03-3303. 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 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 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.

Scavenger Receptor BI Targeting for the Treatment of Infection, Sepsis and Inflammation

Alexander Bocharov et al. (CC)

DHHS Reference No. E-008-03/0 filed 05 Nov 2002

Licensing Contact: Uri Reichman; 301/435-4616; [e-mail]

Proinflammatory bacterial cell wall components including lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN) are major factors determining the development, progression and outcome for a number of infectious diseases. Chaperonin 60 (spn60), another bacterial component, and its human ortholog heat shock protein 60 (hsp60), also play an important role in inflammatory diseases such as arthritis and lupus erythematosus. This invention relates to the discovery that peptides with an amphipathic helical motif block cellular uptake of LPS (lipopolysaccharide) and proinflammatory responses induced by LPS, LTA (lipoteichoic acid), bacterial cpn60 (Chaperonin 60) and human hsp60 (heat shock protein 60) in vitro. These observations suggest that agents with an amphipathic motif targeting SR-BI (scavenger receptor class B type I) could potentially be used to treat sepsis, bacterial and viral infections and inflammatory diseases where LPS, LTA, viral envelope proteins, and/or heat shock proteins contribute to pathogenesis.

4G10, a Monoclonal Antibody Against the Chemokine Receptor CXCR4, Raised Against a Synthetic Peptide of 38 Residues in Length Derived From the N-terminal Sequence of CXCR4

Edward A. Berger and Christopher C. Broder (NIAID)

DHHS Reference No. E-340-2002/0

Licensing Contact: Sally Hu; 301/435-5606; [e-mail]

This invention identifies a monoclonal antibody (4G10) against the chemokine receptor CXCR4 and is a mouse IgG1 antibody. CXCR4 has been identified as a co-receptor mediating entry of HIV-1 into T cells. Subsequently, CXCR4 has been implicated in normal physiological functions, including activation of B cells and B cell progenitors and guiding their migration into the bone marrow (via its ligand SDF-1). CXCR4 also functions in T cell progenitor migration and neural progenitor stem cell activation. Since 4G10 is a monoclonal antibody raised against a synthetic peptide derived from the N-terminus of CXCR4 that may prove useful in the context of the above CXCR4 functions, 4G10 is an excellent reagent for detection and quantitation of CXCR4 by Western blot, immunoprecipitation, ELISA, and flow cytometry. It can also be used to purify CXCR4 by affinity chromatography. With these known characteristics, it would also function in immuno-histochemical assays as well. Thus, this invention is a good research tool and is available for licensing through a Biological Materials License Agreement as no patent application has been filed.

Decreased Side Effects of DRYVAX® Vaccination by Prior Immunization With Highly Attenuated Poxvirus in Immune-Compromised and Competent Hosts

Genoveffa Franchini (NCI)

DHHS Reference No. E-249-02/0 filed 07 Nov 2002

Licensing Contact: Uri Reichman; 301/435-4616; [e-mail]

The invention describes new data relating to a vaccine against smallpox. Smallpox was once worldwide in scope; before vaccination was practiced almost everyone eventually contracted the disease. Variole virus is the etiological agent of smallpox. Symptoms of smallpox begin 12-14 days after exposure to the virus and are characterized by the appearance of multiple, eruptive pustules that cover the entire body. The eradication of smallpox was brought about by the use of the vaccinia virus vaccine, known as DRYVAX”. DRYVAX® is a replication competent vaccinia virus distinct from smallpox. Although the vaccine is highly efficacious, it is also associated with significant serious adverse effects. Specifically, DRYVAX® can cause serious side effects in immunocompromised patients, such as AIDS patients. The last natural case of smallpox occurred in 1977. In 1980 the World Health Organization (WHO) declared the global eradication of smallpox and recommended that all countries cease vaccination. The recent events of September 11, 2001, however, brought the issue of smallpox vaccination to the forefront of the national homeland security efforts.

The current invention describes the use of DRYVAX® in conjunction with (modified vaccinia Ankara strain) MVA or NYVAC, an attenuated poxvirus vector obtained from Connaught Technology Corporation (CTC), an Aventis company. Specifically, the inventors demonstrate, with animal studies, that prior immunization with NYVAC or MVA appear to help contain the adverse effects of the DRYVAX® vaccine. The adverse effects were tempered in immune-competent as well as in immune-compromised hosts. The overall concept of the invention is to immunize first with an attenuated poxvirus or an attenuated vaccinia virus and then with DRYVAX® to overcome the side effects of the latter vaccination.

gp64 Pseudotyped Vectors and Uses Thereof

Mukesh Kumar, Joshua Zimmerberg (NICHD)

DHHS Reference No. E-191-01/0 filed 12 Nov 2002

Licensing Contact: Uri Reichman; 301/435-4616; e-mail: [e-mail]

This invention relates to a general gene therapy technology which uses an HIV-1 based vector containing a baculovirus gp64 protein. HIV-1 based gene therapy vectors hold great promise due to their ability to deliver genes to non-dividing cells including hematopoietic stem cells. However native HIV only binds to cells with a CD4 receptor, while gene therapy vectors would need to be delivered to a variety of cells. Various different envelope proteins have been tried to replace the native envelope protein of HIV with a new envelope protein whose origin is another enveloped virus (pseudotyping) that has more general binding capabilities. However, to date, no one has been successful for practical purposes, due to either low titers or cytotoxic effects of the expressed proteins. The inventors have developed a family of nontoxic vectors using baculovirus gp64 protein (which binds to a variety of cells) and HIV proteins that efficiently deliver genes of interest to target cells. Furthermore, since gp64 expression in producer cells is not accompanied by cytotoxic side effects, this protein is an ideal candidate for the development of cell lines for constitutive expression of gp64 for the process of construction of the hybrid HIV (packaging cell lines).

Novel Acylthiol Compositions and Methods of Making and Using Them

John K. Inman (NIAID), Atul Goel (NCI), Ettore Appella (NCI), Jim A. Turpin (NCI), and Marco Schito

DHHS Reference No. E-329-00/0 filed 03 Aug 2001

Licensing Contact: Sally Hu; 301/435-5606; [e-mail]

This invention provides a novel family of acylthiols and uses thereof. More specifically, this invention provides effective inhibitors of HIV that selectively target its highly conserved nucleocapsid protein (NCp7) by interacting with metal chelating structures of a zinc finger-containing protein. Because of the mutationally intolerant nature of NCp7, drug resistance is much less likely to occur with compounds attacking this target. In addition, these drugs should inactivate all types and strains of HIV and could also inactivate other retroviruses, since most retroviruses share one or two highly conserved zinc fingers that have the CCHC motif of the HIV NCp7. Finally, this invention could be very useful for the large-scale practical synthesis of HIV inhibitors, because these compounds can be prepared by using inexpensive starting materials and facile reactions. Thus, it opens the possibility that an effective drug treatment for HIV could be made available to much larger populations than is now the case.

This research has been described in Turpin et al., J. Med. Chem. 42: 67-86, 1999; Basrur et al., J. Biol. Chem. 275: 14890-14897, 2000; Song et al., Biorganic and Medicinal Chemistry 10: 1263-1273, 2002; Goel et al., Biorganic and Medicinal Chemistry Letters 12: 767-770, 2002; Schito et al., AIDS Research and Human Retroviruses, in press.

Dated: February 4, 2003.

Jack Spiegel,

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