[Federal Register Volume 80, Number 69 (Friday, April 10, 2015)]
[Notices]
[Pages 19329-19331]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-08290]
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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, 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. 209 and 37 CFR part 404 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.
SUPPLEMENTARY INFORMATION: Technology descriptions follow.
Novel Immunotherapy for Cancer Treatment: Chimeric Antigen Receptors
Targeting CD70 Antigen
Description of Technology: Scientists at the National Institutes of
Health have developed anti-CD70 chimeric antigen receptors (CARs) to
treat cancers. CD70 is an antigen that is expressed on a variety of
human cancers such as renal cell carcinoma, glioblastoma, non-Hodgkin's
lymphoma, and chronic lymphocytic leukemia. The anti-CD70 CARs are
hybrid proteins consisting of a receptor portion that recognizes CD70
antigen, and intracellular T cell signaling domains selected to
optimally activate the CAR expressing T cells. Genetically engineered T
cells that express this CARs will bind to CD70 on the cancer cells and
will be activated to induce an immune response that promotes robust
tumor cell elimination when infused into cancer patients. This
technology can rapidly generate a vigorous T-cell response from the
patient's own blood, targeting CD70 expressing cancer cells, and
potentially induce tumor rejection.
Potential Commercial Applications:
Immunotherapeutics to treat cancers that overexpress CD70,
such as renal cell carcinoma, glioblastoma, non-Hodgkin's lymphoma, and
chronic lymphocytic leukemia.
A personalized cancer treatment strategy for patients
whose tumor cells express CD70 whereby the patient's own T cells are
isolated, engineered to express the anti-CD70 CARs, and re-infused into
the same patient to attack the tumor(s).
Competitive Advantages:
CD70-specific CARs expressed on T cells will increase the
likelihood of successful targeted therapy.
CAR-T cells target only CD70 expressing cells and thus may
generate fewer side effects than other cancer treatment approaches.
With the advent of Provenge(R), and Yervoy(R),
immunotherapy is now more widely accepted as a viable cancer treatment
option.
T-cell transfer can provide much larger numbers of anti-
tumor immune cells compared to other approaches such as vaccines.
Development Stage:
Early-stage.
In vitro data available.
In vivo data available (animal).
Inventors: Qiong J. Wang, Zhiya Yu, James C. Yang (all of NCI).
Publication: Wang QJ, et al. Distinctive features of the
differentiated phenotype and infiltration of tumor-reactive lymphocytes
in clear cell renal cell carcinoma. Cancer Res. 2012 Dec 1;
72(23):6119-29. [PMID 23071066]
Intellectual Property: HHS Reference No. E-021-2015/0--U.S. Patent
Application No. 62/088,882 filed 08 Dec 2014.
Licensing Contact: Whitney A. Hastings, Ph.D.; 301-451-7337;
[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
[[Page 19330]]
commercialize chimeric antigen receptors targeting CD70 for cancer
treatment. For collaboration opportunities, please contact Steven A.
Rosenberg, M.D., Ph.D. at [email protected].
Novel Cancer Immunotherapy: HLA-A11 Restricted T Cell Receptor That
Recognizes G12D Variant of Mutated KRAS
Description of Technology: Scientists at the National Institutes of
Health have developed T cell receptor (TCR) derived from mouse T cells
that recognize mutated Kirsten rat sarcoma viral oncogene homolog
(KRAS), in particular the G12D variant. Mutated KRAS, which plays an
essential driver role in oncogenesis, is expressed by a variety of
human cancers, such as pancreatic, colorectal, lung, endometrial,
ovarian, and prostate cancers; but not by normal, noncancerous cells.
KRAS is mutated in nearly a third of the most lethal human cancers and
could serve as a cancer-specific therapeutic target. Most common
mutations occurred at codon 12, as glycine can be substituted with
aspartic acid (G12D), valine (G12V), cysteine (G12C), and arginine
(G12R), and among these codon 12 substitutions, G12D is the most
frequent variant. The TCR is a protein that specifically recognizes the
most frequent mutated KRAS G12D variant in the context of major
histocompatibility complex (MHC) class I molecule HLA-A11 and activates
T-cells. In HLA-A11+ patients, such genetically engineered T cells with
TCRs against mutated KRAS are expected to target and kill cancer cells
with this mutation while sparing normal tissues after infusion into
patients.
Potential Commercial Applications:
Immunotherapeutics to treat a variety of human cancers
that harbor KRAS mutations, in particular, G12D mutation, such as
pancreatic, -colorectal, lung, endometrial, ovarian, and prostate
cancers.
T cells expressing mutated KRAS G12D specific TCR may
successfully treat or prevent the recurrence of mutated KRAS-positive
cancers that do not respond to other types of treatment such as
surgery, chemotherapy, and radiation.
Competitive Advantages:
Genetically engineered T cells with TCRs for HLA-A11-
restricted mutated KRAS will increase the likelihood of successful
targeted therapy.
The targeted therapy minimizes side effect. T cells
expressing anti-mutated KRAS TCRs target tumor cells expressing mutated
KRAS and spare normal tissue. This therapy may have lower tissue
toxicities comparing to traditional chemotherapy and radiotherapy.
With the advent of Provenge(R) and Yervoy(R),
immunotherapy is now more widely accepted as a viable cancer treatment
option.
Development Stage:
Early-stage.
In vitro data available.
Ex vivo data available.
Inventors: Qiong J. Wang and James C. Yang (NCI).
Intellectual Property: HHS Reference No. E-028-2015/0--US
Provisional Patent Application No. 62/084,654 filed 26 Nov 2014.
Related Technologies:
HHS Reference No. E-106-2006/3.
HHS Reference No. E-226-2014/0.
Licensing Contact: Whitney A. Hastings, Ph.D.; 301-451-7337;
[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
anti-mutated KRAS TCRs for cancer treatment. For collaboration
opportunities, please contact Steven A. Rosenberg, M.D., Ph.D. at
[email protected].
Live Attenuated Japanese Encephalitis Virus Vaccine
Description of Technology: Japanese encephalitis virus (JEV), a
member of the genus flavivirus, is maintained in a zoonotic cycle
between Culex mosquitoes and ardeid birds or domestic swine and is
responsible for significant epidemics of viral encephalitis in Asia.
Three billion people live in regions with endemic JEV transmission
resulting in an estimated 60,000 annual cases, of which 20-40% are
fatal and 45-70% of survivors have neurologic sequelae. The live-
attenuated JEV SA14-14-2 vaccine, produced in primary hamster kidney
cells, is safe and effective. Past attempts to adapt this virus to
replicate in cells that are more favorable for vaccine production
resulted in mutations that significantly reduced immunogenicity. The
inventors have isolated 10 genetically distinct Vero cell-adapted JEV
SA14-14-2 variants and a recombinant wild-type JEV clone, modified to
contain the JEV SA14-14-2 polyprotein amino acid sequence, was
recovered in Vero cells. Mutations were also identified that modulated
virus sensitivity to type I interferon-stimulation in Vero cells. A
subset of JEV SA14-14-2 variants and the recombinant clone were
evaluated in vivo and exhibited levels of attenuation that varied
significantly in suckling mice, but were avirulent and highly
immunogenic in weanling mice and are promising candidates for the
development of a second generation, recombinant vaccine.
Potential Commercial Applications:
JEV Vaccine.
JEV Diagnostics.
Competitive Advantages:
Safe and efficacious vaccine.
Extremely low production costs.
Positive preclinical data.
Vero cell manufacture.
Development Stage:
In vitro data available.
In vivo data available (animal).
Inventors: Stephen S. Whitehead and Gregory D. Gromowski (NIAID).
Publications:
1. Gromowski G, et al. Genetic and phenotypic properties of vero
cell-adapted Japanese encephalitis virus SA14-14-2 vaccine strain
variants and a recombinant clone, which demonstrates attenuation and
immunogenicity in mice. Am J Trop Med Hyg. 2015 Jan; 92(1)98-107. [PMID
25311701].
2. Gromowski G, et al. Genetic determinants of Japanese
encephalitis virus vaccine strain SA14-14-2 that govern attenuation of
virulence in mice. J Virol. 2015, in press.
Intellectual Property: HHS Reference No. E-231-2014/0--Research
Material. Patent protection is not being pursued for this technology.
Licensing Contact: Peter Soukas; 301-435-4646; [email protected].
IFN Gamma for Reducing Adverse Ocular Side Effects of MEK-Inhibitor
Therapy in Cancer
Description of Technology: Use of IFN-gamma for treating an adverse
side effect in a cancer patient being treated by a MEK-inhibitor (MEKi)
is disclosed. MAP kinase/ERK kinase (MEK), an oncogene or signal
protein within the P38 mitogen activated protein kinase (MAPK) pathway,
is a crucial point of convergence that integrates a variety of protein
kinases through Ras. MEKis are currently being tested in monotherapies
and combination therapies against a wide variety of cancers. A number
of side effects are noticed with treatment of cancer with MEKis,
including visual disturbances. The inventors have discovered that MEKis
decreases fluid transport from the retina and/or subretinal space of
the retinal pigment epithelium (RPE) resulting in the abnormal
accumulation of fluid in the retina and subretinal space, which causes
retinal detachment and vision loss. Their results also indicate that
apical addition of MEKis alters transepithelial resistance in RPE. For
the first time, the inventors showed that these effects of MEKis are
almost
[[Page 19331]]
completely rescued by basolateral addition of IFN-gamma. These results
suggest that IFN-gamma can be used to reduce adverse events (retinal
edema) associated with the therapeutic use of MEKis.
Potential Commercial Applications: Treatment for or prevention of
adverse side effects in cancer patients undergoing MEK inhibitor
therapy.
Competitive Advantages: A simple and unique mode of reducing or
eliminating ocular side effects in cancer patients undergoing
treatments with MEK inhibitors.
Development Stage:
Early-stage.
In vitro data available.
Inventors: Sheldon S. Miller (NEI), Arvydas Maminishkis (NEI),
Charlotte E. Rem[eacute] (Merck KGaA).
Intellectual Property: HHS Reference No. E-248-2012/0--
US Provisional Application No. 61/721,810 filed 02 Nov
2012.
PCT Patent Application No. PCT/US2013/068056 filed 01 Nov
2013.
Related Technologies: HHS Reference No. E-169-2008/0--
US Patent No. 8,697,046 issued 15 Apr 2014 (Methods of
Administering Interferon Gamma to Absorb Fluid From the Subretinal
Space; Li R, et al.).
US Patent Application No. 14/252,489 filed 14 Apr 2014.
Licensing Contact: Suryanarayana Vepa, Ph.D., J.D.; 301-435-5020;
[email protected].
Lubiprostone To Treat Retinal Diseases Associated With Fluid
Accumulation in Retina & Subretinal Space
Description of Technology: Use of Lubiprostone for treating age-
related macular degeneration, chronic macular edema, diabetic
retinopathy, retinal detachment, glaucoma, or uveitis by decreasing
excess fluid accumulation in the retina and/or subretinal space (SRS)
is described. The retinal pigment epithelium (RPE) is a highly
pigmented, terminally differentiated monolayer of cells at the back of
the eye. The RPE performs numerous processes that are critical for the
maintenance of photoreceptor cell health and function. The pathological
accumulation of fluid beneath the RPE is a symptom and a contributing
factor in the loss of vision in a variety of ocular conditions.
Previously, the inventors have shown that human RPE contains apical and
basolateral membrane receptors that can be activated to increase cell
cAMP or Ca followed by basolateral membrane activation of CFTR or Ca-
activated chloride channels resulting in a clinically significant
increase in fluid absorption across the RPE. For the first time, using
human RPE in vitro, the inventors demonstrated that lubiprostone can
increase fluid transport from the retinal to the choroidal side of the
RPE by activating CLC-2 at the RPE basolateral membrane. Further, they
also showed that this increase can be blocked by addition of methadone,
a specific CLC-2 channel blocker. Lubiprostone added from either the
apical or basolateral side of the epithelium. Methadone also increased
transepithelial potential (TEP) and this increase is consistent with a
lubiprostone-induced increase in basolateral membrane CLC-2 conductance
and subsequent membrane depolarization. These results suggest
lubiprostone can be a therapeutic in retinal disease to increase fluid
absorption from retina and subretinal space.
Potential Commercial Applications: Treatment for or prevention of
age-related macular degeneration, chronic macular edema, diabetic
retinopathy, retinal detachment, glaucoma, or uveitis by decreasing the
amount of fluid present in the subretinal space (SRS).
Competitive Advantages: A simple and novel therapeutic for retinal
diseases characterized by the abnormal fluid accumulation in subretinal
space.
Development Stage:
Early-stage.
In vitro data available.
Inventors: Sheldon S. Miller, Arvydas Maminishkis, Jeffrey
Adijanto, Tina M. Banzon, and Qin Wan (all of NEI).
Intellectual Property: HHS Reference No. E-283-2012/0--
U.S. Provisional Application No. 61/777,073 filed 12 Mar
2013.
PCT Patent Application No. PCT/US2014/024724 filed 12 Mar
2014.
Related Technology: HHS Reference No. E-169-2008/0--
U.S. Patent No. 8,697,046 issued 15 Apr 2014 (Methods of
Administering Interferon Gamma to Absorb Fluid From the Subretinal
Space; Li R, et al.).
U.S. Patent Application No. 14/252,489 filed 14 Apr 2014.
Licensing Contact: Suryanarayana Vepa, Ph.D., J.D.; 301-435-5020;
[email protected].
Dated: March 7, 2015.
Richard U. Rodriguez,
Acting Director, Office of Technology Transfer, National Institutes of
Health.
[FR Doc. 2015-08290 Filed 4-9-15; 8:45 am]
BILLING CODE 4140-01-P