E7-22821. 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.

Inactivation of Enveloped Viruses and Tumor Cells for Infectious Disease and Cancer Vaccines

Description of Invention: The current technology describes the inactivation of viruses, parasites, and tumor cells by the hydrophobic photoactivatable compound 1,5-iodoanpthylazide (INA). This non-toxic compound will diffuse into the lipid bilayer of biological membranes and upon irradiation with light will bind to proteins and lipids in this domain, thereby inactivating fusion of enveloped viruses with their corresponding target cells. Furthermore, the selective binding of INA to protein domains in the lipid bilayer preserves the structural integrity and therefore immunogenicity of proteins on the exterior of the inactivated virus. This technology is universally applicable to other microorganisms that are surrounded by biological membranes like parasites and tumor cells. The broad utility of the subject technology has been demonstrated using influenza virus, HIV, SIV, Ebola and equine encephalitis virus (VEE) as representative examples. The inactivation approach for vaccine development presented in this technology provides for a safe, non-infectious formulation for vaccination against the corresponding agent. Vaccination studies demonstrated that mice immunized with INA inactivated influenza, ebola and VEE mounted a protective immune response against lethal doses of the corresponding virus. A second technology for inactivating HIV and other retroviruses by inactivation of zinc fingers is described in E-174-1993/1,/2.

Applications: Vaccines against enveloped viruses, including influenza and HIV; Cancer vaccines.

Development Status: Animal data (mouse) available for influenza.

Inventors: Yossef Raviv et al. (NCI).

Publication: Y Raviv et al. Inactivation of retroviruses with preservation of structural integrity by targeting the hydrophobic domain of the viral envelope. J Virol. 2005 Oct;79(19):12394-12400.

Patent Status:

PCT application, serial number PCT/US2005/009559 (publication number WO 2005/093049), filed 22 Mar 2005 claiming priority to 22 Mar 2004; National Stage applications pending in Australia, Canada, China, Europe, India, and U.S. (HHS Reference No. E-303-2003/0).

PCT application, serial number PCT/US2007/007338, filed 23 Mar 2007 claiming priority to 24 Mar 2006 (HHS Reference No. E-135-2006/1-PCT-01; influenza-specific inactivation).

U.S. Patent No. 6,001,555, issued 14 Dec 1999 (HHS Reference No. E-174-1993/1); PCT application, serial number PCT/US95/11915 (publication number WO 96/09406), filed 19 Sept 1995 claiming priority to 23 Sept 1994, now EP patent number 0782632, issued 16 April 2003 in Italy, Belgium, Switzerland, Germany, and United Kingdom (HHS Reference No. E-174-1993/2; second HIV inactivation technology).

Licensing Contacts:

For HHS Reference Nos. E-303-2003 and E-135-2006—Susan Ano, PhD; phone: [phone]; e-mail: [e-mail].

For HHS Reference No. E-174-1993—Sally Hu, PhD, MBA; phone: [phone]; e-mail: [e-mail].

Collaborative Research Opportunity: The National Cancer Institute's Membrane Structure and Function Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize non-infectious formulation for vaccination. Please contact John D. Hewes, Ph.D. at 301-435-3121 or [e-mail] for more information.

Monoclonal Antibodies That Bind or Neutralize Dengue Virus

Description of Invention: Among the arthropod-borne flaviviruses, the four dengue virus serotypes, dengue type 1 virus (DENV-1), dengue type 2 virus (DENV-2), dengue type 3 virus (DENV-3), and dengue type 4 virus (DENV-4) are most important in terms of human morbidity and geographic distribution. Dengue viruses cause dengue outbreaks and major epidemics in most tropical and subtropical areas where Aedes albopictus and Aedes aegypti mosquitoes are abundant. Dengue infection produces fever, rash, and joint pain in humans. A more severe and life-threatening form of dengue, characterized by hemorrhagic fever and hemorrhagic shock, has occurred with increasing frequency in Southeast Asia and Central and South America, where all four dengue virus serotypes circulate. A safe and effective vaccine against dengue is currently not available. Passive immunization with monoclonal antibodies from non-human primates or humans represents a possible alternative to vaccines for prevention of illness caused by dengue virus.

The application claims monoclonal antibodies that bind or neutralize dengue type 1, 2, 3, and/or 4 viruses. The application also claims fragments of such antibodies retaining dengue virus-binding ability, fully human or humanized antibodies retaining dengue virus-binding ability, and pharmaceutical compositions including such antibodies. The application also claims isolated nucleic acids encoding the antibodies of the invention. Additionally, application claims prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.

Application: Prophylaxis against dengue serotypes 1, 2, 3 and 4.

Development Status: Antibodies have been synthesized and preclinical studies have been performed.

Inventors: Ching-Juh Lai and Robert Purcell (NIAID).

Publications: The antibodies are further described in:

1. R Men et al. Identification of chimpanzee Fab fragments by repertoire cloning and production of a full-length humanized immunoglobulin G1 antibody that is highly efficient for neutralization of dengue type 4 virus. J Virol. 2004 May;78(9):4665-4674.

2. AP Goncalvez et al. Chimpanzee Fab fragments and a derived humanized immunoglobulin G1 antibody that efficiently cross-neutralize dengue type 1 and type 2 viruses. J Virol. 2004 Dec;78(23):12910-12918.

3. AP Goncalvez et al. Epitope determinants of a chimpanzee Fab antibody that efficiently cross-neutralizes dengue type 1 and type 2 viruses map to inside and in close proximity to fusion loop of the dengue type 2 virus envelope glycoprotein. J Virol. 2004 Dec;78(23):12919-12928.

4. AP Goncalvez et al. Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention. Proc Natl Acad Sci U S A. 2007 May 29;104(22):9422-9427.

Patent Status: U.S. Patent Application No. 10/582,006 filed 07 Jun 2006 (HHS Reference No. E-066-2003/5-US-02); Canadian Patent Application No. 2548808 filed 03 Dec 2004 (HHS Reference No. E-066-2003/5-CA-03).

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

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; [e-mail].

Collaborative Research Opportunity: The NIAID Laboratory of Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Ching-Juh Lai at 301-594-2422 for more information.

Novel Non-Nucleoside Agents for the Inhibition of HIV Reverse Transcriptase for the Treatment of HIV-1

Description of Invention: Despite recent developments in drug and compound design to combat the human immunodeficiency virus (HIV), there remains a need for a potent, non-toxic compound that is effective against wild type reverse transcriptase (RT) as well as RTs that have undergone mutations and thereby become refractory to commonly used anti-HIV compounds. There are two major classes of RT inhibitors. The first comprises nucleoside analogues, which are not specific for HIV-RT and are incorporated into cellular DNA by host DNA polymerases. Nucleoside analogues can cause serious side effects and have resulted in the emergence of drug resistance viral strains that contain mutations in their RT. The second major class of RT inhibitors comprises non-nucleoside RT inhibitors (NNRTIs) that do not act as DNA chain terminators and are highly specific for HIV-RT. This technology is a novel class of NNRTIs (substituted benzimidazoles) effective in the inhibition of HIV-RT wild type as well as against variant HIV strains resistant to many non-nucleoside inhibitors. These NNRTIs are highly specific for HIV-1 RT and do not inhibit normal cellular polymerases, resulting in lower cytotoxicity and fewer side effects that the nucleoside analogues, such as AZT. This novel class of compounds could significantly improve the treatment of HIV by increasing compliance with therapy.

Inventors: Christopher A. Michejda, Marshall Morningstar, Thomas Roth (NCI).

Patent Status: U.S. Patent No. 6,369,235 issued 09 Apr 2002 (HHS Reference No. E-076-1997/1-US-01); U.S. Patent No. 6,894,068 issued 17 May 2005 (HHS Reference No. E-076-1997/1-US-02).

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

Dated: November 9, 2007.

Steven M. Ferguson,

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