[Federal Register Volume 61, Number 154 (Thursday, August 8, 1996)]
[Notices]
[Pages 41417-41418]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-20266]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health


Government-Owned Inventions; Availability for Licensing: HIV 
Protease-Related Technologies

AGENCY: National Institutes of Health.

ACTION: Notice.

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    The inventions referenced 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 U.S. companies and may also be available for licensing.

ADDRESS: Licensing information and a copy of the patent applications 
and issued patents may be obtained by contacting Cindy K. Fuchs, J.D., 
at the Office of Technology Transfer, National Institutes of Health, 
6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804 
(telephone 301/496-7735 ext 232; fax 301/402-0220). A signed 
Confidential Disclosure Agreement will be required to receive copies of 
the patent applications.

Human Immunodeficiency Virus Specific Proteolytic Enzyme and a 
Method for Its Synthesis and Renaturation

S Oroszlan, TD Copeland (NCI)
Serial No. 07/057,183 filed 01 Jun 87
U.S. Patent No. 5,252,477 issued 12 Oct 93

    Inhibition of the HIV protease enzyme is currently an important 
component of combination therapies for HIV infection and AIDS. This 
patent 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 HIV-1 
protease inhibitors and to test their effectiveness against HIV-1. This 
technology is described further in the following publications: 
Copeland, T.D., et al., Gene Anal Techn 5: 109-115 (1988) and Louis, 
J.M., et al., Biochem Biophys Res Comm 164(1): 30-38 (1989). 
(Portfolio: Infectious Diseases--Reagents)

Human Immunodeficiency Virus Specific Proteolytic Enzyme and a 
Method for Its Synthesis and Renaturation

S Oroszlan, TD Copeland (NCI)
Serial No. 08/100,703 filed 30 Jul 1993
U.S. Patent No. 5,354,683 issued 11 Oct 94 (CIP of U.S. Patent 
5,252,477)

    Inhibition of the HIV protease enzyme is currently an important 
component of combination therapies for HIV infection and AIDS. This 
patent 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 HIV-2 protease 
inhibitors and to test their effectiveness against HIV-2. This 
technology is described further in Copeland, T.D., et al., Gene Anal 
Techn 5: 109-115 (1988). (Portfolio: Infectious Diseases--Reagents)

[[Page 41418]]

Synthetic HIV Protease Gene and Method for Its Expression

JL Medabalimi (NIDDK), S. Oroszlan, PT Mona (NCI)
Filed 02 Mar 93
Serial No. 08/024,916 (CIP of U.S. Patent 5,252,477)

    Inhibition of the HIV protease enzyme is currently an important 
component of combination therapies for HIV infection and AIDS. This 
patent application 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 HIV-1 
protease inhibitors and to test their effectiveness against HIV-1. This 
technology is described further in Louis, J.M., et al., Biochem Biophys 
Res Comm 159(1): 87-94 (1989). Foreign intellectual property rights are 
available in Australia, Canada, Israel, and Japan. (Portfolio: 
Infectious Diseases--Reagents)

Transframe Peptide Inhibitor of Viral Protease

JL Medabalimi (NIDDK)
Filed 05 Oct 95
Serial No. 08/539,432

    The inhibition of protease 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. The 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. (Portfolio: Infectious Diseases--Therapeutics, anti-
virals, AIDS; Infectious Diseases--Vaccines, viral, AIDS; Infectious 
Diseases--Reagents)

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

RS Randad, JW Erickson (NCI)
Filed 20 Dec 94
Serial No. 08/359,612

    This invention concerns retroviral protease inhibitors which are 
potential drugs for the treatment of HIV infection and AIDS. 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 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 the in vitro anti-
retroviral activity of the compounds. The concentrations needed to 
inhibit 50% of viral activity were on the order of 5 nM. Therefore, 
these compounds compare favorably in their anti-retorviral potency to 
HIV protease inhibitors currently in clinical trials and on the market. 
These compounds are described in three recent 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); and Randad, R.S., et al., Bioorganic 
& Medicinal Chemistry Letters (1996, in press). Foreign intellectual 
property rights are available in PCT member countries. (Portfolio: 
Infectious Diseases--Therapeutics, anti-virals, AIDS)

Novel Retroviral Agents Containing Anthranilamide, Substituted 
Benzamide and Other Subunits, and Methods of Using Same

RS Randad, JW Erickson, TN Bhat (NCI)
Filed 22 Nov 95
Serial No. 08/562,013

    This invention concerns retroviral protease inhibitors which are 
potential drugs for the treatment of HIV infection and AIDS. 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. 
Pharmacokinetic 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-retroviral potency to HIV protease inhibitors currently in 
clinical trials and on the market. (Portfolio: Infectious Diseases--
Therapeutics, anti-virals, AIDS)

    Dated: July 30, 1996.
Barbara M. McGarey,
Deputy Director, Office of Technology Transfer.
[FR Doc. 96-20266 Filed 8-7-96; 8:45 am]
BILLING CODE 4140-01-M