06-7327. Government-Owned Inventions; Availability for Licensing

AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

SUMMARY:

The inventions listed below are owned by an agency 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 writing to the indicated licensing contact at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

Novel Acylthiol Compositions and Methods of Making and Using Them

Description of Technology: This invention provides a novel family of acylthiols and uses thereof. More specifically, this invention provides effective inhibitors of HIV that selectively target its highly conserved nucleocapsid protein (NCp7) by interacting with metal chelating structures of a zinc finger-containing protein. Because of the mutationally intolerant nature of NCp7, drug resistance is much less likely to occur with compounds attacking this target. In addition, these drugs should inactivate all types and strains of HIV and could also inactivate other retroviruses, since most retroviruses share one or two highly conserved zinc fingers that have the CCHC motif of the HIV Ncp7. Finally, this invention could be very useful for the large-scale practical synthesis of HIV inhibitors, because these compounds can be prepared by using inexpensive starting materials and facile reactions. Thus, it opens the possibility that an effective drug treatment for HIV could be made available to much larger populations. These thioesters may also be used as an active component in topical applications that serve as a barrier to HIV infection.

Inventors: John K. Inman (NIAID), Atul Goel (NCI), Ettore Appella (NCI), James A. Turpin (NIAID), Marco Schito (NCI).

Publications:

1. ML Schito, A Goel, Y Song, JK Inman, RJ Fattah, WG Rice, JA Turpin, A Sher, E Appella. In vitro antiviral activity of novel human immunodeficiency virus type 1 nucleocapsid p7 zinc finger inhibitors in a transgenic murine model. AIDS Res Hum Retroviruses. 2003 Feb;19(2):91-101.

2. P Srivastava, M Schito, RJ Fattah, T Hara, T Hartman, RW Buckheit Jr, JA Turpin, JK Inman, E Appella. Optimization of unique, uncharged thioesters as inhibitors of HIV replication. Bioorg Med Chem. 2004 Dec 15;12(24):6437-6450.

3. LM Jenkins, JC Byrd, T Hara, P Srivastava, SJ Mazu, SJ Stahl, JK Inman, E Appella, JG Omichinski, P Legault. Studies on the mechanism of inactivation of the HIV-1 nucleocapsid protein NCp7 with 2-mercaptobenzamide thioesters. J Med Chem. 2005 Apr 21;48(8):2847-2858.

4. V Basrur, Y Song, SJ Mazur, Y Higashimoto, JA Turpin, WG Rice, JK Inman, E Appella. Inactivation of HIV-1 nucleocapsid protein P7 by pyridinioalkanoyl thioesters. Characterization of reaction products and proposed mechanism of action. J Biol Chem. 2000 May 19;275(20):14890-14897.

5. JA Turpin, Y Song, JK Inman, M Huang, A Wallqvist, A Maynard, DG Covell, WG Rice, E Appella. Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers. J Med Chem. 1999 Jan 14;42(1):67-86.

Patent Status: U.S. Patent Application No. 10/485,165 filed 28 Jan 2004, claiming priority to 03 Aug 2001 (HHS Reference No. E-329-2000/0-US-06).

Licensing Status: Available for non-exclusive or exclusive licensing.

Licensing Contact: Sally H. Hu, Ph.D., M.B.A.; 301/435-5605; [e-mail].

Novel Thioesters and Uses Thereof

Description of Technology: The human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). Drug-resistance is a critical factor contributing to the gradual loss of clinical benefit to treatments for HIV infection. Accordingly, combination therapies have further evolved to address the mutating resistance of HIV. However, there has been great concern regarding the apparent growing resistance of HIV strains to current therapies.

The present invention provides for a novel family of thioesters and uses thereof. These thioesters are capable of inactivating viruses by a variety of mechanisms, particularly by complexing with metal ion-complexing zinc fingers. The invention further provides for methods for inactivating a virus, such as the human immunodeficiency virus (HIV), using these compounds, and thereby also inhibiting transmission of the virus.

Inventors: James A. Turpin (NCI), Yongsheng Song (NCI), John K. Inman (NIAID), Mingjun Huang (NCI), Anders Wallqvist (NCI), David G. Covell (NCI), William G. Rice (NCI), Ettore Appella (NCI), et al.

Patent Status: U.S. Patent No. 6,706,729 issued 16 Mar 2004 (HHS Reference No. E-136-1998/0-US-10); U.S. Patent Application No. 10/738,062 filed 16 Dec 2003 (HHS Reference No. E-136-1998/0-US-11).

Licensing Status: Available for non-exclusive or exclusive licensing.

Licensing Contact: Sally H. Hu, Ph.D., M.B.A.; 301/435-5605; [e-mail].

Dated: August 25, 2006.

Steven M. Ferguson,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.