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.
Prevention of Head and Neck Cancer Using Rapamycin and Its Analogs
Description of Technology: It is frequently observed in head and neck squamous cell carcinoma (HNSCC), a cancer occurring mostly in the mouth, that the Akt/mTOR pathway is abnormally activated. Therefore, inhibiting this signaling pathway may help in treating this disease. Rapamycin and its analogs are known to inhibit the activity of mTOR so in principle they could serve as therapeutics for treating HNSCC.
Researchers at the NIH have developed a method of potentially preventing or treating HNSCC through the inhibition of mTOR activity. The proof of this principle was demonstrated by rapid regression of mouth tumors in mice afflicted with Cowden syndrome with the administration of rapamycin. Like HNSCC, development of this disease is linked to over activation of the Akt/mTOR pathway. Furthermore, the therapeutic potential of rapamycin was demonstrated using mice in experiments that model chronic exposure to tobacco, which promotes the development of HNSCC. Therefore, inhibitors of mTOR have considerable potential in the prevention and treatment of HNSCC.
Applications: Preventing the development of oral cancer using mTOR inhibitors to halt progression of pre-cancerous lesions.
Market: Approximately 500,000 new cases of squamous cell carcinomas of the head and neck arise every year making it the 6th most common cancer in the world.
Frequently, prognosis is poor due to late detection of cancer.
Development Status: Pre-clinical proof of principle.
Inventors: J. Silvio Gutkind et al. (NIDCR).
Publications: 1. CH Squarize, RM Castilho, JS Gutkind. Chemoprevention and treatment of experimental Cowden's disease by mTOR inhibition with rapamycin. Cancer Res. 2008 Sep 1;68(17):7066-7072.
2. R Czerninski, P Amornphimoltham, V Patel, AA Molinolo, JS Gutkind. Targeting mTOR by rapamycin prevents tumor progression in an oral-specific chemical carcinogenesis model. Cancer Prevention Res. 2009 Jan;2(1):27-36.
Patent Status: U.S. Patent Application No. 61/090/414 filed 20 Aug 2008 (HHS Reference No. E-302-2008/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Whitney Hastings; 301-451-7337; firstname.lastname@example.org.
Collaborative Research Opportunity: The National Institute of Dental and Start Printed Page 9253Craniofacial Research, Oral and Pharyngeal Cancer Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David W. Bradley, PhD at email@example.com for more information.
Use of Tetracyclines as Anti-Cancer Agents
Description of Technology: The invention describes compositions of tetracycline compounds and their derivatives as having anti-cancer activity, as well as methods of treating cancer. Tetracyclines are commonly used as antibiotics; however, testing of these compounds in a high throughput screening system revealed certain derivatives to be potent inhibitors of tyrosyl-DNA-phosphodiesterase (Tdp1).
Camptothecins are effective Topoisomerase I (Top1) inhibitors, and two derivatives (Topotecan® and Camptosar®) are currently approved for treatment of ovarian and colorectal cancer. Camptothecins damage DNA by trapping covalent complexes between the Top1 catalytic tyrosine and the 3=-end of the broken DNA. Tdp1 repairs Top1-DNA covalent complexes by hydrolyzing the tyrosyl-DNA bond. This can reduce the effectiveness of camptothecins as anti-cancer agents. In addition, Tdp1 repairs free-radical-mediated DNA breaks.
As disclosed in the instant technology, tetracyclines have the potential to enhance the anti-neoplastic activity of Top1 inhibitors by reducing repair of Top1-DNA lesions through inhibition of Tdp1. Inhibition of Tdp1 may also reduce repair of DNA breaks and increase the rate of apoptosis in cancer cells, making them potential anti-cancer agents on their own.
Development Status: Pre-clinical stage.
Inventors: Yves Pommier, Christophe Marchand, Laurent Thibaut (NCI).
Publications: 1. Z Liao et al. Inhibition of human tyrosyl-DNA phosphodiesterase (Tdp1) by aminoglycoside antibiotics and ribosome inhibitors. Mol Pharmacol. 2006 Jul;70(1):366-372.
2. Y Pommier. Camptothecins and topoisomerase I: A foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: Importance of DNA replication, repair and cell cycle checkpoints. Curr Med Chem Anticancer Agents. 2004 Sep;4(5):429-434. Review.
3. Y Pommier et al. Repair of and checkpoint response to topoisomerase I mediated DNA damage. Mutat Res. 2003 Nov 27;532(1-2):173-203. Review.
Patent Status: U.S. Provisional Application No. 60/786,746 filed 27 Mar 2006 (HHS Reference No. E-097-2006/0-US-01).
International Application No. PCT/US2007/007724 filed 27 Mar 2007 (HHS Reference No. E-097-2006/0-PCT-02).
U.S. Patent Application No. 12/241,011 filed 29 Sep 2008 (HHS Reference No. E-097-2006/1-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Betty Tong, PhD; 301-594-6565; firstname.lastname@example.org.
Collaborative Research Opportunity: The Laboratory of Molecular Pharmacology at the National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize tetracycline derivatives, particularly optimizing them for therapeutic use. Please contact John D. Hewes, PhD at 301-435-3121 or email@example.com for more information.
Glutathione S-transferase Clones for Members of the Ubiquitin-Dependent Protein Degradation Pathway
Description of Technology: Scientists at the National Institutes of Health have developed cDNA for glutathione S-transferase (GST) clones for the following factors: Nedd4, XIAP, UBCH5B, and CBL-B. These proteins are involved in the ubiquitin-dependent pathway of protein degradation in cells, the major cellular system for protein degradation. The ubiquitin-proteosome pathway regulates several cancer regulated proteins. Defects in this pathway can lead to cancer development. The GST clones can be used to produce corresponding GST fusion proteins in order to isolate each protein from the pathway for further analysis. These constructs can also be incorporated into assays/kits to detect proteins in the ubiquitin-dependent pathway.
Applications: Research tools for detection and isolation of ubiquitin-dependent pathway members in order to understand the pathway defects that lead to cancer and develop preventions and treatments to overcome these defects.
Research tools for generating fusion proteins of Nedd4, XIAP, UBCH5B, and CBL-B to further analyze their functions in vivo and in vitro.
Controls for screening inhibitors of the ubiquitin-dependent pathway in order to better understand the different mechanisms of ubiquitin-dependent protein degradation.
Inventors: Allan M. Weissman et al. (NCI).
Patent Status: HHS Reference No. E-245-2003/0—Research Tool. Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a Biological Materials License Agreement.
Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; firstname.lastname@example.org.Start Signature
Dated: February 24, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.
[FR Doc. E9-4477 Filed 3-2-09; 8:45 am]
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