Notice: Government-Owned Inventions; Availability for Licensing

Federal Register: Volume 76, Number 186 (Monday, September 26, 2011)
                  Pages 59410-59413

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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.

A Novel Method To Predict Kidney Tumor Growth

    Description of Technology: The invention pertains to a computerized 
method of predicting kidney tumor growth for early stage treatment 
planning. The method utilizes a finite

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element method (FEM)-based 3D tumor growth prediction system using 
longitudinal kidney tumor images. The kidney tissues are classified 
into three types: Renal cortex, renal medulla and renal pelvis. The 
reaction-diffusion model is applied as the tumor growth model. 
Different diffusion properties are considered in the model: Anisotropic 
for renal medulla and isotropic for renal cortex and renal pelvis. The 
FEM is employed to solve the diffusion model. The model parameters are 
estimated by optimizing of an objective function. Ultimately, 
longitudinal data is used to fit the tumor growth model. The technique 
was tested on two longitudinal studies with seven time points on five 
tumors. The experimental results (average of 91.4% true positive volume 
fraction and 4.0% of false positive volume fraction) showed the 
feasibility and efficacy of the technique.
    Potential Commercial Applications: The technique can be used to 
predict kidney tumor growth pattern using CT data. It can be 
effectively used in planning therapeutic regimen in early stage kidney 
tumors.
    Competitive Advantages: The technique is the first kidney tumor 
growth prediction system. It can be implemented in the oncology package 
that most major imaging companies have in their commercial workstation.
    Development Stage:
     Prototype.
     In vivo data available (human).
    Inventors: Ronald M. Summers et al. (NIHCC).
    Publication: Chen X, et al. FEM-Based 3-D Tumor Growth Prediction 
for Kidney Tumor. IEEE Trans Biomed Eng. 2011 March;58(3):463-467; doi 
10.1109/TBME.2010.2089522.
    Intellectual Property: HHS Reference E-250-2011/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Contact: Michael Shmilovich, Esq.; 301-435-5019; 
shmilovm@mail.nih.gov.

Pharmaceutical Compounds for the Treatment of Spinal Muscular Atrophy 
and Other Uses

    Description of Technology: The SMA Project (http://www.smaproject.org/programs.html) was established by NINDS to identify 
new compounds with improved effectiveness, safety, and pharmacokinetic 
characteristics aimed at finding a new therapeutic treatment for Spinal 
Muscular Atrophy (SMA), a paralyzing and often fatal disease of infants 
and children. The result of the SMA Project medicinal chemistry 
optimization effort is a library of ~1400 indoprofren analogues with 
drug like properties. A lead pre-clinical candidate for SMA has been 
identified based on several factors, including its ability to increase 
SMN expression.
    The mechanism by which these compounds affect ribosomal fidelity 
proves to be useful for many genetic CNS diseases. The ability of these 
compounds to read through nonsense stop codons, coupled with the 
ability to cross the blood-brain barrier and drug like properties, 
makes these compounds attractive as therapeutics for diseases such as 
Muscular Dystrophy and Cystic Fibrosis. Preliminary results in HIV and 
HPV assays show that these compounds potently inhibit viral 
replication, presumably via inducing ribosomal frame shift, suggesting 
potential for antiviral therapy. In addition, these compounds have been 
shown to be non-toxic and well-tolerated at high doses in rodents.
    Potential Commercial Applications: Broad applications based on 
mechanism of action--
     Read through = many genetic CNS diseases.

--Spinal Muscular Atrophy (SMA) .
--Muscular Dystrophy, Rett Syndrome, Diabetes Cancer, Niemann Pick 
disease, Cystic Fibrosis.
     Frame shift = broad anti-viral.
--Efficacy similar to AZT in HIV replication assay.
--Effective suppression of HPV replication.
--Brain penetrant compounds [rarr] neuronal viruses.

    Competitive Advantages:
     No treatments available for SMA.
     First-in-class anti-viral with host-directed mechanism of 
action.
     Optimized activity and pharmaceutical properties:
--nM potency and efficacy in SMN expression assays.
--Good brain penetrance.
--Metabolic stability in multiple species.
--Demonstrated favorable ADMET characteristics.
--Demonstrated safety in 7-day rat tox studies.
--High yield synthesis process.

    Development Stage:
     Early-stage.
     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Jill E. Heemskerk (NINDS), et al.
    Intellectual Property: HHS Reference No. E-050-2011/0--U.S. Patent 
Application No. 61/475,541 filed 14 April 2011.
    Related Technologies:
     HHS Reference No. E-133-2006/1--U.S. Patent Application 
No. 12/293,268 and foreign patent applications.
     HHS Reference No. E-187-2007/0--U.S. Patent Application 
No. 12/680,285 and foreign patent applications.
    Licensing Contact: Charlene A. Sydnor, Ph.D.; 301-435-4689; 
sydnorc@mail.nih.gov.
    Collaborative Research Opportunity: The National Institute of 
Neurological Disorders and Stroke is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate or commercialize treatment for SMA. For 
collaboration opportunities, please contact Melissa Maderia at 
maderiam@mail.nih.gov.

STAMP, A Novel Cofactor and Possible Steroid Sparing Agent, Modulates 
Steroid-induced Induction or Repression of Steroid Receptors

    Description of Technology: Steroid hormones such as androgens, 
glucocorticoids, and estrogens are used in the treatments of many 
diseases. They act to regulate many physiological responses by binding 
to steroid receptors. However, because steroid receptors are expressed 
in many tissues, efforts to therapeutically modify the effects of 
steroid hormones on a specific tissue or on a specific receptor of the 
steroid receptor family often cause undesirable effects in other 
tissues or on other receptors. STAMP (SRC-1 and TIF-2 Associated 
Modulatory Protein), a novel protein that acts to lower the 
concentration of steroid hormone needed to induce (or repress) selected 
target genes by regulating steroid receptor synthesis, offers a novel 
approach for reducing the severity of unwanted side-effects, thereby 
increasing the ability to use steroid hormone therapies.
    Potential Commercial Applications:
     Diseases requiring chronic steroid treatment such as 
rheumatoid arthritis, psoriatic arthritis, asthma, inflammatory and 
auto-immune diseases.
     Diseases characterized by excess or deficiency of 
glucocorticoids such as obesity, diabetes, hypertension, Cushing's 
Syndrome, Parkinson's Disease, Addison's Disease.
     Diseases in which glucocorticoid-responsive gene 
expression is deranged, so deranging carbohydrate, protein or lipid 
metabolism.
     Cancers responsive to androgen or estrogen, such as breast 
cancer or prostate cancer.
     Therapeutic applications related to male or female hormone 
replacement, symptoms related to menopause, birth control, menstrual 
cycle/amenorrhea, fertility or endometriosis.
    Competitive Advantages:

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     STAMP reduces the severity of unwanted side-effects of 
steroid hormone therapies.
     STAMP modulates the gene induction properties of androgen 
and progesterone receptors.
     STAMP modulates both induction and repression properties 
of glucocorticoid receptors.
     STAMP is inactive toward alpha and beta estrogen 
receptors, thyroid receptor beta, PPAR gamma 2, retinoid receptor alpha 
or RXR alpha.
     The siRNAs could be useful as therapeutics.
    Development Stage: Early-stage.
    Inventors: S. Stoney Simons Jr. and Yuanzheng He (NIDDK)
    Publication: He Y, Simons SS Jr. STAMP, a novel predicted factor 
assisting TIF2 actions in glucocorticoid receptor-mediated induction 
and repression. Mol Cell Biol. 2007 Feb;27(4):1467-1485. [PMID 
17116691].
    Intellectual Property: HHS Reference No. E-056-2004/0--U.S. Patent 
No. 7,867,500 issued 11 Jan 2011.
    Related Technology: HHS Reference No. E-226-2009/0--PCT Application 
No. PCT/US10/037452 filed 04 Jun 2010, which published as WO 2010/
144324 on 16 Dec 2010.
    Licensing Contact: Tara L. Kirby, PhD.; 301-435-4426; 
tarak@mail.nih.gov.
    Collaborative Research Opportunity: The National Institute of 
Diabetes and Digestive and Kidney Diseases, Steroid Hormones Section, 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate or commercialize 
STAMP, a steroid cofactor. Please contact Dr. S. Stoney Simons at 
steroids@helix.nih.gov for more information.

A Biomarker and Therapeutic Target for Ovarian Cancer

    Description of Technology: This technology provides methods of 
diagnosing or treating certain ovarian cancers using STAMP, a steroid 
cofactor. There are currently no effective methods for early-stage 
diagnosis of ovarian cancer. Diagnosis is usually made through a 
combination of physical examination, ultrasound imaging, and a blood 
test for the tumor marker CA-125. The CA-125 test only returns a true 
positive result for about 50% of early-stage ovarian cancers, and may 
be elevated in other conditions not related to cancer, so it is not an 
adequate early detection tool when used alone.
    The inventors have shown that STAMP mRNA levels are elevated in 
ovarian cancer samples, including early-stage cancers. They have also 
found that in a subset of ovarian cancer cell lines, introduction of 
STAMP siRNAs slows cell proliferation. These findings suggest that 
STAMP may be useful as a biomarker to detect early stage cancer in 
ovarian tissues, and is also promising as a therapeutic target for a 
subset of ovarian cancers.
    Applications:
     Development of an early-stage diagnostic test for ovarian 
cancer.
     Development of a siRNA-based therapy for ovarian cancer.
    Development Stage:
     Early-stage.
     In vitro data available.
    Inventors: S. Stoney Simons and Yuanzheng He (NIDDK).
    Publication: He Y, et al. STAMP alters the growth of transformed 
and ovarian cancer cells. BMC Cancer. 2010 Apr 7;10:128. [PMID 
20374646].
    Intellectual Property: HHS Reference No. E-226-2009/0--PCT 
Application No. PCT/US10/037452 filed 04 Jun 2010, which published as 
WO 2010/144324 on 16 Dec 2010.
    Related Technology: HHS Reference No. E-056-2004/0--U.S. Patent No. 
7,867,500 issued 11 Jan 2011.
    Licensing Contact: Tara Kirby, Ph.D.; 301-435-4426; 
tarak@mail.nih.gov.
    Collaborative Research Opportunity: The National Institute of 
Diabetes and Digestive and Kidney Diseases, Steroid Hormones Section, 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize STAMP, a steroid cofactor. Please contact Dr. S. Stoney 
Simons at steroids@helix.nih.gov for more information.

Small Molecule Modulators of Adrenomedullin and Gastrin Releasing 
Peptide for the Treatment of Cancer and Other Angiogenesis-Mediated 
Disorders

    Description of Technology: Adrenomedullin (AM) and Gastrin 
Releasing Peptide (GRP) are peptide hormones that are expressed in a 
wide range of tissues and have a variety of biological roles, including 
angiogenesis, cardiovascular disease, renal function, cell growth, 
glucose metabolism, and regulation of hormone secretion.
    The inventors have identified a panel of small molecule, non-
peptide, pharmaceutically active compounds that modulate AM or GRP 
activity at nanomolar concentrations. Certain antagonists in the panel 
were demonstrated to inhibit angiogenesis and inhibit cell 
proliferation in vitro, and to reduce tumor size in an in vivo rodent 
model. These modulatory compounds may be may be useful in the treatment 
of a number of diseases related to aberrant angiogenesis, particularly 
cancer.
    This technology describes methods of inhibiting aberrant activity 
of AM or GRP using a compound identified by the inventors, as well as 
methods of treating a condition by such inhibition, such as cancer, 
hypotension, and other disorders. Also described are pharmaceutical 
compositions, kits, and methods for detecting an AM or GRP peptide 
using the compounds.
    Potential Commercial Applications: Treatment of angiogenesis-
mediated diseases such as cancer, cardiovascular disease, and macular 
degeneration.
    Competitive Advantages:
     Compounds effective at nanomolar concentrations.
     Extensive in vitro and in vivo data available for several 
compounds.
    Development Stage:
     Early-stage.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Frank F. Cuttitta and Alfredo Martinez (NCI).
    Publications:
    1. Martinez A, et al. Identification of vasoactive nonpeptidic 
positive and negative modulators of adrenomedullin using a neutralizing 
antibody-based screening strategy. Endocrinology. 2004 Aug;145(8):3858-
3865. [PMID 15107357].
    2. Martinez A, et al. Gastrin-releasing peptide (GRP) induces 
angiogenesis and the specific GRP blocker 77427 inhibits tumor growth 
in vitro and in vivo. Oncogene. 2005 Jun 9;24(25):4106-4113. [PMID 
15750618].
    3. Mart[iacute]nez-Murillo R, et al. Standardization of an 
orthotopic mouse brain tumor model following transplantation of CT-2A 
astrocytoma cells. Histol Histopathol. 2007 Dec;22(12):1309-1326. [PMID 
17701911].
    4. Fang C, et al. Non-peptide small molecule regulators of 
lymphangiogenesis. Lymphat Res Biol. 2009 Dec;7(4):189-196. [PMID 
20143917].
    Intellectual Property:
     HHS Reference No. E-246-2003/1--U.S. Application No. 10/
571,012 filed 08 Mar 2006.
     Foreign counterparts in Australia, Canada, and Europe.
    Related Technologies:
     HHS Reference No. E-206-1995/3.
     HHS Reference No. E-256-1999/0.
     HHS Reference No. E-293-2002/0.
     HHS Reference No. E-294-2002/0.
     HHS Reference No. E-263-2009/0.
    Licensing Contact: Tara Kirby, Ph.D.; 301-435-4426; 
tarak@mail.nih.gov.


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    Dated: September 20, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-24626 Filed 9-23-11; 8:45 am]
BILLING CODE 4140-01-P