[Federal Register Volume 77, Number 97 (Friday, May 18, 2012)]
[Notices]
[Pages 29668-29671]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-12041]


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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

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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.

FOR FURTHER INFORMATION CONTACT: 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.

Java Applet for Modeling Human Metabolism and Energy Expenditure for 
Adaptive Dieting and Exercise Regimens

    Description of Technology: Known methods for predicting weight loss 
fail to account for slowing of metabolism as weight is lost and 
therefore overestimate the degree of weight loss. While this limitation 
of the 3500 Calorie per pound rule has been known for some time, it was 
not clear how to dynamically account for the metabolic slowing. The 
invention provides a Java applet for modeling of human metabolism to 
improve the weight change predictions. The model has been validated 
using previously published human data and the model equations have been 
published. A web-based implementation of the published dynamic model 
has been created to allow users to perform simulations for planning 
weight loss interventions in adults and accounts for individual 
differences in metabolism and body composition.

Potential Commercial Applications

     Obesity.
     Weight Loss.
    Competitive Advantages: Personalized predictions.
    Development Stage: Prototype.
    Inventors: Kevin Hall, Carson Chou, Dhruva Chandramohan (all of 
NIDDK).
    Intellectual Property: HHS Reference No. E-160-2012/0--Research 
Tool.

Patent protection is not being pursued for this technology.
    Licensing Contact: Michael Shmilovich, Esq.; 301-435-5019; 
[email protected].

Antagonist of A3 Adenosine Receptor Fluorescent Probes for 
the Study of Diseases Such as Cancer, Autoimmune Conditions, Dry Eye 
and Other Indications that Involve A3 Signaling

    Description of Technology: Small molecule drugs, A3AR-
selective agonists, are currently in advanced clinical trials for the 
treatment of hepatocellular carcinoma, autoimmune inflammatory 
diseases, such as rheumatoid arthritis, psoriasis, and dry eye disease, 
and other conditions. This molecular probe may serve as a companion 
tool to identify and stratify patient populations based on the 
prevalence of the target A3 adenosine receptors.
    Potential Commercial Applications: Useful tools to study prevalence 
of this receptor on neutrophils which is predictive of response to the 
agonist drugs.
    Competitive Advantages: Drug screening at this receptor is often 
done currently using radiolabeled agonists or antagonists of the human 
A3AR of nanomolar affinity. This method would avoid the use 
of radioisotopes in this part of the research and development process.

Development Stage

     Early-stage.
     In vitro data available.
    Inventors: Kenneth A. Jacobson, et al. (NIDDK).
    Publication: Novel Fluorescent Antagonist as a Molecular Probe in 
A3 Adenosine Receptor Binding Assays Using Flow Cytometry, manuscript 
submitted for publication.
    Intellectual Property: HHS, Reference No. E-073-2012/0--U.S. 
Provisional Application 61/590,596 filed 25 Jan 2012 (Note: a separate 
license may be required for the fluorescent portion of the molecule.)
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].

Methods for Selection of Cancer Patients and Predicting Efficacy of 
Combination Therapy With Histone Deacetylase (HDAC) and mTOR Inhibitors

    Description of Technology: Available for licensing is a novel gene 
signature of thirty-seven drug responsive genes that links changes in 
gene expression to the clinically desirable outcome of improved overall 
survival. Expression of these genes has been linked to prognosis in 
several cancers, including, but not limited to multiple myeloma, lung, 
breast, and melanoma. Patients identified by this signature would be 
predicted to benefit from combined HDAC inhibitor/mTOR inhibitor 
therapy. Additional information is available upon request.

Potential Commercial Applications

     Development of a clinical diagnostic test to identify 
cancer patients who would benefit most from mTOR and HDAC combination 
therapy.
     Use as a surrogate biomarker related to drug response.
     Development of therapeutics targeting several cancers, 
including multiple myeloma.

Competitive Advantages

     Implements a smaller gene set compared to current 
diagnostic gene signatures.
     Provides a basis for the development of a diagnostic for 
patient stratification or a response measurement related to the 
combined use of mTOR and HDAC inhibitors for cancer treatment.

Development Stage

     Early-stage.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Beverly Mock et al. (NCI).
    Intellectual Property: HHS Reference No. E-013-2012/0--U.S. 
Provisional Application No. 61/558,402 filed 10 Nov 2011.
    Licensing Contact: Patrick McCue, Ph.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The NCI Center for Cancer 
Research, Laboratory of Cancer Biology and Genetics, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
Methods for Selecting Cancer Patients for HDACi/mTORi Combination 
Therapy. For collaboration opportunities, please contact John Hewes, 
Ph.D. at [email protected].

GLI-Similar 3(GLIS3) Knock Out (KO) Mice as Models to Screen 
Therapeutics for Diabetes, Polycystic Kidney Disease, and 
Hypothyroidism

    Description of Technology: GLI-similar (Glis) 1-3 proteins 
constitute a subfamily of the Kr[uuml]ppel-like zinc finger 
transcription factors that are closely related to the Gli family. 
Mutations in human GLIS3 have been implicated in a syndrome 
characterized by neonatal diabetes and congenital hypothyroidism (NDH) 
and in some patients accompanied by polycystic kidney disease, 
glaucoma, and liver fibrosis. To further identify and study the 
physiological functions of GLIS3,

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NIEHS investigators generated mice in which GLIS3 is ubiquitously 
knocked out (GLIS3-KO) or conditionally knocked out in a cell type-
specific manner. GLIS3-KO mice develop polycystic kidney disease, 
hypothyroidism, and neonatal diabetes, as indicated by the development 
of hyperglycemia and hypoinsulinemia. The pancreatic endocrine cells, 
particularly insulin-producing pancreatic beta cells, are greatly 
diminished in these mice. The pancreas-selective knockout mice 
GLIS3(Pdx1-Cre) develop severe diabetes within 2-3 months, much later 
than the GLIS3-KO mice. The kidney-selective knockout of GLIS3 
(GLIS3(Ksp-Cre) mice lack expression of GLIS3 in the collecting ducts 
and develop severe polycystic kidney disease within a period of 2-4 
months. These mice can be used as models to screen therapeutics for 
diabetes, polycystic kidney disease, and hypothyroidism.

Potential Commercial Applications

     Therapeutic target in the management of diabetes, 
polycystic kidney disease, and hypothyroidism.
     Models to test therapeutic drugs for diabetes, polycystic 
kidney disease, and hypothyroidism.

Competitive Advantages

     Provides opportunity to discover upstream signals that 
regulate GLIS3 activity.
     Can be used in stem cell therapy in diabetes treatment.
     Excellent model to study the role of GLIS3 in neonatal 
diabetes.

Development Stage

     Early-stage.
     Pre-clinical.
     In vivo data available (animal).
    Inventors: Anton M Jetten, Hong Soon Kang, Kristin Lichti-Kaiser 
(all of NIEHS).

Publications

    1. Kang HS, et al. Transcription factor Glis3, a novel critical 
player in the regulation of pancreatic beta-cell development and 
insulin gene expression. Mol Cell Biol. 2009 Dec;29(24):6366-79. [PMID 
19805515]
    2. Kang HS, et al. Glis3 is associated with primary cilia and 
Wwtr1/TAZ and implicated in polycystic kidney disease. Mol Cell Biol. 
2009 May;29(10): 2556-69. [PMID 19273592]
    Intellectual Property: HHS Reference No. E-303-2011/0--Research 
Tool. Patent protection is not being pursued for this technology.

Related Technologies

     HHS Reference No. E-253-2010/0 --An In-Vitro Cell System 
Useful for Identification of RORgamma Antagonists.
     HHS Reference No. E-222-2009/0 --RORgamma (RORC) Deficient 
Mice Which Are Useful for the Study of Lymph Node Organogenesis and 
Immune Responses.
    Licensing Contact: Suryanarayana Vepa, Ph.D., J.D.; 301-435-5020; 
[email protected].
    Collaborative Research Opportunity: The NIEHS is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize GLIS3 Knock Out 
Mice. For collaboration opportunities, please contact Elizabeth M. 
Denholm, Ph.D. at [email protected].

Microarray for Detection and Subtyping of Human Influenza Viruses

    Description of Technology: Available for licensing and commercial 
development are a novel influenza virus microarray and methods for 
using the microarray for the identification of existing and new types 
and subtypes of human influenza viruses. There are three types of 
influenza viruses, type A, B and C. Influenza types A or B viruses 
cause epidemics of disease almost every winter, with type A causes 
major pandemic periodically. Influenza type A viruses are further 
divided into subtypes based on two proteins on the surface of the 
virus. These proteins are called hemagglutinin (H) and neuraminidase 
(N). There are 16 known HA subtypes and 9 known NA subtypes of 
influenza A viruses. Each subtype may have different combination of H 
and N proteins. Although there are only three known A subtypes of 
influenza viruses (H1N1, H1N2, and H3N2) currently circulating among 
humans, many other different strains are circulating among birds and 
other animals and these viruses do spread to humans occasionally. There 
is a requirement for sensitive and rapid diagnostic techniques in order 
to improve both the diagnosis of infections and the quality of 
surveillance systems. This microarray platform tiles the genomes of all 
types/subtypes of influenza viruses, and is capable of correctly 
identifying all 3 types/subtypes of influenza viruses from an influenza 
vaccine sample.

Potential Commercial Applications

     Detection and identification of human influenza viruses.
     Efficient discovery of new subtypes of influenza viruses.
     Diagnosis of influenza outbreaks.
    Competitive Advantages: Technology can detect multiple types and 
subtypes of influenza virus.

Development Stage

     Pre-clinical.
     In vitro data available.
    Inventors: Xiaolin Wu, David J. Munroe, Cassio S. Baptista, 
Elizabeth Shannon (all of NCI).
    Intellectual Property: HHS Reference No. E-208-2006/0--U.S. Patent 
Application No. 11/936,530 filed 07 Nov 2007.
    Licensing Contact: Kevin W. Chang, Ph.D.; 301-435-5018; 
[email protected].

M3 Muscarinic Receptor Knockout Mice (Chrm3 tm1Jwe) for the Study of 
Obesity and Other Metabolic Disorders

    Description of Mouse: The five Muscarinic Acetylcholine (ACh) 
receptors are G-protein coupled receptors (M1R-M5R). M3 muscarinic ACh 
receptors are present in the central nervous system and the periphery.
    M3R knockout mice are viable and fertile, and have no major 
morphological abnormalities. They have a lean phenotype due to a 
combination of reduced caloric intake and increased energy expenditure. 
Because of their lean phenotype, M3R knockout mice have improved 
glucose tolerance and increased insulin sensitivity. Pharmacological 
blockade of central M3Rs may be a novel strategy for the treatment of 
obesity and associated metabolic disorders.
    In the airway, vagally-mediated bronchoconstriction responses were 
abolished in M3R knockout mice in vivo, suggesting that M3R antagonists 
may be useful in the treatment of chronic obstructive pulmonary disease 
(COPD) and asthma. Studies with M3R knockout mice also have shown that 
the M3R is the major muscarinic receptor mediating ACh-induced 
glandular secretion from exocrine and endocrine glands, including the 
secretion of insulin from pancreatic beta cells.
    Potential Commercial Applications: Animal model to study COPD and 
metabolism.
    Competitive Advantages: M3R knockout mice are viable and fertile, 
and have no major morphological abnormalities.
    Development Stage: Pre-clinical.
    Developer of Mouse: J[uuml]rgen Wess, Ph.D. (NIDDK).
    Publication: Yamada M, et al. Mice lacking the M3 muscarinic 
acetylcholine receptor are hypophagic and lean. Nature. 2001 Mar 
8;410(6825):207-12. [PMID 11242080]

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    Intellectual Property: HHS Reference No. E-346-2004/2--Research 
Tool. Patent protection is not being pursued for this technology.

Related Technologies

     HHS Reference No. E-346-2004/0--M1 Muscarinic receptor KO 
(Chrm1tm1Jwe) Mice.
     HHS Reference No. E-346-2004/1--M2 Muscarinic receptor KO 
(Chrm2 tm1Jwe) Mice.
    Licensing Contact: Jaime M. Greene, M.S.; 301-435-5559; 
[email protected]

Use of E-Selectin Tolerization as Treatment for Immunological and 
Vascular-Related Disorders

    Description of Technology: This technology relates to the mucosal 
delivery (e.g. intranasal) of an E-selectin fragment as a tolerization 
agent for the prevention and treatment of immunological and vascular-
related disorders, including stroke and multiple sclerosis (MS) as well 
as rare or orphan diseases involving vascular modulated disorders.
    E-selectin is an adhesion molecule that is expressed on endothelial 
cells lining blood vessels in response to certain localized cytokines, 
making the endothelial surface pro-coagulant, pro-inflammatory and/or 
immunoreactive. Such changes on the endothelial surface have been 
linked to the development of vascular-related disorders like stroke, as 
well as immune regulated diseases such as MS.
    Intranasal administration of E-selectin, using a tolerizing dosing 
schedule, induces an immunological tolerance to E-selectin. T 
regulatory cells become targeted to activating blood vessel segments, 
where they release immunomodulatory cytokines such as IL-10. This 
release of cytokines suppresses local pro-coagulant, pro-inflammatory 
and immunoreactive effects. Thus, administration of E-selectin as a 
tolerizing agent will provide a targeted therapeutic approach, 
impacting only affected sites in the endothelium.
    Potential Commercial Applications: Treatment of diseases 
biologically based on vascular initiated immune regulation. Such 
disorders include prevention of secondary stroke, MS, Alzheimer's, 
Parkinson's, rheumatoid arthritis, type 1 diabetes, and psoriasis.

Competitive Advantages

     Low doses utilized thus minimizing potential side effects.
     Animal data are available, with further studies currently 
on-going.
     Administration through the intranasal route represents a 
less invasive mode of delivery.
     FDA pre-IND meetings have been held and FDA communications 
are ongoing.

Development Stage

     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: John M. Hallenbeck, Maria Spatz, Hidetaka Takeda, 
Hideaki Wakita (all of NINDS)

Publications

    1. Li X, et al. Intranasal delivery of E-selectin reduces 
atherosclerosis in ApoE-/- mice. PLoS One. 2011;6(6):e20620. Epub 2011 
Jun 20. [PMID 21701687]
    2. Hallenbeck J. How inflammation modulates central nervous system 
vessel activation and provides targets for intervention--a personal 
perspective. Ann N Y Acad Sci. 2010 Oct;1207:1-7. doi: 10.1111/j.1749-
6632.2010.05785.x. [PMID 20955418]
    3. Ishibashi S, et al. Mucosal tolerance to E-selectin promotes the 
survival of newly generated neuroblasts via regulatory T-cell induction 
after stroke in spontaneously hypertensive rats. J Cereb Blood Flow 
Metab. 2009 Mar;29(3):606-20. [PMID 19107136]
    4. Wakita H, et al. Mucosal tolerization to E-selectin protects 
against memory dysfunction and white matter damage in a vascular 
cognitive impairment model. J Cereb Blood Flow Metab. 2008 
Feb;28(2):341-53. [PMID 17637705]
    5. Nakayama T, et al. Intranasal administration of E-selectin to 
induce immunological tolerization can suppress subarachnoid hemorrhage-
induced vasospasm implicating immune and inflammatory mechanisms in its 
genesis. Brain Res. 2007 Feb 9;1132(1):177-84. [PMID 17188657]
    6. Illoh K, et al. Mucosal tolerance to E-selectin and response to 
systemic inflammation. J Cereb Blood Flow Metab. 2006 Dec;26(12):1538-
50. [PMID 16596122]
    7. Chen Y, et al. Mucosal tolerance to E-selectin provides cell-
mediated protection against ischemic brain injury. Proc Natl Acad Sci U 
S A. 2003 Dec 9;100(25):15107-12. [PMID 14645708]
    8. Takeda H, et al. Induction of mucosal tolerance to E-selectin 
prevents ischemic and hemorrhagic stroke in spontaneously hypertensive 
genetically stroke-prone rats. Stroke. 2002 Sep;33(9):2156-63. [PMID 
12215580]

Intellectual Property

     HHS Reference No. E-237-1999/0--
--U.S. Patent No. 7,261,896 issued 28 Aug 2007.
--U.S. Patent Application No. 11/820,326 filed 19 Jun 2007.
     HHS Reference No. E-237-1999/1--
--U.S. Patent No. 7,897,575 issued 01 Mar 2011.
--U.S. Patent Application No. 12,859,048 filed 18 Aug 2010.
     and Foreign counterparts in Australia, Canada, Europe, and 
Japan
    Licensing Contact: Tara Kirby, Ph.D.; 301-435-4426; 
[email protected].
    Collaborative Research Opportunity: The Stroke Branch, NINDS/NIH, 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate or commercialize 
the applications of E-selectin tolerization in treatment of 
neurological based disease. For collaboration opportunities, please 
contact Laurie Arrants, NINDS at [email protected].

Nucleic Acids and Methods for Expression of the Rat Fc[egr]RI beta 
Subunit, Which Plays a Critical Role in Allergy and the Immune Response

    Description of Technology: Fc[egr]RI is the high-affinity receptor 
for the Fc region of immunoglobulin E (IgE), and plays an important 
role in the allergic response and inflammation. It controls the 
production of important immunomodulatory molecules, such as cytokines 
and histamine.
    This technology describes nucleic acids encoding the beta subunit 
of rat Fc[egr]RI, as well as vectors and transgenic cells including 
such nucleic acids. Also described are methods of expressing functional 
rat Fc[egr]RI in a host cell. These may be useful in studies of allergy 
and the immune response.
    Potential Commercial Applications: Research studies of allergy and 
the immune response.

Development Stage

     Early-stage.
     In vitro data available.
    Inventors: Jean-Pierre Kinet and Henry Metzger (NIAMS).
    Intell ectual Property: HHS Reference No. E-247-1988/4--U.S. Patent 
No. 6,165,744 issued 26 Dec 2000.
    Licensing Contact: Tara L. Kirby, Ph.D.; 301-435-4426; 
[email protected].

    Dated: May 14, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-12041 Filed 5-17-12; 8:45 am]
BILLING CODE 4140-01-P