E8-31239. 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: [phone]; fax: [phone]. 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; [e-mail].

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 [e-mail] 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; [e-mail].

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 [e-mail] 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.