Prospective Grant of Exclusive License: Conformationally Locked Nucleoside Analogs

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 (NIH), Department of Health and Human Services, is contemplating the grant of an exclusive license to practice the following invention as embodied in the following patent applications: DHHS Ref. No. E-231-1993; U.S. Serial Number 08/126,796, filed on September 24, 1993; 08/311,425, filed on September 23, 1994, U.S. Patent No. 5,629,454; 08/818,563, filed on March 14, 1997, U.S. Patent No. 5,869,666; PCT (PCT/US94/10794) filed on September 23, 1994, and National Stage filed in Singapore (9607728-4), Australia (78420/94), Canada (2172534), Europe (94929321.1), Japan (07-506691), Greece (3026166); DHHS Ref. No. E-100-1996; U.S. Provisional 60/023,565, filed on August 7, 1996; U.S. Serial Number 08/908,724, filed on August 7, 1997, U.S. Patent No. 5,840,728; PCT (PCT/US96/12800) filed on August 15, 1996; DHHS Ref. No. E-249-2000; U.S. Provisional 60/220,934, filed on July 26, 2000; U.S. Serial Number 10/346,762, filed on January 15, 2003; PCT (PCT/US01/23246) filed on July 24, 2001, and National Stage filed in Australia (2001278993), Canada (2417251), Europe (01951228.8) to N&N Scientific, having a place of business in Maryland but incorporated in Illinois. The patent rights in these inventions have been assigned to the United States of America.

DATES:

Only written comments and/or application for a license which are received by the NIH Office of Technology Transfer on or before January 24, 2005 will be considered.

ADDRESSES:

Requests for a copy of the patent application, inquiries, comments and other materials relating to the contemplated license should be directed to: Robert M. Joynes, Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, MD 20852-3804; Email: joynesr@od.nih.gov; Telephone: (301) 594-6565; Facsimile: (301) 402-0220.

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 60 days from the date of this published Notice, NIH receives written evidence and argument that establishes that the grant of the license would not be consistent with the requirements of 35 U.S.C. 209 and 37 CFR 404.7.

The compounds of the present invention represent the first examples of carbocyclic dideoxynucleosides that in solution exist locked in a defined N-geometry (C3′-endo) conformation typical of conventional nucleosides. These analogues exhibit increased stability due to the substitution of carbon for oxygen in the ribose ring. The invention includes 4′-6′-cyclopropane fused carbocyclic dideoxynucleosides, 2′-deoxynucleosides and ribonucleosides as well as oligonucleotides derived from these analogues; the preferred embodiment of the invention is carbocyclic-4′-6′-cyclopropane-fused analogues of dideoxypurines, dideoxypyrimidines, deoxypurines, deoxypyrimidines, purine ribonucleosides and pyrimidine ribonucleosides. In addition, oligonucleotides derived from one or more of the nucleosides in combination with the naturally occurring nucleosides are within the scope of the present invention.

The invention also includes a method for the treatment of herpes virus infections by the administration of cyclopropanated carbocyclic 2′-deoxynucleosides to an affected individual. This invention is a method of administration of the compounds described above. The compounds of this invention are particularly efficacious against herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), Epstein-Barr Virus (EBV) and human cytomegalovirus (CMV), although the nucleoside analogues of the invention may be used to treat any condition caused by a herpes virus. Specifically, the N-methanocarba-T (Thymidine) analogue (hereafter (N)-MCT) has been shown to exhibit strong activity against HSV-1 and HSV-2, and moderate to strong activity against EBV. Significantly, the anti-HSV activity of the Thymidine analogue is thirty times more potent than Acyclovir (shown in a plaque reduction assay), a widely used anti-HSV therapeutic. Furthermore, the Thymidine analogue is also non-toxic against stationary cells and is potent against rapidly dividing cells. Dosage amounts for the compounds are similar to those of Acyclovir.

The field of use may be limited to development of antiviral therapeutics.

The licensed territory will be exclusive worldwide.

Properly filed competing applications for a license filed in response to this notice will be treated as objections to the contemplated license. Comments and objections submitted in response 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.