[Federal Register Volume 75, Number 177 (Tuesday, September 14, 2010)]
[Notices]
[Pages 55799-55801]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-22834]
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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.
Assay for Arf GTP-Binding Proteins
Description of Invention: The worldwide laboratory research
reagents market is expected to surpass $13 billion in 2010, and the
field of biotechnology appears key to maintaining the market's growth.
Antibodies are becoming increasingly significant, especially for
targeting the diseased cells and cell compounds.
Researchers at the National Cancer Institute (NCI), NIH, have
developed an antibody-based assay that measures levels of Arf GTP-
binding proteins, some of which have been linked to the invasive
behavior of cancer cells. The assay is robust, can be performed both on
cell lysates and fixed cells, and can distinguish among specific
endogenous Arf-GTP isoforms.
Applications:
Research on Arf function in physiology and cancer.
Research on cancer invasion.
Research on membrane traffic and actin reorganization.
Advantages:
Ability to distinguish between the specific isoforms
(i.e., Arf1, Arf3, Arf4, Arf5, and Arf6).
Antibodies bind preferentially to the GTP-bound form of
Arf.
Inventor: Paul A. Randazzo (NCI).
Relevant Publications:
1. Spang A et al. Arf GAPs: gatekeepers of vesicle generation. FEBS
Lett. 2010 Jun 18;584(12):2646-2651. [PubMed: 20394747].
2. Campa F and Randazzo PA. Arf GTPase-activating proteins and
their potential role in cell migration and invasion. Cell Adh Migr.
2008 Oct; 2(4):258-262. [PubMed: 19262159].
Patent Status: HHS Reference No. E-198-2010/0--Research Material.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing.
Licensing Contact: Patrick P. McCue, PhD, (301) 435-5560;
[email protected].
Collaborative Research Opportunity: The Center for Cancer Research,
Laboratory of Cellular and Molecular Biology, 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, PhD at 301-435-3121 or
[email protected] for more information.
Sequences Encoding Two Novel Human Polyomaviruses
Description of Invention: Researchers at the National Cancer
Institute, NIH, have discovered two species of a previously unknown
polyomavirus genus.
Polyomaviruses are a diverse group of DNA-based viruses that infect
humans and various animals. At least one human polyomavirus, the Merkel
cell polyomavirus (MCV), plays a causal role in the development of an
unusual form of skin cancer called Merkel cell carcinoma. The coat
proteins of polyomaviruses can spontaneously assemble into virus-like
particles (VLPs) similar to those that have been used in the recent
vaccines against human papillomaviruses (HPVs).
Applications:
Development of clinical diagnostic assays to detect
linkages between the new polyomaviruses and human cancers.
Development of a VLP-based prophylactic vaccine similar to
the HPV vaccine.
Advantages: DNA sequences have broad applications in the studies of
polyomavirus infection mechanisms and carcinogenesis. Notably, they
are:
Identification and purification of the normal and mutated
polyomaviral proteins.
Studies of antisense oligonucleotides in polyomavirus
biology.
Development of polyclonal and monoclonal antibodies
against polyomaviruses.
Development Status: Pre-clinical.
Inventors: Christopher B. Buck and Diana V. Pastrana (NCI).
Relevant Publication: Schowalter RM et al. Merkel cell polyomavirus
and two previously unknown polyomaviruses are chronically shed from
human skin. Cell Host Microbe Jun 25;7(6):509-515. [PubMed: 20542254].
Patent Status: U.S. Provisional Application No. 61/318,080 filed 26
Mar 2010 (HHS Reference No. E-051-2010/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Patrick P. McCue, PhD; 301-435-5560;
[email protected].
Fenoterol and Fenoterol Analogues for Treatment of Glioma,
Glioblastoma, and Astrocytoma
Description of Invention: To date there is no effective treatment
for the brain tumors or brain cancers indentified as gliomas,
glioblastomas, or astrocytomas.
This technology relates to the discovery that fenoterol and related
analogues block astrocytoma and glioblastoma cell division at low
doses. In a xenograft model utilizing the 1321N1 astrocytoma tumor
implanted in the flank of SKID mice, the (R,R)-4-methoxyfenoterol
analogue significantly decreased tumor growth relative to a control
group receiving vehicle and studies utilizing [\3\H]-(R,R)-4-
methoxyfenoterol have shown that the compound readily passes the blood-
brain barrier. The anti-tumor effect is associated with the ability of
fenoterol and related analogues to induce production of cyclic
adenosine monophosphate (cAMP), which is normally decreased in
glioblastomas and astrocytomas. Induced cAMP production inhibits brain
tumor growth in vivo. Fenoterol and related analogues are beta-2
adrenergic receptor ([beta]2 AR) agonists and the anti-tumor effect is
associated with the expression of this receptor. Since there is a
heterogeneous expression of [beta]2 AR in human brain tumors, patients
who will respond to fenoterol therapy can be predetermined leading to
individualized treatment. In addition to use in the initial treatment
of brain tumors, the systemic and CNS bioavailability of the drug after
oral
[[Page 55800]]
administration and the minimal systemic toxicity suggest that fenoterol
and it analogs can be used in the adjuvant treatment of patients with
[beta]2 AR-positive gliomas, glioblastomas or astrocytomas. Studies
with a number of fenoterol analogs and CNS-implanted tumors are in
progress.
The fenoterol analogues discussed in this technology are subject to
HHS Ref. No. E-205-2006/3 (U.S. Patent Application No. 12/376,945 and
PCT Publication No. WO/2008/022038).
Applications: Therapeutic in the front line and adjuvant treatment
of glioma, glioblastoma and astrocytoma.
Advantages: Potential first-in-class therapeutic for multiple types
of brain tumors.
Development Status: In vivo: tumor models in SKID mice. In vitro:
cell-based assays using human glioblastoma and astrocytoma cell lines.
Further in vivo studies in animal models are underway.
Market: Approximately 17,000 Americans are diagnosed with gliomas
annually (http://www.mayoclinic.org/glioma/).
Inventors: Irving W. Wainer (NIA), et al.
Publication: Submitted.
Patent Status: U.S. Provisional Application No. 61/312,642 filed 10
Mar 2010 (HHS Reference No. E-013- 2010/0).
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, Laboratory of Clinical Investigation, is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize the use of
fenoterol and fenoterol analogs in the front line and adjuvant
treatment of CNS tumors and other [beta]2 AR expressing tumors. Please
contact Nicole Darack, PhD at 301-435-3101 or [email protected] for
more information.
Chemical Attraction: Cell Lines Expressing the CXCR1 or CXCR2 Chemokine
Receptors
Description of Invention: Chemoattractant receptors have been
identified as important factors in regulating many innate and adaptive
immune responses. Modulation of these receptors have implications for
shifting immune responses to create either a dampening effect in
fighting inflammatory diseases, such as autoimmune diseases or
cardiovascular diseases, or a boosting effect to generate more
effective responses to infectious agents, tumors, and promote wound
healing. Chemokine receptors are expressed on a variety of tumor cells
and play a role in helping cancer cells sense new microenvironments for
metastatic growth.
Scientists at the National Institutes of Health (NIH) have
developed human embryonic kidney (HEK) 293 cell lines that express the
CXCR1 chemokine receptor or the CXCR2 chemokine receptor. These two
receptors are also known as the IL-8 receptor-alpha and IL-8 receptor-
beta, respectively. They both effectively bind IL-8, a potent
neutrophil chemoattractant, as well as other chemokines with varying
affinities. The collection of cell lines produced by these scientists
includes HEK 293 cells that express the wild-type CXCR1, wild-type
CXCR2, or mutant variants of each receptor. The cell lines were created
by stably transfecting vectors containing the cDNA for each receptor
into HEK 293 cells. HEK 293 cells transfected with the wild-type CXCR1
or CXCR2 display strong chemoattractant properties when placed in the
presence of their corresponding CXC family chemokines, such as IL-8.
Application:
Research tools for testing the activity of potential drugs
and chemokine analogs in their ability to block cellular responses
triggered by CXC chemokines, such as inflammatory responses induced by
IL-8
Cell lines expressing the wild-type CXCR1 or CXCR2 can
serve as positive controls in chemokine receptor studies designed to
identify novel chemoattractants or agents that inhibit chemokinetic
functions.
Research tool for screening compounds that block these
receptors as a possible anti-cancer agent to inhibit angiogenesis and
metastasis
Advantages:
Both wild-type and mutant cell lines available: Wild-type
CXCR1/CXCR2 receptors or mutant receptors with point and deletion
mutations have been cloned into HEK 293 cells. These cell lines will
have varying degrees of potency for their chemoattractant responses to
provide a range of functional comparisons in chemokine studies.
Experimental verification of response to CXC family
chemokines: The scientists have compiled years of data over various
publications indicating that these receptors respond appropriately to a
profile of chemokines.
Inventors: Joost Oppenheim, Adit Ben-Baruch, Ji Ming Wang, David
Kelvin (all NCI).
Publications:
1. E Cohen-Hillel, et al. Cell migration to the chemokine CXCL8:
paxillin is activated and regulates adhesion and cell motility. Cell
Mol Life Sci. 2009 Mar;66(5):884-899. [PubMed: 19151925].
2. H Attal, et al. Intracellular cross-talk between the GPCR CXCR1
and CXCR2: role of carboxyl terminus phosphorylation sites. Exp Cell
Res. 2008 Jan 15;314(2):352-365. [PubMed: 17996233].
3. A Ben-Baruch, et al. The differential ability of IL-8 and
neutrophil-activating peptide-2 to induce attenuation of chemotaxis is
mediated by their divergent capabilities to phosphorylate CXCR2 (IL-8
receptor B). J Immunol. 1997 Jun 15;158(12):5927-5933. [PubMed:
9190946].
4. A Ben-Baruch, et al. IL-8 and NAP-2 differ in their capacities
to bind and chemoattract 293 cells transfected with either IL-8
receptor type A or type B. Cytokine 1997 Jan;9(1):37-45. [PubMed:
9067094].
5. A Ben-Baruch, et al. Interleukin-8 receptor beta. The role of
the carboxyl terminus in signal transduction. J Biol Chem. 1995 Apr
21;270(16):9121-9128. [PubMed: 7721826].
Patent Status: HHS Reference No. E-221-2009/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a Biological
Materials License Agreement.
Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282;
[email protected].
DLC-1 Gene Deleted in Cancers
Description of Invention: Chromosomal regions that are frequently
deleted in cancer cells are thought to be the loci of tumor suppressor
genes, which restrict cell proliferation. Recurrent deletions on the
short arm of human chromosome 8 in liver, breast, lung and prostate
cancers have raised the possibility of the presence of tumor suppressor
genes in this location.
The inventors have discovered the deletion of human DLC-1 gene in
hepatocellular cancer (HCC) cells. They have performed in vitro
experiments demonstrating the deletion in over 40% of human primary HCC
and in 90% of HCC cell lines. The DLC-1 gene is located on human
chromosome 8p21.3-22, a region frequently deleted in many types of
human cancer. DLC-1 mRNA is
[[Page 55801]]
expressed in all normal tissues tested, but it has either no or low
expression in a high percentage of several types of human cancer, such
as liver, breast, lung, and prostate cancers. Through in vitro and in
vivo tumor suppression experiments, the inventors further demonstrated
that DLC-1 acts as a new tumor suppressor gene for different types of
human cancer.
Applications:
Method to diagnose HCC.
Method to treat HCC patients with DLC-1 compositions.
Transgenic model to study HCC and other types of human
cancer.
DLC-1 compositions.
Market:
Primary liver cancer accounts for about 2% of cancers in
the U.S., but up to half of all cancers in some undeveloped countries.
251,000 new cases are reported annually.
Post-operative five year survival rate of HCC patients is
30-40%.
Development Status: The technology is currently in the pre-clinical
stage of development.
Inventors: Bao-Zhu Yuan, Snorri S. Thorgeirsson, Nicholas Popescu
(NCI).
Publications:
1. BZ Yuan et al. DLC-1 operates as a tumor suppressor gene in
human non-small cell lung carcinomas. Oncogene. 2004 Feb 19;23(7):1405-
1411. [PubMed: 14661059].
2. BZ Yuan et al. DLC-1 gene inhibits human breast cancer cell
growth and in vitro tumorigenicity. Oncogene. 2003 Jan 23;22(3):445-
450. [PubMed: 12545165].
3. BZ Yuan et al. Promoter hypermethylation of DLC-1, a candidate
tumor suppressor gene, in several common human cancers. Cancer Genet
Cytogenet. 2003 Jan 15;140(2):113-117. [PubMed: 12645648].
4. BZ Yuan et al. Cloning, characterization, and chromosomal
localization of a gene frequently deleted in human liver cancer (DLC-1)
homologous to rat RhoGAP. Cancer Res. 1998 May 15;58(10):2196-2199.
[PubMed: 9605766].
Patent Status:
U.S. Patent No. 6,897,018 issued 24 May 2005 (HHS
Reference No. E-042-1998/0-US-03).
U.S. Patent No. 7,534,565 issued 19 May 2009 (HHS
Reference No. E-042-1998/0-US-05).
Licensing Status: Available for licensing.
Licensing Contact: Jennifer Wong; 301-435-4633;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute,
Laboratory of Experimental Carcinogenesis, is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize diagnostics
based on tumor suppressor genes. Please contact John D. Hewes, PhD, at
301-435-3121 or [email protected] for more information.
Dated: September 7, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-22834 Filed 9-13-10; 8:45 am]
BILLING CODE 4140-01-P