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ALLIANCE '96: "Matchmaking Program" -- June 11, 1996

With Israeli Biotechnology
Companies, Universities and Research Institutions


Institute, Location, (Science)

Tel Aviv U., Ramot (Ag-Bio, Diagnostics, Therapeutic)
Hebrew U., Yissum(Ag-Bio, Diagnostics, Therapeutic)
Hadassah, Hadassit (Diagnostics, Therapeutic, & CRO)
Weizmann Institute (Ag-Bio, Diagnostics, Therapeutic)
Ben Gurion University (Ag-Bio, Marine-BIO, Ind. Biotech, Diagnostics, Therapeutic)

Tel-Aviv University (Ramot)

Ramot--the technology transfer arm of Tel-Aviv University, Israel's largest institution of higher learning, holds title to over 200 patents in a wide range of disciplines, including biotechnology, applied chemistry, and health-care. Ramot offers collaborators both proprietary technology (via licensing, joint ventures, spin-off companies) as well as general academic know-how and contract research. Ramot has successfully licensed over 70 projects. Ramot has several dozen biotech projects available for licensing or other forms of collaboration. Examples of such projects (for which there are many more) are now being sought for the following proprietary projects relating to biotechnology:

Bioremediation & Environmental Protection

--Biological Bioremediation of Oil-Spilled Environment

--Non-chlorine Biobleaching of Paper Pulp (A biotechnological method based on enzyme from bacterial source bleaches paper pulp with no extra environmental hazardous chemicals such as chlorine. Patents pending worldwide.)

Agricultural Biotech

--Transgenic Cereals
A reproducible, efficient and breeder-friendly gene transfer system. Several agronomic, high-yielding cultivars were transformed.

--Specific, Environment-Friendly Insecticide
Highly specific, scorpion venom component was successfully cloned in bacteria and viruses, by genetic engineering. The use of viral vectors promises extra specificity against discrete weed-insects. The method may be used for developing lines of efficient insecticides that are non-toxic to animals but their target insects. Pending patent in U.S.A.

Industrial Biotechnology

--Biofilm Bioreactor
A novel design of a Bioreactor supporting immobilized Biofilm-- useful for the biosynthesis or biotransformation industry--provide a combination of large surface areas, mild mixing and capabilities of maintaining stable suspensions/emulsions and continuous removal of excessive biomass. Potential applications: Continuous production of biochemical by immobilized filamentous fungi, products based on cell cultures, antibiotics, vaccines, etc.
Patent pending in the U.S.A.

--Method for Protein Stabilization

A two-step simple procedure for stabilizing of proteins (enzymes, antibodies, etc.) in solution was developed, yielding a synthetic "cage" surrounding the protein molecule comprised of a monolayer of low m.w. polymeric glutaraldehyde, crosslinked by polyamide. The resulted protein is stabilized against denaturation, loss of enzymatic or immunological activities, caused by heat, presence of organic solvents, or proteolytic digestion. The method is advantageous for immobilized enzymes in the biotechnological industry and for immobilized immunoproteins in ELISA assays. Worldwide patent protection: U.S.A., Canada, Israel, Europe (8 countries) - granted, Japan - pending.

--Continuous Methods for Encapsulation of Cells, Enzymes, etc. in Macro or Micro Beads: Two methods for continuous encapsulation of cells, enzymes, or any other material in beads of controlled, pre-determined size were developed. The beads are made of either bi-layered alginate, crosslinked chitosan. The resulted "encaged" system may be exploited for various utilizations: Entrapment of microbial cells (together with substrates) for carrying out biotransformations or biosynthesis. Worldwide patent protection.

--Immunoelectrodes: A portable, fast, reliable and sensitive immunological biosensor was developed, which can detect very low levels of bacterial, viral, or fungal antigenic proteins. The detection may be done either by direct measurements of electric resistance, or through amperometric immunoassay. Advantages of the immunosensor technology may be noted: Simplicity, sensitivity, versatility, rapidity and low cost. Possible uses: Healthcare (diagnosis), food and pharmaceutical industry, environmental monitoring, military (detection of biological agents). Worldwide patent protected. Japan is still pending.

Medical Biotechnology
--Incorporating Molecules With High M.W. Into Living Cells: A novel method enabling high yield of incorporation of macromolecule (1-400kD) such as enzymes, antibodies, plasmides, etc. into adherent cells in suspension, with minimal (less than 20%) damage to the cells. The technology may be exploited for research, biotechnological industry and in medicine (gene therapy). Patent pending in Israel, U.S.A. and PCT. Further R & D for better product definition is required on part of the licensee.

--Prevention of Protein Aggregation: Protein precipitation is the cause, or an associated pathological symptom, of many diseases, such as Down's syndrome, Alzheimer's disease, diabetes and cataracts, and other amyloidosis disorders.

Selected monoclonal antibodies were isolated that are non-inhibitory to the biological activity of the antigen and bind at strategic sites where protein unfolding is initiated, thereby stabilizing the protein and suppressing further aggregation. Potential applications: Suppression of Alzheimer - amyloid aggregation by immunocomplexation with highly specific monoclonal antibodies.
Patent Pending: Israel, U.S.A., PCT. Seeking a potential licensee that will support further R&D.;

--Biological Resurfacing of Damaged Human Cartilage: A biological approach for the resurfacing of joints was developed The repair of cartilage is accomplished by employing an autogenetic cell culture, introduced into a growth permissive milieu, a cartilaginous implant is formed, which later on undergoes cellular alteration by molecular engineering techniques, forming a population of precartilaginous cells. The cartilaginous implant is transferred to the articular lesion site, either under open joint surgery, or by an arthroscopic device, filling the lumen of the injury. This joint reconstruction procedure exhibited positive results in animal tests.

Potential applications: Repairing both damaged articular cartilage and bone, vertebra-discs, growth manipulations of growth plates, and prevention of cartilaginous tumors.

Patent: Patents were granted in Israel, England, USA and Japan. Further improvements are patent pending in the U.S.A. Seeking a potential licensee.

--A New Anti-Apoptotic Human Gene (RAP-1) Protects Against Radiation: A novel human radiation protecting gene (RAP-1) was isolated. Expression of this gene in SV40 transformed human fibroblasts protects the cells from apoptosis induced by radiation (UV, X-rays and radiomimetic (anti-neoplastic) agents), while having no effect on nucleotide excision repair.

A second novel gene was identified which enhances radio-chemotherapy induced apoptosis by suppressing RAP-1 activity. Potential applications: Cancer therapy, Radiation therapy. Patent Pending: Israel, PCT. Seeking a potential licensee that will support further R&D.

--A Live Recombinant Measles Virus Vaccine: Measles is considered as a candidate for world wide eradication because of its substantial morbidity and mortality. Although its self-limiting nature, serious complications resulted in incapacitation and death are not rare in under developed countries. A novel recombinant measles vaccine in a vaccinia system, based on a new vaccination strategy in which a recombinant vaccinia virus bearing a foreign antigen coding sequence is used as the immunizing agent was developed.. As a consequence, the replication of the non-pathogenic virus vector may provide a general vehicle for effective, long-life, vaccination. Potential applications: An oral live recombinant virus vaccine, against measles and canine distemper virus. Further R & D is required on part of a potential licensee.

--Anticodon Nuclease Preventing Replication of HIV and Other Lentiviruses: A characterized ACNase is considered a potential inhibitor of HIV replication and a drug for AIDS gene therapy. It serves in nature as a bacterial restriction system and exists in the uninfected host cell, in latent form, activated by phage infection. Expression of the core ACNase polypeptide in human cells in culture elicits efficient cleavage of intracellular tRNALys,3. This result has prompted an investigation into the possible application of ACNase as a potential drug for AIDS gene therapy. Potential applications: AIDS and other Lentiviruses therapy, as well as instrumental tool in designing other novel drugs. Patent Pending: Israel, U.S. Seeking a potential licensee that will support further R&D.

--A Novel Approach For Cancer Detection and Therapy By Modulation of the PP2C Gene: A study aimed at understanding the mechanism through which Adeno associated viruses (AAV) acts as onco-suppressive agent in rodents revealed some of the roles of PP2C (Protein Phosphatase 2C) in mammalian cells. For example, it was found that the expression of the gene is altered in colon carcinoma in comparison to the normal colon cells. A PCR assay based on PP2C transcription can be used for the detection of colon carcinoma and probably other tumors.

It has been demonstrated that by integrating AAV in a site specific manner into the control region of PP2C the regulation and expression of the gene can be modulated. Moreover, it was found that PP2C has a key role in the initiation and maintenance of cell transformation. This important role can be controlled and modulated in a way that will enable its utilization for cancer prevention, treatment and detection

Potential applications: Diagnostic kits, treatment and prevention of cancer.

Patent Pending: U.S.A. Seeking a potential licensee that will support further R&D.

-- Receptor - Ligand Interactions: A Development of Novel HIV Drugs and Vaccines based on Molecular Decoys: Viruses such as HIV enter their target cells as a result of association with cell surface receptors. Thus HIV binds to T4 helper lymphocytes through the interaction between the envelope protein gp120 and its receptor CD4. The intermediate, short-lives complex CD4-gp120 is therefore a crucial step in the virus attack and any process which can interfere with the recognition step, or post binding events, would be of therapeutic and diagnostic value. Production and perfection of molecular decoys, mimic receptors designed to intercept the virus before reaching its target. Novel epitomes for the production of broad spectrum vaccines and new diagnostics have been developed. Potential applications: Developing sensitive diagnostic methods, immune-therapy against AIDS and other viral infections. Patent Pending world wide patents.

The Hebrew University of Jerusalem (Yissum)

Yissum is the subsidiary of the Hebrew University of Jerusalem responsible for the commercialization of hundred of agreements with pharmaceutical, medical biotech , agricultural seed and venture capitals firms. Yissum has filled approximately 30-40 patents application per year, with an accumulation of about 400 reigtered patents to its name to date

Agricultural & Environmental Biotech
--Biocontrol of Crop Diseases by Bacterial Antagonists of Nicrobial Phytopathogen: Several promising isolates of soilborne, rhizospheric bacteria mainly of the Enterobacter and Pseudomonas genera have been isolated which could be considered as new potential agricultural biocontrol agents. The application of the bacteria in greenhouse testing reduced the incidence of several fungal plant diseases. Some of the strains possess a unique combination of multiple mechanisms (chitinase, B-1,3 glucanase antibiotics) providing strong antagonists to many phytopathogen.

--Disposable Bioreactors for Large-Scale Plant Micropropagation: The high cost of in vitro propagation still limits the worldwide economic expansion of this industry to a wide range of plant species. Automation and scale-up in bioreactors can reduce high production costs due to labor intensive manipulation. The use of disposable bioreactors can further reduce micropropagation costs. Proliferation and the rate of growth in the dispensable bioreactors was equal to or higher than in Erlenmeyer flasks or in commercial bioreactors. A 2-3 fold biomass increase was observed over a period of 24-30 days in all tested species.

--Biomaterial as a Carrier of Denitrifying Bacteria In Aquariums: Novel beads have been designed which have potential applications in water purification systems for aquariums.

--Development of a Biological Method for the Control of Rodents: A target-specific methodology for the biocontrol of rodent pests has been developed. Parasites can be employed as a substitute to the use of non target-specific poisoned baits which are hazardous to wild animals, domestic stock and humans.

It is proposed to use Sarcocystis to control rodent populations, in fields, poultries, stores, and warehouses. The ecologically safe method deviates from the traditional concept of biological control by release of predators. Chemical poisons can be replaced in rodent baits with a dose of a pathogen capable specifically of killing the target host. Since different species of Sarcocystis infect mice, rats, or voles, a unique option is provided Ear selective eradication. Bait may therefore be adjusted to defined environmental requirements and target pests, e.g., rats may be destroyed without harming other native rodents.

--Novel Compound for Biological Pest Control and Fertilization: A unique method Ear the preparation of novel hydrocolloid has been designed Ear the agricultural industry. The compositions can comprise microorganisms or any other biologically important material such as chemicals and micronutrient. The resultant product can be dispersed in the soil or in water and in aqueous solutions of fertilizers including by drip irrigation and spraying. The process considerably enhances the activity of the product. In greenhouse experiments employing pathogenic fungi, a 60% reduction in the disease occurrence was seen.

--Passive and Active Processes for the Removal and Recovery of Heavy Metals from Aqueous Environment by the Water Fern Azolla: A patented biological process for the removal of heavy metals From effluent by means of the floating fern, Azolla, is offered. The Azolla processes are superior to traditional methods of metal removal From effluent when environmental and ecological constraints exist.

--Breeding Tomatoes Rich in Vitamins: The development of tomato varieties characterized by increased vitamins A, B, C, E and lycopene content is offered. The tomatoes developed are most suitable For processing by the food industry. Plants with prominent genetic variability are being grown at the faculty's farm. These plants have tomatoes with high vitamin content. To select the desired qualities of these "primitive" tomatoes, classical breeding methods will be employed to result in commercial tomato plants that will produce natural tomatoes with high vitamin content.

--Genetic Engineering of Astaxanthin Biosynthesis: Astaxanthin is one of the most expensive commercially used carotenoid compound. It is utilized mainly as a nutritional supplement which provides pigmentation in a wide variety of aquatic animals. In the Far-East it is used also For feeding poultry to yield a typical pigmentation of chickens. It is also a desirable and effective nontoxic coloring For the Food industry and is valuable in cosmetics. Recently it was reported that astaxanthin is a potent antioxidant in humans and thus is a desirable Food additive. Natural (3S,3'5) astaxanthin is limited in availability. The cyanobacterium (blue-green algae) Synechococus PCC 7942 has been transformed with the CrtO gene from the Haematococcus. Expression of CrtO rendered the cyanobacteria the ability to produce astaxanthin up to 5% of their total carotenoid. This result demonstrates the feasibility to synthesize as2taxanthin in genetically equipped algae and plants. Patent pending in the United States.

--Controllable Closing and Opening of Guest-Binding Cavities in Cyclodextrin Derivatives: A number of applications which can exploit this technology including controlled release of chemical substances such as drugs, perfumes, pesticides, bioactive materials, as well as targeted and programmed release of drugs and bioactive chemicals. Light-activated switches are perhaps the most actively studied systems. The technology of this project was initially developed using photochemical reactions and is particularly well-suited for all nature of photoswitchable applications. An important pheromone within a B-Cyclodextrin derivative has been trapped which may be slowly released at a desired rate using sunlight. International patent pending.

--Lysolecithin - Natural Emulsifierprepared by an Enzymatic: Reaction In a Microemulsion Microreactor Lecithin are widely used in food, pharmaceutical and cosmetics. Its disadvantages are related to its relatively low water and oil miscibility. The aim of this study is to explore now methods to hydrolyze lecithin in the C-2 position, selectively and with high conversion to lysolecithin enriched with the choline fraction. The reaction is carried out by phospholipase A2 acting at the interface of the microemulsion. High conversions of lecithin to lysolecithin have been demonstrated. The product obtained proved to complex with amylose and therefore has an advantage over other Food emulsifiers in baked goods, margarine and chocolate. Optimization of the enzymatic reaction is being done at present and now applications for the product obtained are being evaluated. Patent application in progress.

--Edible Protective Coating for Food and Agricultural Products: This simple coating technique for food and agricultural products can either be consumed or easily removed and is biodegradable. The transparent film should not substantially alter the price per unit weight of the product. Since the gloss properties and hence appearance are greatly improved, the market value may actually be significantly increased. The method can be applied to a wide variety of agricultural and food products, including hard cheeses and other mild products, baked goods, meat and meat products and agricultural seeds. International patent pending.

Medical Biotech
--Inactivated Influenza Vaccine: a Novel Approach: The production of a formalin- and BPL (8-propio-lactone)- free inactive influenza vaccine has been developed For: the replacement of the routine inactive vaccines administered by injection; the preparation of a novel vaccine For local immunization via inter nasal administration. This whole-virus vaccine is superior to subunit vaccine and other inactive vaccines because of its uniqueness in establishing local immunity as well as humoral antibody production. International patent pending.

--Constructs and a Bid-Assay for the Determination of Selenium Concentration: Selenium in the diet has been studied by many groups in regard to its relationship with blood and free radical diseases like cancer and malnutrition and AIDS. A bio-assay has been developed that relates linearly and specifically to very low concentrations of selenium in several simple selenium derivatives. The bio-assay is carried out in E. coli and uses specific recombinant DNA constructs that were built for this purpose. The bio-assay measures only selenium compounds which are included in pathways of "real" selanoproteins. Preliminary studies have shown that it is applicable for the determination of selenium in blood. Patent pending in the United States.

--Gene Expression for Early Detectionand Grading Human Cancer: Specific gene expression in cells in voided urine can be used as a screening test for early detection of bladder carcinoma, especially in populations prone to develop such cancer, e.g. workers in certain industries and smokers. Gene expression in biopsies of bladder carcinoma and other types of human neoplasia can be used as a tumor marker for accurate grading and therefore become an important factor for planning the treatment regimen. Very encouraging results have been obtained by computerized image analysis for the correlation of gene expression to tumor grading. International patent pending.

--A Molecular Assay for the Classification and Follow-Up of Chronic Myelogenous Leukemia (Cml) Patients: Upon studying structure of the bcr-able hybrid gene in CML cells, a molecular structure which is modified in the course of the disease has been identified. This modified structure is present in a small proportion of CML patients upon diagnosis in the chronic stage, yet is invariably present in the short "accelerated phase" preceding the blast crisis, and during the blast crisis stage. Patients followed through the course of the disease acquire the modification upon disease progression. Based on this data, it is proposed that the newly identified structure be used to monitor the progression state of the disease. This unique assay could herald the blastic transformation at a stage where BMT is still effective. International patent pending.

--An Experimental Model for Infiltration of Malignant Lymphomas to the Eye and Brain: Ocular and CNS lymphoma are lethal diseases. Currently, there is no adequate experimental model available whereby the lethal infiltration of malignant lymphoma to the eye and CNS can be studied.

Intraperitoneal inoculation of variant lymphoma cells (that were derived laboratory -derivedand demonstrate unique cell adhesion properties) into syngeneic mice resulted in the subsequent development of progressive tumors in the eye and the brain. This unique model could become instrumental in elucidating these mechanisms of homing of lymphoma cells to the eye and CNS. It would be beneficial for companies involved in cancer therapeutics (chemotherapy and immunotherapy), metastasis research, eye and CNS lymphoma, cell adhesion molecules, Multi-Drug Resistance and its reversal, and monoclonal antibodies. United States patent pending.

--A Novel Approach to Treating Alzheimer's Disease: Technology for specifically arresting the production (as opposed to biochemical activity) of acetylcholinesterase in living cells based on disruption of the biosynthetic pathway leading to acetylcholinesterase production by administration of very low doses of chemically synthesized compounds (antisense oligonucleotide) uniquely targeted against the gene encoding acetylcholinesterase. The antisense preparations are patent pending in the United States, Europe, Japan and Australia. International patent application has been filed for the transgenic mouse model.

--Ras Farnesylation Blockers: Oncogenic ras is present in 40% of all cancers and is involved in 90% of cancers of the pancreas and in over 50% of colorectal cancers. The activity of normal Ras as well as of oncogenic Ras depends on its localization to the membrane. Localization is achieved through the farnesylation of a cysteine residue on the C terminal CAAX box, followed by proteolytic cleavage of the AAX, methylation of the terminal franesylated cysteine and palmytoyljation of an upstream cysteine residue. Inhibition of the farnesylation reaction either by site directed mutagenesis (Cys to Ser) or by synthetic Farnesylation inhibitors nullifies Ras activity and therefore reverses transformation by oncogenic Ras. These considerations have led us to design novel Farnesylation inhibitors with the aim to generate a novel class of anti-cancer drugs. Patent application in progress.

--Toxalert: A System for Detecting Biotoxicity: An early-warning biological sensor has been devised for environmental monitoring and for the detection of biotoxic pollutants. In its present form the sensor is intended for batch testing of water, soil, effluent, sediments, etc. Results are obtained in less than 30 minutes. A prototype kit has been constructed and is now available for demonstration. United States patent pending.

--Material for Cleaning and Enchanting Properties of Surfaces: Liquids and products based on a state-of-the-art novel material have been developed which clean as well as enhance the surface properties of a variety of surfaces. These materials which are 100% environmental friendly. This development can be applied in the metal processing industry, in household cleaning, car wash, body care and other unique applications. International patent pending.

--Oral Delivery of Peptide Drugs by Hydrogel Formulated With Protease-Inhibitors and Absorption Enhances: it is proposed that hydrogals formulated with protease inhibitor (e.g. SBTI) and absorption enhance (e.g. sodium cholate) into matrix tablets can serve as a platform Eor sustained oral delivery of peptide drugs. The hydrogel made of natural polymers (e.g. modified egg or soybean albumin) form low-water soluble gels in the presence oE physiological liquids of the GI tract. International patent pending.

--Drug Targeting Byaggregates of Antibodies: This novel method or drug targeting is based on the formation of aggregates of antibodies. These aggregates have unique properties including 1) the capability of solubilizing hydrophobic molecules and 2) the ability to recognize specific antigens. This method can be applied either topically (Herpes or the eye) or intravenously, due to the small size of the whole carrier. Furthermore, they could also be used for diagnostic purposes, namely the detection of specific antigens by in vivo and in vitro tests. Patent pending in the United States.

--Recharging of the Aging Skin by Gag-Like Synthetic Compounds: In recent years a family of novel compounds, which successfully mimic the key regulatory biopolymer, collectively known as glycosaminoglycans (GAGs), in a variety of biological systems has been discovered. The underlying mechanism is related to the ability of the designed molecules to form a superstructure which reproduces the spatial distribution of GAG contact residues. The present studies have revealed that the GAG-mimicking compounds are very potent inhibitors of human leukocyte elastase. This proteolytic enzyme is implicated in a variety of dermatological abnormalities including psoriasis and dermatitis. These compounds might act as a skin tissue modulator which could protect structural proteins against elastase-mediated damage.

--Amidothionophosphates: Novel Antioxidant Molecules: A new group of antioxidants was designed and synthesized based on the chemical structure of the thiourea Eamily of molecules, well known antioxidants and potent hydroxyl radical scavengers, which are also capable of removing hydrogen peroxide and superoxide radicals. Based on our research, we believe that the development will be suitable Eor use as an antioxidant as a drug Eor clinical disorders that involve oxidative stress. Other important applications include cosmetics and food industries. Since AMTPs are considered environmentally friendly, it is also applicable to industrial applications, such as plastics. International patent pending.

--Novel Ocular Polymer Drug Delivery System: A totally absorbable polymeric insert for the controlled delivery to the eye of drugs for periods from 1 to 7 days has been developed. The invention describes the development of a unique long acting absorbable eye insert for the delivery of drugs such as anti-inflammatory and antibiotic drugs to the eye, where the polymer carrier is eliminated simultaneously with the drug release. International patents pending.

Hadassah Medical Organization (HADASIT)

Hadasit is a wholly owned subsidiary of Hadassah Medical Organization (HMO), established in order to promote and commercialize the applied R&D; activity at HMO. Hadasit is authorized by HMO to utilize the know-how, technologies and patents being constantly generated by various research teams for the purpose of commercialization. Also act as CRO contracts for clinical and pre-clinical studies utilizing Hadassah high quality medical service and research facilities.

New strategies for the inhibition of restenosis: A series of negatively charged, non-sulfated aromatic compounds which mimic many of the effects of heparin were identified and synthesized. These synthetic "heparin-mimicking" compounds were found to inhibit, at extremely low and non-toxic concentrations, the proliferation of VSMC promoted by several growth factors (i.e. PDGF, bfgf, thrombin); however, unlike heparin, their anticoagulant activity is negligible. Patents issued: Israel, Australia-, patents pending- U.S.A., Canada, EPO, Japan.

Synthetic novel compounds for the treatment of neurodegenerative diseases: A family of low molecular weight aromatic compounds was discovered, which can inhibit the formation of protease resistant PrP in tissue culture, probably by competition of binding to proteoglyeans like HS. Patent application: Israel.

An SV40 pseudoviral vector for gene therapy: The pseudoviral vector carries the SV40 ori and ses region and facilitates encapsulation of the plasmid constructs as SV40 pseudovirions in COS cells. The pseudovirions transmit their DNA by viral infection with the vector facilitating high. level expression in a wide spectrum of human cells. including hemopoietic cells. Patent applications: Israel, PCT.

Encapsulation of insulin-producing beta cells: The surface of various biopolymers have been modified by ammonium plasma treatment and incorporation of PEG bridges of various lengths. Some of the combinations have been shown to prevent the growth in-vitro of bovine corneal endothelial cells and fibrolasts in tissue culture conditions. Their cell-repellent characteristics have been verified in-vivo under the skin and in the peritoneal cavity in mice. Angiogenesis has been stimulated in-vivo by incorporating into capsules transformed cells that release VEGF, or slow release microcapsule containing several angiogenic substances. Patent application is in preparation.

Regeneration of beta-cells: An endogenous REG protein in a yeast expression was produced and used to stimulate beta-cell replication, and was tested in-vivo models with remarkable effects. The reg gene, as well as other growth-promoting genes have been transfected into rodent and human islets. Patent application is in preparation.

Immortalization of beta-cells: A ubiquitin-based protein degradation system developed in yeasts was adapted to mammalian cells and was utilized for the conditional expression of several genes, among them oncogenes. The system has been calibrated for the beta-cell. Patent application is in preparation.

Factor that mediate insulin synthesis in response to glucose: The elements of the transcriptional regulation of insulin gene expression were characterized. We have cloned the trans-activating protein whose binding to the insulin promoter is activated by glucose, and expressed it in non-beta-cells together with the insulin gene to obtain its activation. Optimal co-transfection systems are being finalized ,initially in liver cells of various origins, to obtain glucose-regulated insulin production in non-beta-cells for transplantation. Patent application, U.S.A.

A topical formulation for treatment (and prevention) of ocular neovascularization and inflammation: Antibodies which were directed against specific cytokines reduced markedly the angiogenic process and also reduced the inflammatory reaction in treated eyes. Most effective and significant results were observed when preparations of anti-interlukin-I or and TNF alone or in combination were used. Patent application: Israel.

The Jerusalem-Capetown solution (JCT) for long term preservation of donor hearts: An "intracellular" type cardioplegic solution was developed and is formulated to- minimize hypothermic-induced cell swelling; prevent intracellular acidosis; prevent the expansion of the interstitial space during the flush-out period; prevent injury from oxygen-free radicals; provide substrates for regenerating high energy phosphate compounds during reperfusion. Patent application: Israel.

A Novel calcium phosphate bio active bone substitute: Calcium phosphate bioapatite is used for synthetic implants to bridge massive bone defects. A new procedure, using microwave irradiation for the production of bioapatite powders (the Ha-Sal series), was developed. The first version has already been evaluated for biocompatability, in vitro, with favorable results; the second version is currently being tested. Patent application- Israel. Recharging of the aging skin by GAG-like synthetic compounds A family of novel compounds, which successfully mimic the key regulatory biopolimers, and collectively known as glycosaminoglycans (GAGS) was discovered. Among the roles of GAGs are stabilization of cell adhesion, and the sequestration and presentation of growth factors. These biological activities can be reproduced by the synthetic compounds. Patents issued: Israel, Australia; Pending: U.S.A., Canada, EPO , Japan.

Synthetic peptides of homeostatic factor as potent inhibitors of angiogenesis and experimental metastasis. The designed synthetic peptides exhibit functional activities of promoting adhesion and intracellular signaling of endothelial cells as well as other cells of the vascular system. Patent application: Israel.

A novel treatment for osteoporosis based on regulated secretion of parathyroid hormone (PTH): A new treatment for osteoporosis using regulation of PTH gene expression and secretion to devise an innocuousregime which increases the endogenous synthesis of PTH. This regime will increase bone density and is anticipated to prevent bone fractures. Patent applications: U.S.A., Japan, Russia.

Early detection and grading of bladder carcinoma and other types of human cancer: An expression of a specific gene present in tumors arising from tissues which normally express the gene during fetal life, was discovered. This situation is similar to the oncodevelopmental genes CEA and aFP. The expression of the specific gene, in transitional bladder epithelium, has been shown to be linked to the grade of differentiation and invasiveness of papillary transitional cell carcinoma of the bladder. Patent applications: Israel, PCT.

Serum bioassay for the detection of early osteoporosis in post menopausal women: The method is based on the effect of sera of osteoporotic women on the differentiation of rat stromal cells in culture. The change in the level of two specific markers in the serum of postmenopausal women induces quantifiable changes in rat stromal cells. This is a reproducible easily applicable method, used to detect early osteoporosis. Patent application: Israel.

An indicator for tumor metastasis based on the differential expression of thrombin-receptor in epithelial carcinoma: A direct correlation between the level of ThR expression, in epithelial carcinoma cell-lines and their metastatic tendencies was discovered. High levels of ThR expression were observed in a highly aggressive metastatic cell line, low-to moderate levels of expression in medium metastatic cells and essentially no detectable expression in non-metastatic tumor cells. This was determined on the level of m-RNA expression and protein levels. Patent application: Israel.

Weizmann Institute (Yeda)

Yeda is the technology transfer arm of the famous Weizman Institute of Science, viewed by many as "Israel's NIH." The Weizman Institute is located on a 1.2 sq km campus in the town of Rehovot, employs over 2,300 and has an operating annual budget of over $ 130 million. The Institute has been the source of many of Israel's most successful and well known biotechnology projects now in the marketplace.

Ben Gurion University (B.G. Technologies & Applications)

B. G . Negev Technologies & Application is the technology transfer company of Ben Gurion University. The University is world class center for desert studies, teaching and research, with 10,000 students enrolled in it's four technical engineering faculty. It includes the Institute of Applied Negev Research and the Jacob Blaustein Institute of Desert Research. Those two specialize in: advance desert agriculture, marine biotech , alternative energy and water resources. Important contributions have been made in the exploitation of the Negev's well known natural resources for use in the biochemical industry. Commercialization of applicable research results and on-going applied research projects has been identified as an essential by-product of the university's general goals.

Marine Biotechnology
Application of Dyes Produced from Microalgae: Purified fluorescent phycobiliproteins are already being produced commercially for use as fluorescent markers. Their high absorptivity and high quantum efficiency contribute to high sensitivity in immunoassay, fluorescence microscopy, and fluorescence - activated cell storing. They have developed blue, purple and pink pigments that could have applications in foods that do not require heating, such as desserts, ice-creams, sweets, cake decorations, milk shakes and other drinks.

Red Microalgal Polysaccharide used as Oral Drug Delivery Matrix The cells of the red microalgae are encapsulated with a sulphated polysaccharide. The external part of the capsule dissolves in the medium, leading to its enrichment with the polysaccharide. Red microalgal polysaccharide has a commercial potential as a new multi-purpose matrix for drug delivery, in particular for controlled release products.

Red Microalgal Biomass as a Dietary supplement for Health Food Products: The biomass of the unicellular red alga Rhodella reticulata contains a sulphated polysaccharide and an unsaturated fatty acid eicosapentaenoic acid. Serum cholesterol, triglyceride and very low density lipoprotein levels were considerable lower in rats receiving bio biomass of polysaccharide than in the control animals.

Biodegradation of RDX: A process for biological treatment of discharge effluent from RDX manufacturing is being developed. he process is based on RDX degrading bacteria using it as nitrogen source, acetone or cyclohexanone as carbon sources.

A procedure for Large-Scale Production of Astaxanthin from Hamatococcus Pluvialis: A two phase cultivating procedure for large scale production of astaxanthin from a green alga Haematococcus Pluvialis has been developed. At the first phase, vegetative growth is maintained and carried out under controlled environmental conditions to support optimal growth.. The characteristics of this stage are continuous cell division, astaxanthin/chlorophyll ration between 0.1-0.4 and increase of chlorophyll content. Under our experimental set-up a production rate of 0.5-0.7 gr/L/day could be obtained.

A Biochemical Assay for Differential Diagnosis in Psychiatry Using G Protein Measurements in Human Lymphocytes: A novel lab developed test that enable to determine the function of G proteins in membranes prepared from human lymphocytes through activated receptor-coupled guanine nucleotide exchange on G proteins. This method offer detection of hyperfunction of both Gs and non-Gs proteins in lymphocytes manic patients, while lymphocytes of depressed patients showed hypofunction. This results indicate that a biochemical assay that enables a differential diagnosis among various psychiatric disorders is possible. A commercial development of such a test into a routine use in Psychiatry, besides its scientific and clinical potential, has an enormous economic potential since 15% of population estimate to have this disorder.

Pharmaceutical Projects
Controlled Delivery of 1,25 - Dihydroxyvitamin D3 from Polymeric Matrix: A Putative System for Chemoprevention of Cancer: These results suggest that controlled release of 1,25(OH)2D3 sequestered in polymeric matrices effective in preventing the carcinogenic process in colon cells.

Slow release ophthalmic Vehicles: A new formulation development for ophthalmic drug delivery based on polymers which undergo a liquid - gel phase transition when applied to the eye. When the drug polymer droplets comes in contact with the eye, they are transformed into a gel matrix capable of sustaining the release of the ophthalmic drug for a day. The polymeric material they utilize is FDA approved for ophthalmic use in humans.

Transdermal Delivery of Insulin (and other peptides): A unique discover of proteinase attached to the skin surface the outer layer of the stratum corneum which powerfully degrades (125)I- carboxymethlated insulin B- chain . This activity was found both in humans and animals. The ability to block the skin surface was found proteinase by specific inhibitor was at extremely low concentrations. The application is to use this inhibitor as part of insulin- containing formulation to facilitate the transderml penetration of the peptide. Seeking for R&D; collaboration to initiate industrial product development.

Treatment of Pediculosis Capitis (Head Lice infection) be Means of Prolonged-Release Drug Delivery Systems: A novel formulated prolonged - release system that will suppress the distribution of lice by immediate killing of the nymphs at the moment they hatch from the eggs. It reduces the toxicity of the product by facilitating a decrease in the close contact dosages applied to the scalp.

This material was prepared for the sole purpose of facilitating private meetings with Israeli companies for registrants of ALLIANCE '96 or the BIO '96 International Meeting. The company and technology descriptions were abbreviated due to space limitations. The technologies summarized are merely exemplary but not exhaustive of those in the companies' portfolios. Many more projects not described herein will be presented at the conference. Additional Israeli companies are expected to register.

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