[Federal Register Volume 77, Number 104 (Wednesday, May 30, 2012)]
[Notices]
[Pages 31859-31861]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-13007]


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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, Public Health Service, 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. 207 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.

Rabbit Polyclonal Antibody To Detect a Pro-Peptide Fragment of NSAID-
Activated Gene (NAG-1)/GDF15, a Protein Associated With Cancer

    Description of Technology: Chronic inflammation is clearly 
associated with an increase in the risk of cancer. Non-steroidal anti-
inflammatory drugs (NSAIDs) are well documented as agents that inhibit 
tumor growth and with long-term use can prevent tumor development. 
NSAID-activated gene (NAG-1), a unique member of the TGF-beta 
superfamily, is highly induced by NSAIDs and numerous drugs and 
chemicals with anti-tumorigenic activities.
    The protein product of NAG-1 is first formed into an immature 
peptide dimer that must be cut at a specific site before it can be 
secreted as a mature protein. Currently available antibodies can only 
detect either the immature form of NAG-1 or the secreted mature 
protein, but do not recognize the peptide fragment that remains when 
the immature dimer is cut to form the mature protein. Now available for 
the first time, the present new antibody recognizes this NAG-1 pro-
peptide fragment.
    Potential Commercial Applications: As a research tool to detect 
expression of the NAG-1/GDF15 cleavage fragment in cells and media from 
cultured cells.
    Competitive Advantages: No other antibody is currently available to 
detect the NAG-1/GDF15 pro-peptide fragment.
    Development Stage: In vitro data available
    Inventor: Thomas Eling (NIEHS)
    Intellectual Property: HHS Reference No. E-177-2012/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Related Technology: HHS Reference No. E-093-2011/0--Transgenic mice 
expressing human GDF15/Nag-1/Mic-1
    Licensing Contact: Patrick McCue, Ph.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The NIEHS is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize this antibody. 
For collaboration opportunities, please contact Elizabeth M. Denholm, 
Ph.D. at [email protected].

Software for Automated Determination of Macromolecular Structure Using 
Cryo-Electron Microscopy

    Description of Technology: Available for licensing is software for 
automated generation of density maps of macromolecular structures from 
series of 2D digital micrographs of frozen hydrated specimens collected 
using an electron microscope equipped with an ultra-cooled computerized 
stage. Series of images of biological specimens collected at different 
tilt angles relative to the electron beam are aligned to compensate for 
mechanical errors of the stage and combined to obtain 3D images 
(tomograms). Sub volumes containing a single macromolecular complex can 
be extracted from the 3D image of a protein solution, or suspension of 
viruses or cells. These individual sub-volumes of identical structures 
are aligned and averaged together to generate a density map of the 
macromolecular complex of interest.
    Potential Commercial Applications:
     Macromolecular imaging
     Molecular interaction
     Molecular structure and reactivity
    Competitive Advantages:
     Noise processing
     Algorithmic averaging
    Development Stage: Prototype
    Inventors: Mario Juan Borgnia, Alberto Bartesaghi, Sriram 
Subramaniam (all of NCI)
    Publications:
    1. Amat F, et al. Markov random field based automatic image 
alignment for electron tomography. J Struct Biol. 2008 Mar;161(3):260-
75. [PMID 17855124]
    2. Kremer JR, et al. Computer visualization of three-dimensional 
image data using IMOD. J Struct Biol. 1996 Jan-Feb;116(1):71-76. [PMID 
8742726]
    3. Mastronarde DN. Dual-axis tomography: an approach with alignment 
methods that preserve resolution. J Struct Biol. 1997 Dec;120(3):343-
52. [PMID 9441937]
    4. Bartesaghi A, et al. An energy-based three-dimensional 
segmentation approach for the quantitative interpretation of electron 
tomograms. IEEE Trans Image Process. 2005 Sep;14(9):1314-23. [PMID 
16190467]
    Intellectual Property: HHS Reference No. E-162-2012/0--Research 
Tool. Patent protection is not being pursued for this technology.
    Licensing Contact: Michael Shmilovich; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The NCI Laboratory of Cell 
Biology 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 John Hewes, Ph.D. at [email protected].

Chimeric Antigen Receptors That Recognize Mesothelin for Cancer 
Immunotherapy

    Description of Technology: Scientists at the National Institutes of 
Health (NIH) have developed chimeric antigen receptors (CARs) with high 
affinity for mesothelin to use as a promising immunotherapy to treat 
cancers, such as pancreatic cancer, ovarian cancer, and mesothelioma. 
Mesothelin is a protein cancer antigen with limited expression on 
normal cells that is overexpressed by

[[Page 31860]]

cancer cells. CARs are hybrid proteins consisting of an antibody 
portion that recognizes a cancer antigen, such as a mesothelin-specific 
antibody, fused to receptor signaling domains that serve to activate 
the CAR-expressing cell to kill tumor cells. Cells that express CARs, 
most notably T cells, are highly reactive against their specific tumor 
antigen in an MHC-unrestricted manner to generate an immune response 
that promotes robust tumor cell elimination when infused into cancer 
patients. The instant technology includes CAR constructs with one of 
three different mesothelin-specific antibody portions, including either 
the mouse-derived SS or SS1 antibody fragments or the human HN1 
antibody fragment. Infusion of cells expressing these mesothelin-
specific CARs into patients could prove to be a powerful new 
immunotherapeutic tool for treating various cancers that express 
mesothelin.
    Potential Commercial Applications:
     Immunotherapeutics to treat and/or prevent the 
reoccurrence of cancers that overexpress mesothelin, including 
pancreatic cancer, ovarian cancer, and mesothelioma and other cancers 
with few effective treatment options.
     A personalized cancer treatment strategy for patients 
whose tumor cells express mesothelin whereby the patient's own T cells 
are isolated, engineered to express a mesothelin-specific CAR, and re-
infused into the body to attack the tumor(s).
     Tools to diagnose the presence of mesothelin-expressing 
tumors in patients.
    Competitive Advantages:
     Minimal side effects: Mesothelin is overexpressed on tumor 
cells. CARs specific for the mesothelin antigen they are expected to 
primarily target tumor cells, and thus, generate fewer side effects 
than other cancer treatment approaches.
     Successful track record: Immunotoxins containing the 
antibody portions of some of these CARs have shown promising results in 
clinical studies for cancer treatment.
     Cutting edge: With the advent of Provenge(R) and 
Yervoy(R), immunotherapy is now more widely accepted as a viable cancer 
treatment option.
    Development Stage:
     Pre-clinical.
     Clinical.
     In vitro data available.
    Inventors: Steven A. Feldman, Steven A. Rosenberg, Ira Pastan (all 
of NCI).
    Intellectual Property: HHS Reference No. E-078-2012/0--U.S. Patent 
Application No. 61/614,612 filed 23 Mar 2012.
    Related Technologies:
     HHS Reference No. E-002-1996/1.
     HHS Reference No. E-021-1998/0.
     HHS Reference No. E-139-1999/0.
     HHS Reference No. E-091-2009/0.
     HHS Reference Nos. E-093-1995/1,/2.
    Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282; 
[email protected].

Low-dose Cardiac Computed Tomography Method for Whole Heart 
Extracellular Volume

    Description of Technology: Myocardial infarction and 
cardiomyopathies result in myocardial scar and diffuse fibrosis. 
Together these result in poor cardiac function. Myocardial scar is a 
specific target for therapy, but is difficult to identify. Cardiac 
Computed Tomography (CCT) struggles to identify large scars, and could 
not previously identify fibrosis. MRI is often used, but MRI is 
expensive and not widely available. We have developed a method to 
quantify both diffuse and focal myocardial scar by CCT using low 
radiation dose methods. Extracellular volume fraction (ECV) is the 
distribution of iodine in the scar relative to blood pool. ECV is 
abnormally elevated in scar. The new CCT technique involves (a) CCT 
data about the myocardium and blood pool is extracted (via a shape 
constrained graph cut technique), (b) an algorithm (Demons deformable 
registration) is applied to pre-contrast and low dose post-contrast 
image information, (c) the ECV value is computed. Along with coronary 
artery depiction on CCT, the ECV can be used to quantitatively measure 
myocardial scar and diffuse myocardial fibrosis for a complete 
depiction of the patient's myocardial status/health.
    Potential Commercial Applications: Medical imaging
    Competitive Advantages: Cardiac Computed Tomography is faster, more 
widely available and comparatively inexpensive versus Cardiac Magnetic 
Resonance Imaging.
    Development Stage:
     Prototype
     Pre-clinical
     Clinical
    Inventors: David Bluemke, Songtao Liu, Marcelo N. Nacif, Jianhua 
Yao, Christopher T. Sibley, Xinjian Chen, Ronald M. Summers (all of 
NIHCC)
    Intellectual Property: HHS Reference No. E-267-2011/0
    Licensing Contact: Tedd Fenn; 301-435-5031; [email protected]
    Collaborative Research Opportunity: The NIH Clinical Center is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
Cardiac CT, Cardiac CTA, myocardial scar, myocardial fibrosis, coronary 
artery disease imaging. For collaboration opportunities, please contact 
Ken Rose, Ph.D. at [email protected].

Quantitative in Vivo Methods To Estimate the Conduction Time of Nerve 
Impulses in the Brain

    Description of Technology: The axon diameter distribution (ADD) is 
an important anatomical feature of nerve fascicles both in normal and 
abnormal development. Axon diameter directly affects nerve function. It 
is well known that in myelinated axons, the conduction velocity is 
directly proportional to axon diameter. Moreover, it is hypothesized 
that in amyotrophic lateral sclerosis (ALS) large diameter axons are 
damaged selectively, while in autism, small-diameter axons are over-
expressed. Despite its importance, the ADD within nerve fascicles has 
not been measurable in-vivo, and currently can only be assessed by 
invasive histological means. Previously, the NICHD inventors developed 
magnetic resonance imaging (MRI) methods to measure the ADD within 
nerve fascicles (e.g., by AxCaliber MRI). This invention extends from 
the inventor's prior work to AxCaliber MRI along with the non-invasive 
measurement of the arc-length of a nerve pathway (e.g., using DTI 
tractography), to estimate the mean conduction time of nerve impulses 
along that pathway, as well as other statistical moments of the 
conduction time distribution. This method could be used to diagnose 
abnormalities in nerve conduction in brain regions and providing a 
neuroanatomical basis for many cognitive and behavior disorders.
    Potential Commercial Applications:
     Used to diagnose abnormalities in nerve conduction in 
brain regions
     Provides a neuroanatomical basis for many cognitive and 
behavior disorders
     A basic tool in neuroscience research to explore the 
dynamic functioning of the brain
    Competitive Advantages:
     Diagnose a number of cognitive and behavioral 
abnormalities, disease and disorders [currently only assessed using 
psychological or psychiatric testing].
     A new quantitative imaging biomarker
     Used to understand and follow brain changes during normal 
aging and in Alzheimer's disease.
     Used to explain motor deficits in ALS disease.

[[Page 31861]]

     Provides way of classifying and understanding various 
neurological and neuropsychiatric conditions according to conduction 
delays.
    Development Stage:
     Prototype
     Clinical
     In vivo data available (animal)
     In vivo data available (human)
    Inventor: Peter J. Basser (NICHD)
    Publications:
    1. Assaf Y, et al. Ax-Caliber: a method for measuring axon diameter 
distribution from diffusion MRI. Magn Reson Med. 2008 Jun;59(6):1347-
54. [PMID 18506799]
    2. Barazany D, et al. In vivo measurement of axon diameter 
distribution in the corpus callosum of rat brain. Brain 2009 May;132(Pt 
5):1210-20. [PMID 19403788]
    Intellectual Property: HHS Reference No. E-226-2010/0--U.S. 
Provisional Application No. 61/535,851 filed 16 Sep 2011
    Related Technology: HHS Reference No. E-079-2003/1--U.S. Patent 
Application No. 12/114,713 filed 02 May 2008
    Licensing Contact: John Stansberry, Ph.D.; 301-435-5236; 
[email protected].
    Collaborative Research Opportunity: The NICHD is seeking statements 
of capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize methods to 
estimate conduction time of nerve impulses in brain. For collaboration 
opportunities, please contact Charlotte McGuinness at 
[email protected].

Simple, Quantitative Sensitive High-Throughput Antibody Detection for 
Lyme Disease

    Description of Technology: This technology is for compositions and 
methods for diagnosis of Lyme disease. Currently, Lyme disease is 
diagnosed by clinical exam and a history of exposure to endemic 
regions. Although, laboratory tests may aid diagnosis, the best tests 
currently available are slow and labor intensive and require 
understanding of the test, and infection stage. A two-step antibody 
based test process is currently the recommended laboratory test. The 
first step is either an enzyme immunoassay (EIA), or an indirect 
immunofluorescence assay (IFA). If the first step is positive, a 
``Western blot'' test is then performed. Because early intervention is 
critical to prevent neurological, rheumatological and cardiac damage 
from advanced infection, more sensitive, specific, simpler, high-
throughput format laboratory diagnostics are needed. This technology 
uses a novel synthetic gene (VOVO) in a highly sensitive, specific and 
high-throughput Luciferase Immunoprecipitation Systems (LIPS) format. 
LIPS screening using VOVO offers an efficient and qualitative approach 
for serological screening of antibodies in Lyme disease in human and 
veterinary applications.
    Potential Commercial Applications: Diagnostic for Lyme disease in 
human and veterinary applications.
    Competitive Advantages: Higher efficiencies, High-throughput Format 
Qualitative
    Development Stage:
     Early-stage
     Pre-clinical
    Inventors: Peter D. Burbelo (NIDCR), Michael J. Iadarola (NIDCR), 
Adriana Marques (NIAID)
    Publication: Burbelo PD, et al. Simple, quantitative, and highly 
sensitive antibody detection for Lyme disease. Clin Vaccine Immunol. 
2010 Jun;17(6):904-9. [PMID: 20392886]
    Intellectual Property: HHS Reference No. E-036-2010/1--PCT 
application PCT/US2011/027888 filed 10 Mar 2011
    Licensing Contact: Tedd Fenn; 301-435-5031; [email protected]
    Collaborative Research Opportunity: The NIDCR, Laboratory of 
Sensory Biology, Neurobiology and Pain Therapeutics Section, 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 David 
Bradley, Ph.D. at [email protected].

    Dated: May 23, 2012.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2012-13007 Filed 5-29-12; 8:45 am]
BILLING CODE 4140-01-P