HIV Protease Licensing Opportunities

Federal Register announcement text, received July 31, 1996.


Human Immunodeficiency Virus Specific Proteolytic Enzyme
And A Method For Its Synthesis And Renaturation

Description of Inventions:
Inhibition of the HIV protease enzyme is currently an important component of combination therapies for HIV infection and AIDS.

U.S. Patent 5,252,477 discloses the amino acid and DNA sequences for natural and biologically active synthetic HIV-1 protease, as well as a method for its synthesis and purification. The synthetic enzyme, which has the correct stereospecific conformation, can be used to design chemical HIV-1 protease inhibitors and to test their effectiveness against HIV-1.

U.S. Patent 5,354,683 discloses the amino acid sequence of natural and biologically active synthetic HIV-2 protease, as well as a method for its synthesis and purification. The synthetic enzyme, which has the correct stereospecific conformation, can be used to design chemical HIV-2 protease inhibitors and to test their effectiveness against HIV-2.

Inventors:
S Oroszlan, TD Copeland (NCI)

Relevant Publications:
Copeland, T.D., et al., Gene Anal Techn 5: 109-115 (1989)
Louis, J.M., et al., Biochem Biophys Res Comm 164(1): 30-38 (1989)

Patent Status:
Serial No. 07/057,183 filed 01 Jun 87; U.S. Patent No. 5,252,477 issued 12 Oct 93
Serial No. 08/100,703 filed 30 Jul 93; U.S. Patent No. 5,354,683 issued 11 Oct 94
(CIP of U.S. Patent 5,252,477)

Licensing Status:
Available for exclusive or non-exclusive licensing

Portfolio:
Infectious Diseases - Reagents

For additional information, please contact:
Cindy K. Fuchs, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 232
Fax: 301/402-0220


Synthetic HIV Protease Gene And Method For Its Expression


Description of Invention:
Inhibition of the HIV protease enzyme is currently an important component of combination therapies for HIV infection and AIDS. This patent discloses a DNA construct for biologically active recombinant HIV-1 protease, as well as a method for its production and purification. The recombinant enzyme can be used to design chemical HIV-1 protease inhibitors and to test their effectiveness against HIV-1.

Inventors:
JL Medabalimi (NIDDK), S Oroszlan (NCI), PT Mona (NCI)

Relevant Publications:
Louis, J.M., et al., Biochem Biophys Res Comm 159(1): 87-94 (1989)

Patent Status:
Serial No. 08/024,916 filed 02 Mar 93 (CIP of U.S. Patent 5,252,477 issued 12 Oct 93)
Foreign intellectual property rights are available in Australia, Canada, Israel, and Japan

Licensing Status:
Available for exclusive or non-exclusive licensing

Portfolio:
Infectious Diseases - Reagents

For additional information, please contact:
Cindy K. Fuchs, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 232
Fax: 301/402-0220


Transframe Peptide Inhibitor of Viral Protease

Description of Invention:
The inhibition of proteases is an increasingly important approach in the control of pathogenic organisms, including retroviruses such as the human immunodeficiency virus (HIV). The present invention embodies small, water-soluble peptides isolated from a native retroviral inhibitory sequence that block maturation of HIV protease and also inhibit the mature enzyme. These peptides may be used in the treatment of HIV-infected cells, in the preparation of HIV vaccine formulations, in the generation of clinically relevant anti-HIV antibodies and anti-idiotypic antibodies, and as components of a screening assay or kit used to identify other similarly acting HIV protease inhibitors. The invention encompasses the inhibitory peptides, pharmaceutical compositions containing the peptides, methods of using the peptides in the treatment and prevention of HIV-induced pathogenesis, a kit and methods for screening test compounds (peptide or non-peptide) for use as HIV protease inhibitors, and antibodies and anti-idiotype antibodies to HIV protease.

Inventor:
JL Medabalimi (NIDDK)

Patent Status:
Serial No. 08/539,432 filed 05 Oct 95

Licensing Status:
Available for exclusive or non-exclusive licensing

Portfolios:
Infectious Diseases - Therapeutics, anti-virals, AIDS
Infectious Diseases - Vaccines, viral, AIDS
Infectious Diseases - Reagents

For additional information, please contact:
Cindy K. Fuchs, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 232
Fax: 301/402-0220


2,5-Diamino-3,4-Disubstituted-1,6-Diphenylhexane Isosteres Comprising Benzamide, Sulfonamide And Anthranilimide Subunits And Methods
Of Using Same

Description of Invention:
This invention concerns retroviral protease inhibitors which are potential drugs for the treatment of HIV infection. The compounds of the invention contain novel nonpeptidic and achiral substituents, wherein achiral benzamide, sulfonamide and anthranilamide subunits are introduced onto the 2,5-diamino-3,4-disubstituted-1,6-diphenylhexane isostere core. The compounds are more resistant to viral and mamalian protease degradation. The best compounds had a Ki (inhibition constant) of less than 100 pM for HIV protease. CEM cells chronically infected with HIV-1 were used to test anti-retroviral activity. The concentrations needed to inhibit 50% of viral activity were on the order of 5 nM. Therefore, these compounds compare favorably in their anti-viral potency to the best HIV protease inhibitors currently in clinical trials and on the market.

Inventors:
RS Randad, JW Erickson (NCI)

Relevant Publications:
Randad, R.S., et al., Bioorganic & Medicinal Chemistry Letters, 5(15): 1707-1712 (1995)
Randad, R.S., et al., Bioorganic & Medicinal Chemistry Letters, 5(21): 2557-2562 (1995)
Randad, R.S., et al., Bioorganic & Medicinal Chemistry Letters (1996, in press)

Patent Status:
Serial No. 08/359,612 filed 20 Dec 94
Foreign intellectual property rights are available in PCT member countries

Licensing Status:
Available for exclusive or non-exclusive licensing

Portfolio:
Infectious Diseases - Therapeutics, antivirals, AIDS


For additional information, please contact:
Cindy K. Fuchs, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 232
Fax: 301/402-0220


Novel Retroviral Agents Containing Anthranilamide, Substituted Benzamide And Other Subunits, And Methods Of Using Same

Description of Invention:
This invention concerns retroviral protease inhibitors which are potential drugs for the treatment of HIV infection. The compounds of the invention are symmetric and asymmetric 2,5-diamino-3,4-disubstituted-1,6-diphenylhexane (DAD) isosteres with achiral, nonpeptidic anthranilimide, substituted benzamide, sulfonamide and other subunits. The DAD isosteres may also include amino acid subunits. The compounds are more resistant to mammalian and viral protease degradation than currently available retroviral protease inhibitors, and therefore, have greater plasma half-life and oral bioavailability. Pharmaco-kinetic and bioavailability studies are currently being conducted. The best compound has a Ki (inhibition constant) of approximately 3 pM for HIV protease. In vitro anti-retroviral activity was tested in CEM cells chronically infected with HIV-1. The concentration required to inhibit 50% of viral activity was on the order of 6 nM. This compound thus compares favorably in its in vitro anti-viral potency to promising HIV protease inhibitors currently in clinical trials and on the market.

Inventors:
RS Randad, JW Erickson, TN Bhat (NCI)

Patent Status:
Serial No. 08/562,013 filed 22 Nov 95

Licensing Status:
Available for exclusive or non-exclusive licensing

Portfolio:
Infectious Diseases - Therapeutics, anti-virals, AIDS

For additional information, please contact:
Cindy K. Fuchs, J.D.
Office of Technology Transfer
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852-3804
Phone: 301/496-7735 ext 232
Fax: 301/402-0220