[Federal Register Volume 65, Number 97 (Thursday, May 18, 2000)]
[Notices]
[Pages 31583-31584]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-12548]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Prospective Grant of Exclusive License: Uridine Prodrug 
Analogues: Uses in Cancer Diagnosis and Therapy

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

ACTION: Notice.

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SUMMARY: This is notice, in accordance with 35 U.S.C. 209(c)(1) and 37 
CFR 404.7(a)(1)(i), that the National Institutes of Health, Department 
of Health and Human Services, is contemplating the grant of an 
exclusive license to practice the inventions embodied in PCT Patent 
Application S/N PCT/US98/23109 (23109) entitled, ``Antitumor Uridine 
Analogs'' which was filed on October 10, 1998 and claims priority to 
U.S. Patent Application S/N 60/063,587 entitled, ``Diagnosis and 
Treatment of Tumors with Drugs Activated by Thymidylate Synthase,'' 
which was filed on October 10, 1997 to Nascent Pharmaceuticals LLC of 
San Francisco, California. 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 human therapeutics and diagnostics 
for the detection and treatment of breast and gastrointestinal cancers.

DATES: Only written comments and/or license applications which are 
received by the National Institutes of Health on or before July 17, 
2000 will be considered.

ADDRESSES: Requests for copies of the patent, inquiries, comments and 
other materials relating to the contemplated exclusive license should 
be directed to: Richard U. Rodriguez, M.B.A., Technology Licensing 
Specialist, Office of Technology Transfer, National Institutes of 
Health, 6011 Executive Boulevard, Suite 325, Rockville, MD. 20852-3804. 
Telephone: (301) 496-7056, X287; Facsimile (301) 402-0220; E-mail 
[email protected].

SUPPLEMENTARY INFORMATION: The technology claimed in `23109 relates to 
methods, compounds and compositions for diagnosing and/or treating 
cancers with anti-tumor agents activated by thymidylate synthase (TS) 
and/or thymidine kinase (TK). In addition, the invention relates to the 
preparation and use of positron emitting nucleoside analogues for 
imaging applications.
    TS is an essential enzyme for DNA synthesis, and it has been shown 
to be

[[Page 31584]]

more abundantly expressed in tumor cells than in normal cells. 
Historically, scientists have tried to capitalize upon this 
overexpression and have attempted to inhibit TS activity with the goal 
of shrinking tumors and/or killing tumor cells. For example, 
fluorouracil and floxuridine have been used to treat breast, colon, 
pancreas, stomach, ovarian and head/neck carcinomas, but the 
effectiveness of these approaches have been limited because many tumors 
are inherently resistant to these treatments, and even those that are 
initially sensitive, develop resistance during the course of treatment. 
It was subsequently shown, that a strong correlation exists between 
resistance and high level expression of TS.
    The inventors have proceeded along another route, again, attempting 
to capitalize upon the high levels of TS in tumor cells. Instead of 
trying to inhibit TS activity, they have proposed the introduction of 
uridine analogue prodrugs into cancer cells. These prodrugs would then 
be converted to more toxic thymidine analogues. This approach seems to 
avoid the observed problems of TS inhibition and shows great promise.
    Detection and diagnostic applications for this technology are also 
possible. In particular, the success of this type of strategy would be 
contingent upon the extent of prodrug incorporation into DNA and 
therefore, the analysis of a tumor cell's DNA could provide diagnostic 
information regarding the optimal therapy for a specific tumor type. 
Traditionally, methods to determine growth rates have been invasive, 
but this technology would provide for non-invasive external imaging 
methods which would avoid the need for biopsies as well as providing 
for the capability of scanning larger areas of the body.
    Thymidine is an excellent probe for monitoring growth/DNA 
synthesis, but it cannot be used in these situations because it is 
quickly degraded in the body. Analogues of thymidine would obviate this 
problem and could be produced upon conversion of the contemplated 
uridine analogue prodrugs.
    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.
    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: April 25, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 00-12548 Filed 5-17-00; 8:45 am]
BILLING CODE 4140-01-P