[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.
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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