[Federal Register Volume 66, Number 119 (Wednesday, June 20, 2001)]
[Notices]
[Pages 33105-33106]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-15459]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing: 
Conformationally Locked Nucleoside Analogs as Antiherpetic Agents

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

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by agencies of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by contacting Peter A. 
Soukas, J.D., at the Office of Technology Transfer, National Institutes 
of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 
20852-3804; telephone: 301/496-7056 ext. 268; fax: 301/402-0220; e-
mail: [email protected]. A signed Confidential Disclosure Agreement 
will be required to receive copies of the patent applications.

SUPPLEMENTARY INFORMATION: These inventions relate to therapeutics for 
Herpes Simplex Virus (HSV), a major public health threat. Results of a 
recent, nationally representative study show that genital herpes 
infection, caused by HSV-2, is common in the United States. Nationwide, 
45 million people ages 12 and older, or one out of five of the total 
adolescent and adult population, is infected with HSV-2. Once infected 
with HSV, people remain infected for life. The inventors' research has 
shown that these compounds are significantly more potent than current 
therapeutics for HSV. Development of these inventions would provide a 
significant benefit to the public health in the form of potentially 
lower cost therapeutics based on the potency of the compounds.

Conformationally Locked Nucleoside Analogues

Victor E. Marquez, Juan B. Rodriguez, Marc C. Nicklaus, Joseph J. 
Barchi, Jr., Maqbool A. Siddiqui (NCI)
U.S. Patent 5,629,454 issued 13 May 1997; U.S. Patent 5,869,666 issued 
9 Feb 1999; PCT/US94/10794 (issued as European Patent Number 0720604 
and Australian Patent Number 677441)
      and

Conformationally Locked Nucleoside Analogs as Antiherpetic Agents

Victor E. Marquez, Juan B. Rodriguez, Marc C. Nicklaus, Joseph J. 
Barchi, Jr., Maqbool A. Siddiqui (NCI)
U.S. Patent 5,840,728 issued 23 Nov 1998

    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 second invention discloses 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 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 stronger than that of 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.
    Descriptions of these inventions may be found in Rodriguez et al., 
J. Medicinal Chemistry 37:3389-3399 (1994) and Marquez et al., J. 
Medicinal Chemistry 39:3739-3747 (1996).

5-Substituted Derivatives of Conformationally Locked Nucleoside 
Analogues

Victor Marquez, Pamela Russ (NCI)
DHHS Reference No. E-249-00/0, U.S. S/N 60/220,934 filed 26 Jul 2000

    This invention relates to 5-substituted derivatives of 
conformationally locked nucleoside analogues and methods of using these 
derivatives as antiviral and anticancer agents. The compounds 
contemplated by the invention are nucleoside analogues where the 5-
substituent is a halogen, alkyl, alkene, halovinyl or alkyne group, and 
the nucleotide base is cytosine or uracil. The analogues are 
particularly effective in treating viral infections, specifically 
infections of DNA viruses such as Herpes simplex virus (HSV), Varicella 
zoster virus (VSV), Epstein Barr virus (EBV), and Cytomegalovirus (CMV) 
as well as members of the Poxviridae family. The inventors have

[[Page 33106]]

demonstrated in plaque reduction assays that 5-substituted uracils 
(bromo, iodo, and bromovinyl) attached to a bicyclo[3.1.0]hexane 
template are thirty times more potent than acyclovir against HSV-1 and 
HSV-2.

    Dated: June 11, 2001.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 01-15459 Filed 6-19-01; 8:45 am]
BILLING CODE 4140-01-P