[Federal Register Volume 77, Number 117 (Monday, June 18, 2012)]
[Notices]
[Pages 36282-36284]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-14703]


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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.

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.

Endothelial Cell Line To Study Prevention of Atherosclerosis

    Description of Technology: Atherosclerosis underlies most cases of 
cardiovascular disease (CVD), which is now the major cause of morbidity 
and mortality in developed countries. An inflammatory reaction is an 
essential component in the appearance and development of an 
atherosclerotic lesion. The inflammatory process is associated with the 
expression of adhesion molecules such as vascular cell adhesion 
molecule (VCAM) at the surface of endothelial cells. Antiatherogenic 
lipoprotein, high density lipoprotein (HDL), is known to down regulate 
the expression of VCAM. Increasing levels of HDL is a promising way to 
reduce the risk of CVD.
    This technology is directed to the generation of a stable 
endothelial cell line expressing a luciferase reporter construct driven 
by the VCAM promoter. This reporter system enables an easier 
measurement of VCAM expression and determination of the effect of HDL 
on endothelial cell inflammation. This technology can be used to screen 
for the effect of drugs that modulate HDL metabolism and it is more 
convenient than doing Western blots.
    Potential Commercial Applications:
     Study of prevention of atherosclerosis
     Screen serum for the effect of HDL on endothelial cell 
inflammation
     Screen for the effect of drugs that modulate HDL 
metabolism
    Competitive Advantages:
     Easy monitoring of down regulation of VCAM with luciferase
     More convenient than doing Western blots
    Development Stage: In vitro data available.
    Inventor: Alan T. Remaley (NHLBI).
    Publication: D'Souza W, et al. Structure/function relationships of 
apolipoprotein a-I mimetic peptides: Implications for antiatherogenic 
activities of high-density lipoprotein. Circ Res. 2010 Jul 
23;107(2):217-27. [PMID 20508181].
    Intellectual Property: HHS Reference No. E-149-2012/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; 
[email protected].
    Collaborative Research Opportunity: The Cardiovascular & Pulmonary 
Branch, NHLBI/NIH, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate or commercialize endothelial cells to study prevention of 
atherosclerosis. For collaboration opportunities, please contact Dr. 
Alan Remaley at [email protected].

Software for Modeling Tumor Delivery and Penetration of Antibody-Toxin 
Anti-Cancer Conjugates

    Description of Technology: Available for licensing is software for 
modeling permeability and concentration of intravenously administered 
antibody anti-cancer agent conjugates in solid tumor. The models can be 
used to determine optimal dosing regimen of a therapeutic in a 
particular cancer type. Thirty factors that affect delivery rates and 
efficiencies are analyzed as variables in generating the models.
    Potential Commercial Applications:
     Drug Design
     Combination Therapy
     Personalized Medicine
    Competitive Advantages:
     Accurate permeability modeling of anti-cancer therapeutics
     Personalized Medicine
    Development Stage:
     Early-stage
     Pre-clinical
    Inventors: Byungkook Lee (NCI), Youngshang Pak (EM), Ira Pastan 
(NCI).
    Publications:

1. Fujimori K, et al. A modeling analysis of monoclonal antibody 
percolation through tumors: a binding-site barrier. J Nucl Med. 1990 
Jul;31(7):1191-1198. [PMID 2362198]
2. Jain RK. Delivery of molecular and cellular medicine to solid 
tumors. Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):149-168. [PMID 11259838]
3. Thurber GM, et al. Antibody tumor penetration: transport opposed by 
systemic and antigen-mediated clearance. Adv Drug Deliv Rev. 2008 
Sep;60(12):1421-1434. [PMID 18541331]
4. Li Y, et al. Delivery of nanomedicines to extracellular and 
intracellular compartments of a solid tumor. Adv Drug Deliv Rev. 2012 
Jan;64(1):29-39. [PMID 21569804]
5. http://www.accelereyes.com/examples/drug_delivery_model
6. Pak Y, et al. Antigen shedding may improve efficiencies for delivery 
of antibody-based anticancer agents in solid tumors. Can Res. 2012 May 
4; Epub ahead of print, doi: 10.1158/0008-5472.CAN-11-3925. [PMID 
22562466]

    Intellectual Property: HHS Reference No. E-060-2012/0--Software. 
Patent protection is not being pursued for this technology.
    Licensing Contact: Michael Shmilovich; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The NCI, CCR, Laboratory of 
Molecular Biology is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate or commercialize targeted delivery of anti-cancer agents in 
solid tumors. For collaboration opportunities, please contact John 
Hewes, Ph.D. at [email protected].

Mouse Model of STAT5 for the Drug Screen and the Research of Cancer and 
Autoimmunity

    Description of Technology: The invention is a STAT5 mutant mouse 
that can be used in research related to cancer, autoimmunity and 
infectious diseases as well as drug screening. The mouse model itself 
has multiple immunological defects resulting in formation of STAT5 
dimers but not tetramers.

[[Page 36283]]

    It reports that only a minority of IL-2-modulated genes is 
regulated by STAT5 tetramers. Therefore, selectively targeting tetramer 
formation might be a relatively specific therapeutic tool wherein one 
could modulate only part of the actions of a cytokine or growth factor, 
which allows a new therapeutic approach to modulating immune responses, 
controlling inflammation, and inhibiting tumor growth.
    The STAT5 tetramer deficient mouse is an ideal tool to screen for 
tetramerization inhibitors that can be used for the treatment of 
cancer, autoimmunity and inflammation in addition to the basic research 
applications.
    Potential Commercial Applications:
     To design and screen tetramerization inhibitors that are 
potential new drugs for cancer, autoimmunity and transplantation.
     To identify and study a key subset of STAT5A and/or 
STAT5B-dependent genes without affecting viability is extremely.
     To seek a new therapeutic approach to modulating immune 
responses, controlling inflammation, and inhibiting tumor growth.
    Competitive Advantages:
     The tetramer-deficient mice of this invention are viable 
while mice completely lacking expression of Stat5a and Stat5b exhibit 
perinatal lethality.
     A model for basic research, to study the cancer, 
autoimmunity, and infectious diseases associated with STAT5 signaling.
    Inventors: Warren J. Leonard and Jian-Xin Lin (NHLBI)
    Publication: Lin JX, et al. Critical role of STAT5 transcription 
factor tetramerization for cytokine responses and normal immune 
function. Immunity. 2012 Apr 20;36(4):586-99. [PMID 22520852]
    Intellectual Property: HHS Reference No. E-080-2011/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Susan Ano, Ph.D.; 301-435-5515; 
[email protected].

Fast Acting Molecular Probes for Real-Time In Vivo Study of Disease and 
Therapeutics

    Description of Technology: This technology is for fast acting 
molecular probes made from a fluorescent quencher molecule, a 
fluorophore, an enzyme cleavable oligopeptide (for example targeted by 
protease) and FDA-approved polyethylene glycol (PEG) as well as 
associated methods to identify cell activity with these probes. 
Proteases regulate many cell processes such as inflammation as well as 
pathological processes in cancer and cardiovascular disease. High 
protease activity is associated with metastatic cancers. Proteases are 
also active in apoptosis, and tissue remodeling in cardiovascular 
disease. Although highly useful in vitro, conventional probes are 
unstable, nonspecific or slow activating in vivo. This new probe is 
faster than standard probes (30 min vs. 24 hrs) and has enhanced 
target-to background ratios. It enables quick screening of animals in 
an array of applications related to protease-associated diseases and 
other diseases. It may detect specific biological targets and monitor 
in vivo therapeutic efficacy in real time. Most drug candidates 
identified by in vitro screening fail in vivo. Failures are costly. 
Identifying in vivo drug efficacy sooner would reduce waste and 
increase successful drug development.
    Potential Commercial Applications:
     Diagnostics
     In vivo therapeutic monitoring
    Competitive Advantages:
     Faster than standard probes
     Enhanced target-to-background ratios
     Allows in vivo therapeutic efficacy study in real time
    Development Stage:
     Early-stage
     Pre-clinical
     In vivo data available (animal)
    Inventors: Xiaoyuan (Shawn) Chen, Seulki Lee, Lei Zhu (all of 
NIBIB)
    Publications:

1. Lee S, et al. Polymeric nanoparticle-based activatable near-infrared 
nanosensor for protease determination in vivo. Nano Lett. 
2009;9(12):4412-6. [PMID 19842672]
2. Lee S, et al. Activatable molecular probes for cancer imaging. Curr 
Top Med Chem. 2010;10(11):1135-44. [PMID 20388112]

    Intellectual Property: HHS Reference No. E-079-2011/0--U.S. 
Provisional Application No. 61/533,014 filed 09 Sep 2011
    Licensing Contact: Tedd Fenn; 301-435-5031; [email protected].
    Collaborative Research Opportunity: The National Institute of 
Biomedical Imaging and Bioengineering is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize fast acting 
molecular probes for real-time in vivo study of disease and 
therapeutics. For collaboration opportunities, please contact Cecilia 
Pazman at [email protected].

New Ammunition to Fight Cancer: The Rapid Isolation of Central Memory T 
Cells for Adoptive Immunotherapy

    Description of Technology: This technology is a new technique to 
rapidly isolate tumor-reactive central memory T cells in a highly 
enriched, non-invasive manner from the peripheral blood of cancer 
patients for cancer adoptive cell immunotherapy. Cells are drawn from a 
patient's blood, divided into subsets, and contacted with the tumor 
antigen of interest to identify T cells whose T cell receptor (TCR) 
recognizes the tumor antigen. Such T cells are identified by measuring 
the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) 
produced by the cells (i.e., the IL-2 index) using high-throughput 
quantitative PCR (HT-qPCR). NIH scientists have identified that cells 
with a specific IL-2 index consistently contain central memory T cells 
for the tumor antigen of interest.
    Preclinical animal studies have suggested that central memory T 
cells can proliferate, persist, and survive better after adoptive 
transfer compared to other T cell types. They also show increased anti-
cancer activity. Clinical trials using central memory T cells represent 
an important extension of these studies. Adoptive immunotherapy is 
showing promise as a cancer treatment, but one drawback to this method, 
prior to this invention, was the laborious and time consuming nature of 
the cell isolation process and the unpredictable and sometimes 
ineffective nature of the cells infused into patients.
    Potential Commercial Applications:
     An improved adoptive immunotherapy approach to treat and/
or prevent the recurrence of a variety of human cancers, infectious 
diseases, and autoimmune diseases by identifying central memory T cells 
to better fight these diseases.
     A valuable component to a combination therapy to treat 
diseases where improving immune response quality is critical, such as 
introducing central memory T cells into a vaccine regimen for longer 
term immune responses or to treat malignancies that thrive by 
circumventing the patient's immune system.
    Competitive Advantages:
     Eliminate the need for invasive surgery to eliminate 
tumors.
     Isolate better cell cultures for adoptive immunotherapy 
than previously available.
     Predict and isolate central memory T cell populations 
consistently using the IL-2 index.

[[Page 36284]]

     Expands the number of patients where adoptive 
immunotherapy can become a cancer treatment option.
     Sensitive, efficient, and rapid approach to identify and 
isolate Central Memory T cells for various therapeutic applications.
    Development Stage:
     Early-stage
     Pre-clinical
     Clinical
     In vitro data available
     In vivo data available (human)
    Inventor: Udai S. Kammula (NCI)
    Publication: Kammula US, Serrano OK. Use of high throughput qPCR 
screening to rapidly clone low frequency tumour specific T-cells from 
peripheral blood for adoptive immunotherapy. J Transl Med. 2008 Oct 
20;6:60. [PMID 18937837]
    Intellectual Property: HHS Reference No. E-228-2010/0--
     U.S. Provisional Patent Application No. 61/374,699 filed 
18 Aug 2010
     PCT Patent Application No. PCT/US2011/047719 filed 15 Aug 
2011
    Related Technology: HHS Reference No. E-003-2000/0--
     U.S. Patent Application No. 12/866,919 filed 10 Aug 2010
     Foreign counterparts in Europe and Australia
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research, 
Surgery Branch, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate or commercialize this novel technology. For collaboration 
opportunities, please contact John Hewes, Ph.D. at [email protected].

A3 Adenosine Receptor Agonists To Treat Chemotherapy-Induced 
Peripheral Neuropathy

    Description of Technology: This invention claims species-
independent agonists of A3AR, specifically (N)-methanocarba 
adenine nucleosides and related pharmaceutical compositions. The 
A3 adenosine receptor (A3AR) subtype has been 
linked with helping protect the heart from ischemia, controlling 
inflammation, and regulating cell proliferation. Agonists of the human 
A3AR subtype have been developed that are also selective for 
the mouse A3AR while retaining selectivity for the human 
receptor. This solves a problem for clinical development because animal 
model testing is important for pre-clinical validation of drug 
function. Novel agonists have been made that exhibit as much as 6000x 
selectivity for A3 versus A1 in humans while 
retaining at least 400x selectivity for A3 versus 
A1 in mice. In addition, the molecules of the invention 
exhibit very low nanomolar affinity. This innovation will not only 
facilitate moving A3 agonists into the clinical phase of 
drug development by being more amenable to animal studies, but also 
provide much greater selectivity in humans, and thereby potentially 
fewer side effects than drugs currently undergoing clinical trials.
    Potential Commercial Applications:
     Cardiac arrhythmias or ischemia
     Inflammation
     Stroke
     Diabetes
     Asthma
     Cancer
     Pain
    Competitive Advantages: Oral dosing as these A3AR 
agonists are selective and not associated with cardiac or hemodynamic 
effects that may result from stimulation of A1 or 
A2A receptors.
    Development Stage:
     Early-stage
     In vivo data available (animal)
    Inventors: Kenneth Jacobson and Dilip K. Tosh (NIDDK)
    Publications:

1. Tosh DK, et al. Structure-guided design of A(3) adenosine receptor 
selective nucleosides: combination of 2-arylethynyl and 
bicyclo[3.1.0]hexane substitutions. J Med Chem. 2012 May 16; Epub ahead 
of print. [PMID 22559880]
2. Chen Z, et al. Controlling murine and rat chronic pain through A3 
adenosine receptor activation. FASEB J. 2012 May;26(5):1855-65. [PMID 
22345405]
    Intellectual Property: HHS Reference No. E-140-2008/1--US Patent 
Application No. 13/371,081 filed 10 Feb 2012
    Related Technologies:
     HHS Reference No. E-140-2008/0--US Patent Application No. 
12/935,461 filed 01 Nov 2010
     HHS Reference No. E-285-2008/0--US Patent Application No. 
13/056,997 filed 18 Mar 2011
     HHS Reference No. E-075-2012/0
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Diabetes and Digestive and Kidney Diseases 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 Marguerite J. Miller at 
301-496-9003 or [email protected].

Use of CD97 Alpha Subunit Antibodies for Treatment of Angiogenesis, 
Atherosclerosis, and Inflammation

    Description of Technology: CD97 is a T-cell glycoprotein that is 
upregulated in activated T-cells and is involved in the onset and 
maintenance of inflammation and angiogenesis. It is a seven-span 
transmembrane heterodimer consisting of one variant alpha subunit, 
which is soluble, and one invariant beta subunit, which is membrane-
bound. Upon activation of T-cells, expression of the alpha subunit is 
dramatically upregulated and it is shed into the extracellular medium. 
The inventors have demonstrated in in vitro and in vivo studies that 
CD97 plays an important role in angiogenesis, inflammation, and 
atherosclerosis.
    This technology describes isolated soluble CD97 alpha subunit 
proteins, selected from three alternatively spliced isoforms, as well 
as antibodies that bind to these subunits. The technology also 
describes methods of inhibiting angiogenesis, CD97-associated chronic 
inflammation, and atherosclerosis in mammals.
    Potential Commercial Applications: This technology may be useful 
for the treatment of angiogenesis-related diseases, as well as 
inflammation and atherosclerosis. It can also be utilized in studies of 
inflammation and angiogenesis.
    Competitive Advantages: CD97 represents a novel target for 
treatment of angiogenesis- and inflammation-mediated diseases.
    Development Stage:
     Early-stage
     In vitro data available
     In vivo data available (animal)
    Inventor: Kathleen Kelly (NCI)
    Publication: Gray J, et al. CD97 is a processed, seven-
transmembrane, heterodimeric receptor associated with inflammation. J 
Immunol.1996 Dec 15;157(12):5438-47. [PMID 8955192]
    Intellectual Property: HHS Reference No. E-009-1996/0--
     US Patent No. 6,365,712 issued 02 Apr 2002
     US Patent No. 6,846,911 issued 25 Jan 2005
    Licensing Contact: Tara L. Kirby, Ph.D.; 301-435-4426; 
[email protected].

     Dated: June 12, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-14703 Filed 6-15-12; 8:45 am]
BILLING CODE 4140-01-P