[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