80_FR_19398 80 FR 19329 - Government-Owned Inventions; Availability for Licensing

80 FR 19329 - Government-Owned Inventions; Availability for Licensing

DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health

Federal Register Volume 80, Issue 69 (April 10, 2015)

Page Range19329-19331
FR Document2015-08290

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.

Federal Register, Volume 80 Issue 69 (Friday, April 10, 2015) 
[Federal Register Volume 80, Number 69 (Friday, April 10, 2015)]
[Notices]
[Pages 19329-19331]
From the Federal Register Online  [www.thefederalregister.org]
[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; 
hastingw@mail.nih.gov.
    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 sar@nih.gov.

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; 
hastingw@mail.nih.gov.
    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 
sar@nih.gov.

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; ps193c@nih.gov.

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; 
vepas@mail.nih.gov.

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; 
vepas@mail.nih.gov.

    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

Federal Register / Vol. 80, No. 69 / Friday, April 10, 2015 / Notices 19329 individuals associated with the grant Contact Person: Camilla E. Day, Ph.D., CARs are hybrid proteins consisting of applications, the disclosure of which Scientific Review Officer, CIDR, National a receptor portion that recognizes CD70 would constitute a clearly unwarranted Human Genome Research Institute, National antigen, and intracellular T cell Institutes of Health, 5635 Fishers Lane, Suite invasion of personal privacy. 4075, Bethesda, MD 20892, 301–402–8837, signaling domains selected to optimally Name of Committee: National Institute of camilla.day@nih.gov. activate the CAR expressing T cells. Child Health and Human Development (Catalogue of Federal Domestic Assistance Genetically engineered T cells that Special Emphasis Panel. Program Nos. 93.172, Human Genome express this CARs will bind to CD70 on Date: May 7, 2015. Research, National Institutes of Health, HHS) the cancer cells and will be activated to Time: 8:00 a.m. to 6:00 p.m. induce an immune response that Agenda: To review and evaluate grant Dated: April 6, 2015. promotes robust tumor cell elimination applications. David Clary, when infused into cancer patients. This Place: Residence Inn Bethesda, 7335 Program Analyst, technology can rapidly generate a Wisconsin Avenue, Bethesda, MD 20814. Office of Federal Advisory Committee Contact Person: Peter Zelazowski, Ph.D., vigorous T-cell response from the Policy. Scientific Review Officer, Scientific Review [FR Doc. 2015–08213 Filed 4–9–15; 8:45 am] patient’s own blood, targeting CD70 Branch, Eunice Kennedy Shriver National expressing cancer cells, and potentially BILLING CODE 4140–01–P Institute of Child Health and Human induce tumor rejection. Development, NIH 6100 Executive Potential Commercial Applications: Boulevard, Room 5B01, Bethesda, MD DEPARTMENT OF HEALTH AND • Immunotherapeutics to treat 20892–9304, (301) 435–6902, cancers that overexpress CD70, such as peter.zelazowski@nih.gov. HUMAN SERVICES renal cell carcinoma, glioblastoma, non- (Catalogue of Federal Domestic Assistance National Institutes of Health Hodgkin’s lymphoma, and chronic Program Nos. 93.864, Population Research; lymphocytic leukemia. 93.865, Research for Mothers and Children; Government-Owned Inventions; • A personalized cancer treatment 93.929, Center for Medical Rehabilitation Availability for Licensing strategy for patients whose tumor cells Research; 93.209, Contraception and express CD70 whereby the patient’s own Infertility Loan Repayment Program, National AGENCY: National Institutes of Health, Institutes of Health, HHS) T cells are isolated, engineered to HHS. express the anti-CD70 CARs, and re- Dated: April 7, 2015. ACTION: Notice. infused into the same patient to attack David Clary, the tumor(s). SUMMARY: The inventions listed below Program Analyst, Office of Federal Advisory Competitive Advantages: are owned by an agency of the U.S. Committee Policy. Government and are available for • CD70-specific CARs expressed on T [FR Doc. 2015–08294 Filed 4–9–15; 8:45 am] licensing in the U.S. in accordance with cells will increase the likelihood of BILLING CODE 4140–01–P 35 U.S.C. 209 and 37 CFR part 404 to successful targeted therapy. • CAR–T cells target only CD70 achieve expeditious commercialization expressing cells and thus may generate of results of federally-funded research DEPARTMENT OF HEALTH AND fewer side effects than other cancer and development. Foreign patent HUMAN SERVICES treatment approaches. applications are filed on selected • With the advent of Provenge(R), and National Institutes of Health inventions to extend market coverage Yervoy(R), immunotherapy is now more for companies and may also be available widely accepted as a viable cancer National Human Genome Research for licensing. treatment option. Institute; Notice of Closed Meeting FOR FURTHER INFORMATION CONTACT: • T-cell transfer can provide much Licensing information and copies of the larger numbers of anti-tumor immune Pursuant to section 10(d) of the U.S. patent applications listed below cells compared to other approaches Federal Advisory Committee Act, as may be obtained by writing to the such as vaccines. amended (5 U.S.C. App.), notice is indicated licensing contact at the Office Development Stage: hereby given of the following meeting. The meeting will be closed to the of Technology Transfer, National • Early-stage. public in accordance with the Institutes of Health, 6011 Executive • In vitro data available. provisions set forth in sections Boulevard, Suite 325, Rockville, • In vivo data available (animal). Maryland 20852–3804; telephone: 301– Inventors: Qiong J. Wang, Zhiya Yu, 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 496–7057; fax: 301–402–0220. A signed James C. Yang (all of NCI). as amended. The grant applications and Confidential Disclosure Agreement will Publication: Wang QJ, et al. the discussions could disclose be required to receive copies of the Distinctive features of the differentiated confidential trade secrets or commercial patent applications. phenotype and infiltration of tumor- property such as patentable material, SUPPLEMENTARY INFORMATION: reactive lymphocytes in clear cell renal and personal information concerning Technology descriptions follow. cell carcinoma. Cancer Res. 2012 Dec 1; individuals associated with the grant 72(23):6119–29. [PMID 23071066] applications, the disclosure of which Novel Immunotherapy for Cancer Intellectual Property: HHS Reference would constitute a clearly unwarranted Treatment: Chimeric Antigen Receptors No. E–021–2015/0—U.S. Patent invasion of personal privacy. Targeting CD70 Antigen Application No. 62/088,882 filed 08 Dec Name of Committee: Date: Center for Description of Technology: Scientists 2014. Inherited Disease Research Access mstockstill on DSK4VPTVN1PROD with NOTICES at the National Institutes of Health have Licensing Contact: Whitney A. Committee. developed anti-CD70 chimeric antigen Hastings, Ph.D.; 301–451–7337; Date: April 23, 2015. receptors (CARs) to treat cancers. CD70 hastingw@mail.nih.gov. Time: 11:30 a.m. to 3:00 p.m. Agenda: To review and evaluate grant is an antigen that is expressed on a Collaborative Research Opportunity: applications. variety of human cancers such as renal The National Cancer Institute is seeking Place: National Institutes of Health, 5635 cell carcinoma, glioblastoma, non- statements of capability or interest from Fishers Lane, Bethesda, MD 20892, Hodgkin’s lymphoma, and chronic parties interested in collaborative (Telephone Conference Call). lymphocytic leukemia. The anti-CD70 research to further develop, evaluate or VerDate Sep<11>2014 20:09 Apr 09, 2015 Jkt 235001 PO 00000 Frm 00054 Fmt 4703 Sfmt 4703 E:\FR\FM\10APN1.SGM 10APN1

19330 Federal Register / Vol. 80, No. 69 / Friday, April 10, 2015 / Notices commercialize chimeric antigen traditional chemotherapy and and are promising candidates for the receptors targeting CD70 for cancer radiotherapy. development of a second generation, treatment. For collaboration • With the advent of Provenge(R) and recombinant vaccine. opportunities, please contact Steven A. Yervoy(R), immunotherapy is now more Potential Commercial Applications: Rosenberg, M.D., Ph.D. at sar@nih.gov. widely accepted as a viable cancer • JEV Vaccine. treatment option. • JEV Diagnostics. Novel Cancer Immunotherapy: HLA– Development Stage: Competitive Advantages: A11 Restricted T Cell Receptor That • Early-stage. • Safe and efficacious vaccine. Recognizes G12D Variant of Mutated • In vitro data available. • Extremely low production costs. KRAS • Ex vivo data available. • Positive preclinical data. Description of Technology: Scientists Inventors: Qiong J. Wang and James C. • Vero cell manufacture. at the National Institutes of Health have Yang (NCI). Development Stage: developed T cell receptor (TCR) derived Intellectual Property: HHS Reference • In vitro data available. from mouse T cells that recognize No. E–028–2015/0—US Provisional • In vivo data available (animal). mutated Kirsten rat sarcoma viral Patent Application No. 62/084,654 filed Inventors: Stephen S. Whitehead and oncogene homolog (KRAS), in particular 26 Nov 2014. Gregory D. Gromowski (NIAID). the G12D variant. Mutated KRAS, which Related Technologies: Publications: plays an essential driver role in • HHS Reference No. E–106–2006/3. 1. Gromowski G, et al. Genetic and oncogenesis, is expressed by a variety of • HHS Reference No. E–226–2014/0. phenotypic properties of vero cell- human cancers, such as pancreatic, Licensing Contact: Whitney A. adapted Japanese encephalitis virus colorectal, lung, endometrial, ovarian, Hastings, Ph.D.; 301–451–7337; SA14–14–2 vaccine strain variants and and prostate cancers; but not by normal, hastingw@mail.nih.gov. a recombinant clone, which noncancerous cells. KRAS is mutated in Collaborative Research Opportunity: demonstrates attenuation and nearly a third of the most lethal human The National Cancer Institute is seeking immunogenicity in mice. Am J Trop cancers and could serve as a cancer- statements of capability or interest from Med Hyg. 2015 Jan; 92(1)98–107. [PMID specific therapeutic target. Most parties interested in collaborative 25311701]. common mutations occurred at codon research to further develop, evaluate or 2. Gromowski G, et al. Genetic 12, as glycine can be substituted with commercialize anti-mutated KRAS TCRs determinants of Japanese encephalitis aspartic acid (G12D), valine (G12V), for cancer treatment. For collaboration virus vaccine strain SA14–14–2 that cysteine (G12C), and arginine (G12R), opportunities, please contact Steven A. govern attenuation of virulence in mice. and among these codon 12 Rosenberg, M.D., Ph.D. at sar@nih.gov. J Virol. 2015, in press. substitutions, G12D is the most frequent Intellectual Property: HHS Reference Live Attenuated Japanese Encephalitis variant. The TCR is a protein that No. E–231–2014/0—Research Material. Virus Vaccine specifically recognizes the most Patent protection is not being pursued Description of Technology: Japanese for this technology. frequent mutated KRAS G12D variant in encephalitis virus (JEV), a member of Licensing Contact: Peter Soukas; 301– the context of major histocompatibility the genus flavivirus, is maintained in a 435–4646; ps193c@nih.gov. complex (MHC) class I molecule HLA– zoonotic cycle between Culex A11 and activates T-cells. In HLA–A11+ IFN Gamma for Reducing Adverse mosquitoes and ardeid birds or patients, such genetically engineered T Ocular Side Effects of MEK-Inhibitor domestic swine and is responsible for cells with TCRs against mutated KRAS Therapy in Cancer significant epidemics of viral are expected to target and kill cancer encephalitis in Asia. Three billion Description of Technology: Use of cells with this mutation while sparing people live in regions with endemic JEV IFN-gamma for treating an adverse side normal tissues after infusion into transmission resulting in an estimated effect in a cancer patient being treated patients. Potential Commercial Applications: 60,000 annual cases, of which 20–40% by a MEK-inhibitor (MEKi) is disclosed. • Immunotherapeutics to treat a are fatal and 45–70% of survivors have MAP kinase/ERK kinase (MEK), an variety of human cancers that harbor neurologic sequelae. The live-attenuated oncogene or signal protein within the KRAS mutations, in particular, G12D JEV SA14–14–2 vaccine, produced in P38 mitogen activated protein kinase mutation, such as pancreatic, primary hamster kidney cells, is safe (MAPK) pathway, is a crucial point of -colorectal, lung, endometrial, ovarian, and effective. Past attempts to adapt this convergence that integrates a variety of and prostate cancers. virus to replicate in cells that are more protein kinases through Ras. MEKis are • T cells expressing mutated KRAS favorable for vaccine production currently being tested in monotherapies G12D specific TCR may successfully resulted in mutations that significantly and combination therapies against a treat or prevent the recurrence of reduced immunogenicity. The inventors wide variety of cancers. A number of mutated KRAS-positive cancers that do have isolated 10 genetically distinct side effects are noticed with treatment not respond to other types of treatment Vero cell-adapted JEV SA14–14–2 of cancer with MEKis, including visual such as surgery, chemotherapy, and variants and a recombinant wild-type disturbances. The inventors have radiation. JEV clone, modified to contain the JEV discovered that MEKis decreases fluid Competitive Advantages: SA14–14–2 polyprotein amino acid transport from the retina and/or • Genetically engineered T cells with sequence, was recovered in Vero cells. subretinal space of the retinal pigment TCRs for HLA–A11-restricted mutated Mutations were also identified that epithelium (RPE) resulting in the mstockstill on DSK4VPTVN1PROD with NOTICES KRAS will increase the likelihood of modulated virus sensitivity to type I abnormal accumulation of fluid in the successful targeted therapy. interferon-stimulation in Vero cells. A retina and subretinal space, which • The targeted therapy minimizes subset of JEV SA14–14–2 variants and causes retinal detachment and vision side effect. T cells expressing anti- the recombinant clone were evaluated loss. Their results also indicate that mutated KRAS TCRs target tumor cells in vivo and exhibited levels of apical addition of MEKis alters expressing mutated KRAS and spare attenuation that varied significantly in transepithelial resistance in RPE. For normal tissue. This therapy may have suckling mice, but were avirulent and the first time, the inventors showed that lower tissue toxicities comparing to highly immunogenic in weanling mice these effects of MEKis are almost VerDate Sep<11>2014 20:09 Apr 09, 2015 Jkt 235001 PO 00000 Frm 00055 Fmt 4703 Sfmt 4703 E:\FR\FM\10APN1.SGM 10APN1

Federal Register / Vol. 80, No. 69 / Friday, April 10, 2015 / Notices 19331 completely rescued by basolateral time, using human RPE in vitro, the DEPARTMENT OF HEALTH AND addition of IFN-gamma. These results inventors demonstrated that HUMAN SERVICES suggest that IFN-gamma can be used to lubiprostone can increase fluid reduce adverse events (retinal edema) transport from the retinal to the Substance Abuse and Mental Health associated with the therapeutic use of choroidal side of the RPE by activating Services Administration MEKis. CLC–2 at the RPE basolateral membrane. Potential Commercial Applications: Further, they also showed that this Agency Information Collection Treatment for or prevention of adverse Activities: Proposed Collection; increase can be blocked by addition of side effects in cancer patients Comment Request methadone, a specific CLC–2 channel undergoing MEK inhibitor therapy. blocker. Lubiprostone added from either Competitive Advantages: A simple In compliance with Section the apical or basolateral side of the 3506(c)(2)(A) of the Paperwork and unique mode of reducing or epithelium. Methadone also increased eliminating ocular side effects in cancer Reduction Act of 1995 concerning transepithelial potential (TEP) and this opportunity for public comment on patients undergoing treatments with increase is consistent with a proposed collections of information, the MEK inhibitors. Development Stage: lubiprostone-induced increase in Substance Abuse and Mental Health • Early-stage. basolateral membrane CLC–2 Services Administration (SAMHSA) • In vitro data available. conductance and subsequent membrane will publish periodic summaries of Inventors: Sheldon S. Miller (NEI), depolarization. These results suggest proposed projects. To request more Arvydas Maminishkis (NEI), Charlotte lubiprostone can be a therapeutic in information on the proposed projects or E. Remé (Merck KGaA). retinal disease to increase fluid to obtain a copy of the information Intellectual Property: HHS Reference absorption from retina and subretinal collection plans, call the SAMHSA No. E–248–2012/0— space. Reports Clearance Officer on (240) 276– • US Provisional Application No. 61/ Potential Commercial Applications: 1243. 721,810 filed 02 Nov 2012. Treatment for or prevention of age- Comments are invited on: (a) Whether • PCT Patent Application No. PCT/ related macular degeneration, chronic the proposed collections of information US2013/068056 filed 01 Nov 2013. are necessary for the proper macular edema, diabetic retinopathy, Related Technologies: HHS Reference retinal detachment, glaucoma, or uveitis performance of the functions of the No. E–169–2008/0— by decreasing the amount of fluid agency, including whether the • US Patent No. 8,697,046 issued 15 present in the subretinal space (SRS). information shall have practical utility; Apr 2014 (Methods of Administering (b) the accuracy of the agency’s estimate Interferon Gamma to Absorb Fluid From Competitive Advantages: A simple of the burden of the proposed collection the Subretinal Space; Li R, et al.). and novel therapeutic for retinal • US Patent Application No. 14/ of information; (c) ways to enhance the diseases characterized by the abnormal 252,489 filed 14 Apr 2014. quality, utility, and clarity of the fluid accumulation in subretinal space. Licensing Contact: Suryanarayana information to be collected; and (d) Development Stage: ways to minimize the burden of the Vepa, Ph.D., J.D.; 301–435–5020; vepas@mail.nih.gov. • Early-stage. collection of information on respondents, including through the use Lubiprostone To Treat Retinal Diseases • In vitro data available. of automated collection techniques or Associated With Fluid Accumulation in Inventors: Sheldon S. Miller, Arvydas other forms of information technology. Retina & Subretinal Space Maminishkis, Jeffrey Adijanto, Tina M. Banzon, and Qin Wan (all of NEI). Proposed Project: Family Treatment Description of Technology: Use of Drug Court Services Evaluation (OMB Lubiprostone for treating age-related Intellectual Property: HHS Reference No. 0930–0330)—REINSTATEMENT macular degeneration, chronic macular No. E–283–2012/0— edema, diabetic retinopathy, retinal • U.S. Provisional Application No. In 2010, the Substance Abuse and detachment, glaucoma, or uveitis by 61/777,073 filed 12 Mar 2013. Mental Health Services Administration decreasing excess fluid accumulation in (SAMHSA), Center for Substance Abuse the retina and/or subretinal space (SRS) • PCT Patent Application No. PCT/ Treatment (CSAT), provided funding to is described. The retinal pigment US2014/024724 filed 12 Mar 2014. 12 existing Family Treatment Drug epithelium (RPE) is a highly pigmented, Related Technology: HHS Reference Courts (FTDCs) for enhancement and/or terminally differentiated monolayer of No. E–169–2008/0— expansion of their FTDC’s capabilities cells at the back of the eye. The RPE • U.S. Patent No. 8,697,046 issued 15 to provide psycho-social, emotional and performs numerous processes that are Apr 2014 (Methods of Administering mental health services to children (0–17 critical for the maintenance of Interferon Gamma to Absorb Fluid From years) and their families who have photoreceptor cell health and function. the Subretinal Space; Li R, et al.). methamphetamine use disorders and The pathological accumulation of fluid involvement in child protective beneath the RPE is a symptom and a • U.S. Patent Application No. 14/ services. This program was authorized contributing factor in the loss of vision 252,489 filed 14 Apr 2014. in House Report 111–220 accompanying in a variety of ocular conditions. Licensing Contact: Suryanarayana HR 3293 in 2010. The Committee Previously, the inventors have shown Vepa, Ph.D., J.D.; 301–435–5020; language stated that ‘‘these grants will mstockstill on DSK4VPTVN1PROD with NOTICES that human RPE contains apical and vepas@mail.nih.gov. support a collaborative approach, basolateral membrane receptors that can Dated: March 7, 2015. including treatment providers, child be activated to increase cell cAMP or Ca welfare specialists, and judges, to followed by basolateral membrane Richard U. Rodriguez, provide community-based social activation of CFTR or Ca-activated Acting Director, Office of Technology services for the children of chloride channels resulting in a Transfer, National Institutes of Health. methamphetamine-addicted parents,’’ clinically significant increase in fluid [FR Doc. 2015–08290 Filed 4–9–15; 8:45 am] and were to be awarded to Family absorption across the RPE. For the first BILLING CODE 4140–01–P Dependency Treatment Drug Courts. VerDate Sep<11>2014 20:09 Apr 09, 2015 Jkt 235001 PO 00000 Frm 00056 Fmt 4703 Sfmt 4703 E:\FR\FM\10APN1.SGM 10APN1


Document Created: 2018-02-21 10:08:26
Document Modified: 2018-02-21 10:08:26
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionNotices
ActionNotice.
ContactLicensing 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.
FR Citation80 FR 19329 
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