[Federal Register Volume 73, Number 180 (Tuesday, September 16, 2008)]
[Notices]
[Pages 53432-53433]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-21507]


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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.

Compositions and Methods for Increasing Recombinant Protein Yields 
Through the Modification of Cellular Properties

    Description of Technology: This technology relates to compositions 
and methods for improving the growth characteristics of cells 
engineered to produce biologically active products such as antibodies 
or glycosylated proteins. Featured is a method that uses gene 
candidates (e.g., cdkl3, siat7e, or lama4), or their expressed or 
inhibited products in cell lines, such as Human Embryonic Kidney 
(including HEK-293), HeLa, or Chinese Hamster Ovary (CHO). The gene 
expression modulates growth characteristics, such as adhesion 
properties, of the cell lines thereby increasing recombinant protein 
yields and reducing product production costs.
    Applications: This technology may be used to improve production of 
therapeutic and/or diagnostic compounds, including therapeutic proteins 
or monoclonal antibodies from mammalian cells. Optimization of 
mammalian cells for use as expression systems in the production of 
biologically active products is very difficult. For certain 
applications, anchorage-independent cell lines may be preferred, 
whereas for other applications, a cell line that adheres to a surface, 
e.g., is anchorage-dependent, may be preferable. This technology 
provides a method for identifying a gene whose expression modulates 
such cellular adhesion characteristics. This method thus leads to an 
increase in the expression or yield of polypeptides, including 
therapeutic biologicals, such as antibodies, cytokines, growth factors, 
enzymes, immunomodulators, thrombolytics, glycosylated proteins, 
secreted proteins, and DNA sequences encoding such polypeptides and a 
reduction in the associated costs of such biological products.
    Advantages: This technology offers the ability to improve yields 
and reduce the cost associated with the production of recombinant 
protein products through the selection of cell lines having:
     Altered growth characteristics.
     Altered adhesion characteristics.
     Altered rate of proliferation.
     Improvement in cell density growth.
     Improvement in recombinant protein expression level.
    Market: Biopharmaceuticals, including recombinant therapeutic 
proteins and monoclonal antibody-based products used for in vivo 
medical purposes and nucleic acid based medicinal products now 
represent approximately one in every four new pharmaceuticals on the 
market. The market size has been estimated at $33 billion in 2004 and 
is projected to reach $70 billion by the end of the decade. The list of 
approved biopharmaceuticals includes recombinant hormones and growth 
factors, mAB-based products and therapeutic enzymes as well as 
recombinant vaccines and nucleic acid based products.
    Mammalian cells are widely used expression systems for the 
production of biopharmaceuticals. Human embryo kidney (including HEK-
293) and Chinese hamster ovary (CHO) are host cells of choice. The 
genes identified in this technology (e.g., cdkl3, sia7e, or lama4) can 
be used to modify these important cell based systems.
    This technology is ready for use in drug/vaccine discovery, 
production and development. The technology provides methods for 
identification of specific gene targets useful for altering the 
production properties of either existing cell lines to improve yields 
or with new cell lines for the production of therapeutic and/or 
diagnostic compounds from mammalian cells.
    Companies that are actively seeking production platforms based on 
mammalian cell lines that offer high

[[Page 53433]]

efficiency, high throughput systems for protein production or analysis 
at lower cost and ease of scale-up would be potential licensors of this 
technology.
    Development Status: Late Stage--Ready for Production.
    Inventors: Joseph Shiloach (NIDDK), Pratik Jaluria (NIDDK).
    Related Publication: P. Jaluria et al. Application of microarrays 
to identify and characterize genes involved in attachment dependence in 
HeLa cells. Metab Eng. 2007 May;9(3):241-251.
    Patent Status: PCT Application No. PCT/US2007/018699 filed 24 Aug 
2007, which published as WO 2008/024459 on 28 Feb 2008; claiming 
priority to 24 Aug 2006 (HHS Reference No. E-149-2006/2-PCT-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Diabetes and Digestive and Kidney Diseases, Biotechnology Core 
Laboratory, is seeking parties interested in collaborative research 
projects directed toward the use of this technology with cells for drug 
and vaccine production and development, including growth optimization, 
production and product recovery processes. For more information, please 
contact Dr. Joseph Shiloach, [email protected], or Rochelle 
S. Blaustein at [email protected].

In Vitro Model for Hepatitis C Virion Production

    Description of Technology: This invention provides an in vitro 
hepatitis C virus (HCV) replication system that is capable of producing 
viral particles in a culture medium. Hepatitis C is a major public 
health problem, the development of therapeutics for which has been 
hampered by a lack of a robust model system to study the complete viral 
life cycle. This invention provides a new model system for the complete 
replication cycle of hepatitis C virus and virion production, assembly 
and release. The model is useful for screening antiviral agents against 
HCV.
    A full length HCV construct, CG1b of genotype 1b which is known to 
be infectious, was placed between two ribozymes designed to generate 
the exact 5' and 3' ends of HCV when cleaved. Using this system, HCV 
proteins and positive and negative RNA strands have been shown to 
reproduce intracellularly, and viral particles that resemble authentic 
HCV virions are produced and secreted into the culture medium.
    The patent application includes claims directed toward the 
following: A construct comprising specific nucleic acid sequences 
including HCV genotype 1b, genotype 1a, genotype 2a or potentially 
other genotypes; a method for identifying a cell line that is 
permissive for infection with HCV; a method for propagating HCV in 
vitro; a method for screening agents capable of modulating HCV 
replication or activity; a method for testing the level of HCV 
replication or activity; a HCV vaccine comprising HCV virus particles.
    Applications: The model offers a novel method for investigating the 
entire HCV life cycle including replication and pathogenesis and is 
useful for high-throughput antiviral screening. This technique may also 
be useful for making infectious particles that are useful in the 
production of HCV vaccines.
    Advantages: This system provides a new, stable and efficient cell 
culture model to further study the life cycle and biology of HCV, and 
to test potential therapeutic targets for hepatitis C. This model has 
also been used to generate in cell culture HCV strains infectious for 
chimpanzees, the only experimental animal susceptible to infection with 
the hepatitis C virus, a critical step in the development of new 
vaccines for Hepatitis C.
    Market: Hepatitis C virus (HCV) chronically infects approximately 
200 million people worldwide and increases the risk of developing 
cirrhosis and hepatocellular carcinoma. This technology would be useful 
for studying the HCV life cycle, screening for therapeutic agents 
against multiple HCV strains, including Genotype 1a, 1b and 2a, and the 
development of HCV vaccines. HCV genotypes 1 and 2 are the major 
genotypes with worldwide distribution; they are known to be associated 
with different clinical profiles and therapeutic responses. Hence, the 
model may be used to screen for varying levels of effectiveness of 
therapeutics against the major HCV genotypes.
    Development Status: This technology is available for use in 
diagnostics, drug/vaccine discovery, production and development. 
Current work is directed toward studies into the HCV life cycle and 
replication and the pathogenesis of HCV screening for antiviral agents 
against multiple HCV strains. This model has been used to generate in 
cell culture HCV strains infectious for chimpanzees, the only 
experimental animal susceptible to infection with the hepatitis C 
virus, a critical step in the development of new vaccines for Hepatitis 
C. Future work may be directed toward the use of this system for 
development of vaccine candidates against HCV.
    Inventors: T. Jake Liang and Theo Heller (NIDDK).
    Related Publications:
    1. Z. Hu et al. Altered proteolysis and global gene expression in 
hepatitis B virus X transgenic mouse liver. J Virol. 2006 
Feb;80(3):1405-1413.
    2. T. Heller et al. An in vitro model of hepatitis C virion 
production. Proc Natl Acad Sci USA. 2005 Feb 15;102(7):2579-2583.
    Patent Status: U.S. Patent Application No. 11/664,375 filed 30 Mar 
2007, claiming priority to 30 Sep 2004 (HHS Reference No. E-324-2004/3-
US-02).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301-435-4646; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Diabetes and Digestive and Kidney Diseases, Liver Diseases Branch, is 
seeking parties interested in collaborative research directed toward 
molecular strategies for vaccine and antiviral development, and animal 
models of viral hepatitis C. For more information, please contact Dr. 
T. Jake Liang at 301-496-1721 or [email protected] or Rochelle S. 
Blaustein at [email protected].

    Dated: September 9, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-21507 Filed 9-15-08; 8:45 am]
BILLING CODE 4140-01-P