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.
Methods To Increase Stability of Recombinant Vaccinia-Vectored Vaccines and Increase Expression of a Foreign Gene Inserted in Such Vaccines
Description of Invention: The technology offered for licensing is in the field of vaccinia-based recombinant vaccines. In particular the invention relates to methods of stabilizing the recombinant virus, thus resulting in efficient production of the vaccine and efficient expression of the inserted gene. Stabilization of the recombinant virus is achieved by the insertion of the exogenous gene into an intergenic region (IGR) of the viral genome (i.e. Modified Vaccinia Ankara, MVA), where the IGR is flanked by open reading frames of conserved poxvirus genes. Furthermore, the invention relates to plasmids vectors useful to Start Printed Page 10287insert the exogenous DNA into the genome of a vaccinia virus. Stability can be further enhanced by incorporating silent mutations that decrease the lengths of homopolynucleotide runs in the foreign gene.
- Efficient production of vaccinia-vectored vaccines for infectious diseases and other diseases such as cancer.
- Efficient production of therapeutic proteins from vaccinia-vectored exogenous genes.
- Enhancing stability of foreign genes in vaccinia-vectored constructs.
- Increasing efficiency of vaccine production and gene expression.
Development Status: The invention is fully developed.
Market: Vaccines development based on vaccinia (e.g. MVA) vector inserted with foreign gene of immunologic or therapeutic interest has become one of the most promising approaches for vaccine development. Several companies established vaccine development programs based on this approach and many research laboratories around the world conduct research in the area. Improvements in the production process and in production yields, such as provided by the subject invention, are therefore of great significance for successful accomplishments in this area. Commercial products for veterinary use already exist. Many applications for human use are now in various stages of clinical trials, in particular applications for HIV, HPV in the infectious disease area and as therapeutic vaccine in the cancer field. The market potential for the subject technology is therefore vast.
Inventors: Bernard Moss et al. (NIAID).
Related Publication: LS Wyatt, PL Earl, W Xiao, J Americo, C Cotter, J Vogt, B Moss. Elucidating and minimizing the loss by recombinant vaccinia virus of human immunodeficiency virus gene expression resulting from spontaneous mutations and positive selections. J Virol. 2009 Jul;83(14):7176-7184. [PubMed: 19420086].
Patent Status: U.S. Provisional Application No. 61/252,326 filed October 16, 2009, entitled “Plasmid Shuttle Vector for Insertion of Foreign Genes into Del III Site of Modified Vaccinia Ankara (MVA) to Increase Stability of Foreign Gene Expression in This Site” (HHS Reference No. E-018-2010/0-US-01).
- WO 2008/142479 A2 (PCT/IB2007/004575)—“Intergenic Sites between Conserved Genes In The Genome of Modified Vaccinia Ankara (MVA) Vaccinia Virus,” Bernard Moss et al.
- US Patent 6,998,252; US Patent 7,015,024; US Patent 7,045,136; US Patent 7,045,313—“Recombinant Vaccinia Virus Containing a Chimeric Gene Having Foreign DNA Flanked by Vaccinia Regulatory DNA,” Bernard Moss et al.
Licensing Status: Available for licensing.
Compounds That Interfere With the Androgen Receptor Complex: Use in Treating Prostate Cancer or Enlargements, Diabetes, and as Contraceptives
Description of Invention: Investigators at the National Institutes of Health (NIH) have discovered compounds that have potential as novel anti-androgen therapeutics. The immunophilin protein FKBP52 is part of a protein complex that helps fold the androgen receptor (AR) protein, a target for treating prostate cancer, and enhances its activity. Disruption of the FKPB52-AR interaction greatly reduces the activity of the AR. With the goal of finding potential therapeutic compounds that inhibit the FKBP52-mediated activation of AR, several small molecules were tested and found to be antagonists of FKBP52 and to inhibit AR activity in prostate cells. These compounds can serve as therapeutics for the treatment of prostate cancer and benign prostate enlargement. Moreover, FKBP52 is also implicated in the regulation of other hormone receptors so these compounds could be used to treat other hormone-dependent diseases such as diabetes or even used as contraceptives.
One of the standard treatments for prostate cancer makes use of anti-androgens, like bicalutamide, which compete for binding with the natural male hormones to AR and inhibit their proliferative activity. The problem with available anti-androgen drugs is that prostate tumors eventually become drug resistant resulting in so-called androgen-resistant prostate cancer. One cause of this is an increase in the levels of AR produced by the prostate cancer cells. A solution to this problem may lie in disrupting the protein folding of AR by interfering with its interaction with FKBP52 using these compounds.
- Use of the compounds for treatment of prostate cancer and benign prostate enlargement
- Use of the compounds in treating insulin-independent diabetes
- Use of the compounds as male or female contraceptives
- Use in screening for compounds that inhibit of FKBP52-enhanced AR activity
- The compounds do not compete with androgens and specifically inhibit FKBP52-enhanced AR function
- Potential for synergistic use with conventional anti-androgens for treatment of androgen resistant prostate cancer
Development Status: Pre-clinical.
Market: Prostate cancer is the second most common type of cancer among men in the United States and is the second leading cause of cancer death in men. It was estimated that in 2009 there would be 192,280 new cases and 27,360 deaths from prostate cancer in the U.S. The prevalence of benign prostate enlargement is much greater as 50% men age 50 are affected and continues to increase with age.
Diabetes is a growing health problem in the U.S. and the world. The most recent estimate (2007 National Diabetes Fact Sheet) in the U.S. was that 7.8% of the population had diabetes and 1.6 million new cases per year would be diagnosed. In the population of people over 60 the prevalence of diabetes is even higher (23%).
Among the 64 million women of reproductive age in the U.S., the leading contraceptive method is hormonal contraceptives. Presently, there are no hormonal contraceptives to reversibly block fertility in men and there is a need for safe and effective hormonal methods as exist for women.
Inventors: Leonard M. Neckers (NCI), Marc Cox (UTEP) et al.
Relevant Publication: J Cheung-Flynn et al. Physiological role for the cochaperone FKBP52 in androgen receptor signaling. Mol Endocrinol. 2005 Jun;19(6):1654-1666. [PubMed: 15831525].
Patent Status: U.S. Provisional Application No. 61/242,541 filed 15 Sep 2009 (HHS Reference No. E-162-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Sabarni Chatterjee, Ph.D.; 301-435-5587; email@example.com.
Collaborative Research Opportunity: The Center for Cancer Research, Urologic Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize antagonists of FKBP52-dependent remodeling of the androgen Start Printed Page 10288receptor. Please contact John D. Hewes, Ph.D. at 301-435-3121 or firstname.lastname@example.org for more information.
Radioprotectants and Tumor Radiosensitizers Targeting Thrombospondin-1 and CD47
Description of Invention: Radiation therapy not only damages cancer cells, but it also damages healthy cells and can cause serious side effects for patients. One effort to enhance the therapeutic potential of radiotherapy, while reducing its detrimental effects on normal tissue and maintaining tumor sensitivity, is centered upon the development of radioprotective agents.
NIH inventors previously discovered that when the secreted protein, thrombospondin-1 (TSP1) binds to its receptor CD47, this signaling pathway prevents nitric oxide from dilating blood vessels and increasing blood flow to organs and tissues. They found that blocking TSP1-CD47 interaction through the use of antisense morpholino oligonucleotides, peptides or antibodies has several therapeutic benefits; one of them being increased blood flow to ischemic tissues.
In the present technology, the inventors discovered that hindlimb irradiated TSP1 and CD47 null mice have less hair loss, and decreased cell death in muscle and bone marrow than untreated TSP1 and CD47 null mice. They also discovered that when irradiated human vascular cells are treated with antibodies towards TSP1 or CD47, viability and proliferative capacity are preserved. Furthermore, the inventors determined that irradiation of wild type mice following treatment with CD47 antisense morpholino resulted in decreased apoptosis in irradiated tissues at 24 hours, preservation of hematopoietic stem cell proliferative capacity in irradiated bone marrow, and less alopecia, ulceration, and desquamation at the end of eight weeks. These results led the inventors to propose that antagonists of TSP1 and/or CD47 preserve cell viability and tissue function following radiation treatment, and these antagonists may be useful as radioprotective agents to reduce side effects associated with radiation therapy. Remarkably, the same treatment dramatically enhanced the delay in melanoma and squamous carcinoma tumor regrowth following irradiation. Thus, these agents are radioprotective agents for normal tissue but radiosensitizers for tumor tissue.
The present technology describes the use of morpholinos, peptides and antibodies that block the TSP1/CD47 signaling pathway as radioprotectants for normal tissue, radioenhancers for tumor tissue, and methods of selectively protecting normal tissue from damage caused by radiation exposure by contacting the tissue with these agents.
- Protect normal tissue from damage following radiation therapy.
- Enhance tumor responses to radiotherapy.
- Enable use of higher therapeutic doses for radiotherapy of cancer.
- Protect personnel from radiation injuries resulting from occupational exposure to ionizing radiation, military exposure, or terrorist acts.
Development Status: Mouse data available. In vitro data available in mouse, bovine, porcine, and human cells.
Inventors: Jeffery S. Isenberg, David D. Roberts, Justin B. Maxhimer (NCI)
1. JB Maxhimer, DR Soto-Pantoja, LA Ridnour, HB Shih, WG DeGraff, M Tsokos, DA Wink, JS Isenberg, DD Roberts. Radioprotection in normal tissue and delayed tumor growth by blockade of CD47 signaling. Sci Transl Med. 21 October 2009; Vol 1, Issue 3, pg. 3ra7; DOI:10.1126/scitranslmed.3000139.
2. JS Isenberg, G Martin-Manso, JB Maxhimer, DD Roberts. Regulation of nitric oxide signaling by thrombospondin-1: implications for anti-angiogenic therapies. Nat Rev Cancer. 2009 Mar;9(3):182-194. [PubMed: 19194382]
3. JS Isenberg, JB Maxhimer, F Hyodo, ML Pendrak, LA Ridnour, WG DeGraff, M Tsokos, DA Wink, DD Roberts. Thrombospondin-1 and CD47 limit cell and tissue survival of radiation injury. Am J Pathol. 2008;173(4):1100-1112. [PubMed: 18787106]
Patent Status: PCT/US2009/052902 filed 05 Aug 2009 (HHS Reference No. E-153-2008/0-PCT-02).
Licensing Status: Available for licensing.
Licensing Contact: Charlene A. Sydnor, Ph.D.; 301-435-4689; email@example.com.
Collaborative Research Opportunity: The Center for Cancer Research, Laboratory of Pathology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize CD47-targeting agents as radioprotectants and tumor sensitizers. Please contact John D. Hewes, Ph.D. at 301-435-3121 or firstname.lastname@example.org for more information.
Mouse Lacking the Chemokine Receptor CX3CR1
Description of Invention: This mouse has been generated by targeted gene disruption. The mouse provides a model to investigate the function of the chemokine receptor CX3CR1, which is a proinflammatory receptor for the leukocyte chemoattractant CX3CL1 (aka fractalkine). As an example, the mouse is in use in the study of atherosclerosis. Further, the mouse may serve as a model study the role of the immune system during infection with pathogens as well as other immunologically mediated diseases and responses to tumors.
Inventors: Philip Murphy, Christopher Combadière, Ji-liang Gao (NIAID).
Related Publication: C Combadière et al. Decreased atheroscelerotic lesion formation in CX3R1/ApoE double knockout mice. Circulation 2003 Feb 25;107(7):1009-1016. [PubMed: 12600915].
Patent Status: HHS Reference No. E-216-2003/0—Research Tool. Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a biological materials license.
Licensing Contact: Susan Ano, Ph.D.; 301-435-5515; email@example.com.
Oligonucleotides Which Specifically Bind Retroviral Nucleocapsid Proteins
Description of Invention: The human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). A retroviral protein species, the gag polyprotein, is involved in the assembly of retrovirus particles and capable of specific interactions with nucleic acids. After the virion is released from the cell, the polyprotein is cleaved by the virus-encoded protease. One of the cleaved products, the nucleocapsid (NC) protein, then binds to genomic RNA, forming the ribonucleoprotein core of the mature particle. The interaction between gag and genomic RNA is known to involve the NC domain of the polyprotein. In addition, the NC protein plays crucial roles in both the reverse transcription and integration steps in the viral life cycle.
The present invention relates to retroviral nucleocapsid proteins, such as NC and the gag precursor, and their ability to bind to specific nucleic acid sequences with high affinity. The high affinity of this interaction has potential applications in the design of new antiviral approaches and in sensitive detection of HIV particles. Accordingly, the invention provides for oligonucleotides which bind to nucleocapsid proteins with high affinity, molecular decoys for retroviral nucleocapsid proteins which inhibit viral replication, targeted molecules Start Printed Page 10289comprising high affinity oligonucleotides, assays for selecting test compounds, and related kits.
Inventors: Alan R. Rein et al. (NCI).
Patent Status: U.S. Patent No. 6,316,190 issued 13 Nov 2001 (HHS Reference No. E-107-1996/0-US-06).
Licensing Status: Available for licensing.
Licensing Contact: Sally Hu, PhD; 301-435-5606; firstname.lastname@example.org.Start Signature
Dated: March 1, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.
[FR Doc. 2010-4757 Filed 3-4-10; 8:45 am]
BILLING CODE 4140-01-P