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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                               ( print page 53431)                            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.                    

## Bifunctional Compounds That Bind to Hormone Receptors

*Description of Technology:*                     The development and progression of prostate cancer is dependent on the androgen receptor (AR), a ligand-dependent transcription factor. In the inactive form AR resides in the cytosolic region of the cell and when activated, AR is imported into the nucleus. Initial hormonal therapy for prostate cancer involves lowering serum levels of testosterone to shut down AR activity. Despite initial patient responses to testosterone-depleting therapies, prostate cancer becomes refractory to hormonal therapy. Notably, AR is reactivated in hormone-refractory prostate cancer and reinstates its proliferative and survival activity.                

Available for licensing is a novel chemical compound which is bifunctional and binds to AR. This compound is comprised of tubulin-binding and steroid receptor-binding moieties. This compound is designed to antagonize AR function in a nonclassical manner by several mechanisms and kills hormone-refractory prostate cells better than both functional moieties. This compound is a first-in-class of bifunctional steroid receptor binding agents that can antagonize steroid receptors in a variety of hormone-dependent diseases, such as breast and prostate cancer.

*Applications:*
      - Therapeutic compounds that selectively target steroid receptor-expressing cancer cells resulting in minimal patient toxicity.
      - Method to treat hormone resistant prostate cancer and potentially other steroid receptor dependent diseases such as breast cancer.

*Market:*
      - Prostate cancer is the second most common type of cancer among men, wherein one in six men will be diagnosed.
      - An estimated 186,320 new diagnosed cases and 28,660 deaths due to prostate cancer in the U.S. will occur in 2008.

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

*Inventors:*                     Nima Sharifi                     *et al.*                     (NCI).                

*Publication:*                     N Sharifi                     *et al.*                     A bifunctional colchicinoid that binds to the androgen receptor. Mol Can Ther. 2007 Aug;6(8):2328-2336.                

*Patent Status:*                     PCT Application No. PCT/US2008/008299 filed 02 Jul 2008, claiming priority to 03 Jul 2007 (HHS Reference No. E-163-2007/0-PCT-02).                

*Availability:*                     Available for exclusive or non-exclusive licensing.                

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

## Vitamin D Receptor Antagonists for Treating Breast Cancer

*Description of Technology:*                     Vitamin D receptor (VDR) is a nuclear receptor that is activated by calcitriol, the active form of vitamin D. It is best known for regulating dietary calcium uptake necessary for bone growth, but it also affects cell proliferation and differentiation. Therefore, it was thought that treatment with calcitriol or its derivatives could be useful to treat the uncontrolled proliferation typical of cancer cells. However, this approach has been unsuccessful to date because it leads to toxic levels of calcium in the blood.                

This invention relates to derivatives of calcitriol that can block cell growth without harmfully raising calcium levels. Specifically, these compounds act as antagonists of VDR blocking its ability to stimulate cell proliferation. This technology can be useful in treating breast cancer or other malignancies.

*Applications:*
      - Potential drugs for treating breast cancer and possibly also prostate cancer, colorectal cancer, leukemia, melanoma, or glioma.
      - Prevention of cancer in high-risk population.
      - Research on vitamin D receptor functions and cancer.

*Market:*                     About 182,460 American women will be diagnosed with invasive breast cancer in 2008.                

*Development Status:*                     Pre-clinical data available.                

*Inventors:*                     Julianna Barsony (NIDDK).                

*Publication:*                     J Barsony                     *et al.*                     Development of a biologically active fluorescent-labeled calcitriol and its use to study hormone binding to the vitamin D receptor. Anal Biochem. 1995 Jul 20;229(1):68-79.                

*Patent Status:*                     U.S. Patent No. 7,361,664 issued 22 Apr 2008 (HHS Reference No. E-213-2001/2-US-02).                

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

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

## A Novel Recombinant Immunotoxin SS1P (anti-mesothelin dsFv-PE38): A Therapeutic Treatment for Lung Cancer and Other Mesothelin Expressing Cancers

*Description of Technology:*                     Mesothelin is a cell surface glycoprotein whose expression is largely restricted to mesothelial cells in normal tissues. Significantly, mesothelin is also highly expressed in many cancers (including malignant mesothelioma, ovarian cancer, lung cancer, pancreatic carcinomas, gastric carcinomas, etc.). As a result, mesothelin is an excellent target for immunotherapy.                

                    NIH inventors have generated high affinity antibodies to mesothelin (SS1) and fused them to various functional fragments of                     *Pseudomonas*                     Exotoxin A (PE) to produce the immunotoxin SSIP. New SS1P constructs include PE fragments and mutants with reduced immunogenicity, resulting in immunotoxins with greater efficacy. SS1P activity was previously shown in patients suffering from mesothelioma and ovarian cancer; laboratory studies now demonstrate cytotoxicity against lung carcinoma cells. Additionally, SS1P has shown synergy with front line cancer therapeutics in a mouse model, making SS1P an excellent candidate both a stand-alone therapeutic and a combination therapeutic.                

*Applications:*
      - SS1P can be used as a therapy for mesothelin expressing cancers, including mesothelioma, ovarian cancer and lung adenocarcinoma.
      - The immunotoxin can be used in combination with standard chemotherapy.

*Advantages:*
      - Immunotoxins are highly selective for cancer cells, reducing side-effects due to the non-specific killing of normal cells.
      - Strong synergy has been shown between SS1P and standard front line cancer therapies in the treatment on lung adenocarcinoma.
      - Less immunogenic PE variants increase the efficacy of the immunotoxin.

*Inventors:*                     Ira Pastan (NCI)                     *et al*.                

*Patent Status:*                     U.S. Patent 7,081,518, entitled “Anti-mesothelin antibodies having high binding affinity” issued on 25 July 2006 [HHS Ref. E-139-1999/0].                

*Related Technologies:*      ( print page 53432)    
      - U.S. Patents 6,051,405, 5,863,745, and 5,696,237 “Recombinant Antibody-Toxin Fusion Protein” [HHS Ref. E-135-1989/0];
      - U.S. Patents 5,747,654, 6,147,203, and 6,558,672 entitled “Recombinant Disulfide-Stabilized Polypeptide Fragments Having Binding Specificity” [HHS Ref. E-163-1993/0];
      - U.S. Patent 6,153,430, and U.S. Patent Application 09/684,599 “Nucleic Acid Encoding Mesothelin, a Differentiation Antigen Present on Mesothelium, Mesotheliomas and Ovarian Cancers” [HHS Ref. E-002-1996/0];
      - U.S. Patent 6,083,502 entitled “Mesothelium Antigen and Methods and Kits for Targeting It” [HHS Ref. E-002-1996/1];
      - U.S. Patent Application 09/581,345: “Antibodies, Including Fv Molecules, and Immunoconjugates Having High Binding Affinity for Mesothelin and Methods for Their Use” [HHS Ref. E-021-1998/0];
      - U.S. Patent Application 10/297,337, “Pegylation of Linkers Improves Antitumor Activity and Reduces Toxicity of Immunoconjugates” [HHS Ref. E-216-2000/2];
      - U.S. Patent Application 11/920,222 entitled “Anti-Mesothelin Antibodies Useful For Immunological Assays” [HHS Ref. E-015-2005/0];
      - U.S. Patent Application 11/997,202 “Mutated Pseudomonas Exotoxins with Reduced Antigenicity” [HHS Ref E-262-2005/0]; and
      - U.S. Patent Application 60/969,929 “Deletions in Domain II of Pseudomonas Exotoxin A that Remove Immunogenic Epitopes without Affecting Cytotoxic Activity” [HHS Ref. E-292-2007/0].

*Licensing Status:*                     The technology is available for exclusive and non-exclusive licensing.                

*Licensing Contact:*                     David A. Lambertson, PhD; 301-435-4632;                     *lambertsond@mail.nih.gov*.                

*Collaborative Research Opportunity:*                     The National Cancer Institute Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop immunotoxin SS1P. Please contact John D. Hewes, PhD at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                

Dated: September 9, 2008.

Richard U. Rodriguez,

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

[FR Doc. E8-21506 Filed 9-15-08; 8:45 am]

BILLING CODE 4140-01-P