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###### Department of Health and Human Services

###### National Institutes of Health 

# 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 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 rr154z@nih.gov. 

# 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                           ( print 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