[Federal Register Volume 74, Number 40 (Tuesday, March 3, 2009)]
[Notices]
[Pages 9252-9253]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-4477]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: 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.

ADDRESSES: 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; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Dental and

[[Page 9253]]

Craniofacial 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 protected] 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[supreg] and Camptosar[supreg]) 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; 
[email protected].
    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 protected] 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; 
[email protected].

    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]
BILLING CODE 4140-01-P