[Federal Register Volume 78, Number 248 (Thursday, December 26, 2013)]
[Notices]
[Pages 78370-78372]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-30745]



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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.

Chimeric Antigen Receptors to ALK for Treating Neuroblastoma and Other 
Solid Tumors

    Description of Technology: Chimeric antigen receptors (CARs) are 
hybrid proteins consisting of an antibody binding fragment fused to 
protein signaling domains that cause T-cells which express the CAR to 
become cytotoxic. Once activated, these cytotoxic T-cells can 
selectively eliminate the cells which they recognize via the antibody 
binding fragment of the CAR. By engineering a T-cell to express a CAR 
that is specific for a certain cell surface protein, it is possible to 
selectively target those cells for destruction. This is a promising new 
therapeutic approach known as adoptive cell therapy.
    Anaplastic lymphoma kinase (ALK, CD246) is a tumor-associated 
antigen that is expressed on the cell surface of pediatric 
neuroblastomas and some non-small cell lung carcinomas (NSCLC). This 
technology concerns the development of four (4) CARs, each comprising a 
different antibody binding fragment to ALK. The CARs, known 
individually as ALKCAR15, ALKCAR48, ALKCAR53 and ALKCAR58, can be used 
in adoptive cell therapy treatment for neuroblastoma and other solid 
tumors which overexpress ALK or variants thereof.

Potential Commercial Applications:

     Treatment of cancers associated with expression of ALK or 
variants thereof.
     Specific cancers include neuroblastoma, NSCLC and other 
solid tumors.

Competitive Advantages:

     High affinity of the ALKCAR15, ALKCAR48, ALKCAR53 and 
ALKCAR58 increases the likelihood of successful targeting.
     Targeted therapy decreases non-specific killing of 
healthy, essential cells, resulting in fewer non-specific side-effects 
and healthier patients.

Development Stage:

     Early-stage
     In vitro data available
     In vivo data available (animal)
    Inventors: Rimas J. Orentas and Crystal L. Mackall (NCI)
    Publication: Orentas RJ, et al. ALK (anaplastic lymphoma kinase, 
CD246)-specific CARs: new immunotherapeutic agents for the treatment of 
pediatric solid tumors. J Immunother Cancer. 2013 Nov 7;1 (Suppl 
1):P27. [doi:10.1186/2051-1426-1-S1-P27] (Poster presentation)
    Intellectual Property: HHS Reference No. E-007-2014/0--U.S. 
Provisional Patent Application No. 61/865,845 filed 06 November 2013

Related Technologies:

     HHS Reference No. E-104-2013/0--US Provisional Patent 
Application No. 61/805,001 filed 25 March 2013 (``Anti-CD276 
Polypeptides, Proteins, and Chimeric Antigen Receptors,'' Orentas RJ, 
et al.)
     HHS Reference No. E-291-2012/0--International Patent 
Application No. PCT/US2013/060332 filed 18 September 2013 (``M971 
Chimeric Antigen Receptors,'' Orentas RJ, et al.)
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The Pediatric Oncology Branch, 
CCR, NCI, is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate or 
commercialize CAR (chimeric antigen receptor) T cells specific for the 
ALK tumor-associated antigen. For collaboration opportunities, please 
contact John D. Hewes, Ph.D. at [email protected].

Acid-Resistant, Attenuated Microbial Vector for Improved Oral Delivery 
of Multiple Targeted Antigens

    Description of Technology: Ty21a, the licensed oral live, 
attenuated bacterial vaccine for Salmonella typhi (the causative agent 
of typhoid fever), has been engineered to stably express a variety of 
target LPS (lipopolysaccharides) and protein antigens to protect 
against shigellosis, anthrax, and plague. Ty21a induces mucosal, 
humoral, and cellular immunity and can be utilized as a multivalent 
vaccine vector that is inexpensive to produce. Salmonella species 
encode inducible acid tolerance, but this genus does not survive well 
below pH 4. Shigella and enterohemorrhagic E. coli isolates have more 
effective acid resistance systems than Salmonella and can survive an 
extreme acid challenge of pH 1-2 (the acidity of the human stomach when 
full).
    This application claims an engineered Ty21a vector that can survive 
a very low pH for two to three hours (i.e.. normal transit time through 
a full stomach), allowing for a final delivery format for Ty21a as a 
rapidly dissolvable wafer, instead of the large bullet-size enteric-
coated capsule, which small children cannot swallow. This formulation 
enhances the ability of the immunogenic composition and/or vaccine to 
stimulate immune responses sublingually and throughout the intestinal 
tract.

Potential Commercial Applications:

     Shigella vaccines
     Biodefense vaccines
     Diagnostics

Competitive Advantages:

     Ease of manufacture
     Inexpensive to manufacture
     Ease of administration
     Known live attenuated bacterial vector

Development Stage:

     Pre-clinical
     In vitro data available
     In vivo data available (animal)
    Inventors: Madushini N. Dharmasena and Dennis J. Kopecko (FDA/CBER)
    Intellectual Property: HHS Reference No. E-535-2013/0--US 
Provisional Application No. 61/862,815 filed 06 August 2013
    Licensing Contact: Peter Soukas; 301-435-4646; [email protected]
    Collaborative Research Opportunity: The Food and Drug 
Administration, Center for Biologics Evaluation and Research, is 
seeking statements of capability or interest from parties

[[Page 78371]]

interested in collaborative research to further develop, evaluate or 
commercialize acid-resistant Shigellosis vaccines. For collaboration 
opportunities, please contact Alice Welch, Ph.D. at 301-796-8449 or 
[email protected].

Assay to Screen Anti-metastatic Drugs

    Description of Technology: Scientists at the NIH have developed a 
research tool, a murine cell line model (JygMC(A)) with a reporter 
construct, of spontaneous metastatic mammary carcinoma that resembles 
the human breast cancer metastatic process in a triple negative mammary 
tumor. The assay is useful for screening compounds that specifically 
inhibit pathways involved in mammary carcinoma and can improve clinical 
management of triple negative breast cancer which are greatly 
refractory to conventional chemo and radiotherapy. The key feature of 
the cell line is that when introduced orthotopically into the mammary 
gland of immunocompromised mice it produces murine mammary tumors that 
rapidly metastasize to distant sites, such as lungs, lymph nodes, liver 
and kidneys. This allows for precise tracking of tumor growth and 
metastasis.

Potential Commercial Applications:

     Laboratory tool to investigate molecular mechanisms and/or 
signaling pathways involved in tumorigenesis, angiogenesis and 
metastasis of breast cancer and its response to therapy (in vivo and in 
vitro).
     Research tool for high through-put screening of libraries 
for compounds that specifically inhibit mechanisms and/or signaling 
pathways involved in metastatic triple negative breast cancer.
     Research tool to optimize therapeutic regimens.
    Competitive Advantages: Dual report construct: enhanced green 
fluorescent protein (eGFP) or a fusion of firefly luciferase and eGFP 
(ffLuc2-eFGP) and mouse Cripto-1 promoter sequence cloned into a vector 
for reporter assays and/or visualization of molecular mechanisms 
involved in tumorigenesis of metastatic breast cancer cells.

Development Stage:

     Pre-clinical
     In vitro data available
     In vivo data available (animal)
    Inventors: Nadia P. Castro, David S. Salomon, Frank F. Cuttitta 
(all of NCI)

Publications:

    1. Castro, Nadia P. ``Role of the Notch signaling in the metastasis 
of a murine breast cancer model.'' Abstract presented at the Mammary 
Gland Biology Gordon Research Conference, Lucca (Barga) Italy, June 10-
15, 2012.
    2. Castro, Nadia P. ``Notch pathway in an experimental model of 
breast cancer metastasis.'' Abstract presented at the Sixth AACR 
Special Conference on Advances in Breast Cancer Research, San 
Francisco, California, October 12-15, 2011.
    Intellectual Property: HHS Reference No. E-088-2013/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Surekha Vathyam, Ph.D.; 301-435-4076; 
[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 
mechanism of tumor growth and lung metastasis. For collaboration 
opportunities, please contact John D. Hewes, Ph.D. at 
[email protected].

Mouse Model for the Preclinical Study of Metastatic Disease

    Description of Technology: The successful development of new cancer 
therapeutics requires reliable preclinical data that are obtained from 
mouse models for cancer. Human tumor xenografts, which require 
transplantation of human tumor cells into an immune compromised mouse, 
represent the current standard mouse model for cancer. Since the immune 
system plays an important role in tumor growth, progression and 
metastasis, the current standard mouse model is not ideal for accurate 
prediction of therapeutic effectiveness in patients. This may 
contribute to increased failure in later phases of clinical trials, as 
appropriate tumor-host interactions are not preserved.
    This technology establishes a system for producing mouse cancer 
models where the model is not immune compromised, providing an 
environment which is more akin to the disease state of cancer patients. 
To establish the model, a tumor is (a) developed in tissue that has 
been propagated by serial transplantation (rather than cell culture), 
(b) labeled (using lentiviral vectors) with bioimaging markers (e.g., 
green fluorescent protein (GFP) and luciferase), and (c) transplanted 
into immunocompetent mice. Once established, the model can be used to 
monitor tumor growth, progression and metastasis through standard 
imaging techniques. The effectiveness of a given therapeutic approach 
can also be monitored using the same techniques.

Potential Commercial Applications:

     Improved mouse model for preclinical testing of drugs to 
treat metastatic disease
     Can be applied to any cancer where tumor cell lines can be 
developed without cell culture propagation
     Can be used to build preclinical models that require 
consistent disease tracking and normal immune context (e.g. bone marrow 
transplantation, stem cell therapy, tissue regeneration)

Competitive Advantages:

     Labeling markers are tolerized, allowing consistent 
expression in this mouse
     Increase in accurate prediction of drug effectiveness 
during preclinical stages; allows better prediction of success at later 
clinical stages
     Mice are not immunocompromised, and thereby more 
accurately representing in vivo disease states
     Labeling of tumors for transplantation allows tumors to be 
traced during growth, progression and metastasis in normal immune 
context
     Labeling also allows more efficient study of the 
effectiveness of treatments

Development Stage:

     Early-stage
     In vitro data available
     In vivo data available (animal)
    Inventors: Chi-Ping Day and Glenn Merlino (NCI)

Publications:

    1. Day CP, et al. Preclinical therapeutic response of residual 
metastatic disease is distinct from its primary tumor of origin. Int J 
Cancer. 2012 Jan 1;130(1):190-9. [PMID 21312195].
    2. Day CP, et al. Immunological naturalization of immunocompetent 
host mice to luciferase-GFP for consistent tracking of transplanted 
tumors. Poster 1556, Annual Meeting 2013, American Association 
of Cancer Research, Washington, DC, April 6-10, 2013.
    Intellectual Property: HHS Reference No. E-296-2012/0--Biological 
Material/Research Tool. Patent protection is not being pursued for this 
technology.
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[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 
preclinical models allowing consistent disease tracking in normal 
immune context. For collaboration opportunities, please

[[Page 78372]]

contact John D. Hewes, Ph.D. at [email protected].

Software for Evaluating Drug Induced Hepatotoxicity

    Description of Technology: This invention pertains to a software 
tool for assisting differential medical diagnosis of drug-induced liver 
injury (hepatotoxicity) using clinical trial data. The software is 
capable of identifying a small subset of patients at risk for 
hepatotoxicity out of a pool of thousands of clinical trial 
participants. This software tool is the only one of its kind developed 
using SAS/IntrNet[supreg].

Potential Commercial Applications:

     Hepatotoxicity detection
     Drug interactions

Competitive Advantages:

     Personalized predictions
     SAS/IntrNet[supreg] compatible
    Development Stage: Prototype
    Inventor: Ted J. Guo (FDA)

Publications:

    1. Guo T, et al. A Tool to Help You Decide [detect potentially 
serious liver injury]. Silver Spring, Maryland: Presentation at the 
Annual Conference of the American Association for the Study of Liver 
Diseases, 2008.
    2. Guo T, et al. How a SAS/IntrNet tool was created at the FDA for 
the detection of potential drug-induced liver injury using data with 
CDISC standard. San Diego, California: Proceedings of the Western Users 
of SAS Software Annual Conference, 2009.
    3. Watkins PB, et al. Evaluation of drug-induced serious 
hepatotoxicity (eDISH): application of this data organization approach 
to phase III clinical trials of rivaroxaban after total hip or knee 
replacement surgery. Drug Saf. 2011 Mar 1;34(3):243-52. [PMID 21332248]
    Intellectual Property: HHS Reference No. E-103-2012/0--Software 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Michael Shmilovich; 301-435-5019; 
[email protected].

Hexanucleotide Repeat in the C9orf72 Gene for the Diagnosis and 
Treatment of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

    Description of Technology: This invention relates to the discovery 
of a pathogenic GGCCCC hexanucleotide repeat expansion in the first 
intron of the C9orf72 gene on chromosome 9p21 in patients exhibiting 
amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia 
(FTD). The inventors have previously identified a strong association 
signal in this genomic region and used this information to identify the 
underlying pathogenic mutation. The pathogenic repeat expansion 
accounts for up to 50% of familial ALS and familial FTD cases and up to 
10% of sporadic ALS and sporadic FTD cases in European ancestry 
populations. The inventors represent that this finding will be the 
basis of diagnostic screening for ALS and/or FTD patients, as well as 
an important target in the development of therapeutics for ALS and/or 
FTD.
    Potential Commercial Applications: Diagnosis and treatment of ALS 
and/or FTD.
    Competitive Advantages: Improved diagnosis and treatment of ALS 
and/or FTD.
    Development Stage: In vitro data available
    Inventors: Stuart Pickering-Brown (The University of Manchester), 
Bryan Traynor (NIA), Andrew Singleton (NIA), Huw Morris (Cardiff 
University), Peter Heutink (Vu University Medical Center Amsterdam), 
John Hardy (University College London), Pentti Tienari (University of 
Helsinki)
    Intellectual Property: HHS Reference No. E-275-2011/0--
     US Provisional Application No. 61/529,531 filed 31 August 
2011
     PCT Application No. PCT/GB2012/052140 filed 31 August 2012
    Licensing Contact: Jaime M. Greene; 301-435-5559; 
[email protected]

     Dated: December 19, 2013.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2013-30745 Filed 12-24-13; 8:45 am]
BILLING CODE 4140-01-P