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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. 

## IL-10 and IFNγ Peptide Inhibitors 

*Description of Invention:*                     Available for licensing are several potent and selective inhibitors of IL-10 and IFN-γ signaling. Although cytokines play important roles in cancer and inflammation, there are no specific inhibitors of any cytokines to date. IL-10 and IFN-γ cytokine signaling play crucial roles in inflammation, cancer growth, and autoimmune diseases. The investigators have developed short peptides that potently and selectively interfere with dimerization of the cytokines and their binding to the corresponding receptor. Included in the patent application are also metabolically stable lipopeptides mimicking conserved regions of IL-10 and IFN-γ receptors that interfere with STAT3 and STAT1 phosphorylation and subsequent signaling. Lipopeptides potently inhibit STAT3 and STAT1-dependent growth of cancer cells. These compounds are promising drug candidates for the treatment of cancer and many infectious and inflammatory diseases.                 

*Application:*                     Cancer, viral infections and anti-inflammatory treatments.                 

*Advantages:*
      - Potent, stable peptide inhibitors.
      - Selective IL-10 and IFN-γ inhibitors.

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

*Market:*                     The annual growth rate for the therapeutic peptide market is estimated at about 7.5%.                 

*Inventors:*                     Nadya Tarasova                     *et al.*                     (NCI).                 

*Patent Status:*                     U.S. Provisional Application No. 61/333,512 filed 11 May 2010 (HHS Reference No. E-167-2010/0-US-01).                 

*Licensing Status:*                     Available for licensing.                 

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

*Collaborative Research Opportunity:*                     The Center for Cancer Research, Cancer and Inflammation Program, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize inhibitors of IL10, IFNγ and STAT3 signaling. Please contact John Hewes, Ph.D. at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                 

## Diagnostic and Prognostic HCC-Related Metabolites 

*Description of Invention:*                     Metabolite profiling identifies and measures changes in cellular metabolites as a means to determine a direct correlation between gene expression and changes in biological function. Investigators at the National Cancer Institute have identified a unique set of metabolite biomarkers associated with hepatocellular carcinoma (HCC), early stage HCC, HCC patient outcome and HCC stem-cell subtype. Subsets of this metabolite/gene signature can distinguish HCC tumors from normal tissues with 88-97% accuracy, identify early stage HCC patients with 62-78% accuracy, wherein early stage is defined as TNM stage I, prognose negative patient outcome, and identify a HCC stem cell subtype with 70-77% accuracy. These metabolites and gene surrogates are elements of the PI3K and Myc signaling networks which can potentially be targeted for therapeutic purposes.                           ( print page 66107)    

HCC represents an extremely poor prognostic cancer, and patients are often diagnosed with end-stage cancer and have poor survival. HCC is also a very heterogeneous disease and often arises from chronic liver disease. Surgery and transplantation remain the only curative option for patients; however, complications due to cirrhosis mean it is a viable option for 5-10% patients. This HCC gene signature can be developed into assays to enable clinicians to accurately diagnose HCC, including early stages and subtype of this disease, and therefore stratify patients for appropriate treatment and prioritizing liver transplantation candidates based on their metabolite profile. 

*Applications:*
      - Method to diagnose HCC, including HCC subtypes.
      - Method to prognose HCC patient outcome.
      - Method to stratify patients for appropriate treatment.

*Advantages:*                     Highly accurate metabolite/gene profile that can be developed into a variety of diagnostic and prognostic applications.                 

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

*Market:*
      - Global oncology biomarker discovery market is expected to grow from $2.5 billion in 2009 to $5.7 billion by 2014.
      - North America has the largest metabolomic market with an estimated value of $161.4 million in 2009, and it is projected to reach $324 million by 2014.
      - HCC is the fifth most common cancer worldwide with an estimated one million new cases diagnosed annually.

*Inventors:*                     Xin Wei Wang and Anuradha S. Budhu (NCI).                

*Patent Status:*                     U.S. Provisional Application No. 61/323,420 filed 13 Apr 2010 (HHS Reference No. E-139-2010/0-US-01).                

*Licensing Status:*                     Available for licensing.                 

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

*Collaborative Research Opportunity:*                     The Center for Cancer Research, Laboratory of Human Carcinogenesis, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize metabolomic signatures for liver cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                 

## Stimulation of Natural Killer T-Cell Anti-Tumor Activity 

*Description of Invention:*                     Natural killer T cells (NKT) are a unique lymphocyte population that has T-cell and NK cell functional properties in order to rapidly elicit an immune response. α-galactosylceramide (α-GalCer) is a potent NKT stimulator and induces of IFN-γ release to promote immunity against tumors and infectious agents. Humans have natural antibodies against α-galactose, which may be one of the reasons why the human clinical trials of α-GalCer or KRN7000 were not very successful.                 

Investigators at the National Cancer Institute have found that β-mannosylceramide (β-ManCer) promotes immunity in an IFN-γ independent mechanism. β-ManCer is a new class of NKT agonist that induces immune responses alone, through nitric oxide and TNF-α-dependent mechanisms, or synergistically with α-GalCer to enhance α-GalCer's efficacy. Since β-ManCer does not have α-galactose, which can be neutralized by natural antibodies, patients could be treated with multiple doses without negative side effects associated with the loss of IFN-γ production. Hence, β-ManCer is a promising anti-cancer treatment either alone or in combinatorial therapies with α-GalCer to selectively induce immune responses. 

*Applications:*
      - Cancer therapeutics.
      - Potent stimulator of NKT activity.

*Advantages:*
      - Induces tumor immunity through a novel mechanism.
      - Decreased possibility of neutralization by natural antibodies.
      - Synergize with α-GalCer.

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

*Market:*                     Global cancer market is worth more than eight percent of total global pharmaceutical sales.                 

*Inventors:*                     Masaki Terabe (NCI)                     *et al.*

*Patent Status:*                     U.S. Provisional Application No. 61/313,508 filed 12 Mar 2010 (HHS Reference No. E-034-2010/0-US-01).                 

*Licensing Status:*                     Available for licensing.                 

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

*Collaborative Research Opportunity:*                     The Vaccine Branch of the National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize β-ManCer. Please contact John Hewes, Ph.D. at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                 

## Modified POTE Peptides for Cancer Immunotherapy 

*Description of Invention:*                     Investigators at the National Cancer Institute have identified and enhanced immunogenicity of POTE epitopes to improve their efficacy in cancer vaccines. POTE is a novel tumor antigen expressed in a variety of cancers including breast, prostate, colon, lung, ovary, and pancreas cancers. POTE has limited expression in normal tissues and therefore a specific target for cancer treatments, including immunotherapy. Immunotherapy has great potential as a cancer therapeutic because of its specificity and freedom from toxic effects of chemotherapies.                 

Antigen-specific cancer immunotherapy often relies on identification of epitopes expressed by cancer cells that can be targeted by cytotoxic T cells (CTL). However, the CTL repertoire against high-affinity cancer epitopes is often ineffective because cancer epitopes may share a similar structure to natural “self” antigens. As a result, cancer cells are not recognized by CTLs and destroyed. The enhanced POTE epitopes induce a stronger immune response than natural responses. These modified epitopes are more effective at inducing CTL against POTE expressing cancer cells and have greater potential to serve as cancer vaccine targets. 

*Applications:*
      - Therapeutic cancer vaccine.
      - Method to treat cancer.

*Advantages:*
      - Enhanced immunogenic peptides.
      - Cancer vaccines that overcome self-tolerance to target a variety of tumor cells.

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

*Market:*                     The therapeutic cancer market will be worth an estimated $633 million in 2014.                 

*Inventors:*                     Jay A. Berzofsky, Yi-Hisang Huang, Ira Pastan, Masaki Terabe (NCI).                 

*Patent Status:*                     U.S. Provisional Application No. 61/313,559 filed 12 Mar 2010 (HHS Reference No. E-003-2010/0-US-01).                 

*Licensing Status:*                     Available for licensing.                 

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

*Collaborative Research Opportunity:*                     The Center for Cancer Research, Vaccine Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or                           ( print page 66108)                        commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                 

Dated: October 21, 2010. 

Richard U. Rodriguez, 

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

[FR Doc. 2010-27181 Filed 10-26-10; 8:45 am] 

BILLING CODE 4140-01-P