[Federal Register Volume 69, Number 30 (Friday, February 13, 2004)]
[Notices]
[Page 7243]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-3167]



[[Page 7243]]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Prospective Grant of Exclusive License: The Use of Geldanamycin 
and Its Derivatives for the Treatment of Cancer

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

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: This is notice, in accordance with 35 U.S.C. 209(c)(1) and 37 
CFR part 404.7(a)(1)(i), that the National Institutes of Health, 
Department of Health and Human Services, is contemplating the grant of 
an exclusive patent license to practice the inventions embodied in:

1. PCT Patent Application No. PCT/US03/31962 filed October 8, 2003 
[DHHS Ref. E-256-2002/0-PCT-02], entitled ``17-AAG Treatment of 
Diseases Sensitive to c-Kit Down Regulation:'',
2. U.S. Provisional Patent Application No. 60/598,752 filed October 3, 
2003 [DHHS Ref. E-169-2003/0-US-01], entitled ``Geldanamycin 
Derivatives With Methyl Substituted Hydrogen Atom At N22 Position As 
Anticancer Agents'',
3. U.S. Provisional Patent Application No. 60/508,795 filed October 3, 
2003 [DHHS Ref. E-064-2003/0-US-01], entitled ``Degradation And 
Transcriptional Inhibition Of HIF-2 Alpha Protein By 17-AAG''

and all related foreign patents/patent applications, to Kosan 
Biosciences, Inc., which is located in Hayward, CA. The patent rights 
in these inventions have been assigned to the United States of America.
    The prospective exclusive license territory will be worldwide and 
the field of use may be limited to pharmaceutical use as anti-cancer 
agents, and as agents to prevent undesired cell growth or the 
deleterious effects thereof such as the prevention of re-stenosis and 
neurodegenerative diseases in humans and animals. This notice should be 
considered a modification of an earlier Federal Register notice (67 FR 
9763, March 4, 2002).

DATES: Only written comments and/or applications for a license which 
are received by the NIH Office of Technology Transfer on or before 
April 13, 2004 will be considered.

ADDRESSES: Requests for copies of the patent application, inquiries, 
comments, and other materials relating to the contemplated exclusive 
license should be directed to: George G. Pipia, Ph.D., Technology 
Licensing Specialist, Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
MD 20852-3804; Telephone: (301) 435-5560; Facsimile: (301) 402-0220; E-
mail: [email protected].

SUPPLEMENTARY INFORMATION: The prospective exclusive license will be 
royalty bearing and will comply with the terms and conditions of 35 
U.S.C. 209 and 37 CFR 404.7. The prospective exclusive license may be 
granted unless within sixty (60) days from the date of this published 
notice, the NIH receives written evidence and argument that establish 
that the grant of the license would not be consistent with the 
requirements of 35 U.S.C. 209 and 37 CFR 404.7.

Description of the Technologies

    (1) E-256-2003/0. This invention directed to the use of 17-
allylamino-17-demethoxygeldanamycin (17-AAG), a derivative of 
geldanamycin, in decreasing levels of a mutated protein called KIT (the 
product of proto-oncogene c-KIT), which has been identified as the 
protein responsible for transformation of certain human cell types into 
pathologic cells. By way of background, this invention is predicated on 
the discovery of a new method of inhibiting the activity of a mutated, 
constitutively active form of the tyrosine kinase, KIT. The method 
involves the administration of 17-AAG to a cell comprising the mutant 
KIT protein, whereby the activity level of KIT in the cell is reduced. 
The invention may prove to be useful for treating diseases such as 
mastocytosis, gastrointestinal stromal tumors (GIST), mast cell 
leukemia, myelogenenous leukemia, and testicular cancer, all of which 
are associated with mutations in the c-KIT proto-oncogene.
    (2) E-169-2003/0. This invention is directed to an N22-methyl 
substituted analogue of geldanamycin. Preliminary studies have shown 
that providing a methyl substituent in the N22 position of geldanamycin 
derivatives stabilizes the cis-conformation of the compounds. Such 
compounds are expected to have an increased binding to and inhibition 
of heat shock protein 90 (Hsp9O). Inhibition of Hsp9O is considered 
useful in the treatment of many cancers.
    (3) E-064-2003/0. The invention is directed to the use of 17-
allylaminogeldanamycin (17-AAG) and, by analogy, other geldanamycin 
derivatives to inhibit the activity of hypoxia inducible factor-
2[alpha] (HIF-2[alpha]). HIF-2[alpha] 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-2[alpha] in cells that overexpress the protein, for example to 
treat cancer. According to the lead inventor, HIF-2[alpha] plays a 
central role behind the mechanism of action of geldanamycin in renal 
cancer. The inventors also predict that certain geldanamycin analogs 
will have therapeutic benefit in tumors overexpressing HIF-2[alpha], 
and that those analogs could also find therapeutic utility in clinical 
conditions involving hypervascularization.
    Applications for a license in the field of use filed in response to 
this notice will be treated as objections to the grant of the 
contemplated exclusive license. Comments and objections submitted to 
this notice will not be made available for public inspection and, to 
the extent permitted by law, will not be released under the Freedom of 
Information Act, 5 U.S.C. 552.

    Dated: February 5, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-3167 Filed 2-12-04; 8:45 am]
BILLING CODE 4140-01-P