[Federal Register Volume 76, Number 155 (Thursday, August 11, 2011)]
[Notices]
[Pages 49777-49778]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-20447]


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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.

Tumor Markers for Potentially Predicting Outcome of Anti-angiogenesis 
Therapy

    Description of Technology: During the past decade, anti-
angiogenesis therapy has evolved as a promising approach to the 
treatment of cancer. However, a significant fraction of patients do not 
benefit from anti-angiogenesis therapy, either by itself or in 
combination with chemotherapy. A significant need remains for a means 
of predicting clinical benefit from anti-angiogenesis therapy.
    Researchers at the National Cancer Institute, NIH, have identified 
tumor cell apoptosis, p53, and HER2 as having potential predictive 
significance for treatment outcome in breast cancer patients who 
received anti-angiogenesis therapy in combination with chemotherapy. 
The researchers have developed a quantitative antibody-based testing 
method for correlating expression of p53 and HER2 and tumor apoptosis 
with clinical outcome. These markers can be potentially applied to 
predict which patients should receive anti-angiogenesis therapy plus 
chemotherapy.
    Potential Commercial Applications:
     A diagnostic kit for predicting benefit of anti-
angiogenesis therapy plus chemotherapy in breast cancer patients.
     A testing service for breast cancer patients.
    Competitive Advantages:
     The clinical predictive markers p53, HER2 and tumor 
apoptosis indicators are easily and readily evaluated using the new 
assay.
     The new assay is potentially useful to determine which 
patients should or should not receive anti-angiogenesis therapy plus 
chemotherapy for longer survival and progression-free survival in 
patients with breast cancer.
     A study with a large sample size will be planned by the 
inventors and potential collaborators.
    Development Stage:
     Pilot.
     In vivo data available (human).
    Inventors: Sherry Yang (NCI), Seth Steinberg (NCI), et al.
    Publication: Yang S, et al. p53, HER2 and tumor cell apoptosis 
correlate with clinical outcome after neoadjuvant bevacizumab plus 
chemotherapy in breast cancer. Int J Oncol. 2011 May; 38(5):1445-1452. 
[PMID 21399868]
    Intellectual Property: HHS Reference No. E-096-2011/0--U.S. Patent 
Application No. 61/448,092 filed 01 March 2011
    Licensing Contact: Patrick McCue, Ph.D.; 301-435-5560; 
[email protected]
    Collaborative Research Opportunity: The National Clinical Target 
Validation Laboratory, DCTD, NCI, NIH, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize p53, tumor 
apoptosis, and HER2 as markers for anti-angiogenesis therapy. For 
collaboration opportunities, please contact John Hewes, Ph.D. at 
[email protected].

TRRAP and GRIN2A Mutations for the Diagnosis and Treatment of Melanoma

    Description of Technology: Using whole-exome sequencing of matched 
normal and metastatic tumor DNAs, researchers at the NIH have 
identified several novel somatic (e.g., tumor-specific) alterations, 
many of which have not previously been known to be genetically altered 
in tumors or linked to melanoma. In particular, the researchers 
identified a recurrent ``hotspot'' mutation in the transformation/
transcription domain-associated protein (TRRAP) gene, found the 
glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A) gene as 
a highly mutated in melanoma, and have shown that the majority of 
melanoma tumors have alterations in genes encoding members of the 
glutamate signaling pathway. Therefore, this technology not only 
provides a comprehensive map of genetic alterations in melanoma, but 
has important diagnostic and therapeutic applications. Mutations in the 
TRRAP and GRIN2A genes can be used as diagnostic markers for melanoma 
and may serve as therapeutic targets in the treatment of melanoma. In 
addition, glutamate antagonists have previously been shown to inhibit 
proliferation of human tumor cells, and therefore further investigation 
of the pathway in melanoma could allow for the identification of new 
therapeutic proteins that target this pathway.
    Potential Commercial Applications:
     Diagnostic array for the detection of TRRAP and GRIN2A 
mutations.
     Method of identifying TRRAP and GRIN2A inhibitors as 
therapeutic agents to treat malignant melanoma patients.
     Method of selecting a therapy based on the presence of 
TRRAP and GRIN2A mutations.
    Competitive Advantages:
     Complete analysis of melanoma exome alterations.
     TRRAP, GRIN2A, and the other identified mutations are 
highly frequent and/or highly mutated in melanomas.
     Glutamate antagonists have already been shown to inhibit 
tumor growth. Thus, this technology may prove useful

[[Page 49778]]

for the development of novel diagnostic tests and therapeutics.
    Development Stage: Pre-clinical.
    Inventors: Yardena Samuels and Xiaomu Wei (NHGRI).
    Publication: Wei X, et al. Exome sequencing identifies GRIN2A as 
frequently mutated in melanoma. Nat Genet. 2011 May;43(5):442-446. 
[PMID: 21499247].
    Intellectual Property:
     HHS Reference No. E-013-2011/0--U.S. Provisional 
Application No. 61/462,471 filed 02 February 2011.
     Research Tool--Patent protection is not being pursued for 
the TRRAP and GRIN2A melanoma metastatic cell lines.
    Related Technologies:
     HHS Reference No. E-272-2008/0--U.S. Patent Application 
No. 13/128,125 filed 06 May 2011, European and Australian applications 
filed; Mutations of the ERBB4 Gene in Melanoma.
     HHS Reference No. E-229-2010/0--Research Tool; ERBB4 
Mutations Identified in Human Melanoma Metastasis Cell Lines (2690, 
2379, 2197, 2183, 2535, 2645, 1770, 2359, 2238, 2319, 2190).
     HHS Reference No. E-232-2010/0--Research Tool; Isocitrate 
Dehydrogenase 1 (IDH1) R132 Mutation Human Melanoma Metastasis Cell 
Line.
    Licensing Contact: Whitney Hastings; 301-451-7337; 
[email protected].

Cells and Nanoparticles With Altered Protein Expression Patterns Useful 
for the Modulation of T Cell Activity for Immunotherapy

    Description of Technology: NIH scientists have developed human 
cells and nanoparticles to enhance immunotherapy. Specifically, 
researchers have identified that cells or nanoparticles expressing a 
high temperature requirement serine peptidase 1 (HtrA1) activator and/
or a cytokine-induced Src homology 2 protein (CIS) inhibitor are 
capable of increasing T cell activity. These compositions can be used 
primarily in T cell immunotherapy against various cancers and 
infectious diseases where enhanced T cell activity is beneficial. 
Conversely, cells or nanoparticles that express a HtrA1 inhibitor and/
or a CIS activator can suppress T cell activity. These compositions can 
be utilized to treat various auto- or alloimmune diseases and can be 
used to prevent transplant rejections.
    HtrA1 (also known as L56, ARMD7, ORF480, and PRSS11) is a serine 
protease that is known to inhibit the TGF-beta family proteins. CIS 
(also known as G18, SOCS, CIS-1, and CISH) is a member of the 
suppression of cytokine signaling (SOCS) family of proteins and inhibit 
the JAK/STAT signaling pathways. CIS acts to inhibit HtrA1 and repress 
cell activation targets. Immunotherapy, although an effective treatment 
strategy, sometimes fails when cells lose activity. T cells adoptively 
transferred into patients where CIS is inhibited and/or HtrA1 is 
activated should maintain their activity and lead to more successful 
adoptive T cell transfers.
    Potential Commercial Applications:
     Immunotherapy for cancer or infectious diseases using 
human cells or nanoparticles expressing an HtrA1 activator and/or a CIS 
inhibitor
     Therapeutic for treating autoimmune diseases using human 
cells and or nanoparticles expressing an HtrA1 inhibitor and/or a CIS 
activator
     Agents expressing an HtrA1 inhibitor and/or a CIS 
activator to prevent organ, tissue, or cell transplant rejection and 
treat alloimmune diseases, such as graft-versus-host disease
     Components of a combination therapy to increase or 
suppress T cell activity in a patient
    Competitive Advantages:
     Some patients do not respond to T cell immunotherapy due 
to lack of cell persistence, survival, or activity as well as for other 
poorly understood reasons. Modifying HtrA1 and CIS in currently 
existing T cell immunotherapies should increase the success rate of 
these therapies by increasing the persistence and survival of the 
infused cells.
     T cells can become ``exhausted'' as they mature following 
activation by target antigen. Cells with altered expression of HtrA1 
and/or CIS may be able to avoid exhaustion after repeated activation.
    Development Stage:
     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Douglas C. Palmer and Nicholas P. Restifo (NCI).
    Publication: Palmer DC and Restifo NP. Suppressors of cytokine 
signaling (SOCS) in T cell differentiation, maturation, and function. 
Trends Immunol. 2009 Dec;30(12):592-602. [PMID 19879803].
    Intellectual Property: HHS Reference No. E-069-2010/0--U.S. Patent 
Application No. 61/420,825 filed 08 December 2010.
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[email protected]

    Dated: August 5, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-20447 Filed 8-10-11; 8:45 am]
BILLING CODE 4140-01-P