[Federal Register Volume 74, Number 171 (Friday, September 4, 2009)]
[Notices]
[Pages 45866-45867]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-21482]


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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, HHS.

ACTION: Notice.

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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: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

Antigenic Chimeric Tick-Borne Encephalitis Virus/Dengue Virus Type 4 
Recombinant Viruses

    Description of Technology: The tick-borne encephalitis virus (TBEV) 
complex is a group of viruses that can cause severe neutrotropic 
disease and up to thirty percent (30%) mortality. While these viruses 
can be found in many parts of the world, the largest impact of the 
disease occurs in Europe and Russia, where approximately fourteen 
thousand (14,000) hospitalized TBEV cases occur annually. TBEV is in 
the family Flaviviridae, genus flavivirus and is composed of a 
positive-sense single stranded RNA genome that contains 5' and 3' non-
coding regions and a single open reading frame encoding ten (10) 
proteins. 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, 
TBEV/DEN4Delta30. This chimeric virus also contains attenuating 
mutations within the E and nonstructural NS5 proteins. Preclinical 
testing results with the derived virus indicate that chimerization of 
TBEV with DEN4Delta30 and introduction of the attenuating mutations 
decreased neuroinvasiveness and neurovirulence in mice. The TBEV/
DEN4delta30 vaccine candidate was safe, immunogenic, and provided 
protection in monkeys against challenge with TBE viruses.
    This application claims live attenuated chimeric TBEV/DEN4Delta30 
vaccine compositions. Also claimed are methods of treating or 
preventing TBEV infection in a mammalian host, methods of producing a 
subunit vaccine composition, isolated polynucleotides comprising a 
nucleotide sequence encoding a TBEV immunogen, methods for detecting 
TBEV infection in a biological sample and infectious chimeric TBEV.
    Applications: Development of Tick-Borne Encephalitis Virus 
vaccines, therapeutics and diagnostics.
    Advantages: Live attenuated chimeric vaccine, known regulatory 
pathway, potential for lasting immunity with fewer doses.
    Development Status: Vaccine candidates have been synthesized and 
preclinical studies have been performed.
    Inventors: Alexander G. Pletnev, Amber R. Engel, Brian R. Murphy 
(NIAID).
    Patent Status: U.S. Provisional Application No. 61/181,982 filed 28 
May 2009 (HHS Reference No. E-078-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[email protected].
    Collaborative Research Opportunity: The NIAID is seeking statements 
of capability or interest from parties interested in collaborative 
research in preclinical study of the long-term immunity induced by the 
TBEV/DEN4 vaccine candidate against highly virulent TBE viruses and in 
the clinical trials of this vaccine in humans. Please contact Michael 
Piziali, NIAID Office of Technology Development, at 301-496-2644 for 
more information.

Monoclonal Antibodies That React With the Capsule of Bacillus anthracis

    Description of Technology: Bacillus anthracis is the causative 
agent of anthrax and is surrounded by a

[[Page 45867]]

polypeptide capsule of poly-[gamma]-D-glutamic acid ([gamma]DPGA). 
[gamma]DPGA is poorly immunogenic and has antiphagocytic properties. 
The bacterial capsule is essential for virulence. Antibodies to the 
capsule have been shown to enhance phagocytosis and killing of 
encapsulated bacilli. These antibodies in combination with antibodies 
that neutralize the toxins of B. anthracis could provide enhanced 
protection by their dual antibacterial and antitoxic activities. Such 
antibodies would be especially useful for antibiotic-resistant strains.
    In order to obtain therapeutically useful anti-[gamma] DPGA 
monoclonal antibodies (MAbs), the inventors immunized chimpanzees with 
conjugates of 15-mer glutamic acid polymers to immunogenic protein 
carriers (recombinant protective antigen (PA) of B. anthracis). After 
several immunizations, chimpanzees developed strong immune responses to 
[gamma]DPGA. A combinatorial Fab library of mRNA derived from the 
chimpanzee's bone marrow was prepared and eight (8) distinct Fabs 
reactive with native [gamma]DPGA were recovered. Two (2) of the Fabs 
were converted into full-length IgG with human [gamma]1 heavy chain 
constant regions. These two (2) MAbs showed strong opsonophagocytic 
killing of bacilli in an in vitro assay. These two (2) MAbs were also 
tested for protection of mice challenged with virulent anthrax spores 
and results showed that both MAbs provided full or nearly full 
protection at a dose of 0.3 mg, the lowest dose tested, which is much 
more potent than previously reported murine anti-PGA MAbs. Since 
chimpanzee immunoglobulins are virtually identical to human 
immunoglobulins, these chimpanzee anticapsule MAbs may have clinically 
useful applications.
    This application claims the antibody compositions described above. 
Also claimed are methods of treating or preventing B. anthracis 
infection in a mammalian host and isolated polynucleotides comprising a 
nucleotide sequence encoding the antibodies of the technology.
    Applications: Development of anthrax vaccines, therapeutics and 
diagnostics.
    Advantages: Strongly neutralizing antibodies, known regulatory 
pathway, potential for use as both a prophylaxis and therapy.
    Development Status: Preclinical studies have been performed 
utilizing the monoclonal antibodies of this technology.
    Inventors: Zhaochun Chen (NIAID), Robert H. Purcell (NIAID), Joanna 
Kubler-Kielb (NICHD), Lily Zhongdong Dai (NICHD), Rachel Schneerson 
(NICHD).
    Patent Status: U.S. Provisional Application No. 61/116,222 filed 19 
Nov 2008 (HHS Reference No. E-125-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[email protected].
    Collaborative Research Opportunity: The NIAID is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize MAbs 
neutralizing anthrax toxins and capsule for comprehensive protection 
against anthrax. Please contact Bill Ronnenberg, NIAID Office of 
Technology Development, at 301-451-3522 for more information.

    Dated: August 28, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-21482 Filed 9-3-09; 8:45 am]
BILLING CODE 4140-01-P