[Federal Register Volume 75, Number 43 (Friday, March 5, 2010)]
[Notices]
[Pages 10283-10285]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-4761]


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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.

Patient-Derived Gastrointestinal Stromal and Paraganglioma Tumor 
Samples Harboring Novel Stem Cell Factor FOXD3 Variants

    Description of Invention: The cancer market is forecast to reach 
$40 billion dollars by the year 2012. There is still a significant need 
to develop new therapies for treating sarcomas and malignant neoplasms.
    Researchers at the National Institute of Child Health and Human 
Development (NICHD), NIH, have made available samples of patient-
derived gastrointestinal tumors (GIST) and paraganglioma tumors that 
harbor genetic mutations that have an effect on early stage 
embrogenesis which plays a role in the fate of stem cells. GISTs are 
one of the most common sarcomas of the gastrointestinal tract with an 
estimated 5,000-10,000 new cases in the U.S. reported each year. GISTs 
affect mainly pediatric and young adult patients, and respond poorly to 
current therapies. Paragangliomas are rare neuroendocrine neoplasms 
that develop primarily in the abdomen.
    The tumor samples made available herein contain deletions in the 
FOXD3 gene and display down-regulated FOXD3 protein expression. While 
the

[[Page 10284]]

majority of GISTs result from activating mutations in the oncogene 
receptor tyrosine kinases c-KIT and PDGFRA, these tumor samples do not 
harbor mutations in c-KIT or PDGFRA (``non-KIT/ PDGFRA-GISTs'') and 
respond poorly to receptor tyrosine kinase inhibitors.
    Applications:
     Useful in the investigation of inactivating genetic 
changes in FOXD3 in non-KIT/PDGFRA-GISTs.
     Useful in the study of new molecules and/or pathways that 
may serve as an appropriate therapeutic target.
    Inventors: Constantine Stratakis et al. (NICHD).
    Patent Status: HHS Reference No. E-058-2010/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing under a biological 
material license.
    Licensing Contact: Patrick P. McCue, PhD; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The National Institute of Child 
Health and Human Development Endocrinology & Genetics Section is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
this technology. Please contact Joseph Conrad, PhD at 301-435-3107 or 
[email protected] for more information.

Novel Kinase Inhibitors Targeting the PH Domain of AKT for Preventing 
and Treating Cancer

    Description of Invention: Activation of the PI3K/Akt signaling 
pathway has been implicated in the development of cancer. Akt, a kinase 
that is central to this pathway, is found at elevated levels in many 
tumors and is associated with a poor disease prognosis. Many research 
studies have validated Akt as a therapeutic target for the development 
of anti-cancer drugs. Most efforts of drug development targeting Akt 
have focused on inhibitors of the ATP-binding domain which tend to 
interfere with other physiologically important kinases. An alternative 
strategy that has been proposed to improve drug specificity is the 
targeting of the unique pleckstrin homology (PH) domain of Akt.
    Investigators at the National Institutes of Health have screened a 
library of small chemical compounds with drug-like characteristics that 
likely bound to the PH domain and have identified several candidates 
previously unknown to interact with Akt. These compounds were tested 
and found to inhibit Akt activity specifically through the PH domain. 
Some of these compounds demonstrated broad cytotoxicity to a wide 
variety of tumor cells. These novel Akt-inhibiting compositions target 
the PH domain and help in the prevention and treatment of cancer. Since 
it has been shown that reducing the activity of the PI3K-Akt pathway 
sensitizes malignant cells to chemotherapy or radiotherapy, these novel 
Akt inhibitors have potential either as single anti-cancer agents or in 
combination with conventional cancer therapies.
    One of the candidate compounds inhibited Colony Stimulating Factor-
1 Receptor (CSF1R) from binding to ATP but had no activity for other 
kinases. CSF1R has been implicated in development of cancers like 
chronic myelomonocytic leukemia, but also in Alzheimer's disease so 
this specific compound may have use in treating other diseases in 
addition to cancer.
    Applications:
     Treating or preventing development of cancer or preventing 
progression of premalignant lesions to cancer.
     Used as a single agent or in combination with other anti-
cancer treatments like chemotherapy, biological therapy, or radiation.
     Inhibiting the activity of CSF1R receptor to treat 
diseases like chronic myelomonocytic leukemia and Alzheimer's disease 
or an adverse condition, such as brain injury.
    Advantages: Targeting the PH domain improves specificity against 
Akt kinase in comparison to inhibitors of the ATP domain which 
typically are unspecific.
    Inventors: Phillip A. Dennis (NCI) et al.
    Patent Status: U.S. Provisional Application No. 61/226,328 filed 17 
Jul 2009 (HHS Reference No. E-212-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Medical Oncology Branch and Affiliates, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize this 
technology. Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

Diagnostic Biomarker of Metastasis for Improved Clinical Management of 
Head and Neck Cancer

    Description of Invention: Squamous Cell Carcinoma of the Head and 
Neck (HNSCC) is associated with poor prognosis due to the advanced 
stage of disease (metastasis) typically found at the time of diagnosis. 
Investigators at the NIH have developed a sensitive method using a 
protein biomarker for detecting even just a few HNSCC tumor cells in 
lymph nodes with occult disease. Combination of this staging technique 
with intraoperative sentinel lymph node mapping would improve the 
management of HNSCC by identifying patients for which radical lymph 
node dissection is most appropriate, sparing those for which it is not, 
and informing decisions for adjuvant cancer therapy during a single 
surgery.
    This technology arose from the discovery that the Desmoglein-3 
(DSG3) protein which is highly expressed in tumors of squamous 
epithelial origin, like HNSCC, is also expressed in invaded lymph nodes 
but it is not found in normal lymph nodes. Therefore, DSG3 can serve as 
a biomarker for detecting metastastatic spread of squamous cell 
carcinoma tumors. This is achieved by performing protein detection 
immunoassays to samples (biopsy, aspirate, or isolated cells) of 
suspect lymph nodes.
    Applications: Use with sentinel lymph node mapping for rapid, 
intraoperational diagnosis of metastatic HNSCC for guiding proper 
therapeutic approach.
    Advantages:
     Rapid diagnosis during surgery increases effectiveness of 
intervention thereby reducing need for subsequent surgery.
     Improved accuracy of direct measurement of protein levels 
over RNA assays.
     More robust assay as protein is more stable than RNA.
    Development Status:
     Early stage.
     Clinical data available.
    Market: HNSCC is the sixth most prevalent cancer among men 
worldwide and is associated with poor prognosis, which has improved 
only marginally over the past three decades. This is reflected by HNSCC 
being the eighth leading cause of cancer death worldwide.
    Inventors: J. Silvio Gutkind et al. (NIDCR).
    Related Publication: Patel V, Hood BL, Molinolo AA, Lee NH, Conrads 
TP, Braisted JC, Krizman DB, Veenstra TD,

[[Page 10285]]

Gutkind JS. Proteomic analysis of laser-captured paraffin-embedded 
tissues: a molecular portrait of head and neck cancer progression. Clin 
Cancer Res. 2008 Feb 15;14(4)1002-1014. [PubMed: 18281532].
    Patent Status: U.S. Provisional Application No. 61/186,582 filed 
June 6, 2009 (HHS Reference No. E-300-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Whitney Hastings, PhD; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The NIDCR, OPCB, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
the use of DSG3 as a biomarker for detecting metastastatic spread of 
squamous cell carcinoma tumors. Please contact David W. Bradley, PhD at 
[email protected] for more information.

    Dated: March 1, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-4761 Filed 3-4-10; 8:45 am]
BILLING CODE 4140-01-P