Technologies available for licensing - Pharma

TASMC case No. 32

Inventors
Dan Caspi; Itzhak Golan

Summary
New variants of human galectin-8 protein expressed in the joints of arthritic patients were found to have anti-inflammatory effect in Rheumatoid Arthritis (RA). This technology may be explored as a therapeutic agent for RA as well as for other inflammatory diseases.

 

Technology
Rheumatoid arthritis (RA) is a common chronic inflammatory arthropathy, leading to joint destruction and disability as a consequence of the chronic inflammatory processes. A team of researchers at TASMC have found three new variants of human galectin-8 protein expressed in the joints of arthritic patients. Galectin-8 variant molecules were shown to have anti-inflammatory effect on synovial fibroblast cultures, synovial fluid cells and PBLs as well as in in-vivo RA model.

Potential applications
Treatment of inflammatory-related chronic diseases such as Rheumatic Arthritis, Inflammatory Bowl Diseases or Pulmonary Emphysema.

Patent status
National phase; Granted in USA, Israel, Australia

TASMC case No. 26

Inventor
Nadir Arber

Summary
Novel antibodies directed at CD24, a mucin-like cell surface molecule highly expressed in various human cancers, were found to inhibit growth of GI tract and prostate CD24-expressing cancer cells in vitro and in vivo and to effectively deliver a cytotoxic agent into these cells.  This technology may be developed for treatment of colorectal cancer as well as for other malignancies.

Technology
CD24, a mucin-like cell surface molecule and P-selectin ligand was found to be highly expressed in various malignant tissues among which are B-cell lymphomas, gliomas, and non-small cell lung carcinomas. Increased expression of CD24 is usually tied with a more aggressive course of the disease. In GI tract, CD24 was found to be over expressed in about 90% of malignant and pre-malignant tissues while only in 17% of normal epithelium. A set of novel monoclonal anti-CD24 antibodies developed by TASMC researchers, specifically induced apoptosis in CD24-expressing human colorectal cancer cells (CRC) and significant tumor growth reduction in xenograft models, supporting a role for CD24 as a potential target for cancer treatment.  In addition, anti-CD24 antibodies could deliver a PE exotoxin derivative to CRC cells and induce cell death by means of apoptosis, without toxicity to normal tissues. Thus, this technology offers a new biological treatment modality which has a potential to be both highly efficient and highly specific for treatment of colorectal and other cancers.

 

Potential applications
Treatment of cancer

Patent status
National phase

 

TASMC case No. 16

Inventors
Naftali Stern; Etty Oscher; Anthony Futerman; Ruth Navon; Ari Zimran

Summary

The present technology is a development of a natural blood brain barrier (BBB) crossing molecule into a carrier protein transporting peptides of interest across the BBB. The invention is based on the Trojan horse principle: one protein which can naturally cross the BBB opens BBB gates by carrying and transporting a second protein, one with therapeutic potential. Granulocyte-Colony-Stimulating-Factor (G-CSF) is one such protein that can cross the BBB through a specific receptor-mediated transport. Several G-CSF based conjugates were developed and were shown to effectively transfer various proteins across the BBB. This technology can serve to enable peptide-based therapeutics for various brain pathologies.

Technology
The delivery of proteins to the brain for therapeutic purpose is generally impractical due to blood–brain barrier (BBB) which tightly regulates the transport of molecules into the brain such that molecules whose size exceeds a molecular weight of 300-500 are usually filtered out of the brain territory. Researchers at TASMC in collaboration with research groups from Tel Aviv University and Weizmann Institute have developed a new approach for the delivery of proteins to the brain, via utilization of Granulocyte-Colony-Stimulating-Factor (G-CSF). G-CSF can cross the BBB through a specific receptor-mediated transport and subsequently interact with target cells within the central nervous system, again through G-CSF receptors. Moreover, G-CSF also possesses neuroprotective and anti-apoptotic properties which might be useful for neurodegenerative brain disorders.  G-CSF-based conjugates were generated and demonstrated to be effective carriers to the brain of several structurally and functionally unrelated "model proteins", such  as Chפoramphenicol Acetyl Transferase  (~25kD), β galactosidase (116 Kd), and the α subunit of hexosaminidase (56kD).
These results lend support to the concept that this line of G-CSF   based conjugates can serve to deliver therapeutic proteins to the brain.

Patent status
National phase

 

TASMC case No. 75

Inventors
Naftali Stern; Gary Weisinger, Rona Limor

Summary
The current invention proposes a new approach for obesity treatment by specifically reducing the number of fat cells. This invention induces weight loss in obese or overweight individuals via the induction of programmed cell death in fat cells and pre-adipocytes using in vivo knockout therapy of the enzyme, platelet-type 12 lipoxygenase (12-LO).

Technology
Obesity has become a global epidemic afflicting both children and adults gradually spreading from the Western countries to the developing nations. It is now widely recognized that obesity is associated with and is a major culprit in numerous co-morbidities, e.g. heart disease, type 2 diabetes, hypertension some cancers and sleep apnea. TASMC researchers have invented a method for reduction of fat cell number using a biological treatment based on the enzyme, platelet-type 12 lipoxygenase (12-LO). This enzyme is expressed in fat cells and pre-adipocytes and was shown to have an anti-apoptotic function;  the lab team showed that 12-LO knockout of adipocytes results in apoptotic cell death that can be prevented in part by exogenous addition of the enzymatic product of 12-LO. They developed a fat specific 12-LO antisense knockout therapy that can be delivered in the form of liposomes or through viral vectors such as the gutless adenovirus- or gutless adeno-associated virus or retroviral moieties already in use for human gene therapy. Moreover, since such apoptosis induction is not massive, damage resulting from abrupt overflow of free fatty acid and / or triglycerides can be minimized while treatment can be repeated until desirable outcome is attained.

Potential applications
Treatment of obesity as well as cosmetic fat loss

Patent status
National phase; Granted in Europe

TASMC case No. 41

Inventors
Nicola J. Mabjeesh

Summary
HIF 1 is known an important player in human tumor growth and thus a rational therapeutic target. The present invention proposes a novel approach for eliminating HIF 1 and thus interfering with tumor growth. This is achieved by elimination of SEPT9, a molecule found to interact and stabilize HIF1. 

Technology
HIF-1 is the key player in the signaling and survival of normal and cancer cells at low oxygen levels. Targeting the HIF system to induce a therapeutic response for the treatment of cancer is currently one the most attractive options of pharmaceutical development.  HIF pathway was shown to be “druggable” and to have a therapeutic utility as an antitumor strategy. TASMC team has recently discovered SEPT9_v1, a member of the “obscure” mammalian septin family, to be a new regulator of the hypoxic response pathway in cancer cellsthroughHIF-1/SEPT9_v1 interaction which stabilizes HIF-1. Disruption of this complex was found to inhibit cancer cell growth in vitro and tumor growth in vivo,thus  presenting an attractive opportunity for  cancer treatment.

Potential applications
Treatment of cancer and ischemic diseases

Patent status
National phase

TASMC case No. 41

Inventors
Patrick Sorkine; Inna Frolkis; Chaim Locker

Summary
The present invention offers a unique approach for treatment of Systemic Inflammatory Responses Syndrome (SIRS) which is an uncontrolled inflammatory state often leading to death. Currently, no effective treatments are available. The proposed approach stems from the finding that viper snake venom may be used medicinally. Low dosages of the snake venom may be used to alter the manifestations of SIRS and to prevent, manage and treat such related conditions as septic shock and sepsis.

Technology
The leading cause of non-coronary death in intensive care units is septic shock. Systemic Inflammatory Responses Syndrome (SIRS) is an uncontrolled inflammatory response characterized by high levels of circulating cytokines. SIRS affects all organ systems and may lead to multiple organ dysfunction syndromes. Currently, no effective treatments are available. The trigger of SIRS is unclear; however a few important cell-to-cell signaling molecules have been implicated in the genesis of this pro-inflammatory state. These messengers include TNFα, interleukin IL-1, IL-5, IL-6, IL-8, IL-11, IL-15 and multiple colony stimulating factors as well as several chemokines. TNFα seems to have a major effect and is highly correlated with mortality. A team of TASMC researchers have shown that Vipera Aspis venom (VAV) treatment significantly attenuated TNF- production in a septic shock rat model leading to substantial decrease in morbidity and mortality. Importantly, other cytokines such as IL-6 and IL-10 were not affected. This technology is based on the development of snake venom for modulation of Systemic Inflammatory Response Syndrome and other serious inflammatory conditions.

Potential applications
Septic Shock, Sepsis, TNFα related conditions such as inflammatory bowl diseases and Rheumatoid Arthritis

Patent status
National phase; Granted in Europe and USA

TASMC case No. 85

Inventors
Shimon Rochkind; Zvi Nevo

Summary
The present technology offers opportunities for the development of a novel biocompatible gel characterized by growth permissive features for tissue reconstruction and cell therapy. 

Technology
The developed transparent, highly viscous GRG is composed of a complex of several substances and is biocompatible and biodegradable. The physically adsorbed-added external agents create gradients that are slowly released to the surroundings. The gel is almost impermeable to liquids and gasses, flexible, elastic, malleable and adaptable to various shapes and formats. The GRG resembles the extracellular matrix (ECM) and was found to support three dimensional growth and differentiation of various cell types including embryonic and adult stem cells in culture, neuronal precursor cells and neuronal accompanying cells. The gel was found as an effective transportation vehicle for cells, explants, biopsies and organs embedded in the gel at room temperature, outside the CO2 incubator for several days regaining the full vitality upon incubation at 37°C and 5-10% CO2.

 
Potential applications:
Regeneration of massive regional losses in tissues and organs; Nerve healing, wound healing, preservation of human and animal tissues

Patent status
National phase

TASMC case No. 66

Inventors
Shahar Lev-Ari; Nadir Arber

Summary

We discovered that the addition of curcumin, a potent antioxidant, to celecoxib synergistically (up to 1000%) augments the growth inhibitory effects of celecoxib and other NSAIDs in in-vitro models of cancer and arthritis, thus rendering effective action of the drug at a tenfold lower dose.  

 

Technology
Th The product is a pharmaceutical composition composed of optimal concentrations of curcumin and celecoxib. The clinical importance of this effect lies in the fact that it can be achieved in the serum of patients treated with a standard anti inflammatory (200-400 mg) or anti-neoplastic (400-800 mg) doses of celecoxib. This may pave the way for a novel strategy to prevent and treat cancer and arthritis, given that this approach will involve a regimen of a low profile of side effects, while maintaining the same therapeutic effect as compared to administering the NSAID / COX-2 inhibitor alone.

 

Potential applications
(NSAID) and the leading COX-2 specific inhibitor. It was shown to provide relief of the pain and inflammation associated with osteoarthritis, adult rheumatoid arthritis, acute pain, and primary dysmenorrhea in adults. In addition, several in vitro, in vivo and clinical studies have indicated that it may prevent colorectal cancer (CRC).

 

Patent status
National phase

TASMC case No. 74

Inventors
Ilan Volovitz; Lea Eisenbach; Irun R. Cohen; Zvi Ram

Summary
Immunological therapy (immunotherapy) harnesses the immune system of the body to combat cancer. Even aggressive immunotherapeutic approaches cause little or no collateral damage to surrounding brain tissue. The present technology presents a novel immunotherapy approach for treatment of brain tumors.

Technology
 Malignant primary brain tumors and especially the highly malignant Glioblastoma multiforme (GBM) are fatal within months of diagnosis in almost all patients. Brain tumors are diagnosed each year in approximately 6.5/100,000 Americans and constitute 1.4% of new cancers diagnosed. Due to its dismal prognosis and early age of onset it represents 2.4% of cancer deaths and constitutes 7% of person-years of life lost (PYLL) due to cancer (forth after lung, colon and breast).  In children it is the second most prevalent cancer after leukemia constituting 17% of new cancers diagnosed. TASMC research team in collaboration with a group from the Weizmann Institute have developed an immunotherapy-based treatment for Gliomas. Gliomas are highly infiltrative tumors, spreading to areas inside the brain that are distant from its initial location. Unlike other treatments that kill tumor cells mostly in their initial location, immunotherapy generates tumor specific immune cells that can locate and kill small unidentified metastatic lesions inside the brain. The researchers have shown in a highly malignant Fischer rat glioblastoma model ('F98') an increase in mean survival time by approximately 300% and 30% complete cure in treated rats following a single immunization. Moreover, a newly developed immunization protocol cured 100% of the rats of their brain tumors. In an additional rat astrocytoma model, 80-100% cure rate was achieved using various immunization protocols. All in-vivo experiments, in both models, showed similar, highly significant results which are unprecedented as compared to the published scientific literature for these models. 

Potential applications:
Treatment of various brain tumors as gliomas, glioblastomas and astrocytomas.

Patent status  

National phase

TASMC case No. 132

Inventors
Naftali Stern; Dalia Somjen; Fortune Kohen; Batia Gayer; Tikva Kulik; Veronika Frydman

Summary
The present technology is a product of a unique modification of the natural Isoflavones present in soybeans enabling its use as a potent anti-cancerous agent. Dramatic effects were demonstrated in in vitro and in vivo models offering an opportunity for treatment of estrogen-responsive cancers

 

Technology
 Isoflavones present in large quantities in soybeans and soy products (e.g.genistein, daidzein) were indicated in multiple studies as having two counter effects on cells expressing the estrogen receptor; in low concentrations they act similarly to estrogens promoting cell growth while in high concentrations, an anti-proliferative effect is observed. The mechanism involves estrogen receptor (ER) α, β, or both, thus affecting estrogen sensitive cancer cell lines (e.g. breast, colon, thyroid etc).
A TASMC team in collaboration with a group from the Weizmann Institute, have applied a novel approach in an attempt to utilize and improve the cytotoxic potency of isoflavones and have succeeded to synthesize an isoflavone-derivative named cD-tboc which exhibits a significant inhibitory effect on cancer cell growth as compared with the parent isoflavone, while retaining no estrogenic activity.  These anti-proliferative effects were demonstrated in vitro in a number of cancer cell types expressing estrogen receptors (ovarian, colon, adrenal and prostatic cell lines) and had little effect in normal cells. In vivo, the compound was capable of reducing tumor volume by >50% in mice implanted with ovarian or thyroid xenografts while causing no death or weight loss. Moreover, cD-tboc was significantly effective as anti-thyroid human cancer agent in aggressive primary thyroid cancer cultured cells harvested from human subjects during surgery.

 

Potential applications:
Treatment of estrogen sensitive tumors such as thyroid or ovarian carcinoma.

Patent status  
National phase