[Federal Register Volume 77, Number 14 (Monday, January 23, 2012)]
[Notices]
[Pages 3275-3277]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-1266]
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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.
Thioxothiazolidinone Derivatives--A Novel Class of Anti Cancer Agents
Description of Technology: The invention provides for a novel class
of heterocyclic compounds (i.e. thioxothiazolidinone derivatives) that
exhibit anticancer activity in a unique mechanism. More specifically,
the compounds of the invention act as inhibitors of the enzyme human
tyrosyl DNA phosphodiesterase1 (Tdp1), a DNA repair enzyme involved in
topoisomerase1 (Top1) mediated DNA damage, such as damage induced by
the Top1 inhibitors and chemotherapeutic agents, camptothecins. As
such, these compounds can serve as potentiators of camptothecins. The
experimental data indeed point at a synergistic effect achieved in a
combination therapy of the thioxothiazolidinone derivatives of the
invention and the established anticancer agents camptothecins.
Moreover, due to this synergistic effect, a lower therapeutic dose of
the latter may be needed, resulting in reduced side effects. In
addition, it is possible that the Tdp1 inhibitors of the invention may
be effective as anti tumor agents on their own. This is based on the
fact that Tdp1 is involved also in repairing DNA damage resulting from
oxygen radicals, and the observation that tumors contain excess free
radicals.
Potential Commercial Applications
Effective cancer therapy in combination with
camptothecins.
Cancer therapy as standalone anti cancer agents.
Competitive Advantages: The compounds of the invention act in
unique mechanism that can enhance the therapeutic efficacy of the
anticancer drugs camptothecins, and at the same time can serve as
standalone anticancer agents.
Development Stage: In vitro data available.
Inventors: Yves G. Pommier (NCI) et al.
Publications
1. Marchand C, et al. Identification of phosphotyrosine mimetic
inhibitors of human tyrosyl-DNA phosphodiesterase I by a novel
AlphaScreen high-throughput assay. Mol Cancer Ther. 2009 Jan;8(1):240-
248. [PMID 19139134].
2. Dexheimer TS, et al. Tyrosyl-DNA phosphodiesterase as a target
for anticancer therapy. Anticancer Agents Med Chem. 2008 May;8(4):381-
389. [PMID 18473723].
3. Dexheimer TS, et al. 4-Pregnen-21-ol-3,20-dione-21-(4-
bromobenzenesufonate) (NSC 88915) and related novel steroid derivatives
as tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors. J Med Chem. 2009
Nov 26;52(22): 7122-7131. [PMID 19883083].
Intellectual Property: HHS Reference No. E-239-2011/0--U.S.
Provisional Patent Application No. 61/545,308 filed 10 Oct 2011.
Licensing Contact: Uri Reichman, Ph.D., MBA; (301) 435-4616;
[email protected].
Monospecific and Bispecific Human Monoclonal Antibodies Targeting IGF-
II
Description of Technology: The type 1 insulin-like growth factor
(IGF) receptor (IGF1R) is over-expressed by many tumors and mediates
proliferation, motility, and protection from apoptosis. Agents that
inhibit IGF1R expression or function can potentially block tumor growth
and metastasis. Its major ligands, IGF-I, and IGF-II are over-expressed
by multiple tumor types. Previous studies indicate that inhibition of
IGF-I, and/or IGF-II binding to its cognizant receptor negatively
modulates signal transduction through the IGF pathway and concomitant
cell proliferation and growth. Therefore, use of humanized or fully
human antibodies against IGFs represents a valid approach to inhibit
tumor growth. The present invention discloses two monoclonal
antibodies, designated m610.27 and m630, and a bispecific monoclonal
antibody, m660, generated by linking domains from m610.27 and m630. All
three antibodies display high affinities for IGF-I and IGF-II in the pM
to nM range. The antibodies inhibited signal transduction mediated by
the IGF-1R interaction with IGF-I and IGF-II and blocked
phosphorylation of IGF-IR and the
[[Page 3276]]
insulin receptor. m610.27 and m630 are the first pair of human
antibodies that target nonoverlapping epitopes on IGF-II. All three
antibodies in an IgG1 or IgG1-like format could lead to irreversible
elimination of IGF-II from circulation making it a viable candidate for
cancer treatment.
Potential Commercial Applications
Therapeutic for the treatment of various human diseases
associated with aberrant cell growth and motility such as breast,
prostate, and leukemia cancers.
Research reagent to study IGF-I and/or IGF-II binding and
its association with tumor growth.
Competitive Advantages
m610.27 and m630 are the first characterized antibodies
that target nonoverlapping epitopes on IGF-II.
m660 was generated from two domains; one each from m610.27
and m630.
Small size of the m610.27 and m630 domains prevent
overlapping in binding to IGF-II.
Development Stage
Pre-clinical.
In vitro data available.
Inventors: Dimiter S Dimitrov, Weizao Chen, Yang Feng (NCI).
Intellectual Property: HHS Reference No. E-212-2011--U.S.
Provisional Application No. 61/548,164 filed 17 Oct 2011.
Related Technologies
HHS Reference No. E-217-2005/2--U.S. Patent No. 7,824,681
issued 02 Nov 2010; U.S. Patent Application No. 12/889,345 filed 23 Sep
2010.
HHS Reference No. E-336-2005/0--U.S. Patent Application
No. 12/296,328 filed 07 Oct 2008.
HHS Reference No. E-232-2009/0--PCT Application No. PCT/
US2010/051784 filed 07 Oct 2010.
HHS Reference No. E-068-2011/0--U.S. Provisional
Application No. 61/474,664 filed 12 Apr 2011.
Licensing Contact: Whitney Hastings; (301) 451-7337;
[email protected].
Collaborative Research Opportunity: The NCI CCR Nanobiology Program
is seeking statements of capability or interest from parties interested
in collaborative research to further develop, evaluate or commercialize
this technology. For collaboration opportunities, please contact John
Hewes, Ph.D. at [email protected].
Genetic Interactions That Predict Attention Deficit Hyperactivity
Disorder Outcome and Severity
Description of Technology: Genotyping of attention deficit
hyperactivity disorder (ADHD) linked chromosomal regions containing
single nucleotide polymorphisms (SNPs) was used by researchers at the
National Human Genome Research Institute (NHGRI) to discover gene
interactions that increase the risk of developing ADHD and predict ADHD
severity.
NHGRI researchers discovered an ADHD linked gene interaction
between the latrophilin 3 (LPHN3) gene and a haplotype on chromosome
11q that contains the gene coding for the dopamine receptor D2 (DRD2)
and neural cell adhesion molecule 1 (NCAM1). In a similar invention,
mutations in LPHN3 were shown to increase the risk of developing ADHD
(HHS E-312-2006, TAB 1504). Expanding on those findings, this invention
describes an interaction between LPHN3 and 11q that not only doubles
the risk of developing ADHD, but also the severity of ADHD.
Furthermore, the LPHN3-11q interaction correlates with patient response
to therapeutic treatments.
In summary, this invention can be used to develop biomarkers for
determining susceptibility to and severity of ADHD, as well as,
developing theranostic assays for determining prognosis of ADHD
treatments. In addition, signaling pathways delineated from these
genetic sites can be used to develop better ADHD therapeutics.
Potential Commercial Applications
Biomarkers for ADHD susceptibility and severity.
Prognostic assays.
Personalized treatment options.
Competitive Advantages: Improved prediction of ADHD susceptibility,
severity, and possibly patient response to treatment.
Development Stage
Early-stage.
In vivo data available (human).
Inventors: Maximilian Muenke, Mauricio Arcos-Burgos, and Maria T.
Acosta (NHGRI).
Publications
1. Jain M, et al. A cooperative interaction between LPHN3 and 11q
doubles the risk for ADHD. Mol Psychiatry. 2011 May 24. (Epub ahead of
print) [PMID: 21606926].
2. Arcos-Burgos M and Muenke M. Toward a better understanding of
ADHD: LPHN3 gene variants and the susceptibility to develop ADHD. Atten
Defic Hyperact Disord. 2010 Nov;2(3):139-147. [PMID: 21432600].
Intellectual Property: HHS Reference No. E-187-2011/0--U.S.
Provisional Application No. 61/505,864 filed on 08 July 2011.
Related Technology: HHS Reference No. E-312-2006/0--U.S. Patent No.
8,003,406 issued on 23 August 2011.
Licensing Contact: Charlene Sydnor, Ph.D.; (301) 435-4689;
[email protected].
Modulating Autophagy as a Treatment for Lysosomal Storage Diseases
Description of Technology: Researchers at NIAMS have developed a
technology for treatment of lysosomal storage diseases by inhibition of
autophagy. Pompe disease is an example of a genetic lysosomal storage
disease caused by a reduction or absence of acid alpha-glucosidase
(GAA). Patients with Pompe disease have a lysosomal buildup of glycogen
in cardiac and skeletal muscle cells and severe cardiomyopathy and
skeletal muscle myopathy. Treatment of Pompe disease by GAA enzyme
replacement therapy is quite ineffective for the skeletal muscle
myopathy. Skeletal muscle resistance to therapy is associated with
increased cellular buildup of autophagic debris. Inactivation of
autophagy results in effective GAA replacement therapy and a reduction
in glycogen back to normal levels. This technology provides a novel
approach for the treatment of Pompe disease as well as other diseases
where autophagy is a critical contributor to disease development.
Potential Commercial Applications
Development of tools for autophagy suppression and
treatment of a variety of diseases.
Development of chemical inhibitors of autophagy.
Development of animal models to study lysosomal storage
diseases.
Competitive Advantages
This technology is the first use of autophagy disablement
to reverse an intracellular pathology.
More effective than enzyme replacement therapy alone for
the treatment of the lysosomal storage disease, Pompe disease.
Development Stage: In vivo data available (animal).
Inventors: Nina Raben, Cynthia N. Schreiner, Paul H. Plotz, Shoichi
Takikita, Tao Xie, Rebecca Baum (NIAMS).
[[Page 3277]]
Publications
1. Raben N, et al. Suppression of autophagy permits successful
enzyme replacement therapy in a lysosomal storage disorder--murine
Pompe disease. Autophagy. 2010 Nov;6(8):1078-1089. [PMID 20861693].
2. Raben N, et al. Suppression of autophagy in skeletal muscle
uncovers the accumulation of ubiquitinated proteins and their potential
role in muscle damage in Pompe disease. Hum Mol Genet. 2008 Dec
15;17(24):3897-3908. [PMID 18782848].
Intellectual Property: HHS Reference No. E-210-2009/0--PCT
Application No. PCT/US2010/047730 filed 02 Sep 2010.
Licensing Contact: Jaime Greene, M.S.; (301) 435-5559;
[email protected].
Collaborative Research Opportunity: The National Institutes of
Health is seeking statements of capability or interest from parties
interested in collaborative research to further develop, evaluate or
commercialize the technology for disabling autophagy as a treatment for
lysosomal storage diseases. For collaboration opportunities, please
contact Cecilia Pazman at [email protected].
Dated: January 17, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-1266 Filed 1-20-12; 8:45 am]
BILLING CODE 4140-01-P