[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: [email protected].

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