[Federal Register Volume 74, Number 139 (Wednesday, July 22, 2009)]
[Notices]
[Pages 36238-36240]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-17319]


-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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.

High Diversity/High Affinity Domain Antibody Library

    Description of Invention: Available for licensing and commercial 
development is a highly diverse domain antibody (dAb) library providing 
antibodies that bind with high affinity to a variety of antigen 
targets. Antibody diversity is inherently limited by using only three 
CDRs of either light chain variable domain (LCDRs) or heavy chain 
variable domain (HCDRs). This novel dAb library is designed using light 
chain variable domain 3 (LCDR3) and heavy chain variable domain 
(HCDR3), which are of primary importance for creating binding site 
diversity in the human immune system. The library contains 2.5 x 10 
\10\ dAbs. Human naturally occurring LCDR3s were grafted onto HCDR1 of 
m0. These antibodies are of very small size (15-17 kDa), high

[[Page 36239]]

stability and can be expressed at high levels as monomers. The library 
can be used for the selection of antibodies to any antigen including 
cancer and viral antigens and exhibit such properties as good 
penetration, stability, solubility, high levels of expression (at 
potentially low cost), and low level of immunogenicity or toxicity.
    Applications: Cancer; Infectious disease; Therapeutics; 
Diagnostics; Research reagents; Research tools; Library panning.
    Inventors: Dimiter S. Dimitrov and Weizao Chen (NCI).
    Relevant Publications:
    1. P Jirholt et al. Exploiting sequence space: shuffling in vivo 
formed complementarity determining regions into a master framework. 
Gene 1998 Jul 30;215(2):471-476.
    2. Y Reiter et al. An antibody single-domain phage display library 
of a native heavy chain variable region: isolation of functional 
single-domain VH molecules with a unique interface. J Mol Biol. 1999 
Jul 16;290(3):685-698.
    3. L Riechmann and S Muyldermans. Single domain antibodies: 
comparison of camel VH and camelised human VH domains. J Immunol 
Methods 1999 Dec 10;231(1-2):25-38.
    4. E S[ouml]derlind et al. Recombining germline-derived CDR 
sequences for creating diverse single-framework antibody libraries. Nat 
Biotechnol. 2000 Aug;18(8): 852-856.
    5. LJ Holt et al. Domain antibodies: proteins for therapy. Trends 
Biotechnol. 2003 Nov;21(11): 484-490.
    6. W Chen et al. Construction of a large phage-displayed human 
antibody domain library with a scaffold based on a newly identified 
highly soluble, stable heavy chain variable domain. J Mol Biol. 2008 
Oct 10;382(3):779-789.
    Patent Status: HHS Reference No. E-216-2009/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
CCR, CCRNP is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize this domain antibody library. Please contact John D. 
Hewes, PhD at 301-435-3121 or [email protected] for more information.

Mouse Monoclonal Antibody Targeting Tetanus Toxin Heavy Chain Fragment 
C

    Description of Invention: The FDA is pleased to announce as 
available for licensing a murine monoclonal antibody that specifically 
binds to Fragment C of tetanus toxin. Tetanus toxin is one of the most 
potent neurotoxins known. It is a complex molecule, composed of a 
linked heavy chain and light chain, each having different domains 
serving different functions. One domain of the heavy chain, known as 
``Fragment C,'' is known to bind the toxin to neurons. Fragment C is 
the focus of much research, including: analysis of the subtle 
differences between neuronal uptake of tetanus toxin and the related 
botulinum toxin, the design of compounds that block the uptake of 
tetanus toxin, and design of drugs that target the same cellular 
mechanism to enhance uptake.
    Applications: Cell-based imaging agents; New drug development, 
including antitoxins.
    Advantages: Toxin specific-site antibodies.
    Development Status: Cell line (mouse-spleen hybridoma) established 
to produce antibodies.
    Inventors: Marjorie A. Shapiro, PhD, and Sean P. Fitzsimmons, PhD 
(FDA).
    Relevant Publication: SP Fitzsimmons, KJ Clark, R Wilkerson, MA 
Shapiro. Inhibition of tetanus toxin fragment C binding to ganglioside 
G(T1b) by monoclonal antibodies recognizing different fragment C 
epitopes. Vaccine 2000 Aug 15;19(1):114-121.
    Patent Status: HHS Reference No. E-061-2009/0--Research Materials. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for non-exclusive Biological Materials 
Licensing.
    Licensing Contact: Bruce Goldstein, J.D., M.S.; 301-435-5470; 
[email protected].
    Collaborative Research Opportunity: The FDA's Office of 
Biotechnology Products in the Center for Drug Evaluation and Research 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize antibodies directed against tetanus toxin. Please contact 
Alice Welch, PhD at (301) 827-0359 or [email protected] for more 
information.

Membrane Proximal Region of HIV gp41 Anchored to the Lipid Layer of a 
Virus-Like Particle Vaccine

    Description of Invention: The HIV-1 envelope glycoproteins (gp120-
gp41), which mediate receptor binding and entry, are the major targets 
for neutralizing antibodies. Although the envelope glycoproteins are 
immunogenic and induce a variety of antibodies, the neutralizing 
antibodies that are induced are strain-specific and the majority of the 
immune response is diverted to non-neutralizing determinants. Broadly 
neutralizing antibodies have been isolated only from natural HIV 
infection, and rarely, as only five broadly-neutralizing antibodies 
have been identified to date. Three are gp41-directed (2F5, 4E10 and 
Z13) and the other two (b12 and 2G12) are gp120-directed. The three 
gp41 neutralizing antibodies recognize the membrane proximal region 
(MPR) of the HIV-1 gp41 glycoprotein. The MPR region includes a series 
of amino acids that lie on the HIV virus surface, just before gp41 
crosses the viral membrane. The MPR is highly hydrophobic (fifty 
percent of its residues are hydrophobic) and is highly conserved across 
many HIV clades. Recently, the hydrophobic context of MPR and the 
presence of lipid membrane were shown to be important for the optimal 
binding of 2F5 and 4E10 antibodies. To date, immunization with 
conserved membrane proximal elements or the core 2F5 epitope in a 
number of contexts has failed to elicit broadly neutralizing 
antibodies.
    Available for licensing is a technology that uses the immunogenic 
hepatitis B surface antigen (HBsAg) platform to array epitopes from the 
conserved, neutralization-sensitive MPR of HIV-1, and use of these 
constructs to induce an immune response to HIV-1. The replacement of a 
membrane spanning domain of HBsAg with a membrane spanning domain of 
gp41 anchors gp41 into HBsAg in virtually the identical orientation as 
on HIV virions and correctly orients the nearby MPR on the lipid layer. 
More specifically, HBsAg variant compositions with one or more 
transmembrane domains of the HBsAg replaced with a gp41 transmembrane 
domain and one or more gp41 MPRs are available for licensing.
    Application: Development of Human Immunodeficiency Virus (HIV) 
vaccines, therapeutics and diagnostics.
    Development Status: Vaccine candidates have been synthesized and 
preclinical studies have been performed.
    Inventors: Ira Berkower (FDA).
    Patent Status: U.S. Provisional Application No. 61/086,098 filed 04 
Aug 2008 (HHS Reference No. E-291-2008/0-US-01).
    Licensing Status: Available for licensing.

[[Page 36240]]

    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[email protected].

A Unique Infectious Hepatitis C Virus Clone, Strain HC-TN (genotype 1a)

    Description of Invention: It is anticipated that this infectious 
clone of hepatitis C virus (HCV) strain HC-TN (genotype 1a) will be 
useful for the development of vaccines and antiviral drugs that target 
HCV, genotype 1a. The HC-TN strain is unique because it has been shown 
to cause fulminant hepatitis. To date, only one other HCV strain, JFH1 
(genotype 1b), has been isolated that is known to cause fulminant 
hepatitis. Additionally, little is known about the etiology of 
fulminant hepatitis C disease. Therefore, the HC-TN strain may be 
useful as a tool for studying the etiology of fulminant hepatitis. This 
invention includes the infectious clone, nucleotide sequences of the 
clone, and polypeptides encoded by the HC-TN clone. Methods are 
included for producing attenuated HCV, and for screening therapeutics 
against HCV and developing vaccines and diagnostics.
    Apparently, no companies or other laboratories have this HC-TN 
strain. The availability of the pHC-TN clone will be highly useful to 
pharmaceutical companies since no further research is required for its 
commercialization into, e.g., assays for testing antiviral compounds 
targeting HCV.
    Applications:
     Production of attenuated viruses and polypeptides.
     HCV vaccines, diagnostics, therapeutics and screening tool 
for anti-HCV compounds.
    Advantages: There is no universally effective therapy against HCV 
infection. This invention enables development of vaccines, diagnostics 
and therapeutics that are specific for the HC-TN strain or HCV genotype 
1a.
    Development Status: The technology is currently in the preclinical 
stage of development.
    Market: More than 80% of the HCV infections in North and South 
America, Europe, Russia, China, Japan and Australia are genotype 1. The 
instant technology may be transferred through biological materials 
licenses for territories in which no patent rights exist.
    Inventors: Jens Bukh, Robert H. Purcell, Suzanne U. Emerson, Akito 
Sakai, Patrizia Farci (NIAID).
    Publication: A Sakai et al. In vivo study of the HC-TN strain of 
hepatitis C virus recovered from a patient with fulminant hepatitis: 
RNA transcripts of a molecular clone (pHC-TN) are infectious in 
chimpanzees but not in Huh7.5 cells. J Virol. 2007 July;81(13):7208-
7219.
    Patent Status: U.S. Patent Application No. 12/061,504 filed 02 
April 2008 (HHS Reference No. E-249-2007/0-US-01); No foreign rights 
available.
    Licensing Status: Available for licensing.
    Licensing Contact: RC Tang, JD, LLM; 301-435-5031; 
[email protected].

    Dated: July 13, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Transfer, National Institutes of Health.
[FR Doc. E9-17319 Filed 7-21-09; 8:45 am]
BILLING CODE 4140-01-P