[Federal Register: April 26, 2007 (Volume 72, Number 80)]
[Notices]
[Page 20856-20858]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26ap07-68]
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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; HuS@mail.nih.gov.
[[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; thalhamc@mail.nih.gov.
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;
soukasp@mail.nih.gov.
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; HuS@mail.nih.gov.
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]]
hewesj@mail.nih.gov 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;
clingmac@mail.nih.gov.
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;
clingmac@mail.nih.gov.
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