[Federal Register Volume 73, Number 99 (Wednesday, May 21, 2008)]
[Notices]
[Pages 29521-29524]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-11317]


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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.

Synthetic Analogs of Juxtamembrane Domain of IGF-1 Receptor as Anti-
Cancer Agents

    Description of Technology: Insulin-like growth factor receptor type 
one (IGF-1R), part of the receptor tyrosine kinase (RTKs) family, is 
integral to cancer cell growth and metastasis. Juxtamembrane domains 
(JM) of RTKs are located in the cytoplasm between the transmembrane and 
kinase domains. JMs play a crucial role in the inhibition of the 
regulation of receptor activity. Studies on other small molecules 
tyrosine kinase inhibitors (TKIs) indicate non-specific binding with 
the insulin receptor which has high homology with IGF-1R.
    The current invention describes synthetic analogs of IGF-1R JM 
which were found to be potent inhibitors of IGF-1-mediated cell 
signaling and cancer cell growth. These analogs provide more binding 
specificity with less likelihood of significant toxic effects.
    Applications and Modality:
    New inhibitors can be used to treat many types of tumors.

[[Page 29522]]

IGR-1R inhibition may be useful as an anti-aging agent.

    IGR-1R plays an inhibitory role in regulation of skin development 
and differentiation. IGF-1R inhibitors may have revitalizing and 
rejuvenating effect on skin and may stimulate wound healing.
    Market:
    An estimated 1,444,920 new cancer diagnoses in the U.S. in 2007.
    600,000 deaths caused by cancer in the U.S. in 2006.
    Cancer is the second leading cause of death in the U.S.
    Cancer drug market will likely double to $50 billion in 2010 from 
$25 billion in 2006.
    Development Status: The technology is currently in the preclinical 
stage of development.
    Inventors: Nadya I. Tarasova and Sergey G. Tarasov (NCI).
    Patent Status: U.S. Provisional Application No. 61,040,203 filed 28 
Mar 2008 (HHS Reference No. E-129-2008/0-US-01).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Adaku Nwachukwu, J.D.; 301-435-5560; 
[email protected].

Protein-Tyrosine Phosphotase Inhibitors as Inhibitors of Human Tyrosyl-
DNA Phosphodiesterase (Tdp1) and Methods of Treating Disorders

    Description of Technology: Tyrosyl-DNA phosphodiesterase (Tdp1) is 
an enzyme that repairs topoisomerase I (Top1)-mediated DNA damage 
induced by chemotherapeutic agents (such as camptothecins) and 
ubiquitous DNA lesions that interfere with transcription and 
replication. Tdp1 is a relevant target for anticancer therapies due to 
its role in repairing Top1-mediated DNA damage and DNA damage 
associated with DNA strand breaks. Tdp1 inhibitors are expected to be 
effective in cancer treatment when used in combination with Top1 
inhibitors.
    The current invention is Me-3,4 dephostatin, and more generally 
protein-tyrosine phosphatase inhibitors, which is a Tdp1 inhibitor. Me-
3,4 dephostatin could potentiate the pharmacological action of Top1 
inhibitors.
    Applications and Modality:
    It is anticipated that Tdp1 inhibitors in association with Top1 
inhibitors can have selective activity toward tumor tissues.
    Tdp1 inhibitors may exhibit antitumor activity by themselves 
because tumors have excess free radicals.
    Market:
    An estimated 1,444,920 new cancer diagnoses in the U.S. in 2007.
    600,000 deaths caused by cancer in the U.S. in 2006.
    Cancer is the second leading cause of death in the U.S.
    Cancer drug market will likely double to $50 billion in 2010 from 
$25 billion in 2006.
    Development Status: The technology is currently in the pre-clinical 
stage of development.
    Inventors: Yves Pommier (NCI) et al.
    Relevant Publication: S Antony et al. Novel high-throughput 
electrochemiluminescent assay for identification of human tyrosyl-DNA 
phosphodiesterase (Tdp1) inhibitors and characterization for furamidine 
(NSC 305831) as an inhibitor of Tdp1. Nucleic Acid Res. 
2007;35(13):4474-4484.
    Patent Status: U.S. Provisional Application No. 61,040,203 filed 28 
Mar 2008 (HHS Ref. No. E-121-2008/0-US-01).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Adaku Nwachukwu, J.D.; 301-435-5560; 
[email protected].

Method of Inhibiting ABCG2 and Related Treatments

    Description of Technology: The technology is directed to a method 
of inhibiting ABCG2, which is a multidrug resistance (MDR) protein. It 
is believed that ABCG2 plays a role in the development of resistance of 
cancer cells to chemotherapeutics. Therefore, inhibition of ABCG2 would 
allow chemotherapeutics to be more effective in killing cancer cells, 
thereby treating cancer. Five compounds were identified in the 
provisional application that inhibit ABCG2. These compounds are known 
in the literature and are part of the NCI Developmental Therapeutics 
Program (DTP).
    Applications: Cancer therapeutics; Research tools to study function 
of ABCG2 proteins.
    Advantages: Valuable tools to further developing understanding or 
normal and cancer cells; Augment efficacy of drugs that are ABCG2 
substrates.
    Development Status: Early stage.
    Market: Cancer is the second leading cause of death in America, 
after heart disease. Multiple drug resistance is a significant 
impediment in the treatment of cancers resulting in a poor prognosis. 
The market for effective cancer treatments is very large.
    Inventors: Curtis J. Henrich (SAIC/NCI), Heidi R. Bokesch (SAIC/
NCI), Susan E. Bates (NCI), Robert W. Robey (NCI), Suneet Shukla (NCI), 
Suresh V. Ambudkar (NCI), Michael C. Dean (NCI), and James B. McMahon 
(NCI).
    Patent Status: U.S. Provisional Application No. 60/986,155 filed 07 
Nov 2007 (HHS Reference No. E-316-2007/0-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: John Stansberry, Ph.D.; 301-435-5236; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
Molecular Targets Development Program is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize Method of 
Inhibiting ABCG2 and Related Treatments. Please contact John D. Hewes, 
Ph.D. at 301-435-3121 or [email protected] for more information.

Method of Inducing Memory B Cell Development and Terminal 
Differentiation

    Description of Technology: Cytokines exert their respective 
biochemical and physiological effects by binding to specific receptor 
molecules, which then stimulate signal transduction pathways. 
Interleukin-21 (IL-21) is a type I cytokine whose receptor is expressed 
on T, B, and NK cells.
    This invention specifically relates to the use of IL-21 to induce 
differentiation of immature B cells into memory B cells and plasma 
cells. This invention includes claims of methods for inducing 
differentiation of a B cell progenitor into memory B cells and/or 
plasma cells. It also includes claims for enhancing an immune response, 
treating subjects that lack memory B cells and plasma cells and methods 
for increasing or decreasing the number of B cells. This invention 
could conceivably be used in treating or preventing inflammatory 
disorders, autoimmune diseases, allergies, transplant rejection, 
cancer, and other immune system disorders.
    Inventors: Peter E. Lipsky (NIAMS) et al.
    Patent Status: U.S. Patent Application No. 11/197,221 filed 03 Aug 
2005, allowed (HHS Reference No. E-120-2003/2-US-01).
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].

The Use of an Inducible Plasmid Vector Encoding for Active TGF-[beta] 
for the Treatment of Autoimmune Diseases

    Description of Technology: This application describes a composition 
and method for treating inflammatory bowel disease or other autoimmune 
diseases.

[[Page 29523]]

The composition utilizes a vector which contains a first promoter which 
controls the expression of a regulatory transcription factor and a 
second inducible promoter which controls the expression of the gene of 
interest. The preferred gene of interest encodes an isoform of TGF-
[beta] such as TGF-[beta]1 or TGF-[beta]3. The isoform of TGF-[beta] 
does not have to be hTGF-[beta] and can be a latent or active isoform 
of TGF-[beta]. The preferred inducible promoter is TRE-CMV which can be 
induced using doxycycline. The usefulness of the composition for 
treating autoimmune diseases is demonstrated in the application in a 
murine model of inflammatory bowel disease in which intestinal 
inflammation was abrogated by the administration of a plasmid vector 
encoding active TGF-[beta]. The composition may be administered by a 
variety of delivery systems and intranasal delivery is exemplified.
    Inventors: Warren Strober et al. (NIAID).
    Patent Status: U.S. Patent Application No. 10/258,109 filed 30 Jun 
2003 (HHS Reference No. E-096-2000/0-US-03).
    Licensing Contact: Jennifer Wong; 301-435-4633; 
[email protected].

Inhibition of Cell Motility, Angiogenesis and Metastasis

    Description of Technology: The present invention relates to potent, 
highly selective antagonists of Grb2 Src homology-2 (SH2) domain 
binding. Grb2, through its SH2 domain, mediates growth factor driven 
cell motility in vitro and angiogenesis in vivo. These synthetic, small 
molecule antagonists have been shown to block cell motility stimulated 
by hepatocyte growth factor (HGF), fibroblast growth factor (FGF), 
epidermal growth factor (EGF), and vascular endothelial cell growth 
factor (VEGF). They also potently inhibit HGF- and VEGF-stimulated 
morphogenesis and angiogenesis, respectively, in several model systems. 
HGF stimulates mitogenesis, motogenesis and morphogenesis in a wide 
range of cellular targets during development and adulthood, and its 
signaling pathway is frequently over-activated in human cancers, 
including colon, gastric, breast, lung, thyroid and renal carcinomas, 
melanoma, several sarcomas as well as glioblastoma. The ability of HGF 
to initiate a program of cell dissociation and increased cell motility 
coupled with increased protease production promotes aggressive cellular 
invasion and is frequently linked to tumor metastasis.
    Metastasis, the primary cause of death in most forms of cancer, is 
a multistep process whereby cells from the primary tumor spread 
systemically and colonize distant new sites. Blocking critical steps in 
this process could potentially inhibit tumor metastasis and 
dramatically improve cancer survival rates. The small, synthetic Grb2 
SH2 domain antagonists described in this invention have been shown to 
inhibit the induced and spontaneous metastasis of melanoma- and 
prostate cancer-derived tumor cells in mice. These results establish a 
critical role for Grb2 SH2 domain-mediated interactions in the 
metastatic process and support the potential efficacy of this class of 
compound in reducing the metastatic spread of primary solid tumors in 
humans.
    Applications and Modality: Inhibition of cell motility-dependent 
processes, including angiogenesis and metastasis, in several types of 
cancer such as prostate, colon, gastric, breast, lung, thyroid and 
renal carcinomas, melanoma and various sarcomas.
    Market:
    An estimated 1,444,920 new cancer cases were diagnosed in the U.S. 
in 2007.
    600,000 deaths caused by cancer in the U.S. in 2006.
    Cancer is the second leading cause of death in the U.S.
    The cancer drug market will likely double to $50 billion in 2010 
from $25 billion in 2006.
    Development Status: In vivo and in vitro studies have been 
conducted on this technology.
    Inventors: Donald P. Bottaro et al. (NCI);
    Relevant Publications:
    1. Atabey N, Breckenridge D, Yao Z-J, Gao Y, Soon L, Soriano JV, 
Burke TR, Bottaro DP. Potent blockade of Hepatocyte Growth Factor-
stimulated cell motility, invasion, and tubulogenesis by antagonists of 
Grb2-c-Met interaction. J Biol Chem. 2001 Apr 27;276(17):14308-14314.
    2. Shi Z-D, Wei C-Q, Wang X, Lee K, Liu H, Zhang M, Vasselli J, 
Bottaro DP, Linehan WM, Yang D, Burke TR Jr. Macrocyclization in the 
design of tetra-tetrapeptide mimetics that display potent inhibition of 
Grb2 SH2 domain binding in whole cell systems. In: Peptide Revolution: 
Genomics, Proteomics Therapeutics. Chorev, M and Sawyer, TK, Eds. 
American Peptide Society, pp 515-517, 2003.
    3. Soriano JV, Lui N, Gao Y, Yao Z-J, Ishibashi T, Underhill C, 
Burke TR Jr, Bottaro DP. Grb2 SH2 domain binding antagonists inhibit 
angiogenesis in vitro and in vivo. Mol Cancer Ther. 2004 
Oct;3(10):1289-1299.
    4. Shi Z-D, Karki RG, Worthy KM, Bindu LK, Dharmawardana PG, 
Nicklaus MC, Bottaro DP, Fisher RJ, Burke TR Jr. Utilization of a 
nitrobenzoxadiazole (NBD) fluorophore in the design of a Grb2 SH2 
domain binding peptide mimetic. Bioorg Med Chem Lett. 2005 Mar 
1;15(5):1385-1388.
    5. Kang S-U, Shi, Z-D, Karki RG, Worthy KM, Bindu LK, Dharmawardana 
PG, Choyke SJ, Bottaro DP, Fisher RJ, Burke TR Jr. Examination of 
phosphoryl-mimicking functionalities within a macrocyclic Grb2 SH2 
domain-binding platform. J Med Chem. 2005 Jun 16;48(12):3945-3948.
    6. Shi Z-D, Peruzzi B, Dharmawardana PG, Leech T, Appella E, Worthy 
KM, Bindu LK, Fisher RJ, Bottaro DP, Burke TR Jr. Synthesis and use of 
C-terminally biotinylated peptidomimetics with high Grb2 SH2 domain-
binding affinity. In: Understanding Biology Using Peptides, Blondelle 
SE (Ed), American Peptide Society, pp 208-209, 2005.
    7. Dharmawardana PG, Peruzzi B, Giubellino A, Bottaro DP. Molecular 
targeting of Grb-2 as an anti-cancer strategy. Anti-Cancer Drugs 2006 
Jan;17(1):13-20.
    8. Liu F, Worthy KM, Bindu L, Giubellino A, Bottaro DP, Fisher RJ, 
Burke TR Jr. Utilization of achiral alkenyl amines for the preparation 
of high affinity Grb2 SH2 domain-binding macrocycles by ring-closing 
metathesis. Org Biomol Chem. 2007 Jan 21;5(2):367-372.
    9. Giubellino A, Gao Y, Lee S, Lee M-J, Vasselli JR, Medepalli S, 
Trepel JB, Burke TR Jr, Bottaro DP. Inhibition of tumor metastasis by a 
Grb-2 SH2 domain binding antagonist. Cancer Res. (Priority Report) 2007 
Jul 1;67(13):6012-6016.
    Patent Status: PCT Patent Application No. PCT/US2007/078494 filed 
14 Nov 2007 (HHS Reference No. E-265-1999/2-PCT-02).
    Licensing Status: Available for exclusive and non-exclusive 
licensing.
    Licensing Contact: Adaku Nwachukwu, J.D.; 301-435-5560; 
[email protected].
    Collaborative Research Opportunity: The Urologic Oncology Branch of 
the National Cancer Institute is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize Grb2 SH2 domain antagonsists as 
anti-cancer drugs. Please contact John D. Hewes, Ph.D. at 301-435-3121 
or [email protected] for more information.


[[Page 29524]]


    Dated: May 15, 2008.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E8-11317 Filed 5-20-08; 8:45 am]
BILLING CODE 4140-01-P