E7-2494. 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.

Integrase Inhibitors for the Treatment of Retroviral Infection Including Human Immunodeficiency Virus-1

Description of Technology: Available for licensing and commercial development are stilbenedisulfonic acid derivatives for treatment of human immunodeficiency virus-1 (HIV-1) and other retroviral infections. Current HIV-1 therapeutic treatments target the viral protease and reverse transcriptase enzymes, which are essential for retroviral infection. However, these drugs often have limitations due to drug resistant variants, which render drugs ineffective. Additionally, such drugs are often toxic when administered in combination therapies. Thus, efficacious inhibitors of retroviral infection that are devoid of toxicity are presently needed.

The subject invention describes stilbenedisulfonic acid derivatives, which target the integrase enzyme of retroviruses. Similar to protease and reverse transcriptase activity, integrase function is essential for retroviral infection. Integrase catalyzes integration of reverse transcribed viral DNA into a host cell's genome. For this reason, integrase is considered a rational therapeutic target for HIV-1 infection. Further, integrase is a favorable target because the enzyme has no human cellular counterpart, which could interact with a potential integrase inhibitor and cause harmful side effects. Recent clinical data with an integrase inhibitor from Merck shows impressive clinical activity. The Merck compound is different from the current invention and is projected for FDA approval mid 2007. Thus, the subject invention is valuable for safe and effective treatment of HIV-1 and other retroviral infections.

Application: Treatment of HIV infection.

Development Status: The technology is ready for use in drug discovery and development.

Inventors: Yves Pommier (NCI), Elena Semenova (NCI), Christophe Marchand (NCI).

Patent Status: U.S. Provisional Application No. 60/849,718 filed 04 Oct 2006 (HHS Reference No. E-264-2006/0-US-01).

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

Licensing Contact: Sally Hu, Ph.D.; 301/435-5606; [e-mail].

Broadly Cross-Reactive Neutralizing Antibodies Against Human Immunodeficiency Virus Selected by ENV-CD4-CO-Receptor Complexes

Description of Technology: This invention provides a novel anti-HIV human monoclonal antibody named X5. This antibody demonstrates promise over conventional anti-HIV antibodies because the X5 antibody exhibits a unique binding activity compared to its counterparts. It has been established that the initial stage of HIV-1 entry into cells is mediated by a complex between the viral envelope glycoprotein (Env) such as gp120-gp41, a receptor CD4 and a co-receptor CCR5. The X5 antibody binds to an epitope on gp120 that is induced by interaction between gp120 and the receptor CD4 and enhanced by the co-receptor CCR5. The X5 antibody also shows strong activity at very low levels (in the range from 0.0001-0.1 Mg/ml concentration is dependent on the isolate). Because it is a human antibody, it can be administered directly into patients so that it is an ideal candidate for clinical trials. It also can be easily produced because it was obtained by screening of phage display libraries and its sequence is known. Finally, since it has neutralized all virus envelope glycoproteins, including those from primary isolates of different clades, the epitope is highly conserved and resistance is unlikely to develop. Therefore, this antibody and/or its derivatives including fusion proteins with CD4 are good candidates for clinical development.

Additional information on the current research in Dr. Dimitrov's laboratory may be found at http://www-lecb.ncifcrf.gov/​dimitrov/​dimitrov.html.

Applications: Antibody for HIV research, diagnostics and therapeutic development.

Development Status: Preclinical data is available at this time.

Inventors: Dimiter Dimitrov (NCI), Xiadong Xiao (NCI), Yuuei Shu (NCI), Sanjay Phogat (NIAID), et al.

Patent Status: Patent Cooperation Treaty Serial No. PCT/US02/33165 filed 16 Oct 2002; National Stage Filing in United States, India, Canada, Australia, Europe (HHS Reference No. E-130-2001/0).

Availability: Available for licensing and commercial development, excluding the field of use of the development of the PEGylated X5, PEGylated X5 derivatives, mutants of PEGylated X5 or a derivative.

Licensing Contact: Sally Hu, Ph.D.; 301/435-5606; [e-mail].

Collaborative Research Opportunity: The NCI Center for Cancer Research Nanobiology Program (CCRNP) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize antibodies for HIV research, diagnostics and therapeutic development. Please contact John D. Hewes, Ph.D. at [phone] or [e-mail] for more information.

Dated: February 2, 2007.

Steven M. Ferguson,

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