[Federal Register Volume 78, Number 81 (Friday, April 26, 2013)]
[Pages 24756-24758]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-09902]



National Institutes of Health

Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, 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. 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.

Zirconium-89 PET Imaging Agent for Cancer

    Description of Technology: This technology is a new generation of 
rationally designed chelating agents which improve the complexation of 
Zirconium-89 for PET imaging of cancers. The technology uses cyclic or 
acyclic chelators made of 4 hydroxamate donors groups for improved 
stability compared to the currently used natural product siderophore 
desferrioxamine B (DFB), a

[[Page 24757]]

chelator that consists of only 3 hydroxamate donors that fails to 
saturate the coordination sphere of Zr(IV). DFB, which has been the 
object of many pre-clinical and clinical studies exhibits insufficient 
stability resulting in progressive radioisotope accumulation in bone 
once injected that can contribute to toxicity and increased background. 
The new chelators described in this invention have shown improved 
kinetic inertness compared to DFB with stability up to 90% after 7 days 
compared to 28% for DFB. In association with an adequate targeting 
agent such as an antibody, toxicity to the bone can be reduced and 
images with better contrast can be obtained with these new chelators.
    Potential Commercial Applications:
     Cancer imaging.
     PET imaging.
    Competitive Advantages:
     High stability.
     Low toxicity.
     Better imaging contrast.
    Development Status:
     In vitro data available.
    Inventors: Francois Guerard (NCI), Yong Sok Lee (CIT), Martin 
Brechbiel (NCI).
    1. Zhou Y, et al. Mapping biological behaviors by application of 
longer-lived positron emitting radionuclides. Adv Drug Deliv Rev. In 
Press; doi: 10.1016/j.addr.2012.10.012. [PMID 23123291].
    2. Deri MA, et al. PET imaging with 89Zr: from radiochemistry to 
the clinic. Nucl Med Biol. 2013 Jan;40(1):3-14. [PMID 22998840].
    3. Vosjan MJ, et al. Conjugation and radiolabeling of monoclonal 
antibodies with zirconium-89 for PET imaging using the bifunctional 
chelate p-isothiocyanatobenzyl-desferrioxamine. Nat Protoc. 2010 
Apr;5(4):739-43. [PMID 20360768].
    4. Nayak TK, et al. PET and MRI of metastatic peritoneal and 
pulmonary colorectal cancer in mice with human epidermal growth factor 
receptor 1-targeted 89Zr-labeled panitumumab. J Nucl Med. 2012 
Jan;53(1):113-20. [PMID 22213822].
    5. Evans MJ, et al. Imaging tumor burden in the brain with 89Zr-
transferrin. J Nucl Med. 2013 Jan;54(1):90-5. [PMID 23236019].
    6. Guerard F, et al. Investigation of Zr(IV) and 89Zr(IV) 
complexation with hydroxamates: progress towards designing a better 
chelator than desferrioxamine B for immuno-PET imaging. Chem Commun 
(Camb). 2013 Feb 1;49(10):1002-4. [PMID 23250287].
    Intellectual Property: HHS Reference No. E-111-2013/0--U.S. 
Provisional Application No. 61/779,016 filed 13 Mar 2013.
    Related Technologies:
     HHS Reference No. E-194-2007/0--U.S. Patent Application 
No. 12/667,790 filed 05 Jan 2010.
     HHS Reference No. E-226-2006/0--U.S. Patent No. 8,288,530 
issued 16 Oct 2012.
     HHS Reference No. E-067-1990/0.
    Licensing Contact: Michael A. Shmilovich; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The Radioimmune & Inorganic 
Chemistry Section, ROB, CCR, NCI, is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate or commercialize Zirconium-89 chelation 
technology for ImmunoPET imaging and other applications. For 
collaboration opportunities, please contact John D. Hewes, Ph.D. at 
[email protected].

Novel Methods for Generating Retinal Pigment Epithelium Cells From 
Induced Pluripotent Stem Cells

    Description of Technology: High efficiency methods for producing 
retinal pigment epithelial cells (RPE) from induced pluripotent stem 
cells (iPSCs) are disclosed. The RPE is a polarized monolayer in the 
vertebrate eye that separates the neural retina from the choroid, and 
performs a crucial role in retinal physiology by forming a blood-
retinal barrier and closely interacting with photoreceptors to maintain 
visual function. Many ophthalmic diseases, such as age-related macular 
degeneration, are associated with a degeneration or deterioration of 
the RPE. The iPSCs are produced from somatic cells, including retinal 
pigment epithelial cells, such as fetal RPE. These methods involve 
producing embryoid bodies from human iPSCs, culturing the embryoid 
bodies using specific media to induce differentiation into RPE and 
growing the differentiated RPE cells in a defined media to generate 
human RPE cells. The investigators also developed methods for detecting 
RPE cells and authenticating RPE cells; determining agents that can 
affect the production of RPE cells from an iPSC; and identifying an 
agent that can increase RPE survival in response to a proteo toxic 
insult or stress. The novel methods and RPE cells disclosed here can be 
useful for both pre-clinical and clinical studies involving RPE.
    Potential Commercial Applications: The methods described here can 
be used to:

     Produce RPE cells for use in screening for novel ocular 
therapeutics and for identifying toxic side effects of drugs.
     Produce RPE cells for use in novel cell-based therapies.
     Produce cells to study pathophysiology of RPE.
    Competitive Advantages: The methods described here:
     Dramatically increase the efficiency of iPSC 
differentiation into RPE.
     Produce superior quality RPE.
     Produce RPE cells that are fully authenticated.
     Provide ways to perform high throughput screens with RPE 
    Development Stage:
     In vitro data available.
    Intellectual Property: HHS Reference No. E-251-2012/3--U.S. 
Provisional Application No. 61/759,988 filed 01 Feb 2013.
    Licensing Contact: Suryanarayana (Sury) Vepa; 301-435-5020; 
[email protected].
    Collaborative Research Opportunity: The National Eye Institute is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate or commercialize 
iPSC to RPE differentiation protocol, its clinical, screening, and 
translational applications. For collaboration opportunities, please 
contact Alan Hubbs, Ph.D. at [email protected].

Novel Tocopherol and Tocopheryl Quinone Derivatives as Therapeutics for 
Lysosomal Storage Disorders

    Description of Technology: Novel tocopherol derivatives and 
tocopheryl quinone derivatives useful in the decrease of lysosomal 
substrate accumulation, the restoration of normal lysosomal size, and 
the treatment of lysosomal storage disorders (LSDs) are provided. The 
inventors have discovered that tocopherol and tocopheryl quinone 
derivatives with side chain modifications (such as terminal tri-
halogenated methyl groups) exhibit improved pharmacokinetics, 
modulation of mitochondrial potential and restoration of some LSDs 
phenotypes. These molecules by themselves or in combination with 
Cyclodextrins (CDs) increase intracellular Ca2+ and enhance exocytosis. 
Also, the treatment with these compounds reduced the pathological 
changes in the ultrastructure of LSD cells as observed using electron 
microscopy analysis. The inventors also found that there is a synergy 
between CDs and the new tocopherol analogues when tested on the NPC 
cells and cells from six other

[[Page 24758]]

lysosomal storage diseases including Wolman, Niemann Pick Type A, 
Farber, TaySachs, MSIIIB and CLN2 (Batten) diseases. These new 
tocopherol analogues are as good or better than natural occurring 
tocopherols and tocotrienols in reducing cholesterol accumulation in 
several LSDs.
    Potential Commercial Applications: To develop new therapeutics to 
treat LSDs.
    Competitive Advantages:
     The main advantage of the compounds disclosed here is 
their improved pharmacokinetics.
     The combination of CD and the novel tocopherol analogues 
may reduce the dosage of each drug and thereby reduce the potential 
side effects.
    Development Stage:
     In vitro data available.
    Inventors: Juan Jose Marugan, Wei Zheng, Jingbo Xiao, and John 
McKew (NCATS).
    Intellectual Property: HHS Reference No. E-148-2012/0--U.S. 
Provisional Application No. 61/727,296 filed 16 Nov 2012.
    Related Technologies:
     HHS Reference No. E-294-2009/0--PCT Application No. PCT/
US2011/044590 filed 19 Jul 2011, which published as WO 2012/012473 on 
26 Jan 2012.
     HHS Reference No. E-050-2012/0--US Provisional Application 
No. 61/679,668 filed 12 Aug 2012.
    Licensing Contact: Suryanarayana (Sury) Vepa; 301-435-5020; 
[email protected].
    Collaborative Research Opportunities: The National Center for 
Advancing Translational Sciences (NCATS) is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate or commercialize Novel Tocopherol 
and Tocopheryl Quinone Derivatives as Therapeutics for Lysosomal 
Storage Disorders. For collaboration opportunities, please contact the 
NCATS Technology Development Coordinator at 
[email protected].

    Dated: April 23, 2013.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2013-09902 Filed 4-25-13; 8:45 am]