[Federal Register Volume 68, Number 228 (Wednesday, November 26, 2003)]
[Notices]
[Page 66466]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-29492]


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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, DHHS.

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.

Geldanamycin Derivatives With Methyl Substituted Hydrogen Atom at the 
N22 Position as Anti Cancer Agents

    Yong-Sok Lee, Leonard Neckers, Monica Marcu (NCI).
    U.S. Provisional Patent Application No. 60/508,752 filed 03 Oct 
2003 (DHHS Reference Nos. E-169-2003/0-US-01).
    Licensing Contact: George Pipia; 301/435-5560; [email protected].
    This invention is directed to an N22-methyl substituted derivatives 
of geldanamycin. Modeling studies have shown that providing a methyl 
substituent in the N22 position of geldanamycin derivatives stabilizes 
the cis-conformation of the compounds. From computer modeling and 
mutational studies inventors concluded that the active form of 
geldanamycin interacting with heat shock protein 90 (Hsp90) has the 
amid bond in cis-configuration, which is energetically less stable than 
in trans-configuration. Using computer-modeling investigators have 
further demonstrated that methyl substitution at the N22 position of 
geldanamycin stabilizes the cis-derivatives of geldanamycin. These 
compounds are currently being synthesized at NCI. These compounds are 
expected to have an increased binding to and inhibition of Hsp90. 
Inhibition of Hsp90 is being investigated in the treatment of many 
cancers.

Degradation and Transcriptional Inhibition of HIF-2alpha Protein by 17-
AAG

    Jennifer Isaacs, Leonard Neckers (NCI).
    U.S. Provisional Patent Application No. 60/508,795 filed 03 Oct 
2003 (DHHS Reference No. E-064-2003/0-US-01).
    Licensing Contact: George Pipia; 301/435-5560; [email protected].
    The technology is directed to the use of 17-allylaminogeldanamycin 
(17-AAG) and, by analogy, other geldanamycin derivatives to inhibit the 
activity of hypoxia inducible factor-2a (HIF-2a). HIF-2a is thought to 
play an important role in tumor growth in the lung and endothelium, and 
is overexpressed in a majority of renal carcinomas. Accordingly, the 
technology suggests the use of 17-AAG and other geldanamycin 
derivatives to reduce levels of HIF-2a in cells that overexpress the 
protein, for example to treat cancer. According to the lead inventor, 
HIF-2a plays a central role behind the mechanism of action of 
geldanamycin in renal cancer. The inventors also predict that certain 
geldanamycin derivatives will have therapeutic benefit in tumors 
overexpressing HIF-2a, and that those derivatives could also find 
therapeutic utility in clinical conditions involving 
hypervascularization.

    Dated: November 13, 2003.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 03-29492 Filed 11-25-03; 8:45 am]
BILLING CODE 4140-01-P