[Federal Register Volume 75, Number 43 (Friday, March 5, 2010)]
[Notices]
[Pages 10282-10283]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-4762]



[[Page 10282]]

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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.

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.

BODIPY[supreg]-FL Nilotinib (Tasigna[supreg]) for Use in Cancer 
Research

    Description of Invention: Investigators at the National Institutes 
of Health have produced a fluorescently labeled derivative of the 
clinically-approved, tyrosine kinase inhibitor (TKI) nilotinib 
(Tasigna[supreg]) for use in research. This was accomplished by 
conjugating the fluorescent dye BODIPY[supreg]-FL to nilotinib.
    The TKI imatinib (Gleevec[supreg]) is the first targeted 
therapeutic developed and is used as first line treatment of 
Philadelphia chromosome-positive (Ph+) cancers like chronic myeloid 
leukemia (CML). Although imatinib is highly effective, after continued 
use the cancer cells frequently become resistant to the drug. Nilotinib 
is a second generation TKI developed to overcome imatinib resistance, 
but eventually it can also result in drug resistance.
    The fluorescent nilotinib conjugate was developed to study the 
mechanism by which cancer cells become resistant to nilotinib and 
better understand its cytotoxic effects.

Applications

     Use in monitoring cellular accumulation of nilotinib using 
flow cytometry, fluorescent microscopy, or other fluorometric 
techniques
     Use as an in vivo probe with experimental models and in 
clinical studies for analyzing drug efficacy, pharmacokinetic profile 
and drug localization
     Use for the study of cytotoxic effects of nilotinib in 
important physiological locations such as the heart and brain
     Use in identifying other potential targets of nilotinib in 
different types of cancer
     Use in in vivo imaging to identify potential physiological 
barriers to drug penetration into tissues

Advantages

     Material is ready for use reducing time and effort to 
duplicate
     BODIPY[supreg]-FL dye is compatible with commonly-used 
fluorescein dye optics and has superior can be used for both in vitro 
and in vivo studies.
    Development Status:
     Ready for use.
     Pre-clinical data available.
    Market: The size of the chronic myeloid leukemia (CML) market is 
expected fluorescent properties to fluorescein
     BODIPY[supreg]-FL Nilotinib (Tasigna[supreg]) is 
compatible and to increase with an aging population. It was estimated 
that in 2009, there were 91,500 patients with CML in the U.S. and other 
major other developed countries, increasing by 9-11% per year. The 
fluorescently- labeled Nilotinib (Tasigna[supreg]) will be useful for 
researchers working to develop next generation tyrosine kinase 
inhibitors.
    Inventors: Suneet Shukla (NCI), Suresh V. Ambudkar (NCI), Craig J. 
Thomas (NHGRI/NCGC), Amanda P. Skoumbourdis (NHGRI/NCGC).
    Publications: None currently available for this technology.
    Patent Status: HHS Reference No. E-009-2010/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for biological materials licensing.
    Licensing Contact: Sabarni Chatterjee, Ph.D.; 301-435-5587; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute, 
Transport Biochemistry Section, Laboratory of Cell Biology, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
bodipy conjugated tyrosine kinase inhibitors that are currently used in 
the clinic for the treatment of CML or gastric cancers. We are also 
interested in evaluating third generation tyrosine kinase inhibitor 
derivatives as modulators of ABC drug transporters to improve the 
efficiency of chemotherapy in animal (mouse) model system. In addition, 
we can identify possible pharmacokinetic interactions of the novel 
kinase inhibitors with ABC drug transporters. Please contact John 
Hewes, Ph.D. at 301-435-3131 or [email protected] for more 
information.

Diagnosis and Treatment of Cancer Using Histone Deacetylase Inhibitors 
and Radiolabeled Metaiodobenzylguanidine

    Description of Invention: Pheochromocytoma is a neuroendocrine 
tumor of the adrenal glands. Pheochromocytoma patients display the 
signs and symptoms of those of sympathetic nervous system 
hyperactivity. Up to 36% of patients worldwide with pheochromocytoma 
develop metastatic disease and have a 5-year survival rate of 
approximately 50% after diagnosis. Patients with metastatic 
pheochromocytoma exhibit excessive levels of circulating 
catecholamines, which results in increased risk of strokes, cardiac 
arrhythmias, and hypertensive complications. Current treatments for 
malignant pheochromocytoma include targeted radiation using [\131\I]-
metaiodobenzylguanidine ([\131\I]-MIBG), cytotoxic chemotherapy, 
octreotide, tumor hemoembolization, etc. The success of these 
treatments varies based on the sites and growth rate of metastatic 
lesions.
    The present invention provides a method for treating a mammalian 
tumor with a histone deacetylase inhibitor (HDACi), and followed by 
administering [\131\I]-MIBG. Methods of diagnosis and imaging of 
mammalian tumors are also disclosed. These findings suggest that HDACi 
could enhance the therapeutic efficacy of [\131\I]-MIBG treatment in 
patients with malignant pheochromocytoma.
    Applications and Market:
     Diagnosis and therapeutic for treating cancer, such as 
pheochromocytoma.
     Approximately 1000 cases of pheochromocytoma are diagnosed 
in United States yearly.
    Development Status: Pre-clinical stage of development.
    Inventors: Karel Pacak et al. (NICHD).
    Publications: Manuscript submitted.
    Patent Status: U.S. Provisional Application No. 61/260,991 filed 13 
Nov 2009 (HHS Reference No. E-299-2009/0-US-01).
    Licensing Status: Available for licensing.

[[Page 10283]]

    Licensing Contact: Betty B. Tong, PhD; 301-594-6565; 
[email protected].
    Collaborative Research Opportunity: The National Institute of Child 
Health and Human Development, Reproductive Biology and Adult 
Endocrinology Branch, is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize [\131\I]-MIBG treatment of malignant/
metastatic pheochromocytoma, paraganglioma, and neuroblastoma; also 
[123/131I]-MIBG scintigraphy--in all situations histone 
deacetylase to be used before MIBG is used. Please contact Joseph 
Conrad, PhD at 301-435-3107 or [email protected] for more 
information.

Specific Binding Agents for KSHV vIL-6 That Neutralize a Biological 
Activity

    Description of Invention: Kaposi's sarcoma-associated herpes virus 
(KSHV) is an oncogenic herpes virus originally identified in AIDS 
associated Kaposi's sarcoma (KS) lesions, the most common tumor 
associated with HIV infection. KSHV encodes various proteins that have 
characteristics associated with cellular growth and transformation, 
including viral (v) IL-6 (KSHV vIL-6). These viral proteins display 
structural homology to their cellular counterparts, and human and vIL-6 
are multifunctional cytokines that have been shown to induce vascular 
endothelial growth factor and other factors.
    Available for licensing are binding agents that neutralize vIL-6 
biological activities, methods of diagnosing and treating KSHV 
disorders, and methods to monitor KSHV patient response to treatment. 
Deregulation of cellular IL-6 expression is known to contribute to 
tumor development, suggesting that KSHV-derived vIL-6 could be part of 
a viral strategy to promote malignant transformation. Neutralizing 
activity of anti-vIL-6 antibodies may provide a potential therapeutic 
for KSHV disorders such as HIV, Castleman's disease, and primary 
effusion lymphoma.
    Applications:
     Therapeutic compositions to treat KSHV disorders such as 
KS, Castleman's disease, and primary effusion lymphoma.
     Method to diagnose and treat KSHV disorders.
     Method to monitor patient response to KSHV treatment.
    Market:
     Approximately 476,095 persons currently living with HIV/
AIDS in the United States.
     Estimated annual incidence rate for KS is 5 cases per 
100,000/year in the U.S.
     KS contributes to approximately 30% of AIDS related 
deaths.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Giovanna Tosato (NCI) et al.
    Publications:
    1. Y Aoki and G Tosato. Therapeutic options for human herpesvirus-
8/Kaposi's sarcoma-associated herpesvirus-related disorders. Expert Rev 
Anti Ther. 2004 Apr;2(2):213-225. [PubMed: 15482187].
    2. Y Aoki et al. Detection of viral interleukin-6 in Kaposi 
sarcoma-associated herpesvirus-linked disorders. Blood. 2001 Apr 
1;97(7):2173-2176. [PubMed: 11264189].
    3. Y Aoki et al. Kaposi's sarcoma-associated herpesvirus-encoded 
interleukin-6. J Hemathother Stem Cell Res. 2000;9(2):137-145. [PubMed: 
10813527].
    Patent Status:
    U.S. Patent No. 6,939,547 issued 06 Sep 2005 (HHS Reference No. E-
180-2000/0-US-03).
    U.S. Patent No. 7,108,981 issued 19 Sep 2006 (HHS Reference No. E-
180-2000/0-US-04).
    U.S. Patent No. 7,235,365 issued 26 Jun 2007 (HHS Reference No. E-
180-2000/0-US-05).
    U.S. Patent No. 7,374,756 issued 20 May 2008 (HHS Reference No. E-
180-2000/0-US-06).
    Licensing Status: Available for licensing.
    Licensing Contact: Jennifer Wong; 301/435-4633; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute's 
Laboratory of Cellular Oncology is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize therapeutics for Kaposi's sarcoma-
associated herpes virus (KSHV). Please contact John D. Hewes, PhD at 
301-435-3121 or [email protected] for more information.

    Dated: March 1, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-4762 Filed 3-4-10; 8:45 am]
BILLING CODE 4140-01-P