Document Headings

                    Document headings vary by document type but may contain                    the following:                  
                -                       the agency or agencies that issued and signed a document                    
                -                       the number of the CFR title and the number of each part                      the document amends, proposes to amend, or is directly                      related to                    
                -                       the agency docket number / agency internal file number                    
                -                       the RIN which identifies each regulatory action listed in                      the Unified Agenda of Federal Regulatory and Deregulatory                      Actions                    

                    See the                                          Document Drafting Handbook                                        for more details.                  

###### 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                               ( print page 57636)                            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.                     

## Matriptase Hypomorphic Mouse Model of a Human Ichthyosis 

*Description of Technology:*                     Available for licensing are mice with greatly reduced levels of matriptase, a membrane protease involved in epithelial development, immune function, and carcinogenesis. These mice were created to study autosomal recessive ichthyosis with hypotricosis (ARIH), an inherited human disease that has been linked to a mutation in the ST14 gene that encodes matriptase. These mice manifest the same defects seen in people afflicted by ARIH, so it can be an effective model for studying the role of matriptase in disorders that affect skin development.                 

*Applications:*
      - Research tool for skin development research.
      - Model to develop and test therapeutics for treating skin disorders, including skin cancer.
      - Model immunity and allergy.

*Advantages:*                     Well characterized animal model closely related to a human genetic disorder.                 

*Market:*                     Ichthyosis is a series of genetic skin diseases characterized by dry, thickened, scaling skin that affects more than one million Americans. Presently, there is no cure for ichthyosis, only treatments to help manage symptoms.                 

*Development Status:*                     Well characterized mouse model of human ARIH.                 

*Inventors:*                     Thomas H. Bugge (NIDCR)                     *et al.*

*Publication:*                     K List et al. Autosomal ichthyosis with hypotrichosis syndrome displays low matriptase proteolytic activity and is phenocopied in ST14 hypomorphic mice. J Biol Chem. 2007 Dec 14;282(50):36714-36723.                 

*Patent Status:*                     HHS Reference No. E-323-2008/0—Biological Material. Patent protection is not being pursued for this technology.                 

*Licensing Status:*                     Available for non-exclusive licensing under a Biological Materials License Agreement.                 

*Licensing Contact:*                     Adaku Nwachukwu, J.D.; 301-435-5560;                     *madua@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The National Institute of Dental and Craniofacial Research, Oral and Pharyngeal Cancer Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact David W. Bradley, Ph.D. at 301-402-0540 or                     *bradleyda@nidcr.nih.gov*                     for more information.                 

## Prostatic Adenocarcinoma Cells Expressing or Lacking the Tumor Suppressor Gene PTEN 

*Description of Technology:*                     PTEN is a tumor suppressor gene that is frequently deleted or mutated in a variety of human cancers, including prostate, breast, endometrial, lung, and ovarian cancers. In prostate cancer cells, PTEN deletion is the most common event observed. The loss of PTEN is thought to play and important role in tumor cell proliferation and metastasis due to a lack of control of the signaling pathways that mediate cellular processes such as apoptosis and migration. Previously PTEN had been shown to downregulate cyclin D1 expression as well as regulate p53 protein levels and transcriptional activity, and recently the inventors of this technology have shown that PTEN decreases surface IGF-IR protein levels in prostate cancer cell lines in an Akt-independent manner.                 

PC3 cells are prostate cancer cells that lack PTEN gene. This technology describes PC3 cells that overexpress the PTEN gene. These cell lines can be used to study the role of the PTEN gene in cancer growth and metastasis. 

*Market:*
      - Prostate cancer is the most common type of cancer found in American men, and it has been estimated that there were more than 230,000 new cases in the U.S. in 2007. Prostate cancer is also the second leading cause of cancer death in men.
      - In the U.S. over 2 million women have been treated for breast cancer, with more than 200,000 women diagnosed in the year 2007 alone. Breast cancer is the second leading cause of cancer death in women.

*Development Status:*                     The technology is currently in the pre-clinical stage of development.                 

*Inventors:*                     Derek LeRoith and Michael Quon (NIDDK).                 

*Publication:*                     H Zhao et al. PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. Oncogene 2004 Jan 22;23(3):786-794.                 

*Patent Status:*                     HHS Reference No. E-292-2008/0—Research Tool. Patent protection is not being pursued for this technology.                 

*Licensing Status:*                     Available for licensing.                 

*Licensing Contact:*                     Whitney A. Hastings; 301-451-7337;                     *hastingw@mail.nih.gov*.                 

## Fully Human Anti-Human NKG2D Monoclonal Antibody 

*Description of Technology:*                     Available for licensing is a fully human monoclonal antibody (KYK-2.0 IgG1) with high specificity and affinity to human NKG2D, a stimulatory or costimulatory receptor located on the cell surface of natural killer (NK) cells and CD8+ T cells. NKG2D plays a role in mediating immune responses in autoimmune and infectious diseases and cancer and it makes NKG2D an attractive target for therapeutic intervention. Nonetheless, monoclonal antibodies to NKG2D that are suitable for clinical investigations have not been available. In solution, KYK-2.0 IgG1 interferes with the cytolytic activity of human NK cells. When immobilized, KYK-2.0 IgG1 induces human NK cell activation. The dual antagonistic and agonistic activity promises a broad range of therapeutic applications.                 

*Application:*                     Therapeutic fully human monoclonal antibody for a variety of indications including autoimmune and infectious diseases, cancer, and transplantation.                 

*Advantage:*                     The dual antagonistic and agonistic activity in concert with low immunogenicity suggests broad and potent therapeutic utility of KYK-2.0 IgG1 and its derivatives.                 

*Development Status:*                     The technology is currently in the pre-clinical stage of development.                 

*Market:*
      - Monoclonal antibody market is one of the fastest growing and most lucrative sectors of the pharmaceutical industry with a 48.1% growth between 2003 and 2004.
      - Monoclonal antibody market is estimated to be worth $30.3 billion in 2010.

*Inventors:*                     Christoph Rader and Ka Yin Kwong (NCI)                 

*Related Publication:*                     KY Kwong, S Baskar, H Zhang, CL Mackall, C Rader. Generation, affinity maturation, and characterization of a human anti-human NKG2D monoclonal antibody with dual antagonistic and agonistic activity. J Mol                           ( print page 57637)                        Biol., in press (available online 2008 Sep 16,                     *doi:10.1016/j.jmb.2008.09.008*).                 

*Patent Status:*                     U.S. Provisional Application No. 61/086,027 filed 04 Aug 2008 (HHS Reference No. E-211-2008/0-US-01).                 

*Licensing Status:*                     Available for exclusive or non-exclusive licensing.                 

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

*Collaborative Research Opportunity:*                     The Experimental Transplantation and Immunology Branch, 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 the fully human anti-human NKG2D monoclonal antibody KYK-2.0 IgG1. Please contact John D. Hewes, Ph.D. at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                 

## Methods for the Detection and Treatment of Lung Cancer 

*Description of Technology:*                     Lung cancer is the third most common malignant disease and the first leading cause of cancer death in the western world. Non-small cell lung cancer (NSCLC) is one of the leading causes of death accounting for nearly 30% of all cancer deaths. Despite considerable research, lung cancer remains difficult to diagnose and treat effectively. Current chemotherapeutic regimens provide poor survival benefits and the unmet clinical need among lung cancer patients is very high. The prognosis is very bleak since most patients are diagnosed with lung cancer at a late stage.                 

The inventors have discovered that approximately 20% of common adult NSCLC have an aberrant activation of CRTC gene members with marked induction of CRTC regulated genes. CRTC activation is linked with the loss of LKB1/STK11 kinases which results in CRTC underphosphorylation and enhanced nuclear localization. As the LKB1/STK11 signaling pathways has been exploited in potential cancer therapeutic treatments, this novel unrecognized consequence the loss of LKB1/STK11 function associated with aberrant CRTC activation in cancer offers new candidate diagnostic and therapeutic targets for NSCLC. 

*Applications:*
      - Novel cancer diagnostics and therapeutic treatments.
      - Method to detect and treat lung cancer.

*Development Status:*                     The technology is currently in the pre-clinical stage of development.                 

*Market:*
      - Lung cancer is the leading cause of cancer deaths among both men and women in the U.S.
      - The NSCLC market was estimated to be worth US$3.7 billion in 2006 and will increase by 17% by 2012.

*Inventors:*                     Frederic Kaye and Amy Coxon (NCI).                 

*Patent Status:*                     U.S. Provisional Application No.61/036,830 filed 13 Mar 2008 (HHS Reference No. E-069-2008/0-US-01).                 

*Licensing Status:*                     Available for exclusive or non-exclusive licensing.                 

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

## Human Perilipin Proteins 

*Description of Technology:*                     Perilipins are important regulators of lipid storage in fat cells. These proteins stabilize fat droplets and control their breakdown by controlling access of lipid-degrading enzymes. Since these proteins are central to the storage and breakdown of body fat it very likely that they are crucial for the regulation of body weight. Perilipin expression is elevated in obese animals and humans. Mutations in the perilipin gene are associated with increased risk of obesity in women. Importantly, when the perilipin gene is inactivated the obesity of model mice is reversed. Therefore, perilipin could be a good candidate for therapeutic targeting to treat obesity in humans.                 

This NIH invention claims DNA sequences of splice variants that code for human perilipin protein isoforms and methods of expressing the recombinant protein in bacteria or mammalian cells. It also claims substantially purified perilipin proteins and methods for detecting their presence in a biological sample. 

*Applications:*
      - Drug development for obesity.
      - Diagnostics for detection of perilipins.
      - Antigens for antibody production.
      - Markers for identifying true adipocytes.

*Advantages:*
      - Cloned DNA sequences ready for protein expression.
      - Isoforms allow greater flexibility in designing therapeutics.

*Development Status:*                     Pre-clinical.                 

*Inventors:*                     Constantine Londos, Andrew S. Greenberg, Alan R. Kimmel, John J. Egan (NIDDK).                 

*Related Publication:*                     AS Greenberg et al. Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets. J Biol Chem. 1991 Jun 15;266(17):11341-11346.                 

*Patent Status:*
      - U.S. Patent No. 6,074,842 issued 13 Jun 2000 (HHS Reference No. E-111-1991/0-US-03).
      - U.S. Patent No. 5,585,462 issued 17 Dec 1996 (HHS Reference No. E-111-1991/1-US-01).

*Licensing Status:*                     Available for exclusive or non-exclusive licensing.                 

*Licensing Contact:*                     Surekha Vathyam, PhD; 301-435-4076;                     *vathyams@mail.nih.gov.*

 Dated: September 29, 2008. 

Richard U. Rodriguez, 

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

[FR Doc. E8-23436 Filed 10-2-08; 8:45 am] 

BILLING CODE 4140-01-P