[Federal Register Volume 78, Number 120 (Friday, June 21, 2013)]
[Notices]
[Pages 37554-37556]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-14821]


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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. 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.

GPR116 Knockout and Conditional Knockout Mice

    Description of Technology: Pulmonary surfactant plays a critical 
role in preventing alveolar collapse by decreasing surface tension at 
the alveolar air-liquid interface. Surfactant deficiency contributes to 
the pathogenesis of acute lung injury (ALI) and acute respiratory 
distress syndrome (ARDS), common disorders that can afflict patients of 
all ages and carry a mortality rate greater than 25%. Excess surfactant 
leads to pulmonary alveolar proteinosis. The NCI investigators created 
a G-protein coupled receptor GPR116 mutant mouse model and showed that 
GPR116 plays a previously unexpected, essential role in maintaining 
normal surfactant levels in the lung.
    The mouse model could aid in the development of drug screens to 
identify agents that can modulate surfactant levels. Alveolar type II 
cells have also been isolated from the GPR116 wildtype and knockout 
mice that could be directly used in such assays. The identification of 
surfactant modulating agents could be important to a number of lung 
surfactant disorders.
    Potential Commercial Applications: Research materials to study lung 
surfactant homeostasis and disorders.
    Competitive Advantages: Not available elsewhere.
    Development Stage:
     Prototype.
     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Bradley Dean St. Croix and Mi Young Yang (NCI).
    Publication: Yang MY, et al. Essential Regulation of Lung 
Surfactant Homeostasis by the Orphan G Protein-Coupled Receptor GPR116. 
Cell Rep. 2013 May 30;3(5):1457-64. [PMID 23684610]
    Intellectual Property: HHS Reference No. E-269-2012/0--Research 
Tool. Patent prosecution is not being pursued for this technology.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].
    Collaborative Research Opportunity: The Center for Cancer Research 
Mouse Cancer Genetics Program is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate or commercialize GPR116 Knockout and Conditional 
Knockout Mice. For collaboration opportunities, please contact John 
Hewes, Ph.D. at [email protected].

Engineered Anthrax Toxin Variants That Target Cancer

    Description of Technology: This technology describes the use of 
novel mutated anthrax protective antigen (PA) protein variants to 
target tumor cells and tumor vasculature. NIH scientists have 
engineered two PA variants that selectively complement one another and 
combine to form active octamers that target tumor cells. This 
controlled oligomeric activation of the PA proteins makes the 
likelihood of toxicity to non-tumor cells very low since non-tumor 
tissue does not express certain cell-surface proteases required to 
activate the PA variants. Using proteases that are highly expressed in 
tumor cells, e.g., matrix metalloproteases (MMP) and urokinase 
plasminogen activator (uPA), the scientists have shown significant 
tumor growth suppression with the oligomer in a mouse model. 
Furthermore, other tumor-specific proteases could also be used to 
control formation of the targeted octameric anthrax toxin structures. 
Moreover, the structures can be expanded to include several PA 
variants. In summary, this technology provides a unique, expandable 
platform that reduces toxicity to normal tissues compared to other 
systems and can be used to treat cancers more effectively.
    Potential Commercial Applications: Therapeutic treatment for solid 
tumors, cancers, and infectious diseases.
    Competitive Advantages:
     Specificity in targeting tumors while eliminating side 
effects associated with non-specific targeting of normal cells.
     Method can be expanded to include different proteases and 
up to eight PA variants.
    Development Stage:
     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Clinton E. Leysath, Stephen H. Leppla, Damilola D. 
Phillips (NIAID).
    Publication: Phillips DD, et al. Engineering anthrax toxin variants 
that exclusively form octamers and their application to targeting 
tumors. J Biol Chem. 2013 Mar 29;288(13):9058-65. [PMID 23393143]
    Intellectual Property: HHS Reference No. E-246-2012/0--U.S. 
Provisional Application No. 61/692,143 filed 22 Aug 2012.
    Related Technologies:
     HHS Reference No. E-293-1999--Mutated Anthrax Toxin 
Protective Antigen Proteins That Specifically Target Cells Containing 
High Amounts of Cell-Surface Metalloproteinases or Plasminogen 
Activator Receptors (Leppla/NIAID).

[[Page 37555]]

     HHS Reference No. E-070-2007--Human Cancer Therapy Using 
Engineered Metalloproteinase-Activated Anthrax Lethal Toxin That Target 
Tumor Vasculature (Leppla/NIAID).
     HHS Reference No. E-059-2004--Multimeric Protein Toxins to 
Target Cells Having Multiple Identifying Characteristics (Leppla/
NIAID).
    Licensing Contact: Whitney Hastings; 301-451-7337; 
[email protected].

Intra-Bone Drug Delivery Device and Method

    Description of Technology: The invention pertains to devices for 
directly infusing cellular therapeutics into patient bone. The device 
monitors intra-bone pressure using pressure sensors disposed at its 
proximal end and adjusts infusion pressures during infusion such that 
intra-bone pressure does not exceed levels of systemic blood pressure. 
Such devices, apparatus and methods are particularly suitable for use 
in performing bone marrow transplants, particularly transplants that 
utilize cord blood as a stem cell source.
    Potential Commercial Applications: Drug delivery to bones.
    Competitive Advantages:
     Therapeutic uptake efficiency.
     Drug delivery efficiency.
     Target specificity.
    Development Stage:
     Prototype.
     In vitro data available.
    Inventors: Robert Hoyt (NHLBI), Jeremy Pantin (NHLBI), Timothy Hunt 
(NHLBI), Randall Clevenger (NHLBI), Omer Aras (NIHCC), Richard Childs 
(NHLBI), Peter Choyke (NCI).
    Publication: Pantin JM, et al. ``Optimization of an Intra-Bone 
Hematopoietic Stem Cell Delivery Technique in a Swine Model.'' Poster 
abstract presented at the 54th ASH Annual Meeting and Exposition, 
Atlanta, Georgia, December 8-11, 2012. [https://ash.confex.com/ash/2012/webprogram/Paper53150.html]
    Intellectual Property: HHS Reference No. E-165-2012/0--U.S. 
Provisional Patent Application No. 61/771,463 filed 01 Mar 2013.
    Related Technology: HHS Reference No. E-196-1998/2--U.S. Patent No. 
8,409,166 issued 02 Apr 2013.
    Licensing Contact: Michael Shmilovich; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The National Heart, Lung, and 
Blood Institute is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate or commercialize Intra-bone Drug Delivery Device and Method. 
For collaboration opportunities, please contact Denise Crooks at 
[email protected].

Method of Inducing Pluripotent or Multipotent Stem Cells by Blocking 
CD47 Receptor Signaling

    Description of Technology: NIH researchers have discovered that 
blockade of the signaling activity of a single cell-surface receptor, 
CD47, without transfection or introduction of potentially transforming 
viral vectors, results in high frequency, spontaneous generation of 
self-renewing cells with a high proliferative capacity. Induced 
pluripotent stem cells (iPS cells) are currently produced by 
transforming cells with viral or other constitutive expression vectors 
encoding four stem cell transcription factors (c-Myc, Sox2, Klf4, and 
Oct4), but this method presents challenges such as over-expression of 
c-Myc, which can result in malignant transformation. The present 
invention relates to a method of using CD47-modulating compounds to 
induce multipotent stem cells without the concomitant risk of malignant 
transformation and without requiring the use of feeder cells. The 
cellular phenotypes are associated with increased expression of the 
hallmark stem cell-inducing transcription factors, c-Myc, Sox2, Klf4, 
and Oct4. The current invention builds on the NIH's previous 
discoveries of antibodies, antisense morpholino oligonucleotides, 
peptide compounds and other small molecules that modulate CD47.
    Potential Commercial Applications: Regenerative medicine and stem 
cell therapy.
    Competitive Advantages:
     Does not require use of viral vectors.
     Eliminates risk of malignant transformation for clinical 
applications.
     Eliminates need for feeder cells.
     Allows generation and maintenance of a ready supply of iPS 
cells using a single defined agent.
     Avoids loss of differentiated phenotype associated with 
telomerase or T antigen transfection.
    Development Stage:
     In vitro data available.
     In vivo data available (animal).
    Inventors: David D. Roberts, Sukhbir Kaur, Jeff S. Isenberg (NCI)
    Publications:
    1. Kaur S, et al. Thrombospondin-1 signaling through CD47 inhibits 
self-renewal by regulating c-Myc and other stem cell transcription 
factors. Sci Rep. 2013;3:1673. [PMID 23591719]
    2. NCI News Note: A drug target that stimulates development of 
healthy stem cells. 2013 Apr 17. [http://www.cancer.gov/newscenter/newsfromnci/2013/cd47stemcell]
    Intellectual Property:
     HHS Reference No. E-086-2012/0--U.S. Application No. 61/
621,994 filed 09 Apr 2012.
     HHS Reference No. E-086-2012/1--U.S. Application No. 61/
735,701 filed 11 Dec 2012.
     HHS Reference No. E-086-2012/2--International Application 
PCT/US2013/035838 filed 09 Apr 2013.
    Related Technologies: HHS Reference No. E-227-2006/5--
     U.S. Application No. 12/444,364 filed 3 Apr 09.
     CA Application No. 2,665,287 filed 5 Oct 07.
     EP Application No. 07868382.8 filed 27 Mar 09.
     U.S. Application No. 13/546,941 filed 11 Jul 12.
    Licensing Contact: Charlene Sydnor, Ph.D.; 301-435-4689; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Laboratory of Pathology, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
CD47 modulators for regenerative medicine and stem cell therapy 
applications. For collaboration opportunities, please contact John 
Hewes, Ph.D. at [email protected].

Human Monoclonal Antibodies to Glypican-3 Protein and Heparan Sulfate 
for Treatment of Cancer

    Description of Technology: Hepatocellular carcinoma (HCC) is the 
most common form of liver cancer, and is among the more deadly cancers 
in the world due to its late detection and poor prognosis. No effective 
treatment is available for liver cancer therapy.
    Glypican-3 (GPC3) is a cell surface protein that is preferentially 
expressed on HCC cells, making it an attractive potential target for 
developing a therapeutic. This invention concerns human monoclonal 
antibodies against GPC3 and their use for the treatment of GPC3-
expressing cancers such as HCC.
    Specifically, the inventors have generated two distinct human 
monoclonal antibodies to GPC3. The first antibody (HN3) binds to a 
conformational epitope on the cell surface domain of GPC3. The second 
antibody (HS20) binds specifically to heparan sulfate chains on GPC3. 
These antibodies can inhibit the growth of HCC cells, thereby 
decreasing the ability of tumors to grow and metastasize. Furthermore, 
by using the antibodies to target a toxic moiety to only those cells 
that express GPC3, cancer cells can be eliminated while allowing 
healthy,

[[Page 37556]]

essential cells to remain unharmed. Thus, monoclonal antibodies to GPC3 
(and corresponding immunotoxins) represent a novel therapeutic 
candidate for treatment of HCC, as well as other cancers associated 
with the differential expression of GPC3.
    Potential Commercial Applications:
     Therapeutic antibodies against cancers that overexpress 
GPC3.
     Therapeutic immunotoxins or antibody-drug conjugates for 
killing cancer cells that overexpress GPC3.
     Diagnostics for detecting cancers associated with GPC3 
overexpression.
     Specific cancers include hepatocellular cancer (HCC), 
melanoma, ovarian cancer, thyroid cancer, lung squamous cell carcinoma, 
Wilms' tumor, neuroblastoma, hepatoblastoma, and testicular germ-cell 
tumors.
    Competitive Advantages:
     Monoclonal antibodies create a level of specificity that 
can reduce deleterious side-effects.
     Multiple treatment strategies available including the 
killing of cancer cells with a toxic agent or by inhibiting cell 
signaling.
     Non-invasive and potentially non-liver toxic alternative 
to current HCC treatment strategies.
    Development Stage:
     Pre-clinical.
     In vitro data available.
     In vivo data available (animal).
    Inventors: Mitchell Ho (NCI) et al.
    Publications:
    1. Feng M, et al. Therapeutically targeting glypican-3 via a 
conformation-specific single-domain antibody in hepatocellular 
carcinoma. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):E1083-91. 
[PMID 23471984]
    2. Feng M, et al. Recombinant soluble glypican 3 protein inhibits 
the growth of hepatocellular carcinoma in vitro. Int J Cancer 2011 
May1;128(9):2246-7. [PMID: 20617511]
    3. Zitterman SI, et al. Soluble glypican 3 inhibits the growth of 
hepatocellular carcinoma in vitro and in vivo. Int J Cancer 2010 Mar 
15;126(6):1291-1301. [PMID: 19816934]
    Intellectual Property: HHS Reference No. E-130-2011/0--U.S. 
Provisional Application No. 61/477,020 filed 19 Apr 2011; PCT 
Application No. PCT/US2012/034186 filed 19 Apr 2012.
    Related Technology: HHS Reference No. E-136-2012/0--U.S. 
Provisional Application No. 61/654,232 filed 01 Jun 2012.
    Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Center for Cancer Research, Laboratory of Molecular Biology, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
novel antibody or antibody-drug conjugate therapies for the treatment 
of liver cancer. For collaboration opportunities, please contact John 
Hewes, Ph.D. at [email protected].

    Dated: June 14, 2013.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2013-14821 Filed 6-20-13; 8:45 am]
BILLING CODE 4140-01-P