A Set of Small Molecule Inhibitors of Human Galactokinase (GALK)
Scientific Relevance
Galactosemia is a genetic disorder, in which the body becomes deficient in a liver enzyme, galactose 1-phosphate uridyltransferase (GALT), required for the digestion of galactose. The only treatment for galactosemia is eliminating lactose and galactose from the diet. Even with an early diagnosis and a restricted diet, however, some individuals with galactosemia experience long-term complications such as speech difficulties, premature ovarian failure, and neurological impairment.
Commercial Opportunity
Primary Opportunity: This technology fills an unmet need within the pharmaceutical industry: a method to inhibit GALK as a therapeutic approach for Classic Galactosemia. Expanded Opportunities: It is noteworthy that some GALK inhibitors have cross-inhibitory action against other members of the GHMP kinase superfamily, which includes the medically important enzymes: Galactokinase, Homoserine kinase, Mevalonate kinase, Phosphomevalonate kinase, and CDP-ME kinase. As a result, these inhibitors might be used to treat diseases beyond Classic Galactosemia.
Competitive Advantage
Primary Opportunity: Novel and
effective treatment for Classic Galactosemia will qualify as Orphan
Drug according to the US Federal Orphan Drug Act (Amended);
Expanded Opportunities: CDP-ME kinase, a member of the GHMP
kinase superfamily, is an essential enzyme present exclusively in
many pathogenic bacteria, chlamydia, and protozoa. Therefore, novel
inhibitors for this unique enzyme can target these pathogens with
minimal side-effects on the infected human patients and animals.
The invention is a method to identify and characterize CD4+ T cells that may be used in therapies for autoimmune diseases such as mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE).
Commercial Opportunity
MCTD, SLE and rheumatoid arthritis are individually relatively rare conditions, but taken together, affect a substantial number of people. MCTD has an estimated prevalence of up to 15 cases per 100,000 people in the US. Lupus and rheumatoid arthritis are estimated to affect 1.4 million and 2.5 million persons respectively, in the US. Currently, there are no cures for these conditions, and treatment is very limited, or do not exist.
Competitive Advantage
This technology presents an opportunity to expand market share by introducing a novel product that does not have much competition. At the present time, there are limited treatment options for autoimmune diseases such as MCTD and lupus.
The invention uses immunomodulating agents that can both stimulate the immune system or have an immunosuppressive effect. TNFR25 agonists and antagonists have pro and anti-inflammatory action, respectively. TNFR25 agonists can support tumor vaccination, while TNFR25 antagonists can treat disease caused by chronic inflammation and autoimmunity (e.g. inflammatory bowel disease, ulcerative colitis and Crohn's Disease).
Commercial Opportunity
Inflammatory bowel disease, ulcerative colitis and Crohn's disease cost between $3-5 billion annually to treat. To have a novel approach to these diseases that would also apply to transplantation autoimmunity is a unique commercial opportunity.
Competitive Advantage
Tumor vaccines that are currently available are often suppressed in the tumor environment. This approach increases the vaccine's ability to act on the tumor due to increased stability. The myriad of biological effects that this immunomodulating agent can achieve is far superior to anything currently in use.
This invention demonstrates that hyaluronidase (HAase) inhibitors may be used to inhibit tumor cell proliferation and/or progression through the cell cycle. These inhibitors are being developed to treat cancer or a precancerous condition with special emphasis on solid tumors. In addition these compounds may be anti-angiogenic and reduce the risk of cancer cell metastases. These compounds are likely to be effective with little or no side effects.
Commercial Opportunity
Cancer is the second leading cause of death in the U.S. with over 500 thousand per year.
Competitive Advantage
This non-toxic anti-cancer therapeutic can be administered alone or as an adjunct to traditional chemotherapy or radiation therapy. This feature allows for reduced use of toxic chemotherapy and an improved quality of life.
Early Detection of Head and Neck Squamous Cell Carcinoma (HNSCC)
Scientific Relevance
This invention is a saliva based test (ELISA) incorporating a panel of four biomarkers that can detect early stage HNSCC and very early pre-cancerous lesions. At this early stage the cancer or pre-cancer is treatable or reversible. At this point, the complete biomarker panel has 93% sensitivity and 75% specificity.
Commercial Opportunity
HNSCC accounted for $3 billion in expenditures in 2004 or 4.4% of all cancer expenditures. 85% of HNSCC occurs in drinkers and smokers. There are currently 56 million smokers and 15 million alcohol abusers in the U.S and significantly more worldwide.
Competitive Advantage
This early detection panel of biomarkers is simple and low cost, detecting cancer without visual examination of the patient by a primary care provider or dentist.
Inventors
Elizabeth Franzmann, Vinata Lokeshwar, Erika Reategui and Rakesh Sihgal
The invention involves an 11 amino acid peptide (IEP11) which corresponds to a unique region of the secreted form of human mucin protein (sec-mucin). The 11 amino acid peptide can be used as a vaccine adjuvant to enhance in vivo immune responses, to induce the production of cytokines, as a mitogen of one or more cell subpopulations, or to enhance cellular cytotoxicity.
Commercial Opportunity
Cancer is the second leading cause of death in the U.S. with over 500 thousand per year.
Competitive Advantage
This small protein drug has the potential to be a universal adjuvant for use with or without traditional chemotherapy. Immunomodulation to help one's body fight cancer can reduce the need for toxic chemotherapy and increase the survival rate and quality of life.
Inventors
Diana Lopez, Lynn Herbert, Mantley Dorsey Jr., Gunter Kraus and James Hnatyszyn
Method of Treating Multiple Myeloma by Targeting CD28
Scientific Relevance
Targeting CD28 on myeloma cells can be used as a single agent for the treatment of multiple Myeloma. This approach can also be used in combination with other chemotherapy.
Commercial Opportunity
Multiple Myeloma is the second most common hematological malignancy behind non-Hodgkin' lymphoma, with 15,000 new cases diagnosed each year. It is currently incurable. Patients characteristically respond initially to chemotherapy, but then relapse with increasingly more chemoresistant disease. Thus novel therapies that can bypass the underlying resistance mechanisms are clearly needed.
Competitive Advantage
Targeting CD-28 on myeloma cells could be a single agent treatment as opposed to the existing highly toxic treatments available.
Perforin 2 Proteins as a Novel Antibacterial Therapy
Scientific Relevance
This invention relates to the fields of antibiotics, anti-cancer agents and drug discovery. More specifically, it relates to a compound useful in activating the body's natural defenses to both infections and tumors.
Commercial Opportunity
The incidences of serious bacterial infections are increasing at home and in hospitals due to the development of antibiotic resistance. Furthermore, there are certain bacteria such as those causing tuberculosis that are naturally resistant to most antibiotics. For biological reasons alone, there is an urgent need to discover novel antibacterial agents. Antibiotics, many of which have patents that will expire in the next few years, are currently a multi billion dollar industry.
Competitive Advantage
This is a unique antibacterial approach in that it will not lose efficacy due to the development of resistance.
Antibody NKG2D Ligand Fusion Protein for Cancer Therapy
Scientific Relevance
Certain anticancer drugs (e.g. Herceptin for breast cancer) act by attaching to specific receptors (HER2/neu) and thereby destroy tumor cells that express the receptor. However, these drugs have reduced efficacy when the target antigen is inadequately expressed, or if immune function is impaired. One approach to overcome this is to take advantage of a protein NKG2D-Ligand (NKG2D-L) that is ubiquitously expressed during times of infection and stress. When NKG2D-L is bound to its specific receptor, there is increased cell killing potential. Linking anti-tumor antibodies to NKG2D-L proteins increases the ability of immune effector cells to recognize and eliminate tumor cells. This approach could be used for a variety of anti-oncogenic applications.
Commercial Opportunity
Adjuvant therapy for cancer is a multi billion dollar industry. In the near future, as the population ages, it is expected that expenditure for this type of drug will increase at a faster rate than any other category of medication.
Competitive Advantage
Targeting molecules for cancer therapy allow much lower concentration of the toxic chemotherapeutic agent to be used. The advantage of this approach over non-targeted molecules is its stability and the ability to use lower concentration.
Inventors
Joseph D. Rosenblatt, Seung-Uon Shin and Khaled A. Tolba
Antibody-Endostatin Fusion Protein and its Variants
Scientific Relevance
This invention relates to compositions and methods for targeting and modulating the activity of tumor cells. In particular, the invention relates to chimeric fusion molecules which have a tumor antigen targeting domain and an anti-tumor effector function domain.
Commercial Opportunity
The sale of anti angiogenic molecules have reached the $600 million level and it is predicted by Forbes magazine to reach the billion dollar level in the next few years when it becomes applicable to colon, bladder, head and neck and prostate cancer. This approach is a huge improvement over these drugs.
Competitive Advantage
As effective as anti angiogenic molecules are, they have half-life and concentration problems that this technology addresses.
Inventors
Sherrie Morrison (UCLA), Joseph D. Rosenblatt and Seung-Uon Shin
Transgenic Mice Expressing a Real-Time Reporter for Cellular cAMP in a Tissue-Selective and Inducible Manner
Scientific Relevance
Cyclic AMP (cAMP) mediates the response to hormones, neurotransmitters and other molecules in practically every tissue of the body. The inventors have generated a unique transgenic mouse that is able to express an inducible fluorescent cAMP reporter in targeted cells and tissues. To achieve this, transgenic mice carrying the newly generated and unique cAMP reporter are mated with mice carrying an appropriate, tissue-specific, antibiotic-sensitive triggering mechanism in their genome. Mice tailored to a specific tissue can be readily generated. By injecting a commonly available antibiotic, researchers can then induce the synthesis of the cAMP reporter in pre-specified cells. Using this mouse model, cAMP can be examined in intact organs, tissues and cells both in vitro and in vivo. The transgenic mouse will make it possible to monitor how intracellular cAMP levels change in response to metabolites, transmitters, hormones, and drugs in real time and with high spatial resolution (i.e., single cells and even subcellular regions).
Commercial Opportunity
This mouse is an important drug discovery tool. Pharmaceutical industry scientists as well as academic researches can use this mouse to monitor responses to existing drugs and develop new ones. Additionally, this mouse could be used to test the effects of treatments affecting the brain, spinal cord or autonomic nervous system.
Competitive Advantage
This is the only mouse model available that allows responses to drugs, metabolites, transmitters, hormones, pharmaceuticals, etc. to be monitored visually in vivo. Furthermore, the response can be seen in real time with high spatial resolution.
This invention is a novel three component combination therapy which entails:
1) the use of specialized nerve growth promoter cells in a bridge-like manner grown from the patient's own cells (Schwann cell bridge),
2) a class of drugs to reduce the inhibition to heal (phosphodiesterase inhibitors) and
3) a specific protein activator (cyclic adenosine monophosphate, cAMP).
Commercial Opportunity
In an average year, there are greater than 11,000 spinal cord injuries (SCI) in the United States. About 40% occur in motor vehicle accidents and 25% result from violent encounters. Approximately 250,000 - 400,000 people in the U.S. are paralyzed as a result of SCI. The economic impact is estimated at $9.7 billion each year and the cost of treating pressure sores alone is estimated at $1.2 billion. A therapeutic approach to a cure or an improvement would have an enormous socio-economic impact.
Competitive Advantage
This is the only treatment that uses the patient's own cells to regenerate the central nervous system. The combination of cells and bioactive agents is unique and together they bridge the gap of the injury and facilitate directional nerve growth.
Ubiquitin for the Treatment of Inflammation in Surgery and in Trauma
Scientific Relevance
Extracellular ubiquitin, when released after trauma, has anti-inflammatory actions. When administered to an animal model for endotoxic shock, ubiquitin was found to reduce almost all classical symptoms of inflammation. When ubiquitin was given to animals with severe brain injuries, pressure within the skull was reduced significantly, and lung malfunction was prevented.
Commercial Opportunity
Each year in the United States, at least 1.4 million people sustain a traumatic brain injury (TBI). Of these people, about 50,000 die, and an estimated 80,000 to 90,000 people with TBI experience permanent disability from their injury. Direct medical costs and indirect costs such as lost productivity due to TBI totaled an estimated $60 billion in the U.S. in 2000.
Competitive Advantage
Ubiquitin does not produce any detectable, adverse side effects, and is extremely effective in reducing inflammation, regardless of the cause.
Peptides that Enhance Acetylcholinesterase Expression
Scientific Relevance
This invention uses peptides based on the amino terminal domain of the acetylcholinesterase (AChe) subunits ColQ and PRiMA together with an endoplasmic reticulum localization signal. When these peptides are administered to tissue cultured cells, the expression of AChe is enhanced several fold potentially neutralizing the toxic effect of nerve gas and pesticide poisoning.
Commercial Opportunity
There are close to 2 million acute pesticide poisonings reported per year with over 50,000 resulting in death. Furthermore, the risk of terrorist poisoning is increasing continually. An injectable peptide that can increase endogenous AChe levels is a potential therapy for nerve agent exposure of both military and civilian populations that has far reaching commercial and societal importance.
Competitive Advantage
This is the only method that neutralizes toxic effects of nerve gas and pesticides by increasing levels of a naturally occurring enzyme. Furthermore, this is the only approach that can be used preventively, thus increasing the chance of survival of first responders.
Microparticles as a Treatment Method for Bleeding Disorders
Scientific Relevance
Microparticles (MP) derived from blood can be administered to a patient to help stop bleeding and decrease blood clotting time. This would be important in cases involving internal bleeding, trauma, surgery, and chemotherapy, where the patient's own blood prior to treatment could be banked for later use.
Commercial Opportunity
This technology addresses a critical necessity because of the endless need, and short supply, of blood and its products. The market for a platelet substitute product is significant. It is estimated that over 10,000,000 units of platelets were transfused in the United States last year at an average cost of $50 per unit, which equates to an a market potential of $500 million annually.
Competitive Advantage
At present, no synthetic microparticles or blood cells have emerged as being clinically useful. In addition, since the patient's own blood can be used, the risk of acquiring infectious agents from an external blood supply is decreased substantially.
Inventors
Wenche Jy, Joaquin Jimenez, Lawrence Horstman, Yeon Ahn and Eugene Ahn
Molecular Targets for Modulating Intraocular Pressure and Differentiation of Steroid Responders versus Non-Responders
Scientific Relevance
This invention predicts which patients will have a common side effect from corticosteroid therapy. Corticosteroid therapy is common for various diseases of the eye, such as exudative age-related macular degeneration, macular edema, and uveitis. However, corticosteroid therapy may cause an increase in intraocular pressure (IOP) in about 40% of patients, which may result in permanent optic neuropathy. It is impossible to predict with certainty which patients will develop a potentially dangerous increase in IOP.
Commercial Opportunity
Identification of responders prior to corticosteroid therapy may make steroid use safer and more widespread.
Competitive Advantage
This is the only method that has the capacity to predict what patients might suffer adverse reactions to corticosteroid therapy.
This discovery allows the administration of chemotherapeutic or radio-sensitizing agents, making them more selective for the tumors and less toxic for the patient because it exploits the elevation, in tumors, of an enzyme which activates these novel drugs for a therapeutic advantage.
Commercial Opportunity
Pancreatic cancer is the fifth leading cause of cancer deaths following breast cancer, lung cancer, colon cancer, and prostate cancer. It is known as the "Kiss of Death" due to a certain rapid lethal progression. Approximately 27,000 patients are diagnosed annually in the U.S. and the same number die despite the cost of $50-100,000 per patient. Extending the life span of those diagnosed with this disease with better therapy would not only make a significant difference in these patients' lives but is also an important commercial niche.
Competitive Advantage
There is no treatment other than classic chemotherapy which has been ineffective in treating this disease.
The cornea accounts for 80% of the eye's optical power, thus injury of the cornea due to severe damage or disease can cause severe vision loss. Current treatment for the majority of these cases is by transplantation of the cornea, but risks from surgical corneal transplantation include infection and graft failure. It is much more advantageous for patients to retain their natural corneas to minimize complications.
Commercial Opportunity
Approximately 40,000 corneal transplant procedures are performed in the US (100,000 worldwide) annually.
Competitive Advantage
A less invasive alternative to corneal transplantation has been developed. In addition, there is no need for a corneal transplant donor. After treatment by this invention, patients are expected to recover more quickly, and complications from scarring are greatly reduced.
Myocarditis is a common inflammatory disease of the heart, estimated to account for about 30% of heart failure. Conventional diagnostic methods include 4-6 endomyocardial biopsies with consequent histologic evaluation. However, this standard technique results in a false negative rate of about 55%. The currently developed biomarker enables prediction of the likelihood of having inflammatory heart disease from a single endomyocardial biopsy with a sensitivity that greatly exceeds current standards. Furthermore, there is evidence that the biomarker may be detected in blood cells. Therefore, a simple venipuncture to detect the developed biomarker may replace the need for a diagnostic biopsy.
Commercial Opportunity
Myocarditis is an inflammatory disease of the heart, accounting for about 30% of heart failure. Given that specific treatment for myocarditis can reverse the disease process, the need for accurate identification of patients becomes apparent.
Competitive Advantage
There is no simple way to predict myocarditis especially in asymptomatic patients. Having access to a unique molecular signature associated with various aspects of cardiac diseases and disorders may allow for identification of patients with myocarditis with a positive predictive value of 80%. This would allow for patient treatment prior to symptoms and would add a huge number of potential patients to the market.
Glutamate Receptors in Pancreatic Cells as a Pharmacological Target for Prevention of Hypoglycemia in Diabetes
Scientific Relevance
A novel discovery was made in that receptors for glutamate were found in alpha cells of human pancreatic islets, and that added glutamate stimulated glucagon release, but not insulin release. Glucagon is released in response to low blood sugar levels or hypoglycemia, and causes the conversion of glycogen stored in the liver to glucose. Therefore, the modulation of these receptors is an alternative pathway in the management of glucose levels, and may be used as an adjuvant therapy for diabetes and hypoglycemia.
Commercial Opportunity
An estimated 21 million people, or approximately 7% of the population in the U.S., have diabetes for which there is presently no cure. New cases of diabetes are reported to be about 1.5 million people per year, and approximately $116 billon annually is spent on direct medical costs associated with this condition. Hypoglycemia is a major clinical problem for patients with diabetes, with 65% and 11% of people with Type 1, and Type 2 diabetes, respectively, suffering episodes of severe and temporarily disabling hypoglycemia.
Competitive Advantage
In contrast to current approaches to treat hypoglycemia, this therapy enhances endogenous glucagon secretion and would prevent recurrent occurrences of hypoglycemia.
Inventors
Per-Olof Berggren, Alejandro Caicedo and Over Cabrera
Gene Targets in Anti-aging Therapy and Tissue Repair
Scientific Relevance
This invention describes novel therapeutic target genes, Rad50 and SMG6, which participate in DNA and cell repair. In addition, RAD50 has been described for its fundamental role in stem cell viability and telomerase activity, suggesting its high potential to function as a regenerative gene. Interestingly, RAD50 and SMG6 were highly overexpressed in patients with excellent clinical outcome after presentation with new onset heart failure, while patients who had a very poor prognosis, appeared to have only low gene expression levels of RAD50 and SMG6. This data supports the hypothesis that RAD50 and SMG6 have great potential to function in regenerative medicine and tissue repair.
Commercial Opportunity
Several implications of these pathways are apparent and novel:
1) This is the first demonstration that Rad50 and SMG6 are over-expressed in patients who recover from heart failure compared to those with poor prognosis who succumb to their disease;
2) As such, these may represent novel therapeutic targets which could be manipulated by gene therapy or small molecule strategies;
3) Since these pathways are important in stem cell viability, modifying stem cells to over-express these regenerative genes could enhance stem cell effectiveness for tissue repair.
Competitive Advantage
While various types of cell therapy, such as mesenchymal or embryonic stem cells, have been successfully applied in organ regeneration, there has not been agreement on the optimal type of cell. Furthermore, the question rises if cells should be modified to increase their survival after implantation into the diseased organ and to enhance their therapeutic potential. RAD50 and SMG6 may be important targets for gene therapy that seek to enhance stem cell efficacy in organ failure and tissue repair.
Algorithm for Age Related Macular Degeneration Prediction
Scientific Relevance
Age-related macular degeneration (AMD) is the leading cause of irreversible severe vision loss in Caucasians over the age of 50. Typically diagnosis of AMD does not occur until the disease has progressed significantly and the patient experiences vision difficulties. Currently, there is no cure for the disease and very few preventative measures can be taken to prevent onset of the disease. There are several risk factors both environmental and genetic that allow certain individuals to contract the disease while others never get the disease. If it were possible to identify individuals that were at a high risk for developing AMD prior to disease onset preventative measures may delay onset. In addition, these individuals may respond to emerging therapies better allowing delay or even prevention of AMD. This technology uses a unique algorithm in which known risk factors are statistically factored and weighed to predict an individuals risk profile for the development of AMD. This algorithm uses currently known factors such as specific SNPs, environmental factors, as well as a newly identified mitochondrial gene. Data has shown that this algorithm can be about 90% accurate, meaning that approximately 90% of individuals that will develop AMD can be identified using this algorithm. This technology is a powerful way to pull together the latest AMD research and accurately identify individuals at high risk for developing AMD.
Commercial Opportunity
AMD affects more than 1.75 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to almost 3 million by 2020.
Competitive Advantage
Currently an individual can be sampled for particular polymorphisms that have been linked to AMD however there is no way to weigh these for relevance. Moreover there is no way to combined these with environmental factors and accurately predict an individuals risk for developing AMD. This algorithm uses all the currently know markers, both genetic and environmental, as well as a novel mitochondrial gene recently implicated in AMD to accurately predict individual risk factor.
Inventors
Jeffrey A. Canter, Margaret A. Pericak-Vance, Kylee M. Spencer and
Jonathan Haines
Endostatin is a potent anti-angiogenic protein capable of inhibiting the growth of oncogenic tumors. The utility of endostatin is limited due to the fact that the protein has a short half-life. Thus, it needs frequent dosing, and invariably results in low concentration at the site of tumors. To increase efficacy, the inventors have combined endostatin with the targeting specificity of an anti-tumor antibody by producing antibody-endostatin fusion proteins specific for the HER2/neu tumor antigen.
Commercial Opportunity
This approach could be used for a variety of anti-oncogenic applications. Adjuvant therapy for cancer is a multi-billion dollar industry. In the near future, as the population ages, it is expected that expenditure for this type of drug will increase at a faster rate than any other category of medication.
Competitive Advantage
Improving molecules useful for cancer therapy allow much lower concentration of the toxic chemotherapeutic agents to be used. The advantage of this approach over non-targeted molecules is its stability and the ability to use a lower concentration.
Inventors
Joseph D. Rosenblatt, Seung-Uon Shin and Khaled A. Tolba
Aptamer Targeted siRNA to Prevent Attenuation or Suppression of T-Cell Function
Scientific Relevance
Extended T cell function is critical for protective immunity. Various attenuating and/or tumor-induced suppressive pathways limit T cell persistence and anti-tumor activity. Delivery of siRNA in vivo would potentially overcome attenuation/suppression of T cells and result in more potent anti-tumor specific immunity. The therapeutic implication is that countering immune-attenuating/suppressive regulatory circuits will contribute to successful immune control of cancer.
Commercial Opportunity
An important distinction between drugs which target the cancer cell directly and immunomodulatory agents is that in order for the cancer drug to be effective it has to reach and eliminate the vast majority of tumor cells disseminated throughout the body. By contrast, the immunomodulatory agents will be effective if they reach a fraction of the immune cells because the ensuing antitumor immune response is systemic. Thus, whether targeting or not, immune-potentiating drugs do not have to reach all the target cells in vivo. This has important implications, including reduced cost and less toxicity; because in all likelihood the amount of immunomodulatory agent that needs to be injected will be significantly less than that of agents targeting the tumor cell directly.
Competitive Advantage
Use of aptamers to target gene silencing to the appropriate cells in vivo provides a drug/reagent that can be chemically synthesized in cell-free systems which significantly enhances the clinical applicability of this targeting approach (compared to antibody-based targeting). Consequently, the amount of siRNA reagent needed for treatment can be drastically reduced which also reduces treatment cost and toxicity.
Aptamers are superior to antibodies for the following reasons:
1) Can be synthesized chemically in cell free system;
2) Have a cost effective manufacturing process;
3) Have a simple regulatory approval process for clinical use;
4) and since they are not attached to protein carriers, they should be much less immunogenic than antibodies.
Furthermore, a key advantage of immune modulating drugs, whether targeted or not, is that only a fraction of the target cells need to be accessed in vivo for the approach to be successful.
The novel cell lines that have been developed would eliminate the time and cost-consuming steps of constantly isolating and propagating cells from primary Retinal Pigmented Epithelial (RPE) cells. Many studies on human retinal diseases have thus far used the RPE cell line ARPE-19. However, obtaining human eyes suitable for culture is difficult. Mouse RPE cells are advantageous in that they are more easily obtained and their supply is more constant. In addition, physiological differences between donors are minimized, thus quality control is improved. Mice that are pharmacologically or genetically manipulated can also be used to obtain cell lines.
Commercial Opportunity
The National Institutes of Health funding for eye disease research is approximately $700 M annually. In addition, age-related macular degeneration (AMD) and retinal disease is estimated to affect 10 million and 1.8 million people, respectively, in the US. Approximately 200,000 people are diagnosed with AMD annually, and this incidence is expected to rise.
Competitive Advantage
At present, no other immortalized mouse RPE cell lines are available.
A Transcriptomic Biomarker of Cardiac Diseases and Disorders
Scientific Relevance
Although heart failure is a common disease with about 550,000 newly diagnosed patients every year, individual risk assessment is still an unsolved issue. Many prognostic factors have been suggested, but there is no agreement on a reliable standard. Furthermore, there is a need for improvements in the accuracy of diagnoses for heart disease. Conventional methods include endomyocardial biopsy and histologic evaluation of 4-6 samples. However, this standard technique results in a false negative rate of about 55%. Genetic biomarkers may allow us to predict the likelihood of having cardiac disease and related disorders and may be able to do so from a simple non-invasive blood test.
Commercial Opportunity
Myocarditis is an inflammation of the myocardium, the thick muscular layer of the heart that accounts for about 30% of heart failure.
Competitive Advantage
There is no simple way to predict myocarditis especially in asymptomatic patients. Having access to a unique molecular signature associated with various aspects of cardiac diseases and disorders may allow us to have up to 80% positive predictive correlation. This would allow patient treatment prior to symptoms and add a huge number of potential patients to the market.
Glucose and Mannose Derivatives for Killing Tumor Cells
Scientific Relevance
This is a new method that exploits the difference in glucose metabolism between tumor vs normal tissues (as shown by the PET scan) using sugar analogs.
Commercial Opportunity
A wide variety of tumors that are driven by different combinations of oncogenes can be targeted for growth inhibition or cell death with 2-deoxyglucose and other mannose and glucose derivatives by the following mechanisms:
(1) Inhibiting the growth of most or all tumor cells via inhibition of glycolysis/glycosylation and or nuceltide precursors.
(2) As an adjunct to chemotherapy for killing slow-growing hypoxic tumor cells by inhibiting glycolysis (Phase I trial nearing completion).
(3) Has shown synergistic activity against hypoxic tumor cells with mTOR inhibitors;
(4) Kills a select number of tumor cells under normoxia via interference with N-linked glycosylation.
Competitive Advantage
(1) Although molecular biology allows targeting of cancer cells without harming normal cells, clinical chemotherapy still relies on methods that kill rapidly-dividing cells thus affecting many normal cells. The approach of this technology takes advantage of the fact that solid tumor cells are in a hypoxic microenvironment and selectively targets them without affecting normoxic cells.
(2) Since glucose has been shown to be selectively taken up more by tumor vs normal cells a natural therapeutic window exists that can be exploited using sugar analogs that interfere with various pathways of glucose metabolism that support tumor growth and survival.
(3) This biologic can be orally administered and is expected to be effective at low dosage.
A Method to Amplify Cardiac Stem Cells In-Vitro and In-Vivo
Scientific Relevance
Mesenchymal stem cells (MSCs) are bone marrow derived stem cells that may have clinical applicability for the treatment of diseases such as myocardial infarction and heart failure. The discovery by University of Miami researchers that MSCs stimulate proliferation of Cardiac Stem Cells (CSCs) may eliminate the need for tissue biopsy when using CSCs for therapeutic purposes.
Commercial Opportunity
Heart disease has been the leading cause of death in the United States for the past 80 years and is a major cause of disability. Heart disease also results in substantial health-care expenditures. For example, coronary heart disease is projected to cost an estimated $151.6 billion in direct and indirect costs in 2007. CSC are already being used as a therapy to treat patients with heart disease. This invention makes the use of CSCs more accessible since it accelerates their growth in the heart.
Competitive Advantage
Cardiac stem cells, while highly promising as a therapy, require a tissue biopsy and a long period of growth in the laboratory. Results shown by the University of Miami demonstrate that injections of MSCs into pig hearts cause massive proliferation of CSCs. MSCs can thus be used to accelerate the growth of CSCs in vitro or can be used to amplify CSCs in vivo, and thereby may eliminate the need for the tissue biopsy.
Altered Ca2+ homeostasis is a salient feature of heart disease, where the calcium channel ryanodine receptor (RyR) plays a major role. Nitric oxide synthase deficiency causes diminished ryanodine receptor S-nitrosylation leading to increased diastolic calcium. It is known that nitric oxide is important in maintaining electrical stability of the heart. This invention relates to a novel way to monitor and modulate the nitric oxide levels to diagnose and treat heart disease and those patients at risk of a heart attack.
Commercial Opportunity
Heart disease has been the leading cause of death in the United States for the past 80 years and is a major cause of disability. Heart disease also results in substantial health-care expenditures; for example, coronary heart disease is projected to cost an estimated $151.6 billion in direct and indirect costs in 2007.
Competitive Advantage
Understanding the mechanisms related to nitric oxide synthase, are important in the development of agents that would effectively and rapidly treat a person undergoing a heart attack. Just as significant would be the ability to modulate the nitric oxide levels in patients at risk for heart attacks, thus prophylactically treating these populations and saving lives, productivity and healthcare costs.
Pulmonary Hypertension remains a significant cause of morbidity and mortality especially severe in neonates who have been perinatally exposed to hypoxia. This discovery made by University of Miami researchers and physicians has found a potential new use for an existing drug a CXCR4 antagonist (AMD3100).
Commercial Opportunity
About 2% of newborn babies suffer from pulmonary hypertension.
Competitive Advantage
The main therapy currently utilized in neonates with pulmonary hypertension is nitric oxide. Unfortunately, this therapy is expensive, and does not reverse the vascular remodeling. Based on preliminary data, stem cells, as well as inflammation, play a significant role in the vascular remodeling that is evidenced during neonatal pulmonary hypertension. AMD3100 provides an alternative which is cheaper than inhaled nitric oxide and would decrease the vascular remodeling by addressing the root cause. Since patients with long standing pulmonary hypertension die because of irreversible vascular remodeling and right heart failure, this therapy will be significantly useful in reducing morbidity and mortality.
Method for Preparing the Recipient Site and Implanting Allogeneic Bone Grafts to the Jaws
Scientific Relevance
The present invention is a simplified allogeneic bone grafting technique that augments jaw bone volume in preparation for dental implants.
Commercial Opportunity
The present invention provides an opportunity to manufacture a surgical kit that includes circular drills of varying diameters, a surgical hand guide, and multiple units of cylindrical allogeneic bone with dimensions matching that of the circular drills.
Competitive Advantage
Conventional allogeneic bone grafting to the jaws is a difficult surgical process that involves exposure of an area of the jaw that is deficient in bone volume, requiring adaptation of a bone block to the jaw, and fixation of this block. The present invention is an improved procedure in which the recipient site in the native jaw is manipulated rather than the allogeneic bone graft, and a graft of standard size is utilized instead of a manually contoured block of allogeneic bone. The efficiency and reduced complexity of the present invention may increase the number of jaw augmentation grafts performed by dental professionals.
Novel Antagonistic Analogs of GH-RH for Cancer Treatment
Scientific Relevance
Novel antagonists of growth hormone - releasing hormone (GH-RH) have been synthesized. Compounds of this class have not yet been developed for clinical use in cancer therapy, but hold great promise as a treatment approach as they have been shown to be effective in vivo and would have minimal side effects. The peptides synthesized were tested against human prostate cancer, non- small-cell lung cancer and breast cancer tumor tissues xenografted on nude mice, and showed an anti-proliferative effect on tumor growth in these models. The new compounds have high receptor binding affinities and are more potent than antagonists discovered and patented earlier by this research group.
Commercial Opportunity
Approximately 22 million people are living with cancer worldwide, with an estimated 1.3 million new cases diagnosed each year in the US. The world market for cancer therapeutics is estimated to be close to $50 billion, with a steady forecast in growth.
Competitive Advantage
Current therapies for cancer are not satisfactory and new therapeutic agents are needed to develop more effective and/or less toxic therapeutic regimens. Because GH-RH antagonists are devoid or relatively free of side-effects, the new therapy should be superior to other existing therapies for cancer. Also, GH-RH antagonists may increase the effectiveness of chemotherapy in combination regimens.
Inventors
Andrew Schally, Jozsef Varga, Marta Zarandi and Ren-Zhi Cai
Current efforts in HIV vaccine design include developing formulations that elicit neutralizing antibodies. In designing these vaccines, the antibody response is tested against a panel of prototype viruses that are insufficient in representing the diversity of the viral quasispecies population. For HIV, this is especially inadequate, as the virus mutates rapidly to generate a number of quasispecies. By using a fast and efficient recombineering approach, viral recombinants can be produced that more effectively represent the quasispecies population present in a given geographic area. This information can then be used to develop more effective tools to test for vaccine efficacy and therapeutic agents.
Commercial Opportunity
An estimated 33 million people were living with HIV/AIDS, with 2.5 million new cases diagnosed by the end of 2007, according to the World Health Organization. Treatment consists of a drug cocktail that is taken for the rest of the patient's life. In addition, vaccines for other infectious diseases, for example, influenza, need to be developed every year because of the ever changing diversity of viral quasispecies.
Competitive Advantage
More effective vaccines and therapeutic agents for pathogenic viruses can be rapidly developed using this approach. Furthermore, the method is a vast improvement over the existing ones in generating a greater number of viral recombinants quickly and efficiently.
Activated Rac1, Aging and Male Gender Predispose Mice to Kaposi's Sarcoma-Like Tumorigenesis
Scientific Relevance
University of Miami researchers have discovered that the small GTP triphophatase Rac1, if activated and selectively expressed, results in tumors that are identical to Kaposi's Sarcoma tumors. Based on this, they have developed a small interference ribonucleic acid (siRNA) molecule that is capable of down regulating the expression of Rac1.
Commercial Opportunity
Kaposi's sarcoma is a tumor that is a significant complication of HIV infection. It also occurs in immune-compromised patients. The treatment of choice for Kaposi's sarcoma is highly active antiretroviral therapy (HAART) which is used to slow the progression of AIDS.
Competitive Advantage
On HAART therapy, there may be
immune reconstitution inflammatory syndrome which may mimic progression of Kaposi's sarcoma. The treatment based on this discovery would be applicable to any form of Kaposi's Sarcoma whether related to human immune-deficiency virus infection or not.
Inventors
Qi Ma; Enrique Mesri; Chunming Dong and Pascal J. Goldschmidt-Clermont
STING (Stimulator of Interferon Genes), A Regulator of Innate Immune Responses
Scientific Relevance
The invention relates to the identification, cloning and characterization of a molecule that regulates the innate immune signaling processes
Commercial Opportunity
STING may be useful in developing vaccines against pathogens and cancer, and could be targeted by drugs or used as a therapeutic target to boost the immune system. The importance of STING in innate immune responses also suggests that it may be suppressed in cancer, especially in viral-associated malignant disease.
Potentially, this approach can be implemented by vaccine companies, cancer prognostic companies, viral therapeutic companies and cancer immunotherapy companies as synergistic adjuvant to existing therapies.
Competitive Advantage
Unique activator of primary innate immune responses, including the production of Type I IFN.
Biomarkers to Predict Functional Lymphocytes and Immunoglobulins in Humans
Scientific Relevance
A particular set of biomarkers for functional B lymphocyte and immunoglobulin activity in humans has been identified. As part of the immune system, B-lymphocytes are important for making antibodies and helping fight infections. Specifically, antibodies made by B lymphocytes prevent colonization by pathogens and provides immunity against invading pathogens. In the elderly and in patients with weakened immune systems, vaccines and therapeutic agents may not be as effective because the number of functional B lymphocytes and immunoglobulins are fewer than in healthy people. By using the newly identified biomarkers, responses to vaccines and therapeutic agents can be followed more accurately, thus better dosing schedules and/or therapeutic approaches can be developed and followed.
Commercial Opportunity
Infectious pathogenic diseases are fairly common, with influenza alone affecting up to an estimated 50 million people each year in the US. Approximately 40,000 deaths are attributed to the flu, with most of the affected being the elderly and those patients with weak immune systems.
Competitive Advantage
A unique set of biomarkers have been identified in humans. These biomarkers would more accurately track immune responses and activity than the murine models currently used, and would be better indicators of vaccine and therapeutic agent effectiveness in humans.
Small Molecule Inhibitors of Costimulatory Protein-Protein Interactions
Scientific Relevance
A novel group of small molecule inhibitors of costimulatory protein-protein interactions has been identified. These interactions, in particular, CD40/CD154 interactions, are important in the activation of immune responses mediated by T- and B- cells. This activation may result in autoimmune diseases, which can affect virtually every site in the body, including the endocrine system, connective tissue, gastrointestinal tract, heart, skin, and kidneys. At least 15 diseases are known to be the direct result of an autoimmune response. Until now, drug discovery and development to treat these conditions has been hindered because drug-binding pockets, the traditional target for drugs, are not well defined in protein-protein interactions.
Commercial Opportunity
Autoimmune diseases are the third most common category of disease after cancer and heart disease, and affect an estimated 22 million people in the United States. Currently, there are no cures for most of these conditions, and treatments are very limited, or do not exist.
Competitive Advantage
The development of compounds that interfere with protein-protein interactions is an emerging field, as traditional approaches for drug development are ineffective. A novel drug discovery tool has been developed by using azo dye related small molecules as a scaffold.
Inventors
Peter Buchwald, Emilio Margolles-Clark, Norma Kenyon and Camillo Ricordi
Isolation of Stem Cell Precursors and Expansion in Non-Adherent Conditions
Scientific Relevance
The invention relates to stem cell isolation, expansion and culturing.
Commercial Opportunity
The use of bone marrow derived mesenchymal stem cells (MSC) has been proposed for a number of regenerative therapies including repair of myocardial tissue. However, in vivo studies have demonstrated minimal integration of MSC into cardiac tissue. As the MSC are grown as adherent cells in plastic tissue culture flasks we have hypothesized that the lack of a substrate for the MSC to adhere results in apoptosis. A number of stem cell populations have been shown to grow as spheres, including neural stem cells and cardiac stem cells suggesting that stem cells exist as spheres in vivo and not as adherent cells. Therefore we developed culture conditions for generation of MSC that proliferate in spheres. We have identified methods for isolating MSC precursors and expanding MSC under non adherent conditions. Inventors at the University of Miami have discovered a novel way to formulate MSC to enable enhanced integration of MSC into cardiac tissue and provide repair of ischemic tissue.
Competitive Advantage
Unique method that cultures and expands stem cells providing a formulation with greater potential for integration into tissues in vivo.
This technology was developed for rapid cloning of full-length open reading frame (ORF) cDNA sequences.
Commercial Opportunity
To separate out of frame from in-frame clones. This is extremely important to clone cDNA with full-length open reading frame
Competitive Advantage
Compared with commercially available cloning kits, this technology has the following advantages:
oHigh ligation efficiency,
oGuaranteed cloning of full-length ORF cDNA sequences with streptavidin enrichment
oRapid re-verification for ORF cDNA sequences by streptavidin binding assay.
oDoes not need expression plasmid with a C-terminal peptide tag, such as FLAG tag or c-Myc tag.
Antibodies for Modulating Inflammasome Activity and Inflammation in the Central Nervous System
Scientific Relevance
Inflammasomes are multi-protein complexes that have recently been discovered to play an important role in the inflammatory response after traumatic injury and disease. Traumatic injury to the central nervous system (CNS) includes traumatic brain injury (TBI), spinal cord injury (SCI) and stroke. Often, it is the inflammation response that causes tissue damage and minimizes the chance for recovery from these injuries. The inventors have made and purified an antibody that specifically binds to a component of the inflammasome, resulting in reduced inflammation and improved functional recovery in a rodent model.
Commercial Opportunity
Each year in the United States, at least 1.4 million people sustain a traumatic brain injury. Of these people, about 50,000 die, and an estimated 80,000 to 90,000 people with TBI experience permanent disability from their injury. Direct medical costs and indirect costs such as lost productivity due to TBI totaled an estimated $60 billion in the US in 2000. Approximately 250,000 people in the US live with spinal cord injury, and there are about 11,000 new cases per year. Stroke affects approximately 500,000 people per year.
Competitive Advantage
This is a novel compound that reduces the inflammation response. There is an urgent need to develop new therapeutic agents, as currently available anti-inflammatory agents have been shown in large clinical trials to not offer significant benefits to this patient population.
Inventors
Robert W. Keane, W. Dalton Dietrich, Juan Pablo de Rivero Vaccari and Helen M. Bramlett
Practical Device for In-Office Measurement of Heart Rate Variability
Scientific Relevance
Heart Rate Variability (HRV) has been shown to be an excellent indicator of a patient's cardiac health and their susceptibility to Sudden Cardiac Death (SCD). However, HRV is not a routinely employed cardiac diagnostic tool due to the need for a patient to wear a cumbersome holter monitor over an extended period of time to collect sufficient data and/or off-line data analysis that requires significant computational resources not amenable to a portable device. The inventors have developed a portable Heart Rate Variability (HRV) device, and current efforts of the research team are focused on miniaturizing the device to make it suitable for routine use in hospitals and physician's offices. This device should prove extremely useful in predicting a patient's susceptibility to SCD.
Commercial Opportunity
The market opportunity for this new device is enormous as it would be easily employed by a technician in hospitals and physicians' offices. It is expected that this invention would become a routine test for all patients middle aged and older.
Competitive Advantage
There is no currently available HRV diagnostic tool that provides a quick response (minutes as opposed to hours) and it also employs novel analysis to help risk stratify cardiology patients.
Novel Method for Identifying Compounds for Treating Obesity and Neurological Disorders
Scientific Relevance
A novel approach, based on rapid screening for compounds that modulate the conformation of a G5 neuronal protein complex, has been developed. By using Fluorescence Resonance Energy Transfer (FRET) or a similar protein-protein interaction assay, potential therapeutic compounds for treating obesity and neurological disorders can be identified rapidly, and with a high degree of specificity. The Gﾲ5 complex is known to regulate cell signaling only in the nervous system, and our investigators have shown its importance in influencing weight gain in a mouse model. It is known that about 50% of mutations that cause obesity in humans occur in genes that are expressed the central nervous system, where they regulate processes involved in control of appetite and metabolism. In addition, the Gﾲ5 protein complex has also been implicated in seizures and drug addiction.
Commercial Opportunity
The economic impact of obesity and the associated health conditions (e.g., cancer, diabetes, osteoarthritis and hypertension) is estimated to be $120 billion annually in the US. An effective weight loss therapeutic could be a billion dollar market, as about 1/3rd of the US population is obese. While obesity is caused and influenced by a number of factors, the Gﾲ5 protein complex can be added to the suite of potential drug target sites.
Competitive Advantage
A new drug target site for treating obesity and neurological diseases has been identified, and a more specific method than the current biochemical assays for identifying conformational changes at the target site has been developed. By this method, the conformational change and active state of the molecule in real time can be determined, and also in a single cell, allowing for localization.
Novel Off-Label, Combined Therapy for the Treatment of Multiple Myeloma and Other Conditions
Scientific Relevance
This invention identifies a novel combination therapy for two FDA-approved drugs. This off-label use has been shown to induce apoptosis in cancer cells by exploiting a mechanism that occurs in various types of cancer. The inventors have demonstrated the efficacy of this technology in multiple myeloma cell lines, and have also validated that the therapy does not destroy other cell lines that do not possess this mechanistic property. Advantageously, because this mechanism is associated with other, non-cancer conditions of major clinical concern, this novel treatment strategy may have broad applicability.
Commercial Opportunity
There are approximately 45,000 people in the United States living with multiple myeloma, and the American Cancer Society estimates that ~14,600 new cases of myeloma are diagnosed each year in the United States. Considering other non-cancer conditions, the market opportunity for the technology is huge; this invention could potentially treat a disease that affects over 30 million people in the United States alone.
Competitive Advantage
Employs already FDA-approved drugs that have been used and tested long term in patients with little to no serious side effects.
Long-term, Controlled, In Situ Oxygen Releasing Materials for Cell and Tissue Implants
Scientific Relevance
In order to immediately meet the inherent need of cells to have access to adequate oxygenation, a novel material has been created that has the capacity to release a sustained and appropriate level of oxygen over the course of several weeks. Co-implantation of this material with cells allows the cells to be exposed to adequate oxygen levels in vivo, providing time for blood vessels to grow and reach the tissue. Advantageously, the release of oxygen can either be in a short burst (24-36 hours) or sustained over a duration ranging from 14 to 45 days depending on how the material is designed.
Commercial Opportunity
This technology could enhance the efficacy of a plethora of various tissue engineering and cells transplantation applications: two areas of medicine that are currently in a phase of rapid market growth. Collectively, Life Science Intelligence projects the global market for tissue engineering and regenerative medicine products will exceed $118 billion by 2013. In 2008, the market was estimated at $1.5 billion.
Competitive Advantage
Cell viability is increased on the order of 2-fold.
The release of oxygen can either be in a short burst (24-36 hours) or sustained over a duration ranging from 14 to 45 days depending on how the material is designed.
Inventors
Cherie Stabler, Benjamin Harrison, Chris Fraker, Eileen Pedraza, Camillo Ricordi and Anthony Atala.
Antioxidant Activity of GH-RH Antagonists for Treatment of Cancer and Conditions Caused by Oxidative Stress
Scientific Relevance
Novel antagonists of growth hormone releasing hormone (GH-RH) have been synthesized for the treatment of cancer. These antagonists were newly discovered to act as antioxidant agents and inhibit the growth of human prostate cancer cells. Oxidants are harmful products generated by the body's metabolic processes, and the accumulation of oxidants, or oxidative stress, contributes to the development of cancer and the progression of many other diseases and conditions, including diabetes, heart disease, and neurodegenerative disorders. Compounds of this class have not yet been developed for clinical use in cancer therapy, but hold great promise as a treatment approach as they have been shown to be effective in vivo and would have minimal side effects. Because of their antioxidant activity, these compounds could also lead to novel therapies against many other conditions and disorders caused by oxidative stress.
Commercial Opportunity
Approximately 22 million people are living with cancer worldwide, with an estimated 1.3 million new cases diagnosed each year in the US. The world market for cancer therapeutics is estimated to be close to $50 billion, with a steady forecast in growth. In addition, the incidence of other diseases and conditions caused by oxidative stress, including atherosclerosis, diabetes, and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases is increasing worldwide. The world market for neurotherapeutic drugs is estimated to be $42 billion, with a double digit increase in growth forecasted.
Competitive Advantage
Current therapies for cancer are not satisfactory and new therapeutic agents are needed to develop more effective and/or less toxic therapeutic regimens. In addition, many neurodegenerative disorders and conditions have as yet, no cure. Because GH-RH antagonists are devoid or relatively free of side-effects, the new therapy should be superior to other existing therapies for cancer, and for other diseases and conditions caused by oxidative stress.
Inventors
Andrew Schally, Nektarios Barabutis, Marta Zarandi, Jozsef Varga and Ren-Zhi Cai
Targeting IL-7R Signaling as a Therapy for Autoimmune Disorders
Scientific Relevance
Interleukin-7 (IL-7) is an essential cytokine for the development and maintenance of T and B lymphocytes. Binding of IL-7 to its receptor, the IL-7 receptor (IL-7R), activates multiple pathways that regulate lymphocyte survival, and thus, impact the autoimmune system. Inhibition of IL-7R signaling has been newly discovered to confer a therapeutic effect to an autoimmune disease in a mouse model. This has important implications in diseases such as Multiple Sclerosis (MS) and other autoimmune diseases which currently have limited treatment options.
Commercial Opportunity
The prevalence of MS is up to 150 per 100,000 people in the US, and the therapeutic market for this disease alone is estimated to be $3 billion. The potential market for therapeutics in the treatment of autoimmune diseases is relatively large, despite the sometimes small patient populations. In addition, there is a major unmet market need for therapeutics for autoimmune disorders, as nothing placed on the market has been designed specifically for the treatment of these conditions.
Competitive Advantage
A novel therapeutic target site specifically for the treatment of MS and other autoimmune diseases has been identified.
Aptamer-targeted Costimulatory Ligand Aptamer to Tumor Cells
Scientific Relevance
Cancer treatment
Commercial Opportunity
Enhancing the magnitude and durability of vaccine-induced immune response is essential to achieve therapeutic benefit. Using enineered ligand to engage positive and negative immune stimulatory receptors on the vaccine-activted immune cells is an approach that has shown much promise in preclinical murine models and and recent clinical trials in cancer patients. This invention described a novel, clinically feasible and cost effective way to stimulate immunity in cancer patients whereby oligonucleotide-based immune modulatory aptamer ligands are targeted to the disseminated tumor lesions of the patient. This has important implications, reduced cost and less toxicity, because in all likelihood the amount of immunomodulatory agent that need to be injected will be significantly less than that of agents targeting the tumor cell directly.
Competitive Advantage
Use of aptamers to target aptamer-based ligands cargo to the appropriate cells in vivo provides a drug/reagent that can be chemically synthesized in cell-free systems which significantly enhances the clinical applicability of this targeting approach (compared to antibody-based targeting), drastically reducing the amount of reagents needed for treatment and consequently the cost-effectiveness and toxicity of the treatment. Aptamers are superior to antibodies inasmuch as they
1) Can be synthesized chemically in cell free system
2) Have a cost effective manufacturing process
3) Have a simple regulatory approval process for clinical use
4) Since they are not attached to protein carriers they should be much less (or non) immunogenic than antibodies
Furthermore, a key advantage of immune modulating drugs, whether targeted or not, is that only a fraction of the target cells need to be accessed in vivo for the approach to be successful.
An Adjuvanted / Targeted Nanoparticle-Based Platform for Genetic Vaccination
Scientific Relevance
The present invention is a method of enhancing the efficiency of genetic immunization.
Commercial Opportunity
Global Vaccine is projected to capture 23 billion dollars by the year 2010.
Competitive Advantage
This unique technologies targets/uses host antigen-presenting-cells, in vivo, makes them express the antigen(s) of interest and activates CD4 T helper cells.
Inventors
P. Daftarian, V. Lemmon, A. Kaifer, V. Perez, W. Li
A Nanoparticle Based Platform for Immunomonitoring upon Vaccination
Scientific Relevance
The present invention is a method of transfection of target cells for establishing immune response upon vaccination.
Commercial Opportunity
Global Vaccine that is projected to capture 23 Billion Dollars by the year 2010, relies on accurate measurement of immune responses.
Competitive Advantage
Unlike current methods for immunomonitoring, this platform not only solves the HLA compatibility but also negates the need for cocktail of epitopes. The transfected cells can be prepared using plasmid containing gene encoding for the protein used in a vaccine ahead of time, and frozen viably in multiple aliquots for subsequent use as autologous APC when co-cultured with PBMC from the same individual.
Breast cancer is the second-most common cause of mortality among women with approximately 40,000 women, but also 480 men, newly affected with this disease every year. Despite improved treatment options, breast cancer remains a devastating illness, because it can progress into metastatic disease that no longer is curable. Metastatic breast cancers are mostly triple-negative for prognostic markers that are currently used for adjuvant therapies. Therefore, there is an imminent need for the discovery of new biomarkers of triple negative breast cancer. Having a new biomarker for triple-negative breast cancer allows us to predict the likelihood of having metastatic breast disease and may enable us to develop more specific therapies to treat metastatic forms of breast cancer.
Commercial Opportunity
Triple-negative breast cancer is characterized by an early onset, highly metastatic undifferentiated tumor phenotype with poor clinical outcome and accounts for about 30% of human breast cancers. Having a new biomarker for triple-negative breast cancer holds the possibility to develop new drugs for this market.
Genetic Risk Factor for Trichotillomania and Obsessive Compulsive Disorder
Scientific Relevance
Trichotillomania (TTM), an impulse control disorder characterized by the urge to repeatedly pull out ones own body hair, and Obsessive Compulsive Disorder (OCD) are complex disorders with a strong genetic component. Rare variants in the human SAPAP3 gene have now been identified as contributing to disorders in the OCD spectrum, indicating that there is a genetic risk factor in developing these disorders.
Commercial Opportunity
Obsessive Compulsive Disorder and the spectrum of associated conditions is the fourth most commonly diagnosed mental disorder and afflicts at least one in 50 adults in the US and more than 40 million people worldwide. Trichotillomania is estimated to affect 2.5 million people in the US. The worldwide market for therapeutics used in the management of these disorders is more than $0.5 billion.
Competitive Advantage
Using genomic information will better predict the risk for developing OCD and the spectrum of associated conditions such that early intervention measures can be taken. Currently, no such approaches exist for these disorders.
Inventors
Stephan Zchner, Margaret Pericak-Vance, Michael Cuccaro, Dennis Murphy (NIH), Jens Wendland (NIH), Guoping Feng (Duke), Allison Ashley-Koch (Duke) and Ranga Krishnan (Duke)
Multilineage-inducible (MIAMI) cells and uses thereof
Scientific Relevance
MIAMI cells are one of the most homogeneous and potent stem cell populations currently available for applications in regenerative and reparative medicine.
Commercial Opportunity
MIAMI cells represent a great commercial opportunity because they can treat virtually any person that suffers from any acute/chronic condition, including aging.
Competitive Advantage
Compared to other adult stem cells on the market, MIAMI cells are a highly immature, homogeneous, potent and extensively characterized population. This gives them a stronger, more consistent and broader regenerative and reparative potential. Furthermore, the isolation of a developmentally immature adult stem cell population gives the capacity to differentiate cells into functionally mature cells found in tissues derived from all three embryonic germ layers (i.e. the three major groups of cells in the embryo that will give rise to all individual tissues in the human body). Potentially, MIAMI cells should be able to regenerate or repair virtually any human tissue when properly implanted in the organism.
Composite Bone Grafts and Constructs for Treating Joint Injuries
Scientific Relevance
A novel assembly using donor fascia lata and composite bone dowels using particulate or powdered bone materials has been made for the surgical treatment of cruciate ligaments. The anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL) are frequently subject to traumatic injury, most often related to sports activities. Damaged and ruptured cruciate ligaments of the knee (anterior and posterior) can be corrected with surgical treatment, and the current method is to use the patient's own ligaments in the reconstruction. This surgical intervention method is an effective one, but it is associated with a relatively high morbidity rate and increased operation duration to harvest and prepare the autograft.
Commercial Opportunity
Over 100,000 ACL and PCL reconstructions are performed annually in the US. In addition, it is estimated that allograft bone technology is a $1 billion market.
Competitive Advantage
Allograft material from donors is a good alternative to autograft material from the patient, as it can be used off the shelf and is relatively abundant. By using the novel surgical implant assembly, operation duration and its associated detrimental effects are substantially reduced. In addition, this construct eliminates the need for fixation of the ligament with interference screws or any other screws, pins, nails or similar entities, again, greatly minimizing the drawbacks of using these fixation devices.
System and method for molecular in vivo imaging and theranostics
Scientific Relevance
This invention allows examination of disease within the eye at a more detailed level than previously possible.
Commercial Opportunity
Characterizing tissue in vivo in the eye will help in screening and monitoring therapeutics in the eye.
Competitive Advantage
This is a method to perform in vivo diagnostic imaging of the eye.
Inventors
Richard Awdeh (Bascom Palmer Eye Institute),
Victor Perez (Bascom Palmer Eye Institute),
Adam de La Zerda (Stanford University),
Sanjiv Sam Gamhir (Stanford University)
Isolation and expansion of human natural T regulatory cells for cellular therapy
Scientific Relevance
Several subsets of T regulatory cells (Tregs) have been described in humans. These cells are of considerable interest from the viewpoint of cellular therapy in the therapeutic management of autoimmune disorders such as diabetes type 1, for short term immunosuppression in graft versus host disease, and for induction of tolerance in solid organ transplantation to prevent graft rejection. This invention allows isolation and expansion of human natural T regulatory cells in cGMP conditions for cell therapy in clinical trials.
Commercial Opportunity
Autoimmune diseases, Diabetes type I, Chronic heart failure, Graft versus host disease, graft rejection in solid organ transplantation, selective immune deficiency disease of defective nTregs are major causes of disability resulting in substantial health care expenditures.
Competitive Advantage
The resulting cell population exhibits the following properties
" Stable phenotype, without evidence of conversion or contamination.
" Potent suppressor activity
" No production of pro-inflammatory cytokines upon in-vitro stimulation
" From a single buffy coat, approximately 80 million pure nTregs can be harvested after expansion under cGMP conditions; these cell numbers are adequate for infusion of approximately one million cells Kg-1 for cell therapy in clinical trials.
