[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