[Federal Register Volume 72, Number 80 (Thursday, April 26, 2007)]
[Notices]
[Pages 20856-20858]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-7930]


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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.

Biotinylated Alkylating Acridine for Pull-downs of Viral Pre-
integration Complexes (PIC) or Other Cytosol Localized DNAs

    Description of Technology: The invention describes a DNA-binding 
molecule that allows recovery of viral DNA and associated proteins. An 
acridine orange based molecule was modified and the resulting 
alkylating acridine molecule intercalates with viral pre-integration 
complexes (PIC) or other DNAs localized in cytosol. Because the 
molecule is also biotinylated, streptavidin beads can be used to purify 
the molecule and the bound DNA and associated protein can subsequently 
be eluted and analyzed. The invention provides a useful tool to 
facilitate the studies for viral PIC and other cytosol DNAs.
    Applications: Research Tool.
    Development Status: In vitro data available.
    Inventors: Gunnar Thor Gunnarsson and Rafal Wierzchoslawski (NCI).
    Patent Status: HHS Reference No. E-131-2007/0--Research Tool.
    Licensing Status: Available for non-exclusive licensing as 
biological material and research tool.
    Licensing Contact: Sally Hu, Ph.D.; 301/435-5606; [email protected].

[[Page 20857]]

Structure of TIM Family Members

    Description of Technology: Available for licensing and commercial 
development are methods to produce and/or enhance therapeutic agents 
based on models of the three-dimensional structures of the Ig-like 
domains of various TIM family members to a) develop agonists and 
antagonists of the T-cell immunoglobulin mucin (TIM) family of 
receptors and b) design specific TIM receptor-mutants with altered 
binding capabilities. The TIM receptors are involved in the regulation 
of immune responses, tissue regeneration, cancer, and viral cell entry. 
The invention provides models of the three-dimensional structures of 
the Ig-like domains of TIM family members developed after several 
crystal structures were resolved. The structures were further validated 
by mutagenesis and biochemical analysis.
    The TIM family comprises type 1 integral membrane glycoproteins 
containing a characteristic six-cysteine Ig-like domain extended above 
the cell surface by a mucin-like domain. The crystal structures 
revealed diverse homophylic interactions between TIM family members. 
The three-dimensional structure of all TIM family members can be used 
in the making of agonists and antagonists of homophilic, heterophilic, 
and ligand interactions of these receptors.
    Applications:
    1. Therapies that target the interaction of TIM family members with 
their ligands, such as small molecules or monoclonal antibodies, can 
control immune responses and the development of a variety of diseases.
    2. TIM receptor-mutants with enhanced, reduced, or destroyed 
binding capabilities to ligands and TIM family receptors can control 
TIM receptor-functions.
    3. Furthermore, the homophylic, heterophylic, and ligand 
interactions between the TIM receptors and the TIM receptor-mutants can 
be used as targets to develop therapeutic agents for medical and 
veterinary purposes, to prevent viral infection, regulate immune 
responses, modulate cell adhesion and tissue regeneration, treat and 
prevent cancer, and treat autoimmune and atopic diseases.
    Development Status: The technology is in early stages of 
development.
    Inventors: Gerardo Kaplan (CBER/FDA), et al.
    Related Publications:
    1. C Santiago, A Ballesteros, C Tami, L Mart[iacute]nez-
Mu[ntilde]oz, GG Kaplan, JM Casasnovas. Structures of T cell 
immunoglobulin mucin receptors 1 and 2 reveal mechanisms for regulation 
of immune responses by the TIM receptor family. Immunity. 23 Mar 
2007;26(3):299-310.
    2. A Anderson, S Xiao, VK Kuchroo. Tim protein structures reveal a 
unique face for ligand binding. Immunity. 23 Mar 2007;26(3):273-275.
    Patent Status: U.S. Provisional Application No. 60/865,642 filed 13 
Nov 2006 (HHS Reference No. E-098-2006/0-US-01)
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., M.B.A.; 301/
435-4507; [email protected].

A Method With Increased Yield for Production of Polysaccharide-Protein 
Conjugate Vaccines Using Hydrazide Chemistry

    Description of Technology: Current methods for synthesis and 
manufacturing of polysaccharide-protein conjugate vaccines employ 
conjugation reactions with low efficiency (about twenty percent). This 
means that up to eighty percent of the added activated polysaccharide 
(PS) is lost. In addition, inclusion of a chromatographic process for 
purification of the conjugates from unconjugated PS is required.
    The present invention utilizes the characteristic chemical property 
of hydrazide groups on one reactant to react with aldehyde groups or 
cyanate esters on the other reactant with an improved conjugate yield 
of at least sixty percent. With this conjugation efficiency the 
leftover unconjugated protein and polysaccharide would not need to be 
removed and thus the purification process of the conjugate product can 
be limited to diafiltration to remove the by-products of small 
molecules. The new conjugation reaction can be carried out within one 
or two days with reactant concentrations between 1 and 25 mg/mL at PS/
protein ratios from 1:2 to 3:1, at temperatures between 4 and 40 
degrees Centigrade, and in a pH range of 5.5 to 7.4, optimal conditions 
varying from PS to PS.
    Application: Cost effective and efficient manufacturing of 
conjugate vaccines.
    Inventors: Che-Hung Robert Lee and Carl E. Frasch (CBER/FDA)
    Patent Status: U.S. Patent Application No. 10/566,899 filed 01 Feb 
2006, claiming priority to 06 Aug 2003 (HHS Reference No. E-301-2003/0-
US-10); U.S. Patent Application No. 10/566,898 filed 01 Feb 2006, 
claiming priority to 06 Aug 2003 (HHS Reference No. E-301-2003/1-US-
02); International rights available.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Identification of Anti-HIV Compounds Inhibiting Virus Assembly and 
Binding of Nucleocapsid Protein to Nucleic Acid

    Description of Technology: The subject invention identified two 
groups of active anti-viral compounds. The first group comprises 
aromatic, antimony-containing compounds, while the second group 
comprises aromatic tricarboxylic acid. Both groups were shown to 
inhibit viral particle assembly and inhibit the binding of nucleocapsid 
protein to nucleic acid. Recently, the first group also demonstrated 
the capability of blocking HIV-1 viral entry into CD4+ cells through 
binding to CD4 and inhibiting gp120-CD4 interaction, and they are well 
tolerated in vivo. Hence, these compounds are potent inhibitors of HIV 
and act via a novel mechanism, ideal for developing a new generation of 
anti-HIV medicine.
    Applications: HIV treatment and prevention.
    Development Status: In vivo preclinical data available, including 
data from efficacy, pharmacokinetics and preliminary toxicity studies.
    Inventors: Robert H. Shoemaker (NCI), Michael J. Currens (NCI), 
Alan R. Rein (NCI), Ya-xiong Feng (NCI), Robert J. Fisher (SAIC/NCI), 
Andrew G. Stephen (SAIC/NCI), Karen Worthy (SAIC/NCI), Shizuko Sei 
(SAIC/NCI), Bruce Crise (SAIC/NCI), Louis E. Henderson (SAIC/NCI).
    Related Publication: QE Yang et al. Discovery of small-molecule 
human immunodeficiency virus type 1 entry inhibitors that target the 
gp120-binding domain of CD4. J Virol. 2005 May;79(10):6122-6133.
    Patent Status: U.S. Patent Application No. 10/528,747 filed 22 Mar 
2005 (HHS Reference No. E-121-2002/0-US-03); European Patent 
Application No. 03773233.6 filed 08 May 2005 (HHS Reference No. E-121-
2002/0-EP-04).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Sally Hu, Ph.D.; 301/435-5606; [email protected].
    Collaborative Research Opportunity: The NCI HIV DRP Retroviral 
Replication Laboratory is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize these active anti-viral compounds. Please 
contact John D. Hewes, Ph.D. at 301-435-3121 or

[[Page 20858]]

[email protected] for more information.

Monoclonal Antibodies Specific for the E2 Glycoprotein of Hepatitis C 
Virus and Their Use in the Diagnosis, Treatment and Prevention of 
Hepatitis C

    Description of Technology: Hepatitis C virus is an enveloped, 
single-stranded RNA virus, approximately 50 nm in diameter, that has 
been classified as a separate genus in the Flaviviridae family. Most 
persons infected with hepatitis C virus develop chronic infection. 
These chronically infected individuals have a relatively high risk of 
developing chronic hepatitis, liver cirrhosis and hepatocellular 
carcinoma. There is currently no vaccine to prevent the hepatitis C 
virus infection. The present invention relates to human monoclonal 
antibodies which exhibit immunological binding affinity for the 
hepatitis C virus E2 glycoprotein and are cross-reactive against 
different hepatitis C virus strains. These antibodies may be used in 
passive immunoprophylaxis for the prevention of hepatitis C virus 
infection and/or in passive immunotherapy for the treatment of 
hepatitis C.
    Applications: In vitro diagnostic assay for identifying patients 
infected with hepatitis C virus and contaminated blood samples; method 
of preventing infection using monoclonal antibodies that neutralize E2 
glycoproteins from different genotypes of hepatitis C virus.
    Market: Over 4 million people in the U.S. are infected with 
hepatitis C virus. An estimated 150 to 200 million people are infected 
with hepatitis C virus worldwide.
    Inventors: Suzanne U. Emerson (NIAID), Robert H. Purcell (NIAID), 
Harvey J. Alter (NIAID), et al.
    Related Publication: DJ Schofield et al. Human monoclonal 
antibodies that react with the E2 glycoprotein of hepatitis C virus and 
possess neutralizing activity. Hepatology. 2005 Nov;42(5):1055-1062.
    Patent Status: U.S. Provisional Application No. 60/250,561, filed 
01 Dec 2000 (HHS Reference No. E-017-2001/0-US-01); PCT Application No. 
PCT/US01/45221, filed 30 Nov 2001, published as WO 02/055560 on 18 Jul 
2002 (HHS Reference No. E-017-2001/0-PCT-02); U.S. Patent Application 
No. 10/432,006 filed 16 May 2003, issued as U.S. Patent No. 6,924,362 
on 02 Aug 2005 (HHS Reference No. E-017-2001/0-US-03)
    Licensing Contact: Chekesha S. Clingman, Ph.D.; 301/435-5018; 
[email protected].
    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 these monoclonal antibodies. For more 
information, please contact Robert H. Purcell, M.D., Co-chief, 
Laboratory of Infectious Diseases, National Institute of Allergy and 
Infectious Diseases, National Institutes of Health, 50 South Drive, 
Bldg. 50, Rm. 6523, Bethesda, MD 20892-8009; Phone (301) 496-5090; Fax 
(301) 402-0524.

Major Neutralization Site of Hepatitis E Virus and Use of This 
Neutralization Site in Methods of Vaccination

    Description of Technology: Hepatitis E is endemic in many countries 
throughout the developing world, in particular on the continents of 
Africa and Asia. The disease generally affects young adults and has a 
very high mortality rate, up to 20%, in pregnant women. This invention 
relates to the identification of a neutralization site of hepatitis E 
virus (HEV) and neutralizing antibodies that react with it. The 
neutralization site is located on a polypeptide from the ORF2 gene 
(capsid gene) of HEV. This neutralization site was identified using a 
panel of chimpanzee monoclonal antibodies that are virtually identical 
to human antibodies. Since this neutralization site is conserved among 
genetically divergent strains of HEV, the neutralizing monoclonal 
antibodies may be useful in the diagnosis, treatment and/or prevention 
of hepatitis E. Furthermore, immunogens that encompass this 
neutralization site may be used in vaccination to effectively prevent, 
and/or reduce the incidence of HEV infection. Polypeptides containing 
this neutralization site may be useful in evaluating vaccine candidates 
for the production of neutralizing antibodies to HEV.
    Inventors: Suzanne U. Emerson (NIAID), Robert H. Purcell (NIAID), 
et al.
    Related Publications:
    1. YH Zhou et al. A truncated ORF2 protein contains the most 
immunogenic site on ORF2: antibody responses to non-vaccine sequences 
following challenge of vaccinated and non-vaccinated macaques with HEV. 
Vaccine 2005 May 2;23(24):3157-3165.
    2. DJ Schofield et al. Monoclonal antibodies that neutralize HEV 
recognize an antigenic site at the carboxyterminus of an ORF2 protein 
vaccine. Vaccine 2003 Dec 12;22(2):257-267.
    3. YH Zhou et al. An ELISA for putative neutralizing antibodies to 
hepatitis E virus detects antibodies to genotypes 1, 2, 3, and 4. 
Vaccine 2004 Jun 30;22(20):2578-2585.
    Patent Status: U.S. Patent No. 6,930,176, issued 16 Aug 2005 (HHS 
Reference No. E-043-2000/0-US-04); EP Application 00982311.3, filed on 
30 Nov 2000, published as 1235862 on 04 Sept 2002 (HHS Reference No. E-
043-2000/0-EP-03); U.S. Patent No. 7,148,323, issued 12 Dec 2006 (HHS 
Reference No. E-043-2000/0-US-05)
    Licensing Contact: Chekesha S. Clingman, Ph.D.; 301/435-5018; 
[email protected].
    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 these antibodies or structures they interact 
with. For more information, please contact Robert H. Purcell, M.D., Co-
chief, Laboratory of Infectious Diseases, National Institute of Allergy 
and Infectious Diseases, National Institutes of Health, 50 South Drive, 
Bldg. 50, Rm. 6523, Bethesda, MD 20892-8009; Phone (301) 496-5090; Fax 
(301) 402-0524.

    Dated: April 17, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E7-7930 Filed 4-25-07; 8:45 am]
BILLING CODE 4140-01-P