[Federal Register Volume 77, Number 130 (Friday, July 6, 2012)]
[Notices]
[Pages 40073-40076]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-16500]


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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.

Exposing T Cells to Fas Ligand (FasL)-Fas Receptor (FasR) Antagonists 
Withholds Differentiation and Increases Expansion Making T Cells More 
Suitable for Use in Cancer Immunotherapy

    Description of Technology: NIH scientists have developed methods to 
make a better immunotherapy by exposing T cells to Fas ligand (FasL) or 
Fas receptor (FasR) antagonists and agonists. Researchers have found 
that FasL-FasR antagonists suppress T cell differentiation leaving them 
in a na[iuml]ve state. These T cells are a more ideal cell type for 
adoptive cell transfer therapies since they have not exhausted their 
effector functions and demonstrate greater proliferation, enhanced 
persistence and survival, and better activity against their target 
antigen when infused in vivo to treat cancer. Also, the prevention of T 
cell differentiation/effector function in vivo

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has implications for autoimmune diseases and syndromes. FasL-FasR 
agonists enhance T cell differentiation towards more effector-like 
cells. Enhancing the differentiation of T cells is expected to be 
useful in treating cell proliferation disorders, such as leukemias, 
lymphomas, or Wiskott-Aldrich syndrome.
    FasL (or cluster of differentiation 95L) is a transmembrane protein 
in the tumor necrosis factor (TNF) family. FasR (or apoptosis antigen 
1, CD95, or TNF receptor superfamily member 6) is a transmembrane 
protein belonging to the TNF receptor/nerve growth factor receptor 
superfamily. Normally, when FasL binds to FasR, a cell death signal is 
triggered in the cell. Antagonists of FasL-FasR interaction may include 
caspase inhibitors, mutated FasL/FasR, RNAi, or FasL/FasR antibodies. 
Agonists may include FasL/FasR encoding nucleotides.

Potential Commercial Applications

     Immunotherapy for cancer and other diseases or disorders 
using FasL/FasR antagonist exposed T cells.
     Methods for generating better T cells to utilize for 
infusion into patients in adoptive cell transfer therapies.
     Therapeutic to prevent T cell mediated toxicity in vivo 
(i.e. autoimmunity like lupus, Crohn's disease, MS, vitiligo, etc.).
     Components of a combination therapy to increase or 
suppress T cell differentiation and activity in patients.

Competitive Advantages

     Some patients do not respond to T cell immunotherapy due 
to lack of cell persistence, survival, or activity or other reasons. 
Administering a FasL/FasR antagonist to a patient's T cells before 
immunotherapy should increase the success rate of treatment by 
increasing the persistence and survival of the infused cells.
     Differentiation and effector function of T cells can be 
suppressed by an antibody (molecular product) rather than a drug 
(chemical product) like rapamycin.

Development Stage

     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Anthony J. Leonardi, Christopher A. Klebanoff, Luca 
Gattinoni, Nicholas P. Restifo (all of NCI).
    Intellectual Property: HHS Reference No. E-142-2012/0--U.S. 
Provisional Application No. 61/623,733 filed 13 Apr 2012.
    Related Technology: HHS Reference No. E-069-2010/0--PCT Application 
No. PCT/US2011/63375 filed 08 Dec 2010.
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[email protected].
    Collaborative Research Opportunity: The Surgery Branch of the NCI 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize the prevention of T cell differentiation and effector 
function as part of Immunotherapy. For collaboration opportunities, 
please contact Steven A. Rosenberg, M.D., Ph.D. at [email protected].

Benign Tissue or Malignant Tumors? Using CpG Dinucleotide Methylation 
Patterns To Diagnose Cancer in the Adrenal Glands and Adrenal Cortex

    Description of Technology: Scientists at the National Institutes of 
Health (NIH) have developed new methods to distinguish malignant 
adrenocortical tumors from benign tumors and normal tissue in the 
adrenal glands/cortex using the methylation patterns of cytosine-
phosphate-guanine dinucleotide (CpG) sequences. A biopsy or other 
noninvasive means of tissue or fluid collection to obtain patient 
nucleic acid can allow clinicians to test an individual's CpG 
methylation patterns to diagnose if the individual's sample is 
malignant and if a malignancy is a primary or metastatic adrenocortical 
tumor. Different CpG methylation patterns comparing normal/benign and 
malignant tissues may also serve as target sites for developing 
adrenocortical cancer therapies. Genes where increased CpG methylation 
is predictive of malignancy include KCTD12, KIRREL, SYNGR1, and NTGN2, 
as well as other secondary sequences.
    Adrenal glands sit atop the kidneys and release stress response 
hormones. The CpG methylation patterns of 5-methylcytosines at CpG 
sites can alter gene expression, which can impact if a tumor will 
develop benign or malignant properties and influence its metastatic 
potential. Effective diagnosis of these tumors will improve adrenal 
cancer therapy and help avoid unnecessary surgery or chemotherapy for 
patients with benign tumors.

Potential Commercial Applications

     Nucleic acid-based diagnostic tests or kits to identify 
malignant adrenocortical tumors and distinguish them from common benign 
tumors or normal adrenocortical tissue.
     Identify CpG methylation sequences and patterns that could 
serve as targets for nonsurgical therapeutic interventions against 
adrenocortical tumors.
     Companion diagnostic test for candidate demethylation 
agent therapies for treating adrenocortical malignancies.

Competitive Advantages

     Removal of adrenal malignancies is currently the only 
cure, but most patients are not candidates for surgery. Benign adrenal 
tumors are common, but treated by clinicians as a precaution, mainly 
with harsh chemotherapy. Now, malignant adrenocortical tumors can be 
differentiated from benign tumors, so that individuals with benign 
tumors are not treated unnecessarily.
     A minimally invasive biopsy or tissue collection to 
measure DNA methylation could avoid unnecessary invasive surgery/harsh 
chemotherapy and lead to more assured treatment of malignant tumors.

Development Stage

     Pre-clinical.
     In vitro data available.
    Inventors: Electron Kebebew, Nesrin S. Rechache, Paul S. Meltzer, 
Yonghong Wang (all of NCI).
    Publication: Rechache N, et al. DNA methylation profiling 
identifies global methylation differences and markers of adrenocortical 
tumors. J Clin Endocrinol Metab. 2012 Jun;97(6):E1004-13. [PMID 
22472567]
    Intellectual Property: HHS Reference No. E-135-2012/0--U.S. 
Provisional Application No. 61/615,869 filed 26 Mar 2012.
    Related Technology: HHS Reference No. E-026-2011/0--PCT Application 
No. PCT/US2011/040648 filed 16 Jun 2011.
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[email protected].

Mouse-Derived T Cell Receptor for Use in Immunotherapy That Recognizes 
NY-ESO-1, a Cancer Testis Antigen Expressed by Many Human Cancers

    Description of Technology: Scientists at the National Institutes of 
Health have developed a T cell receptor (TCR) derived from mouse T 
cells (i.e. murine TCR) that can be expressed in human T cells to 
recognize the cancer testis antigen (CTA), NY-ESO-1, with high 
specificity. This anti-NY-ESO-1 TCR has murine variable regions that 
recognize the NY-ESO-1 epitope and murine constant regions. The 
inventors performed in vitro studies comparing this murine NY-ESO-1 TCR 
with a previously developed human NY-ESO-1 TCR counterpart, which 
yielded promising clinical outcomes in patients with a variety of 
cancers. The murine

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TCR functioned similarly to the human counterpart in their ability to 
recognize and react to NY-ESO-1 tumor targets.
    NY-ESO-1 is a CTA, which is expressed only on tumor cells and 
germline cells of the testis and placenta. CTAs are ideal targets for 
developing cancer immunotherapeutics, such as anti-CTA TCRs, since 
these TCRs are expected to target cancer cells without harming normal 
tissues and thereby minimize the harsh side effects associated with 
other types of cancer treatment. NY-ESO-1 is expressed on a wide 
variety of cancers, including but not limited to breast, lung, 
prostate, thyroid, and ovarian cancers, melanoma, and synovial 
sarcomas, so this technology should be applicable in adoptive cell 
transfer therapies for many types of cancer.

Potential Commercial Applications

     Personalized immunotherapy with high probability for 
mediating tumor regression in patients with a variety of cancers 
expressing NY-ESO-1.
     Component of a combination immunotherapy regimen 
consisting of a variety of immune receptors and other immune molecules 
(cytokines, etc.) targeting multiple tumor antigens.
     A research tool to investigate the progression and 
metastasis of NY-ESO-1 expressing cancers in mouse models.
     An in vitro diagnostic tool to identify cancer tissues 
that express the NY-ESO-1 cancer testis antigen.

Competitive Advantages

     Predicted high probability of clinical success: Murine 
TCRs from this invention exhibited similar in vitro properties to a 
human NY-ESO-1 TCR that has mediated tumor regression in many patients 
in a recent clinical trial.
     Lower toxicity than other cancer treatments: NY-ESO-1 is 
overexpressed on a wide variety of cancers, but not on any normal human 
tissues that could be reactive with an engineered TCR. TCRs engineered 
to recognize NY-ESO-1 could be utilized as an immunotherapy to treat 
many different cancer types.

Development Stage

     Pre-clinical.
     In vitro data available.
    Inventors: Maria R. Parkhurst, Richard A. Morgan, Steven A. 
Rosenberg (all of NCI).
    Intellectual Property: HHS Reference No. E-105-2012/0--U.S. 
Provisional Patent Application No. 61/650,020 filed 22 May 2012.

Related Technologies

     HHS Reference No. E-304-2006/0.
     HHS Reference No. E-312-2007/1.
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[email protected].
    Collaborative Research Opportunity: The NCI Surgery Branch is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
this murine NY-ESO-1 reactive TCR. For collaboration opportunities, 
please contact Steven A. Rosenberg, M.D., Ph.D. at [email protected].

Antagonists of Hyaluronan Signaling for Treatment of Airway 
Inflammation and Hyperresponsiveness

    Description of Technology: Airway inflammation and 
hyperresponsiveness are hallmarks of airway disease. Investigators at 
NIEHS identified a new class of compounds that can block hyaluronan 
signaling and inhibit airway hyperresponsiveness and inflammation. 
Airway diseases, such as asthma and chronic obstructive airway disease, 
affect tens of millions of patients worldwide, and are chronic diseases 
with limited options for treatment (bronchodilators and inhaled 
steroids are the two classes of drugs currently in common use). 
Therefore, a novel class of treatment agents could have significant 
public health and market impact.
    Potential Commercial Applications: Treatment of Airway Inflammation 
and Hyperresponsiveness.
    Competitive Advantages: Potentially cost-effective treatment for 
widespread conditions.
    Development Stage: In vitro data available.
    Inventors: Stavros Garantziotis (NIEHS), John W. Hollingsworth, 
Bryan P. Toole, Jian Liu.
    Intellectual Property: HHS Reference No. E-080-2012/0--U.S. 
Provisional Application No. 61/647,101 filed 15 May 2012.
    Licensing Contact: Jaime M. Greene, M.S.; 301-435-5559; 
[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 the use of 
hyaluronan antagonists to treat chronic respiratory diseases. For 
collaboration opportunities, please contact Elizabeth M. Denholm, Ph.D. 
at [email protected].

Individualized Cancer Therapy That Suppresses Tumor Progression and 
Metastasis Through Decreased Expression of TGF-Beta Receptor II in Bone 
Marrow Derived Cells

    Description of Technology: Scientists at the NIH have developed a 
method of suppressing tumor progression and metastasis by targeting a 
pathway. This novel treatment method is an individualized therapy that 
first screens patients to determine if they are a candidate for the 
treatment, and then utilizes their own altered bone marrow to inhibit 
tumor progression.
    Tumor inhibition is achieved through decreased expression of TGF-
beta receptor II (TGF[beta] r2) in bone marrow derived myeloid cells, 
which is essential in tumor metastasis. The inventors have devised a 
patient selection method whereby the patient's blood is drawn and 
screened for TGF[beta] r2 expression, and those patients with above 
normal expression are candidates for treatment. After candidate 
screening the patient's bone marrow is harvested and divided into two 
parts: One part for cell culture and the other for storage and later 
use. The patient's cell culture bone marrow is treated to remove 
TGF[beta] r2 in myeloid cells through either virus, non viral particle, 
or nanoparticle. The patient is treated with total body radiation and 
then receives an infusion of the treated cell culture bone marrow. 
After tumor metastasis is suppressed, the altered bone marrow is 
removed, and the stored bone marrow is returned to the patient.

Potential Commercial Applications

     Novel immunotherapy for cancer.
     Treatment method to suppress tumor metastasis in patients 
overexpressing TGF[beta] r2 in myeloid cells.
     TGF[beta] r2 RNAi with specific myeloid cell promoters 
delivered by virus, non viral particle, or nanoparticle.

Competitive Advantages

     Specifically targets myeloid cells and not other host 
cells.
     Individualized therapy.
     Patient selection process; treatment is specific to 
eligible patients reducing cost.

Development Stage

     In vitro data available.
     In vivo data available (animal).
    Inventor: Li Yang (NCI).
    Publication: Abrogation of transforming growth factor [beta] 
signaling in myeloid cells significantly inhibit tumor progression and 
metastasis; submitted.

[[Page 40076]]

    Intellectual Property: HHS Reference No. E-151-2011/0--U.S. Patent 
Application No. 61/525,025 filed 18 August 2011.
    Licensing Contact: Sabarni Chatterjee, Ph.D., MBA; 301-435-5587; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate or commercialize 
technologies including but not limited to RNAi viral particle or 
nanoparticle, or miRNA. For collaboration opportunities, please contact 
John Hewes, Ph.D. at [email protected].

    Dated: June 29, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-16500 Filed 7-5-12; 8:45 am]
BILLING CODE 4140-01-P