National Institutes of Health, Public Health Service, HHS.
The inventions listed below are owned by an agency of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected inventions to extend market coverage for companies and may also be available for licensing.
Licensing information and copies of the U.S. patent applications listed below may be obtained by writing to the indicated licensing contact at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301-496-7057; fax: 301-402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.
Improved Standard for Immune System Recovery Assay
Description of Invention: Monitoring an immune system that has been depleted by infection (e.g., HIV), chemotherapy, or progenitor cell transplantation is vital to assessing individual's recovery status. This technology provides a new plasmid standard to be used as part of the existing TREC assay. This new plasmid has a shorter insert than the commercially available one, which means it now matches the PCR product generated in the qPCR reaction in the TREC assay. Additionally, the new plasmid is easier to grow up than the existing standard.
Applications: TREC assay for T-cell concentration measurements.
- The insert of standard plasmid is shorter and directly matches the PCR product generated in the qPCR reaction.
- The standard plasmid is easy to grow up.
Development Status: Fully developed.
Inventors: Daniel C. Douek, Richard A. Koup, Brenna J. Hill (NIAID.)
1. Douek et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998 Dec 17;396(6712):690-695. [PubMed: 9872319.]
2. Douek et al. Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution. Lancet 2000 May 27;355(9218):1875-1881. [PubMed: 10866444.]
Patent Status: HHS Reference No. E-067-2011/0—Research Material. Patent protection is not being pursued for this technology.
Licensing Status: Research tool available for non-exclusive licensing.
Licensing Contact: Susan Ano, Ph.D.; 301-435-5515; firstname.lastname@example.org.
Glucocerebrosidase Activators as a Treatment for Gaucher Disease
Description of Invention: This technology is a collection of small molecule activators of a genetically defective version of the enzyme called glucocerebrosidase (GCase), which causes Gaucher disease. Gaucher disease is a rare disease affecting 1 in 40,000 babies born. Ashkenazi Jews of eastern European descent (about 1 in 800 live births) are at particular risk of carrying this genetic defect. It is caused by inherited genetic mutations in the gene that encodes GCase, which result in reduced activity of the enzyme. This enzyme is normally made and then transported to an organelle called a lysosome, which is dedicated to the degradation and disposal of molecules the cell no longer needs. GCase is responsible for the breakdown of a fatty material called glucocerebroside (or glucosylceramide). The accumulation of this lipid occurs inside specific cells called macrophages and macrophage-derived cells. The disease has been categorized into three types: neuronopathic (types 2, 3) and non-neuronopathic (type 1) with mild to severe symptoms that can appear at anytime from infancy to adulthood. Clinical manifestations can include an enlarged spleen and liver, anemia, decreased platelets, bone disease and neurodegeneration, with varying severity depending on the type of disease and time of diagnosis. The deficient GCase activity has been attributed to insufficient GCase enzyme in the lysosome. After production in the endoplasmic reticulum (ER), defective GCase does not fold properly and is therefore degraded in the ER and not transported to the lysosome where it would hydrolyze glucocerebroside. The small molecule activators may act by increasing the concentration of GCase that reaches the lysosome by facilitating the proper folding of GCase so that it can be released from the ER and transported to lysosomes. Thus, these small molecules could be acting like “chaperones,” because they facilitate proper folding which results in some active enzyme. Prior failed attempts to use small molecule chaperones to improve GCase folding and transport were made with inhibitors of GCase, which ironically properly folded active GCase that was subsequently transported to the lysosome, but the molecule also inhibited the GCase co that it could not break down glucocerebroside. On the other hand, these proposed small molecules were Start Printed Page 25698screened for their ability to activate defective GCase in the presence of a fluorogenic mimic of glucocerebroside, and their ability to facilitate translocation of defective GCase to lysosomes as well. This creates the opportunity to induce proper folding, while avoiding inhibition of enzyme function.
Application: Treatment of Gaucher Disease.
Development Status: Early development.
Inventors: Juan Marugan, Noel T. Southall, Ehud M. Goldin, Wei Zheng, Samarjit Patnaik, Ellen Sidransky, Omid Motabar, Wendy Westbroek (NHGRI.)
Related Publications: None.
Patent Status: U.S. Provisional Application No. 61/420,946, filed December 8, 2010, (HHS Reference No. E-257-2010/0-US-01.)
Licensing Status: Available for licensing.
Licensing Contact: Steve Standley, PhD; 301-435-4074; email@example.com.
A Novel Strategy for Development of an Effective HIV/AIDS Vaccine
Description of Invention: The invention offered for licensing and commercial development relates to the field of HIV/AIDS Vaccines. More specifically, the invention describes a novel strategy that can be useful in effective vaccination and treatment of HIV/AIDS infected persons. In this strategy (called ‘trigger-and-neutralize’ strategy) the infected subject is primed with HIV trimeric gp 120 immunogen to induce the production of CD4i (CD4-induced) antibodies. The patient is then treated with a compound that stabilizes the ‘open’ conformation of the gp120 of the HIV virus, at which conformation the gp120 epitope is better exposed and effectively neutralized by the CD4i antibodies.
Applications: Vaccination and treatment of HIV/AIDS infected patients.
Advantages: The unique strategy of eliciting CD4i antibodies in vivo and ensuring their neutralizing effect by stabilizing the gp120 open conformation, will provide more effective treatment compared to other published methods that utilize neutralizing antibodies to treat HIV/AIDS.
Development Status: The subject matter of the invention continues to be researched. Proof-of-principle of some of the aspects of the invention have been demonstrated.
Market: Although there are currently many commercial drugs available for treatment of HIV/AIDS, there still exists an urgent need to develop vaccines against the disease. This need (no approved vaccine is available yet) is particularly important because of the resistance developed by many patients to commercial drugs and thus the need for the use of drug cocktails, as well as the severe side effects that many of the drugs exhibit. At present, the World Health Organization estimates that over 30 million people are infected with HIV and that over 25 million individuals have died from AIDS-related illnesses. The potential market for HIV vaccines is therefore huge and thus this invention may be commercially attractive for vaccine and drug manufacturers.
Inventors: Sriram Subramaniam (NCI.)
1. Liu J, Bartesaghi A, Borgnia MJ, Sapiro G, Subramaniam S. Molecular architecture of native HIV-1 gp120 trimers. Nature. 2008 Sep 4;455(7209):109-113. [PubMed: 18668044.]
2. White TA, Bartesaghi A, Borgnia MJ, Meyerson JR, M. de la Cruz MJ, Bess JW, Nandwani R, Hoxie JA, Lifson JD, Milne JL, Subramaniam S. Molecular architectures of trimeric SIV and HIV-1 envelope glycoproteins on intact viruses: strain dependent variation in quaternary structure. PLoS Pathog. 2010 Dec 23;6(12):e1001249. [PubMed: 21203482.]
3. Felts RL, Narayan K, Estes JD, Shi D, Trubey CM, Fu J, Hartnell LM, Ruthel GT, Schneider DK, Nagashima K, Bess JW Jr, Bavari S, Lowekamp BC, Bliss D, Lifson JD, Subramaniam S. 3D visualization of HIV transfer at the virological synapse between dendritic cells and T-cells. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13336-13341. [PubMed: 20624966.]
Patent Status: U.S. Provisional Application No. 61/356,326 filed 18 Jun 2010 (HHS Reference No. E-201-2010/0-US-01), entitled “Immunogenic Compositions Derived from Structural Alteration of HIV Envelope Proteins.”
Licensing Status: Available for licensing and commercial development.
- Uri Reichman, PhD, MBA; 301-435-4616; UR7a@nih.gov.
- John Stansberry, PhD; 301-435-5236; firstname.lastname@example.org.
Collaborative Research Opportunity: The Center for Cancer Research, NCI/NIH is seeking statements of capability or interest from parties interested in collaborative research to further develop, produce, evaluate, or commercialize trimeric gp120 immunogens. Please contact John Hewes, PhD at 301-435-3121 or email@example.com for more information.
Epoxy-guaiane Cancer Inhibitors: New Class of Natural Products Isolated From the African Plant Phyllanthus englerii
Description of Invention: The present invention involves the observation of renal selective inhibitory activity by the extracts of the African plant Phyllanthus englerii. Bioassay-guided fractionation of the purified extracts revealed a series of novel chemical entities which are named Englerin A-F. The englerins and their derivatives are useful in the treatment of a number of cancers, particularly renal cancer. The englerins exhibit selective and potent renal cell inhibitory activity in vitro.
These compounds are recoverable in reasonable yield from natural product extracts and are considered to be reasonably tractable for synthetic chemistry schemes. Sufficient supply of several analogs had been extracted from repository samples for identification and initial biological characterization. Subsequent five-dose testing in the NCI60 screening panel indicated and confirmed impressive renal-selective activity.
Applications: The new chemical entities can be potential cancer therapeutics, especially for renal cancer.
- There is reasonable yield and recovery of the compounds from the natural product extracts.
- The synthetic chemistry schemes for synthesis of these compounds are considered to be reasonably tractable.
Development Status: Proof of concept in vitro studies have been completed and further in vitro and in vivo animal model studies are ongoing.
Inventors: John A. Beutler et al. (NCI)
Relevant Publication: S. Sutthivaiyakit et al. A novel 29-nor-3,4-seco-friedelane triterpene and a new guaiane sesquiterpene from the roots of Phyllanthus oxyphyllus. Tetrahedron 2003 Dec 8; 59(50):9991-9995.
Patent Status: U.S. Patent Application No. 12/811,245 filed 29 Jul 2010 (HHS Reference No. E-064-2008/2-US-06) and related international filings.
Licensing Status: Available for licensing.
Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; firstname.lastname@example.org.
Collaborative Research Opportunity: The National Cancer Institute Molecular Targets Development Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize epoxy-guaiane cancer inhibitors. Please contact John D. Hewes, PhD at 301-435-3121 or email@example.com for more information.Start Printed Page 25699
Imidazoacridones With Anti-Tumor Activity
Description of Invention: The present invention relates to novel bifunctional molecules with potent and selective activity against colon, liver and pancreatic tumors. Compounds have low animal toxicity, excellent PK/PD characteristics and proved to be very effective in several preclinical animal models of cancer. Extensive mechanistic studies have demonstrated that compounds inhibit tumor growth through a novel mechanism. These agents are composed of an imidazoacridone moiety linked by a nitrogen containing aliphatic chain of various length and rigidity to another aromatic ring system capable of intercalation to DNA.
Previous studies on related symmetrical bis-imidazoacridones revealed that only one planar imidazoacridone moiety intercalates into DNA. The second aromatic moiety, which is crucial for biological activity, along with the linker resides in DNA minor groove, and is believed to interact with DNA-binding proteins (most likely, transcription factors and/or repair proteins). The symmetrical bis-imidazoacridones arrest the growth of sensitive cancers (especially colon cancers) but do not kill the tumors. It was hypothesized that the growth arrest was due to the inability of the affected tumor cells to repair DNA damage caused by the compounds. Remarkably, bis-imidazoacridones are very well tolerated, are very tissue selective and do not appear to damage normal tissues.
Since the binding of the symmetrical bis-imidazoacridones to DNA was unsymmetrical, the inventors have developed unsymmetrical compounds in which one imidazoacridone moieties was replaced by other intercalating groups, with the expectation that this would enhance biological activity while retaining the remarkable tissue selectivity and low systemic toxicity. The new compounds contain intercalating moieties such as 3-chloro-7-methoxyacridine or naphthalimide along with the original imidazoacridones.
These new compounds, especially those containing naphthalimide moiety, are extremely cytotoxic against a variety of tumor cells in vitro (IC50 at low nanomolar range) and kill tumor cells by inducing apoptosis. In vivo, in nude mice xenografted with human tumors, the compounds significantly inhibited the growth of such tumors as colon tumor HCT116 and Colo205 as well as pancreatic tumors (lines 6.03 and 10.05 freshly established from a patient). These compounds are extremely potent agents against hepatocellular carcinoma as evidenced by their ability to eradicate liver cancer in an orthotopic liver cancer model in rats. Remarkably, no toxicity was observed at the therapeutic doses. These are among the most potent agents known against cancers of the GI tract and appear to be tolerated very well.
Inventors: Wieslaw M. Cholody et al. (NCI)
- U.S. Patent 6,664,263 issued 16 Dec 2003 (HHS Reference No. E-289-1999/0-US-07) and related international patents/patent applications.
- U.S. Patent 6,541,483 issued 01 Apr 2003 (HHS Reference No. E-065-1996/2-US-25) and related international patents/patent applications.
Licensing Status: Available for licensing.
Licensing Contact: Betty B. Tong, PhD; 301-594-6565; firstname.lastname@example.org.
Collaborative Research Opportunity: The National Cancer Institute, Center for Cancer Research, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize imidazoacridones as therapeutic agents for cancer treatment. Please contact John Hewes, PhD at 301-435-3121 or email@example.com for more information.Start Signature
Dated: April 29, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.
[FR Doc. 2011-11055 Filed 5-4-11; 8:45 am]
BILLING CODE 4140-01-P