[Federal Register Volume 80, Number 83 (Thursday, April 30, 2015)]
[Notices]
[Pages 24263-24265]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-10013]


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

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.

A Novel T Cell Therapy Against Patient-Specific Cancer Mutations

    Description of Technology: This invention is a novel T cell therapy 
against cancer mutations that are patient specific. Scientists at the 
National Institutes of Health have developed a method to identify T 
cells that specifically recognize immunogenic mutations expressed only 
by cancer cells. Human cancers contain genetic mutations that are 
unique to each patient. Some of the mutated peptides are immunogenic, 
can be recognized by T cells, and therefore, may serve as therapeutic 
targets. The inventors identified cancer-specific mutations from a 
patient with widely metastatic cholangiocarcinoma by sequencing tumor 
samples and comparing with normal cells. Using tandem minigene 
constructs encoding all of the mutations expressed by a patient's 
tumor, the inventors identified T cells that recognized the immunogenic 
mutations from the same patient. These mutation-reactive T cells have 
the potential to eliminate the cancer cells while sparing normal 
tissues since normal tissues do not express the mutations. The 
inventors expanded these mutation-reactive T cells in vitro, and 
infused a highly pure population of these T cells back into the same 
patient. The patient experienced tumor regression when she was treated 
with this approach.

Potential Commercial Applications

     Personalized immunotherapy with mutation-reactive T cells 
for mediating tumor regression in patients with immunogenic mutations.
     Mutation-reactive T cell therapy especially beneficial for 
cancer patients refractory to other therapies.
     A research tool to identify patient-specific immunogenic 
mutations in the tumor.

Competitive Advantages

     This patient-specific therapy has the potential 
application to most epithelial cancers, which account for about 90% of 
cancer deaths in the United States.
     Personalized mutation-specific T cells recognize mutations 
harboring tumor cells only and spare normal tissues. This therapy has 
no tissue toxicities comparing to traditional chemotherapy and 
radiotherapy.
     The infusion of a highly pure population of these 
mutation-specific T cells may maximize therapy and result in regression 
of all target lesions.

Development Stage

     Early-stage
     In vitro data available
     In vivo data available (human)
     Ex vivo data available
    Inventors: Eric Tran, Yong-Chen W. Lu, Paul F. Robbins, Steven A. 
Rosenberg (all of NCI).

Publications

    1. Tran E, et al. Cancer immunotherapy based on mutation-
specific CD4+ T cells in a patient with epithelial cancer. Science. 
2014 May 9; 344(6184):641-5. [PMID 24812403]
    2. Robbins P, et al. Mining exomic sequencing data to identify 
mutated antigens recognized by adoptively transferred tumor-reactive 
T cells. Nat Med. 2013 Jun;19(6):747-52. [PMID 23644516]
    3. Tran E, et al. T-cell therapy against cancer mutations. 
Oncotarget. 2014 Jul 15;5(13):4579-80. [PMID 25046408]

    Intellectual Property: HHS Reference No. E-229-2014/0--PCT 
Application No. PCT/US2014/058805 filed October 2, 2014.
    Related Technology: HHS Reference No. E-233-2014/0--PCT Application 
No. PCT/US2014/058796 filed October 2, 2014.
    Licensing Contact: Whitney A. Hastings, Ph.D.; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Surgery Branch, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate or commercialize T-cell therapy against cancer mutations. For 
collaboration opportunities, please contact Steven A. Rosenberg, M.D., 
Ph.D. at [email protected].

A Novel, Personalized T Cell Therapy: T-Cell Receptor Engineered T 
Cells Targeting Tumor Specific Mutations

    Description of Technology: This invention is a novel T cell therapy 
against cancer mutations that are patient specific. Scientists at the 
National Institutes of Health have developed a method to identify and 
generate T-cell receptor (TCR) engineered T cells for personalized 
cancer therapy. The TCR is a complex of integral membrane proteins that 
recognizes antigens and activates T cells. Human cancers

[[Page 24264]]

contain genetic mutations that are unique in each patient. The 
inventors found cancer-specific mutations by sequencing tumors and 
comparing with normal cells. Using tandem minigene constructs encoding 
all of the patient's tumor mutations, they first identified T cells 
that were reactive with the unique mutated antigens expressed only in 
the patient's tumors. Next, they isolated the mutation-reactive TCRs 
and engineered peripheral blood T cells from the same patient to 
express these mutation-reactive TCRs. These personalized TCR engineered 
T cells can be expanded and infused back into the same patient with the 
potential to induce tumor regression.

Potential Commercial Applications

     Personalized immunotherapy to treat primary and recurrent 
epithelial cancer.
     A research tool to identify patient-specific immunogenic 
mutations in tumors.
     A research tool to identify and isolate mutation-specific 
T cell receptors.

Competitive Advantages

     This patient-specific therapy has the potential 
application to most epithelial cancers, which account for about 90% of 
cancer deaths in the United States.
     Personalized TCR engineered T cells target tumor cells and 
spare normal tissues. This therapy has no tissue toxicities comparing 
to traditional chemotherapy and radiotherapy.
     The infusion of a highly pure population of these T cells 
expressing mutation-specific TCRs may maximize therapy and result in 
regression of all target lesions.

Development Stage

     Early-stage
     In vitro data available
     Ex vivo data available
    Inventors: Eric Tran, Yong-Chen W. Lu, Paul F. Robbins, Steven A. 
Rosenberg (all of NCI).

Publications

    1. Tran E, et al. Cancer immunotherapy based on mutation-
specific CD4+ T cells in a patient with epithelial cancer. Science. 
2014 May 9;344 (6184):641-5. [PMID 24812403].
    2. Robbins P, et al. Mining exomic sequencing data to identify 
mutated antigens recognized by adoptively transferred tumor-reactive 
T cells. Nat Med. 2013 Jun;19(6):747-52. [PMID 23644516].
    3. Tran E, et al. T-cell therapy against cancer mutations. 
Oncotarget. 2014 Jul 15;5(13):4579-80. [PMID 25046408].
    4. Gros A, et al. PD-1 identifies the patient-specific CD8+ 
tumor-reactive repertoire infiltrating human tumors. J Clin Invest. 
2014 May 1;124(5):2246-59. [PMID 24667641].

    Intellectual Property: HHS Reference No. E-233-2014/0--PCT 
Application No. PCT/US2014/058796 filed October 2, 2014.
    Related Technology: HHS Reference No. E-229-2014/0--PCT Application 
No. PCT/US2014/058805 filed October 2, 2014.
    Licensing Contact: Whitney A. Hastings, Ph.D.; 301-451-7337; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Surgery Branch, is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate or commercialize TCRs reactive with tumor associated antigens. 
For collaboration opportunities, please contact Steven A. Rosenberg, 
M.D., Ph.D. at [email protected].

Recombinant Paramyxoviruses Expressing Optimized Heterologous Antigens

    Description of Technology: The invention pertains to recombinant 
paramyxoviruses that express one or more heterologous antigens, such as 
the human respiratory syncytial virus (RSV) F protein, that have been 
optimized for increased expression and immunogenicity. The recombinant 
constructs induce a bivalent immune response to the paramyxovirus 
vectors and the heterologous antigen. Potential vectors include 
parainfluenza virus (PIV) serotype 1 and 3, Sendai virus, Newcastle 
disease virus, PIV2, and PIV5. An exemplary modified heterologous 
antigen includes the ectodomain of RSV F protein linked to the 
transmembrane and cytoplasmic domains of the F protein from the PIV 
vector, which results in efficient incorporation into the vector 
particle. The RSV F ectodomain can be engineered to be stabilized in an 
optimal conformation, such as the highly immunogenic prefusion 
conformation. Additionally, the exemplary heterologous RSV F ectodomain 
can include one or more amino acid substitutions to modify ectodomain 
expression, conformation, phenotype, or stability.

Potential Commercial Applications

     RSV vaccine
     Paramyxovirus vaccines
     Prophylactic vaccines

Competitive Advantages

     Multi-valence
     Immunogenicity

Development Stage

     Early-stage
     In vitro data available
    Inventors: Peter Collins, Bo Liang Shirin Munir, Anne Schaap-Nutt, 
Ursula Buchholz, Natalie Mackow, Peter Kwong, Barney Graham, Jason 
McLellan (all of NIAID).
    Intellectual Property: HHS Reference No. E-241-2014/0--US 
Provisional Patent Application 62/105,667 filed January 20, 2015.
    Related Technologies: HHS Reference No. E-081-2013/0-/5--US Patent 
Application 14/207,372 filed March 12, 2014; International Patent 
Application PCT/US2014/026714 filed March 13, 2014. Priority documents 
as follows:
    (1) US Provisional Application 61/780,910 filed March 13, 2013;
    (2) US Provisional Application 61/798,389 filed March 15, 2013;
    (3) US Provisional Application 61/857,613 filed July 23, 2013; and
    (4) US Provisional Application 61/863,909 filed August 9, 2013.
    Licensing Contact: Peter A. Soukas; 301-435-4646; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize this technology. For collaboration 
opportunities, please contact Jenish Patel at [email protected].

Adaptor for Suspending a Cryovial Over a Centrifuge Tube

    Description of Technology: The invention pertains to a device and 
system for expediting the thawing of frozen specimens (e.g., 
cryopreserved cells) contained in cryo-vials. An adaptor support 
suspends cryo-vials over a centrifuge tube containing culture medium in 
an inverted position. The adaptor has an elongated tubular body. While 
relatively basic, the adaptor dramatically expedites the process of 
recovering viable cells from frozen specimens. It reduces the labor 
time for thawing from several minutes to a few seconds. There is 
virtually no labor involved and enables a single person to load 
hundreds of samples within minutes. The cells, once thawed, spend 
essentially no time in liquid cryopreservative, since they are diluted 
instantly into growth medium contained in the centrifuge tubes. This 
process ensures the highest viability as well as recovery from each 
specimen while dramatically increasing throughput. Importantly, the 
elimination of multiple labor-intensive steps minimizes variation in 
viability and yield.

[[Page 24265]]

Potential Commercial Applications

     Sample preparation
     Cell culturing

Competitive Advantages

     High throughput
     Low labor
     Speed
     Reduced variability
    Development Stage: Prototype.
    Inventors: Mario Roederer, Margaret Beddall, Pratip Chattopadhyay 
(all of NIAID).
    Intellectual Property: HHS Reference No. E-080-2015/0--US Patent 
Application No. 14/661,449 filed March 18, 2015.
    Licensing Contact: Vince Contreras, Ph.D.; 301-435-4711; 
[email protected].
    Collaborative Research Opportunity: The National Institutes of 
Allergy and Infectious Diseases is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize this technology. For collaboration 
opportunities, please contact Barry Buchbinder at 
[email protected] or 240-627-3678.

    Dated: April 24, 2015.
Richard U. Rodriguez,
Acting Director, Office of Technology Transfer, National Institutes of 
Health.
[FR Doc. 2015-10013 Filed 4-29-15; 8:45 am]
 BILLING CODE 4140-01-P