[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]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

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