Notice (C): Government-Owned Inventions; Availability for Licensing

Federal Register: September 16, 2008 (Volume 73, Number 180)      
                  Page 53430-53432

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

[[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:

[[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