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Biotechnology, Pharma and Diagnostics

Category
Technology Name
Briefcase
Scientist
1774
A novel method for treating tyrosine kinase inhibitor (TKI)-resistant cancer, by using a combination of three different antibodies. Lung cancer is known as one of the most fatal forms of cancer. Notably, standard treatments for other cancer types (e.g. TKIs and mAbs), have shown only a limited effect...

A novel method for treating tyrosine kinase inhibitor (TKI)-resistant cancer, by using a combination of three different antibodies.

Lung cancer is known as one of the most fatal forms of cancer. Notably, standard treatments for other cancer types (e.g. TKIs and mAbs), have shown only a limited effect on this specific malignancy. The reason is that lung cancer cells regularly acquire resistance through multiple compensatory mechanisms, including secondary (new) mutations in receptors which block the effects of TKIs; up-regulation of specific genes; or rewiring of signaling networks.

The current technology works around these compensatory mechanisms by using a mixture of antibodies that function in a synergistic manner, to effectively and specifically target lung cancer cells, without affecting healthy cells.

Applications


·         Treatment of non-small cell lung cancer (NSCLC).

·         A method for augmenting currently available TKIs.


Advantages


·         Specificity – treatment was able to target EGFR-mutated NSCLC cancer cells, and showed no effect on healthy cells.

·         Effective – able to strongly inhibit NSCLC cancer cell lines and inhibit xenografted NSCLC cells in a mouse model.

·         Novel Approach – utilizing data derived from both clinical and laboratory research to devise a method for counteracting compensatory mechanisms of cancer cells.


Technology's Essence


Prof. Yosef Yarden and his group have discovered that by simultaneously inhibiting multiple receptors, namely HER2 and HER3 along with EGFR, they could effectively circumvent the compensatory mechanisms and inhibit NSCLC cell growth. This was determined using a combination of clinical, in vitro, and in vivo data. In addition, in vivo experimental work included xenograted mouse models where only the triple combination of antibodies effectively reduced tumor volume relative to standard mAb treatments.

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  • Prof. Yosef Yarden
1790
A novel method of preventing secondary infections, by inhibition of membrane type I matrix-metalloproteinase-1 (MT1-MMP), which reduces degradation of the extra-cellular matrix. Pathogens that infect the respiratory system are the cause of some of the most dangerous infections, especially for...

A novel method of preventing secondary infections, by inhibition of membrane type I matrix-metalloproteinase-1 (MT1-MMP), which reduces degradation of the extra-cellular matrix.

Pathogens that infect the respiratory system are the cause of some of the most dangerous infections, especially for vulnerable populations such as children and seniors. This is due to the host immune response which can damage the lung tissue, serving as a prime target for secondary infections. Consequently, there is a need for a method that provides better control over inflammatory response and reduces tissue damage caused by the host immune response to an infection.

Prof. Irit Sagi’s research team has discovered that by specifically inhibiting MT1-MMP they can limit tissue damage in the lungs of mice, help prevent secondary infections, and subsequently improve overall survival rates.  

Applications


·         Limiting tissue damage for the prevention and treatment of secondary infections.


Advantages


·        Novel mechanism – targeting MT1-MMP to limit inflammation due to an immune response, rather than targeting the pathogen directly.

·        Usage of an antibody for prophylaxis or treatment

·        Synergism – possibly combined with an anti-pathogen agent to assist in treatment. 

·        Better outcomes – reduction of tissue damage and inhibition of secondary infections improves overall survival rates.


Technology's Essence


The research team of Prof. Irit Sagi has shown a novel mechanism of treating and preventing secondary infections by inhibition of MT1-MMP using an anti-MT1-MMP antibody. The team used mice as an infection model. They performed in vitro experiments on extracted mice lungs to characterize MT1-MMP’s role in the infection pathology. They also calculated survival rates following both primary and secondary infections of mice, with and without inhibition of MT1-MMP. Which showed that the inclusion of the anti-MT1-MMP antibody improved overall survival rates in the infected mice.

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  • Prof. Irit Sagi
1776
A novel method for treating ovarian cancer by intercepting the EGFR ligand amphiregulin, when elevated expression levels are found in a patient. Ovarian cancer represents a relatively common type of cancer that affects women. However, the primary therapeutic option for ovarian cancer has remained the...

A novel method for treating ovarian cancer by intercepting the EGFR ligand amphiregulin, when elevated expression levels are found in a patient.

Ovarian cancer represents a relatively common type of cancer that affects women. However, the primary therapeutic option for ovarian cancer has remained the same since the 1970’s, involving systemic chemotherapy treatment, and surgery. The problem of limited treatment options is further exacerbated due to the high proportion of patients who relapse following chemotherapy.

The group of Prof. Yosef Yarden at the Weizmann Institute of Science (WIS) has discovered that amphiregulin (AREG) levels are elevated in the body fluids of a high percentage of ovarian cancer patient samples they tested. Prof. Yarden’s group has found that by intercepting AREG in combination with chemotherapy, they were able to inhibit the growth of ovarian tumors.

Applications


·         Inhibiting growth of ovarian cancer.

·         Possible treatment for other types of cancer.

·         Using AREG as a possible theranostic for ovarian cancer.


Advantages


·         Innovative Target – Intercepting the EGF-ligand AREG.

·         Flexible – Anti-AREG mAbs could be used alone or in combination with current chemotherapy treatments for different malignancies.


Technology's Essence


Prof. Yosef Yarden and his group have found that the EGFR ligand, Amphiregulin (AREG) was elevated in the bodily fluids of 80% of cancer patient samples tested. These results were further supported by in vitro work with varying cancer cell lines, again showing elevated AREG concentrations in their media. The Yarden group then generated an anti-AREG antibody, and performed experiments in vivo using mouse models xenografted with ovarian cancer cells. The results show that co-administering the anti-AREG antibody re-sensitized the tumors to standard chemotherapy treatments. This emphasizes the value of AREG not only as an anti-cancer target but also as a possible diagnostic marker.  

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  • Prof. Yosef Yarden
1760
Antibiotic resistant bacteria are a growing problem worldwide, leading to increasingly difficult to treat infections due to the reduced number of effective antibiotics. The problem is further exacerbated that even antibiotics of “last resort” are becoming ineffective in treating infections, along with...

Antibiotic resistant bacteria are a growing problem worldwide, leading to increasingly difficult to treat infections due to the reduced number of effective antibiotics. The problem is further exacerbated that even antibiotics of “last resort” are becoming ineffective in treating infections, along with issues of harsh side-effects of using said drugs.

Currently one of the most problematic antibiotic resistant bacterium is methicillin-resistant Staphylococcus aureus (MRSA). MRSA is becoming prevalent in hospitals and care homes, increasing the risk associated with hospitalization and invasive medical procedures. Therefore there is an urgent need to develop new antibiotics to combat MRSA.

The present technology from the lab of Nobel Prize winning Prof. Ada Yonath offers a tool in designing and developing new types of novel antibiotics. It is a high resolution crystal structure of the large ribosomal (50S) subunit from Staphylococcus aureus. The structure is based on a pathogenic strain giving new insight and capacity to target specifically the bacterium (Eyal Z, et al. (2015) Proc Natl Acad Sci and Eyal Z, et al. (2016) Sci. Rep.).

Applications


·         Designing and developing new types of antibiotics.

·         Computational screening of chemical libraries, reducing the number of physical compounds to screen.

·         Improving overall understanding of the ribosome in S. aureus.

·         New potential antibiotics binding sited which are species specific.


Advantages


·         High Resolution – the structure gives high detail and possible target positions for antibiotics.

·         Crystal Structures soaked with antibiotics – certain antibiotics have been soaked with the structure giving insight in how they interact with the ribosome, improving rational design of new antibiotics.

·         Structure based on pathogenic bacterium – improving targeting of antibiotics, as current bacterial ribosomal structures are based on non-pathogenic species.


Technology's Essence


The invention is a high resolution crystal structure of the large ribosomal subunit from the pathogenic S. aureus. The crystal structures importance is that it originates from a pathogenic species allowing for a high-degree of specificity in targeting the S. aureus ribosome. Rather than the currently available ribosomal structures based on non-pathogenic bacteria, where small differences between species may limit the effectiveness in a designed antibiotic. The importance of the technology is that MRSA (methicillin-resistant S. aureus), is becoming more common place in hospitals, care homes, and even in the agricultural sector. Thus there is a clear need for new types of antibiotics that can help to counteract the ever growing problem of bacterial antibiotic resistance.  

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  • Prof. Ada Yonath
1549
A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one...

A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one or more ErbB ligands correlates with decreased patient survival. The currently approved drugs for the treatment of cancers driven by the ErbB family target the receptors rather than the ligands, and they include either monoclonal anti-receptor antibodies, or tyrosine kinase inhibitors (TKIs). Because of resistance and moderate clinical efficacies of anti-receptor antibodies and TKIs it is worthwhile considering alternative strategies. The present technology combines several antibodies, capable of blocking ErbB ligands, with chemotherapy.

Applications


  • Treatment of cancers that possess the ErbB receptors (e.g. colorectal, liver, bladder, and head and neck tumors)

Advantages


  • Effective blockade of the tumorigenic action of ErbB-specific ligands
  • The combination protocol may enhance the sensitivity to chemotherapy

Technology's Essence


In the outlined technology, monoclonal antibodies were generated against two ligands, namely TGF-? and heparin-binding EGF-like growth factor. Combining the two antibodies with a chemotherapeutic drug enhanced the ability of chemotherapy to inhibit pancreatic tumors in mice. Therefore, this technology offers a general cancer therapeutic strategy that entails profiling the repertoire of growth factors secreted by a tumor, and combining with chemotherapy several antibodies capable of blocking autocrine ligands, in a way that sensitizes tumors to cytotoxicity and delays onset of chemoresistance.

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  • Prof. Yosef Yarden
1736
Biomass production by plants and other photosynthetic organisms involves carbon fixation, the process of incorporating inorganic carbon dioxide into organic compounds. Currently carbon fixation by plants and other photosynthetic organisms is the limiting factor in biomass production. Improvement in the...

Biomass production by plants and other photosynthetic organisms involves carbon fixation, the process of incorporating inorganic carbon dioxide into organic compounds. Currently carbon fixation by plants and other photosynthetic organisms is the limiting factor in biomass production.

Improvement in the metabolic pathway related to carbon fixation would have great value in increasing crop yields, synthesizing high value compounds in algae, and developing means in removing CO2 from the atmosphere to combat climate change.

The present technology is an engineered E. coli with a carbon fixation pathway. The unique innovation can be used to efficiently screen the activity of RuBisCO, the most abundant carbon fixing enzyme on earth, which is further applicable to improving biomass production in different photosynthetic organisms such as plants and algae.

Applications


·      Powerful platform for screening and improving various enzymes in the carbon fixation process.

·      Unique metabolic pathway for use in Synthetic Biology applications.

·      Possible Carbon Credits for developing improved means of carbon fixation.


Advantages


·      E. coli is fast growing and easily manipulated by various genetic tools.

·      Novel source of biomass production.

·      Potentially low cost R&D system.


Technology's Essence


The technology functions by the recombinant insertion of two enzymes from the Calvin-Benson-Bassham (CBB) into E. coli, kinase prk and the carboxylating enzyme RuBisCO. With further modifications, the engineered E. coli’s metabolism was divided into two subsections. First a carbon fixing metabolism that can incorporate inorganic CO2 into sugar production, the second subsection consumes organic pyruvate to produce energy to drive the aforementioned carbon fixing cycle. Subsequently the technology is overall carbon neutral, but is an inexpensive and fast platform for screening improvements in the CBB carbon fixation pathway.

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  • Prof. Ron Milo
1686

Applications


  • Co-treatment with chemotherapy
  • Co-treatment with statin treatmen

Advantages


  • Lower collateral toxicities allow for greater flexibility in treatment dosage.
  • Enhanced patient survival rate.
  • More favorably considered as a line of therapy due to decreased side effects.
  • Utilization of well-characterized compounds alleviates safety and toxicity considerations.

Technology's Essence


ER stress, elicited by chemotherapeutic agents such as doxorubicin, 5FU, vincristine and bortezomib, or statins such simvastatin, triggers cell death at least in part through generation of leukotriene C4 (LTC4), which induces ROS accumulation, DNA damage and subsequent cell death. LTC4 can be produced by two parallel pathways. Cells of hematopoietic origin express C4 synthase (LTC4S) and secrete their LTC4 load, thereby affecting nearby tissues. In contrast, as discloses by the present invention, non-hematopoietic cells generate LTC4 by the enzyme MGST2 (an isoenzyme of LTC4S), and retain it to act internally leading to their demise. This difference is the basis for the present invention. Thus, LTC4 receptor antagonists (montelukast, pranlukast, etc.) will alleviate the toxicity of chemotherapy towards non-hematopoietic tissues and cells, but retaining the therapeutic effectiveness of chemotherapy on lymphocytic leukemia, lymphoma and myeloma patients. In conjuction, it was found that pranlukast attenuated cell death triggered by a broad range (0.5-4 µg/ml) of simvastatin (a statin) concentrations.

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  • Prof. Menachem Rubinstein
1782
L-DOPA is a high value compound used in the treatment of Parkinson’s disease and a precursor for other high value compounds. Current industrial methods for producing L-DOPA are problematic in terms of complexity, yield, or toxic byproducts.Betalains are robust, flavorless, natural water soluble dyes,...

L-DOPA is a high value compound used in the treatment of Parkinson’s disease and a precursor for other high value compounds. Current industrial methods for producing L-DOPA are problematic in terms of complexity, yield, or toxic byproducts.
Betalains are robust, flavorless, natural water soluble dyes, in the color ranges of both red-violet and yellow-orange. Currently there is no natural quality source for water soluble natural yellow dyes, with present natural yellow dyes being water insoluble.
The present technology offers an alternative method that is simple, does not produce side-products, and is non-toxic with Tyrosine being the only feedstock. The technology produces L-DOPA and natural water soluble yellow and red Betalain dyes, both within yeast and in different plant species.

Applications


  • Production of L-DOPA for use in pharmaceuticals or dietary supplements.
  • Synthesis of water soluble yellow and red natural dyes for use as colorants, antioxidants, and food supplements.
  • Altering coloration of ornamental plants by inserting the metabolic pathway.

Advantages


  • One-step reaction for L-DOPA synthesis from Tyrosine.
  • Non-toxic and non-hazardous synthesis.
  • Ecologically friendly - no waste management issues.
  • Multiple colors can be produced with yellow, red, or orange if pathways combined.
  • Flavorless - avoid influencing the taste of different products.
  • Flexibility in biosynthetic production - multiple possible host systems.
  • Specificity - no side products produced
  • Mild Conditions - enzyme(s) requires ambient temperatures.

Technology's Essence


The present technology takes advantage of the Betalain biosynthetic pathway to selectively produce L-DOPA and natural Betalain dyes. A newly discovered, specific, cytochrome P450-CYP76AD6 begins the pathway, with the capacity to convert Tyrosine to L-DOPA. Then L-DOPA is converted to Betalamic acid via DOPA 4, 5-dioxygenase.
With the Betalamic acid intermediate, the biosynthetic pathway diverges to make either Betaxanthins (yellow dyes) or Betacyanins (red dyes). In the production of yellow dyes an amine (e.g. amino acid) spontaneously reacts with Betalamic acid. In the case of red dyes, cycloDOPA (generated by the enzyme CYP76AD1 modifying Tyrosine and L-DOPA) and a Betalain-related glucosyltransferase react with Betalamic acid. Furthermore the two pathways can be done in parallel to produce an orange color.

 

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  • Prof. Asaph Aharoni
1704
Neuropathic Gaucher’s (nGD), is a rare but very severe manifestation of the disease, with a varying degree of involvement of the central nervous system, in addition to systemic symptoms. As of today, there is no cure for these severe conditions. The search for such cure is tremendously hindered by the...

Neuropathic Gaucher’s (nGD), is a rare but very severe manifestation of the disease, with a varying degree of involvement of the central nervous system, in addition to systemic symptoms. As of today, there is no cure for these severe conditions.
The search for such cure is tremendously hindered by the unmet need for a reliable biochemical biomarker for nGD.
The present invention identifies the glycoprotein non-metastatic B (GPNMB) as a potential powerful nGD biomarker for use in early diagnosis, determination of disease severity, as well as a straight forward readout in clinical and preclinical experiments.

Applications


Diagnosis and drug development for neuropathic GD

Advantages


Straight forward diagnostic tool – based on standard biochemical assays
Relatively simple clinical procedure – samples are collected from CSF and not brain
High sensitivity – for the diagnosis of disease severity
Compatible with preclinical experiments

Technology's Essence


Prof. Futerman and his team preformed a quantitative global proteomic analysis (using LC-MS/MS) of cerebrospinal fluid (CSF) samples from four patients with Type 3 GD, to identify mis-regulated proteins, compared with healthy subject.
Glycoprotein non-metastatic B (GPNMB), a protein that was previously associated with several lysosomal storage disorders, exhibited very high levels (a 42-fold increase) in the CSF of type 3 GD patients.  Two peptides were identified from GPNMB, both located in the non-cytosolic domain, suggesting that GPNMB is cleaved and secreted into the CSF from the brain. LC-MS/MS results were validated by ELISA and by western blot analysis in CSF and in human brain samples.
Several proof of principle experiments were conducted in order to prove the validity of using GPNMB as a biomarker for monitoring disease state and treatments efficacy in neuropathic GD in patients and mouse models:
GPNMB levels were shown to be correlated with the severity of type 3 Gaucher’s disease patients, as measured by lower IQ score and lower score in Purdue Pegboard test, assessing eye-hand coordination. In addition, using conduritol b epoxide (CBE)-injection based mouse model that simulate different severities and recovery periods, it was shown that GPNMB levels rapidly rise or decline to reliably reflect progress/remission states of the diseases.

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  • Prof. Anthony H. Futerman
1712
  • Prof. Yechiel Shai
1671
A novel method to revert human iPSC to a fully naive state, retaining stable pluripotency. The feasibility for the existence of ground state naive pluripotency in human embryonic stem cells (hESC) has long been researched. This innovative technology supplies the composition of chemically defined...

A novel method to revert human iPSC to a fully naive state, retaining stable pluripotency. The feasibility for the existence of ground state naive pluripotency in human embryonic stem cells (hESC) has long been researched. This innovative technology supplies the composition of chemically defined conditions required for derivation and long term maintenance of such cells, without genetic modification.
Human naive pluripotent cells can be robustly derived either from already established conventional hESC lines, through iPSC reprogramming of somatic cells, or directly from ICM of human blastocysts. The new human pluripotent state was isolated and characterized; it can open up new avenues for patient specific disease relevant research and the study of early human development.

Applications


  • Reprogramming kits - Somatic cells to iPSC at near 100% efficiency (7days), iPSC to fully naive state.

Advantages


  • Deterministic iPSC reprogramming with no genetic modification required.
  • Stable pluripotency, with low propensity for differentiation
  • Reagents available off-the-shelf.

Technology's Essence


Hallmark features of rodent naive pluripotency include driving Oct4expression by its distal enhancer, retaining a pre-inactivation state of X chromosome in female pluripotent cell lines amongst others. Naive mouse ESCs epigenetically drift towards a primed pluripotent state; while human embryonic stem cells (hESCs) share several molecular features with naive mESCs (e.g. expression of NANOG, PRDM14 and KLF4 naive pluripotency promoting factors), they also share a variety of epigenetic properties with primed murine Epiblast stem cells (mEpiSCs). These observations have raised the question of whether conventioal human ESCs and induced pluripotent stem cells (iPSCs) can be epigenetically reprogrammed into a different pluripotent state, extensively similar with rodent na?ve pluripotency. Researchers at the Weizmann Institute discovered that supplementation of certain chemically defined conditions, synergistically facilitates the isolation and maintenance of pluripotent stem cells that retain growth characteristics, molecular circuits, a chromatin landscape, and signaling pathway dependence that are highly similar to naive mESCs, and drastically distinct from conventional hESCs.

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  • Dr. Jacob (Yaqub) Hanna
1750
Organophosphates are toxic compounds found in chemical warfare agents, such as nerve gases, and insect pesticides.Use of volatile nerve gas agents by terrorist organizations is a key concern of governments around the world. V-type nerve agents (e.g. VX, RVX, and CVX) are particularly toxic nerve gases...

Organophosphates are toxic compounds found in chemical warfare agents, such as nerve gases, and insect pesticides.
Use of volatile nerve gas agents by terrorist organizations is a key concern of governments around the world. V-type nerve agents (e.g. VX, RVX, and CVX) are particularly toxic nerve gases, with an exceptionally high potency. Although not as lethal as nerve agents, organophosphate insecticides can be harmful in large or prolonged doses. The standard therapy has limited efficacy, carry risks of serious adverse effects and have relatively short shelf life in field conditions.
Bioscavengers represent a preferred to rapidly detoxify organophosphates in the blood, before they had the chance to reach its physiological targets and cause damage, but usually require the use of very high doses.
The present invention provides genetically modified phosphotriesterase (PTE) variants, which serve as catalytic bioscavengers for V-type nerve agents, with exceptional detoxification activity at low doses, and improved stability.

Applications


  • Prophylactic or post exposure treatment for nerve gases attack, in particular V-type agents
  • Treatment for pesticides poisoning

Advantages


  • High catalytic activity – allow high efficacy at low doses
  • Reduced effective doses allows to reduce adverse effects
  • High stability increasing shelf life
  • Compatible with both prophylaxis and post exposure
  • Compatible for both surface decontamination and administration to patients

Technology's Essence


Researchers at Prof. Tawfik lab use directed evolution to drive protein mutagenesis towards desired traits. Appling this approach, using the actual threat agents, the present inventors generated recombinant phosphotriesterase (PTE) variants with improved catalytic efficiencies towards V-type nerve agent hydrolysis. Serving as catalytic bioscavengers, these recombinant PTE variants hydrolyze organophosphates without being consumed and thus can be applied at low doses (catalytic efficiency (kcat/KM) greater than 3.106 M-1min-1).
Importantly, PTE is efficient both as a prophylactic agent that may be given several hours prior to exposure as a preventive measure, and as post exposure antidote, even days after in a single or multiple-doses.
It is compatible with both decontamination of surfaces and detoxification administrated to a patient by standard routes such as orally or injectables.
Finally, some PTE variants show superior stability properties, retaining at least 50% of their catalytic activity at 50?C, indicating extended shelf life. This may be especially critical in field conditions, where the risk for nerve agent exposure is high.

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  • Prof. Dan S. Tawfik
1679
A novel therapy for Triple Negative Breast Cancer (TNBC) using mAbs combinationBreast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) representing about 15% of all breast cancer cases, is the deadliest form of all breast cancer subtypes, and tends to affect...

A novel therapy for Triple Negative Breast Cancer (TNBC) using mAbs combination
Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) representing about 15% of all breast cancer cases, is the deadliest form of all breast cancer subtypes, and tends to affect women at a younger age. Unfortunately TNBC cannot be treated with the common receptor targeted therapies since it does not express these targets, the estrogen, progesterone and Her2/neu receptors. Therefor systemic treatment options are currently limited to cytotoxic chemotherapy. The lack of effective targeted therapies, resistance to chemotherapy, and early metastatic spread have contributed to the poor prognoses and outcomes associated with TNBC.
The current technology offers a novel therapeutic strategy for TNBC. The application of two novel, noncompetitive antibodies against EGFR, achieves a robust degradation EGFR resulting in tumor inhibition.

Applications


  • Novel and unique antibody targeted therapy for TNBC.
  • The novel anti EGFR antibodies can cooperate synergistically with the currently marketed EGFR antibodies.

Advantages


  • A promising therapeutic scenario to treat TNBC.
  • Enhanced EGFR degradation and improved anti-tumor activity, in contrast to clinically approved anti-EGFR mAbs, which display no cooperative effects.
  • Lysosomal EGFR degradation pathway induced by epitope-distinct antibody mixture may potentially lead to improved therapeutic outcome, and reduced resistance.

Technology's Essence


Prof. Yosef Yarden and his team demonstrated that a combination of novel antibodies that target distinct regions on the human EGF receptor resulted in its robust and synergistic down-regulation, leading to pronounced tumor growth inhibition. Furthermore, the combined mAbs induced lysosomal degradation of EGFR, while avoiding the recycling route. Such irreversible mode of EGFR degradation may potentially increase response rate or delay the onset of patient resistance.
Conversely, combining cetuximab and panitumumab, the mAbs routinely used to treat colorectal cancer patients, did not improve receptor degradation because they are both attracted to the same epitope on EGFR.

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  • Prof. Yosef Yarden
1772
MTCH2 as a novel target for the treatment of obesity.Obesity is an escalating public health problem with an increasing prevalence worldwide, and a primary contingency of many life-threatening diseases, as well as early mortality. In the U.S. alone, more than one-third of adults are obese. Obesity-...

MTCH2 as a novel target for the treatment of obesity.
Obesity is an escalating public health problem with an increasing prevalence worldwide, and a primary contingency of many life-threatening diseases, as well as early mortality. In the U.S. alone, more than one-third of adults are obese. Obesity-related conditions include heart disease, stroke, type 2 diabetes and certain types of cancer, some of the leading causes of preventable death. Physicians and patients alike consider the weight-loss efficacy of the current therapeutics to be unsatisfactory. Therefore, there is an unmet need for innovative options that are at once safe and efficacious, and allow the patient to maintain weight loss.
The present invention describes the identification of Mitochondrial Carrier Homolog 2 (MTCH2) as a novel player in muscle metabolism and the therapeutic potential of inhibiting MTCH2 for the treatment of diet-induced obesity and diabetes.

Advantages


  • A fresh approach for targeting weight-related disorders
  • Direct effect on metabolism instead of indirect mechanisms of current therapeutics which target appetite modulation.
  • Protection from diet-induced obesity can be used as a prevention treatment for people with a tendency for weight gain.  

Technology's Essence


MTCH2 functions as a receptor-like protein for the pro-apoptotic BID protein in the mitochondria.
MTCH2 was identified as one of six new gene loci associated with Body Mass Index (BMI) and obesity in humans suggesting that MTCH2 may also play a role in metabolism.
MTCH2 was recently shown by the Gross’s lab to also function as a repressor of   mitochondria oxidative phosphorylation (OXPHOS) in the hematopoietic system.
Deletion of MTCH2 in skeletal muscle increases mitochondrial OXPHOS and mass, and increases capacity for endurance exercise. In addition, loss of MTCH2 increases mitochondria and glycolytic flux in muscles as measured by monitoring pyruvate and lactate levels.
MTCH2 knockout mice are protected from diet-induced obesity, hyperinsulinemia, and are more prone to weight loss upon caloric restriction.
Therefore, the association of MTCH2 with mitochondrial function offers a potential novel target for muscle metabolism modulation in the fight against metabolic disorders such as obesity and diabetes.

 

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1690
Optimal growth and metabolic activities of Lactic Acid Bacterial (LAB) starters are critical for assuring high-quality fermentation in the manufacturing process of numerous dairy products. Despite extensive efforts, phage infection of starter cultures for dairy processing remains the most common cause...

Optimal growth and metabolic activities of Lactic Acid Bacterial (LAB) starters are critical for assuring high-quality fermentation in the manufacturing process of numerous dairy products. Despite extensive efforts, phage infection of starter cultures for dairy processing remains the most common cause of slow or incomplete fermentation and product downgrading. Standard anti-phage measures (sanitation, culture handling) fail to provide sufficient protection, exposing the production process to massive economic setbacks.
Extensive R&D efforts have led to the discovery of phage resistance systems, however many phages can circumvent these systems, and in addition not all LABs can accommodate them.
Therefore, there is a strong need for additional defense systems that could naturally protect LABs against phages.
The Sorek laboratory at the Weizmann Institute of Science has recently identified hundreds of novel functional toxin/antitoxin systems in bacterial genomes. These systems were discovered using analysis of data from millions of shotgun cloning experiments across 388 bacterial species. Acting as an abortive infection agent to prevent phage spread, some of these systems were already validated as conferring resistance against phage infection upon introduction to E.coli cells.
In another novel technology, researchers at Dr. Rotem Sorek’s lab identified a novel anti phage gene cassette, termed BREX (Bacteriophage Exclusion), which confers complete or partial resistance against phages spanning a wide phylogeny of phage types, including lytic and temperate ones.

Applications


  • Tools for conferring anti-phage traits to bacterial starters.

Advantages


  • Provides efficient phage-resistance features.
  • Robust: confers resistance to a broad range of phages, including both lytic and temperate ones.
  • General: the same defense system may be applied in various cultures, not confined to specific strains.
  • Novel systems, provides a fresh approach to the field of phage resistance 

Technology's Essence


Toxin/antitoxin (TA) modules, composed of a toxic protein and a counteracting antitoxin, are proposed to function in phage defense via abortive infection. The two genes, which reside on the same operon, code for small proteins where inhibition of the toxin is carried out through protein-protein interaction. Upon a specific signal (phage infection) the antitoxin degrades rapidly by one of the housekeeping bacterial proteases, resulting in either bacteriocidic (cell-killing) or bacteriostatic (growth-inhibiting) effects, thus protecting the colony against phage spread. The inventors took advantage of the concept that toxins could only be cloned when the neighboring antitoxin was present on the same clone to systematically reveal active TA pairs. Following extensive statistical and experimental validations, 8 novel families of TA pairs that are likely to play a role in phage defense were identified. By introducing these systems into new bacteria, the inventors showed that the toxin/antitoxin pairs could protect the engineered bacteria from phage infection.
BREX is a novel cassette of six genes that confers protection against a wide range of phages, including virulent and temperate ones. This cassette is composed of genes not typically found in other defense systems, and hence employs a novel mechanism of anti-phage protection. Scientists at the Sorek lab further uncovered the mode of action of this novel system. It was shown that the system is not an abortive infection system (i.e., does not lead to suicide of the infected cell), and that it allows phage adsorption but blocks phage replication in a DNA degradation independent manner.

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  • Prof. Rotem Sorek

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