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###### Department of Health and Human Services

###### National Institutes of Health

# 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:*                         301/496-7057;                         *fax:*                         301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.                    

## A Plasmid System for Monitoring Double-Stranded DNA Breaks in the Live Cell

*Description of Technology:*                     This technology is useful for studying the role of chromosomal breaks in cancer and for drug and assay development related to treating cancer. The technology is a two-plasmid system for inducing and monitoring individual double-stranded DNA breaks in the nuclei of live cells. The first plasmid, lac-I-SceI-tet, which is stably transfected into cells, has a rare 18 base pair restriction endonuclease site called ISceI. This site is flanked by an array of 256 copies of the lac-repressor binding site and 96 copies of the tetracycline response element. Plasmids expressing tet and lac repressor proteins labeled in a complementary fashion can be cotransfected to visualize these arrays of repressor binding sites. The second                           ( print page 48570)                        plasmid, RFP-I-SceI-GR, is a chimera between the ISceI endonuclease and the ligand binding domain of the glucocorticoid receptor (GR) in frame with red fluorescent protein (RFP). This GR chimera will translocate from the cytoplasm to the nucleus upon addition of triamcinolone acetonide, leading to rapid induction of a double-stranded break between the lac and tet arrays.                

*Applications:*
      - Tool for drug studies relating to DNA stability and repair.
      - Tool to probe the role of nuclear and DNA binding proteins in stability and repair.

*Inventors:*                     Thomas A. Misteli and Evi Soutoglou (NCI).                

*Related Publication:*                     E Soutoglou, JF Dorn, K Sengupta, M Jasin, A Nussenzweig, T Ried, G Danuser, T Misteli. Positional stability of single double-strand breaks in mammalian cells. Nat Cell Biol. 2007 Jun;9(6):675-682.                

*Patent Status:*                     HHS Reference No. E-264-2009/0—Research Tool. Patent protection is not being pursued for this technology.                

*Licensing Status:*                     This technology is available as a research tool under a Biological Materials License.                

*Licensing Contact:*                     Steve Standley, PhD; 301-435-4074;                     *sstand@od.nih.gov.*

## Mouse Embryonic Stem Cell-Based Functional Assay To Evaluate Mutations in BRCA2

*Description of Technology:*                     Mutations in breast cancer susceptibility genes BRCA1 and BRCA2 have up to an 80 percent life time risk in developing breast cancer. There are no “mutation hot spots” and to date, more than 1,500 different mutations have been identified in BRCA2. The absence of tumor cell lines expressing various mutant BRCA2 alleles has hindered evaluations to determine the functional differences between different mutations.                

A simple, versatile and reliable mouse embryonic stem cell and bacterial artificial chromosome based assay to generate cell lines expressing mutant human BRCA2 has been developed and it has been used to classify 17 sequence variants. Available for licensing are wild-type and eleven mutant BRCA2 cell lines developed from this assay that have either truncations or point mutations. These cell lines may be used to evaluate the effect of DNA damaging agents, genotoxins and chemotherapeutic efficacy.

*Applications:*
      - Research tool to generate and study BRCA2 mutations.
      - Method to screen for chemotherapeutics.
      - Method to evaluate DNA damaging agents.

*Advantages:*                     Ready to use portfolio of BRCA2 mutant cell lines to study BRCA2 mutant functional analysis.                

*Market:*                     An estimated 194,280 new cases of breast cancer will be diagnosed and may cause 40,610 deaths in the U.S. in 2009.                

*Inventors:*                     Shyam K. Sharan and Sergey Kuznetsov (NCI).                

*Publication:*                     SG Kuznetsov et al. Mouse embryonic stem cell-based functional assay to evaluate mutations in BRCA2. Nat Med. 2008 Aug;14(8):875-881.                

*Patent Status:*                     HHS Reference No. E-261-2007/0—Research Tool. Patent protection is not being pursued for this technology.                

*Licensing Status:*                     Available for licensing.                

*Licensing Contact:*                     Jennifer Wong; 301-435-4633;                     *wongje@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize mouse embryonic stem cell lines suitable for functional analysis of BRCA2 variants. Please contact John D. Hewes, Ph.D. at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                

## Establishment of Two Cell Lines That Stably Express Luciferase for In Vivo Tracking

*Description of Technology:*                     Available for licensing are two renal carcinoma cell lines, 786-O(luc) and 786-O/VHL/(luc) which both stably express luciferase. 786-O(luc) lacks von Hippel-Landau (VHL) protein expression and it has constitutively high expression of hypoxia-inducible transcription factor-2alpha (HIF-2alpha). The second stably expresses VHL, a tumor suppressor, and has minimal HIF-2alpha expression. These cell lines can be tracked in vivo and can be used to study VHL-dependent and HIF-2alpha dependent events such as tumorigenesis. VHL mutations lead to the clinical manifestations of von Hippel-Lindau disease, a rare autosomal dominant syndrome characterized by abnormal growth of blood vessels in multiple organs, including the brain and kidneys.                

*Applications:*                     Model to study VHL pathology.                

*Advantages:*                     Cell lines that stably express luciferase for in vivo tracking.                

*Benefits:*                     Easy, ready to use positive and negative VHL and HIF-2alpha cells that stably express luciferase for in vivo tests.                

*Market:*
      - Incidence of VHL syndrome is 1 in 38,951.
      - HCC is the third leading cause of cancer death worldwide.
      - HCC is the fifth most common cancer in the world.
      - Post-operative five-year survival rate of HCC patients is 30-40 percent.

*Inventors:*                     Leonard M. Neckers and W. Marston Linehan (NCI).                

*Patent Status:*                     HHS Reference No. E-005-2007/0—Research Tool. Patent protection is not being pursued for this technology.                

*Licensing Status:*                     Available for licensing.                

*Licensing Contact:*                     Jennifer Wong; 301-435-4633;                     *wongje@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The National Cancer Institute, Urologic Oncology Branch, is seeking statements of capability or interest from parties interested in collaborative research to develop further uses for these two cell lines that stably express luciferase for in vivo tracking. Please contact John D. Hewes, Ph.D. at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                

Dated: September 17, 2009.

Richard U. Rodriguez,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.

[FR Doc. E9-22974 Filed 9-22-09; 8:45 am]

BILLING CODE 4140-01-P