[Federal Register Volume 74, Number 1 (Friday, January 2, 2009)]
[Notices]
[Pages 113-114]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-31239]


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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

[[Page 114]]

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.

Knockout of Aryl Hydrocarbon Receptor (AhR) and Its Binding Partner 
Aryl Hydrocarbon Receptor Nuclear Translocator (Arnt) Each in Separate 
Mouse Models

    Description of Technology: The technology relates to two separate 
knockout mouse models of related transcription factors that bind each 
other. The aryl hydrocarbon receptor (AhR) and the aryl hydrocarbon 
receptor nuclear translocator (Arnt) protein are transcription factors 
that play an important role in mediating the effects of man-made 
environmental toxins. They also play a role in mammalian development 
and physiological homeostasis. Members of the PAS domain/bHLH family of 
transcription factors, they are obligate dimerization partners with 
each other and other members of this family, such as hypoxia-inducible 
factor 1alpha (HIF1alpha). These transcription factors have been shown 
to be important in a number of specific tissues including ovary, 
vascular endothelium, keratinocytes, T-cells, and liver.
    Available for licensing is a knockout mouse line in which the AhR 
receptor has been knocked-out, and a mouse line containing a floxed 
allele of the Arnt gene. The Arnt mouse line can be used to disrupt the 
Arnt gene in different tissues by breeding the Arnt-floxed mice with 
transgenic mice in which the Cre recombinase is under the control of 
tissue-specific promoters. These mice may be used as a research tool 
for drug development where PAS/bHLH transcription factors are targeted.
    Applications:
     Tool for drug studies targeting PAS/bHLH transcription 
factors.
     Tool to probe the role of the Arnt protein in a tissue-
specific manner.
    Inventors: Frank J. Gonzalez and Pedro M. Fernandez-Salguero (NCI).
    Related Publications:
    1. S Tomita, CJ Sinal, SH Yim, and FJ Gonzalez. Conditional 
disruption of the aryl hydrocarbon receptor nuclear translocator (Arnt) 
gene leads to loss of target gene induction by the aryl hydrocarbon 
receptor and hypoxia-inducible factor 1alpha. Mol Endocrinol. 2000 
Oct;14(10):1674-1681.
    2. SH Yim, Y Shah, S Tomita, HD Morris, O Gavrilova, G Lambert, JM 
Ward, and FJ Gonzalez. Disruption of the Arnt gene in endothelial cells 
causes hepatic vascular defects and partial embryonic lethality in 
mice. Hepatology. 2006 Sep;44(3):550-560.
    3. P Fernandez-Salguero et al. Immune system impairment and hepatic 
fibrosis in mice lacking the dioxin-binding Ah receptor. Science 1995 
May 5;268(5211):722-726.
    Patent Status: HHS Reference Nos. E-046-2009/0 and E-047-2007/0--
Research Tools. Patent protection is not being pursued for these 
technologies.
    Licensing Status: This technology is available as a research tool 
under a Biological Materials License.
    Licensing Contact: Steve Standley, Ph.D.; 301-435-4074; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Metabolism, Center for Cancer Research, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

Recombineering Vector

    Description of Technology: Transgenic mouse models have become a 
common experimental tool for unraveling gene function. Bacterial 
artificial chromosome (BAC) mediated transgenesis has proven to be a 
highly reliable way to obtain accurate transgene expression for in vivo 
studies of gene expression and function. A rate-limiting step in 
characterizing large numbers of genes by this approach has been the 
speed and ease by which BACs can be modified. NIH investigators have 
developed a highly efficient recombineering vector that can be used for 
modifying BACs in bacteria. This new vector contains tetracycline and 
chloramphenical resistance as well as the ccdB gene that encodes a 
protein that interferes with E. coli DNA gyrase. This vector can be 
propagated in ccdB resistant E. coli strains but not in other strains 
(DH5a, Top10, DH10B, etc.) unless the ccdB is replaced by DNA inserts 
flanked by attB1 and attB2 sites. This vector was generated to modify 
BAC plasmids by RecA-mediated recombination.
    The vector disclosed here bypasses the rate-limiting step in 
recombineering protocols; the efficient cloning of a modifying vector. 
It is well suited for efficient production of engineered BACs for use 
in a variety of in vivo studies.
    Applications:
     The fusion of fluorescent protein or cre recombinase genes 
to a gene of interest.
     Generation of dominant negative mutations.
     Introduction of gene mutations that would mimic disease 
conditions.
     Insertion of lox sites for conditional deletion of 
transgenes.
     Generation of knock-out or knock-in constructs.
    Inventors: Rafael C. Casellas and Susan E. Lim (NIAMS).
    Patent Status: HHS Reference No. E-026-2009/0--Research Material. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for Biological Material Licensing.
    Licensing Contact: Suryanarayana (Sury) Vepa, Ph.D., J.D.; 301-435-
5020; [email protected].
    Collaborative Research Opportunity: The NIAMS/NIH Genomics and 
Immunity group is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize the engineering of mouse transgenic 
constructs using the new vector and BAC recombineering. Please contact 
Rafael Casellas, Ph.D. at 301-402-7858 or e-mail to 
[email protected] for more information.

    Dated: December 22, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E8-31239 Filed 12-31-08; 8:45 am]
BILLING CODE 4140-01-P