[Federal Register Volume 64, Number 179 (Thursday, September 16, 1999)]
[Notices]
[Pages 50288-50290]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-24122]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

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 John Peter Kim, 
J.D., M.B.A., Technology Licensing Specialist, at the Office of 
Technology Transfer, National Institutes of Health, 6011 Executive 
Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/
496-7056 ext. 264; fax: 301/402-0220; e-mail: [email protected]. A signed 
Confidential Disclosure Agreement will be required to receive copies of 
the patent applications.

Oligonucleotides Which Specifically Bind Retroviral Nucleocapsid 
Proteins

Alan Rein, Jose Casas-Finet, Robert Fisher, Matthew Fivash, Louis E. 
Henderson (NCI)
Serial No. 09/180,903 filed 12 Jul 1999; PCT/US97/08936 filed 19 May 
1997; Serial No. 60/017,128 filed 20 May 1996

    The human immunodeficiency virus (HIV) is the causative agent of 
acquired immunodeficiency syndrome (AIDS). A retroviral protein 
species, the gag polyprotein, is involved in the assembly of retrovirus 
particles and capable of specific interactions with nucleic acids. 
After the virion is released from the cell, the polyprotein is cleaved 
by the virus-encoded protease. One of the cleaved products, the 
nucleocapsid (NC) protein, then binds to genomic RNA, forming the 
ribonucleoprotein core of the mature particle. The interaction between 
gag and genomic RNA is known to involve the NC domain of the 
polyprotein. In addition, the NC protein plays crucial roles in both 
the reverse transcription and integration steps in the viral life 
cycle.
    The present invention relates to retroviral nucleocapsid proteins, 
such as NC and the gag precursor, and their ability of bind to specific 
nucleic acid sequences with high affinity. The high affinity of this 
interaction has potential applications in the design of new antiviral 
approaches and in sensitive detection of HIV particles. Accordingly, 
the invention provides for oligonucleotides which bind to

[[Page 50289]]

nucleocapsides proteins with high affinity, molecular decoys for 
retroviral nucelocapsid proteins which inhibit viral replication, 
targeted molecules comprising high affinity oligonucleotides, assays 
for selecting test compounds, and related kits.

Human Monoclonal Antibodies to HIV-1 Envelope Glycoprotein gp120

Brynmor A. Watkins and Marvin S. Reitz, Jr. (NCI) Serial No. 60/141,701 
filed 30 Jun 1999

    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 relates to human monoclonal antibodies to 
type 1 human immunodeficiency virus (HIV-1) envelope glycoprotein 
gp120, to phage display libraries, and to diagnostic methods and 
pharmaceutical compositions which employ these antibodies 
therapeutically and prophylactically.

Antiviral Genetic Target Within HIV gag-pol Transframe Region

Shizuko Sei and Hiroaki Mitsuya (NCI)
Serial No. 60/141,072 filed 25 Jun 1999

    The human immunodeficiency virus type 1 (HIV-1) is a retrovirus 
that infects CD4+ T-lymphocytes, causing immunosuppression and the 
acquired immunodeficiency syndrome (AIDS). The subject invention 
provides the methods for the potent inhibition of HIV-1 replication, 
thus effective measure to treat HIV-1 infection, utilizing 
oligonucleotides and oligonucleotide analogues, including peptide 
nucleic acids, that can target either DNA or RNA sequences within the 
HIV gag-pol transframe region. Blocking the expression of the sequences 
mentioned in the subject invention leads to a decreased and 
discoordinated synthesis of viral protease, resulting in a significant 
reduction in the virion production from HIV-1-infected cells.

Identification and Use of High Efficacy Vaccine Antigens Which 
Modulate Antigen Presenting Cells

Polly Matzinger and John P. Ridge (NIAID)
Serial No. 09/313,487 filed 17 May 1999

    Through modulation of the activation state of an antigen presenting 
cell (APC), the activation of a T cell is concordantly governed, e.g., 
the activation of a killer T cell. The subject invention accordingly 
provides uses and applications in the field of immunology for novel 
pharmaceuticals, therapeutic and prophylactic agents, and vaccine 
components for the treatment and prevention of cancer, systemic 
infection, and autoimmune responses.

Thiazepine Inhibitors of HIV-1 Integrase

Yves Pommier, Nouri Neamati, Antonio Garafalo, Vito Nacci (NCI)
Serial No. 60/133,726 filed 12 May 1999

    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.
    It has been found that a certain class of compounds including 
thiazepines and analogs and derivatives thereof are effective and 
selective anti-integrase inhibitors. These compounds have been found to 
inhibit both viral replication and the activity of purified HIV-1 
integrase. The subject invention provides for such compounds and for 
methods of inhibiting HIV integrase.

Acetylated and Related Analogues of Chicoric Acid as HIV Integrase 
Inhibitors

Terrence R. Burke, Jr., Zhaiwei Lin, He Zhao, Nouri Neamati, Yves 
Pommier (NCI)
Serial No. 60/121,127 filed 22 Feb 1999

    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.
    Chicoric acid has been found to have potential in HIV therapies. 
The subject invention provides for new chicoric acid analogues and 
derivatives that inhibit HIV-1 integrase, as well as improved synthetic 
methods for enantiomers of chicoric acid itself as well as its 
analogues and derivatives. Also provided are methods for inhibiting the 
replication of HIV-1 either alone or in combination therapies.

Identification of Globotriaosylceramide as a Promoter of HIV-1 
Entry Into Cells

Robert Blumenthal, Anu Puri, Peter Jug (NCI)
Serial No. 60/108,903 filed 17 Nov 1998

    The human immunodeficiency virus (HIV) is the causative agent of 
acquired immunodeficiency syndrome (AIDS). It has been noted that human 
immunodeficiency virus type 1 (HIV-1) enters permissive cells by 
binding to the cellular receptor, CD4, and chemokine receptors specific 
for the envelope glycoprotein (gp120-g41) of a given HIV-1 isolate, 
followed by gp120-gp41 mediated fusion of the viral and target cell 
membranes.
    The subject invention relates to the discovery of glycosphingolipid 
cofactors which are essential for entry of a broad range of HIV-1 
isolates into cells expressing CD4 and appropriate chemokine receptors. 
The invention provides for diagnostics, prophylactics, therapeutics, 
and methods of use for the treatment and prevention of HIV-1 infection 
and/or AIDS.

Inhibition of Retroviral LTR Promoters by Calcium Response 
Modifiers

Elise C. Kohn, Kevin Gardner, Lance A. Liotta (NCI)
Serial No. 09/103,519 filed 23 Jun 1998; Serial No. 08/353,765 filed 12 
Dec 1994

    The human immunodeficiency virus (HIV) LTR is synergistically 
activated by the phorbol ester 12-myristic 13-acetate (PMA) and T cell 
specific mitogenic lectin phytohemagglutinin A (PHA). This reflects the 
activation of the HIV LTR by endogenous T cell mechanisms in vitro. A 
class of non-voltage-gated calcium influx inhibitor compounds is 
disclosed which is newly discovered to inhibit the activation of 
retroviral LTR promoters, including HIV-LTR, by PHA and PMA. This class 
of compounds can be used to delay or suppress the transition of HIV 
infection from a latent to a virulent condition, thereby preventing or 
ameliorating retroviral diseases such as Acquired Immune Deficiency 
Syndrome (AIDS). The compounds are also useful in cancer treatment, 
allowing for coordinated therapeutic approaches to retroviral diseases 
and related cancers such Kaposi's Sarcoma. The compounds can also be 
used to standardize in vitro assays of commercial importance for 
clinical and experimental application.

[[Page 50290]]

Inhibition of HIV Replication Using Soluble Tat Peptide Analogs

Fatah Kashanchi (NCI), M.R. Sadaie (FDA), John M. Brady (NCI)
Serial No. 09/269,991 filed 02 Oct 1997; PCT/US97/17704 filed 02 Oct 
1997; Serial No. 60/027,658 filed 04 Oct 1996

    The subject invention embodies the identification of a domain 
within the transactivator Tat protein of HIV-1, a protein which is 
necessary for replication of the virus. A number of peptide derivatives 
of this domain have been constructed. It has been demonstrated that 
some of these derivatives inhibit Tat transactivation of the human 
immunodeficiency virus (HIV) LTR (long terminal repeat) promoter. Most 
importantly, the peptide derivatives also inhibit virus replication and 
thus provide the basis for potential therapeutic antiviral agents for 
the treatment of HIV infections.

    Dated: September 8, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 99-24122 Filed 9-15-99; 8:45 am]
BILLING CODE 4140-01-M