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 and neurological impairment.
Commercial Opportunity
Pharmaceutical industry has been searching for a way of inhibiting GALK as a therapeutic approach for galactosemia.
Competitive Advantage
Novel and effective treatment for Classic Galactosemia will qualify as Orphan Drug according to the US Federal Orphan Drug Act (amended).
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.
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.
Papillary Muscle Attachment Device for the Purpose of Left Ventricular Reduction in Patients with Dilated Cardiomyopathy
Scientific Relevance
This invention encompasses novel minimally invasive methods and instruments to treat a common and deadly heart disease (Dilated Cardiomyopathy) that is currently difficult to treat and control. A small tether is implanted in the left ventricle chamber of the heart to prevent further abnormal expansion of the chamber.
Commercial Opportunity
Cardiomyopathy is a growing public health problem. In the United States alone, 3 million people are currently living with cardiomyopathy, and another 400,000 are diagnosed each year.
Competitive Advantage
This less invasive surgery to treat cardiomyopathy reduces the use of drugs and the risk of heart failure. The competitive treatment drugs have side effects and do not alter the course of the disease. This procedure is much less invasive than a heart transplant.
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.
Use of Tetracycline to Treat Lymphangioleiomyomatosis (LAM)
Scientific Relevance
The invention demonstrated that systemic administration of doxycycline reduces the progression of LAM, an aggressive and destructive, eventually fatal, lung disease of women by interfering with the mechanism of tissue destruction by decreasing the production of molecules involved in the progression of the disease (metalloproteases MMP-2 and MMP-9). The preclinical testing is well advanced and preliminary human clinical trials have demonstrated proof of principle in twenty patients.
Commercial Opportunity
LAM is characterized by an unusual type of muscle cell that invades the tissue of the lungs, including the airways, blood and lymph vessels. The only known cure for patients with this severe disease is lung transplantation. Over 1,000 women with LAM have been identified in the U.S.; however, the precise number of people who have LAM is unknown. Scientists who study LAM estimate that there are over 250,000 women with LAM worldwide. More recent estimates are close to 3,000,000 worldwide.
Competitive Advantage
This is the only known treatment for LAM which has the potential to delay or eliminate the need for lung transplant. While being treated in preliminary clinical testing, the patients were able to be more active and enjoyed a better quality of life.
Inventors
Marilyn K. Glassberg, Sharon J. Elliot and Michael Karl
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.
Compositions and Methods for Treating and Preventing Gastroenteric Diseases
Scientific Relevance
A novel murine neonatal model of infection with an enteric pathogenic bacterium and ensuing intestinal inflammation has been created. Because of their underdeveloped immune systems, neonatal mice are often highly susceptible to gastrointestinal pathogens. This sensitivity is associated with dampened intestinal inflammatory responses. However, neonatal mice infected with a selected gastroenteric pathogen showed enhanced survival compared to infected adults and this was associated with robust inflammation of the gut. Furthermore, the route of infectivity (orogastric vs. intraperitoneal) was also important, with enhanced survival observed only via the natural oral route of exposure. These findings are novel, indicating that protective immunity can be achieved in the intestinal tissues when neonates are first exposed.
Commercial Opportunity
Gastrointestinal diseases and their effects cause approximately 14 million deaths per year in children under the age of 5 worldwide. Therapeutic agents are usually directed to adults, and are very limited or do not exist for newborns and children.
Competitive Advantage
No other models exist for neonates that have a marked resistance to infection with a known pathogen. Therefore, this novel approach could lead to new potent vaccines and therapeutic agents for intestinal pathogens that can be administered by oral/intestinal routes, especially in newborns and children. Moreover, the findings describe a novel system for pre-clinical modeling of pediatric inflammatory bowel disease.
Inventors
Rebecca Adkins, Kurt Schesser, and Andrea Echeverry
