzyme
Glucoamylases family
Total
Number of genes
19
5
1
6
2
5
1
1
7
1
6
2
15
63
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Comments:
Patents granted
Partnership/other contractual agreements
Two patents covering the methodology of GenemingTM and some of the discovered novel genes have been applied for. Most of the enzymes and genes discovered were hoverver not published and are still proprietary property of Prokaria
end can therefore be lisenced exclusively.
Exploitation potential
Innovative Aspects
Main advantage
The methodology of GenemingTM has been proven very useful for discovery
of starch modifying enzymes and other gene families, including DNA polymerases and more. Prokaria has already used this approach in several inhouse
and customer projects with good success. Further main advantage is that the
enzymes can be preselected based on DNA sequence to ensure novelty and
avoid genes already published and patented by others.
119
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CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
C
H
Organisation/Firm
Prokaria Ltd
N
Address:
Gylfaflöt 5, IS-112 Reykjavik,
Iceland
Title:
First Name:
Surname:
Dr. CEO
Jakob
Kristjansson
Phone:
Fax:
E-mail:
+354-570-7908
+354-570-7901
[email protected]
O
Organisation Type: University
L
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
O
G
A P P L I C AT I O N D O M A I N S
Y
120
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
H
N
O
L
O
G
Y
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7. P o r ta b l e o n s i te a n a l y t i ca l s y s te m s
b a s e d o n f u l l y e l e c t r i ca l b i o ch i ps
H
Title of result:
N
Portable on site analytical systems based on fully electrical biochips
Ownership: eBiochip Systems GmbH
O
L
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
G
Electrical biochip techology using eBioChipSticks and minaturized measuring systems
Y
Detailed description of the technology:
Multichannel electrical read out of micro arrays made in silicon technology and loaded with DNA or
protein or hapten capturing molecules; automated processing of biochemical assays of ELISA type formats employing lab on a chip functions
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
Exploitation potential
Innovative Aspects
Main advantage
122
world wide technology leader , no competitor at market
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G
Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Address:
Phone:
Fax:
E-mail:
+48 (4821) 17-4221
+48 (4821) 17-4250
[email protected]
L
O
Dr.
Rainer
Hintsche
N
Fraunhoferstr. 1, 25524 Itzehoe,
Germany
Title:
First Name:
Surname:
O
Organisation/Firm
eBiochip Systems GmbH
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
T
E
A P P L I C AT I O N D O M A I N S
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8 . R o b u s t b i o s e n s o rs f o r p o l l u ta n t s
C
Title of result:
H
Robust biosensors for pollutants
N
Ownership: Consejo Superior De Investigaciones Científicas - Eez
O
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
O
G
Y
Pseudomonas putida DOT-T1E is a solvent tolerant microorganism able to grow in the presence of very
high concentrations of pollutants. This property allows the strains to survive in extreme niches and
enables us to develop biosensors. The sensor uses light emission, based on the lux genes whose expression is driven from the Pu or Phbx promoters. Transcription of these promoters is mediated by broad
effector-recognizing regulators such as XylR and HbpR. Compounds that have been successfully monitored include toluene, xylenes and other aromatic compounds.
Detailed description of the technology:
The most relevant development of this technology is that of high throughput mutagenesis and the selection process that allows us to extend the number of substrates recognized by the three-domain regulators, XylR and HbpR, to infinitum. The mutant regulators otherwise retain their ability to recognize
target DNA sequences and to promote high level transcription from its cognate promoter. When the
promoter is fused to the ‘lux genes light emission takes place. Several devices are under development so
that multiple pollutants at different concentrations can be monitored in a single assay, all at one go, by
determining the level of light output. A portable device will allow for in situ determination of pollutants.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
124
Patents granted
Partnership/other contractual agreements
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41cq77_one_hundred
O
Cheap and easy-to-use biomonitoring system.
T
E
C
H
N
O
L
Innovative Aspects
Main advantage
G
Exploitation potential
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
Consejo Superior De Investigaciones Científicas
- Eez
Title:
First Name:
Surname:
Prof.
Juan-Luis
Ramos
Address:
Phone:
Fax:
E-mail:
34 958 181608
34 958 135740
[email protected]
C/ Prof. Albareda, 1
E-18008 Granada – Spain
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Pharma
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
125
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9 . S T R E PTO M YC E S
C
Title of result:
H
1. Streptomyces: a suitable host for the production of heterologous proteins
N
2. Construction and screening of environmental DNA libraries for novel biocatalysts and
bioactive molecules
O
L
Ownership: Katholieke Universiteit Leuven
O
T EC H N O LO GY D E S C R I PT I O N
G
Abstract of the technology:
Y
1. For the production of recombinant proteins several hosts are available, but none is ideal for all kind
of proteins. Escherichia coli is often the first host of choice, but many heterologous proteins
expressed in E.coli are produced as insoluble protein aggregates in the cytoplasm or periplasm, hampering downstream processing. Gram-positive bacteria possess a proven excellent secretion capacity
increasing the chance for a correct folding of the proteins, and hence, reducing the downstream processing costs. Experience with Streptomyces showed that besides its use as producer of an extensive
array of secondary metabolites, it is also a valuable host for the production of industrially important
proteins. Streptomyces can be considered as an invaluable host for the production of a number of
eukaryotic proteins and industrial enzymes originating from other bacteria including extremophiles
or isolated from the metagenome (see below). It has been shown that some heterologous proteins are
secreted as biologically active compounds in a commercially significant yield (up to 300mg/L), they
can be easily purified and have the same characteristics as the native proteins. As a result, some of
these heterologous proteins are now in industrial production using expression/secretion signals we
have isolated. Moreover, we have shown that some proteins which could not be produced in E. coli
or Bacillus, could efficiently be secreted in Streptomyces.
2. The assessment and exploitation of the vast microbial diversity offers an almost unlimited resource
of new genes, gene products, and biosynthetic pathways for biotechnological and other purposes.
One of the major bottlenecks of conventional natural product discovery strategies is that the various
approaches depend on the screening of microbial products (e.g., enzymes and metabolites) from cultured organisms, and that less than 1 % of the microorganisms present in an environment can be cultivated by standard techniques. Consequently, molecular methods that do not rely on the isolation
of microorganisms have been developed. Our strategy is based on direct isolation of DNA from
environmental samples and then construction of complex gene libraries. For retrieval of novel products, the constructed so-called metagenomic libraries are then screened by sequence-based or function-based methods for genes encoding stable biocatalysts and other microbial products of interest.
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41cq77_one_hundred
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Comments:
Patents granted
Partnership/other contractual agreements
Streptomyces expression/secretion vectors and integrative vectors can be
obtained via license agreement. The same counts for screening the metagenomic libraries.
127
L
O
N
H
C
E
T
1. The consortium has an extensive experience in the use of Streptomyces lividans as a host for the production of proteins from different origin. To this purpose, the consortium has suitable
expression/secretion vectors at its disposal, which directs the proteins to the Sec- or Tat-dependent
secretion pathway. To test the production of proteins of interest isolated from different sources,
available vectors can be adapted when needed. Large scale production facilities are available to optimize growth and maximize production, eventually supported by DNA array analysis. Downstream
processing and structure determination to look for correct folding of the produced proteins and biological activity testing allows to further evaluating the production process.
2. The consortium has also much experience in isolating and developing novel biocatalysts and biomolecules for the use in chemical, agricultural, pharmaceutical and industrial applications from gene
libraries, which have been directly constructed from environmental habitats such as soil, sediments,
biofilms and extreme environments. To construct complex metagenomic libraries methods have been
developed that allow the isolation of high-quality DNA from environmental samples and the direct
cloning of the isolated DNA in various vector systems. In this way, more than 150 DNA libraries
from different environments have been already constructed. These libraries are ready to screen for
the genes of interest. To exploit the unknown microbial diversity stored in the generated libraries
methods to rapidly screen for new biocatalysts, novel metabolites, or drugs are at hand. Combined
with a high-throughput screening and DNA sequencing facility efficient enrichment, isolation, and
characterization of novel enzymes and pathways with traits required in a broad range of applications
can be performed. The genes isolated from the metagenome can be expressed in different expression
systems including in S. lividans.
O
G
Detailed description of the technology:
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Exploitation potential
C
Innovative Aspects
Main advantage
H
N
O
Notwithstanding its potential, Streptomyces is so far less well-known as a host
for heterologous protein production. It has, however several advantages as
mentioned above. Also larger proteins (~100 kDa) have been efficiently produced in this host.
Metagenome libraries are so far a rarely explored resource to mine for genes
coding for enzymes with novel properties and metabolites. Nevertheless,
results have shown that indeed enzymes can be isolated with new interesting
properties.
L
O
G
Y
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
Katholieke Universiteit Leuven
Address:
Rega Institute,
Minderbroedersstraat 10
3000 Leuven, Belgium
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Prof.
Jozef
Anné
Phone:
Fax:
E-mail:
(32-16) 337371
(32-16) 337340
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
128
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
H
N
O
L
O
G
Y
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C
10. Relationship between ABA and
sugar sensing
H
Title of result:
N
Relationship between ABA and sugar sensing
Ownership: University of Utrecht
O
L
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
G
Y
The sun6 gene was cloned and sequence analysis showed that the gene is identical to the previously
described abi4 gene. The sun6 mutant showed not only a sugar sensing phenotype when seeds were
placed on different sugars but was also able to germinate on concentrations of aba normally inhibitory
for wild type. Several known aba mutants were also able to germinate and develop on the sugar media
(6 % glucose and 7mM mannose) and several mutants that were isolated as sugar sensing mutants were
also able to germinate on aba.
Detailed description of the technology:
The sun6 gene mutant is able to germinate and develop on several sugar containing media. Adult sun6
plants also show a reduced 2-dglc-mediated repression of phtosynthesis, a glucose analogue that is a
substrate for hexokinase whereeas photosynthesis is strongly reduced in wt plants by 2-dGlc addition.
These studies suggest that the sun6 mutation results in the loss of an essential component of a sugar
induced signaling cascade that leads to down regulation of photosynthesis genes. The sun6 gene was
cloned and is identical to the abi4 gene. The abi4 gene encodes a putative AP2 domain transcription factor that is proposed to be involved in aba signal transduction. Several aba mutants (with a reduced aba
level) and abi mutants (with lowered sensitivity to aba) were tested for their sensitivity to mannose and
glucose. The aba and abi mutants displayed a reduced sensitivity to 5 mM mannose and 6 % glucose.
Current stage of development of the technology:
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Result is still in the basic research phase. Manipulation of abi4 gene is being
undertaken to determine how it can be used to improve plant performance.
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41cq77_one_hundred
G
Intellectual Property Rights
O
US patent 09/181,270 Plants with modified sugar sensing mechanism
O
Comments:
Patents granted
Partnership/other contractual agreements
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
Molecular Plant Physiology group, University
of Utrecht
Title:
First Name:
Surname:
Prof
Sjef
Smeekens
Address:
Phone:
Fax:
E-mail:
+31 30 2533184
+31 30 2533655
[email protected]
Padualaan 8, NL-3584 CH Utrecht,
The Netherlands
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
131
H
C
E
The potential application of the result is to increase yield in crops. The users of
the result are the plant breeding industry as well as the farmers that grow the
varieties. The main innovative feature is to use a single gene involved in regulation of carbohydrate metabolism which has a potentially profound effect on
overall plant growth and performance. Potential barriers are of scientific, technical, legal and commercial nature. First of all the potential value of the gene
needs to be determined then efficacy of the method(s) need to be confirmed in
different elite genetic background under field conditions. These field experiments need to be conducted over a number of years in different geographical
areas. The benefit must be exploitable i.e. there must be justification for a margin on the seed price which results in an acceptable rate of return level. Additionally in order to exploit the improved material it must be sure that licences
are in place preventing the blocking by third parties. As a final point, due to the
transgenic nature of the end product there is a high additional cost for registration research and the risk that the consumer avoid products of this nature.
T
Innovative Aspects
Main advantage
N
Exploitation potential
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H
N
1 1 . E m b r yo s a c s p e c i f i c g e n e s f o r
t h e g e n e r a t i o n o f f e m a l e s te r i l i t y a n d
the induction of
p a r t h e n o g e n e s i s / a u to n o m o u s
endosperm development
O
Title of result:
L
O
Embryo sac specific genes for the generation of female sterility and the induction of
parthenogenesis/autonomous endosperm development
Ownership: University of Hamburg
G
T EC H N O LO GY D E S C R I PT I O N
Y
Abstract of the technology:
Four highly homologous genes specifically expressed in the cells of the female gametophyte (embryo
sac) were identified in the project. Gene expression of all four genes is suppressed after IVF (in vitro fertilization) and expression in cells outside the embryo sac or in other tissues of maize could not be detected. The genomic upstream sequences of two genes, probably containing all the regulatory sequences,
which drive the very specific expression of the genes, were isolated. These regulatory sequences can now
be used to drive the expression of e.g. toxin genes or regulatory genes in the cells of the embryo sac,
with the aims to ablate the embryo sac and thus obtain a seedless fruit/sterile seeds, to obtain seeds with
an apomictic embryo, while the sexual embryo is absent or to induce autonomous embryo (parthenogenesis) or endosperm development (autogamy), which are components necessary to engineer the
apomixis trait.
Detailed description of the technology:
The results are regulatory sequences which are useful for the genetic engineering plants with the aim to
modify seed development. At present such regulatory sequences are not available and the genetic engineering e.g. of the apomixis trait is not possible. This comprises a further exploratory phase of evaluation in model crops like Arabidopsis and maize. Once the result is established in Arabidopsis, its effectiveness in other species will be investigated. This will take at least three years. Then results can be considered for commercial potential and a commercialisation phase will be entered. Such a phase takes several years to produce a potential commercial product and 3 years for registration.
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41cq77_one_hundred
L
O
N
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Applied research. Constructs have been generated and plants are currently
transformed to evaluate the potential of the regulatory sequences for the
modification of seed development.
O
G
Current stage of development of the technology:
C
Cordts, S., Amien, S., Lörz, H., Dresselhaus, T. (2001) Embryo sac specific
genes.
WO 01/64924.
Exploitation potential
Innovative Aspects
Main advantage
The potential application of the result is to facilitate breeding and indirectly to
increase yield in crops. The users of the result are the plant breeding industry
as well as the farmers that grow the varieties. The main innovative feature is the
use of very specific promoters that allow the expression of modifying genes at
the target site. Potential barriers are of technical, legal and commercial nature.
First of all the concept has to be proven in model crops. Then the efficacy of
the method needs to be confirmed in different elite genetic background under
field conditions. These field experiments need to be conducted over a number
of years in different geographical areas. The benefit must be exploitable i.e.
there must be justification for a margin on the seed price which results in an
acceptable rate of return level. Additionally in order to exploit the improved
material it must be sure that licences are in place preventing the blocking by
third parties. As a final point, due to the transgenic nature of the end product
there is a high additional cost for registration research and the risk that the consumer may avoid products of this nature. The estimated costs during the commercialisation track are in the range of 8 to 10 million €. The potential returns
are difficult to estimate but should be substantial to allow this level of investment. This kind of project is considered to have a high risk profile due to the
fact that it is technical stage, IP considerations and the transgenic nature of the
end-product.
133
E
Comments:
Patents granted
Partnership/other contractual agreements
T
Patents applied for but not yet granted
Exclusive rights
License agreement reached
H
Intellectual Property Rights
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CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
C
H
Organisation/Firm
University of Hamburg
N
Address:
Title:
First Name:
Surname:
Biocenter Klein Flottbek, EBBT
Ohnhorststrasse 18
D-22609 Hamburg, Germany
Phone:
Fax:
E-mail:
PD Dr.
Thomas
Dresselhaus
+49 40 42816 312
+49 40 42816 229
[email protected]
O
Organisation Type: University
L
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
O
G
A P P L I C AT I O N D O M A I N S
Y
134
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
H
N
O
L
O
G
Y
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C
1 2 . B i o re m e d i a t i o n te ch n o l o g y f o r re m o v a l
o f m e rc u r y f ro m a q u e o u s w a s te s t re a m s
H
Title of result:
N
Bioremediation technology for removal of mercury from aqueous waste streams.
Ownership: National Research Institute for Biotechnology (GBF)
O
L
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
G
Y
A biotechnological process for removal of mercury from aqueous waste streams based on the enzymatic
reduction of ionic mercury to ater insoluble metallic mercury by mercury resistant bacteria has been developed and demonstrated in technical scale at chloralkali electrolysis factories in Europe. The process is based
on mercury resistant bacteria immobilized on porous carrier material in a packed bed bioreactor. Mercury
is accumulated in the carrier material of the bioreactor, from where it can be recovered and recycled or
deposited. The process operates continuously and fully automated. It works at ambient temperature
(between 10°C and 45°C). No chemicals are needed except for feeding solution for the bacteria. Mercury is
recovered periodically by backflushing. The wastewater discharge limit for mercury is reliably reached. The
process is simple, robust, environemntally friendly, efficient and cost effective.
Detailed description of the technology:
The biotechnological process consists of (1) process design, including wastewater neutralization, measurement and control devices, automated online process control, nutrient amendment, (2) the microbial
inoculum, (3) protocols for inoculation, operation, hazard response and backflushing.
Current stage of development of the technology:
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Ready for commercialisation. The demonstration reactor is operating at
SPOL Chemie, Usi nad Labem, Czech republic since July 2000. Since 2001
it has been rented by SPOL from Preussag Wassertechnik.
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
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Partnership/other contractual agreements
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CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
National Research Institute for Biotechnology
(GBF)
Title:
First Name:
Surname:
Dr
Irene
Wagner-Döbler
Address:
Phone:
Fax:
E-mail:
+49 531 6181408
+49 531 6181974
[email protected]
Mascheroder Weg 1
D-38124 Braunschweig, Germany
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
137
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This process is particularly interesting for countries which are in the process of
joining the European Union and have to adjust their wastewater standards to
EU norms, because it is cost effective and relatively simple.
This new biotechnological process is applicable to all mercury contaminated
wastewater, with concentrations above 1 ppm, e.g.
- chloralkali electrolysis wastewater
- soil wash water
- gas pipe flushing water
- gas scrubber solutions
- waste water from gold mining
- hazardous waste storage site leakage water
- mining effluents
- other wastewater containing mercury.
• The investment required will be pursued through contracts with potential users
• The biotechnological process is significantly more cost effective than
existing technologies based on physical/chemical means.
• There are few technical risks fro chloralkali electrolysis wastewater, but
each new application requires additional R&D efforts.
T
Innovative Aspects
Main advantage
G
Exploitation potential
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Title of result:
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On-line analysis of mercury by sequential injection stripping analysis (SISA) using a
chemically modified electrode
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Ownership: Hebrew University of Jerusalem
O
T EC H N O LO GY D E S C R I PT I O N
E
13 . O n - l i n e a n a l y s i s o f m e rc u r y b y s e q u e n t i a l i n j e c t i o n s t r i p p i n g a n a l y s i s ( S I SA )
u s i n g a ch e m i ca l l y m o d i f i e d e l e c t ro d e
C
G
Abstract of the technology:
Y
A highly flexible, automatic sequential-injection stripping analysis (SISA) system has been developed
and applied for monitoring the levels of mercury in aqueous solution using a chemically modified electrode. The preparation of the modified electrode comprises spin coating of an ethanolic solution of
poly(4-vinylpyridine) and Kryptofix-222 onto a glassy carbon electrode (GCE) followed by cross-linking the polymer. The analysis is based on the anodic stripping voltammetry of mercury using differential pulse voltammetry. A sequence of 36 operations was needd to complete a full cycle of cleaning, calibration and analysis.
Detailed description of the technology:
The analysic device consists of (1) the chemically modified electrode, (2) the tubes, valves and pumps
for sequential injection, (3) program and computer for control of operation.
Current stage of development of the technology:
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Prototype completed; user-friendly software and integrated instrumentation
required. The applicability of the system has been demonstrated at the chloralkali electrolysis factory SPOL Chemie, Usti nad Labem, Czech republic
for analysis of effluents of biological mercury removal.
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A selective electrode for ultra-low levels of mercury (USA patent 5,385,708)
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Comments:
Patents granted
Partnership/other contractual agreements
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Patents applied for but not yet granted
Exclusive rights
License agreement reached
G
Intellectual Property Rights
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This type of mercury measurement is a highly flexible alternative to AAS based
detection methods. It can be adjusted to a wide range of mercury concentrations. It requires less costly instrumentation, is fast and precise. This method
can be used to monitor mercury concentrations in wastewater, drinking water,
lakes, rivers, and the sea. Moreover, the method is very sensitive and basically
can measure the levels of Hg(II) down to the sub ppb range.
Demonstration of mercury analysis by sequential injection stripping analysis
(SISA) for wastewater of the chloralkali electrolysis plant SPOL Chemie, Usti
nad Labem, Czech Republic. The new analytical technique is applicable to all
mercury contaminated waters wastewaters, e.g.
- chloralkali electrolysis wastewater
- soil wash water
- gas pipe flushnig ater
- waste from gold mining
- depony waste water
- other washing solutions
- drinking water
- sewage plants
- surface water (lakes, rivers)
- monitoring of estuaries and marine stations
• For commercialisation of this result an interested company is needed.
• The investment required will be pursued through contracts with interested companies.
• The voltammetric detection method is significantly more cost effective
than existing technologies based on AAS.
• There are few technical risks. In principle, only a user-friendly software
and instrumentation are needed.
T
Innovative Aspects
Main advantage
N
Exploitation potential
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Organisation/Firm
Hebrew University of Jerusalem
N
Address:
Department of Inorganic and
analytical Chemistry
Jerusalem 91904, Israel
Title:
First Name:
Surname:
Prof
Daniel
Mandler
Phone:
Fax:
E-mail:
+972 2 658 5831
+972 2 658 5319
[email protected]
O
Organisation Type: University
L
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
O
G
A P P L I C AT I O N D O M A I N S
Y
140
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
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O
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Title of result:
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Gas/solid technology for the production of natural molecules for the food and fragrance
industry, synthons for the fine chemistry and VOCs biodepollution
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Ownership: Université de La Rochelle
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T EC H N O LO GY D E S C R I PT I O N
E
1 4 . Industrial exploitation of gas/solid
technology for the production of natural
esters for the food and fragrance industry
C
G
Abstract of the technology:
Y
Solid/gas biocatalysis appears today as a promising technology for fundamental research and for the development of new cleaner industrial processes. The use of enzymes or whole cells at the solid/gas interface
appears now concurrent to liquid processes and presents some very interesting features since total thermodynamic control of the system can be achieved easily. Moreover, on a technological point of view, solid/gas
systems offer very high production rate for minimal plant sizes, allow important reduction of treated volumes and permit simplified downstream processes. These advantages result from the ability to control precisely all the thermodynamic parameters influencing not only the kinetics of the reactions performed, but
also the stability of the biocatalysts when working with biological catalyst at elevated temperatures. As an
example, natural esters represent an important class of aromatic compounds. The gas/solid technology has
been used for the development of an efficient process for the production of these molecules. The advantages
of the technology consist in a great reduction of the volumes that have to be treated per kg of product compared to conventional existing processes in liquid media. Gas/solid technology also offers an alternative
“green” solution by involving only the substrates of the reaction, plus water. Then, the use of solvent
encountered in liquid systems such a hexane is avoided, simplifying greatly the downstream process, and
thus reducing the direct costs. The work, done within the frame of the demonstration project allowed to
enhance the productivity coupled to a size reduction of the installation, as well as catalyst consumption. Up
to date, the system operates at a minimum of 2 kg (up to 5 kg/hour) in a complete continuous automated
way. The gas/solid technology has been retained by the EU in the list of processes compatible with the natural label. Different fields of application can now get benefit of the technology. The work actually going on
concerns mainly the production of fine chemical (enantiomerically pure compounds) or the bioremediation
of polluted gases involving whole dead cells as catalyst. The technical feasibility has already been demonstrated. Fundamental research and process optimisation are now on progress, in order to be able to reach in
the next few years the industrial level.
Detailed description of the technology:
The industrial pilot used for kosher natural esters using immobilised lipase as catalyst is depicted on the
following diagram and photo. The process is developed on a closed loop of nitrogen, circulating in three
different zones, thus reducing the nitrogen consumption to zero during continuous operation. This
loop is realized between a low pressure zone (flashing unit, heat exchanger and bioreactor), a medium
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pressure zone (gas/liquid separator) and a high pressure zone (final condenser). Liquid substrates (acid
and alcohol for esterification reactions), water and nitrogen are injected into a flashing unit using a pressurized loop with a mass controlled leak going to the flashing unit of each liquid substrate. Once the
liquid/gas flash is realized in the flashing unit, the gas enters in a heat exchanger and its outlet temperature is set to the working temperature of the bioreactor. Then, the thermodynamic activity of each
compound in the gaseous stream is fixed at this stage by controlling each partial pressure.
G
Y
41cq77_one_hundred
FIC
N
N2
H
EV01
C
EC03
PIC
FIC
C01
WATER
V 05
E
EC01
FIC
TIC
LIC
PV01
PIC
ACID
FIC
V 02
R01
T
V 01
V 04
LIC
ALCOHOL
EC04
V 03
EC02
TIC
V 06
V01/02/03: substrates storage drums
EVO1: evaporator
EC01: feed gas heater/cooler
R01: packed bed bioreactor
PV01: liquid ring vacuum pump EC02: liquid ring cooler
V04: medium pressure phase separator
C01: compressor
EC03: compressed gas cooler
V05: high pressure phase separator
EC04: liquid product cooler
V06: decanting unit
2
3
1
4
1
SUBSTRATE
STORAGE DRUMS
3
2
FLASHING UNIT
4
INLET GAS
HEATER/COOLER
PACKED BED
BIOREACTOR
ESTER
A packed bed type reactor follows the heat exchanger, and all
this part of the system is maintained under regulated vacuum
using a liquid ring vacuum pump and a vacuum regulation
valve. After catalysis, the end of the process is solely dedicated to the removal of condensable molecules from the nitrogen fraction, and is performed by a two stage condensation
operation involving a cooling of the gas stream coupled to an
increase of absolute pressure performed by the liquid ring
vacuum pump itself and a compressor for finishing the condensation process. Then, clean nitrogen at the outlet of the
pressurized heat exchanger can be depressurized and recycled to the flashing unit. In order to control proper operation of the installation, an automated sampling system is
available for automated on-line gas chromatograph analyses.
Thus, recycled nitrogen, inlet and outlet gaseous streams on
the bioreactor can be sampled and analyzed for on line monitoring purposes. Complete automated supervision was
developed, in order to define a process able to operate with-
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out any human supervision. Same system is operational for applications such as racemates resolution or
enantioselective reduction with in situ cofactor regeneration. For the bio treatment of waste gases, the
system can be operated in an open mode (no recycling), at lower temperature. Nevertheless, because of
the higher volumetric flows encountered in depollution applications, this set-up only represents a pilot
plant scale for the bio treatment of polluted gases.
N
Current stage of development of the technology:
O
L
O
G
Y
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Up to now, syntheses of more than 25 kosher natural molecules have been
optimised for the aroma industry. Commercial products are obtained after
simple purification steps and distributed to end. The process has been fully
automated and don’t need any human presence during production/tests
runs, minimizing greatly direct production/functioning costs. A start-up
GASZYME SARL has been created and now beneficiates of a worldwide
license for the production of kosher natural esters used as flavours for the
food industries. Different unitary operations for downstream process were
implemented on the platform including a liquid/gas pervaporation unit and
a distillation unit. The platform is now accessible either for production purposes, or for new developments concerning resolution of racemates or enantioselective reduction of ketones for the fine chemistry or for tests of bioremediation of polluted gases.
Intellectual Property Rights
Patents applied for but not yet granted
Patents granted
Exclusive rights
Partnership/other contractual agreements
License agreement reached
Comments:
International patent: WO 99/04894
License agreement: worldwide license to GASZYME for the production of natural esters. Different partnerships with worldwide companies have been concluded concerning the development of new processes for the biotreatment of
gases polluted by chloroalkanes using whole cells as catalyst.
Exploitation potential
Innovative Aspects
Main advantage
144
Many field of applications can get benefit of the technology. Three main topics
are now under development.
- First, applications relative to the production of compounds with medium or
high added value for the fine chemistry involving either purified enzymes or
whole cells as catalyst are under development. All the tested systems were
found to be active at the solid/gas interface. The actual work concerns mainly the use of lipases for the resolution of racemic mixtures of secondary alcohols, used as synthons or the enantioselective reduction of prochiral ketones
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for the production of optically active pure alcohols. In this last case, the system we developed allows in situ cofactor regeneration by the addition of a
co substrate, using the same enzymatic activity.
- Second, there is an important demand concerning the development of new
efficient processes for the bioremediation of polluted gases and the VOCs
removal. We are actually working on the development of a new process for
the bio treatment (bio filtration) of haloalkanes polluted gases. Although
numerous bioprocesses have already been developed to this purpose, the
majority present limitations especially concerning the biodegradation of
these molecules for two main reasons; haloalkanes present very low solubility in classical liquid bio oxidation processes, and are of high toxicity for the
biomass used in these treatments. The use of whole dead cells working at the
gas solid/interface appears now as a very efficient pre-treatment of such
gases, allowing efficient dehalogenation of haloalkanes, leading to the production of alcohols easily metabolised in a second step in classical liquid bio
treatments. Besides this topic, and because it is possible in solid/gas technology to modulate the absolute working pressure, we are developing a process
for the bio decontamination of military materials exposed to chemical
weapons such as VX for example. The process includes in the same step the
extraction and the treatment of the chemical compound. Linked to these
subject, we are also starting, with colleagues of civil engineering department
the development of an air conditioning bio catalytic system.
- Third, because of the ability to control in an totally independent way the
thermodynamic activity of each component of the gas, which is impossible
in liquid systems, solid/gas biocatalysis represents a very powerful tool that
enables a more accurate approach for studying the effect of the microenvironment on enzymatic activity and stability. This allows to have an access to
intrinsic parameters, thus providing additional information for a molecular
understanding of enzyme catalysis in general. Solid/gas catalysis then
appears probably as the most appropriate and the most complementary
experimental tool for validating molecular modelization experiments.
Solid/gas technology then represents a clean technology, since, compared to the
organic liquid systems, the use of organic solvent can be reduced to zero. Its use
shall lead to the definition of new “green processes” and numerous applications
should get benefit of this technology. Beside these application fields, biosensors
and analytical techniques should beneficiate from the technology. Some examples
have already been described concerning the use of a biological part constituting
the body of detection, and a transmitter for detection in gaseous media. For example, the detection of formaldehyde by a formaldehyde dehydrogenase coated onto
a piezoelectric crystal was performed at the ppm level. Detection of pesticides and
organophosphorous compounds at the level of ppb has been rendered possible by
the same technique involving either acetylcholinesterase or butyrylcholinesterase.
Concerning analytical developments, one can imagine easily that affinity gas chromatography set-ups can be envisaged seriously, as well as the realization of on-line
specific derivatization precolumns for GC analysis.
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CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
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Organisation/Firm
Université de La Rochelle
N
Address:
O
LBCB, FRE CNRS 2766,
Bat. M. Curie, Avenue M. Crépeau
F-17042 La Rochelle Cedex 1,
France
L
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Pr
Sylvain
Lamare
Phone:
Fax:
E-mail:
+33 5 46458275
+33 5 46458247
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
O
G
A P P L I C AT I O N D O M A I N S
Y
146
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Fine chemistry
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N
O
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O
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Y
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15. Guidelines for design and
i m p l e m e n ta t i o n o f a s u s ta i n a b l e
b i o l o g i ca l re m e d i a t i o n s y s te m b a s e d o n
s u b s t r a te i n j e c t i o n a n d g ro u n d w a te r
c i rc u l a t i o n
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Title of result:
L
O
Guidelines for design and implementation of a sustainable biological remediation system based on substrate injection and groundwater circulation
Ownership: TAUW bv
G
T EC H N O LO GY D E S C R I PT I O N
Y
Abstract of the technology:
Practical guidelines for a design and implementation of a sustainable biological remediation system
based on substrate injection and groundwater circulation are developed. These guidelines are needed to
overcome complicating factors like clogging of the groundwater system, which seriously frustrate the
implementation of bioremediation. As a result from the guidelines, a new filtration device (an anaerobic sand filtration set-up) was developed during the project. Also guidelines for efficient and sustainable
substrate injection into or near groundwater injection deepwells of a groundwater circulation system
are developed. The guidelines prescribe the possibilities and impossibilities of the biological remediation system. In the guidelines also alternative ways of substrate injection such as for example anaerobic
gas injection with methanol and nitrogen gas are described (LINER-gas injection). The guidelines are
at this moment (May ’01) used by different consultancy-agencies in the Netherlands for the design and
implementation of remediation systems all over the Netherlands. By means of these guidelines biological remediation systems can perform better and at lower operational costs.
Detailed description of the technology:
The result is a practical product that can easily be applied to the design and implementation of (biological) remediation systems. An increasing percentage of the ongoing soil remediation systems in the
world are based on the stimulation of in-situ processes in the soil. In situ soil remediation has strong
advantages in densely populated areas where soil contamination hampers the economical development.
The developed guidelines fit in the ongoing development of the state of the art and stimulate the application of biological remediation systems in those areas. The alternative way of substrate injection, as
described in the guidelines, with the use of nitrogen gas (LINER) is a breakthrough in dispersing substrate in the soil and will stimulate the application of biological remediation systems in areas with a lot
of buildings or more rural areas with contamination deep beneath the soil surface.
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Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Results of demonstration trials available. The guidelines for design and
implementation of biological remediation systems based on substrate injection and groundwater circulation are available to be used by consultancy
agencies and constructors. The Chlorem-project in Bunnik is an example of
the demonstration of the results and lately also other soil remediation systems in the Netherlands show the results of the guidelines.
O
G
Current stage of development of the technology:
E
Patents granted
Partnership/other contractual agreements
T
Patents applied for but not yet granted
Exclusive rights
License agreement reached
C
Intellectual Property Rights
Exploitation potential
Innovative Aspects
Main advantage
Spin off or business creation, consultancy.
Exploitable result of interest for third parties. Information exchange. Financial
support. Private-public partnership. Tauw bv offers expertise and know how to
design and implement a biological remediation system based on substrate injection and groundwater circulation to owners or governmental agencies which
are dealing with contaminated sites. Besides Tauw bv is able to implement and
control biological remediation systems in collaboration with constructors.
Tauw bv uses the guidelines in the design and implementation of biological soil
remediation system. The guidelines are free to be used by other consultancy
agencies or constructors. Tauw bv will exploit the guidelines in marketing the
knwohow and developed guidelines to governmental agencies and other parties
which possess a contaminated site. The purpose of Tauw is to obtain the consultancy of the design and implementation of biological remediation systems
on polluted sites. The achieved results are in general applicable by all soil remediation systems based on groundwater infiltration and/or recirculation. Use of
the guidelines in design of the remediation system will minimize clogging problems of the recirculation systems during operation and (consequently) will
reduce maintenance costs. Besides remediation systems the guidelines also are
applicable to e.g. the installation of sewage systems in areas with a high groundwater level. In these areas groundwater recirculation sytems are used to temporarily and locally lower the groundwater level. The guidelines will specifically be used by consultancy agencies and constructors. These guidelines offer the
possibility to improve the design of existing remediation systems and will
probably give a boost to the development of new remediation systems.
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Organisation/Firm
TAUW bv
N
Address:
Zekeringstraat 43G
NL-1014 BV Amsterdam
The Netherlands
Title:
First Name:
Surname:
ing.
Jeroen J.
Mooy
ir
Anette
A.H. Oosterhoff
Phone:
Fax:
E-mail:
+31 20 606 3228/3232
+31 20 684 8921
[email protected] [email protected]
O
Organisation Type: University
L
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
O
G
A P P L I C AT I O N D O M A I N S
Y
150
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
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Title of result:
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Cliniporator™
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Ownership: IGEA s.r.l.
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T EC H N O LO GY D E S C R I PT I O N
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Abstract of the technology:
O
G
A device, Cliniporator was developed. It has unique technological characteristics: it is able to deliver
high voltage and low voltage pulses, it can record in real time current and voltage changes during tissue
pulsing; a dedicated software allows pulse characteristics settings and recording of electrical parameters
during pulses.
Y
Detailed description of the technology:
The Cliniporator Consortium has developed the most advanced and flexible electronic system for cell
poration. The algorithm for the modulation for the optimisation of high voltage pulse is implemented,
the Cliniporator™ will have unique capabilities of optimising gene transfer to the cell. Furthermore, in
its present configuration the Cliniporator™ can already be used in clinical settings for the treatments of
solid tumours in association with chemotherapic drugs. Namely, the Cliniporator™ is already used in
various EU countries (F, I, IRL, SI, E, DK, UK) for electrochemotherapy using the Standard Operating Procedures elaborated in the ESOPE project (QLK3-2002-02003), a continuation of the Cliniporator project. In association with this we have completed the development of new sterile electrodes that
are suitable for use in humans. We can offer to a partner the technology developed. The potential partner should have access to the oncological centres so that it can ease the introduction of this new technology.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
152
Patents granted
Partnership/other contractual agreements
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The ESOPE study has demonstrated that the ECT (Electro Chemo Therapy)
performed with the Cliniporator™ is safe, effective and simple; it is well tolerated by the patient, with no side effects. The treatment can be applied to any
skin metastases independently of histology. The treatment is performed in one
session even if in presence of multiple nodules, on an outpatient basis. The
treatment can be repeated on the same patient. The cost benefit ratio is extremely favourable.
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N
Innovative Aspects
Main advantage
G
Exploitation potential
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
IGEA s.r.l.
Address:
Via Parmenide 10A
Carpi 41012 (Mo) Italy
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Dr.
Ruggero
Cadossi
Phone:
Fax:
E-mail:
+39 059 699600
+39 059 695778
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
153
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E
C
1 7. U l t r a f l a t s u r fa ce f o r A F M ;
AFM for biomolecules
H
Title of result:
N
Ultraflat surface for AFM; AFM for biomolecules
Ownership: DME – Danish Micro Engineering A/S
O
L
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
G
Y
The study of biomolecules with imaging of details on the micro and nano meter scale requires a deposition of the molecule structure on a near atomically flat surface, this is made possible through the cooperation with ID-DLO and Ingenasa.
Detailed description of the technology:
Current stage of development of the technology:
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Applied research, experimental development state (laboratory prototype),
prototype/demonstrator available for testing
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Comments:
Patents granted
Partnership/other contractual agreements
Ultraflat surface: dutch patent application n° 10.09704 “AFM-oppervlak”
(AFM surface).
Agreement among ID-DLO, DME and Ingenasa.
Licence agreement.
Exploitation potential
Innovative Aspects
Main advantage
154
DME develops, produces, and markets SPN instruments for the study of e.g.
bio material of various kinds in vacuum, gases (incl. atmospheric air) as well as
in liquids, including buffer solutions. ID-DLO and Ingenasa participate in the
further development of ultra Flat vio surfaces.
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Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Transformevej 12
DK-2730 Herlev
Dennmark
Phone:
Fax:
E-mail:
+45 4484 9211
+45 4484 9197
[email protected]
L
O
Dr
Curt
Sander
N
Address:
Title:
First Name:
Surname:
O
Organisation/Firm
DME – Danish Micro Engineering A/S
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
T
E
A P P L I C AT I O N D O M A I N S
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E
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18. Biosynthesis and Biodegradation of
B i o s i l i ca ( S i l i ca N a n o b i o te ch n o l o g y )
H
Title of result:
N
Biosynthesis and Biodegradation of Biosilica (Silica Nanobiotechnology)
Ownership: Johannes Gutenberg-Universität Mainz
O
L
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
G
Y
Two enzymes involved in formation and dissolution of biosilica have been isolated, cloned and characterized; the recombinant enzymes have been prepared. These enzymes, silicatein und silicase, are at present the
worldwide only key enzymes available for silica nanobiotechnology. These enzymes are lead catalysts for
the development of novel production methods for, and products from biosilica. This success gives biochemistry and technology two unique tools in hands, to combine two worlds – the mineral (inorganic) and the
biochemical world – thus opening new possibilities of products and production techniques.
Detailed description of the technology:
Sponges are able to form their “biosilica” skeleton enzymatically at room temperature. Until recently, it was
not possible to mimic this ability. The research team could isolate and demonstrate the function of first
genes and proteins that are active in biosilica formation. The biosilica synthesizing enzyme, silicatein, could
be cloned and produced as catalytically active recombinant protein. Furthermore the enzyme that can dissolve biosilica, the silicase, was discovered. These enzymes allow the production of glass-like structures for
the coating of biomaterials as well as their modification. This basic innovation has been patented (worldwide first - granted - patents on biosilica / use of recombinant silica forming enzymes, silicateins, and biosilica dissolving enzyme, silicase, for the production / dissolution of biosilica). The identification of the
enzymes involved in synthesis and degradation of biosilica opens new ways for nanobiotechnology.
Patents on silicatein (formation of biosilica) and silicase (degradation of biosilica):
EP1320624 (European Patent; granted). Silicatein-mediated synthesis of amorphous silicates and siloxanes
and use thereof. Inventors: Müller WEG, Lorenz B, Krasko A, Schröder HC.
DE10246186 (granted). In vitro and in vivo degradation or synthesis of silicon dioxide and silicones, useful e.g. for treating silicosis or to prepare prosthetic materials, using a new silicase enzyme. Inventors:
Müller WEG, Krasko A, Schröder HC.
PCT/EP03/10983 (announced to be granted). Abbau und Modifizierung von Silicaten und Siliconen
durch Silicase und Verwendung des reversiblen Enzyms. Inventors: Müller WEG, Krasko A, Schröder HC.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
156
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
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Y
41cq77_one_hundred
G
Intellectual Property Rights
O
Patents granted
Partnership/other contractual agreements
H
C
By the discovery of the silica enzymes and first outlines of applications it is
now possible to produce glass like material (biosilica) at room temperature.
More important, it is possible to develop - using these enzymes - novel products for medicine, cosmetics, food industry, electronic industry and many
more. The enzymes of the biosilica metabolism, silicatein and silicase, are available in recombinant form. It is possible to establish a production or it can be
performed by a licensed company.
T
Innovative Aspects
Main advantage
E
Exploitation potential
N
O
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
Johannes Gutenberg-Universität Mainz
Address:
Institut für Physiologische Chemie,
Abteilung für Angewandte
Molekularbiologie,
Johannes Gutenberg Universität,
Duesbergweg 6, D-55099 Mainz,
Germany
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Prof. Dr.
Werner E.G.
Müller
Phone:
Fax:
E-mail:
+49-6131-3925910
+49-6131-3925243
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
157
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H
N
Title of result:
O
A novel multiplex high accuracy automated DNA Sequencer with high throughput of 500
kilobases per day
L
Ownership: Biochemical Instrumentation EMBL
O
T EC H N O LO GY D E S C R I PT I O N
E
1 9 . A n o v e l m u l t i p l e x h i g h a cc u r a c y
a u to m a te d D N A S e q u e n ce r w i t h h i g h
t h ro u g h p u t o f 5 0 0 k i l o b a s e s p e r d a y
C
G
Abstract of the technology:
Y
About 20 MegaBases of full length cDNAs and ESTs, and about 2 MegaBases of genomic DNA libraries
and SAGE clones were sequenced. The goal to reduce the sequencing cost to 0,1 € per base was reached.
Detailed description of the technology:
Owing to its technical features, including accessibility of real raw data, the high throughput single passhigh accuracy ARAKIS automated DNA sequencing technology developed at EMBL has met this performance goals. In its current configuration, the ARAKIS system works with up to five lasers and five
independent detectors, allowing the simultaneous and independent sequencing of up to five differently
labelled DNA samples in the same sets of lanes on the gel. Run twice a day, or 800-1000 clones, competing well with all other available sequencing devices. Up to 5000 bases in a single sequencing reaction
could be obtained. In the routine system with four lasers, 4000 bases were obtained in the same set of
lanes on the gel. Data acquisition and Lane tracking software were developed. The high throughput is
achieved with automated porous comb loading technology developed at EMBL. ARAKIS presents a
new tool fir high resolution comparative multiplex-dye protein analysis, high resolution 2D technique,
analysis of protein-DNA interactions and footprinting.
Current stage of development of the technology:
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : In routine application in institutes
158
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Y
41cq77_one_hundred
G
Intellectual Property Rights
O
Patents granted
Partnership/other contractual agreements
T
E
C
H
N
O
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
Biochemical Instrumentation EMBL
Address:
Meyerhofstrasse 1
D-69117 Heidelberg - Germany
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Prof
Wilhelm
Ansorge
Phone:
Fax:
E-mail:
0049-6223-9739992
0049-6223-9739992
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
159
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E
2 0 . P ro g r a m m a b l e re s t r i c t i o n e n z y m e
C
Title of result:
H
Programmable restriction enzyme
N
Ownership: Justus-Liebig-University
O
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
O
G
Y
We have generated a programmable restriction enzyme by fusing a triple helix forming oligodeoxyribonucleotide to a restriction endonuclease using a bifunctional crosslinker. This conjugate specifically
cleaves double stranded DNA at a bipartite recognition site, consisting of the recognition site of the
restriction endonuclease and a triple helix forming site in a distance of 3 to 12 base pairs to the restriction endonuclease recognition site.
Detailed description of the technology:
In principle, the specificity of restriction endonucleases (REases) can be extended by fusion to sequence
recognition modules, e.g. specific DNA binding domains or triple-helix forming oligonucleotides
(TFO). We have chosen to extend the specificity of REases using TFOs, given the combinatorial flexibility this fusion offers in addressing a short, yet precisely recognized restriction site next to a defined
triple-helix forming site. We have succeeded in producing conjugates of the single chain variant of the
REase PvuII (scPvuII) and a triple helix forming oligonucleotide (TFO). The fusion was achieved
between an amino link at the 5’-end of the oligonucleotide and the SH-group of a C-terminal Cys
residue of scPvuII using a bifunctional crosslinker, N[-γ-maleimidobutyryloxy] succinimide ester
(GMBS). The scPvuII-TFO conjugates proved to be specific for cleavage of a DNA substrate containing a PvuII site next to a triple helix forming site (TFS), provided scPvuII-TFO conjugate and DNA
substrate were preincubated in the absence of Mg2+ ions, to allow for triple helix formation and at the
same time to prevent cleavage at unaddressed sites (i.e. normal PvuII sites). Cleavage at addressed sites
(i.e. PvuII sites next to a TFS) could then be initiated by addition of 1.5 mM Mg2+ ions. The specificity of the scPvuII-TFO under these conditions is such that addressed sites can be cleaved specifically in
a 1,000 to 10,000-fold excess of unaddressed sites. This specificity is sufficient for genome mapping in
vitro, which is limited by the availability of rare cutting REases. In principle, REase-TFO conjugates
could also be used for gene targeting in vivo.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
160
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
04-11-2005
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Y
41cq77_one_hundred
G
Intellectual Property Rights
O
Patents granted
Partnership/other contractual agreements
Exploitation potential
A useful reagent for large genome mapping and cloning, which could also be
used for gene targeting in vivo.
T
E
C
H
Innovative Aspects
Main advantage
N
O
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Title:
First Name:
Surname:
Organisation/Firm
Justus-Liebig-University
Phone:
+49 641 9935400
Fax:
+49 641 9935409
E-mail:
[email protected]
Address:
Heinrich-Buff-Ring 58,
D-35392 Giessen, Germany
Organisation Type: University
Organisation size: < 50 employees
Professor
Alfred
Pingoud
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
161
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E
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H
N
2 1 . A d e d i ca te d w i d e - b o re u l t r a - h i g h - f i e l d
M A S N M R s p e c t ro m e te r, p ro b e s ,
a cce s s o r i e s , s o f t w a re a n d s a m p l e
p re p a r a t i o n m e t h o d s f o r b i o l o g i ca l
M A S N M R a n d I m a g i n g re s e a rch
O
Title of result:
L
O
A dedicated wide-bore ultra-high-field MAS NMR spectrometer, probes, accessories,
software and sample preparation methods for biological MAS NMR and Imaging
research
G
Ownership: Leiden University
Y
T EC H N O LO GY D E S C R I PT I O N
Abstract of the technology:
A new ultra high field and wide bore NMR spectrometer operating at 17.6 Tesla (750 MHz proton resonance frequency) i.e. a system based on a newly developed highly homogeneous superconducting
magnet system with 89mm room temperature bore has been developed. The increase of field strength
combined with the large access bore facilitate higher sensitivity and dispersion, essential for biological
solid state NMR, including magic angle spinning (MAS), and for magnetic resonance microscopy
(micro-imaging). New improved pulse programming and pulse sequence execution capabilities were
developed for this system as required particularly for the intended solid state experiments. A new generation of flat-coil solid state NMR probes and of triple resonance NMR probes, optimized for protein
analysis at ultra high magnetic field at variable temperatures was realized. Furthermore, micro-imaging
facilities for applications involving small objects up to 30 mm diameter at ultra high field have been
developed and implemented for applications involving small animal models (mice, fish, chicken
embryos) e.g. to resolve the relationship between the genetic program and biological functionality.
Since the system operates at highest magnetic field strength available for a wide bore configuration with
imaging capabilities, it is the most powerful magnetic resonance microscope in the world. Furthermore,
it represents the state of the art in the field of solid state NMR in the context of material and biological
sciences. The system does not rely on any additional technology and is fully self-sustained. Demonstrations in the field of solid structure determinations, ligand-protein interactions, protein functional mechanisms and micro imaging have been successfully completed. All these new products have immediately
been made commercially available by Bruker BioSpin GmbH. The groundbreaking results obtained
during the demonstration project have in addition resulted in a dramatic increase in further scientific
research and as a consequence in a large interest in the new probe technologies for common solids NMR
spectrometers and in high field solid state NMR spectrometers in general.
162
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Y
41cq77_one_hundred
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
Exploitation potential
Innovative Aspects
Main advantage
Marketing started as soon as the demonstrator was ready for measurements.
The exploitation is successfully in progress, several orders for the
AVANCE750WB were already received within one year after completion of
the project. The application of the instrumentation is steadily increasing and is
in Structural Genomics, systems biology, high resolution NMR imaging of animals and materials science such as in Nanotechnology.
163
L
O
N
H
C
E
T
At the start of the new millennium, the world's first ultra high field wide bore spectrometer for biological research was inaugurated in Leiden. It is the outcome of a demonstration project funded by the EC's
Biotechnology programme, which through its improved sensitivity and resolution allows researchers to
tackle one of the most difficult questions of the post-genomic era: how do membrane proteins work?
Every organism, including ourselves, is built of billions of cells separated by membranes containing proteins, the molecular machinery of cells. According to the first bioinformatics estimates from human
genome analyses, 30% of all proteins are membrane proteins. Virtually every life process proceeds
sooner or later via membrane proteins. Yet, very little is known about how they look and how they
work due to a lack of instruments and methods. With thousands of membrane receptor targets awaiting
analysis in pharmaceutical companies worldwide, the importance of progress in this area is clear. Only
with access to detailed information about hormones or drugs bind to their (protein)membrane receptor
target in the membrane in vivo, can rational drug design become reality. The new approach is based on
superconducting magnets which have many applications in scientific research, including Magnetic Resonance Imaging (MRI), a technique used to examine tissues in the human body , and Nuclear Magnetic Resonance (NMR) to visualize individual molecules. An extremely powerful, stable magnet with a
large useable space (wide bore) has been constructed and optimized for biological research on membrane proteins. This unique research facility will provide scientists with new insights into the biological interactions which control sight, taste, smell and a host of internal processes central to diseases ranging from depression to arthritis. MAS stands for Magic Angle Spinning, which refers to the way the
sample is presented for analysis and forms the basis of the novel approach. Among the new research
possibilities are: snapshots of hormones and drugs bound to their protein targets, membrane structures
and ultimately, detailed knowledge into how these biological devices work in living cells.
O
G
Detailed description of the technology:
41cq77_one_hundred
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E
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
C
H
Organisation/Firm
Leiden University
N
Address:
Einsteinweg 55
2333 CC Leiden
The Netherlands
Title:
First Name:
Surname:
Prof. Dr.
Huub J.M
de Groot
Phone:
Fax:
E-mail:
+31(0)71 5274539
+31(0)71 5274603
[email protected]
O
Organisation Type: University
L
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
O
G
A P P L I C AT I O N D O M A I N S
Y
164
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
H
N
O
L
O
G
Y
Pagina 165
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T
H
N
Title of result:
O
Modification of cellular stress responses for improved protein production in filamentous fungi
E
2 2 . M o d i f i ca t i o n o f ce l l u l a r s t re s s
re s p o n s e s f o r i m p ro v e d p ro te i n
p ro d u c t i o n i n f i l a m e n to u s f u n g i
C
L
Ownership: Technical Research Center of Finland, VTT Biotechnology
Institute of Food Research
O
T EC H N O LO GY D E S C R I PT I O N
G
Y
Abstract of the technology:
Efficient systems for production of extracellular enzymes are essential for many fields of industrial
biotechnology including the concepts of White Biotechnology and Biorefinery and for production of
proteins for pharmaceutical purposes. We have recently identified a novel type of feed-back mechanism
which is activated under secretion stress conditions in fungal cultures and which results in transcriptional down-regulation of many of the genes encoding secreted proteins. Targeted modifications in the regulatory mechanism provide tools to improve either production of the endogenous extracellular proteins
or heterologous proteins produced under the control of the promoters subjected to the regulation.
Detailed description of the technology:
Impaired protein folding and transport in the secretory pathway induces various stress responses in
eukaryotic cells. In filamentous fungi, in particular, the production of extracellular proteins in vast
quantities sets a requirement for an efficient system to adjust the secretory capacity of the cells and the
amount of protein produced. Recently, we have described a novel type of feedback mechanism which is
activated in response to secretion stress in the filamentous fungi Trichoderma reesei and Aspergillus
niger and which leads to repression of genes encoding extracellular proteins (RESS, repression under
secretion stress) and thus to reduction in the amount of protein produced (Pakula et al., 2003; Al-Sheikh
et al., 2004). The original finding of down-regulation of the genes encoding extracellular proteins was
obtained in cultures of T. reesei and A. niger treated with chemical agents known to inhibit either protein folding or transport, and in cultures of a A. niger strain with reduced folding capacity due to expression of an antisense construct for pdiA (protein disulphide isomerase) mRNA. Analysis of reporter gene
systems showed that the feed-back regulation took place at transcriptional level rather than affecting
mRNA stability and that particular promoter regions were involved in mediating the response. The
genes subjected to the repression mechanism include genes whose promoters are widely used for production of recombinant proteins in these host systems, e.g. the major cellulase genes of T. reesei and the
glucoamylase gene of A. niger.
166
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O
L
O
Modification of the components involved in the RESS response, either the transcriptional factors or specific regions in the production promoters, provides tools to improve protein production in the fungal
systems, especially during production of heterologous proteins or during production of endogenous
proteins in large excess when the capacity of the cells to fold and secrete the proteins might become limiting.
G
Y
41cq77_one_hundred
Current stage of development of the technology:
H
N
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
C
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Patents granted
Partnership/other contractual agreements
T
Patents applied for but not yet granted
Exclusive rights
License agreement reached
E
Intellectual Property Rights
Exploitation potential
Innovative Aspects
Main advantage
Modification of the novel stress response (RESS) mechanism to improve
protein production in filamentous fungi
167
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E
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
H
Title:
First Name:
Surname:
Prof
Merja
Penttilä
N
C
Organisation/Firm
Technical Research Center of Finland,
VTT Biotechnology
Address:
Phone:
Fax:
E-mail:
+ 358 20 722 4504
+ 358 20 722 7071
[email protected]
P.O. Box 1500 (Tietotie 2, Espoo),
FIN-02044 VTT, Finland
O
Organisation Type: University
L
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
O
G
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Y
Organisation/Firm
Institute of Food Research
Address:
Colney Lane, Norwich, NR4 7UA,
UK
Present address: School of Biology,
University Park, Nottingham,
NG7 2RD, UK
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Prof
David
Archer
Phone:
Fax:
E-mail:
+44 115 951 3313
+44 115 951 3251
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
168
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
protein production,
production of hydrolytic
enzymes
H
N
O
L
O
G
Y
Pagina 169
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T
H
N
Title of result:
O
Change in material chemistry induces cell attachment for low adhesion materials 14452
L
Ownership: University of Glasgow
O
T EC H N O LO GY D E S C R I PT I O N
E
23 . C h a n g e i n m a te r i a l ch e m i s t r y i n d u ce s
ce l l a t ta ch m e n t f o r l o w a d h e s i o n
m a te r i a l s
C
G
Abstract of the technology:
Y
Industrial development and health uses. Development of ultra low and ultra high adhesion surfaces on
a wide variety of materials with specific concentration and patternings of nanoprinted proteins or peptides fon the biomedical device industry. Could have effects on improving the environment, in developing better systems for waste water treatment and improvements in developments for healthcare in
respect of a wide variety of diseases. Increased employment and wealth creation by the production and
sales of devices.
Detailed description of the technology:
Nanofabricated master patterns reproduced into polymers by hot embossing followed by Nanoprinting proteins and peptides.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
170
Patents granted
Partnership/other contractual agreements
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Y
41cq77_one_hundred
O
Nanofeatured surfaces of specified ultra-low adhesion
Long life sine there is no surface chemistry to degrade.
T
E
C
H
N
O
L
Innovative Aspects
Main advantage
G
Exploitation potential
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
University of Glasgow
Address:
University Avenue,
Glasgow G12 8QQ
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Prof.
Adam
Curtis
Phone:
Fax:
E-mail:
0044 141 330 5147
0044 141 330 3730
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
171
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100 Technology Offers stemming from EU biotechnology RTD results
T
H
N
Title of result:
O
Tissue scaffolds and stents: Fabrication of a nanofeatured surface on the inside wall of
a tube. - 14454
L
Ownership: University of Glasgow
O
T EC H N O LO GY D E S C R I PT I O N
E
2 4 . T i s s u e s ca f f o l d s a n d s te n t s :
Fa b r i ca t i o n o f a n a n o f e a t u re d s u r fa ce
on the inside wall of a tube.
C
G
Abstract of the technology:
Y
Industrial development and health uses. Development of ultra low and ultra high adhesion surfaces
inside tubes. A. wide variety of materials with specific concentration on the biomedical device industry.
Could have effects on improving the environment, in developing better systems for waste water treatment and improvements in developments for healthcare in respect of a wide variety of diseases.
Increased employment and wealth creation by the production and sales of devices especially for vascular prostheses.
Detailed description of the technology:
Nanofabricated master patterns reproduced into polymers by or by polymer demising inside tunes
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
Exploitation potential
Innovative Aspects
Main advantage
172
Nanofeatured surfaces of specified adhesiveness inside tubes.
Long life sine there is no surface chemistry to degrade.
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G
Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Address:
Phone:
Fax:
E-mail:
0044 141 330 5147
0044 141 330 3730
[email protected]
L
O
Prof.
Adam
Curtis
N
University Avenue
Glasgow G12 8QQ
Title:
First Name:
Surname:
O
Organisation/Firm
University of Glasgow
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
T
E
A P P L I C AT I O N D O M A I N S
173
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100 Technology Offers stemming from EU biotechnology RTD results
T
E
C
2 5 . E m b o s s i n g a n d ca s t i n g n a n o s ca l e
p a t te r n i n to s o f t m a te r i a l s
H
Title of result:
N
Embossing and casting nanoscale pattern into soft materials
Ownership: University of Glasgow
O
L
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
G
Y
Methods for making multiple high accuracy replicas of nanotopographic surfaces in polymers, some
natural products and the softer metals. The technology includes fast writing of e-beam masters, making nickel shims and the embossing or casting of various materials on the shims so that large numbers
can be made rapidly. Methods related to those used in DVD production but not identical.
Detailed description of the technology:
Nanofabricated master patterns reproduced into polymers by hot embossing
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
Exploitation potential
Innovative Aspects
Main advantage
174
Nanofeatured surfaces of specified ultra-low adhesion
Long life sine there is no surface chemistry to degrade.
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G
Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Address:
Phone:
Fax:
E-mail:
0044 141 330 5147
0044 141 330 3730
[email protected]
L
O
Prof.
Adam
Curtis
N
University Avenue
Glasgow G12 8QQ
Title:
First Name:
Surname:
O
Organisation/Firm
University of Glasgow
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Nanofabrication
T
E
A P P L I C AT I O N D O M A I N S
175
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100 Technology Offers stemming from EU biotechnology RTD results
T
E
C
2 6 . U l t r a - h i g h a d h e s i o n n a n o f e a t u re d
s u r fa ce s
H
Title of result:
N
Ultra-high adhesion nanofeatured surfaces - 14449
Ownership: University of Glasgow
O
L
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
G
Y
Industrial development and health uses. Development of ultra low and ultra high adhesion surfaces on
a wide variety of materials with specific concentration on the biomedical device industry. Could have
effects on improving the environment, in developing better systems for waste water treatment and
improvements in developments for healthcare in respect of a wide variety of diseases. Increased employment and wealth creation by the production and sales of devices.
Detailed description of the technology:
Nanofabricated master patterns reproduced into polymers by hot embossing
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
Exploitation potential
Innovative Aspects
Main advantage
176
Nanofeatured surfaces of specified ultra-low adhesion
Long life sine there is no surface chemistry to degrade.
04-11-2005
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G
Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Address:
Phone:
Fax:
E-mail:
0044 141 330 5147
0044 141 330 3730
[email protected]
L
O
Prof.
Adam
Curtis
N
University Avenue
Glasgow G12 8QQ
Title:
First Name:
Surname:
O
Organisation/Firm
University of Glasgow
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
T
E
A P P L I C AT I O N D O M A I N S
177
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100 Technology Offers stemming from EU biotechnology RTD results
T
E
C
2 7. U l t r a - l o w a d h e s i o n n a n o f e a t u re d
s u r fa ce s
H
Title of result:
N
Ultra-low adhesion nanofeatured surfaces - 14448
Ownership: University of Glasgow
O
L
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
G
Y
Industrial development and health uses. Development of ultra low and ultra high adhesion surfaces on
a wide variety of materials with specific concentration on the biomedical device industry. Could have
effects on improving the environment, in developing better systems for waste water treatment and
improvements in developments for healthcare in respect of a wide variety of diseases. Increased employment and wealth creation by the production and sales of devices.
Detailed description of the technology:
Nanofabricated master patterns reproduced into polymers by hot embossing
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
Exploitation potential
Innovative Aspects
Main advantage
178
Nanofeatured surfaces of specified adhesiveness inside tubes.
Long life sine there is no surface chemistry to degrade.
04-11-2005
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G
Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Address:
Phone:
Fax:
E-mail:
0044 141 330 5147
0044 141 330 3730
[email protected]
L
O
Prof.
Adam
Curtis
N
University Avenue
Glasgow G12 8QQ
Title:
First Name:
Surname:
O
Organisation/Firm
University of Glasgow
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
T
E
A P P L I C AT I O N D O M A I N S
179
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100 Technology Offers stemming from EU biotechnology RTD results
T
E
C
H
2 8 . T h e r m o s ta b l e e n z y m e s o f i n d u s t r i a l
i n te re s t f ro m S u l f o l o b u s a n d g e n e t i c
s y s te m s f o r t h e i r o v e re x p re s s i o n i n
Sulfolobus
N
O
Title of result:
L
Thermostable enzymes of industrial interest from Sulfolobus and genetic systems for
their overexpression in Sulfolobus
O
Ownership: University of Copenhagen
G
T EC H N O LO GY D E S C R I PT I O N
Y
Abstract of the technology:
Genomes of the crenarchaeal species Sulfolobus solfataricus, Sulfolobus acidcaldarius and Sulfolobus
islandicus, as well as Hyperthermus butylicus, have been sequenced, together with several viruses and
plasmids from the order Sulfolobales. Some enzymes have been selected of potential industrial interest,
and also a genetic system has been developed for Sulfolobus expression, and patents have been applied
for.
Detailed description of the technology:
A few enzymes of industrial interest were identified during the genome analyses. They have each been
expressed in bacterial expression systems and they have been tested by Biotech companies for their possible use in industrial processes. Some of them can potentially replace chemicals which are relatively
damaging for the environment. Two enzymes, one a highly robust DNA polymerase from a virus, have
been submitted for patenting and, in addition, the Sulfolobus genetic system has been patented.
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
180
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
04-11-2005
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Y
41cq77_one_hundred
G
Intellectual Property Rights
O
O
Rights belong to Copenhagen University, Institut Pasteur and Technical
University of Darmstadt. Co-applicants are David Prangishvili, Xu Peng,
Roger A. Garrett and Christa Schleper
N
Comments:
Patents granted
Partnership/other contractual agreements
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
C
Novel thermostable enzymes and genetic systems for Archaea
T
E
Innovative Aspects
Main advantage
H
Exploitation potential
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation/Firm
University of Copenhagen
Address:
Institute of Molecular Biology
and Physiologym Soelvgade 83H,
1307 Copenhagen K, Denmark
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Professor
Roger
Garrett
Phone:
Fax:
E-mail:
+45 35322010
+45 35322040
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
181
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100 Technology Offers stemming from EU biotechnology RTD results
T
E
29. RemaLog Xray
C
Title of result:
H
RemaLog Xray
N
Ownership: RemaControl Sweden AB
O
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
O
Measurement system for X-ray scanning and automatic grading of logs.
G
Detailed description of the technology:
Y
Current stage of development of the technology:
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
182
Patents granted
Partnership/other contractual agreements
04-11-2005
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G
Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Pilgatan 21
S-72130 Västerås
Sweden
Phone:
Fax:
E-mail:
+46 21 81 21 00
+46 21 81 18 81
[email protected]
L
O
Kjell
Petterson
N
Address:
Title:
First Name:
Surname:
O
Organisation/Firm
RemaControl Sweden AB
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Sawmill industry
T
E
A P P L I C AT I O N D O M A I N S
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© Digital stock, 1996
Plant
Biotechnology
41cq77_one_hundred
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100 Technology Offers stemming from EU biotechnology RTD results
P
L
1 . R H I ZO R E M E D I AT I O N O F P O L LU TA N T S
A
Title of result:
N
Rhizoremediation of pollutants
T
Ownership: Consejo Superior de Investigaciones Científicas - EEZ
T EC H N O LO GY D E S C R I PT I O N
B
Abstract of the technology:
I
O
T
Pseudomonas putida JLR11 is a microorganism that is able to use explosive compounds as an N source.
In addition, it is able to colonize the root system of a number of plants. Pseudomonas putida adheres to
plants seeds and once the seeds germinate, they form biofilms on the root surface and spread at high numbers in surrounding soils. Along with soil colonization, bacteria remove large amounts of explosives.
E
Detailed description of the technology:
C
H
N
O
L
A number of surface proteins of P. putida allow the strain to coat seeds of almost any tested plant. In
the case of corn and maize plants, a single seed can be coated by 107 cells. Seeds are sown in polluted
soils and upon irrigation they germinate and produce roots and stem. With lux marked JLR11 we
observed that bacteria formed loose microcolonies on the root surface that colonized the surrounding
bulk soil to levels as high as 109 CFU/g soil. These bacteria are metabolically active and take up TNT,
which is inactivated by the action of a number of denitrases and nitroreductases present in bacteria thus
removing the pollutant. Field tests have revealed that a after a period of one month, soil originally polluted with 1 g TNT/Kg soil is free of pollutants as determined by HPLC analysis. Further developments of this rhizoremediation action include transgenic trees expressing bacterial genes to treat deep
soils and aquifers polluted with TNT.
O
Current stage of development of the technology:
G
Y
Development phase
Tested, available for demonstration
Already on the market
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
Exploitation potential
Innovative Aspects
Main advantage
186
Easy treatment of soils and underground waters polluted with TNT
04-11-2005
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G
Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Title:
First Name:
Surname:
Prof.
Juan-Luis
Ramos
Address:
Phone:
Fax:
E-mail:
34 958 181608
34 958 135740
[email protected]
L
O
N
C/ Prof. Albareda, 1
E-18008 Granada – Spain
O
Organisation/Firm
Consejo Superior de Investigaciones Científicas
- EEZ
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
B
I
O
T
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
T
N
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
A
L
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
P
E
A P P L I C AT I O N D O M A I N S
187
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100 Technology Offers stemming from EU biotechnology RTD results
P
N
T
Title of result:
L
2 . G I Q S B a ck b o n e - i n te r e n te r p r i s e d a ta
w a re h o u s i n g f o r q u a l i t y m a n a g e m e n t i n
f o o d ch a i n s
A
GIQS Backbone - Inter enterprise data warehousing for quality management in food
chains
B
Ownership: GIQS e.v.
I
T EC H N O LO GY D E S C R I PT I O N
O
T
Abstract of the technology:
E
C
The central food chain information system (GIQS Backbone) is an inter enterprise data warehouse and
built on standard IT technology. It links existing data sources and locally available information from
actors along the food chain. Through Business Intelligence Tools it supports a variety of analyses,
including elaborate queries on large amounts of data for the various chain stakeholders.
N
The inter enterprise data warehouse for food chains couples the information with smallest identifiable
units and supports three functions:
• Information exchange: An efficient form of information exchange; this does not only save costs, but
meets better with the needs of the company because the information can be used directly.
• Traceability: In the backbone important process data can be tracked up and downstream; this system is flexible and can be quickly adjusted to changing standards. In case of a quality problem, necessary data for recall management is available in the right form.
• Chain Business Intelligence: Efficient decision support tools are of high importance to make use of
the newly available information. A key driver is the aim to reduce uncertainty in decision making,
through prior knowledge on emerging decision alternatives at control points. The data warehouse
supports decision making in organisations. It is structured to enable a variety of analyses, including
elaborate queries on large amounts of data that can require extensive searching. Through its long
term availability the data warehouse enables better comparisons and prognostic views on the available information. With Business Intelligence tools the data can be specifically prepared for information needs of the various chain stakeholders:
– as standard reports that provide chain actors with regular information in a fixed format;
– as easy-to-use interactive reports that enable users more flexible views on specific information;
– for ad-hoc analyses and queries through multi dimensional analyses of available chain information.
This tool is currently implemented and validated in Dutch German pork as well as fruits and vegetable
chains.
O
H
Detailed description of the technology:
L
O
G
Y
188
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Pagina 189
Y
41cq77_one_hundred
L
O
N
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : system on the market and reference implementation scenarios for pork
chain, further implementation scenarios developed in applied research
projects
O
G
Current stage of development of the technology:
C
Patents granted
Partnership/other contractual agreements
E
Patents applied for but not yet granted
Exclusive rights
License agreement reached
H
Intellectual Property Rights
O
Innovative and integrated approach to fulfil food chain actors information
requirements for quality management, traceability and process improvement
B
I
Innovative Aspects
Main advantage
T
Exploitation potential
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation Type: University
Organisation size: < 50 employees
Industry
+49228 732821
+49228 736515
[email protected]
Research Institute
50-249 employees
N
T
Phone:
Fax:
E-mail:
Start-up company
250-500 employees
A
c/o University of Bonn
Katzenburgweg 7
53115 Bonn
Germany
Prof. Dr.
Brigitte
Petersen
L
Address:
Title:
First Name:
Surname:
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
food chain quality information management
189
P
Organisation/Firm
GIQS e.v.
41cq77_one_hundred
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100 Technology Offers stemming from EU biotechnology RTD results
P
L
A
3 . R P E , a g e n e i n v o l v e d i n p l a n t re s p o n s e to
n e m a to d e s
N
Title of result:
T
RPE, a gene involved in plant response to nematodes
Ownership: INRA – Institut National de Recherche Agronomique
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
T
E
C
H
N
O
The identification and cloning of nematode responsive plant genes and promoters constitute a major
challenge for the knowledge in understanding the plant-nematode interaction and the development of
novel approaches to engineer plant resistance. Nematode responsive promoters may be used to express
anti-nematode proteins, phytotoxic proteins or essential genes (anti-sense approaches) that interfere
with the development of feeding cells. In this BIO4-96-0318, we have developed a ‘tagging approach’
using a promoter trapping strategy with a promoterless b-glucuronidase (GUS) construct introduced
randomly into the Arabidopsis genome via Agrobacterium T-DNA transformation.
We have isolated an A. Thaliana gene that is essential for the early steps of the nematode feeding site
(NFS) formation induced by the root-knot nematode Meloidogyne incognita. It encodes a protein similar to the D-ribulose-5-phosphate 3-epmerase (RPE), a key enzyme of the pentose phosphate pathway.
The RPE promoter analysis showed that this promoter is functional in Arabidopsis and potato and will
be usable for engineering resistance against nematodes. The RPE gene can be used as antisense construct
under the control of specific nematode responsive promoters to interfere with the development of NFS.
L
Detailed description of the technology:
O
G
Y
We developed a promoter trapping strategy using the collection of T-DNA tagged A. Thaliana lines generated at INRA Versailles, which was obtained by in planta transformation. The aim of our project is to
characterize plant genes which are upregulated during the process of initiation and maintenance of feeding structures induced by root-knot nematodes. During the 3 years of this project, 3000 T-DNA tagged
T3 plants were screened for activation of the GUS reporter gene in the NFS induced by root-knot
nematodes, at early and later time points after inoculations. Of the 25 transgenic lines that showed
increased gus expression in NFS, the A3 line has been further characterized. It showed an upregulation
of the transgene in early steps of NFS formation induced by the root-knot nematode Meloidogyne
incognita. This pattern of expression is similar to that of key regulators of cell cycle, but it is not
observed with cyst nematodes. Later in NFS development, this gene is induced by both root-knot and
cyst nematodes. This gene encodes a protein similar to the D-ribulose-5-phosphate 3-epimerase (RPE)
(EC5.1.3.1), a key enzyme in the reductive Calvin cycle and the oxidative pentose phosphate pathway
(OPPP). Quantitative RT-PCR showed the accumulation of RPE transcripts in potato as in Arabidopsis NFS. Homozygous rpe plants have a germination mutant phenotype that can be rescued in dwarf
plants on sucrose-supplemented medium. To test the implication of RPE in ginant cell formation, we
have infected dwarf mutants with M. incognita and H. schachtii and we showed RPE is really needed
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O
in the giant cell formation. The full-lenth RPE promoter fused to gus is functional in Arabidopsis. To
test the functionality of the RPE promoter in plants, A. rhizogenes transformation experiments were
planned in different plant species and we have shown that the full-lengh RPE promoter is also active in
potato since gus expression was found in most of root apexes and galls after infection with M. incognita.
G
Y
41cq77_one_hundred
Current stage of development of the technology:
C
H
N
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : basic and applied research
Main advantage
I
O
T
The RPE promoter is widely expressed in different parts of the plant and we are
trying to improve its specificity to the nematode feeding site by analysing different parts of this promoter in order to identify nematode responsive elements.
Experiments are in progress to produce the RPE antisense under the control of
a specific promoter for nematode feeding sites.
Plant-parasitic nematodes are major pests of temperate and tropical agriculture
and they have a global economic effect on crops of more than $100 billion each
year. Among them, the sedentary endoparasitic nematode genera Meloidogyne,
Golobodera and Heterodera, in particular, are responsible for major crop losses. Dependence on chemical control is likely to decline as more nematicides are
either withdrawn or used more restrictively because of perceived toxicological
hazard or environmental harm. Commercially successful resistant cultivars are
available but the restricted number of know genes for resistance limits their
widespread use in breeding programmes. Therefore, novel approaches to engineer novel defences against these nematodes have been developed through different strategies based on the understanding of the plant/nematode interactions.
The anti-feeding strategy looks promising since nematode development and
reproduction fully depend on the successful formation of the nematode feeding
site. The RPE gene has been shown to be essential for nematode feeding sites in
the case of Meloidogyne infestation. This gene is regulated in potato in a manner similar to that of Arabidopsis after infection with sedentary parasitic nematodes. In addition to maximise the chances on public acceptance and to reduce
the genetic load on the plant, highly specific and restricted spatial and tempo191
N
Innovative Aspects
A
Exploitation potential
T
B
PCT application No. FR99/01398 – Gene de la D-ribulose-5-phosphate-3epimerase de réponse aux nematodes
L
Comments:
Patents granted
Partnership/other contractual agreements
P
Patents applied for but not yet granted
Exclusive rights
License agreement reached
E
Intellectual Property Rights
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L
ral expression of the transgene is necessary. At the moment, the RPE promoter
is widely expressed in different parts of the plant. We are trying to improve its
nematode responsive elements. However, experiments are in progress to produce RPE antisense under the control of a specific promoter for nematode feeding sites.
A
N
T
B
I
O
T
E
C
H
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
N
O
Organisation/Firm
INRA – Institut National de Recherche
Agronomique
Address:
L
O
G
UMR INRA/CNRS/
Université de Nice Sophia Antipolis
Interactions PlantesMicroorganismes et santé végétale
BP 167, 400 Route des Chappes
F-06903 Sophia Antipolis cedex,
France
Y
Organisation Type: University
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Mr
Pierre
Abad
Phone:
Fax:
E-mail:
+33 492 38 64 02
+33 492 38 65 87
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
192
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
N
T
B
I
O
T
E
C
H
N
O
L
O
G
Y
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L
A
4 . B i o ch e m i ca l m a r ke rs f o r d o r m a n c y b re a k
i n p o ta to t u b e rs
N
Title of result:
T
Biochemical markers for dormancy break in potato tubers
Ownership: Scottish Crop Research Institute
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
T
E
C
We have identified biochemical markers for dormancy break in potato tubers. These markers develop
in the tuber buds several days in advance of any visible sign of bud growth. Protocols for the quantification of these markers are currently available and can be adapted to develop diagnostic kits for the
rapid determination of the dormancy status in potato tubers. These markers can find use in research for
the identification of novel methods for the manipulation of potato dormancy by chemical or genetic
means. In addition, these tools may be very valuable for commercial store managers or retailers for
defining storability of tuber stocks. It is predicted that the use of these markers may be extended to
other commercially important species for applications in forestry or horticulture.
H
N
Detailed description of the technology:
O
L
O
G
Y
A large increase (between 6 and 20-fold) in the concentration of certain compounds was consistently
observed in the apical bud of tubers stored at 4° or 10° C between 7-10 days prior to any visible swelling
in the bud. Biochemical and molecular investigations have confirmed that the increase is associated with
the process of dormancy break in tubers. These observations have been carried out over two consecutive harvests. It is anticipated that it will be possible to develop a diagnostic kit for the identification of
these dormancy-break markers. Analytical techniques for the quantification of these compounds are
routine in most laboratories and may be adapted for such use. For application development we will need
to scale down the quantity of material analysed i.e. optimise the assay sensitivity by evaluating the available range of immobilised enzymes, biosensors and other reaction indicators. The kit may find use in
scientific research or for the testing of the dormancy status of tuber stocks by store managers or large
scale retailers.
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41cq77_one_hundred
L
O
N
H
C
E
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Applied research. Identification of markers repeated in tubers from third
(1999-2000) harvest and in tubers bought from local stores. Some variability observed in the absolute amount of individual markers between years but
strong consistency in the concentration ration between markers.. Biochemical markers used to select genes up-regulated specifically during dormancy
break. Screening of buds from other commercially important plants (woody
species) for cross-species extension of diagnostic technology.
Further Research or development – Venture Capital – Private-public partnership
O
G
Current stage of development of the technology:
O
Patents granted
Partnership/other contractual agreements
I
Patents applied for but not yet granted
Exclusive rights
License agreement reached
T
Intellectual Property Rights
195
T
N
A
L
Product development: refinement of existing analytical protocols for development of the diagnostic kit. Testing of the kit in potatoes stored under various
regimes (extensive storage facilities). Screening of dormancy status in other
commercially important plants (i.e. woody species). Use of markers for identification of genes associated with dormancy break in plants of commercial value.
Tuber weight loss during storage amounts to 5 % of the stored crop: 24 million
€ in the UK alone. The pressure for the removal of a number of chemical sprout
suppressant will reduce the choice of tools to the store manager to limit these
losses. Store managers and processors will benefit through the accessibility of
predicitive tools for dormancy break. It is predicted that such a tool will be
invaluable for decision making on storage strategies. Use of the kit in scientific
research may lead to the identification of the mechanisms involved in dormancy break which may provide targets for new specific (non-toxic) chemical
sprout suppressants. Alternatively the transgenic approach may be used, pending social acceptability (the technology is available). There may be IP and profit returns from development of a user-friendly tool for the determination of
dormancy status. Further benefits may drive from the use of the kit in other
commercially important plants (e.g. to woody species) with applications in
forestry and horticulture.
P
Innovative Aspects
Main advantage
B
Exploitation potential
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L
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
A
N
Organisation/Firm
Scottish Crop Research Institute
T
Address:
Invergowrie
Dundee DD2 5DA, UK
Organisation Type: University
Industry
Title:
First Name:
Surname:
Dr
Roberto
Viola
Phone:
Fax:
E-mail:
+44 1382 562731
+44 1382 562426
[email protected]
Research Institute
Start-up company
Other
B
Organisation size: < 50 employees
50-249 employees
250-500 employees
>500 employees
I
O
A P P L I C AT I O N D O M A I N S
T
E
C
H
N
O
L
O
G
Y
196
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
N
T
B
I
O
T
E
C
H
N
O
L
O
G
Y
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A
5 . Me t h o d f o r e n h a n c i n g t h e co n te n t o f
s u l p h u r co m p o u n d s i n p l a n t s
N
Title of result:
T
Method for enhancing the content of sulphur compounds in plants
Ownership: Biogemma
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
T
E
C
H
N
O
L
O
G
Y
Sulphur rich amino acids (cysteine and methionine) as well as lysine are amino acids which are not produced by monogastric animals and need therefore to be supplied by their diet. Corn seeds, which are
extensively used as animal feed, have a limited amount in those sulphur rich amino acids. As a mean to
over-produce cysteine production in maize, a gene encoding Adenosine 5’ Phosphosulfate Reductase, a
key enzyme in cysteine production, has been isolated from Lemna minor, cloned behind constitutively
expressed or seed specific promoters and introduced into maize plants. Leaves or grains of such transformed maize plants contain increased amounts of cysteine and cysteine derived compounds.
Lysine belongs to the family of amino acids which is not produced by monogastric animals and needs
therefore to be supplied by their diet. Corn seeds, which are extensively used as animal feed, have a limited amount in Lysine. Lysine, present at high levels is toxic to the plant cell and is therefore tightly regulated at its level of synthesis and/ore degradation. Dihydrodipicolinate synthase is a key enzyme
involved in the synthesis of lysine and its activity is regulated by the lysine amount in the cell compartment (negative feedback). A mean to increase lysine production in maize cells is to introduce in those
cells a mutated lysine insensitive form of this enzyme. The resulting overproduced lysine can then be
trapped into lysine-riche storage proteins (modified gamma Zein High Lysine). Lysine keto-glutarate
(LKR) is the first enzyme participation in Lysine degradation. A mean to increase Lysine content in
maize plants, is to decrease the production of LKR either by an antisense approach aimed at down-regulating Lysine keto-glutarate reductase gene or by knocking out this gene via transposon insertion and
to trap the resulting lysine into lysine-rich storage proteins. Those approaches were developed in maize
plants by P09. Serine acetyl transferase (SAT) is a key enzyme in the syteine biochemical pathway in
activating L-serine by transfer of an acetyl group to generate O-actyl-serine, an intermediate in cysteine
production. It has been shown by P02 that transgenic potato plants expressing an E. colin SAT gene
under the control of the constitutively expressed 35S promoter present more cysteine and glutathione
in their leaves. As a mean to over-produce cysteine in maize, a similar approach will be undertaken in
maize. The over-produced cysteine could then be trapped into sulphur-rich proteins, i.e. the sunflower
seed albumin protein.
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L
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C
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P
Adenosyl Phosphosulfonate Reductase gene from Lemna minor
Transformation vectors HMWG promoter - APR gene – NOS terminator
Actin promoter plus first intron – APR gene – NOS terminator
Transformed plants with either HMWG promoter construct or Actin promoter construct
Transformed plants presenting an increase in cysteine and cysteine derived products
DHDPS mutated (lysine insensitive) genes from N. Sylvestris (Ns) A. thaliana (At)
Transformation vectors HMWG promoter – At-dhdps gene – NOS terminator
35S promoter – Ns-dhdps gene – NOS terminator
Ubiquitin promoter – Ns-dhdps gene – NOS terminator
Modified gamma Zein gene enriched in Lysine
Transformation vector gamma Zein promoter – gamma Zein High Lysine – gamma Zein terminator
Particle gun transformed plants with the above mentioned transformation vectors
Transformed plants presenting increased lysine content
Agrobacterium transformation vector bearing two genes of interest:
Gamma Zein promoter – gamma Zein High Lysine gene – gamma Zein terminator and HMWG promoter – Sunflower seed albumin (Sfa8) gene – NOS terminator
Agrobacterium – transformed plants with modified gamma Zein gene and Sfa8 gene.
LKR knock-out (transposon inserted) mutants from maize
LKR genomic fragments from maize
Agrobacterium transformation vector HMWG promoter –a/s Lkr – NOS terminator
Agrobacterium transformed plants with Lkr fragment in antisense orientation
Modified gamma zein gene enriched in lysine residus
Particle gun transformation vector (gamma Zein promoter – gamma Zein High Lysine – gamma Zein
terminator)
Agrobacterium transformation vector bearing 2 genes of interest: gamma Zein promoter – gamma Zein
High Lysine gene – gamma Zein terminator and HMWG promoter – Sunflower seed albumin (Sfa8)
gene – NOS terminator
Particle gun transformed plants with modified gamma Zein gene
Agrobacterium-transformed plants with modified gamma Zein gene and Sfa8 gene.
Serine acteyl transferase gene from E. coli
35S promoter – SAT – transformed potato plants overproducing cysteine
Maize transformation vector HMWG promoter – SAT gene – NOS terminator, rice actin promoter with
its first intron – SAT gene – NOS terminator
Particle gun transformed maize plants with the above mentioned SAT transformation vectors
Sunflower seed albumin gene (Sfa8) from helianthus annuus
Maize transformation vectors HMWG promoter – sfa8 gene – NOS terminator, HMWG promoter plus
rice actin first intron – sfa8 gene – NOS terminator
Transformed maize plants with the above mentioned sfa8 transformation vectors
Transformed maize palnts expressing the sunflower seed protein in their grains
O
G
Detailed description of the technology:
41cq77_one_hundred
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P
L
Current stage of development of the technology:
A
N
T
B
I
O
T
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Applied Research. Current status is Proof of Concept since the plants were
generated by particle bombardment and present mainly multiple insertion
sites. New maize transformation using Agrobacterium in order to generate
transgenic plants with a simple integration pattern. Screening of transformants (high cysteine producer). Generation of homozygous events and
introgression into commercial varieties. Agronomical evaluation, i.e. stress
resistance (cold tolerance, pathogen resistance …). Feeding studies.Commercialisation, marketing. Seeds from mutated Ns-DHDPS gene transformed plants, mutated At-DHDPS gene transformed plants, modified
gamma Zein (High Lysine) transformed maize plants (particle bombardment), modified gamma Zein (High Lysine) + Sunflower seed albumin transformed maize plants (Agrobacterium)
E
Intellectual Property Rights
C
H
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Comments:
N
O
L
O
G
Y
200
Patents granted
Partnership/other contractual agreements
Patent (‘Procédé d’obtention de plantes à teneur enrichie en cysteine et glutathion’) submitted the 06.01.2000 in France under the number FR-00139.
Patent (public) WO97/28247 (biocern-Biogemma) ‘Amino acid-enriched plant
protein reserves, particularly lysine-enriched maize gamma-zein, and plants
expressing such proteins’; WO99/15004 (CSIRO) ‘Methods of altering storage
organ composition’; WO97/41239 (Pioneer Hi Bred International Inc) ‘transgenic plants with enhanced sulphur amino acid content’; WO98/42831
(DuPont) ‘chimeric genes and methods for increasing the lysine content of the
seeds of plants’; EP429458 (Molecular Genetics Research) ‘Method of inducing
lysine overproduction in plants’, WO00/01833 (Garching Innovation) ‘Method
for enhancing the content of sulphur compounds in plants’.
FR97/00167, covering lysine enriched storage proteins (maize gamma Zein) and
plants expressing such proteins.
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41cq77_one_hundred
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L
O
N
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C
E
T
O
Biogemma is a biotechnological company specialised in gene isolation, crop
transformation and genomics technology to improve molecular and classical
breeding. It is owned by two of the largest French breeding companies (Limagrain and Pau-Euralis, 55 and 25 % of the shares respectively), together with
the financial support of Unigrains and Sofiproteol (10 % of the shares each).
Biogemma’s mission is to develop new maize lines which can then be introduced in Limagrain’s and Pau-Euralis’ breeding programmes. Maize plants,
which are largely used as animal feed, have a low rate of sulphur containing
amino-acids (cysteine and methionine). Those amino-acids are not synthesized
by monogastric animals, and need to be supplied by the diet, where they are
usually limiting. The use of APR transformed lines should therefore allow an
increase in the cysteine and methionine proportion in animal feed. Biogemma
intends to introgress this new trait into its shareholders maize varieties, to
apply for a marketing release and to officially deliver the new lines to the breeders. Methionine and threonine have in common the same precursor in their biochemical pathway: O-phospho homoserine. The use of antisense Threonine
Synthase transformed lines should therefore allow a shift towards methionine
synthesis and an increase in the methionine proportion in animal feed.
B
I
Innovative Aspects
Main advantage
G
Exploitation potential
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
24 avenue des Landais
F-63170 Aubière, France
Organisation Type: University
Organisation size: < 50 employees
Industry
Phone:
Fax:
E-mail:
+33 473 427977
+33 473 427981
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
A
N
Dr
Pascual
Perez
L
Address:
Title:
First Name:
Surname:
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
anaesthetics, aquaculture,
community medecine
201
P
Organisation/Firm
Biogemma
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A
6 . E x t r a c t i o n p ro ce s s o f p e c t i n f ro m
p o ta to e s , w i t h l o w re s i d u a l s ta rch
N
Title of result:
T
Extraction process of pectin from potatoes, with low residual starch
Ownership: CP Kelco APS
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
T
The result is a process that can be used in large, commercial scale to extract pectin from potatoes with
low amounts of residual starch. The resulting product bears resemblance to existing sugar-beet pectin
products, i.e. non-gelling and viscosifying. No valuable application has been identified yet and the
potential is unknown but is intended to be explored.
E
C
Detailed description of the technology:
H
N
The process developed is state-of-the-art in the sense that it can be applied in large, commercial scale,
contrary to most processes described in literature. A significant problem is co-extraction of starch when
starting from fresh potatoes. This problem is solved by the use of starch-degrading enzymes. It will be
advantageous to combine this process with a starch extracting process (in commercial scale), i.e. use the
waste product from starch processing as a raw material. This is intended explored.
O
L
Current stage of development of the technology:
O
G
Y
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Results of demonstration trials available
The process has been tried in pilot plant scale and the resulting pectin is
available for testing. It is intended to repeat the trial with fresh potato pulp
during next harvest campaign.
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
202
Patents granted
Partnership/other contractual agreements
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41cq77_one_hundred
O
We can provide an extraction process that is simple and works in large scale to
extract pectin with low residual starch.
B
I
O
T
E
C
H
N
O
L
Innovative Aspects
Main advantage
G
Exploitation potential
Brian
Rudolph
Phone:
Fax:
E-mail:
+45 56165616
+45 56169446
@cpkelco.com
N
Title:
First Name:
Surname:
Ved Banen 16
DK-4623 Lille Skensved, Denmark
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
203
P
Address:
L
A
Organisation/Firm
CP Kelco APS
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
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7. N e w m a p p i n g p o p u l a t i o n s , m o l e c u l a r
m a r ke rs a n d g e n e s f ro m m a i ze
N
Title of result:
T
New mapping populations, molecular markers and genes from maize
Ownership: University of Bristol
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
T
E
C
H
N
O
L
O
G
Y
The overall success of this project can be assessed in terms of the number of substantial results which
have been obtained, markers produced and in the chromosomal regions which have been characterised
via YAC and BAC clones. The Map Maize consortium members have generated results for each of the
original four traits. For instance, we have generated and utilised several very large mapping populations.
We have used these populations to generate fine genetic maps for two of the four traits: the Early Maturity Gene: VGT1, and the Gametophytic Male Fertility Gene: GaMS-1. For three of the four traits, we
have used the F2 maize BAC library, generated as part of work package five, to identify clones in the
chromosomal region of the trait. These BAC clones have been fingerprinter to identify possible contigs.
The clones are currently being further characterised to identify overlaps and transcribed sequences. In
the case of Rp1 locus we have identified several Rp1 copies within a region of over 300kb in the genotypes F2 (Flint) and LH82 (Dent). A significant part of the Rp1 contig is now being sequenced to further understand this complex region. The Map Maize Consortium has generated the following new
materials of potential commercial interest as tools for analysing and modifying maize to make it more
suitable for European conditions:
- a Maize BAC library which is free for public use
- numerous molecular markers linked to traits of agronomical and industrial important to EU maize
breeding
- several mapping populations for traits of agronomical and industrial important to EU maize breeding.
Two contigs for the Rp1 disease resistance locus.
All of the material generated may be used for generation of new maize varieties with agronomical and
industrial useful traits leading to development of new varieties by commercial seed companies.
Detailed description of the technology:
1. The result is a set of products, namely, a range of mapping populations, libraries, markers and genes
that extend the options of agi-biotechnology companies to manipulated and breed new varieties of
maize.
2. The result is relevant to the field of biotechnology, with the most immediate potential applications
likely to be in agriculture.
3. The number of large insert libraries and markers available for the characterisation of monocot crops
is restricted; the present result significantly increases the range of such elements available to plant
biotechnology.
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O
L
O
4. Methods used to identify and analyse the material described in this result are amongst the best currently available and include more efficient procedures for the production of large insert libraries,
mapping populations and markers development.
5. Exploitation of this result will rely on a range of IP-protected technologies related to marker technology and would require licensing or other agreements to proceed beyond pre-competitive R&D.
G
Y
41cq77_one_hundred
H
C
E
T
O
I
B
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Applied research
The following materials are available to the consortium for exploitation:
1. Two large insert maize libraries, including individual YAC and BAC
clones containing specific sequences.
2. Several mapping populations for traits of importance to European maize
breeders.
3. Approximately 50 CAP, RAPD and AFLP markers for traits of importance to European maize breeders.
4. Trait data on three agronomically important traits.
5. Sequence data derived from genomic regions containing the agronomically important traits.
N
Current stage of development of the technology:
Intellectual Property Rights
T
Patents granted
Partnership/other contractual agreements
205
L
Identification de genes associés ą un locus QTL de digestibilité du maēs. Application number 0001152.
1. Five mapping populations made with proprietary line of Limagrain Genetics
2. Characterisation of those lines for silage quality by near Infra Red technology with the use of a proprietary know-how
3. A previous and continuing collaboration with partner 4 on genes involved
in silage quality.
4. Two cDNA’s called X71 and R8 mapped in close linkage on a locus on chromosome 3.
Twenty two (22) other cDNA’s putatively involved in silage quality traits have
been isolated and mapped during this collaboration. Those are not included in
the project and are therefore not included in the project and are therefore not
included nominatively in this list. If requested for scientific purposes of the
project, some of those cDNA’s may be included after they have been added to
this background technology list.
P
Comments:
A
N
Patents applied for but not yet granted
Exclusive rights
License agreement reached
41cq77_one_hundred
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100 Technology Offers stemming from EU biotechnology RTD results
P
L
Exploitation potential
A
Innovative Aspects
Main advantage
N
T
B
I
O
T
1. Potential applications include: delivery of new genes, traits and technologies
to maize breeders to improved production traits and provide environmental
benefits, ie modification of composition of the crop and its products for
food, feed and industrial uses; fundamental work on gene action in crop
species.
2. Users: plant biotechnologists, breeding companies, research institutions.
3. Innovative features and benefits: under many circumstances work on the
crop of interest is preferable to work on model species as these are in limited supply for monocot crops (ie rice).
4. Markets and barriers: there are no problems with conventional plant breeding, however, biotechnology based on plant genetic manipulation is going
through a difficult time in Europe and any immediate market for this result
looks to be centred on the United States, with perhaps China and South
America as possibilities. Commercial exploitation routes are likely to be via
companies with a strong presence in these markets. The five companies in
the present Consortium have some of these characteristics.
E
C
H
N
O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
L
Title:
First Name:
Surname:
Dr
Keith
Edwards
Address:
Phone:
Fax:
E-mail:
+44 117 331 7079
+44 117 925 7374
[email protected]
O
Organisation/Firm
IACR – Long Ashton Research Station,
University of Bristol
G
Long Ashton
Bristol, BS41 9AF, UK
Y
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
206
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
N
T
B
I
O
T
E
C
H
N
O
L
O
G
Y
Pagina 207
A
12:55
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41cq77_one_hundred
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100 Technology Offers stemming from EU biotechnology RTD results
P
L
A
8 . D D RT- P C R p ro to co l s f o r p o ta to g e n e
cloning.
N
Title of result:
T
DDRT-PCR protocols for potato gene cloning. Protocol for transformation and selection
of potato transgenic plants.
B
DDRT-PCR sequences and antisense transformation vectors. Transgenic potato plants
carrying a modified expression of genes G1-1 and A2-1.
Ownership: University of Parma
I
O
T EC H N O LO GY D E S C R I PT I O N
T
Abstract of the technology:
E
C
H
N
O
L
O
G
Y
DDRT-PCR performed starting from messenger RNA extracted from potato tubers harvested at different developmental stages (dormant tubers; tubers with apical sprout 1mm and 2mm long). This technique allowed for the isolation of genes expressed at low level. Therefore is very suitable for the isolation of potato tuber sequences considering the general low level of transcription in these tissues.
Transformation protocol was performed by starting from leaf discs and stem cuttings via Agrobacterium tumefaciens. The efficiency of the method was evaluated measuring different parameters: 1. Influence of the organ explants; 2. Influence of the age of explants on the shoot production; 3. Influence of
the explant permanence on the selecting media on the shoot production. Protocol for selection of transformed lines was performed by single leaf PCR analysis and Southern blot analysis. The genes G1-1 and
A2-1 were isolated by means of DDRT-PCR performed starting from messenger RNA extracted from
potato tubers harvested at different developmental stages (dormant tubers; tubers with apical sprout 1
mm and 2 mm long). These genes are differentially expressed in potato tubers during dormancy and
breakage of dormany. The expression of G1-1 is induced during the end of dormancy. While A2-1 is
strongly repressed during transition from dormancy to sprouting. These genes are, thus, potentially
involved in regulation of the process and the modificaton of their expression could represent a mean to
modify the length of dormancy. In order to determine the role of these genes in dormancy regulation
and on establish their potential for exploitability in conservation of seed tubers, their expression was
inactivated. Therefore the coding regions were inserted in the binary vecto pBI121 under the control of
constitutive promoter CaMV35S in antisense orientation. The construct obtained were used to transform potato plants (var. Desirée)
The preliminary analysis of transgenic tubers, showed that several lines displayed a modification in the
duration of dormancy.
Detailed description of the technology:
The use of DDRT-PCR utilising 12 primer combinations allowed for the isolation of more than 50
sequences that are expressed in a different way in dormant and sprouting tubers. The transformation
protocol evidenced that: 1. The transformation efficiency is higher starting from leaf explants than from
stems cuttings; 2. There is no significative correlation between the age of organ explant and the efficien-
208
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O
L
O
N
H
cy of transformation; 3. The permanence of the explants on the selective medium reduced the production of transgenic plantlets. The use of molecular genetics tools, allowed for the isolation of two genes
that are expressed in a different way in formant and sprouting tubers. The G1-1 is a short gene (0,45 kb)
which is specifically induced at the end of dormancy and during the early phases of sprouting; A2-1 has
a length of 1,5 kb, is expressed during dormancy and gradually repressed in the tubers progressing
toward sprouting. The analysis of tubers obtained from transgenic plants in which G1-1 was silenced
by use of the antisense technology, showed that several lines displayed a delay in sprouting comparing
with the wild type control. The analysis of tubers obtained from transgenic plants silencing A2-1
showed a great variability in the length of dormancy among the different lines obtained. Nevertheless,
some lines showed a shortening in the length of dormancy.
G
Y
41cq77_one_hundred
T
O
I
B
T
N
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Laboratory prototype: These results starting from a basic research could
become interesting for laboratory prototype research: DDRT-PCR applied
to potato tubers could be a tool for isolating DNA sequences available for
understanding tuber characteristics; the evaluation of parameters affecting
the transformation efficiency could be a useful tool to improve and facilitate
the transformation protocols. Application of protocols and methodologies
in an advanced state of implementation to different problem related with
gene cloning and transformation in potato plants. The first analysis of transgenic tubers carrying the inactivation of genes G1-1 and A2-1 showed a
modification in the duration of dormancy. These results are interesting for
an applied research with the goal to modify the dormancy characteristics of
tubers and to improve the conservatibility of potato seed tuber.
E
C
Current stage of development of the technology:
L
Patents granted
Partnership/other contractual agreements
P
Patents applied for but not yet granted
Exclusive rights
License agreement reached
A
Intellectual Property Rights
Comments:
Registered design: description of methodology for molecular analysis on potato tuber; description of transformation methodology for modification of potato characteristics
Patent will be apply for G1-1 and A2-1 antisense constructs under the control
of 35S CaMV Promoter and transgenic lines showing modification of dormancy length.
Licence agreement – Joint venture – Marketing agreement – Financial support
209
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100 Technology Offers stemming from EU biotechnology RTD results
P
L
Exploitation potential
A
Innovative Aspects
Main advantage
N
T
B
I
O
T
E
C
H
N
O
L
O
G
Y
210
Joint venture – Financial support
These results can be a starting point for setting up the methodologies for
improving potato tuber results. However more research is required to establish
the robustness of the system. At this stage more financial support is required.
DDRT-PCR could be applied for isolating many genes in potato tubers. Transformation analysis could be helpful to determine the efficiency of the methodology. These results could be useful for laboratories interested in studying the
expression analysis of potato tubers, both for basic and applied research.
Utilisation of potato plants transgenic for antisense constructs carrying G1-1
and A2-1 in improvement of agriculture and food industry. Application of
genes for Marker Assisted Selection. Transgenic plants can be a start point for
improving the quality of potato seeds. However, further research is required to
elucidate the genetic and physiological modifications and to establish the
robustness of the system. Meantime financial support will be required for: 1.
Obtaining licence agreement and trademarks 2. Small scale production of material for field trials and for evaluation on industrial transformation characteristics 3. Obtaining the authorisation following EU directives in terms of OGM.
Commercialisation decisions can only be taken place after this work has done.
Transgenics tubers with a modification in the length of dormancy, and in particular with a delay in tuber sprouting could be useful in Southern European
countries where the premature sprouting, due to high temperature is one of the
major problem for potato crop. Moreover, premature sprouting is an
undesiderable characteristic for potato industrial transformation. Therefore
seed and food industries could benefits from these researches. However, the
potentiality could not be easily accepted by public opinion.
04-11-2005
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G
Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation Type: University
O
+39 521 905606
+39 521 905665
[email protected]
N
H
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
T
E
Organisation size: < 50 employees
Phone:
Fax:
E-mail:
O
Section of Genetics and
Environmental Biotechnology
Department of Environmental
Sciences
V. le delle Scienze, 11/A
I-43100 Parma, Italy
Prof
Nelson
Marmiroli
C
Address:
Title:
First Name:
Surname:
L
Organisation/Firm
University of Parma
A P P L I C AT I O N D O M A I N S
B
I
O
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
T
N
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
A
L
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
P
211
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100 Technology Offers stemming from EU biotechnology RTD results
P
L
A
9 . A p o ro u s - m a t r i x s e n s o r to m e a s u re
t h e m a t r i c p o te n t i a l o f s o i l w a te r
N
Title of result:
T
A porous-matrix sensor to measure the matric potential of soil water
Ownership: Wageningen-UR
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
T
E
C
H
N
O
The matric potential of soil water is probably the most useful assessment of soil water status. However, the water-filled tensiometer (the benchmark instrument for measuring matric potential) typically
only operates in the range 0 to –85 kPa. In this project, we developed a porous-matrix sensor to measure matric potential in the approximate range –50 to –300 kPa. This sensor uses a dielectric probe to
measure the water content of a ceramic material with known water retention characteristics. The calculation of matric potential takes into account hysteresis through the application of an appropriate model
to measured wetting and drying loops. It is important that this model uses closed, rather than open scanning loops. The calibrated sensors were tested in the field and the output compared with data from
water-filled tensiometers and dielectric measurements of soil water content. These comparisons indicated that conventional tensiometers gave stable but false readings of matric potential when soil dried to
matric potentials more negative than –80 kPa. The porous-matrix sensors appeared to give reliable readings of matric potential in soil down to –300 kPa and also responded appropriately to repeated wetting
and drying. This porous-matrix sensor has considerable potential to help understand plant responses to
drying soil.
L
O
Detailed description of the technology:
G
Y
A full technical description of this sensor and recent developments are described in the following:
1. Whalley, W.R., Watts, C.W., Hilhorst, M.A., Bird, N.R.A., Balendonck, J. and Longstaff, D. J. (2001)
The design of porous material sensors to measure matric potential of water in soil. European Journal of Soil Science 52: 511-519.
2. Whalley, W.R., Clark, L.J., Take, W.A, Bird, N.R.A., Leech, P.K., Cope, R.E. and Watts C.W. (2005)
A porous-matrix sensor to measure the matric potential of soil water in the field. European Journal
of Soil Science (Submitted).
Both of these are available on request. The key features of the sensor are
1. A sensor to measure matric potential that needs no maintenance.
2. A new computer model to interpret the output of porous matrix sensors.
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Y
41cq77_one_hundred
H
Patents granted
Partnership/other contractual agreements
T
The method has been published in the literature and patents are not appropriate.
E
C
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Comments:
L
N
Intellectual Property Rights
O
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : We have had discussions with an industrial partner who has shown preliminary interest.
O
G
Current stage of development of the technology:
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
I
Matric potential can be measured with a sensor that needs no maintenance. This
makes it possible to use sensor based irrigation control that is controlled
according to plant stress or the likelihood of irrigation water leaching into the
ground water. The use of the sensor for advanced irrigation control remains to
be tested.
B
Innovative Aspects
Main advantage
O
Exploitation potential
Title:
First Name:
Surname:
ir.
Jos
Balendonck
Address:
Phone:
Fax:
E-mail:
+31(0)317-476654
+31(0)317-475347
[email protected]
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
213
P
PO Box 17, 6700AA
Wageningen The Netherlands
L
A
N
Organisation/Firm
Wageningen-University and Research
Agrotechnology and Food Innovations
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100 Technology Offers stemming from EU biotechnology RTD results
P
L
A
10. Real-time PCR for analysis of
g e n e / t r a n s c r i p t co p y n u m b e rs
N
Title of result:
T
Real-time PCR for analysis of gene/transcript copy numbers
Ownership: National Institute of Biology
B
T EC H N O LO GY D E S C R I PT I O N
I
Abstract of the technology:
O
T
E
C
Real-time PCR is currently the most accurate method for quantification of nucleic acids in biological
samples. We have applied the system for high throughput analysis of nucleic acids in different samples
for different applications - food and feed samples for quantification of GMO presence, analysis of plant
and mammalian lines for transgene copy number, analysis of plant tissues for analysis of gene expression. The system has been build to enable repeatable quantification system, with defined precision and
sensitivity using appropriate quality controls and statistical means. The high sample throughput is
achieved using 384-well setting of real-time PCR in combination with pipetting device.
H
Detailed description of the technology:
N
O
L
O
G
Y
Real-time PCR is an up-grade of conventional PCR. It enables following of PCR product synthesis in
the time course of reaction. The cycle at which the amount of PCR product increases over detection
threshold (Ct value) is used as a measure of initial amount of nucleic acid in the sample. The system for
assuring reproducible high accuracy (to fit into ISO and CEN standards) was set. Different systems of
internal and external controls were developed in addition to dilution controls included for every quantification. Every step of the procedure from nucleic acid extraction, through reverse transcription and
real-time PCR amplification were evaluated and validated to check the repeatability, reproducibility and
accuracy of a separate method. All parameters were evaluated using statistical approaches; a system for
measurement uncertainty was established. Accuracy is, in the case of GMOs measured also through
time, to check for any possible long term effects. In addition, the high sample throughput is achieved
using 384-well setting of real-time PCR in combination with pipetting device. This is enabling a large
number of samples/genes analyses in rather short time. A bioinformatics support for the analysis of
obtained data is built in parallel.
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Y
41cq77_one_hundred
L
O
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
O
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
G
Current stage of development of the technology:
H
Patents granted
Partnership/other contractual agreements
B
I
O
T
E
C
Patents applied for but not yet granted
Exclusive rights
License agreement reached
N
Intellectual Property Rights
Dr.
Kristina
Gruden
Phone:
Fax:
E-mail:
+386 1 4233388
+386 1 2573847
[email protected]
N
Title:
First Name:
Surname:
Vecna pot 111, Ljubljana
Slovenia
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
215
P
Address:
L
A
Organisation/Firm
National Institute of Biology
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
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100 Technology Offers stemming from EU biotechnology RTD results
P
N
T
Title of result:
L
1 1 . I d e n t i f i ca t i o n o f p a t h o g e n i c i t y - re l a te d
s e c re t i o n s f ro m ro o t k n o t a n d c y s t
n e m a to d e s
A
Identification, function & importance of nematode and plant factors involved in the
interaction between plant parasitic nematodes and their hosts
B
Ownership: Wageningen University
I
T EC H N O LO GY D E S C R I PT I O N
O
T
Abstract of the technology:
E
C
H
N
O
L
O
To identify crucial elements in the interaction between plant parasitic nematodes and plants, and to
exploit these elements for engineering broad and durable resistance against root knot and cyst nematodes by creating multiple barriers. First of all, the nematode will be prevented to migrate to the site
where it starts the initiation of a feeding cell. Secondly - if it nevertheless would reach this spot - it will
be prevented to form a feeding cell. Proper targeting will be guaranteed because either nematode
responsive elements from available promoters will be used or sets of promoters with common activity
at the site of interest only. Finally, these promoters will be used to drive a localised expression of multiple nematode-disturbing genes and the resulting plants will be tested for cyst and root knot nematode
resistance. RNA interference, the degradation of specific mRNAs by exposure to homologous doublestranded RNA, is potentially a useful tool to knock out individual pathogenicity factors in nematodes
and /or in their host plants. The outcome of this research project includes protocols to check the relevance of individual pathogenicity factors of nematode origin (for root knot nematodes: Rosso et al. 2005
- MPMI; for cyst nematodes: Chen et al. 2005 - MPMI). Moreover, dsRNAs against pathogenicity factors of plant or nematode origin were expressed in host plants. In various instances knocking out these
factors had a severe impact on nematode development.
G
Detailed description of the technology:
Y
To characterize and understand the interaction between cyst (genera Globodera and Heterodera) and
root knot (genus Meloidogyne) nematodes and two of their host plants, namely tomato and potato. By
unravelling the details of this interaction, we would be able to pinpoint the Achilles’ heel(s) of the interaction. During the NONEMA project we showed this assumption is indeed correct, and the deliverables of this project can directly be exploited for the engineering broad and durable resistance against
root knot and cyst nematodes. First of all, the nematode will be prevented to migrate to the site where
it starts the initiation of a feeding cell. Secondly - if it nevertheless would reach this spot - it will be prevented to form a feeding cell. Proper targeting will be guaranteed because either nematode responsive
elements from available promoters will be used or sets of promoters with common activity at the site of
interest only. Finally, these promoters will be used to drive a very localised expression of multiple nematode-disturbing genes and the resulting plants will be tested for cyst and root knot nematode resistance. First, research efforts focused on: the identification of pathogenicity factors from potato cyst and
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O
L
O
N
H
C
E
T
O
I
B
T
N
A
L
P
root knot nematodes, the determination of expression patterns of a range of cell cycle genes in and
around nematode-induced feeding structures, the identification of plant cell wall-degrading enzymes as
recruited by cyst nematodes, the analysis of promoters that have been identified in a preceding EC project (ARENA; BIO4-CT96-0318) and a search for new promoters that could be used for the targeting
of anti-nematode genes. A major research effort was invested into the identification and the functional
characterisation of pathogenicity factors from cyst and root knot nematodes1, the determination of
expression patterns of a range of cell cycle genes in and around nematode-induced feeding structures,
and the identification of plant b-1,4-endoglucanases and expansins that are recruited by cyst nematodes
during syncytium proliferation. Specific antibodies were raised that will allow localisation studies of
these proteins in young developing syncytia. In another workpackage, deletions studies are done on
promoters that have been identified. This will result in the identification of nematode-responsive promoter fragments that will be used to drive the expression of protein or a dsRNA construct that could
inhibit nematode invasion or the establishment of a feeding site. Research efforts are gradually shifting
from the identification of pathogenicity factors from cyst and root knot nematodes towards the determination of their biological role and the assessment of their relative importance. RNA interference, the
degradation of specific mRNAs by exposure to homologous double-stranded RNA, is potentially a useful tool to knock out individual pathogenicity factors in nematodes. Encouraging progress was made in
the development of a protocol to degrade mRNAs that are (mainly) residing in the oesophageal glands
of the infective nematodes. For the generation of nematode resistant plant, post-transcriptional gene
silencing (PTGS) seems to be to a promising, time & labour efficient approach. Partners started PTGSbased plant transformation targeting either pathogenicity factor from the nematode or plant genes
recruited by the invading nematode. In parallel, a number of Arabidopsis promoters were identified that
show similar expression patterns in tomato. Research focussed on the assessment of the importance of
putative pathogenicity factors from cyst and root knot nematodes in relation its infectivity. Infective
second stage juveniles from cyst and root knot nematodes are essentially non-feeding. To assess the relative importance of these putative pathogenicity factors, it is essential to realize an uptake of double
standed RNA into these juveniles. A method was developed to deliver dsRNA in the dorsal and the subventral esophageal glands of pre-parasitic juveniles from cyst nematodes. In parallel, the “dsRNA delivary by soaking protocol” was adapted in such a way that it can be used as well to knock out genes in
root knot nematodes. Finally the proof of concept - knocking out specific pathogenicity factors results
in host plant resistance - was delivered. Potato was transformed with so-called hair-pin constructs
encoding dsRNA against two pathogenicity factors produced by infective juveniles of the potato cyst
nematode Globodera rostochiensis. In both cases, transformed plants looked normal and several lines
were selected that are de facto resistant against potato cyst nematodes. Host plant resistance was also
created by silencing specific plant genes, viz. genes that are actively recruited by the invading nematode.
In two different approaches the silencing of cell cycle genes and plant cell wall-degrading enzymes
(CWDE) resulted in a significant level of resistance; in case of the cell cycle genes a reduction of about
70%, in case of the CWDE the developing females did not contain viable eggs (IP issues do not allow
us to be publicly more specific on the nature of the above-mentioned plant and nematode targets).
Hence, NONEMA research efforts identified specific nematode and plant targets that were shown to
be effective handles to create host plant resistances with limited or no undesired effect on the condition
of the host plant.
G
Y
41cq77_one_hundred
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P
L
Current stage of development of the technology:
A
N
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : basic and applied research
T
Intellectual Property Rights
B
Patents applied for but not yet granted
Exclusive rights
License agreement reached
I
Comments:
Patents granted
Partnership/other contractual agreements
At least two partners have a research & development collaboration with a
European biotech company
O
Exploitation potential
T
Innovative Aspects
Main advantage
E
C
H
N
O
L
O
G
Y
218
The consequences of nematode infestations for agriculture are enormous:
economic losses caused by nematodes worldwide are estimated to be in the
order of $77 billion each year. Agronomically important crops that suffer heavily from nematode infections include potato, tomato, sugar beet, barley, wheat,
soybean and peanut. Crop rotation is the most simple method to restrict yield
losses by nematodes but has a number of practical draw-bacs. The major means
of nematode control has been the application of chemical nematicides. Chemical nematicides are generally highly toxic compounds known to cause substantial environmental impact. In the past several years, issues such as ground water
contamination, mammalian and avian toxicity, and residues in food have caused
much tighter restrictions on the use of chemical nematicides. Some successes
have come forward from breeding programmes. Genetic resistance to certain
nematodes is available in some cultivars and several resistance genes have been
mapped and cloned. Programmes for the introduction of these genes in sensitive varieties have been initiated. However, strategies based on breeding or
genetic engineering of resistance genes have some inherent weaknesses. Firstly,
resistance genes usually operate against a very limited number of nematode
races. Secondly, resistance genes apparently work only in related plant species.
Alternative molecular strategies are being developed that should lead to a more
durable and broad range resistance against plant-parasitic nematodes. These
strategies are either based on the constitutive expression of proteins in plants
that have a nematicidal impact or on local expression of an anti-nematode or
anti-feeding site construct.
The identification of secretion compounds allows for the generation of
inhibitors (proteins or dsRNA) that hamper the interaction between the nematode and its host plant. By the identification of a range of secreted compounds,
the ones that play a major role in the pathogenicity of these pathogens can be
selected. If specificity is combined with proper targeting – the expression of
inhibitory molecules outside the target tissues should be reduced to an absolute
minimum – these resistant plant will be a viable and durable alternative that
replaces the use of nematicides.
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Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Binnenhaven 5
NL-6709 PD Wageningen,
The Netherlands
Phone:
Fax:
E-mail:
+31 317 483136/482197
+31 317 484254
[email protected]
L
O
Dr.
Johannes
Helder
N
Address:
Title:
First Name:
Surname:
O
Organisation/Firm
Wageningen University
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
B
I
O
T
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
T
N
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
A
L
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
P
E
A P P L I C AT I O N D O M A I N S
219
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L
12. MAX4 gene
A
Title of result:
N
MAX4 gene
T
Ownership: University of York
T EC H N O LO GY D E S C R I PT I O N
B
Abstract of the technology:
I
O
T
E
Despite its importance, little is known about the mechanisms controlling branching In the shoot, lateral branches develop from meristems formed in the leaf axils. However, meristem development is arrested unless auxin-mediated apical dominance can be overcome. An Arabidopsis mutant, Max4, that has
reduced apical dominance has been identified. The MAX4 gene has been isolated. In addition, it can be
used in marker assisted breeding. The MAX4 gene is expected to be used to manipulated shoot architecture in crops such as oilseed rape, as a mean to control pod shatter by coordinating synchronous floral development of apical and side branches.
C
Detailed description of the technology:
H
N
Current stage of development of the technology:
O
L
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
O
G
Intellectual Property Rights
Y
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Comments:
Patents granted
Partnership/other contractual agreements
Patent application P30154GB
Exploitation potential
Innovative Aspects
Main advantage
220
The MAX4 gene will be used to manipulate shoot architecture in GM crops
such as oilseed rape and in marker-assisted breeding.
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G
Y
41cq77_one_hundred
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Address:
Phone:
Fax:
E-mail:
+44 1904 328680
+44 1904 328612
[email protected]
L
O
Prof.
Ottoline
Leyser
N
Department of Biology
Helsington, York, YO1 5YW, UK
Title:
First Name:
Surname:
O
Organisation/Firm
University of York
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
C
Organisation size: < 50 employees
Industry
H
Organisation Type: University
B
I
O
T
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
T
N
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
A
L
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
P
E
A P P L I C AT I O N D O M A I N S
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100 Technology Offers stemming from EU biotechnology RTD results
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L
13 . N e w g e n e t i c p ro m o te rs f ro m m a i ze
A
Title of result:
N
New genetic promoters from maize
T
Ownership: IGER – Institute of Grassland & Environmental Research
T EC H N O LO GY D E S C R I PT I O N
B
Abstract of the technology:
I
O
T
E
C
H
This result relates to the major objective of the project, the isolation and characterisation of promoter
motifs conferring tissue specificity on the expression of associated genes in maize. The tissue targets are
leaf senescence; kernel development; pollen and seedling development; pathogenesis; and constitutive.
Approximately 40 new promoter sequences have been isolated and sequenced, and over half this number have been further characterised by GUS, Mu insertion or deletion analysis. They include: 5 senescence, at least 2 showing Mu insertions, 3 analysed by GUS, 1 showing developmentally-specific action
in another monocot. 7 MADS box promoters, all analysed by transient expression in the Opaque-2
based system. 3 histone deacetylase complex promoters, transformed into maize with GUS. 10 pollenspecific, 2 of which transformed with GUS into maize. 2-seedling-specific. 7 constitutive, two of which
have been transformed with GUS into maize. 4 pathogen-induced, transformed into maize with GUS.
2 guard cell-specific, 1 transformed with GUS.
N
Detailed description of the technology:
O
L
O
G
Y
1. The result is a set of products, namely, a range of genetic promoters that extend the options for controlled expression of new genes introduced to maize in a tissue- or development-specific fashion.
2. The result is relevant to the field of biotechnology, with the most immediate potential applications
likely to be in agriculture.
3. The number of characterised promoters available for manipulation of monocot crops is restricted;
the present result significantly increases the range of such elements available to plant biotechnology.
4. Methods used to identify and analyse the promoters described in this result are amongst the best currently available and include efficient procedures for EST generation, PCR-based cloning, reverse
genetics using maize mutator, high-output maize transformation procedures and transient expression
analysis.
5. Exploitation of this result will rely on a range of IP-protected technologies related to transformation
methodology and would require licensing or other agreements to proceed beyond pre-competitive
R&D.
222
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Y
41cq77_one_hundred
L
O
N
H
C
E
T
O
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : basic research
The following materials are available for exploitation:
- Almost 500 developmentally-specific ESTs, including both cDNA fragments and full-length clones, characterised by sequencing, homology
searches and expression patten.
- Approximately 40 promoters active in the following tissues or developmental stages: senescence; grain development; cell cycle; pathogen interaction; pollen; seedlings; and promoters with constitutive expression.
- Expression cassettes based on these promoters, validated by homologous
transformation and measured as GUS reporter gene expression.
- Maize regenerant lines transformed with more than 20 of these promoter-GUS constructs.
- Approximately 30 maize mutants with transposon insertions in coding or
upstream regions of the genes analysed in this project.
O
G
Current stage of development of the technology:
B
T
I Donnison, CM Griffiths, P Robson, H Thomas (1999) Senescence promoters.
UK Patent application GB00/01849
Aventis: Fusarium-inducible promoters (in preparation)
GB00/0189 (PCT application) patent search carried out
A
Comments:
Patents granted
Partnership/other contractual agreements
N
Patents applied for but not yet granted
Exclusive rights
License agreement reached
I
Intellectual Property Rights
1. Potential applications include: delivery of new genes to maize under the
control of tissue- or development-specific promoters; modification of crop
development for improved production traits and environmental benefits;
modification of composition of the crop and its products for food, feed and
industrial uses; fundamental work on gene action in crop species.
2. Users: plant biotechnologists, breeding companies, research institutions.
3. Innovative features and benefits; under many circumstances homologous
promoters are preferable to those from other species and these are in limited supply for monocot crops. The extended range of promoters isolated
from a major crop species increases the options for genetic manipulation. In
some cases the promoters have been shown to be effective in species other
than maize, thus extending potential benefits further.
223
P
Innovative Aspects
Main advantage
L
Exploitation potential
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100 Technology Offers stemming from EU biotechnology RTD results
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L
4. Markets and barriers: biotechnology based on plant transformation is going
through a difficult time in Europe and any immediate market for this result
looks to be centred on the United States, with perhaps China and South
America as possibilities. Commercial exploitation routes are likely to be via
companies with a strong presence in these markets. The two companies in
the present Consortium have some of these characteristics.
A
N
T
B
I
O
T
E
C
H
N
O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
L
Title:
First Name:
Surname:
Dr
Tony
Fentem
Address:
Phone:
Fax:
E-mail:
+44 1970 823002
+44 1970 820212
[email protected]
O
Organisation/Firm
IGER – Institute of Grassland &
Environmental Research
G
Plas Gogerddan, Aberystwyth
Ceredigion, SY23 3EB, Wales, UK
Y
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
224
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
N
T
B
I
O
T
E
C
H
N
O
L
O
G
Y
Pagina 225
A
12:55
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04-11-2005
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100 Technology Offers stemming from EU biotechnology RTD results
P
N
T
Title of result:
L
1 4 . K n o w - h o w a n d d a ta a b o u t m o l e c u l a r
g e n e t i c d i v e rs i t y i n a g e n e b a n k
co l l e c t i o n o f l e t t u ce
A
Know-how and data about molecular genetic diversity in a genebank collection of lettuce
Ownership: Plant Research International
B
I
T EC H N O LO GY D E S C R I PT I O N
O
Abstract of the technology:
T
E
C
H
N
O
L
The main objective of the demonstration project “Molecular Markers for Genebanks: Application of
Marker Technology for the Improvement of Ex Situ Germplasm Conservation Methodology’ was “to
demonstrate the possibilities of applying molecular marker technology for improving genebank
methodology. Know-how about large scale tissue sampling, DNA extraction, and characterisation with
modern molecular markers (FLP and Microsatellites) has been build up. Furthermore, unique insight in
issues related to applying molecular data to genebank management have been gained, collection management issues have been formalised. Also, dataset with fingerprints of genebank material have been
generated. These comprise of up to three AFLP primer combinations and ten microsatellites scored on
two to five plants of each accession in the CGN lettuce genebank. Furthermore ten accessions have been
characterised by 60 plants, and five of these ten accessions has been sampled both before and after regeneration. The resulting data sets comprise a total of 1330169 AFLP datapoints and 66360 Microsatellite
datapoints on all 2332 accessions in the CGN lettuce genebank. Based on this know-how and data, a
number of papers are in preparation, and more importantly a follow up project has been started (also
EU funded), which is much larger that the current project, and which will generate exploitable results.
O
Detailed description of the technology:
G
Y
The datasets are unique in their kind; never before such large and complete datasets have been generated. The collection is well documented and of moderate size, as a result all hypothesis on the application
of molecular markers in genebank management can be tested using these datasets (restricted to maily
selfing crops). The know-how generated provides the second prerequisite for further studies; it
appeared that the field is so underdeveloped that neither concepts nor tools are available. The first steps
towards these tools and concepts have been made, and the continuation project builds on these.
Current stage of development of the technology:
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Applied research. The datasets have been generated, the development of
tools and concepts have been initiated.
226
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Y
41cq77_one_hundred
G
Intellectual Property Rights
O
Patents granted
Partnership/other contractual agreements
H
C
E
T
Plant Research Int’l, Keygene and the International Plant Genetic Resources
Institute are all involved in the follow-up project ‘Improved use of germplasm
collections with the aid of novel methodologies for integration, analysis and
presentation of genetic data sets’, a 42 months EU funded RTD project (QLK52000-00722) with 10 partners and a total budget of € 2 726 000.
Plant Research Int’l uses the results in its daily management of the lettuce collection by supporting decisions concerning the selection of material to users,
identification and elimination of duplicates etc.
The main exploitation activity was the conception, formulation, and submission
of the follow-up EU RTD project QLK5-2000-00722 which started January 2001.
This follow-up project will yield exploitable software and possibly even identify
exploitable genes, etc. For more information please refer to this project.
B
I
Innovative Aspects
Main advantage
O
Exploitation potential
N
O
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Organisation Type: University
Organisation size: < 50 employees
Phone:
Fax:
E-mail:
Industry
Research Institute
50-249 employees
N
+31 317 477078
+31 317 418094
[email protected]
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
227
A
Centre for Genetic Resources
PO Box 16
NL-6700AA Wageningen,
The Netherlands
L
Address:
Dr
Théo
van Hintum
P
Title:
First Name:
Surname:
Organisation/Firm
Plant Research International
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
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L
1 5 . A t S E R K 1 t r a n s g e n i c A r a b i d o ps i s p l a n t s
A
Title of result:
N
SSLP based screen to detect rare apomictic events in a sexually propagating population
of plants
T
Ownership: Wageningen University
T EC H N O LO GY D E S C R I PT I O N
B
I
Abstract of the technology:
O
T
The technique is based on SSLP markers to follow a particular combination of genomic origins. As little as in 200 plants that show the identical combination as the mother plant can be detected. Such plants
could have arisen from a rare apomictic event.
E
Detailed description of the technology:
C
H
N
O
L
O
Here we present a screening method to evaluate the potential of genes to transfer aspects of apomixis
into sexual crop plants. Based on the assumption that an apomictic progeny is an exact genetic replica
of the mother plant we employed a set of Single Sequence Length Polymorphism (SSLP) markers to
identify individuals displaying heterozygosity fixation in segregating sexual populations as an indication
of rare apomictic events. Here we present the results of such a study using the Arabidopsis thaliana
SOMATIC EMBRYOGENESIS RECEPTOR KINASE 1 (AtSERK1) gene expressed under the control of the AtLTP1 promoter in sexual Arabidopsis plants. In only one of the three tested F2 transgenic
populations expressing the AtLTP1::AtSERK1 construct we observed two plants (1.8%) with heterozygosity maintenance for the full set of SSLP markers indicating a possible clonal inheritance. However,
as their offspring revealed a close to binomial segregation for number of heterozygous loci, it was concluded that these two putative apomictic plants resulted from either incidental recombination events
displaying the genotype of the parent, or that they lost their clonal ability in the next generation.
G
Current stage of development of the technology:
Y
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
228
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
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Y
41cq77_one_hundred
G
Intellectual Property Rights
O
Patents granted
Partnership/other contractual agreements
H
If apomixes (conal propagation through seed) can be introduced into crops, it
will require a method to detect successful events. Since most crops are sexually
propagated it is unlikely that this mode of propagation can be reduced in order
to better “see” the potential apomicts. This SSLP method can therefore be
adapted to identify plants of maternal origin developed from embryos that have
been surrounded by normally produced triploid endosperm.
B
I
O
T
E
Innovative Aspects
Main advantage
C
Exploitation potential
N
O
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Title:
First Name:
Surname:
Prof. Dr.
Sacco
de Vries
Address:
Phone:
Fax:
E-mail:
31/317/483866
31/317/484801
[email protected]
Organisation Type: University
Organisation size: < 50 employees
Industry
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A P P L I C AT I O N D O M A I N S
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
229
P
Dreijenlaan 3,
NL/6703 HA Wageningen
The Netherlands
L
A
N
Organisation/Firm
Dept of Biochemistry
Wageningen University
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Biomedical
technology –
therapy
© Digital Stock, 1996
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
1 . I m p ro v e m e n t o f B a c i l l u s s t r a i n s
f o r p ro d u c t i o n o f s e c re te d p ro te i n s
E
Title of result:
D
Improvement of Bacillus strains for production of secreted proteins
I
Ownership: Bacell
C
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
C
A toolbox of Bacillus subtilis strains and technologies for the engineering of these strains are available
for improved production of native and heterologous proteins. These proteins include both cytoplasmic
and secreted proteins and their application is in the fields of general biotechnology (mainly enzyme production) and bio-therapeutics.
H
N
Detailed description of the technology:
O
L
O
G
Y
–
Modern technologies, including tools for molecular genetics, gene cloning and engineering, proteomics,
transcriptomics, and (large scale) fermentation technology, are available for Bacillus subtilis, the paradigm for Gram-positive bacteria. A toolbox of B.subtilis strains and technologies is available for the
improved production of native and heterologous secreted proteins. This includes both the Sec-dependent and the TAT (Twin-arginine-transport)-dependent pathways for protein secretion. A detailed
understanding of networks of gene regulation, including those for stress management, has been
obtained, which enables the directed engineering of strains for improved protein productions. In current EU-funded projects on protein secretion and cellular stress management, B. subtilis is increasingly
used as the model for the understanding of host-pathogen interactions of pathogenic Gram-positive
bacteria. This holds promise for the production of novel anti-infectives against Gram-positive
pathogens.
H
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
E
T
Current stage of development of the technology:
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
R
A
P
Intellectual Property Rights
Y
Patents applied for but not yet granted
Exclusive rights
License agreement reached
232
Patents granted
Partnership/other contractual agreements
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P
Y
41cq77_one_hundred
E
Production of improved and novel enzymes for biotechnological application
and identification of novel drug targets and production of novel anti-infectives
against Gram-positive pathogens
C
H
N
O
L
O
G
Y
–
T
H
Innovative Aspects
Main advantage
R
A
Exploitation potential
Dr
Sierd
Bron
Phone:
Fax:
E-mail:
+31 50 363 8037
+31 50 363 2348
[email protected]
T
Title:
First Name:
Surname:
C
University of Groningen;
Biological Sciences;
Kerklaan 30; 9751 NN Haren,
Netherlands
I
Address:
A
L
Organisation/Firm
Bacell
E
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Industry
Research Institute
Start-up company
Other
D
Organisation Type: University
50-249 employees
250-500 employees
>500 employees
M
E
Organisation size: < 50 employees
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
A P P L I C AT I O N D O M A I N S
233
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
E
2 . Peptides mimicking Vibrio Cholerae O 139
Ca ps u l a r P o l y s a cch a r i d e a n d t h e i r u s e to
e l i c i t p ro te c t i v e i m m u n e re s p o n s e
D
Title of result:
I
C
Peptides mimicking Vibrio cholerae O139 Capsular Polysaccharide and their use to elicit protective immune response
A
Ownership: Karolinska Institutet
L
T EC H N O LO GY D E S C R I PT I O N
T
E
Abstract of the technology:
C
H
N
O
L
O
G
Y
–
T
H
E
R
A
Peptides mimicking Vibrio cholerae O139 capsular polysaccharide elicit protective immune response. V.
cholerae is the etiological agent of the disease cholera. V. cholerae serogroup O1 has been, until 1992,
the only serogroup responsible for large epidemics and pandemics of cholera. In 1992, a new serotype
of V. cholerae emerged in South-East Asia that caused a massive outbreak of cholera in India and neighboring countries. The new serotype was named V. cholerae O139. The main differences between V.
cholerae O139 and O1 are that the former possess a capsular polysaccharide and different lipopolysaccharide. Capsular polysaccharides are, in general, T-independent antigens giving rise to poor immune
responses lacking immunological memory. In order to overcome this, monoclonal antibodies against the
capsular polysaccharide of V. cholerae O139 were used to screen different phage-displayed random peptide libraries on pVIII (F. Felici et al. 1995 Biotechnology Annual Review 1:149-183). More than 20
phage clones have been identified and characterized using enzyme immunoassay with the monoclonal
antibodies, and then tested for specificity by competition with V. cholerae O139 capsular polysaccharide. Eight clones were selected for further characterization. The selected peptides have been sequenced,
synthesized and conjugated to Bovine Serum Albumin (BSA) and Keyhole Limpet Hemocyanin
(KLH). The KLH-peptide conjugates have been used to immunize mice. The antibodies against all the
peptides showed reactivity with capsular polysaccharide from V. cholerae O139. This has been shown
both in direct and competition assays. The anti-peptide sera have also been tested in a mouse model for
protection. Sera against some of the peptides possess a protective efficacy of up to 70%. This can be
compared with the protective efficacy of the original monoclonal antibody that could protect up to 90%
in this assay. In addition, the protective efficacy could be specifically abolished after absorption with the
homologous peptide. Antisera against a heterologous peptide or KLH carrier alone did not show any
protective efficacy. Also, the protective efficacy could be shown to be dose dependent. NOTE. This
work has been performed in collaboration with Prof. Franco Felici (University of Messina, Italy) who
is also a joint inventor in the PCT/IT03/00489 filed patent.
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E
H
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Y
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The present invention relates to compounds, methods for their preparation, compositions containing
them and to their use as medicaments, in particular in the field of infectious diseases, more in particular
for the prevention of cholera. Object of the invention are peptide mimics against the capsular polysaccharide of V. cholerae O139. Also disclosed are monoclonal antibodies against the capsular polysaccharide of V. cholerae O139. Said antibodies are used to screen different phage-displayed random peptide
libraries. A further object of the present invention is the use of the above peptides as medicaments, in
particular for the prevention of cholera infections. Still another object of the present invention are compositions comprising the above peptides, in particular pharmaceutical compositions. Peptide libraries
displayed on the surface of filamentous phages have been used to produce mimics to several different
bacterial surface polysaccharides (Meloen, R.H., Puijk, W.C. & Slootstra, J.W. J. Mol. Recognit. 13, 3529. (2000)) that when used for immunization in animals, induce antibodies with the same biological activity as the antibody used as template. We have selected eight different phage clones, characterized them
using enzyme immunoassay (EIA) with the mAbs, and then tested the specificity by competition with
the V. cholerae O139 capsular polysaccharide. The peptide sequences were then determined and peptides were synthesised and conjugated before immunization of mice.
The preferred peptides are
Vc1-1:
AEGEFSPGVWKAAFQGDKLPDPAK
SEQ ID No. 1
Vc1-4:
AEGEFYCSGPPDRVCWGPDPAK
SEQ ID No. 2
Vc1-10:
AEGEFPSRMQFHGDQDYGDPAK
SEQ ID No. 3
Vc1-12:
AEGEFMGDICSWCYSSAPDPAK
SEQ ID No. 4
Vc1-22:
AEGEFCSPPDSPGVCGDPAK
SEQ ID No. 5
Vc2-1:
AEGEFSYDMLWMMTPQTGDPAK
SEQ ID No. 6
Vc12-1:
AEGEFCGFVWPFKCHRIGDPAK
SEQ ID No. 7
Vc12-2:
AEGEFKVPFRMLNRQVNGDPAK
SEQ ID No. 8
Due to the presence of cys residues, the peptides can also be in cyclic form. Advantageously, the peptides of the present invention are relatively short and can be synthesized and conjugated to different carrier proteins and be used for oral, nasal or transcutanous immunization in order to give rise to a protective mucosal immunity. The application of such a vaccine for the prevention of cholera is novel for the
field of enteric vaccines. The present invention comprises also antigenic portions and equivalent of the
peptides. The peptides of the present invention can be also conjugated with another substance useful in
immunization, preferably a protein, such as for example Bovine Serum Albumin or Keyhole Limpet
Hemocyanin, tetanus toxoid, diphteria toxoids and B-subunit of the cholera toxin. The peptides of the
present invention can be prepared by a process comprising the following steps:
a) producing a monoclonal antibody against the capsular polysaccharide of V. cholerae O139;
b) using monoclonal antibody to screen different phage-displayed random peptide libraries;
c) isolating the peptides displayed on the surface of the filamentous phages selected in step b). The peptides of the present invention, once characterized by their amino acid sequence, can be scaled up to
industrial preparation by classical chemical synthesis, such as disclosed for example Methods in
Enzymology, Volume 289: Solid-Phase Peptide Synthesis by Gregg B. Fields, Sidney P. Colowick,
Melvin I. Simon (Editors) 1997, Academic Press, Inc., New York.
Given their amino acid sequence, the peptides of the present invention can be also obtained by polynucleotides coding for them. Said polynucleotides can be derived from the amino acid sequence and, once
obtained, they can be used for producing the peptide by means of conventional genetic engineering
techniques currently used in the field. The peptides of the present invention are used to immunize subjects against Vibrio cholerae O139. The present invention also provides a diagnostic method for detect-
R
A
Detailed description of the technology:
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ing antibodies against Vibrio cholerae O139 in a subject, for example a subject suspected to be infected
or having been infected, the method comprising:
a) contacting a biological sample of the subject with at least one peptide of the present invention;
b) detecting peptide-antibody complex formation.
In the above method, the peptide can optionally be isolated. Conveniently, in one possible embodiments
of the present invention, the peptides used in the above method will be contained in a suitable diagnostic kit, which is comprised in the scope of this invention.
I
A
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
L
C
Current stage of development of the technology:
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
T
C
Patents applied for but not yet granted
Exclusive rights
License agreement reached
H
E
Intellectual Property Rights
N
Comments:
Patents granted
Partnership/other contractual agreements
O
Application No. PCT/IT03/00489 Date Jul. 31, 2003. (Publication number
WO 2004/056851, 08 July 2004)
L
O
Exploitation potential
G
Innovative Aspects
Main advantage
Y
–
T
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236
One of the major global challenges for the past 20-30 years has been the development of vaccines to control diseases like cholera that affects millions of people especially in developing countries. Most of the affected are children less than
five years of age. Different approaches for vaccines have been used such as liveattenuated bacteria; killed bacteria in combination with recombinant B-subunit
of a cholera toxin; component vaccines. None of them have been shown to
induce a long lasting protective immunity. The critical part is to develop safe and
efficacious vaccines against diseases that are widely spread in endemic areas. A
protective immunity against surface carbohydrates is crucial. The approach of
selecting peptides mimicking polysaccharides may circumvent the problems of
low efficacy of purified polysaccharides. The peptides that are able to mimic
immunologically the carbohydrate and to generate a strong T-dependent protective immune response can be tailored to different needs using recombinant
DNA techniques and additional immunogenic sequences can be incorporated or
mimotope-coding genes can be used for direct insertion into live vectors or plasmids for DNA immunization. This opens a completely new field of generating
DNA-based vaccines against polysaccharide antigens. The low cost and the simplicity of administration of peptide or DNA based vaccines would be of great
benefit to combat the major enteric diseases in developing countries. This
approach, if proven successful, could be used to protect against a majority of diseases where immunity against carbohydrate structures is crucial.
04-11-2005
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41cq77_one_hundred
Organisation Type: University
H
E
R
+46 8 58587831
+46 8 7113918
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
G
Organisation size: < 50 employees
Industry
Phone:
Fax:
E-mail:
T
Karolinska Insitiutet,
Division of Clinical Bacteriology,
Karolinska University Hospital,
Huddinge, F82, S-14186 Stockholm,
Sweden
Professor
Andrej
Weintraub
–
Address:
Title:
First Name:
Surname:
Y
Organisation/Firm
Karolinska Institutet
A
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
D
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C
A
L
T
E
C
H
N
O
L
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
E
M
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
A P P L I C AT I O N D O M A I N S
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3 . A n i m a l v e n t i l a to r f o r s m a l l a n i m a l s f u l l y
M R I co m p a t i b l e
E
Title of result:
D
I
Bruker method for spiral and radial MRI, and animal MRI compatible ventilator for small
animals
C
Ownership: Universidad Complutense Madrid
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
C
H
N
A new approach for an animal MRI-compatible ventilator was developed, which might be very useful
for some applications, such as those dependent on the gas flow. It has been optimized for small rodents,
although the instrument may easily be conveyed to human scale. Their essential features are a real-time
module, which also avoids lung overpressure, control from a personal computer through a versatile parallel port, small dead volume (0.24 ± 0.02 cm3 and about 0.8 cm3 including the endotracheal or tracheotomy tube volume), and a specifically designed breathing pneumatic module compatible with hyperpolarized gases.
O
O
The MRI compatible ventilator consists in a pneumatic module with three pneumatic ports: one for the
control of the oxygenated gas inspiration (including, if it is needed, an anesthetic gas), a second one for
the control of the especial gas inspiration (such as hyperpolarized or fluorinated gases), and the last one
for the control of the expiration. These pneumatic ports are controlled by electromechanical valves
(EVs) located at the real-time module. The EVs (MTV-3R-NN4, Takasago Electric Inc., Nagoya, Japan)
and the pneumatic module are connected by 3 mm internal diameter semi-rigid tubes. The air pressure
applied to each EV for closing its corresponding pneumatic port was around 300 mbar. These ports were
opened connecting the corresponding EV to air at atmospheric pressure. The real–time module was
implemented to provide autonomy and reproducibility in the breathing cycle and for safety reasons.
This module allows the synchronization with a MRI instrument and enables pressure triggering after
animal demands of spontaneous ventilation. The input to the oxygenated gas inspiration port is flow
controlled and it is also used as input to the air-tight box. This box contains a commercial Tedlar® bag
that is used as a special gas buffer. The output of this flexible bag is conveyed to its corresponding inspiration port and, practically the same input pressure is expected at the entrance of both inspiration valves.
Two additional pneumatic valves (shown as PV in the same figure) were introduced for automatic refilling of the Tedlar® bag. A pressure transducer was included to register the animal breath, to minimize
the risk of ventilator induced lung injury and to maintain an adequate breathing cycle. The peak inspiratory pressure (PIP) and the positive end-expiratory pressure (PEEP) are programmed in the real-time
module. The inspiration ports are closed and the expiration one is opened when lung pressure reaches
the PIP value, allowing spontaneous animal breathing and avoiding lung overpressure. The pneumatic
module, the air-tight box containing the Tedlar® bag and the pressure transducer are close to the sub-
G
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Detailed description of the technology:
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ject. The transducer power supply and its pressure signal are filtered using low-pass filters to avoid noise
externally generated. The device is controlled from a PC (in our case a laptop with an AMD AthlonTM
XP processor) through the bi-directional enhanced parallel port. The lung pressure, tidal volume, temperature and other physiological parameters (such as arterial oxygen partial pressure, pH, etc.) can also
be monitored through the interface that includes eight analogue-to-digital conversion channels.
A
P
Y
41cq77_one_hundred
–
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Y
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
T
Current stage of development of the technology:
G
Intellectual Property Rights
O
Patents granted
Partnership/other contractual agreements
O
L
Patents applied for but not yet granted
Exclusive rights
License agreement reached
H
C
No commercially available. MRI Compatibility. Reprodubility and versality.
E
Innovative Aspects
Main advantage
N
Exploitation potential
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Instituto de Estudios Biofuncionales.
Paseo Juan XXIII, 1. Madrid 28040
Phone:
Fax:
E-mail:
+34913943288
+34913943245
[email protected]
A
L
Dr.
Jesús
Ruiz-Cabello
I
Address:
Title:
First Name:
Surname:
C
Organisation/Firm
Universidad Complutense Madrid
Industry
Research Institute
Start-up company
Other
D
Organisation Type: University
50-249 employees
250-500 employees
>500 employees
M
E
Organisation size: < 50 employees
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
A P P L I C AT I O N D O M A I N S
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4 . A n t i - b a c te r i a l ( M R SA ) d r u g s e r i e s
(the xf drugs)
E
Title of result:
D
Anti-bacterial (MRSA) drug series, (the XF drugs).
I
Ownership: Destiny Pharma Ltd
C
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
C
The anti-MRSA drug series are potent bacteriocidal agents which through their mechanism of action,
i.e. photo-dynamic, have the following key properties:
• Active against Gram positive & negative bacteria, irrespective of antibiotic-resistance status
• No emergence of resistance to XF treatment observed with bacteria (MRSA)
• Wide Therapeutic Window, Potent & Safe
H
N
Detailed description of the technology:
O
L
O
G
Y
The XF Drug series are anti-bacterial compounds, which are active by a photo-dynamic process. This
mechanism of action has endowed the compounds with a low propensity for the emergence of resistant
bacterial strains. The compounds are selective for bacterial cell membranes and a clear therapeutic window of activity has been demonstrated. The compounds are active against Gram positive and negative
bacteria and antibiotic resistant strains e.g. MRSA. The compounds have a good safety profile. Compounds are undergoing clinical evaluation and have the potential for prophylactic as well as therapeutic
applications in infection control.
Current stage of development of the technology:
–
Development phase
Tested, available for demonstration
Already on the market
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
T
H
Intellectual Property Rights
E
R
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
A
P
Exploitation potential
Y
Innovative Aspects
Main advantage
240
XF Drugs have the potential to treat MRSA and other bacteria in preventive
and therapeutic modes and due to the photo-dynamic action, there is a low
propensity for resistant bacterial strain emergence.
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Y
41cq77_one_hundred
Sussex Innovation Centre, Falmer,
Brighton, BN1 9SB, UK
Industry
+44 (0) 1273-704440
+44 (0) 1273-704499
[email protected]
Research Institute
E
R
Phone:
Fax:
E-mail:
Start-up company
Other
–
Organisation Type: University
Dr
Bill
Love
H
Address:
Title:
First Name:
Surname:
T
Organisation/Firm
Destiny Pharma Ltd
A
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
50-249 employees
250-500 employees
>500 employees
Y
Organisation size: < 50 employees
D
I
C
A
L
T
E
C
H
N
O
L
O
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
E
M
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
G
A P P L I C AT I O N D O M A I N S
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5 . D i s co v e r y B A S E S c re e n i n g W o r k f l o w
f o r T a rg e t P ro te i n I d e n t i f i ca t i o n
E
Title of result:
D
DiscoveryBASE Screening Workflow for Target Protein Identification
I
Ownership: emergentec biodevelopment GmbH
C
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
C
H
N
O
L
We have established a virtual screening workflow – discoveryBASE - which, based on genomic / proteomic data, identifies disease associated proteins. A wide range of statistics pinpoints significant findings in genomics and proteomics raw data, complemented by a set of bioinformatics to unravel co-regulation at the transcription, as well as at the protein network level. Candidate protein sets identified are
subsequently analyzed applying structural bioinformatics with particular emphasis on solvent accessibility and antigenicity. Result of the workflow is accessible / antigenic determinants on disease associated proteins valuable for both, diagnostic (e.g. ELISA assays), as well as therapeutic (e.g. vaccines, therapeutic antibodies) applications. Our workflow is fully operative, scientifically documented, and has
been validated in the area of cancer, infectious diseases, autoimmune disorders, and organ transplantation.
O
Detailed description of the technology:
G
Y
–
T
H
E
R
A
P
Y
Our discoveryBASE workflow includes two major modules: Targeting for identification of disease
associated proteins, and Profiling for characterization of accessible and antigenic sites on such proteins.
Targeting: This module screens for disease relevant genes / proteins by either starting with full genome
sequence data (e.g. in the case of pathogen analysis), or with data from differential gene expression / proteomics in the case of diseases as cancer or autoimmune disorders. For infectious diseases every single
protein of the pathogen under analysis is characterized to predict function and sub-cellular location of
proteins, as well as to evaluate the relevance of proteins in the regulatory context. Targeting result for
pathogens is a list of proteins with high propensity for essential function, as well as membrane bound
or secreted location. Such proteins are ideal candidates for diagnostic as well as therapeutic applications.
For diseases as cancer or autoimmune disorders we mainly use data from differential gene expression
derived from the target tissue as start point. We cross-compile raw data from public domain, and also
include data from proprietary sources, if available. Initial analysis includes statistics to derive a first, disease associated expression profile. Genes / proteins given by this profile are then expanded utilizing promoter module analysis. This procedure allows identification of co-regulation at the transcription level,
enabling the ex-, as well as inclusion of further potential candidate proteins. This Ansatz includes,
besides a purely statistical, also a biological interpretation of differential gene expression data. The
extended, disease associated gene profile is in a next step expanded by available protein regulatory network analysis, and finally filtered by predicted protein location, again mainly focusing on membrane
bound and secreted proteins. Result of the Targeting module is sets of candidate proteins which are dis-
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Y
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ease associated, carry vital function, and are membrane bound or secreted. Usually a significant reduction of proteins of interest is achieved in the Targeting step, cutting the total number of proteins of interest to 1 – 5 % of all proteins initially considered. This refined protein set is forwarded to the next analysis step, Profiling.
Profiling: Major element of Profiling is an estimate of protein structure applying state of the art structural bioinformatics. Secondary structure elements, folds, and 3D models are computed. Numerical
routines are then applied to derive protein sites with good solvent accessibility, as well as sites with high
antigenic propensity including both, B-and T-cell epitopes. In particular our B-cell epitope identification routine E-Score shows unmatched predictive power when compared to public domain reference
standards in this research area. Result of Profiling is accessible and antigenic determinants on disease
associated proteins. The candidate epitope lists are furthermore ranked by propensities, additionally
easing experimental verification, which usually includes ELISA assays, functional epitope analysis, generation of antibodies, or immunostaining.
Experimental Verification and Exploitation areas: Depending on disease area and envisioned diagnostic
/ therapeutic concept the following areas are supported by our technologies:
Infectious diseases: Identification of relevant B-cell (Immunodiagnostics, Vaccines, targets for Therapeutic Antibodies) and T-cell epitopes (Vaccines)
Cancer, Autoimmune Disorders: Identification of B-cell Autoantigens (Immunodiagnostics), as well
as B- and T-cell antigens (Vaccines, targets for Therapeutic Antibodies)
Other areas: The screening workflow is in principle applicable for all disease areas where respective
genomic base data are available. Furthermore, distinct functionalities of Targeting (e.g. gene expression
analysis, promoter analysis) or Profiling (e.g. computation of solvent accessibility, antigenicity) can be
applied on a stand alone basis.
A
P
Y
41cq77_one_hundred
L
D
I
Patents granted
Partnership/other contractual agreements
Compared to purely experimental screening procedures our technology
exhibits clear advantages in identifying novel protein targets. Our approach is
fast and cost extensive, and is centred on the full set of experimental data readily available. Diverse methods of statistics and data mining, bioinformatics,
database knowledge, and numerical algorithms are aggregated in an end to end
technology workflow, resulting in distinct candidate targets ready for straight
forward experimental verification.
243
I
Innovative Aspects
Main advantage
B
Exploitation potential
O
M
E
Patents applied for but not yet granted
Exclusive rights
License agreement reached
C
Intellectual Property Rights
A
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Our lead identification workflow is in use along our proprietary R&D, as
well as in cooperative research and services projects.
T
E
Current stage of development of the technology:
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I
O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
E
D
M
Organisation/Firm
emergentec biodevelopment GmbH
Address:
I
Rathausstrasse 5/3, A-1010 Vienna,
Austria
C
Organisation Type: University
A
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Dr
Bernd
Mayer
Phone:
Fax:
E-mail:
+43 (0) 699 113 49 173
+43 (1) 4034966
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
L
T
A P P L I C AT I O N D O M A I N S
E
C
H
N
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
O
L
O
G
Y
–
T
H
E
R
A
P
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244
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
M
E
D
I
C
A
L
T
E
C
H
N
O
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O
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Y
–
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6 . N o v e l A n t i b a c te r i a l D r u g C a n d i d a te s
b a s e d o n T ox i n - A n t i tox i n M o d u l e s
E
Title of result:
D
Novel Anti Bacterial Drug Candidates based on Toxin-Antitoxin Modules
I
Ownership: Tel Aviv University
C
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
C
H
N
O
L
O
G
Toxin-Antitoxin modules (TA) attracted much interest due to their potential use as novel antibacterial
targets. The absolute lack of TA systems in euokaryotes, as oppose to their ubiquitous presence in bacteria and archea, makes toxin-antitoxin systems a very attractive antibacterial target. Unlike conventional antibiotics, there is no need for the external introduction of toxic material that may affect the host as
well. The blockage of the toxin-antitoxin physical interaction may result in the execution of the inherent toxic potential of the toxin. We demonstrate that the Escherichia coli YefM protein is a natively
unfolded antitoxin, lacking secondary structure. Due to the unfolded state of the protein, a linear determinant rather than a conformational one is being recognized by its toxin partner, YoeB. We have identified this determinant in the YefM-YoeB toxin-antitoxin systems in a large number of bacteria including major pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium
tuberculosis. The identification was done by using a peptide array technology and pair-constrained
bioinformatics analysis. The finding of this novel recognition element paves the way towards the development of a new class of anti bacterial drugs which may be more specific towards bacteria and avoid
resistance and other critical problems of antibiotics.
Y
Detailed description of the technology:
–
T
H
E
R
A
P
Y
Presently, treatment of infections caused by pathogenic bacteria relies predominantly on the administration of antibiotics. Despite being successful in controlling or eliminating bacterial infections, widespread use of antibiotics both in human medicine and as a feed supplement in poultry and livestock production has led to drug resistance in many pathogenic bacteria (McCormick J. B., Curr Opin Microbiol 1:125-129, 1998) and as such, the effectiveness of such antibiotics has greatly diminished in the last
decade. The economic impact of managing infections caused by antibiotic-resistant bacteria is substantial, and current costs are estimated to be more than $4 billion annually [Harrison and Lederberg (ed.),
Antimicrobial resistance: issues and options. National Academy Press, Washington, D.C. pp. 1-7, 1998].
Furthermore, as resistance spreads among bacteria, there is grave concern that antibiotics treatment will
become increasingly less effective and, in some cases, completely ineffective. The Toxin-antitoxin complex of bacteria includes a pair of polypeptides that is encoded by bacterial plasmids and chromosomes.
It is postulated that in bacteria these polypeptides function to induce programmed cell death or growth
inhibition in response to starvation or other adverse conditions (Hayes, Science 301:1496-1499, 2003).
The antitoxins neutralize the cognate toxins by forming tight complexes therewith. The antitoxins are
unstable due to degradation by cellular proteases (e.g., Lon or Clp), whereas toxins are stable polypep-
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E
H
T
–
Y
G
tides. We have invastigated the YefM-YeoB module, a ubiquitous toxin-antitoxin module with major
bacterial pathogens and demonstrate that the Escherichia coli YefM protein is a natively unfolded antitoxin, lacking secondary structure. Due to the unfolded state of the protein, a linear determinant rather
than a conformational one is being recognized by its toxin partner, YoeB. We have developed a method
of identifying a molecules capable of inducing death of a bacterial cell. The method includes (i) exposing toxin and antitoxin polypeptides of a toxin-antitoxin pair produced by the bacterial cell to a plurality of molecules; and (ii) identifying a molecule of the plurality of molecules capable of preventing or
disrupting binding between the antitoxin and the toxin polypeptides.
Using this method we had identified the recognition sequences that mediate toxin-antitoxin interactions
within the YefM-YeoB module. The novel target was verified using surface plasmon resonance analysis
and the study of mutant peptides. These newly discovered short sequences can serve as a platform for
the design of novel peptide and peptidomimetic inhibitors of toxin-antitoxin interactions.
Our lab has much experience in the development of peptide and peptide-derived drugs including those
related to amyloid disease as well as nano-scale peptide assemblies.
A
P
Y
41cq77_one_hundred
N
O
L
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
H
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
O
Current stage of development of the technology:
Exploitation potential
I
O
M
E
D
I
1. A completely novel target for antibiotic development
2. Platform that is based on well-defined biochemical and biophysical analysis
3. A model for rapid and efficient screen of new inhibitor compounds
B
Innovative Aspects
Main advantage
A
L
T
E
Patents granted
Partnership/other contractual agreements
C
Patents applied for but not yet granted
Exclusive rights
License agreement reached
C
Intellectual Property Rights
247
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
E
D
M
Organisation/Firm
Tel Aviv University
Address:
I
C
Department of Molecular
Microbiology and Biotechnology
Tel Aviv University, Tel aviv 69978,
Israel
A
Organisation Type: University
L
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Dr.
Ehud
Gazit
Phone:
Fax:
E-mail:
+972-3-640-9030
+972-3-640-5448
: [email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
T
A P P L I C AT I O N D O M A I N S
E
C
H
N
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
O
L
O
G
Y
–
T
H
E
R
A
P
Y
248
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
M
E
D
I
C
A
L
T
E
C
H
N
O
L
O
G
Y
–
T
H
E
R
A
P
Y
Pagina 249
O
12:55
I
04-11-2005
B
41cq77_one_hundred
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
E
7. S c re e n i n g s t r a te g y o f m i c ro b e s i n v o l v i n g
g e n e t i c a n d ch e m i ca l f i n g e r p r i t i n g a s
w e l l a s b i o a c t i v i t y p ro f i l e d e te r m i n a t i o n
D
Title of result:
I
C
Screening strategy of microbes involving genetic and chemical fingerprinting as well as
bioactivity profile determination
A
Ownership: Galilaeus Oy
L
T EC H N O LO GY D E S C R I PT I O N
T
E
Abstract of the technology:
C
H
A versatile screening technique was demonstrated with 600 microbes. DNA- and chemical fingerprinting will be offered as a service to the companies that screen new microbial metabolites for drug discovery purposes.
N
O
Detailed description of the technology:
–
T
Current stage of development of the technology:
L
There are different ways to screen microbial metabolites for drug discovery. However, combination of
chemical and DNA fingerprinting was considered as a powerful technique to distinguish known
metabolites from new ones in the very beginning. Bacterial DNA is first analyzed by PCR to characterize possible secondary metabolites. After that, the chemical characterization takes place.
Cyanomyces project analysis altogether 600 bacterial strains belonging to actinomycetes and cyanobacteria. In DNA-fingerprinting approach we used DNA-probes for typical chemical classes of secondary
metabolites. The bacterial strains were characterized also by HPLC and MALDI-TOF-MS to focus on
those chemical classes that do not belong to the general chemical classes. The screening approach was
especially good for screening of metabolites from actinomycetes.
O
G
Y
H
E
R
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
A
P
Y
250
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
04-11-2005
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P
Y
41cq77_one_hundred
R
Main advantage of the technology is to avoid rediscovery of the natural
compounds which is very typical in general screening procedures.
E
C
H
N
O
L
O
G
Y
Innovative Aspects
Main advantage
–
Exploitation potential
H
The technique is ready to use. However, as a lot of background information is
needed for evaluation of the results, the technology will be provided as a
service.
T
Comments:
Patents granted
Partnership/other contractual agreements
E
Patents applied for but not yet granted
Exclusive rights
License agreement reached
A
Intellectual Property Rights
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
+358-2-274 1450
+358-2-273 1460
[email protected]
L
Phone:
Fax:
E-mail:
I
Kairiskulmantie 10,
FIN-20781 Kaarina, Finland
CEO
Kristiina
Ylihonko
A
Address:
Title:
First Name:
Surname:
C
Organisation/Firm
Galilaeus Oy
Industry
Research Institute
Start-up company
Other
D
Organisation Type: University
50-249 employees
250-500 employees
>500 employees
M
E
Organisation size: < 50 employees
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
A P P L I C AT I O N D O M A I N S
251
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
E
D
8 . D e v e l o p m e n t o f p ro ce d u re s f o r p l a s m a
p ro ce s s i n g f l a t s u b s t r a te s to p ro d u ce
m i c ro m e t r i c p a t te r n s u s i n g p h y s i ca l
masks
I
Title of result:
C
A
Development of procedures for plasma glow discharge processing flat substrates to produce micrometric patterns using physical masks - 14453
L
Ownership: University of Bari
T
T EC H N O LO GY D E S C R I PT I O N
E
C
Abstract of the technology:
H
N
Glow discharges are utilized to transfer reliefs of nanometric dimensions and micro-domains of defined
different chemical composition and properties (e.g. protein adhesive; e.g. non fouling) on a wide variety
of materials, with specific concentration on biomedical devices. Such patterned surfaces have potential
uses in biosensors technology and tissue engineering, as well as in certain non biomedical applications.
O
O
Glow discharges can deposit thin films or graft chemical groups at the surface of materials (e.g. polymers),
in a way that surfaces stable in water and biological media result. In certain experimental conditions thin
films characterized by nanometric reliefs are synthesized, that can induce faster adhesion and growth of cells
at the surface of the substrates. In other conditions a physical mask with a pre-determined pattern (e.g. bars
and voids) can be utilized, in order to develop domains of different chemical composition and properties at
the surface of the substrates, where seeded cells can grow and be aligned along specific directions on tracks
or on other geometrical areas, while being repelled in other areas of the substrates.
G
L
Detailed description of the technology:
Y
–
H
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
E
T
Current stage of development of the technology:
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
R
A
P
Intellectual Property Rights
Y
Patents applied for but not yet granted
Exclusive rights
License agreement reached
252
Patents granted
Partnership/other contractual agreements
04-11-2005
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P
Y
41cq77_one_hundred
C
H
N
O
L
O
G
Y
–
T
H
Main advantage
Nano-micro-featured surfaces of specified adhesion/chemistry for biological
systems.
Wide range of specific chemistries can be added at the surface of substrates.
E
Innovative Aspects
R
A
Exploitation potential
E
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Phone:
Fax:
E-mail:
+ 39 080 5443430
+ 39 080 5443405
[email protected]
C
A
L
Dipartimento di Chimica
Universita degli Studi di Bari
Via Orabona 4
70126 Bari
Italy
Prof.
Piero
Favia
I
Address:
Title:
First Name:
Surname:
T
Organisation/Firm
University of Bari
Industry
Research Institute
Start-up company
Other
D
Organisation Type: University
50-249 employees
250-500 employees
>500 employees
M
E
Organisation size: < 50 employees
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
A P P L I C AT I O N D O M A I N S
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
9 . U s e o f p a r v o v i r u s - l i ke p a r t i c l e s a s
v a cc i n e v e c to rs
E
Title of result:
D
Use of parvovirus-like particles as vaccine vectors
I
Ownership: Inmunologia Y Genetica Aplicada S.A. (Ingenasa)
C
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
C
H
N
Virus-like particles (VLPs) constitute a new generation of non-replicative vectors for delivery heterologous epitopes and induction of immune responses. We have engineered porcine parvovirus-like particles (PPV-VLPs), formed by the self-assembly of 60 copies of the major estructural protein VP2 of PPV
expresed using the baculovirus expression system, to deliver T-cell epitopes inserted into the N terminus of PPV VP2. Insertion of T-cell epitopes at the N-terminus does not alter the particle formation and
provide a very efficient strategy to stimulate Th and CTL responses against the foreing antigens without additional adjuvant in mice.
O
Detailed description of the technology:
L
O
G
Y
–
T
H
E
R
A
P
Y
Expression of VP2 gene of porcine parvovirus (PPV) in insect cells with the use of the baculovirus system had led the production of VLPs formed by the self-assembly of VP2. These VLPs are expressed at
high levels and can easily be purified by salt fractionation. VP2 gene was manipulated to facilitate the
insertion of the epitope sequences upstream of its iniciation codon. All mutant genes containing insertions can be rescued from the respective plasmids and subcloned into baculovirus transfer vectors
(under p10 or polyhedrin promotor). The next step involves the transfection of insect cells with a mixture of transfer vector and baculovirus DNA in the presence of Lipofectine. After several days, culture
supernatants are plated for baculovirus isolation. When recombinant baculoviruses have been obtained,
they are used to overexpress large amounts of the protein. The assembly of parvovirus VLPs can be
assessed by several techniques, including SDS-PAGE and immunoblot analysis, sedimentation in CsCl
gradients, hemagglutination analysis and electron microscopy. Quimeric VLPs containing the
LCMVepitope were tested for their ability to elicit a CTL response in immunized mice. For this purpose, Balb/c mice were injected intraperitoneally with the recombinant particles in the absence of adjuvant. When spleen cells were removed from the immunized animals and stimulated in vitro with the
peptide, a strong CTL-specific response was induced against the effector cells coated with the epitope.
This CD8+ class I restricted cytotoxic activity persisted in vivo for at least 9 months. To analyze the
ability of hybrid particles to protect mice against lethal viral infection, Balb/c mice were immunized
twice on days 0 and 21 with the quimeric particles, and after 7 or 49 days, mice were challenged with a
letal dose of LCMV by the intracerebral route. Mice immunized with the quimeric particles were fully
protected against a viral inoculation. In addition, mice immunized with PPV-LCMV VLPs were also
protected against a challenge performed on day 70, indicating that these particles induce a long-term
protective immunity against LCMV. These results demonstrate that non-replicative parvovirus-like par-
254
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E
H
T
–
G
Y
ticles carrying a single viral CTL epitope are able to induce complete protection of mice against a lethal
viral infection through the inductionof virus-specific MHC class I-restricted CD8+ cytotoxic T lymphocytes, providing a novel and safe strategy for the development of vaccine applications. The significance of epitope flanking sequences on the presentation of the OVA epitope was analized. We have
demonstrated that PPV-VLPs carrying the minimal sequence of the OVA epitope were not recognized
by B3Z cells, showing that the minimal epitope was not efficiently processed by DCs or/and delivered
to MHC class I molecules. However, PPV-VLPs with sort natural flanking sequences induced a very
good IL-2 production by B3Z cells. The length of the flanking sequences did not seem crucial because
addition of different natural sequences to the N or C terminus of the epitope did not affect antigen presentation. Interestingly, the flanking sequences of the LCMV T-cell epitope, which work efficiently for
the presentation of this epitope, were ineffective for the OVA epitope. We have also demonstrated the
ability of the PPV-VLPs to carry more than one copy of the same epitope, or one copy of two different epitopes. These results open up the possibility of incorporation multiple epitopes from a pathogen.
A
P
Y
41cq77_one_hundred
O
L
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
N
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
O
Current stage of development of the technology:
C
E
T
L
A
I
O
M
E
D
I
In this project, two non-replicating delivery systems have been employed to
deliver antigens to the immune system and to elicit the appropiate protective
immune responses against different diseases. These are the Porcine Parvovirus
Particles (PPV-VLPs) and Bluetongue NS1 Tubules (NS1-TUBs).
INGENASA is the industrial partner and the owner of the intellectual property related with PPV-VLPs. The immunological assays has been performed at
the Pasteur Institute in collaboration with Dr.Claude Leclerc.
B
Comments:
Patents granted
Partnership/other contractual agreements
C
Patents applied for but not yet granted
Exclusive rights
License agreement reached
H
Intellectual Property Rights
255
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
Exploitation potential
O
M
Innovative Aspects
Main advantage
E
D
I
C
A
L
Non-replicative PPV VLPs carrying inserted epitopes are structurally stable
and highly immunogenic, and present the advantages of high level of expression
and relative simplycity because it is based on a single protein. Moreover, PPVVLPs are very stable and can be stored at 4ľC for months without significant
alteration in their properties. This delivery system is indeed able to accept more
than one epitope which would allow the development of vaccines for several
diseases. The particles could be subjected to high purification methods suitable
for human vaccines. Finally, PPV-VLPs, in contrast to other systems, do not
require CD4+ T cell help for CTL activation. All these findings suggest the
suitability of these VLPs to provide an efficient and safe strategy for vaccination and immunotherapy.
T
E
C
H
N
O
L
O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
G
Y
–
Organisation/Firm
Inmunologia Y Genetica Aplicada S.A.
(Ingenasa)
Title:
First Name:
Surname:
Manager Director
Carmen
Vela
Address:
Phone:
Fax:
E-mail:
(+34) 91 368 0501
(+34) 91 408 7598
[email protected]
C/ Hermanos García Noblejas, 39.
28037 Madrid. Spain
T
Organisation Type: University
Industry
Research Institute
Start-up company
Other
H
Organisation size: < 50 employees
50-249 employees
250-500 employees
>500 employees
E
R
A
A P P L I C AT I O N D O M A I N S
P
Y
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
256
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
M
E
D
I
C
A
L
T
E
C
H
N
O
L
O
G
Y
–
T
H
E
R
A
P
Y
Pagina 257
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12:55
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B
41cq77_one_hundred
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
1 0 . E n z y m e - m e d i a te d s e r i a l c u l t i v a t i o n o f
a n ch o r a g e - d e p e n d e n d ce l l s
E
Title of result:
D
Enzyme-mediated serial cultivation of anchorage-dependent cells
I
Ownership: CILBIOTECH s.a.
C
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
Using MicroHex™ (NUNC), a polystyrene-based microsupport with 2D geometry, all the operations
required for serial cultivation i.e. the passage of cells from one microsupport to another are performed
in the same bioreactor.
C
H
Detailed description of the technology:
N
With MicroHex™ varying between 20- and 60 cm2 per ml of culture, cells are expanded some 20-fold
within 13 days. The process lends itself to automation.
O
O
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
G
L
Current stage of development of the technology:
Y
–
Intellectual Property Rights
T
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
Patents granted
Partnership/other contractual agreements
H
E
R
Exploitation potential
A
Innovative Aspects
Main advantage
P
Y
258
Reduced footprint, ease of operation, strict confinement make serial cultivation-based scale-up the method of choice for:
- the production of human veterinary vaccines (influenza etc)
- the long term cultivation of human embryonic stem cells.
04-11-2005
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P
Y
41cq77_one_hundred
c/o FPMS
Rue de l'Epagne 56
B-7000 Mons
Industry
+32 (0)65.37.45.78
+32 (0)65.37.45.79
[email protected]
Research Institute
E
R
Phone:
Fax:
E-mail:
Start-up company
Other
–
Organisation Type: University
Director
Alain, O.A.
Miller
H
Address:
Title:
First Name:
Surname:
T
Organisation/Firm
CILBIOTECH s.a.
A
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
50-249 employees
250-500 employees
>500 employees
Y
Organisation size: < 50 employees
D
I
C
A
L
T
E
C
H
N
O
L
O
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
E
M
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
G
A P P L I C AT I O N D O M A I N S
259
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
E
1 1 . A s s a y s to s c re e n f o r i n h i b i to rs o f F t s A
i n te r a c t i o n s , a p ro te i n v i ta l f o r
b a c te r i a l p ro l i f e r a t i o n
I
Assays to screen for inhibitors of FtsA interactions, a protein vital for bacterial
proliferation.
C
D
Title of result:
A
L
Ownership: Centro Nacional de Biotecnología. Consejo Superior de Investigaciones
Científicas
T EC H N O LO GY D E S C R I PT I O N
T
C
Y
FtsA, is a bacterial protein of known structure that is required for the proliferation of many bacteria.
The absence of FtsA produces severe morphological changes and usually results in the loss of viability.
FtsA molecules interact with each other and a correlation between the presence of the Carboxy end of
the protein, its ability to interact and the function of the protein has been observed (Yim et al. 2000. J.
Bacteriol. 182: 6366-6373). The FtsA protein is present in a number of Gram positive and Gram negative bacteria including pathogens responsible for community acquired and nosocomial infections making it a suitable target to search for inhibitory compounds of pharmacological interest. The structure
FtsA shows significant differences to that of its human homologues, actin and Hsp70, and also to the
kinase proteins, suggesting that it would be possible to obtain specific inhibitors of FtsA that would not
act on the human proteins. Essentiality, ubiquity and selectivity versus its human counterparts, make
FtsA a suitable target to search for inhibitory compounds of pharmacological interest.
–
Detailed description of the technology:
H
E
Abstract of the technology:
N
O
L
O
G
T
H
E
R
A
P
Y
The truncated FtsA protein from Escherichia coli lacking domain 1C (FtsA∆1C) localises, together with
FtsZ and ZipA (other essential cell division proteins), at correctly placed division rings. Domain 1C
occupies a radically different position in the bacterial FtsA relative to its position in Actin, the eukaryotic homolog. However FtsA∆1C does not interact with other FtsA molecules in the yeast two-hybrid
assay, and it fails to recruit other proteins like FtsQ and FtsN that assemble at a later stage into the division ring. The deletion of the S12-S13 strands of the FtsA protein from E. coli generates another protein (FtsA∆S12-13) that retains the ability to interact with FtsA+ and localizes into division rings but
cannot fully replace the function of the wild type protein. Although FtsA∆S12-13 recruits FtsQ and
FtsN into rings they frequently occupy abnormal positions in the cell and are weakly active in septation, leading to filamentation and production of a fraction (15%) of small cells without nucleoid. As
these properties of FtsA are essential for cell division (Rico et al. 2004. Mol. Microbiol. 53: 1359-1371)
the results can be exploited to develop new HTS assays to screen for inhibitors. The purified FtsA protein from Streptococcus pneumoniae polymerises in vitro in the presence of ATP. It forms double strands
that adopt a corkscrew conformation when observed by electron microscopy (Lara, et al. 2005. Mol.
Microbiol. 55: 699–711). This property can easily be converted into a HTS assay to screen for inhibitors.
260
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R
In vivo validation of the target is required, or alternatively a preliminary screen to select inhibitors could
be performed to test if the potential inhibitors block bacterial proliferation.
A
P
Y
41cq77_one_hundred
H
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
T
Development phase
Tested, available for demonstration
Already on the market
E
Current stage of development of the technology:
–
Intellectual Property Rights
Y
Patents granted
Partnership/other contractual agreements
O
G
Patents applied for but not yet granted
Exclusive rights
License agreement reached
N
H
C
FtsA, as it happens to most of the proteins needed for bacterial division,
remains as an underexploited source of potential inhibitable targets. The main
advantages of this protein are that it has a sufficiently different structure from
analogous proteins from eukaryotic origin to avoid adverse effects of the potential inhibitors on the human cell, and that it is essential in a wide range of Gram
positive and Gram negative bacteria what can yield potential wide spectrum
antibacterial drugs.
E
Innovative Aspects
Main advantage
O
L
Exploitation potential
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Title:
First Name:
Surname:
Prof.
Miguel
Vicente
Address:
Phone:
Fax:
E-mail:
+34 91 585 46 99
+34 91 585 45 06
[email protected]
A
C
I
C/ Darwin n° 3. CSIC Campus de
Cantoblanco. E-28049 Madrid.
Spain
L
Organisation/Firm
Centro Nacional de Biotecnología. Consejo
Superior de Investigaciones Científicas
Industry
Research Institute
Start-up company
Other
D
Organisation Type: University
50-249 employees
250-500 employees
>500 employees
M
E
Organisation size: < 50 employees
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
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B
I
O
M
E
1 2 . D e v e l o p m e n t o f re ce p to rs to o p t i m a l l y
re ta rg e t h u m a n T ce l l s to
M H C- re s t r i c te d t u m o r o r v i r a l a n t i g e n s
D
Title of result:
I
C
Development of receptors to optimally retarget human T cells to MHC-restricted tumor
or viral antigens.
A
Ownership: Erasmus MC Daniel den Hoed
L
T EC H N O LO GY D E S C R I PT I O N 1
T
E
Abstract of the technology:
C
H
N
1. T cell receptors (TCR)
We constructed full-length (non-modified) TCR and TCR chimerized to CD3 components with
specificities ranging from the melanoma antigens MAGE-A1 and gp100, the universal tumor antigen
HDM2 to the Epstein-Barr viral antigens EBNA-3A/B and BMLF-1. Chimeric TCR were made as
two-chain as well as single-chain receptors.
O
L
O
G
Y
2. Antibodies (Ab)
Antigen-binding fragments (Fab) with a MHC-restricted specificity for the melanoma antigen
MAGE-A1 (i.e. MAGE-A1/HLA-A1) were isolated via phage display. Using this entirely in vitro
technology, which is independent of available CTL clones, MHC- restricted antibodies can be rapidly selected and isolated against peptide/MHC complexes of interest. Single and two-chain Abs,
isolated via phage display, were chimerized to CD3 components.
–
Receptors were functionally introduced into primary human T cells and mediated antigen-specific T cell
responses. Importantly, receptors can be functionally introduced into primary human T lymphocytes
without loss of antigen reactivity and peptide fine-specificity, which holds great promise for the application of receptor gene transfer in cancer immunotherapy.
T
E
Receptors have been developed which dictate MHC-restricted anti-tumor and virus responses following gene-transfer into primary human T cells. Specificities range from the melanoma antigens MAGEA1 and gp100, the universal tumor antigen HDM2, to the Epstein Barr antigens EBNA-3A/B and
BMLF-1. The receptor formats we have developed include full-length (non-modified) T cell receptors
(TCR), as well as two-chain or single-chain TCR or antibodies chimerized to a CD3 component. Antibodies with a MHC-restricted tumor specificity are isolated via phage display. Using this entirely in
vitro technology, which is independent of available CTL clones, MHC-restricted antibodies can be rapidly selected and isolated against peptide/MHC complexes of interest. Up until now, phage-display and
peptide/MHC tetramer selections yielded more than a dozen MHC-restricted antibodies and constitutes a formally proven in vitro method to obtain ‘’TCR-like’’ molecules. TCR as well as ‘’TCR-like’’
R
H
Detailed description of the technology:
A
P
Y
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Y
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O
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receptors can be functionally introduced into T cells after which they mediate antigen-specific T cell
responses. Importantly, receptors can be genetically transferred into primary human T lymphocytes
without loss of antigen reactivity and peptide fine-specificity, which holds great promise for the application of receptor gene transfer in cancer immunotherapy. Our ongoing studies into the receptor format that optimally retargets T cells to tumor antigens have shown the following.
TCR-based receptors. Two-chain TCRs chimerized to the complete CD3 ζ chain (i.e. TCRα:CD3ζ and
TCRb:CD3z chains) are good candidate receptors for in vivo studies and future clinical trials.
Antibody-based receptor. Antibody-mediated T cell responses are significantly improved via either one
of two receptor modifications: increase of the ligand-binding affinity or incorporation of the CD28 costimulatory domain. First, the phage display methodology enables the in vitro evolution of affinitymatured antibodies, which after expression by T cell-transductants result in high ligand-binding affinity and, consequently, improved ligand-specific T cell responses. Second and in contrast to “classical”
non MHC-restricted antibodies that comprise the CD28 co-stimulatory domain, we have observed a
dramatic increase in receptor-mediated cytolysis of T cells equipped with CD28-containing single-chain
(sc)Fv. For the clinical use of MHC-restricted scFv, we therefore recommend receptors that comprise
the transmembrane and intacellular domains of the CD28 co-stimulatory molecule followed by the
intracellular domain of either the CD3 ζ or Fc(ε)RI γ chain.
A
P
Y
41cq77_one_hundred
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H
N
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
E
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
O
Current stage of development of the technology:
L
Patents granted
Partnership/other contractual agreements
D
E
M
O
The generation of virus-specific and, particularly, tumor-specific CD4+ and
CD8+ T lymphocytes through conventional tissue culture procedures is time
consuming (weeks and outcomes are uncertain. Our technology provides the
possibility to retarget T lymphocytes to the desired antigens through transfer
of the genes coding for (chimeric) receptors (antibody-type or T-cell-receptortype). This procedure allows only short-term culturing to activate the T cells;
following gene transfer, the redirected T cells can be expanded in cytokine-containing medium until the desired numbers have been achieved, typically within
1-2 weeks time)
B
Innovative Aspects
Main advantage
I
Exploitation potential
I
C
A
Patents applied for but not yet granted
Exclusive rights
License agreement reached
T
Intellectual Property Rights
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I
Title of result:
O
M
Development of a highly efficient retroviral vector and gene delivery system to transduce primary human T cells under GMP conditions.
E
T EC H N O LO GY D E S C R I PT I O N 2
D
I
Abstract of the technology:
C
A
L
We constructed a retroviral vector termed pSTITCH, followed up by a further improved vector termed
pBULLET. This latter vector was distributed to Partners 1, 2, 3, 5, as well as collaborators outside the
Consortium. Thorough comparative studies including a variety of vectors performed by Partner 3
demonstrated that the pBULLET is the vector of choice for gene delivery into human T cells.
T
Detailed description of the technology:
E
C
H
N
O
L
O
G
Y
–
To improve gene transfer into primary human T cells, we have constructed a retroviral vector termed
pSTITCH, followed up by a further improved vector termed pBULLET. Thorough comparative studies including a variety of vectors demonstrated that the pBULLET is the vector of choice for gene delivery into human T cells. In addition, we have set up an optimal retroviral gene transduction/expansion
protocol for primary human T lymphocytes that meets GMP standards for the renal cancer specific single-chain (sc)Fv receptor G250. The combination of the optimized retroviral vector and gene transduction protocol routinely results in 60-90% surface expression of transgenes on human T cells, and is currently implemented in an immunogene clinical trial to treat renal cell carcinoma. We further demonstrated that human phoenix packaging cells, producing MLV-pseudotyped viruses, clearly outperform
PG13 packaging cells, producing GaLV-pseudotyped viruses, with respect to the transduction efficiency of activated primary human T cells. The phoenix packaging cells, positive for scFv G250, is approved
by the Dutch Ministry of Health Care and gene regulatory authorities for its clinical use. A master and
working cell bank of the Phoenix packaging cells have been established, which was shown not to produce replication competent retroviruses (RCR) and contain one to two genome-integrated and intact
copies of the provirus. A phase I study with therapeutic intent of the treatment of metastatic renal cell
cancer with autologous gene-modified T-lymphocytes, the first clinical immunogene trial in Europe, has
subsequently been initiated in March 2003 by the Rotterdam group.
T
H
Current stage of development of the technology:
E
R
A
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
P
Y
Intellectual Property Rights
Patents applied for but not yet granted
Exclusive rights
License agreement reached
264
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Partnership/other contractual agreements
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Highly efficient delivery of genes to dividing T lymphocytes, followed by highlevel expression of the transferred genes. The high-level expression of the transferred genes typically by 60-90% of the cultured T cells ensures good specificity for the desired target antigen, combined with high potency (specific cytotoxicity and cytokine production).
T
Innovative Aspects
Main advantage
R
A
Exploitation potential
Title of result:
–
Clinical immunogene therapy trial to treat renal cell carcinoma patients.
G
Y
T EC H N O LO GY D E S C R I PT I O N 3
L
O
A phase I study with therapeutic intent of the treatment of metastatic renal cell cancer with autologous
gene-modified T-lymphocytes has been initiated in March 2003 by the Rotterdam group.
O
Abstract of the technology:
C
E
T
L
A
I
C
A phase I study with therapeutic intent of the treatment of metastatic renal cell cancer with autologous
gene-modified T-lymphocytes has been initiated in March 2003 by the Rotterdam group.
The following parameters will be analyzed.
(1) Determination of safety of escalating doses of intravenous infusions of receptor-transduced T cells;
(2) Appearance and persistence of receptor-transduced T cells in peripheral blood;
(3) Assessment of anti-tumor response: WHO criteria;
(4) Proof of Principle;
(5) Determination of immune reactivity versus receptor.
In extension to the generation of new and improved MHC-restricted anti-melanoma receptors, their in
vitro and in vivo validation, a second clinical immunogene trial to treat melanoma will be prepared and
initiated.
H
N
Detailed description of the technology:
M
E
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
O
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
D
Current stage of development of the technology:
Patents granted
Partnership/other contractual agreements
B
Patents applied for but not yet granted
Exclusive rights
License agreement reached
I
Intellectual Property Rights
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I
Exploitation potential
O
M
Innovative Aspects
Main advantage
This is the first trial in its kind in Europe. Future immuno-gene therapy trials
of cancer will greatly benefit from the experiences of the current trial.
E
D
I
C
A
L
T
E
C
H
N
O
L
O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
G
Y
Organisation/Firm
Erasmus MC Daniel den Hoed
–
Address:
Groene Hilledijk 301
3075 EA Rotterdam,
the Netherlands
Title:
First Name:
Surname:
Dr.
Debets
Reno
Phone:
Fax:
E-mail:
+31 10 439 17 18
+31 10 439 10 05
[email protected]
T
Organisation Type: University
Industry
Research Institute
Start-up company
Other
H
Organisation size: < 50 employees
50-249 employees
250-500 employees
>500 employees
E
R
A
A P P L I C AT I O N D O M A I N S
P
Y
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
266
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
M
E
D
I
C
A
L
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O
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E
13 . CIM® monolithic chromatographic supports
- enabling technology for analysis and
purification of novel biotherapeuticals
D
Title of result:
I
C
CIM® monolithic chromatographic supports – enabling technology for analysis and
purification of novel biotherapeuticals
A
Ownership: BIA Separations d.o.o.
L
T EC H N O LO GY D E S C R I PT I O N
T
E
Abstract of the technology:
C
H
N
O
CIM® monolithic chromatographic supports are very short monolithic columns, which are optimized
for the efficient purification of viruses, plasmids, proteins, peptides, olignucleotides, etc. to meet the
research and production needs of the biotechnology industry. These novel supports allow fast separations
and increase productivity by at least one order of magnitude over traditional chromatographic columns
packed with porous particles. Columns provide high rates of mass transfer at lower pressure drops and
enhance the speed of the separation process which reduces the backpressure, unspecific binding, product
degradation and minor changes in the structure of the biomolecule without sacrificing resolution.
L
G
CIM Convective Interaction Media® is composed of a short continuous homogenous methacrylate or
styrene-divinylbenzene rigid polymeric block that is highly cross-linked with uniform 3D interconnected channels resulting in 62% porosity. The macro channels have a diameter around 1500 nm and the
meso channels diameter is below 100 nm. The larger channels contribute to the column’s low back pressure even while operating at elevated flow rates; the smaller ones provide a large surface area resulting
in a high dynamic binding capacity. CIM® monolithic columns are resistant to chemical and thermal
stress. The monolith itself can withstand temperatures ranging from 4°C (39°F) to over 120°C (248°F),
they have a working pH range from 1-14, and can easily withstand 1M NaOH. Being a single block of
porous material with highly interconnected channels, CIM® monolithic chromatographic supports
have a very fast mass transfer (due to convective flow). The short length of the monolithic column
enhances the speed of the separation and reduces the backpressure, unspecific binding, and product
degradation. Further, the supports exhibit low non-specific binding of biomolecules thereby preventing
minor changes in the biomolecule’s structure. The channel size and surface have been optimized so that
the biomolecule can easily access ligands for binding and have an extremely high capacity for very large
molecules (e.g. 10 mg of plasmid DNA/ml, 20 mg of genomic DNA/ml, 25 mg of Tomato Mosaic
Virus/ml) ensuring they can easily permeate the matrix. These features decrease the purification time by
an order of magnitude which in turn reduces the purification costs. Therefore CIM® supports combine
the separation power, capacity, and sample distribution of conventional porous particle chromatographic columns and the convective mass transport of membrane technology. CIM® monolithic chromatographic supports can be prepared for analytical and QA use (disks, minidisks, 96 well plates, or
Y
O
Detailed description of the technology:
–
T
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R
A
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H
C
syringes) and for production (tubes). The analytical disks can be used for proteomics, screening, and as
pre-columns for MS-MS. The tubes are used for both preclinical, pilot and full cGMP production. The
process of scaling up from screening to small scale purification to pilot scale purification and then production is quick and easy as these short monoliths (no matter what size or shape) have identical performance and purification profiles. Once method optimization is completed, it takes only a few days to
go from the lab bench to full scale production. This results in significant time and cost savings. Both
small and large columns are easy to operate and adjustable to meet the biochromatographers needs. It
takes seconds to set up or change the configuration of a column and they have a fast equilibration and
regeneration. There is no packing of particles, like conventional columns, and no need to worry about
air bubbles as they are not trapped in the monolithic structure; they are just washed out with the mobile
phase. The separation quality does not change with fast separations. Lastly, the support has no diffusion
limitations, due to the flow through channels, making all pores accessible to the biomolecules. Other
advantages are they operate at high flow rates in all chromatographic modes on an analytical and preparative scale. Lastly, they are compatible with any peristaltic pump or conventional LC/HPLC or FIA
system. CIM® supports come in a complete range of chemistries to meet the biochromatographers
needs. These include: Ion Exchange (anion, cation), Reversed Phase, Hydrophobic Interaction, Affinity/Immunoaffinity, and Epoxy. The ability to bind a wide range of enzymes, immunoglobulins, and
peptides makes them ideally suited to serve as bioreactors, affinity columns, and for on-line and off-line
in-process control. The existing chemistries have applications for: virus purification, virus concentration
and vaccine production; pDNA production, monoclonal antibody isolation; biomolecule discovery;
purification of basic and acidic proteins; oligonucleotide and peptide separations and bioconversions as
well for complex nanoparticles designed for efficient drug delivery (PEG-ylated drugs, liposomes, polymer-drug conjugates, polymer micelles, viral vectors, dendrimers).
A
P
Y
41cq77_one_hundred
L
T
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
A
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
E
Current stage of development of the technology:
D
I
Patents granted
Partnership/other contractual agreements
Increased productivity of the purification processes of large biomolecules by an
order of magnitude
B
Innovative Aspects
Main advantage
I
Exploitation potential
O
M
E
Patents applied for but not yet granted
Exclusive rights
License agreement reached
C
Intellectual Property Rights
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I
O
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
E
D
M
Organisation/Firm
BIA Separations d.o.o.
Address:
I
Teslova 30, SI-1000 Ljubljana
Slovenia
C
Organisation Type: University
A
Organisation size: < 50 employees
Industry
Title:
First Name:
Surname:
Dr.
Aleš
Štrancar
Phone:
Fax:
E-mail:
+386-1-426-5649
+386-1-426-5650
[email protected]
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
L
T
A P P L I C AT I O N D O M A I N S
E
C
H
N
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
O
L
O
G
Y
–
T
H
E
R
A
P
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270
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Purification
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1 4 . M i c ro f l u i d i c n e t w o r k s o n s u r fa ce
p l a s m o n re s o n a n ce ch i ps
E
Title of result:
D
Microfluidic networks on surface plasmon resonance chips
I
Ownership: University of Copenhagen
C
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
C
Based on micro contact printing technology developed for semiconductor purposes by IBM, the
BIOPATT project transferred the printing technology to the manufacture of multichannel chips for an
analytical instrumentation using the surface plasmon resonance principle. To succeed the microcontact
printing had to be optimised for generation of microfluidic channels. The goal was to demonstrate the
operation of 16 parallel channels and prepare for up to 128 channels.
H
O
Micro contact printing uses a polymer for generation of a stamp. The negative version of the stamp is
created by some auxiliary technique (photo lithography. Electron beam lithography or x-ray lithography). This stamp is vetted by the liquid monomer. By use of a suitable initiator the polymerisation is
performed. An accurate positive replica of the stamp is generated. The replica can be reproducing details
down to 20 nm provided that the proper polymer is selected and provided the aspect ratio of the structures is kept at a moderate value. If the stamp is prepared in a soft polymer like PDMS the stamp can
make perfect sealing to a glass surface . Thereby channels may be formed having three sides made up by
the PDMS and one side by glass. Channels of this type have been used to flow bio fluids through. The
size and shape of the channels have been modelled and optimised in order to make uniform plug flow
prevalent. Binding of biomolecules on the glass surface have been found to happen extremely rapid
when the dimension of the channels is less than 100 mikrometer. Under this conditions unidirectional
mass transport to the surface takes place. Using the microcontact printing to create a passivating layer
on silica it has been possible to etch the trenches in silica. The trenches can be converted to microfluidic channels by contact to a planar PDMS. The latter structure shows mechanical rigidity, while the first
may be udsed on curved surfaces. Both approaches were used in BIOPATT to make microfluidic networks available for use in the surface plasmon resonance equipment. Surface plasmon resonance instrumentation relies on the ability to match the Brewster angle and force an electromagnetic ray to follow
the surface of a material. The evanescent field extending into the near region above the substrate permits
registration of the polarization of the material in this region by the delay in propagation. The delay is
depending on the polarizability of the material on the surface. The interaction falls off exponentially
depending on the distance to the surface. Binding of bimolecules on the surface will therefore in general result in an increased polarizability and change in propagation. The method is extremely sensitive and
may be used to register time response for on-off reactions on surfaces. With the state of the art instrumentation 10% coating of a surface with a monolayer of a protein can be detected. It is obvious that
L
N
Detailed description of the technology:
O
G
Y
–
T
H
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R
A
P
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D
I
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changes in temperature and pressure may influence the observed propagation rate and influence the registered instrument response. It has therefore been customary to require milli Kelvin accuracy in the temperature control for optimum performance. The state of the art when BIOPATT was initiated had surfaces prepared for plasmon resonance with active area of 0.8 – 0.5 cm2. The BIOPATT proposal was to
divide this surface into multiple channels each with a much smaller surface and use these channels as
individual detection areas . Innovative Aspects: Surface plasmon resonance equipment has been available for two decades. It has been a very sensitive and potential useful analytical technique, but is has
been expensive due to the price of instrumentation, and slow to use since the surfaces have been coded
for a single species at a time. By making the surfaces divided in multiple channels the instrumentation
can perform multiple analysis simultaneously. The patterning of a surface with the sufficient control of
geometry in the micrometer range has not been developed before in this analytical field due to excessive
cost. The same problem was solved with massive investments in the semiconductor industry (by IBM )
with the aim of nanometer resolution. The technique developed was termed micro contact printing. It
was found during the development of the method that it had potential for application outside the semiconductor area, most notably in patterning of bio molecules. Since IBM does not operate in this field
the technology transfer from IBM to a small bio oriented instrument company – Affinity Sensors- was
suggested. The BIOPATT project was set up to facilitate this technology transfer with the University of
Copenhagen as mediator. In a previous EU project NANOWIRES, IBM and University of Copenhagen cooperated on making nanometer wires by the micro contact method. An innovation in this project was to use the same technique to create micro fluidic channels with the same precision. The channels can be used in a first step to prepare an analytical surface with multiple channels on the plasmon
surface. Each channel is filled separately and thus the channels may be coated by the same or by different compounds. In a subsequent step a microfluidic network is used to administer solution/solutions to
be analysed to the surface. A new surface plasmon resonance equipment was constructed for the purpose of multiple channel detection. A large sensitive CCD array had to be built and the optics had to
be designed for resolution of 100-200 micrometer channels. Computer programs to control the instrument were developed. The layout of micofluidic channels was optimised to ensure efficient filling of
channels and flow control. The main advantages of the instrument designed were that faster and cheaper analysis could be performed with the instrument produced by Affinity Sensors. The design also
demonstrated the feasibility of making cheaper and better instruments by exploiting the multi channel
system to its limits. Thus internal referencing using some of the channels allowed for relaxed demands
on temperature stability, and thereby portable instrumentations may be designed.
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B
I
Current stage of development of the technology:
O
M
E
D
I
C
A
L
T
E
C
H
N
O
L
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : The project BIOPATT was completed by 2000. The 16 channel system was
by then constructed and available in the laboratory of Affinity Sensors. In
the field test with a costumer we used a 4 channel system during the last 6
month of the project with positive results. During the last 12 month of the
project an injunction case against Affinity sensors was going on in Delaware
in USA. Here the Swedish company BIACORE claimed that Affinity sensor violated their patent by production of their instrumentation. On December 30th, 1999 the local court laid down an injunction for production of
instruments by Affinity Sensors. This development was not brought to the
attention of the partners or the EU commission. The reason was that Affinity Sensors believed they were innocent and consequently appealed the local
court decision. In april 2001 after termination of the BIOPATT contract the
court of appeal in USA confirmed the injunction. Apparently Affinity Sensors closed down rather quickly thereafter. The majority of shares were in
the hand of an American conglomerate Thermo Inc. This company moved
the responsibility of support for earlier costumers to various other companies in the conglomerate and Affinity Sensors had wanished. The conclusion
on the BIOPATT technology transfer is thus rather sad: the transfer of technology succeeded but the company was terminated for unrelated legal reasons.
O
G
Intellectual Property Rights
Y
Patents applied for but not yet granted
Exclusive rights
License agreement reached
–
Comments:
T
H
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R
A
P
Y
274
Patents granted
Partnership/other contractual agreements
The fundamental patents covering the micro contact printing were established
by IBM prior to BIOPATT. IBM granted licenses to Affinity Sensors accrding
to the IP agreement valid for BIOPATT. Affinity Sensors were preparing additional patent claims for the multiple channel system. In a patent search today
none of these can be found under Affinity Sensor heading.
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41cq77_one_hundred
Phone:
Fax:
E-mail:
+45 4674 2533
+45 3927 1207
[email protected]
Universitetsparken 5
DK-2100, Copenhagen, Denmark
Industry
Research Institute
Start-up company
Other
–
Organisation Type: University
R
Address:
E
Prof
Kjeld
Schaumburg
H
Title:
First Name:
Surname:
T
Organisation/Firm
University of Copenhagen Department of
Chemistry, CISMI
A
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
50-249 employees
250-500 employees
>500 employees
Y
Organisation size: < 50 employees
D
I
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A
L
T
E
C
H
N
O
L
O
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
E
M
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
G
A P P L I C AT I O N D O M A I N S
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I
O
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E
1 5 . I n te g r a te d te ch n o l o g y f o r e f f i c i e n t
t h e r a p e u t i c re t ro v i r u s p ro d u c t i o n b a s e d
o n m o d u l a r ce l l l i n e s
D
Title of result:
I
C
Integrated technology for efficient therapeutic retrovirus production based on modular
cell lines
A
Ownership: IBET
L
T EC H N O LO GY D E S C R I PT I O N
T
E
Abstract of the technology:
C
H
N
O
L
O
G
Y
This technology was developed to facilitate and speed-up the development of retroviral vector production
from gene to final product. The technology development strategy was defined taking into account the final
intended distinctive characteristics of the technology namely, high productivity in terms of infectious and
more stable retroviral vectors, flexibility regarding different applications and targeted diseases and, ultimately, assurance of safety and efficacy. Experimental validation has always been attained for these claims. The
flexibility of the vectors has been demonstrated by using different genetic constructs and the proving possibility to change therapeutic genes, in this case human collagen VII. Vector stability has been defined at all
process levels - production, purification and storage – thus ensuring the compliance of the specifications and
the subsequent efficacy of the final product. In what regards safety, the same 3D culture technology that has
been extremely helpful in the evaluation of the tropism, transduction efficiency and efficacy of the retroviral vectors produced is also used to evaluate the toxicity of the produced vectors. At this moment, master
cell bank for the flexible master cell line is established. In parallel, further optimization for the selection of
clones with higher productivities and the production, purification and storage protocols is being completed, with the SOPs being prepared to support technology transfer to GMP facilities.
–
Detailed description of the technology:
T
H
E
R
A
P
Y
For the establishment of cell lines that allow targeted integration so called “master cell clones” that contain a tagging construct in a chromosomal hot-spot were constructed. The tagging vector was constructed in a way that a subsequent exchange can be done with a gene of interest by site specific recombinases. Using this technology, a resulting producer cell line can be obtained within a few weeks, less than
half the time needed when using traditional screening methods. This part was developed by GBF (Germany) and complemented by the tropism and toxicity studies performed at the Hadassah Medical
School (Israel). Vector production is defined for fixed bed bioreactors, thus ensuring process scaleability. Production parameters are defined so that reproducibility can be assured (Genethon, France). The
downstream processing of the vectors produced is based on both membrane and chromatographic
methods being able to achieve yields consistently between 50 and 70%. The storage method developed
is based on lyophilization and is able to ensure a half-life of the vectors in excess of 6 months (IBET,
Portugal). A master cell bank for 293 modular cells having GFP as a reporter gene is already available.
The master cell bank was produced under GMP conditions at Henogen (Belgium).
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Y
41cq77_one_hundred
E
R
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
H
Development phase
Tested, available for demonstration
Already on the market
A
Current stage of development of the technology:
Intellectual Property Rights
T
Patents granted
Partnership/other contractual agreements
–
Patents applied for but not yet granted
Exclusive rights
License agreement reached
G
O
L
O
N
H
C
To select overexpressing cell clones, various automated screening procedures
are currently used. Together with the time required for adaptation of a new cell
clone to the cultivation conditions for large scale bioreaction this procedure
may take up to 2 years, although by using state-of-the-art technology, some
companies have been able to reduce this time frame to 6 month. The proposed
technology is able to further reduce the development of overexpressing clones
to 4-8 weeks. Then, as culture conditions and purification and storage processes are essentially standardised, process development times can be reduced by
half. Therefore, this technology may be particularly useful for companies wishing to create a platform for the production and testing of different target genes
without performing process optimization fir each product.
E
Innovative Aspects
Main advantage
Y
Exploitation potential
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
(+351) 21 442 77 87
(+351) 21 44211 73
[email protected]
L
Phone:
Fax:
E-mail:
I
Av. Republica, Apartado 12
2781-901 Oeiras Portugal
Prof.
Manuel
Carrondo
A
Address:
Title:
First Name:
Surname:
C
Organisation/Firm
IBET
Industry
Research Institute
Start-up company
Other
D
Organisation Type: University
50-249 employees
250-500 employees
>500 employees
M
E
Organisation size: < 50 employees
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Gene Therapy
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
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I
O
M
1 6 . P ro to co l s f o r Cl i n i p o r a to r ™ u s e i n
t u m o rs , s k i n , l i v e r, m u s c l e
E
Title of result:
D
Protocols for Cliniporator™ use in tumors, skin, liver, muscle
I
Ownership: UMR 8121 CNRS – Institut Gustave-Roussy
C
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
C
The development of gene therapy has been hampered by the problems linked to the use of viral vectors.
Non-viral methods for in vivo gene transfer are needed. DNA electrotransfer is a very efficient nonviral method. The use of combination of HV and LV pulses makes the method very safe. Moreover algorithms exist to control on real time the electrical parameters of the pulse ensuring the protection of the
tissues to potentially damaging electric pulses.
H
O
The Cliniporator project Demonstration phase has shown that gene transfer can be achieved by means
of the Cliniporator™ in different tissues: muscle, liver, tumor and skin. It has also shown that the
parameters to be applied are different as a function of the treated tissue. One important difference is
linked to the use of transcutaneous pulses (tumors, muscle) versus the use of pulses in direct contact
with the targeted organ ( e.g. liver). There are also clear differences in the parameters to apply on skeletal muscle, on tumors, on liver and on skin. The specific protocols for each tissue include specific electrode description, procedure for DNA injection, procedure for animal preparation, parameters for the
HV (permeabilizing) pulse, parameters for the LV (electrophoretic) pulse. These protocols should help
new users in starting the delivery of pulses using the Cliniporator™ even without specific training at
one of the Consortium laboratories.
L
N
Detailed description of the technology:
O
G
Y
–
H
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
E
T
Current stage of development of the technology:
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
R
A
P
Intellectual Property Rights
Y
Patents applied for but not yet granted
Exclusive rights
License agreement reached
278
Patents granted
Partnership/other contractual agreements
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Y
41cq77_one_hundred
Safety and efficacy of the gene transfer in vivo in different tissues by a non-viral
means for which equipment – adaptability to various tissues of the organism.
C
H
N
O
L
O
G
Y
–
T
H
E
Innovative Aspects
Main advantage
R
A
Exploitation potential
E
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Phone:
Fax:
E-mail:
+33 1 42 11 47 92
+ 33 1 42 11 52 45
[email protected]
C
A
L
UMR 8121 CNRS –
Institut Gustave-Roussy
39 rue C. Desmoulins
F-94805 VILLEJUIF Cédex FRANCE
Dr.
Luis M.
MIR
I
Address:
Title:
First Name:
Surname:
T
Organisation/Firm
UMR 8121 CNRS – Institut Gustave-Roussy
Industry
Research Institute
Start-up company
Other
D
Organisation Type: University
50-249 employees
250-500 employees
>500 employees
M
E
Organisation size: < 50 employees
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
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D
1 7. H i g h a n d s ta b l e re co m b i n a n t v i r u s
p ro d u c t i o n b y re co m b i n a s e m e d i a te d
ta rg e t i n g o f h o t - s p o t ch ro m o s o m a l
i n te g r a t i o n s i te s
I
Title of result:
C
A
High and stable recombinant virus production by recombinase mediated targeting of
hot-spot chromosomal integration sites
L
Ownership: GBF – German Centre for Biotechnology
T
T EC H N O LO GY D E S C R I PT I O N
E
C
Abstract of the technology:
H
N
O
L
O
G
Y
Recent successes in gene therapy clinical trials have demonstrated the high potential of the use of gene
therapy to cure and slow down a wide scope of diseases. However, the efficient introduction of therapeutic genes into human cells or tissues remains the main problem to be solved. Recombinant virus producer cells with optimal production conditions are usually generated upon transduction of the recombinant vector. Screenings have to be undertaken in order to isolate clones with optimal production properties. In order to speed up this and to improve the technology we generated retrovirus producer cells
into which the recombinant therapeutic vector is integrated into preselected chromosomal sites via
recombinase mediated cassette exchange. This procedure is combined to a stringent selection regimen
that leads to more than 98% of isogenic clones with uniform and predictable production properties.
Depending on the vector, titres up to 2x107/106cells could be generated from a precharacterized chromosomal hot spot. This procedure has been successfully applied for a number of different retroviral vectors including MLV, MPSV and self-inactivating vectors. The strategy can be translated to other types
of recombinant viruses which depend on stable helper cell lines.
–
Detailed description of the technology:
T
H
E
R
A
P
Y
A novel generation of retroviral producer cell lines have been generated. Chromosomal hot spots were
screened for optimal expression of the retroviral vector. These sites were tagged with Flp recombinase
target sites (FRT) linked to a stringent selection principle. An amphotropic retroviral producer cell line
generated thereof is now ready to be used for targeted integration of any therapeutic vector of choice.
For this purpose a vector of choice is flanked with FRTs and transfected to the producer cell line. Transient expression of the Flp recombinase results in site specific integration of the therapeutic vector. Due
to the stringent selection procedure virtually all isolated clones show site specific integration, thereby
rendering time consuming screening procedures superfluous. Producer clones with high and stable virus
titers are established within 4 weeks.
280
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P
Y
41cq77_one_hundred
E
R
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
H
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
A
Current stage of development of the technology:
T
Intellectual Property Rights
–
Patents granted
Partnership/other contractual agreements
Y
Patents applied for but not yet granted
Exclusive rights
License agreement reached
O
L
The main advantage of the described procedure is that therapeutic viruses can
be produced within a minimum of time and with a maximum of predictability.
Thus, it will be of interest in particular for orphan drug productions.
E
C
H
N
O
Innovative Aspects
Main advantage
G
Exploitation potential
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
++49-531-6181-232
++49-531-6181-262
[email protected]
L
Phone:
Fax:
E-mail:
I
Mascheroder Weg 1
D-38124 Braunschweig
Dr.
Hansjörg
Hauser
A
Address:
Title:
First Name:
Surname:
C
Organisation/Firm
GBF – German Centre for Biotechnology
Industry
Research Institute
Start-up company
Other
D
Organisation Type: University
50-249 employees
250-500 employees
>500 employees
M
E
Organisation size: < 50 employees
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Gene Therapy
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
A P P L I C AT I O N D O M A I N S
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I
O
M
E
1 8 . G e n e t i ca l l y re d i re c te d e f f e c to r
l y m p h o c y te s f o r a d o p t i v e
i m m u n o t h e r a p y o f ca n ce r
D
Title of result:
I
Genetically Redirected Effector Lymphocytes for Adoptive Immunotherapy of Cancer
C
Ownership: The Weizmann Institute of Science
A
L
T EC H N O LO GY D E S C R I PT I O N
T
Abstract of the technology:
E
C
H
N
O
L
O
G
Y
The immunotherapy of cancer and viral diseases has several advantages over the classical therapies of
chemotherapy and radiation. Immunotherapy is expected to be more specific for diseased tissue, and
less toxic to the healthy organs of the patient. Nonetheless, in most cancer and AIDS cases, the immune
system of the patient fails to cure the disease. To overcome this problem and to enhance the ability of
the patient’s own immune cells to fight fatal diseases, our group has pioneered several aspects of the
chimeric receptor (CR) (also known as ‘T-body’) approach. In this approach, patient-derived effector
cells (T or natural killer (NK) cells) are transduced with a vector encoding a chimeric receptor comprised of antibody-derived variable regions, specific for a tumor antigen, and linked to lymphocytes
activation molecules. The transduced effector cells are thereby redirected to anti-tumor activity, and
upon reintroduction into the patient, are expected to kill target cells expressing the selected antigen. In
this Consortium we optimizing the design of the chimeric receptior and successfuly demonstrated in
pre-clinical studies in animal model that erbB2-specific CR bearing human T-cells can eradicatte and
cure local as well as diseminated breast and prostate human cancer xenografts. These pre-clinical studies pave the way for clinical trials of advanced incurable cancer.
–
Detailed description of the technology:
T
H
E
R
In the T-body technology, the peripheral lymphocytes of a cancer patient are transduced with chimeric
receptor containing vectors made of scFV of an antibody that is specific to antigen that is over-expressed
on the surface of the patient’s cancer. Following expansion ex-vivo, for about 10 days the cells are reinfused into the patient. In the patient the effector lymphocytes now can traffic to the tumor and its
metastasis recognize and eliminate it. Different chimeric receptor designs can be made with several
specificities and functions to fit best its anti-cancer reactivity.
A
Current stage of development of the technology:
P
Y
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
282
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
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Y
41cq77_one_hundred
R
H
E
C
H
N
O
L
O
Main advantage
Innovative Aspects: The CR design redirects T and NK cells towards any predefined antigen in non-MHC restricted manner.
The T-body approach offers treatment and hopefully cure to otherwise incurable advanced and disseminated cancer
Y
Innovative Aspects
–
Exploitation potential
T
1. One Patent has been granted World –wide.
2. More recent patent was granted in Europe, Australia, Japan. Pending in the
USA. Zelig Eshhar holds the IP rights
G
Comments:
Patents granted
Partnership/other contractual agreements
E
Patents applied for but not yet granted
Exclusive rights
License agreement reached
A
Intellectual Property Rights
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
+972-8-9344014
+972-8-947403
[email protected]
L
Phone:
Fax:
E-mail:
A
Department of Immunology,
The Weizmann Institute of Science
Rehovot, 76100 Israel
Professor
Zelig
Eshhar
I
Address:
Title:
First Name:
Surname:
C
Organisation/Firm
The Weizmann Institute of Science
Industry
Research Institute
Start-up company
Other
D
Organisation Type: University
50-249 employees
250-500 employees
>500 employees
M
E
Organisation size: < 50 employees
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
A P P L I C AT I O N D O M A I N S
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I
O
M
1 9 . Co m b i n a to r i a l f u n g a l P KS e n z y m e s f o r
n o v e l p o l y ke t i d e s
E
Title of result:
D
Combinatorial fungal PKS enzymes for novel polyketides.
I
Ownership: University of Iceland
C
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
A set of fungal polyketide synthase genes is used as a source for recombining the different functional
domains of the enzymes leading to production of novel polyketide molecules in appropriate fungal
hosts.
C
H
Detailed description of the technology:
N
O
L
O
G
Y
Well characterized fungal polyketide synthase (fPKS) genes are cloned in specially constructed vectors
allowing enzyme expression and polyketide production in a range of filamentous fungal hosts
(Aspergillus, Fusarium and Penicillium species). The PKS backbone is assembled in the yeast host Saccharomyces cerevisiae where functional domains (KS, AT, DH, CeMeT, ER, KR, ACP, PP) from available fPKS genes can readily be exchanged using efficient homologous recombination of engineered
hybrid sequences. In addition, non-ribosomal peptide synthase (NPS) domains present in fPKS-NPS
genes can be added and exchanged. After domain exchange, the recombinant plasmid is transferred to
E. coli, the plasmid structure verified and transformed into a filamentous fungal production host. After
verifying that the hybrid fPKS gene has recombined into the host chromosome, the recombinant is cultured and assayed for novel products by HPLC-MS.
–
Current stage of development of the technology:
T
H
E
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
R
Intellectual Property Rights
A
P
Y
Patents applied for but not yet granted
Exclusive rights
License agreement reached
284
Patents granted
Partnership/other contractual agreements
04-11-2005
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P
Y
41cq77_one_hundred
E
Innovation: Utilization of genetic diversity for biosynthesis of novel fungal
polyketides in an environmentally friendly manner.
Advantages: Cost-effective “green chemistry” in the synthesis of high-value
compounds for use in the pharmaceutical industry and other fields.
E
C
H
N
O
L
O
G
Y
–
T
H
Innovative Aspects
Main advantage
R
A
Exploitation potential
Address:
Phone:
Fax:
E-mail:
(354) 525 4627
(354) 525 4069
[email protected]
A
Professor
Ólafur
Andrésson
I
Sturlugata 7, 101 Reykjavík, Iceland
Title:
First Name:
Surname:
C
Organisation/Firm
Institute of Biology, University of Iceland
L
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Industry
Research Institute
Start-up company
Other
D
Organisation Type: University
50-249 employees
250-500 employees
>500 employees
M
E
Organisation size: < 50 employees
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
O
A P P L I C AT I O N D O M A I N S
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I
O
M
2 0 . B i o a r t i f i c i a l l i v e r, I m m o r ta l i s e d h u m a n
l i v e r ce l l l i n e
E
Title of result:
D
Bioartificial liver, Immortalised human liver cell line
I
Ownership: Hep-Art Medical Devices BV
C
A
T EC H N O LO GY D E S C R I PT I O N
L
Abstract of the technology:
T
E
Bioartificial liver to be connected extracorporeally to the patients circulation to support temporarily the
failing liver.
Immortalised human fetal liver cell line..
C
H
Detailed description of the technology:
N
O
Bioreactor based on non-woven polyester matrix, to which 10 billion of liver cells are attached, which
are oxygenated at site by multiple oxygen fibres.
Immortalisation of human fetal liver cells by hTERT
L
O
Current stage of development of the technology:
G
Y
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
–
Intellectual Property Rights
T
H
Patents applied for but not yet granted
Exclusive rights
License agreement reached
E
Comments:
Patents granted
Partnership/other contractual agreements
Both inventions to be licensed
R
A
Exploitation potential
P
Innovative Aspects
Main advantage
Y
286
Novel bioreactor, easily to handle, simple and cheap. Novel cell line to be used
for bioartificial liver and for in vitro pharmacological, toxicological and virological studies
04-11-2005
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Y
41cq77_one_hundred
Meibergdreef 9,
1105 AZ Amsterdam
The Netherlands
Industry
31-20-5662422
31-20-5669240
[email protected]
Research Institute
E
R
Phone:
Fax:
E-mail:
Start-up company
Other
–
Organisation Type: University
Dr
Robert
Chamuleau
H
Address:
Title:
First Name:
Surname:
T
Organisation/Firm
Hep-Art Medical Devices BV
A
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
50-249 employees
250-500 employees
>500 employees
Y
Organisation size: < 50 employees
D
I
C
A
L
T
E
C
H
N
O
L
O
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
E
M
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
G
A P P L I C AT I O N D O M A I N S
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I
O
M
E
2 1 . B i o a c t i v e p e p t i d e s - F l u o re s ce n t
Analogues for rapid binding and
f u n c t i o n s c re e n i n g
D
Title of result:
I
Bioactive Peptides – Fluorescent-Analogues for rapid binding and function screening
C
Ownership: piCHEM Forschungs- und Entwicklungs- GmbH.
A
L
T EC H N O LO GY D E S C R I PT I O N
T
Abstract of the technology:
E
C
Peptides can be labelled and be used as carrier for cell targeting and the screening of construct function.
The company has the know-how to produce peptide-conjugates for life science research (non radioactive), for diagnostic, and therapeutic use.
H
N
Detailed description of the technology:
O
Non radioactive peptide conjugates (Fluorescence, etc. ) for analogue function screening, receptor binding studies, etc.
L
O
Current stage of development of the technology:
G
Y
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
–
Intellectual Property Rights
T
H
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
E
R
A
Exploitation potential
P
Innovative Aspects
Main advantage
Y
288
Fluorescent labelled peptides in combination with cell culture can substitute
radiolabelled peptides in receptor–binding or protein interaction screening allow rapid analysis in medical applications and high-through put screening.
04-11-2005
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Y
41cq77_one_hundred
Address:
Kahngasse 20, 8045 Graz - Austria
Industry
Phone:
Fax:
E-mail:
+43 (0)316 68 17 11 0
+43 (0)316 68 17 11-4
[email protected]
Research Institute
Start-up company
H
E
R
Dr.
Fritz
Andreae
Other
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Organisation Type: University
Title:
First Name:
Surname:
T
Organisation/Firm
piCHEM Forschungs- und
Entwicklungs- GmbH.
A
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
50-249 employees
250-500 employees
>500 employees
Y
Organisation size: < 50 employees
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Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
E
M
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
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Biomedical
technology –
diagnostic
© Digital Stock, 1996
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100 Technology Offers stemming from EU biotechnology RTD results
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1 . D i a g n o s t i c te s t a n d m e a n s f o r t h e
i d e n t i f i ca t i o n o f b a c te r i a l p a t h o g e n s
ca u s i n g p n e u m o n i a
D
I
Title of result:
C
A
Diagnostic tests and means (e.g. labelling kits; monoclonal antibodies; microarray,
biosensor, and multiplex PCR formats) for the identification of bacterial pathogens
causing pneumonia.
L
Ownership: KREATECH Biotechnology B.V.
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T EC H N O LO GY D E S C R I PT I O N
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H
Diagnostic tests were developed for the simultaneous detection of five bacteria causing pneumonia.
Also, in the course of this project several enabling tools were developed. These tools have a broad field
of use, such as nucleic acid microarrays, protein microarrays, biosensors, and general labelling and
detection means.
N
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Abstract of the technology:
O
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Infectious pulmonary diseases form a serious threat to human welfare. Pneumonia continues to be a
major health problem despite the availability of potent antimicrobial drugs. Pulmonary diseases are
often caused by bacteria. Diagnostic tests are available for pulmonary bacterial diseases but there is still
an urgent need for more accurate (high sensitivity and specificity) and rapid diagnosis (hours instead of
days or even weeks). The wellbeing of patients suffering from pneumonia will be enhanced significantly by a differential diagnostic test with improved characteristics. The best way to achieve this is by combining and simplifying existing test principles. In this PulmInfect project a multi-parameter diagnostic
test is developed based on the combination of the detection of both the pathogen (antigen and nucleic
acid) and the immune response (antibodies) directed towards the pathogen. Combining these test into
an optimised single test will significantly increase both reliability and speed of diagnosis. Combining the
detection of multiple pathogens, even for a single parameter, in one test format has several major advantages: (i) The clinician does not have to decide (based on vague clinical symptoms) for which pathogen
to test. Multiple sequential testing is not necessary anymore, saving both time and money; (ii) When
pneumonia is caused by multiple pathogens, all of these pathogens will be detected. Treatment can be
directed towards multiple pathogens at the same time; (iii) The fact that the other pathogens tested for
are not detected increases the diagnostic value of the positive test result, increasing overall sensitivity
and specificity. Consequently, treatment can be highly specific. Especially in case only one pathogen is
detected, broad-spectrum antibiotic use can be prevented, which is important in the prevention of resistance development; and (iv) Underlying diseases causing increased susceptibility may be detected. The
underlying cause may appear to be just as important to treat as the pneumonia itself. The main objective of the PulmInfect project was the development of specific and sensitive diagnostic assays for the differential diagnosis of respiratory infectious diseases. These tests are each targeted to diagnose important
Y
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Detailed description of the technology:
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respiratory bacterial pathogens simultaneously. The tests are based on either ELISA, microarray,
biosensor, or multplex PCR. The prototypes were developed in such a way that they are adjustable to
the needs of the market at the end of this CRAFT project (i.e. other pathogens may be included, or the
prototype set-up may be copied to another format). Sub-objectives are the development of specific and
sensitive diagnostic tests for single pulmonary pathogens on different test formats, and the development
of enabling technology products in order to make possible the design, development, production, and
use of diagnostic tests for pathogen detection and identification. The bacteria selected are Streptococcus
pneumoniae, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and
Legionella pneumophila.
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41cq77_one_hundred
Current stage of development of the technology:
Y
–
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
G
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) : licensing opportunity
O
L
Patents granted
Partnership/other contractual agreements
N
Patents applied for but not yet granted
Exclusive rights
License agreement reached
O
Intellectual Property Rights
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Project's actual outcome
1) Proteomics highlights: Antigens of Mycobacterium tuberculosis, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia trachomatis and
Legionella pneumophila were isolated and used for the production of monoclonal antibodies (Mabs). Mabs – antigen combinations displaying high affinity were selected and used in reference and prototype test development. The M.
tuberculosis Mabs were successfully used in (i) the development of a TB antigen detection ELISA test, (ii) the development of a TB antigen immunosensor
biosensor test, and (iii) the TB Mabs turned out to be extremely useful in TB
antigen production and quality control. The TB antigen ELISA and
immunosensor test with electrochemical detection displayed the same TB
detection limit. In general, this technology can be applied to any pathogen upon
availability of appropriate antigen – antibody pairs. A protein microarray was
designed and optimised for M. tuberculosis. TB antigen mixtures were spotted
on glass slides and analysed with patient sera. This test showed a high test performance in the diagnosis of TB (ROC value of 0.95). An ELISA test was
developed for antigen and antibody detection of Mycoplasma pneumoniae.
Legionella pneumophila recombinant antigens were produced and subsequently used for the production of Mabs. The selected antigens were analysed in
ELISA and showed positive signal with samples from positive patients suffering from pneumonia. Also, several Mabs were identified and successful used in
B
Innovative Aspects
Main advantage
H
Exploitation potential
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ELISA. They showed very specific reaction with L. Pneumophilia
2) Genomics highlights: A multiplex PCR test was developed for three nucleic acid targets of S. pneumoniae. This single pathogen multiplex PCR test
showed very high specifications (100% sensitivity and specificity) on a small
sample panel of patients. Single pathogen PCR tests were developed for
Mycobacterium tuberculosis and Legionella pneumophila. A multiple
pathogen prototype multiplex PCR test, incorporating all five bacteria (Streptococcus pneumoniae, Mycobacterium tuberculosis, Mycoplasma pneumoniae,
Chlamydia pneumoniae, and Legionella pneumophila) was developed. This
required design of well defined PCR oligoprimers which resulted in excellent
test specificity. The oligoprimers and nucleic acid fragments made possible the
development of a microarray diagnostic test for Mycobacterium tuberculosis,
Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia trachomatis,
and Legionella pneumophila. This multiple pathogen microarray test showed
good determination and discrimination of the pathogens. A genosensor, this is
a single pathogen biosensor test, was developed for Streptococcus pneumoniae.
This type of test displayed both selectivity and base-mismatch detection.
3) Other highlights: Mabs raised against fluorescent dyes proved to be excellent tools in the development of a signal amplification technology. Mabs were
identified displaying high affinity towards corresponding dyes, with even very
little if any cross reactivity towards other dyes. Cy3 and Cy5 are the preferred
fluorescence dyes in the Life Sciences research market. The chemical structure
of the two dyes is nearly identical. Nevertheless, Mabs are developed against
both Cy3 and Cy5 displaying a high affinity to the dye and lacking cross activity to the other dye. With two of said Mabs a dye specific amplification system
was developed.
Optimal conditions for ULS target labelling of nucleic acid probes was established. Special emphasis was on PCR post labelling in view of the multiplex
PCR prototype approach. A lot of progress was made in serum ULS target
labelling.
From the start of the project it was stated that ELISA tests would be produced,
marketed and distributed from within the consortium, whereas production,
marketing and distribution of differential diagnostic tests would be out licensed
to third parties. Within the consortium ELISA tests are developed for all
pathogens. At present, several of them are in the stage of product development
(= final fine-tuning) and/or clinical testing. The TB Mabs made possible production of high quality TB antigen mixtures. KREATECH uses the TB Mabs
to produce TB antigen mixtures on behalf of third parties showing interest in
TB immunodiagnostics. The consortium showed that biosensor and multiplex
PCR technologies are suitable tools for simultaneous detection of various pulmonary pathogens. Those technologies are up for out licensing to third parties.
The fluorescence labels cyanine 3 and cyanine 5 are used in many Life Science
research applications. Research on how to improve sensitivity is ongoing. One
approach is signal amplification. The consortium developed such system for
several fluorescence dyes including cyanine 3 and 5. The cyanine 3 and 5 Mabs
are available to the research community and KREATECH is looking for third
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parties interested in these materials. The progress made on optimising nucleic
acid ULS labelling in DNA, RNA, and protein microarray applications assisted KREATECH in its development of microarray labelling kits. KREATECH
released several new ULS labelling kits for direct, non-enzymatic labelling of
aRNA for Gene Expression microarray analysis, genomic DNA for arrayCGH
analysis, and antibody microarray labelling and analysis. KREATECH is looking for distributors to market these kits and for licensees who want to use the
ULS technology in their own applications.
T
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41cq77_one_hundred
Organisation Type: University
Research Institute
50-249 employees
Start-up company
250-500 employees
L
T
E
+31 20 6919181
+31 20 6963531
[email protected]
Other
>500 employees
E
D
Organisation size: < 50 employees
Industry
Phone:
Fax:
E-mail:
A
Vlierweg 20, 1032 LG Amsterdam,
The Netherlands
Jack
Veuskens
C
Address:
Title:
First Name:
Surname:
I
Organisation/Firm
KREATECH Biotechnology B.V.
C
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Infectious diseases
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
M
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2. Demonstration of the superior
s e n s i t i v i t y o f l u n g d e n s i to m e t r y o n
m u l t i - s l i ce C T i m a g e s f o r t h e a s s e s s m e n t
o f p ro g re s s i o n o f e m p h y s e m a a s
co m p a re d to co n v e n t i o n a l l u n g f u n c t i o n
te s t s i n a m u l t i - ce n t re s t u d y
A
L
Title of result:
T
E
Demonstration of the superior sensitivity of lung densitometry on multi-slice CT images
for the assessment of progression of emphysema as compared to conventional lung
function tests in a multi-centre study
C
Ownership: Leiden University Medical Center
H
T EC H N O LO GY D E S C R I PT I O N
N
O
Abstract of the technology:
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The present (SPREAD) study assessed the progression of pulmonary emphysema with our newly
developed analytical software called Pulmo-CMS. In this study, CT images of 96 patients with alpha-1antitrypsin deficiency (AAD) from 5 European sites, were acquired at baseline and after 2.5 years of follow-up analysed with Pulmo-CMS (Medis medical imaging systems, Leiden, the Netherlands). The sensitivity of the density measurement was compared with that of conventional lung function tests.The
progression of emphysema between baseline and follow up was calculated for the density parameter
15th percentile point (Perc15) and the lung function parameter FEV1 and compared with progression
measured in normal subjects. This multi-centre study, using different brands of CT equipment, confirmed that the new CT-derived parameter, the 15th percentile, was more sensitive in the assessment of
the progression of emphysema than conventional lung function tests. This reproduction of the results
on a larger scale is a major scientific advancement in the R&D area of this disease. This software application has great potential to replace pulmonary function tests as a measurement tool for future clinical
drug trials because it may prove drugs effects much earlier with fewer patients involved, thus making
the trial more cost-effective. The goal of this particular application is to further develop/extend the software for additional applications in other lung diseases such as fibrosis, asthma etc. The end-product will
be a software package that allows the accurate and reproducible assessment of changes in the degree of
the disease over a wide range of lung diseases.
S
I
All CT images of the thorax were analysed by the software package Pulmo-CMS, which has been developed by partner 1 in collaboration with Medis medical imaging systems, Leiden, the Netherlands. This
software package has been developed for a standard PC and runs under the Windows operating system.
The software tool can therefore communicate with other Windows-based programs, such as MS-Office’s
C
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Detailed description of the technology:
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Word, Excel, Access etc. Pulmo-CMS is able to read CT images acquired with scanners from different
manufacturers through the image standards ACR-NEMA 1.0, ACR-NEMA 2.0 and DICOM 3.0.
Images can be read from several storage media, such as hard disks, CDs or a connected network. Basically, the image analysis consists of five steps: 1) recalibration for blood and/or air; 2) (semi-) automatic
selection of the lungs; 3) if needed, manual adjustment of the detected contours; 4) calculation and subsequent analysis of the density distributions; and 5) presentation of the measurement results. First, the
mean blood density is calculated from regions within the descending aorta in the patient and the density
of air is measured from automatically detected regions outside the patient. Subsequently, these two measured values are used for recalibrating the CT images. By this calibration procedure, changes in the spectrum of the X-ray tube, due to tube ageing, and changes in the patient’s blood density, due the emphysema, are taken into account. In the second step, the lungs are selected semi-automatically by having the
user define a location within the trachea. Subsequently, the software carries out a so-called region growing, which lets this initial location expand (like a balloon) until it reaches the borders of the lungs. The
septum (the border between the left and right lung), the trachea and the two main stem bronchi are
detected separately. In some cases the oesophagus is erroneously included into the lung region. In these
cases the oesophagus is detected in a separate processing step. Finally, the lung parenchyma (the functional element of the lungs: i.e. the lung tissue without large airways and blood vessels) is defined by excluding the septa, trachea, oesophagus, and mean stem bronchi from the initial segmentation result. By doing
so, the lungs are selected with a high degree of reproducibility: two CT scans of the same subject will give
the same analysis results. In the third step the detected contours can be manually corrected by the user,
if needed, while using semi-automatic editing tools. In the fourth step, the histograms of the left and right
lung parenchyma are calculated. From these histograms five parameters are calculated: the total lung volume, mean lung density, the lung weight (which is equal to the product of volume and density), the 15th
percentile point and the area of the lungs (in %) below a certain density value, called the relative area. The
15th percentile point (Perc(15)) was chosen as the effect variable. The 15th percentile point is extracted
from the frequency distribution of lung pixels and is defined as the density value in Hounsfield Units
(HU) at which the lowest 15% of the densities occur in the histogram. As recommended during an international workshop (Newell et al., 2004), we used the 15th percentile point (Perc(15)) for the assessment
of emphysema in this study and calculated the variability in this parameter. Finally (step 5) , these results
are presented to the user, and can be saved on disk to facilitate further statistical analysis by spreadsheet
programs or statistical packages.
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41cq77_one_hundred
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Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
M
E
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
A
Current stage of development of the technology:
Intellectual Property Rights
Comments:
I
O
Patents granted
Partnership/other contractual agreements
B
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Research version of the software has been used during the project for image
analysis of CT data.
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Exploitation potential
The current study has demonstrated that objective and reproducible assessment
of progression of emphysema is possible by the implemented technique. Further innovation towards other lung disease is now warranted, so that a very
cost-effective tool becomes available for clinical research and diagnosis in these
areas. This will improve patient-care and support clinical research in its search
for optimal treatment strategies. These new application areas include:
Application to other lung diseases
We are planning to apply CT-densitometry of the lungs to other lung diseases
such as cystic fibrosis and fibrosis, which are likely to increase the lung density. Other parameters will be developed that are most sensitive to the progression of these particular diseases.
Application to treatment evaluation such as lung volume reduction surgery
Lung densitometry can be used to study the treatment effect of lung volume
reduction surgery, since the improved blood perfusion in the lungs is expected
to be measurable by the software.
Standardization of CT scanners
In addition, we have found over the past years that much is to be gained in the
standardization of CT-scanners. In order to further standardize/optimize CT
equipment, these issues will be discussed with the four major CT manufacturers. Especially calibration issues and technical shortcomings will be discussed.
Strategy to change guidelines on drug trials for assessing efficacy of new
drugs for emphysema
- To advise CPMP (Committee for Proprietary Medicinal Products) by
EFPIA (European Federation for Pharmaceutical Industry Associations ) to
change the guidelines
- Members of AIR (Alpha1 International Registry) are in a position to advise
the ERS that the guidelines from CPMP should be changed, based on the
scientific results of the current project
Main advantage
- New accurate diagnostic tool. The problem of lung emphysema is obvious
because lung disease is a disease that affects men and women all over the
world. Early and accurate diagnosis of the disease and the subsequent follow-up of the treatment are of enormous importance from a health-care and
cost-effectiveness point-of-view. Therefore, accurate diagnostic and clinical
research tools are required. With the results of this project a new accurate
diagnostic tool has been added on a European scale.
- Changing guidelines on drug trials for assessing efficacy of new drugs for
emphysema. The high reproducibility of the developed measurement has
been achieved by standardization of the image acquisition protocols of the
CT scanners from the different manufacturers and through standardization
of the image analysis procedures, including recalibration of the CT images
and correction for differences in inspiration levels. The standardisation has
been evaluated with a phantom study and by assessing the influence of the
standardization on the variability between centres, between repeated measurements and between observers. With this result, pharmaceutical compa-
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nies will most likely start trials with new drugs, using density measurements
as outcome parameter of drug efficacy. This will likely influence the regulations for carrying out clinical trials in this field. The performance of our
software is a very important asset in the development of new treatments.
- Improving the quality of life. Although AAD is a rare disorder, lung
emphysema is not. The pathology between subjects with and without AAD
is different, but the result of lung tissue destruction is the same. It is for this
loss of tissue that software analysis of CT data in the SPREAD project was
centred on. Therefore, the successful reproduction of previous findings
based on AAD patients will most likely be used for extrapolation to emphysema in general. This condition is projected to become the third leading
cause of death in the EU in 2020. Application of our results already leads to
clinical trials with new drugs, hopefully to reduce the ranking of the cause
of death of emphysema. Treatment of subjects with AAD and emphysema
may have impact on their employment prospects, because their disease starts
around the age of 30 and progresses during their adult life over a period of
20 years. Altering the course of their disease will most likely keep them economically active.
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41cq77_one_hundred
Organisation Type: University
Research Institute
50-249 employees
Start-up company
250-500 employees
L
T
E
+31 71 526 3935
+31 71 526 6801
[email protected]
Other
>500 employees
E
D
Organisation size: < 50 employees
Industry
Phone:
Fax:
E-mail:
A
Albinusdreef 2
2333 ZA Leiden, The Netherlands
Prof.dr.
Johan H.C.
Reiber
C
Address:
Title:
First Name:
Surname:
I
Organisation/Firm
Leiden University Medical Center
C
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
M
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3 . M E LV I R - D i a g n o s i s o f m e l a n o m a
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Title of result:
E
MELVIR- diagnosis of melanoma
D
Ownership: Green Hills Biotechnology
I
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T EC H N O LO GY D E S C R I PT I O N
A
L
Abstract of the technology:
T
MELVIR is based on GHBęs finding that melanomas are associated with the expression of endogenous
retroviruses. This finding provides the foundation for early diagnosis and therapy of melanoma.
E
H
An immunodominant peptide located in the env protein of MERV was analyzed utilizing 81 samples
from stage I – stage IV melanoma patients and 95 sera from healthy subjects. ELISA was performed to
screen for sera antibodies reactive to the selected epitope. Statistically significant differences between
ELISA signal distributions comparing early stage (I, II) and late stage (III, IV) patient sera with ELISA
signals derived from sera of healthy subjects were identified. Sensitivity of 90 % at a specificity of 70 %
indicates the potential of this novel marker.
N
C
Detailed description of the technology:
O
L
O
G
Current stage of development of the technology:
Y
–
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
D
I
Intellectual Property Rights
A
G
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Patents granted
Partnership/other contractual agreements
N
O
Exploitation potential
S
T
Innovative Aspects
Main advantage
I
C
300
The key advantage of GHB’s MELVIR-diagnostic tool is the finding, that
retrovirus–specific antibodies are prevalent in more than 90 percent of
melanoma patients. Importantly, antibodies can be detected at an early stage of
disease, which is vital for the cure of melanoma.
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Dr.
Thomas
Muster
Phone:
Fax:
E-mail:
0043 1 31 99 670
0043 1 31 96 099
[email protected]
O
Title:
First Name:
Surname:
Organisation Type: University
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
A
–
Organisation size: < 50 employees
Industry
I
Gersthofers Straße 29-31
A-1180 Wien
Austria
D
Address:
G
N
Organisation/Firm
Green Hills Biotechnology
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
A P P L I C AT I O N D O M A I N S
D
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A
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C
H
N
O
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Y
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
E
M
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
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4 . Te s t k i t s , a n t i b o d y / D N A , d a ta b a s e ,
t r a i n i n g , p a te n t
E
Title of result:
D
Test kits, Antibody/DNA, Database, Training, Patent (Brandname)
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C
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Ownership: GeneMaLK SA
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T EC H N O LO GY D E S C R I PT I O N
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Abstract of the technology:
C
H
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G
Y
Our studies and corporate activities are dealing with the infectious risks involved in xenotransplantation and xenogeneic cell-based therapies. Diagnostic tools are needed that can be used for validation of
pig-derived materials and medicinal products, e.g. cell such as hepatocytes for bioreactors, prior to clinical xenotransplantation. Xenotransplants could harbor animal pathogens which are transmitted to the
immunosuppressed human recipient. Viruses pose the most serious risk. As it has been shown that
xenotropic porcine endogenous retrovirus PERV-A and ecotropic PERV-C have the capacity to recombine in the course of infections of human cells in vitro yielding viruses with higher titers, we aimed at
the generation of specific antibodies. Thus, specific antisera commonly directed against PERV Gag and
Env per se and antisera against ecotropic PERV-C envelope protein (Env) were generated which have
the capacity to differentiate the latter virus from humantropic PERV-A and PERV-B. In addition,
exogenous agents such as herpesviruses exist in pigs (PHV) for which the capacity of infections in vivo
needs to be further characterized. Pilot diagnostic tools covering this item were generated.
–
Detailed description of the technology:
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I
C
Porcine kidney cell cells (PK15) and human embryonic kidney (HEK, 293) cells infected and constitutively producing porcine endogenous retroviruses have been the basis for the expression of cognate
PERV mRNAs and related proteins such as Gag and Env. Appropriate preparations of PERV proteins
have been used for setting up specific immunoblots. Antipeptide antibodies (polyclonal) against the Cterminus of PERV nucleocapsid (p 10) were initially raised. In the second project period reported here,
polyclonal antipeptide antibodies against PERV capsid (p30), PERV envelope surface protein (Env-SU
gp70) and PERV envelope transmembrane protein (Env-TM p15) were generated and tested. Human
293 cells producing infectious virions were used for functional testing (QC) of antibodies. In parallel,
polyclonal antibodies against porcine herpesviruses (PHV) have been generated. Two families of herpesviruses have been identified in pigs, porcine cytomegalovirus (PCMV) and porcine lymphotropic
herpesvirus, types 1, 2, and 3 (PLHV 1-3). PLHV are homologous to Eppstein Barr Virus (EBV) and
human herpesvirus 8 (HHV-8). Hence, PLHV in pigs are associated with a lymphoproliferative disorder with characteristics of post-transplantation lymphoproliferative disease (PTLD) after activation of
EBV observed in human allotransplant recipients.
302
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C
41cq77_one_hundred
O
S
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
G
N
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
T
Current stage of development of the technology:
A
Intellectual Property Rights
I
Pateting of brand name at “Deutsches Patentamt München“ prepared
–
Comments:
Patents granted
Partnership/other contractual agreements
D
Patents applied for but not yet granted
Exclusive rights
License agreement reached
G
Unique products, Xenogeneic cell therapy and Xenotransplantion can not be
assassed or further developed without our products
H
N
O
L
O
Innovative Aspects
Main advantage
Y
Exploitation potential
C
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Organisation Type: University
T
L
[email protected]
Research Institute
50-249 employees
E
+41 91 9401001/+41 61 965 1321
Start-up company
250-500 employees
Other
>500 employees
E
D
Organisation size: < 50 employees
Industry
Phone:
Fax:
E-mail:
A
Via Massagno 20
6952 Canobbio, Switzerland
Dr.
Marco
Traub
C
Address:
Title:
First Name:
Surname:
I
Organisation/Firm
GeneMaLK SA
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Moleculare
Medicine
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
M
A P P L I C AT I O N D O M A I N S
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
E
D
I
5. Use of a human skin explant model for
t h e te s t i n g o f n o v e l ce l l l i n e s , d r u g s e t c .
i n t h e m o d u l a t i o n o f a l l o re a c t i v i t y.
Ce l l l i n e a n d D N A b a n k f o r g e n e t i c
a s s e s s m e n t i n t r a n s p l a n ta t i o n
C
A
Title of result:
L
T
Use of a human skin explant model for the testing of novel cell lines, drugs etc. in the
modulation of alloreactivity. Cell line and DNA bank for genetic assessment in transplantation
E
Ownership: University of Newcastle upon Tyne
C
T EC H N O LO GY D E S C R I PT I O N
H
N
Abstract of the technology:
O
L
O
A human skin explant model has been developed for the testing of novel cell lines/drugs etc. to assess
their immunomodulatory capacity. A cell line and DNA bank (EUROBANK) has been developed with
over 3-400 patient/donor pairs for genetic typing for assessment of transplant outcome.
G
Y
Detailed description of the technology:
In vitro culture system of human skin biopsies for histopathology, immunocytochemistry etc. EBV
transformed cell line bank for DNA genotyping.
–
D
Current stage of development of the technology:
I
A
G
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
N
O
Intellectual Property Rights
S
T
Patents applied for but not yet granted
Exclusive rights
License agreement reached
I
Comments:
C
304
Patents granted
Partnership/other contractual agreements
Use of the EUROBANK collection requires consortium agreement before
release of DNA.
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C
41cq77_one_hundred
S
Human model system; novel collection of clinical material and information,
anonymised, coded and with informed consent for research.
O
L
O
G
Y
–
D
I
A
G
N
O
Innovative Aspects
Main advantage
T
Exploitation potential
H
Professor
Anne
Dickinson
Phone:
Fax:
E-mail:
+44 191 282 4959
+44 191 222 6794
[email protected]
C
Title:
First Name:
Surname:
E
Organisation/Firm
University of Newcastle upon Tyne
N
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
L
A
Research Institute
50-249 employees
Start-up company
250-500 employees
Other
>500 employees
E
D
Organisation size: < 50 employees
Industry
C
Organisation Type: University
T
School of Clinical and
Laboratory Sciences
The Medical School
Framlington Place
Newcastle upon Tyne
NE2 4HH
I
Address:
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Transplantation
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
M
A P P L I C AT I O N D O M A I N S
305
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
6 . S e q u e n c i n g o f H e p a r a n S u l p h a te
M
Title of result:
E
Sequencing of heparan sulphate
D
Ownership: WITA GmbH
I
C
T EC H N O LO GY D E S C R I PT I O N
A
L
Abstract of the technology:
T
E
C
H
N
O
L
O
G
Heparan sulphate (HS) is becoming recognised as a molecule which is very abundant on cell surfaces
and in the intracellular matrix. It is apparent that it plays a key role in many stages in growth development and in malignancy. This is a complex polysaccharide molecule which interacts with a large number of regulatory molecules via specific binding sites along the chain. This chain is, however very complex in structure, and not amenable to analysis by most conventional techniques. Technology for
sequencing heparan sulphate fragments is now available and can be applied to identify the sequence of
regions of HS binding to molecules of interest. A number of monoclonal antibodies directed against
specific regions of heparan sulphate have been produced and we have successfully demonstrated the
application of these to visualisation of HS in tissue and for separating HS fragments of biological interest. Defined sequences of heparan sulphate can be produced in a size up to 15 monomer units suitable
for studies of interaction with biological molecules. Alternatively fragments from a pool of HS oligosaccharides which have binding properties may be separated and subjected to sequence analysis. This
analysis required specialised expertise and reagents and there are few, if any, other providers of such a
service on a commercial basis.
Y
–
Detailed description of the technology:
D
I
A
G
N
O
S
T
I
C
The application of novel sequencing technology for the identification of binding sites on heparan sulphate for molecules of immunological interest has been demonstrated. The separation and purification
of fragments containing those biding sites in a sufficiently pure form for sequencing has been shown to
be possible. A novel technique for fluorescent labelling suitable for use on gels has been developed. A
number of specific monoclonal antibodies against heparan sulphate have been evaluated for use in separation of HS fragments and for visualisation of HS in tissue sections. HS fragments which bind to
chemokines and selections have bee identified and separated. A range of characterised HS and heparin
fragments suitable for use as standards have been produced. Technology for production of such fragments and for complete sequence analysis is now available through the consortium and can be offered
as a service on a commercial basis. Full sequence analysis can at present be offered on fragments of up
to 15mer in length. Alternative techniques such as tritium labelling and mass spectrometry are available
to supplement the fluorescent labelling technology. The exact amount of material required will depend
on the complexity of the sample and would need to be assessed for each analysis to be performed.
Development may allow the minimum amount of sample required to be lowered to the microgram
range required for some material from biological sources.
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C
41cq77_one_hundred
O
N
G
A
I
D
–
Y
O
G
Development phase
Available for testing or assessment
Tested, available for demonstration
Preliminary design, feasibility study
Already on the market
Intermediate design, research phase
Other (please specify) : Prototype/demonstrator available for testing, results of demonstration trials
available. The viability of the technique has been demonstrated on a number
of standard HS fragments with success. The application to biological material is still being examined with regard to the complexity of fragment that
can be sequenced and amount of material required. Fractionation procedures for isolation of single fragments by use of specific antibodies have
been developed. An improved fluorescent label (ANDSA) has been developed. Data is available on sequencing studies with comparison to other
established techniques, such as tritium labelling. Data has been published
using the technique. The combined expertise of the consortium is available
for analysis and interpretation of HS sequence analysis. This may be applied
to studies on the interactions of HS with other molecules involved in cell
regulation, such as growth factors.
S
T
Current stage of development of the technology:
O
N
H
C
Patent, HS sequence analysis by partial nitrous acid/exoglycosidase sequencing
– Metabolic labelling.
Secret know-how: Fragment isolation / Partial cleavage / Labelling techniques
/ Exoglycosidase sequencing.
Licence agreement – information exchange – private-public partnership
T
Comments:
Patents granted
Partnership/other contractual agreements
E
Patents applied for but not yet granted
Exclusive rights
License agreement reached
L
Intellectual Property Rights
307
A
C
I
D
E
M
O
I
Groups of the consortium can perform services for industrial companies and
research foundations or medical institutions where heparan sulphate analysis
are wanted. With the knowledge gained and special experiences in the field we
can offer collaborations with private or public partners on a commercial basis.
The potential application of the results on HS sequencing are:
1. analysis of HS fragments which bind to biologically important molecules
2. design of sequences blocking HS binding
3. definition of antibody epitopes
Potential users are groups working on the activities of HS binding sites, basic
research groups working on modulation of cytokine and growth factor activities, drug development programmes for controlling HS activities. Many of
these are in the academic sector but there is growing commercial interest.
B
Innovative Aspects
Main advantage
L
Exploitation potential
41cq77_one_hundred
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
Innovative aspects are the commercial availability of HS sequencing technology and of defined HS fragments. The market sector at present seems to be small
but it is anticipated to grow over the next five years. The existing base of WITA
will be targeted in addition to contact made by the partners. The potential barriers to uptake of the technology are the perceived high costs in relation to protein and nucleic acid sequencing, difficulties in purifying material to sufficiently pure state for sequencing and the amount of HS material required which may
be limiting for HS isolated from natural sources. WITA has the potential to
offer HS analysis service, but as it does not fall into the mainstream of their proteomic activities no additional future investment is planned. Exploitation will
require skills in the isolation and preparation of HS fragments, in their chemical and enzymatic cleavage, analysis by gel electrophoresis and in data interpretation. All of these skills required for the provision of the service are already
available within the consortium and cross-training of staff at WITA could be
provided as required. All software required for data analysis is already available. All equipment required for the services is available to WITA and no additional capital expenditure is required for the provision of such an analytical
service. Marketing of the service would be included in promotional activities of
other services offered by WITA. The skills required for the analysis are available to staff as a result of participation in the project. Additional skills which
may be required can be called upon from other members of the consortium.
Partner 3 would be able to offer consultancy. The inclusion of the company
Iduron which was set up by partner 2 is expected following negotiation of suitable terms between partners 1 and 2. Asd partners of the consortium and in particular partners 2 and 3 have an ongoing development programme it is anticipated that any improvement in the technology as may be required can be made
available by these partners to WITA on favourable terms. The potential market
for such a service is uncertain but if offered alongside with other services from
WITA it will not involve any additional expenditure. All resources required are
therefore available to WITA and Iduron. In view of the high risk and doubtful
return on investment no other internal financing will be provided and no
sources of outside funding would be approached. WITA is responsible for
commercialisation of technology, dissemination of knowledge and marketing
of the sequencing service.
M
E
D
I
C
A
L
T
E
C
H
N
O
L
O
G
Y
–
D
I
A
G
N
O
S
T
I
C
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Dr
Brigitte
Wittman-Liebold
Phone:
Fax:
E-mail:
+49 3328 394912
+49 3328 394949
[email protected]
O
S
Title:
First Name:
Surname:
Organisation Type: University
Research Institute
50-249 employees
Start-up company
250-500 employees
A
Other
>500 employees
–
Organisation size: < 50 employees
Industry
I
Warthestrasse 21
D-14513 Teltow, Germany
D
Address:
G
N
Organisation/Firm
WITA GmbH
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
A P P L I C AT I O N D O M A I N S
D
I
C
A
L
T
E
C
H
N
O
L
O
G
Y
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
E
M
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
309
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I
O
M
7. D e v e l o p m e n t o f Me d i ca l X- r a y
d i g i ta l Sy s te m
E
Title of result:
D
Development of Medical X-ray digital System
I
C
Ownership: Institut de Fisica d’Altes Energies
A
T EC H N O LO GY D E S C R I PT I O N
L
T
Abstract of the technology:
E
C
The development is devoted for mammography system in particular and for chest and bone analysis in
general. The development is based on the use of room temperature pixel solid-state detectors coupled
to photon counting ASIC via bump bonding.
H
N
Detailed description of the technology:
O
L
O
G
The direct capture of the X-ray photon of energy greater than 15KeVin the solid-state detector leads to
a significant electric signal than can be shaped and discriminated from noise. The photon counting ASIC
makes sure that only good signals are counted and hence set the electronics noise level to zero. Then
only noise left is the statistical and the scattered ones. Over all, one can achieve a very good signal to
noise ratio and hence a very good contrast image.
Y
Current stage of development of the technology:
–
D
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
I
G
Patents applied for but not yet granted
Exclusive rights
License agreement reached
N
A
Intellectual Property Rights
Patents granted
Partnership/other contractual agreements
O
S
T
Exploitation potential
I
Innovative Aspects
Main advantage
C
310
High contrast image at low radiation dose. Allowing seeing small micro
calcifications.
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C
41cq77_one_hundred
Phone:
Fax:
E-mail:
+34 93 581 2846
+34 93 581 1938
[email protected]
S
Dr.
Mokhtar
Chmeissani
O
Title:
First Name:
Surname:
Organisation Type: University
Research Institute
50-249 employees
A
Start-up company
250-500 employees
Other
>500 employees
–
Organisation size: < 50 employees
Industry
I
Edifici CN, UAB Campus,
Bellaterra, 08193 Spain
D
Address:
G
N
Organisation/Firm
Institut de Fisica d’Altes Energies
T
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
A P P L I C AT I O N D O M A I N S
D
I
C
A
L
T
E
C
H
N
O
L
O
G
Y
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
E
M
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
E
D
8. Development and validation of
a D N A - ch i p te ch n o l o g y f o r t h e
a s s e s s m e n t o f t h e b a c te r i o l o g i ca l
q u a l i t y o f b a t h i n g a n d d r i n k i n g w a te r
I
C
Title of result:
A
L
Development and validation of a DNA-chip technology for the assessment of the bacteriological quality of bathing and drinking water
Ownership: German Research Center for Biotechnology
T
E
C
T EC H N O LO GY D E S C R I PT I O N
H
N
Abstract of the technology:
O
L
O
G
Y
A DNA-chip technology was developed and validated to assess rapidly and accurately potential human
health risks arising from bacterial contamination in drinking and bathing waters. This main objective
can be divided in three parts: i) Develop molecular methods to identify and quantify the presence of
important pathogenic and indicator bacteria in any given water sample and to assess their state of activity and pathogenicity. ii) Compare laboratory and field data to assess health risks in aquatic environments and design a multiparametric assay based on molecular probes. iii) Combine quantitative PCR
and DNA-chip technology to validate a DNA-array suitable for mass application that leads to scientifically sound new procedures for the assessment of the hygienic quality of drinking and bathing water.
–
Detailed description of the technology:
D
I
A
A DNA-chip based technology for the detection of pathogenic and indicator bacteria in bathing and
drinking water was developed and validated. This technology includes: i) a kit for the extraction of
nucleic acids from water samples, ii) several DNA-chips for specific waterborne pathogens and indicators, and iii) a computer-based analytical systems that quantifies and identifies the response of the aquatic DNA on the chip.
G
N
Current stage of development of the technology:
O
S
T
I
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) :
C
312
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
04-11-2005
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I
C
41cq77_one_hundred
T
Intellectual Property Rights
S
Patents granted
Partnership/other contractual agreements
I
D
Future activities will be: i) market the developed extraction kits, ii) market the
chip technology for specific target bacteria, e.g. Legionella and Salmonella, and
iii) seek new funds for general validation of the chip technology and approval
as new regulation for the assessment of the hygienic quality of bathing and
drinking water. The technology is open to automation and mass application.
Potential end users are public health authorities, water authorities, drinking
water industries and tourism information systems.
H
N
O
L
O
G
Y
Innovative Aspects
Main advantage
–
Exploitation potential
A
G
N
O
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Title:
First Name:
Surname:
Dr.
Manfred
Höfle
Address:
Phone:
Fax:
E-mail:
+49 531 6181 419
+49 531 6181 411
[email protected]
Research Institute
50-249 employees
T
L
A
Start-up company
250-500 employees
Other
>500 employees
E
D
Organisation size: < 50 employees
Industry
C
Organisation Type: University
I
Mascheroder Weg 1,
D 38124 Braunschweig, Germany
E
Organisation/Firm
German Research Center for Biotechnology
Dept. Environmental Microbiology
C
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
M
A P P L I C AT I O N D O M A I N S
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
E
D
9 . A n e w d i a g n o s t i c to o l to i d e n t i f y m i c ro
a n d n a n o s i ze d i n o rg a n i c f o re i g n b o d i e s
i n s i d e p a t h o l o g i ca l t i s s u e s , f o o d a n d
e n v i ro n m e n t
I
C
Title of result:
A
L
Development at a new diagnostic tool to identify micro and nanosized inorganic foreign
bodies inside pathological tissues, food and environment. Verification at a close correlation between environmental pollution and pathologies in humans and animals
Ownership: Nanodiagnostics Srl
T
E
T EC H N O LO GY D E S C R I PT I O N
C
N
Investigation of the presence and significance of very small particles of micro- and nano-meter size in various diseases of unknown origin, like cancer of all the organs, lymphoma, leukemia. There is currently
increased concern for the possible detrimental effects of environmentally-derived foreign materials and
micro- and nano-particles on human health. With a modified Environmental Scanning Electron Microscope, and X ray microprobe and a sensor of cathodoluminescence, more 300 hundred cases of cancer
and pathologies of unknown origin were analysed and in all of them, foreign bodies were found. In order
to investigate the possible origin of the debris, samples of food and polluted environment were analysed.
In some cases the origin of the pollution to what the patient or animal were exposed, were identified.
O
H
Abstract of the technology:
L
O
G
Y
–
Detailed description of the technology:
D
I
A
G
N
O
S
T
I
C
The investigation is carried out mainly by means of a specially modified ESEM (Environmental Scanning Electron Microscope). This analysis offers the possibility to observe biological samples in wetmode, i.e. in condition of normal hydration, at environmental pressure, without the need to desiccate
them or make them electro-conductive through a coating that can be made of carbon, or metals like gold
and palladium. By applying appropriate protocols to be adapted to each kind of observation, this feature allows to check biological samples, including living cells, without impairing their integrity, and to
repeat the test every time one wishes. The main objective of the study is the detection of inorganic
micro- and nano-particulate matter, in case there should be any in the sample, and this is achieved without the need of any process of the specimen. An EDS (Energy Dispersive Spectroscopy) supplements
the investigation, as it measures the energy which is a characteristic of each element making up the particles in the specimen, and which is returned as X-rays after the sample has been hit by the electron beam
delivered by the ESEM. The spectrum thus obtained shows the chemical elemental composition of the
particulate matter. So, through such an integrated analysis, the micro- and nano-sized inorganic particles are photographed, measured and chemically characterized in a non-invasive, non-destructive,
repeatable way, the only exception being fluids, which are often impossible to recover. The investigation can be carried out on specimens of biological origin like biopsies, autopsies, organic fluids or food,
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S
O
but is equally feasible on many other kinds of materials like, for example, environmental samples, drugs
or cosmetics. As the principal object of the investigation is inorganic and non biodegradable, there is no
particular difficulty in detecting such particulate matter either in fresh or in archived samples.
T
I
C
41cq77_one_hundred
A
G
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
I
Development phase
Tested, available for demonstration
Already on the market
N
Current stage of development of the technology:
D
Intellectual Property Rights
–
Patents granted
Partnership/other contractual agreements
Y
Patents applied for but not yet granted
Exclusive rights
License agreement reached
Via E.Fermi 1/L
41057 San Vito - Modena - Italy
Organisation Type: University
Research Institute
50-249 employees
Start-up company
250-500 employees
L
O
N
E
T
+39059798778
+390597579182
[email protected]
L
Phone:
Fax:
E-mail:
Other
>500 employees
E
D
Organisation size: < 50 employees
Industry
Dr
Antonietta
Gatti
A
Address:
Title:
First Name:
Surname:
C
Organisation/Firm
Nanodiagnostics Srl
C
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
H
The technology allowed to confirm that some pathologies of unknown origin
can be related to a specific also nanosized pollution. At present we are collaborating with the Italian and British government for the Gulf War and Balkan
Syndrome. Collaborations were set up for the present victims of the Twin Towers collapse. This knowledge is essential for a Detoxification project. This
knowledge will help in new medical treatment of similar pathologies, in prevention and in the construction of instrument for the deep detoxification.
I
Innovative Aspects
Main advantage
O
G
Exploitation potential
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
M
A P P L I C AT I O N D O M A I N S
315
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100 Technology Offers stemming from EU biotechnology RTD results
B
I
O
M
E
D
I
1 0 . G e n o t y p i n g o f p a r a s i te s i n b re a k t h ro u g h ca s e s i n RT S , S / A S 0 2 a n d
Co n t ro l g ro u ps i n T h e G a m b i a , 1 9 9 9 a n d
i n t h e M o za m b i q u e P h a s e I I e f f i ca c y
s t u d y, 2 0 03 - 2 0 0 4
C
A
Title of result:
L
Genotyping of parasites in breakthrough cases in RTS,S/AS02 and Control groups in The
Gambia, 1999 and in the Mozambique Phase II efficacy study, 2003-2004.
T
Ownership: London School of Hygiene and Tropical Medicine
E
C
T EC H N O LO GY D E S C R I PT I O N
H
N
Abstract of the technology:
O
L
O
We have adapted standard high-throughput PCR and DNA sequencing technologies to enable genotyping evaluations of large numbers of field samples from participants in a clinical trial of this malaria vaccine. This builds on high-throughput hybridisation protocols formerly used for this purpose, but still
in use in our laboratory for certain applications including screening for mutations in parasite genes
implicated in antimalarial drug resistance.
G
Y
Detailed description of the technology:
–
DNA extraction from dried filter-paper blood spots is performed in 96-well format and these sample
arrays are carried through all subsequent manipulations, including single-or double-round PCR amplification, sequencing, dot-blot hybridisation or RFLP analysis.
D
A
Development phase
Tested, available for demonstration
Already on the market
Other (please specify) : Applied research
G
I
Current stage of development of the technology:
Available for testing or assessment
Preliminary design, feasibility study
Intermediate design, research phase
N
O
T
Patents applied for but not yet granted
Exclusive rights
License agreement reached
I
S
Intellectual Property Rights
C
Comments:
316
Patents granted
Partnership/other contractual agreements
Applications of existing techniques; no IPR sought.
04-11-2005
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I
C
41cq77_one_hundred
S
O
N
G
A
I
The London School of Hygiene & Tropical Medicine developed and validated
a novel, high resolution and high throughput technique (PCR-SSOP) for genotyping malaria parasites, and has now added high-throughput sequencing as an
alternative approach. These methods, respectively, have been used in the analysis of samples from two field trials to assess allele specificity of the RTS,S/AS02
candidate malaria vaccine, in The Gambia and Mozambique, respectively.
Molecular typing is now an integral part of the evaluation of malaria drug and
vaccine trials in natural settings, facilitating monitoring of interactions between
parasite and treated /vaccinated host at individual and population levels.
H
N
O
L
O
G
Y
–
D
Innovative Aspects
Main advantage
T
Exploitation potential
C
CO N TA C T A N D O R G A N I SAT I O N D E TA I L S
Title:
First Name:
Surname:
Dr
Colin
Sutherland
Address:
Phone:
Fax:
E-mail:
+44 20 7927 2338
+44 20 7636 8739
[email protected]
Research Institute
50-249 employees
250-500 employees
A
L
T
Start-up company
Other
>500 employees
E
D
Organisation size: < 50 employees
Industry
C
Organisation Type: University
I
Keppel street, London WC1E 7HT,
UK
E
Organisation/Firm
London School of Hygiene and
Tropical Medicine
GMO
Nanotechnology
Genomics/Proteomics
Genetic engineering
Functional biomolecule
Genetic diversity exploitation
Therapeutics
Diagnostics
In-vitro testing
Biological sciences
Veterinary
Vaccines
Others (Please specify)
Medicine
O
I
Agriculture
Plant
Food
Feed
Dairy
Bioassays, biosensors, analytical instruments
Biodegradation/Bioremediation
B
M
A P P L I C AT I O N D O M A I N S
317
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Pagina 319
Index
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08-11-2005
08:19
Pagina 320
100 Technology Offers stemming from EU biotechnology RTD results
I n d e x o f t h e O w n e rs o f te ch n o l o g y
Bacell
233
BIA Separations d.o.o.
270
BIOGEMMA
201
Bruker BioSpin GmbH
104
Centro nacional de biotecnologia. Consejo
de investigaciones cientificas
261
Chiron Bering GmbH & Co
34
CILBIOTECH s.a.
259
Combinature Biopharm AG
31
Consejo superior de investigaciones
cientifica - EEZ
125,187
CP KELCO APS
203
CSK Food Enrichment
71
Destiny pharma Ltd
241
DME – Danish Micro Engineering A/S
155
eBiochips Systeme GmbH
123
EMBL
159
emergentec biodevelopment GmbH
244
Erasmus MC Daniel den Hoed
266
Flemish Institute for technological research,
VITO
110
Fraunhofer Institute for silicon Technology
53
Galilaeus Oy
251
GBF – German Research Centre
for Biotechnology
137, 281, 313
GeneMaLK SA
303
General High Voltage Industries Ltd
113
GIQS e.v.
189
Gothia Yeast Solutions AB
96
Green Hills Biotechnology
301
Hebrew University of Jerusalem
140
Hep-Art Medical Devices BV
287
IACR - Long Ashton Research,
University of Bristol
206
IBET
277
IGEA s.r.l
153
IGER
224
Immunologia y genetica aplicada S.A.
(INGENASA)
256
INRA Institut National de Recherche
Agronomique
192
Institute de Fisica d'Altes Energies
311
Institute of Biology, University of Iceland
285
Institute of food research (IFR)
49, 168
320
Institute of Technical Microbiology,
Hamburg University of Technology
79
Johannes Gutenberg-Universitaet Mainz
157
Justus-Liebig-University
161
Karolinska Institutet
237
Katholieke Universiteit Leuven
128
Keygene nv
63
KREATECH Biotechnology B.V.
295
Leiden University
164
Leiden University Medical Center
299
London School of Hygiene and Tropical
Medicine
317
Milteny Biotec GmbH
26
NANODIAGNOSTICS srl
315
National Institute of Biology
215
PharmaMar S.A.U.
38
Philipps University Marburg
41
piCHEM Forschungs-und EntwicklungsGmbH
289
Plant Research International
227
Polymun Scientific, Immunobiologische
Forschung GmbH
22
Probiomics Ltd.
92
Prokaria Ltd
120
RemaControl Sweden AB
183
Ribo Technologies BV
83
Roslin Institute
74
Scanbec Oy
51
Scottish Crop Research Institute
196
Swedish Institute for Infectious disease
control
116
Swedish University of agricultural sciences
99
Sygen International plc.
56, 66
TAUW bv
150
Technical Research Center of Finland,
VTT
77, 168
Tel Aviv University
248
The Weizmann Institute of science
283
UMR 8121 CNRS –
Institut Gustave-Roussy
279
Universitad Complutense Madrid
239
Université de la Rochelle
146
Université Pitié-Salpétrière
107
University College Cork
89
41cq77_one_hundred_p321
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08:26
Pagina 321
Index
University of Athens
46
University of Bari
253
University of Copenhagen
181, 275
University of Glasgow
171, 173, 175, 177, 179
University of Hamburg
134
University of Newcastle Upon Tyne
305
University of Oxford
29
University of Parma
211
University of Stuttgart
59
University of Utrecht
131
University of York
221
Wageningen-UR Agrotechnology
and Food Innovations
81, 86, 213, 219, 229
WITA GmbH
309
321
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08:20
Pagina 322
100 Technology Offers stemming from EU biotechnology RTD results
I n d e x o f t h e co n ta c t p e rs o n s
Abad Pierre
192
Andersson Leif
99
Andreae Fritz
289
Andrésson Ólafur
285
Anné Josef
128
Ansorge Wilhelm
159
Antranikian Garabed
79
Balendonck Jos
213
Breitenstein Antije
51
Bron Sierd
233
Cadossi Ruggero
153
Carrondo Manuel
277
Chamuleau Robert
287
Chmeissani Mokhtar
311
Conway Patricia
92
Curtis Adam
171, 173, 175, 177, 179
de Groot Huub J.M.
164
De Vries S.C.
229
Debets Reno
266
Dickinson Anne
305
Diels Ludo
110
Dimitrios Nikolelis
46
Dresselhaus Thomas
134
Edwards Keith
206
Effenberger Franz
59
Eshhar Zelig
283
Esveld Erik
81
Favia Piero
253
Fentem Tony
224
Garrett Roger
181
Gatti Antonietta
315
Gazit Ehud
248
Gorochov Guy
107
Gruden Kristina
215
Gustafsson Lena
96
Haley Chris
74
Hauser Hansjörg
281
Heijbel Harald
116
Helder Johannes
219
Hendrix Jules
113
Hintsche Rainer
53, 123
Hoefle Manfred
313
Jeroen Mooy/Annette A.H.Oosterhoff
150
Jimeno José
38
322
Katinger Hermann
Kristjansson Jacob
Lamare Sylvain
Leyser Ottoline
Love Bill
Mandler Daniel
Marahiel Mohamed
Marmiroli Nelson
Mayer Bernd
Miller Alain O.A.
Mir Luis M.
Mueller Werner
Muster Thomas
Pelzer Stefan
Penttilä Merja
Perez Pascual
Petersen Brigitte
Petterson Kjell
Pingoud Alfred
Plastow Graham
Ramos Juan-Luis
Reiber Johan H.C.
Rest Michel van der
Rudolph Brian
Ruiz-Cabello Jesus
Saarela Maria
Sander Curt
Schaumburg Kjeld
Schofield Christopher
Smeekens Sjef
Strancar Ales
Sutherland Colin
Traub Marco
Van Boven Aart
Van Eijk Michiel
Van Hintum Théo
Van Sinderen Douwe
Vela Carmen
Veuskens Jack
Vicente Miguel
Viola Roberto
Vorlop Juergen
Wagner Roland
Wagner-Döbler Irene
22
120
146
221
241
140
41
211
244
259
279
157
301
31
168
201
189
183
161
56, 66
125, 187
299
83
203
239
77
155
275
29
131
270
317
303
71
63
227
89
256
295
261
196
34
26
137
41cq77_one_hundred_p323
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Pagina 323
Index
Weintraub Andrej
Wickham Martin
Wittman-Liebold Brigitte
237
49
309
Wolff Gerd
Ylihonko Kristiina
Zonderavan Charon
104
251
86
323
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Pagina 324
100 Technology Offers stemming from EU biotechnology RTD results
I n d e x o f a p p l i ca t i o n d o m a i n s
Agriculture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56, 59, 63, 66, 74, 99, 187, 189, 192, 196, 211, 213,
215, 219, 221, 224, 227, 229
Antigen discovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Aquaculture
Bioassays, biosensors, analytical instruments . . . . . . 46, 51, 53, 66, 83, 123, 125, 155, 157, 171, 173, 175,
177, 179, 253, 270, 275, 295, 309, 315
Biodegradation/Bioremediation . . . . . . . . . . . . . . . . 110, 125, 137, 140, 146, 150, 171, 173, 175, 177, 179,
187, 213, 233, 253, 289
Biological sciences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22, 38, 41, 56, 66, 79, 83, 96, 104, 107, 125, 128,
134, 155, 168, 171, 173, 175, 177, 179, 187, 213, 233,
237, 248, 253, 261, 266, 279, 287, 289, 303, 305, 309,
313
Dairy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51, 77, 83, 86, 89, 92
Diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51, 83, 99, 123, 153, 155, 159, 171, 173, 175, 177,
179, 244, 253, 275, 289, 295, 299, 301, 303, 305, 309,
311, 313, 315
Drug develoment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Feed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51, 59, 77, 79, 83, 96, 201
Fine chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
Food . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46, 49, 51, 56, 59, 63, 66, 71, 77, 79, 83, 89, 92, 96,
99, 123, 146, 189, 203
Food chain quality information management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Functional biomolecules . . . . . . . . . . . . . . . . . . . . . . . 31, 38, 41, 89, 92, 104, 113, 134, 155, 157, 164, 171,
173, 175, 177, 179, 181, 219, 253, 266, 275, 285, 289,
309
Gene therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277, 281
Genetic diversity exploitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31, 63, 79, 96, 120, 128, 221, 285, 317
Genetic engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31, 63, 71, 96, 107, 125, 128, 131, 134, 161, 168,
187, 192, 206, 219, 233, 237, 251, 256, 279, 281, 285,
287, 309
Genomics/proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51, 56, 66, 92, 96, 104, 113, 128, 134, 159, 164,
181, 215, 227, 233, 244, 259, 270, 275, 295, 303, 305,
309
Glycopeptide antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
GMO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49, 71, 125, 131, 134, 168, 211, 215, 219, 221, 279
Hydrolytic enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
Infectious diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
Information System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
In-vitro testing
Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49, 239, 251, 289, 303, 305, 309
Molecular Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Molecular medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
Nanofabrication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Nanotechnology . . . . . . . . . . . . . . 46, 104, 137, 155, 157, 164, 171, 173, 175, 177, 179, 253, 275, 289, 315
324
41cq77_one_hundred_p325
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08:26
Pagina 325
Index
Pharmaceutical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22, 26, 29, 31, 34
Plant. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134, 189, 192, 201, 203, 206, 211, 213, 215, 219, 221,
224, 227, 229, 279
ProGiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Protein production. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
Purification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270
Quality Information Management
Sawmill industry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29, 31, 59, 92, 153, 171, 173, 175, 177, 179, 233,
239, 241, 244, 248, 251, 253, 256, 259, 261, 266, 270,
277, 279, 281, 283, 285, 287, 289, 299, 303
Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
Vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34, 96, 107, 116, 237, 244, 256, 259, 270, 279, 283,
289, 317
Veterinary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56, 63, 66, 74, 83, 189, 239, 241, 259, 279, 289
325
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Pagina 326
41cq77_cover_EN.qxd
09-11-2005
13:10
Pagina 2
Interested in European research?
RTD info is our quarterly magazine keeping you in touch with main developments
(results, programmes, events, etc). It is available in English, French and German.
European Commission
EUR 20603 —100 Technology Offers stemming from EU biotechnology RTD results
A free sample copy or free subscription can be obtained from:
Luxembourg: Office for Official Publications of the European Communities
European Commission
Directorate-General for Research
Information and Communication Unit
2005 — 325 pp. — 21 x 29.7 cm
B-1049 Brussels
Fax : (32-2) 29-58220
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Werner E.G. Müller, Johannes Gutenberg Universität, Mainz
Nikolaj Gadegaard, Glasgow University
Elke van de Capelle and Godelieve Ghyesen, Universiteit Gent
Rolf Bernander, Uppsala University
Matthew Dalby, The Center for Cell Engineering at Glasgow
Janice de Almeida-Engler, Universiteit Gent
EUROPEAN COMMISSION
Directorate-General for Research
Directorate F — Health
Unit F.5 — Biotechnology and Applied Genomics
Contact: Torbjörn Ingemansson
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E-mail: [email protected]
09-11-2005
13:10
Pagina 1
15
100 Technology Offers stemming from EU Biotechnology RTD results
KI-NA-20-603-EN-C
Innovation is fed by research. Poor exploitation of research results is a European
weakness which holds back the innovation process. In an attempt to remedy this,
the European Union’s Fifth Research Framework Programme specified, for the first
time, that a Technological Implementation Plan (TIP) should be delivered as a part
of the final report of all research contracts. It was an effort to support the spirit of
entrepreneurship and to sensitize European scientists towards intellectual property and ownership of research results. This booklet contains 100 technology offers
deriving from biotechnology projects supported since 1994 under the last three EU
Research Framework Programmes, and selected on the basis of the TIPs and with
the help of scientific officers of the European Commission at DG Research. The
booklet’s objective is to raise interest among Europeans to create new successful
partnerships. Industrial participation is an important factor in EU translational
research. Exploitation is a key to innovation.
EUR 20603
GENERAL INFORMATION
41cq77_cover_EN.qxd
EUR 20603