[Federal Register Volume 63, Number 28 (Wednesday, February 11, 1998)]
[Notices]
[Page 6946]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-3471]
[[Page 6946]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Licensing Opportunity and/or Cooperative Research and Development
Agreement (CRADA) Opportunity for Novel Treatment of Tumors With
Anticancer Drugs Activated by Thymidylate Synthase
AGENCY: National Institutes of Health, Public Health Service, DHHS.
ACTION: Notice.
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SUMMARY: The National Institutes of Health and the Laboratory of
Clinical Pharmacology, Center for Drug Evaluation and Research, of the
Food and Drug Administration are seeking licensees and/or CRADA
partners for the further development, evaluation, and commercialization
of materials and methods for a novel class of chemotherapeutic agents
and a novel treatment strategy. The invention claimed in DHHS Reference
No. E-058-97/0, ``Novel Treatment of Tumors With Anticancer Drugs
Activated by Thymidylate Synthase'' (J Collins, R Klecker, A Katki),
filed 29 Oct 97, is available for licensing (in accordance with 35
U.S.C. 207 and 37 CFR Part 404) and/or further development under one or
more CRADAs in the clinically important applications described below in
the Supplementary Information section.
DATES: There is no deadline by which license applications must be
received. CRADA proposals should be received on or before May 12, 1998
for priority consideration. However, CRADA proposals submitted
thereafter will be considered until a suitable CRADA Collaborator is
selected.
ADDRESSES: Questions about the licensing opportunity should be
addressed to Joseph Contrera, M.S., J.D., Technology Licensing
Specialist, Office of Technology Transfer, National Institutes of
Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-
3804; Telephone: 301/496-7056 ext. 244; Fax: 301/402-0220; E-mail:
[email protected]
CRADA proposals and questions should be addressed to Ms. Beatrice
A. Droke, Food and Drug Administration, 5600 Fishers Lane, Park 3-30
HFA 500, Rockville, MD 20853; Telephone: 301/443-6890; Fax: 301/443-
3690; E-mail: bdroke@bangate.fda.gov.
SUPPLEMENTARY INFORMATION: Thymidylate Synthase (TS) is an enzyme of
metabolism which is part of the DNA synthesis pathway in both normal
and tumor cells. It has been known for decades that TS is expressed in
tumor cells in quantities that are significantly higher than most non
cancerous tissues. There has been much research into developing
chemotherapeutic drugs which attempt to block or inhibit TS in tumor
cells in an effort to shrink or slow their growth in vivo. Drugs such
as fluorouracil and floxuridine are examples of this class of TS
inhibitors.
The problem with enzyme inhibiting drugs is that over a short
period of time, if the tumor cells are not killed, they become
tremendously resistant to the inhibitors by various mechanisms. Usually
the tumors boost expression of TS to overcome the inhibitor, but many
other avenues are available to the tumor, such as pumping the drug out
of the cell and mutating the enzyme to minimize the drug effect. At
present, once the treated tumors start producing high levels of TS
there is no effective therapy available.
Instead of inhibiting TS, this new strategy involves using TS to
turn a uracil analog with low toxicity into highly toxic thymidine
analog. The treatment would benefit patients with resistant tumors who
were previously treated with TS inhibitors. The benefits of this type
of prodrug are obvious. Patients could be treated with relatively high
doses of the low toxicity prodrug thus ensuring high enough
concentrations to penetrate the patients tissues and only the tumor
cells will be actively converting the prodrug to its toxic metabolite
thus dramatically lowering the severity of chemotherapeutic side
effects. Moreover, there is less chance of the cells becoming resistant
because they cannot down-regulate TS synthesis without slowing their
own growth while making more and more toxic metabolites which in turn
will kill the cancer cells.
Information about the patent application and pertinent information
not yet publicly described can be obtained under a Confidential
Disclosure Agreement. Respondees interested in licensing the
invention(s) will be required to submit an Application for License to
Public Health Service Inventions. Respondees interested in submitting a
CRADA proposal should be aware that it may be necessary to secure a
license to the above patent rights in order to commercialize products
arising from a CRADA.
Dated: February 3, 1998.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 98-3471 Filed 2-10-98; 8:45 am]
BILLING CODE 4140-01-M
