Notice: Government-Owned Inventions; Availability for Licensing

Federal Register: January 7, 2010 (Volume 75, Number 4)              
                  Page 989-990

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

ACTION: Notice.

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.

Method of Preventing and Treating Metastatic Disease

    Description of Technology: Cancer that recurs as metastatic disease 
many years after primary tumor resection and adjuvant therapy appears 
to arise from tumor cells that disseminated early in the course of 
disease but did not develop into clinically apparent lesions. These 
long-term surviving, disseminated tumor cells maintain a state of 
dormancy, but may be triggered to proliferate through largely unknown 
factors. Inventors at the National Institutes of Health have discovered 
agents that prevent or treat recurrent metastatic cancer by inhibiting 
type I collagen production and downstream signaling through beta 1 
integrin activation. Blocking activation of beta-1 integrin signaling 
using pharmacological approaches or using RNA interference was found to 
prevent reorganization of the cytoskeleton that is associated with 
proliferation of the dormant tumor cells. The technology provides 
compositions and methods for modulating the switch from tumor cell 
dormancy to proliferation clinical metastatic disease in a patient by 
administering beta-1 integrin signaling inhibitors.

Applications

     Method of treating metastatic disease by targeting 
components of the beta-1 integrin signaling pathway.
     Method of preventing metastatic disease after removal of 
primary tumors.
    Advantage: Discovery of beta-1 integrin signaling pathway 
involvement provides a number of therapeutic targets for development of 
novel cancer therapeutics.
    Market: In the U.S., it is estimated that 192,370 women will be 
diagnosed with and 40,170 women will die of cancer of the breast in 
2009. Although improved detection and treatment of primary tumors has 
raised the rate of survival there remains a high probability of 
recurrence of metastatic disease leading to mortality.
    Inventors: Dalit Barkan and Jeffrey E. Green (NCI).
    Publications: None related to this technology.
    Patent Status: U.S. Provisional Application No. 61/179,641 filed 19 
May 2009 (HHS Reference No. E-192-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD, 301-435-4076; 
vathyams@mail.nih.gov.
    Collaborative Research Opportunity: The Center for Cancer Research, 
Laboratory of Cancer Biology and Genetics, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize this 
technology. Please contact John D. Hewes, PhD at 301-435-3121 or 
hewesj@mail.nih.gov for more information.

Diamidine Inhibitors of Tdp1 as Anti-Cancer Agents

    Description of Technology: Available for licensing and commercial 
development are methods and compositions for treating cancer, using 
novel compounds derived from diamidine. Diamidine and its derivatives 
are potent inhibitors of tyrosyl-DNA-phosphodiesterase (Tdp1). which 
may be useful in chemotherapy.

[[Page 990]]

    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. Thus, the 
presence and activity of Tdp1 can reduce the effectiveness of 
camptothecins as anticancer agents. In addition, Tpd1 repairs free-
radical-mediated DNA breaks.
    Inhibition of Tpd1 using diamidine or its derivatives. may reduce 
repair of DNA breaks and increase the rate of apoptosis in cancer 
cells. In addition. diamidine derivatives have the potential to enhance 
the anti-neoplastic activity of Top1 inhibitors, by reducing repair of 
Top1-DNA lesions through inhibition of Tdp1.
    Development Status: Pre-clinical stage.
    Inventors: Yves G. Pommier and Christoph Marchand (NCI).

Publications

    1. Z Liao et al. Inhibition of human tyrosyl-DNA 
phosphodiesterase 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. Patent Application No. 12/225,672 filed 26 Sep 
2008 (HHS Reference No. E-165-2006/0-US-04).
    Licensing Status: Available for licensing.
    Licensing Contact: Betty Tong, PhD; 301-594-6565; 
tongb@mail.nih.gov.
    Collaborative Research Opportunity: The Laboratory of Molecular 
Pharmacology is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize Tdp1 inhibitors for the treatment of 
cancers. Please contact John D. Hewes, PhD at 301-435-3121 or 
hewesj@mail.nih.gov for more information.

    Dated: December 23, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-31284 Filed 1-6-10; 8:45 am]

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