[Federal Register Volume 72, Number 122 (Tuesday, June 26, 2007)]
[Notices]
[Pages 35056-35057]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-12337]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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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 Novel Discriminatory Small Peptide Inhibitor of Hsp90 Targeting 
Oncogenic Kinases

    Description of Technology: Heat shock protein 90 (Hsp90) is a 
molecular chaperone required for stability and function for many 
proteins (clients). Presently, there are clinical trials focusing on 
small molecule Hsp90 inhibitors; however, pharmacologic Hsp90 
inhibition causes destabilization, ubiquitination and proteasome-
degradation of all client proteins indiscriminately.
    Hsp90 was found to be overexpressed in tumor cells; thereby making 
Hsp90 a promising molecular target for cancer therapy. Additionally, 
some Hsp90-dependent client proteins (non-kinases) were identified as 
putative tumor suppressors, suggesting that indiscriminate degradation 
of all Hsp90 client proteins is not ideal. Finding a molecular 
inhibitor that discriminately inhibits Hsp90 that would target only 
client kinase proteins would be an ideal therapeutic agent for cancer 
treatment.
    The current invention is a short peptide that inhibits Hsp90 that 
prevents the recognition and function of client kinase proteins, and 
promotes the degradation of client kinase proteins, while not affecting 
other non-kinase client proteins.
    Applications and Modality: Current applications include targeting 
client kinase proteins promoting degradation, and preventing 
recognition and function of the client kinase proteins; restriction of 
Hsp90 inhibition to client kinases that utilize similar Hsp90 
recognition sequences to the oncogenic tyrosine kinase Hsp90 client 
ErbB2; and having kinase-specific chaperone inhibitors preferentially 
active as anti-cancer agents compared to indiscriminate pharmacologic 
inhibitors of Hsp90.
    Market: 600,000 deaths from cancer related diseases were estimated 
in 2006; In 2006, cancer drug sales were estimated to be $25 billion; 
There is a burgeoning drug market for Hsp90 inhibitors for cancer 
treatment.
    Development Status: The technology is currently in the preclinical 
stage of development.
    Inventors: Leonard M. Neckers et al. (NCI).
    Patent Status: U.S. Provisional Application No. 60/895,313 filed 16 
Mar 2007 (HHS Reference No. E-121-2007/0-US-01); U.S. Provisional 
Application No. 60/909,834 filed 03 Apr 2007 (HHS Reference No. E-121-
2007/1-US-01).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Adaku Nwachukwu, J.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The NCI Urologic Oncology 
Branch is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize peptide inhibitor of Hsp90. Please contact John D. Hewes, 
Ph.D. at 301-435-3121 or [email protected] for more information.

A Novel Treatment for Non-Small Cell Lung Cancer Using Mesothelin-
Targeted Immunotoxins

    Description of Technology: Mesothelin is a glycoprotein, whose 
expression has been largely restricted to mesothelial cells in normal 
tissues, although epithelial cells of the trachea, tonsil, fallopian 
tube, and kidney have shown immunoreactivity. Mesothelin has been shown 
to be expressed in several cancers including pancreatic carcinomas, 
gastric carcinomas and

[[Page 35057]]

ovarian carcinomas, and has the potential of being used as a tumor 
marker and a novel target for the development of new treatments.
    The technology relates to the finding that some non-small cell lung 
cancers (NSCLC) express the antigen mesothelin. Targeting the tumors 
with antibodies or immunotoxins that specifically bind mesothelin can 
be a potential new treatment for non-small cell lung cancer. The SSIP 
immunotoxin and its variants that specifically bind to mesothelin can 
be used for the treatment of NSCLC.
    Applications and Modality: NSCLC can be treated by targeting 
mesothelin.
    Advantage: Anti-mesothelin antibodies and immunotoxins are already 
available and being tested for several cancers.
    Development Status: The technology is in pre-clinical stage of 
development.
    Inventors: Ira H. Pastan (NCI) et al.
    Patent Status: U.S. Provisional Application No. 60/891,923 filed 27 
Feb 2007 (HHS Reference No. E-120-2007/0-US-01), entitled ``Treatment 
of Non-Small Cell Lung Cancer with Mesothelin-Targeted Immunotoxins.''
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Jesse S. Kindra, J.D.; 301-435-5559; 
[email protected]
    Collaborative Research Opportunity: The National Cancer Institute's 
Laboratory of Molecular Biology is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize anti-mesothelin antibodies and 
immunotoxins. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.

A Gene Expression Profile That Predicts Ovarian Cancer Patient Response 
to Chemotherapy

    Description of Technology: Ovarian cancer is a poor prognosis 
disease that remains the most lethal of all gynecologic malignancies. 
Warning symptoms do not occur until the tumor has already spread beyond 
the ovary, resulting in diagnosis at an advanced stage. As a result, 
there is a poor patient prognosis with only fifteen percent of women 
possessing advanced stage disease surviving for five years. Despite an 
initial clinical response of 80% to surgery and chemotherapy, most 
patients experience tumor recurrence within two years of treatment. The 
overwhelming majority of these patients will eventually develop 
chemoresistant disease and die.
    Available for licensing are two gene signatures. One gene signature 
can predict whether a patient will initially respond to standard 
platinum-paclitaxel chemotherapy, but will relapse within six months of 
completing treatment. A second gene signature identifies patients who 
will show no response to therapy. This methodology may enable 
clinicians to identify patients who may be candidates for additional 
and/or novel chemotherapy drugs, and effectively choose appropriate 
cancer treatment. A unique feature of this signature is its derivation 
from pure, microdissected isolates of ovarian tumor cells, rather than 
undissected tissue. By utilizing this approach, the resulting gene list 
is specific to the cell type that causes the disease.
    Applications: Method to detect if an ovarian cancer patient is 
sensitive to treatment with chemotherapeutic agents; Method to evaluate 
ovarian cancer patient chemoresponsiveness; Diagnostic tool to aid 
clinicians in determining appropriate cancer treatment; Methods to 
treat ovarian cancer identified by chemoresistant biomarkers 
compositions.
    Market: Ovarian cancer is the fourth most common form of cancer in 
the U.S.; Ovarian cancer is three times more lethal than breast cancer; 
15,310 deaths in the U.S. in 2006.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Michael J. Birrer (NCI) et al.
    Publication: SC Mok et al. Biomarker discovery in epithelial 
ovarian cancer by genomic approaches. Adv Cancer Res. 2007;96:1-22.
    Patent Status: U.S. Provisional Application No. 60/899,942 filed 06 
Feb. 2007 (HHS Reference No. E-060-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].

Potent, Easy to Use Targeted Toxins as Anti-Tumor Agents

    Description of Technology: The invention discloses synthesis and 
use of novel derivatives of 2-[2'-(2-aminoethyl)-2-methyl-ethyl]-1,2-
dihydro-6-methoxy-3H-dibenz-[de,h]isoquinoline-1,3-dione as targeted 
anti-tumor agents. The use of targeted toxin conjugates with anti-
cancer antibodies, such as herceptin, is increasing. Based on a 
comparison with the structurally complex toxins, such as DM1, available 
in the market, these novel toxins are more stable in circulation, thus 
making the toxin-conjugates more tumor-selective and less toxic. As 
such, these compounds are superior alternatives to the existing toxins.
    The invention describes a potent and easy to synthesize toxin that 
can be used for generating a variety of prodrugs. These compounds can 
be attached to a ligand that recognizes a receptor on cancer cells, or 
to a peptide that is cleaved by tumor-specific proteases. The compounds 
are topoisomerase inhibitors and are mechanistically different from DM1 
that targets tubulin.
    The structure of the toxin allows it to be modified with a peptide 
linker that is stable, but rapidly cleaved in lysosomes after the 
compound is specifically taken up by cancer cells.
    Applications: The compounds can be used for preparation of a 
variety of potent anti-cancer agents with low systemic toxicity.
    Advantages: Easy to prepare; Structural features make these 
compounds more stable in circulation; Toxin conjugates are more tumor-
selective and less toxic.
    Benefits: 600,000 cancer deaths occurred in 2006 in spite of 
advances in cancer therapeutics. A major limitation of current 
therapeutics is their toxic side effects. This technology can 
effectively treat cancer with low systemic toxicity and thus improve 
overall survival and quality of life of patients suffering from cancer. 
The current cancer chemotherapeutic market is valued at $42 billion and 
expected to grow.
    Inventors: Nadya I. Tarasova, Marcin D. Dyba, Christopher J. 
Michejda (NCI).
    Development Status: In vitro studies are completed and in vivo 
animal model studies are ongoing.
    Patent Status: U.S. Provisional Application No. 60/844,027 filed 12 
Sep. 2006 (HHS Reference No. E-160-2006/0-US-01).
    Licensing Contact: Mojdeh Bahar, J.D.; 301/435-2950; 
[email protected].

    Dated: June 19, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E7-12337 Filed 6-25-07; 8:45 am]
BILLING CODE 4140-01-P