E8-3164. 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.

Development of Antigenic Chimeric St. Louis Encephalitis Virus/Dengue Virus Type Four Recombinant Viruses (SLEV/DEN4) as Vaccine Candidates for the Prevention of Disease Caused by SLEV

Description of Invention: St. Louis Encephalitis Virus (SLEV) is a mosquito-borne flavivirus that is endemic in the Americas and causes sporadic outbreaks of disease in humans. SLEV is a member of the Japanese encephalitis virus serocomplex and is closely related to West Nile Virus (WNV). St. Louis encephalitis is found throughout North, Central, and South America, and the Caribbean, but is a major public health problem mainly in the United States. Prior to the outbreak of West Nile virus in 1999, St. Louis encephalitis was the most common human disease caused by mosquitoes in the United States. Since 1964, there have been about 4,440 confirmed cases of St. Louis encephalitis, with an average of 130 cases per year. Up to 3,000 cases have been reported during epidemics in some years. Many more infections occur without symptoms and go undiagnosed. At present, a vaccine or FDA-approved antiviral therapy is not available.

The inventors have previously developed a WNV/Dengue4Delta30 antigenic chimeric virus as a live attenuated virus vaccine candidate that contains the WNV premembrane and envelope (prM and E) proteins on a dengue virus type 4 (DEN4) genetic background with a thirty nucleotide deletion (Delta30) in the DEN4 3'-UTR. Using a similar strategy, the inventors have generated an antigenic chimeric virus, SLE/DEN4Delta30. Preclinical testing results indicate that chimerization of SLE with DEN4Delta30 decreased neuroinvasiveness in mice, did not affect neurovirulence in mice, and appeared to overattenuate the virus for non-human primates. Modifications of the SLE/DEN4Delta30 vaccine candidate are underway to improve its immunogenicity.

This application claims live attenuated chimeric SLE/DEN4Delta30 vaccine compositions and bivalent WNV/SLE/DEN4Delta30 vaccine compositions. Also claimed are methods of treating or preventing SLEV infection in a mammalian host, methods of producing a subunit vaccine composition, isolated polynucleotides comprising a nucleotide sequence encoding a SLEV immunogen, methods for detecting SLEV infection in a biological sample and infectious chimeric SLEV.

Application: Immunization against SLEV or SLEV and WNV.

Development Status: Live attenuated vaccine candidates are currently being developed and preclinical studies in mice and monkeys are in progress. Suitable vaccine candidates will then be evaluated in clinical studies.

Inventors: Stephen S. Whitehead, Joseph Blaney, Alexander Pletnev, Brian R. Murphy (NIAID).

Patent Status: U.S. Provisional Application No. 60/934,730 filed 14 Jun 2007 (HHS Reference No. E-240-2007/0-US-01).

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

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 live attenuated virus vaccine candidates for St. Louis encephalitis virus. Please contact Dr. Whitehead at 301-496-7692 for more information.

Methods of Glycosylation and Bioconjugation

Description of Technology: Eukaryotic cells express several classes of oligosaccharides attached to proteins or lipids. Animal glycans can be N-linked via beta-GlcNAc to Asn (N-glycans), O-linked via -GalNAc to Ser/Thr (O-glycans), or can connect the carboxyl end of a protein to a phosphatidylinositol unit (GPI-anchors) via a common core glycan structure. Beta (1,4)-galactosyltransferase I catalyzes the transfer of galactose from the donor, UDP-galactose, to an acceptor, N-acetylglucosamine, to form a galactose-beta (1,4)-N-acetylglucosamine bond, and allows galactose to be linked to an N-acetylglucosamine that may itself be linked to a variety of other molecules. Examples of these molecules include other sugars and proteins. The reaction can be used to make many types of molecules having great biological significance. For example, galactose-beta (1,4)-N-acetylglucosamine linkages are important for many recognition events that control how cells interact with each other in the body, and how cells interact with pathogens. In addition, numerous other linkages of this type are also very important for cellular recognition and binding events as well as cellular interactions with pathogens, such as viruses. Therefore, methods to synthesize these types of bonds have many applications in research and medicine to develop pharmaceutical agents and improved vaccines that can be used to treat disease.

The invention provides in vitro folding method for a polypeptidyl-alpha-N-acetylgalactosaminyltransferase (pp-GalNAc-T) that transfers GalNAc to Ser/Thr residue on a protein. The application claims that this in vitro-folded recombinant ppGalNAc-T enzyme transfers modified sugar with a chemical handle to a specific site in the designed C-terminal polypeptide tag fused to a protein. The invention provides methods for engineering a glycoprotein from a biological substrate, and methods for glycosylating a biological substrate for use in glycoconjugation. Also included in the invention are diagnostic and therapeutic uses.

Application: Enzymes and methods are provided that can be used to promote the chemical linkage of biologically important molecules that have previously been difficult to link.

Developmental Status: Enzymes have been synthesized and characterization studies have been performed.

Inventors: Pradman Qasba and Boopathy Ramakrishnan (NCI/SAIC).

Patent Status: U.S. Provisional Application No. 60/930,294 filed 14 May 2007 (HHS Reference No. E-204-2007/0-US-01).

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 National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or [e-mail] for more information.

Chlamydia Vaccine

Description of Invention: Chlamydia trachomatis is an obligate intracellular bacterial pathogen that colonizes and infects oculogenital mucosal surfaces. The organism exists as multiple serovariants that infect millions of people worldwide. Ocular infections cause trachoma, a chronic follicular conjunctivitis that results in scarring and blindness. The World Health Organization estimates that 300-500 million people are afflicted by trachoma, making it the most prevalent form of infectious preventable blindness. Urogenital infections are the leading cause of bacterial sexually transmitted disease in both industrialized and developing nations. Moreover, sexually transmitted diseases are risk factors for infertility, the transmission of HIV, and human papilloma virus-induced cervical neoplasia. Control of C. trachomatis infections is an important public health goal. Unexpectedly, however, aggressive infection control measures based on early detection and antibiotic treatment have resulted in an increase in infection rates, most likely by interfering with natural immunity, a concept suggested by studies performed in experimental infection models. Effective management of chlamydial disease will likely require the development of an efficacious vaccine.

This technology claims vaccine compositions that comprise an immunologically effective amount of PmpD protein from C. trachomatis. Also claimed in the application are methods of immunizing individuals against C. trachomatis. PmpD is an antigenically stable pan-neutralizing target that, in theory, would provide protection against all human strains, thus allowing the development of a univalent vaccine that is efficacious against both blinding trachoma and sexually transmitted disease.

Application: Prophylactics against C. trachomatis.

Developmental Status: Preclinical studies have been performed.

Inventors: Harlan Caldwell and Deborah Crane (NIAID).

Publication: DD Crane et al. Chlamydia trachomatis polymorphic membrane protein D is a species-common pan-neutralizing antigen. Proc Natl Acad Sci USA. 2006 Feb 7;103(6):1894-1899.

Patent Status: PCT Patent Application No. PCT/US2007/001213 filed 16 Jan 2007, which published as WO 2007/082105 on 19 Jul 2007 (HHS Reference No. E-031-2006/0-PCT-02).

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 Intracellular Parasites is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize PmpD vaccine development. Please contact Harlan D. Caldwell, at [e-mail] or 406-363-9333 for more information.

Dated: February 11, 2008.

Steven M. Ferguson,

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