[Federal Register Volume 74, Number 199 (Friday, October 16, 2009)]
[Notices]
[Pages 53267-53269]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-24869]


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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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[[Page 53268]]

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.

ADDRESSES: 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.

Engineered Biological Pacemakers

    Description of Invention: A common symptom of many heart diseases 
is an abnormal heart rhythm or arrhythmia. While effectively improving 
the lives of many patients, implantable pacemakers have significant 
limitations such as limited power sources, risk of infections, 
potential for interference from other devices, and absence of autonomic 
rate modulation.
    The technology consists of biological pacemakers engineered to 
generate normal heart rhythm. The biological pacemakers include cardiac 
cells or cardiac-like cells derived from embryonic stem cells or 
mesenchymal stem cells. The biological pacemakers naturally integrate 
into the heart. Their generation of rhythmic electric impulses involves 
coupling factors, such as cAMP-dependent PKA and Ca\2+\-dependent CaMK 
II, which are regulatory proteins capable of modulating/enhancing 
interactions (i.e. coupling) of the sarcoplasmic reticulum-based, 
intracellular Ca\2+\ clock and the surface membrane voltage clock, 
thereby converting irregularly or rarely spontaneously active cells 
into pacemakers generating rhythmic excitations.
    Applications: This technology can be utilized in heart disease 
characterized by arrhythmia or situations requiring an implantable 
cardiac pacemaker.
    Advantages: In contrast to current implantable cardiac pacemaker 
technology, this technology is not externally powered, has a lower risk 
of infection, has decreased potential for interference from other 
devices, and has full autonomic rate modulation.
    Development Status: Early stage.
    Inventors: Victor A. Maltsev et al. (NIA).
    Publications:

1. VA Maltsev and EG Lakatta. Synergism of coupled subsarcolemmal 
Ca\2+\ clocks and sarcolemmal voltage clocks confers robust and 
flexible pacemaker function in a novel pacemaker cell model. Am J 
Physiol Heart Circ Physiol. 2009 Mar;296(3):H594-H615.
2. VA Maltsev and EG Lakatta. Dynamic interactions of an intracellular 
Ca\2+\ clock and membrane ion channel clock underlie robust initiation 
and regulation of cardiac pacemaker function. Cardiovasc Res. 2008 Jan 
15;77(2):274-284.

    Patent Status: U.S. Provisional Application No. 61/180,491 filed 22 
May 2009 (HHS Reference No. E-134-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521; 
[email protected].
    Collaborative Research Opportunity: The National Institute on 
Aging, Cellular Biophysics Section, is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate, or commercialize this technology. Please 
contact Vio Conley at 301-496-0477 or [email protected] for more 
information.

Sensitizing Cancer Cells to DNA Targeted Therapies

    Description of Invention: Chk2 is a protein kinase activated in 
response to DNA double strand breaks. In normal tissues, Chk2 
phosphorylates and thereby activates substrates that induce programmed 
cell death, or apoptosis, via interactions with p53, E2F1, PML 
proteins. In cancer tissues, where apoptosis is suppressed, Chk2 
phosphorylates and inactivates cell cycle checkpoints (via interactions 
with Cdc25, phosphatases and Brca1 proteins), which allows cancer cells 
to repair and tolerate DNA damage. Hence, Chk2 inhibitors would be 
expected to protect normal tissues by reducing apoptosis, and to 
sensitize cancer cells to DNA-targeted agents.
    Applications:
     Combination with DNA targeted chemotherapeutic agents for 
the treatment of cancers.
     Single agents therapy for cancers with endogenously 
activated (``addicted to'') Chk2.
     Antiviral agent against hepatitis, herpes viruses and 
retroviral infections (HIV).
    Advantages: Selective enhancement of the antiproliferative and 
proapoptotic activities of DNA targeted chemotherapeutic agents in 
tumors with inactivated p53, while protection of normal tissues by 
blocking p53-mediated apoptosis (``side effects'') induced by the DNA 
targeted agents.
    Development Status: Optimization of chemical structure for 
improving drug delivery and pharmacokinetics.
    Inventors: Yves G Pommier et al. (NCI).
    Related Publications:

1. AG Jobson, JH Cardellina 2nd, D Scudiero, S Kondapaka, H Zhang, H 
Kim, R Shoemaker, Y Pommier. Identification of a Bis-guanylhydrazone 
[4,4'-Diacetyldiphenylurea-bis(guanylhydrazone); NSC 109555] as a Novel 
Chemotype for Inhibition of Chk2 Kinase. Mol Pharmacol. 2007 
Oct;72(4):876-884.
2. AG Jobson, GT Lountos, PL Lorenzi, J Llamas, J Connelly, D Cerna, JE 
Tropea, A Onda, G Zoppoli, S Kondapaka, G Zhang, NJ Caplen, JH 
Cardellina, SS Yoo, A Monks, C Self, DS Waugh, RH Shoemaker, Y Pommier. 
Cellular inhibition of Chk2 kinase and potentiation of camptothecins 
and radiation by the novel Chk2 inhibitor PV1019. J Pharmacol Exp Ther. 
2009 Sep 9; In press (Epub ahead of print).
3. GT Lountos, JE Tropea, D Zhang, AG Jobson, Y Pommier, RH Shoemaker, 
DS Waugh. Crystal structure of checkpoint kinase 2 in complex with NSC 
109555, a potent and selective inhibitor. Protein Sci. 2009 
Jan;18(1):92-100.

    Patent Status: U.S. Patent Application No. 11/989,737 filed 29 Jan 
2008 (HHS Reference No. E-211-2005/0-US-06); Related international 
patent application filings.
    Licensing Status: Available for licensing.
    Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Laboratory of Molecular Pharmacology, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize this 
technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or 
[email protected] for more information.


[[Page 53269]]


    Dated: October 5, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-24869 Filed 10-15-09; 8:45 am]
BILLING CODE 4140-01-P