[Federal Register Volume 77, Number 60 (Wednesday, March 28, 2012)]
[Notices]
[Pages 18831-18833]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-7420]


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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.

Lenalidomide Analogs for the Treatment of Neurodegenerative Disorders 
and Cancer

    Description of Technology: Inflammatory processes associated with 
the over-production of tumor necrosis-alpha (TNF-[alpha]), a potent 
activator of the immune system accompany numerous neurodegenerative 
diseases. TNF-[alpha] has been validated as a drug target with the 
development of the inhibitors Enbrel and Remicade (fusion antibodies) 
as prescription medications. Both, however, are large macromolecules 
that require direct injection and have limited brain access. The 
classical drug, thalidomide is being increasingly used in the clinical 
management of a wide spectrum of immunologically-mediated and 
infectious diseases, and cancers. The NIA inventors developed and 
assessed novel thio analogs of lenalidomide (Celegene's Revlimid and an 
analog of thalidomide) as immunomodulatory agents, with the potential 
to reduce chronic systemic and central nervous system inflammation. 
These compounds were synthesized and evaluated for their TNF-[alpha] 
inhibitory activity. This invention was extended from the inventors' 
prior work to develop potent compounds to reduce neuroinflammation as a 
treatment strategy for neurodegenerative disorders. The current studies 
focus the compounds activity in classical models of neurodegeneration 
as well as cancer.
    Potential Commercial Applications:
     Treatment for blood disorders (myelodysplastic syndrome), 
cancer (multiple myeloma), inflammatory processes and erythema
     Immunomodulatory agents
     Reduce chronic systemic and central nervous system 
inflammation
    Competitive Advantages:
     Effective smaller molecular weight compound that can enter 
brain among current agents
     Experimental therapeutic to reduce inflammation 
systematically and within the brain
     Effective in reducing proinflammatory cytokines than 
existing agents
    Development Stage:
     Prototype
     Clinical
     In vitro data available
     In vivo data available (animal)
    Inventors: Nigel H. Greig, Weiming Luo, David Tweedie, Harold W. 
Holloway, Qian-sheng Yu (all of NIA).
    Publication: Luo W, et al. Design, synthesis and biological 
assessment of novel N-substituted 3-(phthalimidin-2-yl)-2,6-
dioxopiperidines and 3-substituted 2,6-dioxopiperidines for TNF-alpha 
inhibitory activity. Bioorg Med Chem. 2011 Jul 1;19(13):3965-3972. 
[PMID 21658960]
    Intellectual Property: HHS Reference No. E-045-2012/0--U.S. Patent 
Application No. 13/310,242 filed 02 Dec 2011.
    Related Technologies: HHS Reference No. E-189-2003/0--
     U.S. Patent No. 7,973,057 issued 05 Jul 2011
     U.S. Application No. 13/153,355 filed 03 Jun 2011
     and related international patents/patent applications
    Licensing Contact: Whitney Hastings, Ph.D.; 301-451-7337; 
[email protected].

Use of Englerin A, a Small Molecule HSF1 Activator, for the Treatment 
of Diabetes, Obesity, and Other Diseases Associated With Insulin 
Resistance

    Description of Technology: Insulin resistance is a causative factor 
for type

[[Page 18832]]

2 diabetes, obesity and a number of other conditions. This technology 
claims methods for treating diseases or conditions associated with 
insulin resistance using the small molecule epoxy-guaiane derivative 
englerin A and related compounds. The compounds are claimed separately 
in a related NIH technology.
    The inventors have shown that englerin A, a compound originally 
isolated from the Phyllanthus plant and previously identified as an 
anti-cancer agent, can also be used to treat insulin resistance. 
Insulin resistance is associated with reduced gene expression and 
production of heat shock protein 70 (HSP70). Using a mouse with tumor 
model, the inventors discovered that administration of englerin A 
decreases blood glucose levels by activating transcription of HSF1, 
thereby increasing the expression and secretion of HSP70. Thus, 
englerin A and related compounds represent potential drugs for the 
treatment of a variety of conditions associated with insulin 
resistance.
    Potential Commercial Applications: Treatment of diseases or 
conditions associated with insulin resistance, such as type 2 diabetes, 
obesity, inflammation, metabolic syndrome, polycystic ovary disease, 
arteriosclerosis, non-alcoholic fatty liver disease, reproductive 
abnormality of a female, and growth abnormality.
    Competitive Advantages: Use of small-molecule compounds targeting 
HSF1 represents a novel approach to the treatment of type 2 diabetes 
and other conditions caused by insulin resistance.
    Development Stage:
     In vitro data available
     In vivo data available (animal)
    Inventors: Leonard Neckers et al. (NCI).
    Publication: Ratnayake R, et al. Englerin A, a selective inhibitor 
of renal cancer cell growth, from Phyllanthus engleri. Org Lett. 2009 
Jan 1;11(1):57-60. [PMID 19061394]
    Intellectual Property: HHS Reference No. E-042-2012/0--U.S. 
Application No. 61/584,526 filed 09 Jan 2012.
    Related Technologies: HHS Reference No. E-064-2008/2--U.S. 
Application No. 12/811,245 filed 29 Jul 2010 and related international 
applications.
    Licensing Contact: Tara Kirby, Ph.D.; 301-435-4426; 
[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 epoxyguaianes as anti-type 2 diabetes agents. For 
collaboration opportunities, please contact John Hewes, Ph.D. at 
[email protected].

A Novel, Non-invasive Test for the Detection of Chromaffin Cell Tumors 
Associated With SDHB Mutation

    Description of Technology: Pheochromocytomas/paragangliomas (PHEOs/
PGLs) are hormone producing tumors of the sympathetic nervous system 
located in the adrenal glands (which sit atop the kidneys) or the 
paraganglia, which are distributed throughout the upper body. Mutations 
in the gene of a mitochondrial protein, succinate dehydrogenase B 
(SDHB), can cause PHEOs/PGLs that have a high rate of malignancy. 
Normally, PHEOs/PGLs can be diagnosed by measuring increased stress 
hormone metabolites in blood or urine. However, detection of SDHB-
related PHEOs/PGLs can be difficult as up to ten percent do not show 
elevated stress hormone metabolites, and thus proper diagnosis requires 
expensive and often not-widely-available imaging. In addition, SDHB-
PHEO/PGL patients need regular imaging to rule out development of 
metastases and family members of patients with SDHB-PHEOs/PGLs need 
genetic testing for risk evaluation. A significant need remains for 
additional diagnostic methods to prevent misdiagnosis of patients with 
non-secreting or metastatic SDHB-PHEOs/PGLs and risk evaluation of 
family members.
    Researchers at the Eunice Kennedy Shriver National Institute of 
Child Health and Human Development (NICHD) have developed methods to 
identify SDHB mutation based on the presence/absence of just four 
urinary peptides. Further data from the researchers suggests that 
metastatic PGLs can also be identified in patients based on their 
urinary peptide pattern.
    Potential Commercial Applications: Diagnostic kits for non-
secreting or metastatic PHEOs/PGLs in patients, or for risk assessment 
of their family members.
    Competitive Advantages:
     Cost-effective
     Non-invasive
     Sample collection could occur at home or doctor's office
    Inventors: Karel Pacak (NICHD) et al.
    Intellectual Property: HHS Reference No. E-201-2011/0 -- U.S. 
Provisional Application No. 61/498,428 filed 17 Jun 2011.
    Licensing Contact: Patrick P. McCue, Ph.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The Eunice Kennedy Shriver 
National Institute of Child Health and Human Development is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize a 
urine-based diagnostic to detect proteins associated with 
pheochromocytoma/paraganglioma (PHEO/PGL). For collaboration 
opportunities, please contact Joseph M. Conrad III, Ph.D., J.D. at 
[email protected].

T Lymphocyte (T Cell) Clones That Recognize the Tumor Associated 
Antigens gp100 and MART-1

    Description of Technology: Scientists at the National Institutes of 
Health (NIH) have developed cytotoxic, CD8+ T lymphocyte (T cell) 
clones, designated R6C12 and JKF6, derived from tumor infiltrating 
lymphocytes (TIL) of cancer patients. The R6C12 clone recognizes the 
tumor associated antigen (TAA) gp100 and has been shown to be specific 
for amino acids 209-217 of the gp100 protein, known as the 210M or 
g209-2M peptide. The JKF6 clone recognizes the TAA MART-1, specifically 
the peptide represented by amino acids 27-35 of the MART-1 protein. TIL 
are a subset of T cells found within tumors that have high specificity 
for the antigen(s) expressed by that tumor.
    MART-1 (also known as Melan-A) and gp100 are TAAs expressed 
primarily by melanomas and at low levels in normal melanocytes. MART-1 
is a melanocyte differentiation antigen found on the surface of these 
cells and gp100 is a transmembrane glycoprotein. Both proteins are 
located in the melanosomes of normal melanocytes, the melanin producing 
organelle of these cells. In cancer patients with gp100+ and or MART-1+ 
tumors, T cells, such as TIL, have been identified that recognize 
particular epitopes of these TAAs to mediate tumor cell killing. Cancer 
vaccines and adoptive T cell immunotherapies have been developed to 
generate immune responses to target one or both of these antigens for 
cancer regression.
    Potential Commercial Applications:
     Characterize and develop T cell receptors for use in 
adoptive immunotherapy of MART-1+ and gp100+ cancers
     Develop molecular screens to characterize tumor antigen 
expression of patient samples and/or laboratory cell lines
     Develop research materials to better understand T cell 
functions, including antigen recognition, cell signaling, and immune 
responses
     Positive controls for T cells with high reactivity to 
gp100 and MART-1

[[Page 18833]]

    Competitive Advantages:
     These T cell clones were isolated and selected from the 
bulk TIL cultures of the respective patients from which they were 
derived due to their superior reactivity to their TAA antigen.
     Significant data has been collected on their 
characteristics, including identification of the tumor associated 
antigen and specific cancer peptide recognized by the T cell receptor 
of each clone.
    Development Stage:
     Pre-clinical
     Clinical
     In vitro data available
     In vivo data available (human)
    Inventors: Mark E. Dudley and Steven A. Rosenberg (both of NCI).
    Publications:
    1. Dudley M, et al. Cancer regression and autoimmunity in patients 
after clonal repopulation with antitumor lymphocytes. Science. 2002 Oct 
25;298(5594):850-854. [PMID 12242449]
    2. Dudley M, et al. Adoptive transfer of cloned melanoma-reactive T 
lymphocytes for the treatment of patients with metastatic melanoma. J 
Immunother. 2001 Jul-Aug;24(4):363-373. [PMID 11565838]
    Intellectual Property: HHS Reference No. E-267-2010/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Related Technologies:
     HHS Reference No. E-057-1994--elanoma Antigens and Their 
Use in Diagnostic and Therapeutic Methods
     HHS Reference No. E-086-2001--Peptides of a Melanoma 
Antigen and Their Use in Diagnostic, Prophylactic, and Therapeutic 
Methods
     HHS Reference No. E-106-2004--Compositions Comprising T 
cell Receptors and Methods of Use Thereof
     HHS Reference No. E-304-2006--Modified T cell Receptors 
and Related Materials and Methods
     HHS Reference No. E-059-2007--gp100-specific T cell 
Receptors and Related Materials and Methods
     HHS Reference No. E-312-2007--Modified T cell Receptors 
and Related Materials and Methods
     HHS Reference No. E-257-2008--Melanoma Associated Peptide 
Analogues and Vaccines Against Melanoma
     HHS Reference No. E-261-2008--Melanoma Associated 
Antigenic Polypeptide, Epitopes Thereof and Vaccines Against Melanoma
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[email protected].

    Dated: March 22, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-7420 Filed 3-27-12; 8:45 am]
BILLING CODE 4140-01-P