Government-Owned Inventions; Availability for Licensing, 66108-66110 [2010-27177]
Download as PDF
<![CDATA[
66108
Federal Register / Vol. 75, No. 207 / Wednesday, October 27, 2010 / Notices
commercialize this technology. Please
contact John Hewes, Ph.D. at 301–435–
3121 or hewesj@mail.nih.gov for more
information.
Dated: October 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2010–27181 Filed 10–26–10; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
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.
srobinson on DSKHWCL6B1PROD with NOTICES
SUMMARY:
Photosensitizing Antibody-Fluorophore
Conjugate for Photo-Immunotherapy
Description of Invention: A major goal
of targeted cancer therapy is to improve
the sensitivity and specificity of the
therapy so that cancer cells can be
detected and targeted for elimination,
while normal cells in the surrounding
area remain largely intact.
Photodynamic therapy (PDT) is a
treatment for cancer and non-cancerous
lesions involving light and a
photosensitizer. The photosensitizer can
be targeted to a specific cell using
antibodies specific for proteins
expressed on the target cell surface, the
target cells will then be destroyed after
being exposed to light at appropriate
wavelength.
VerDate Mar<15>2010
17:00 Oct 26, 2010
Jkt 223001
The NIH technology describes a
method of photosensitizing cancerous
cells by irradiating an antibody
fluorophore conjugate. The NIH
investigators have conducted in vitro
studies using a proprietary IRDye
700DX NHS Ester. The IR700 dye was
conjugated to a proprietary humanized
anti-HER1 or anti-HER2 or anti-PSMA
antibody, Panitumumab or Trastuzumab
or huJ591. Subsequent irradiation of
non-ionizing near infrared light showed
rapid cell death of tumor cells, while
normal cells were not noticeably killed.
The studies were repeated in mice with
similar results.
Applications and Market:
• Photodynamic therapy for cancer by
selective targeting and killing of cells
without suffering normal tissue side
effects.
• Cancer was responsible for about
13% of all human deaths in 2007. There
remains a need for therapies that
effectively kill the tumor cells while not
harming non-cancerous cells.
Development Status: Both in vitro and
in vivo data available.
Inventors: Hisataka Kobayashi, Peter
L. Choyke, Makoto Mitsunaga (NCI)
Publications: Manuscript in
submission.
Patent Status: U.S. Provisional Patent
Application No. 61/363,079, filed July 9,
2010 (HHS Reference No. E–205–2010/
0–US–01)
Licensing Status: Available for
licensing.
Licensing Contact: Betty B. Tong,
PhD; 301–594–6565;
tongb@mail.nih.gov.
Soluble Glypican-3 Protein for
Treatment of Cancer
Description of Technology:
Hepatocellular carcinoma (HCC) is a
form of liver cancer that is among the
more deadly cancers in the world. HCC
is typically only detected at the later
stages of cancer development, which is
always associated with poor prognosis.
Because HCC is often associated with
liver disease, traditional chemotherapy
is not an option, making surgery the
most common form of treatment. As a
result, there is a need for new
treatments.
Glypican-3 (GPC3) is a cell surface
protein that is normally involved in cell
growth and differentiation. GPC3 has
been shown to act through the Wntsignaling pathway, a pathway that is
often activated in a number of different
cancer cell types. Significantly, the
ability of GPC3 to activate signaling
through Wnt requires that GPC3 be
bound to the cell membrane. GPC3 is
also preferentially expressed on HCC
cells, suggesting it could play a
PO 00000
Frm 00049
Fmt 4703
Sfmt 4703
particularly important role in
tumorigenesis in HCC.
This invention concerns a soluble
form of GPC3 that lacks its cell
membrane anchoring domain. This
soluble form of GPC3 maintains its
ability to interact with the Wnt signaling
pathway, but cannot induce the
activation of the pathway because it is
not bound to the cell membrane. By
competing with fully functional GPC3,
the soluble GPC3 is able to inhibit the
growth of HCC cells, thereby decreasing
the ability of tumors to grow and
metastasize. This suggests that soluble
GPC3 represents a possible therapeutic
for HCC.
Applications:
• Soluble GPC3 represents a potential
therapeutic for patients with cancer
with hyperactivated Wnt-signaling
pathways.
• Specific cancers include
hepatocellular cancer (HCC), melanoma,
thyroid cancer, lung squamous cell
carcinoma, Wilms’ tumor,
neuroblastoma, hepatoblastoma, and
testicular germ-cell tumors.
Advantages:
• Removal of the glycosylphosphatidylinositol (GPI) anchor
results in a soluble form of GPC3 that
can interrupt Wnt-signaling.
• Soluble GPC3 maintains the ability
to compete with fully functional GPC3
despite its inability to activate signaling.
• For treatment of HCC, offers a noninvasive, potentially non-liver toxic
alternative to current strategies.
Development Status: Preclinical stage
of development; cell culture data with
HCC cells
Inventors: Ho (NCI) et al.
For more information, see:
• ‘‘Recombinant soluble glypican 3
protein inhibits the growth of
hepatocellular carcinoma in vitro’’ Feng
et al. Int. J. Cancer: E-pub (8 July 2010).
• ‘‘Soluble Glypican 3 inhibits the
growth of Hepatocellular Carcinoma in
vitro and in vivo’’ Zitterman et al. Int.
J. Cancer: 126, 1291–1301 (2010).
Patent Status: U.S. provisional
applications 61/334,135 (E–176–2010/
0–US–01) and 61/350,722 (E–176–2010/
1–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: David A.
Lambertson, PhD; 301–435–4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute,
Laboratory of 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 Hewes,
E:\FR\FM\27OCN1.SGM
27OCN1
Federal Register / Vol. 75, No. 207 / Wednesday, October 27, 2010 / Notices
PhD, at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
srobinson on DSKHWCL6B1PROD with NOTICES
Drug Combination of DNA
Topoisomerase I (TOP1) Inhibitors and
Extracellular ATP Produces a
Significant Increase in Beneficial AntiCarcinoma Cytotoxicity
Description of Invention: DNA
Topoisomerase inhibitors are a category
of drugs used for cancer therapy. DNA
topoisomerase 1 (TOP1) inhibitors, such
as Camptothecin (CPT) and its
structurally related analogues, bind to
the TOP1 complex and prevent the
religation of the single strand DNA
molecules, ultimately leading to cell
death. CPT and close analogues show
anticancer activity in clinical trials
treating ovarian, small-cell lung, and
colorectal cancers, but also adverse drug
reaction. By reducing the cytotoxic dose
in the thousands of folds, the NIH
scientists are able to target the tumor
and reduce the cytotoxicity to normal
cells. The instant invention discloses
that the drug combination of DNA
topoisomerase 1 (TOP1) inhibitors, such
as the anti-cancer drug Camptothecin
(CPT), and extracellular ATP produces a
significant increase in beneficial anticarcinoma cytotoxicity.
Applications and Market:
• This invention may provide a new
combination of drug with extracellular
ATP to target various cancers for
treatment.
• Cancer is the second leading cause
of death in the U.S. The National Cancer
Institute estimate the overall annual
costs for cancer in the U.S. at $107
billion; development of more effective
therapies with less adverse drug
reaction is always in high demand.
Development Status: Pre-clinical stage
of development.
Inventors: Joseph Riss, Glenn Merlino,
J. Carl Barrett (NCI).
Publications: Manuscript in
preparation.
Patent Status: U.S. Provisional
Application No. 61/350,660 filed 02 Jun
2010 (HHS Reference No. E–098–2010/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Betty B. Tong,
PhD; 301–594–6565;
tongb@mail.nih.gov.
Novel Prognostic and Therapeutic
Biomarker for Cancer and
Inflammatory Diseases
Description of Invention: There
remains a significant unmet need for
diagnostics, prognostics, and
therapeutics for conditions that involve
inflammation and the formation of
VerDate Mar<15>2010
17:00 Oct 26, 2010
Jkt 223001
blood clots such as bleeding disorders,
trauma, and diseases such as sepsis,
cardiovascular disease, stroke, and
cancer. The global market for such
products is varied and competitive, and
is forecast to be over $40 billion by
2010.
Researchers at the National Cancer
Institute (NCI) have identified that
levels of a novel soluble protein
involved in the repair mechanism for
damaged blood vessels correlate with
outcome in sepsis and with the
diagnosis of disseminated intravascular
coagulation, a contributing factor to the
morbidity and mortality associated with
sepsis.
Further, the NCI researchers have
demonstrated that a recombinant
version of this novel protein facilitates
the clotting of blood, suggesting a
potentially significant therapeutic
benefit for the treatment of bleeding
disorders or trauma.
Applications:
• Diagnostic and prognostic
biomarker for diseases that involve
inflammation and blood clot formation
(i.e., sepsis, cardiovascular disease,
stroke, cancer).
• Treatment of bleeding disorders or
trauma.
• Treatment of cerebral bleeding
associated with aneurism or stroke.
• Therapy for patients with low
platelet counts.
• Therapy for women suffering from
preeclampsia or thrombotic episodes.
Advantages:
• High specificity.
• Protein levels correlate with disease
state/outcome.
• Administration of recombinant
protein accelerates the formation of
blood clots.
Development Status: Pre-clinical.
Inventors: Daniel McVicar et al. (NCI).
Relevant Publications:
1. Washington AV et al. TREM-like
transcript-1 protects against
inflammation-associated hemorrhage by
facilitating platelet aggregation in mice
and humans. J Clin Invest. 2009
Jun;119(6):1489–1501. [PubMed:
19436112].
2. Ford JW, McVicar DW. TREM and
TREM-like receptors in inflammation
and disease. Curr Opin Immunol. 2009
Feb;21(1):38–46. [PubMed: 19230638].
Patent Status:
• U.S. Provisional Application No.
61/177,242 filed 11 May 2009 (HHS
Reference No. E–197–2009/0–US–01).
• PCT Application No. PCT/US10/
34263 filed 10 May 2010 (HHS
Reference No. E–197–2009/0–PCT–02).
Licensing Status: Available for
licensing.
PO 00000
Frm 00050
Fmt 4703
Sfmt 4703
66109
Licensing Contact: Patrick P. McCue,
PhD; 301–435–5560;
mccuepat@mail.nih.gov.
Treatment and Prevention of
Inflammatory Bowel Disease (IBD)
Using Mutant and Chimeric IL–13
Molecules
Description of Invention: Ulcerative
colitis (UC) is a chronic inflammatory
disease of the colorectum and affects
approximately 400,000 people in the
United States. The cause of UC is not
known, although an abnormal
immunological response to bacterial
antigens in the gut microflora is thought
to be involved. Present treatments for
UC include anti-inflammatory therapy
using aminosalicylates or
corticosteroids, as well as
immunomodulators and diet. However,
25–40% of ulcerative colitis patients
must eventually have their colons
removed due to massive bleeding,
severe illness, rupture of the colon, risk
of cancer or due to side effects of
corticosteroids and novel treatments are
still actively being sought. NIH
scientists and their collaborators have
used a mouse model of experimental
colitis (oxazolone colitis, OC) to show
that IL–13, a Th2 cytokine, is a
significant pathologic factor in OC and
that neutralizing IL–13 in these animals
effectively prevents colitis.
OC is a colitis induced by intrarectal
administration of a relatively low dose
of the haptenating agent oxazolone
subsequent to skin sensitization with
oxazolone. A highly reproducible and
chronic colonic inflammation is
obtained that is histologically similar to
human ulcerative colitis. Studies show
that Natural Killer T (NKT) cells, rather
than conventional CD4+T cells, mediate
oxazolone colitis and are the source of
IL–13 as well as being activated by CD1expressing intestinal epithelial cells.
Tissue removed from ulcerative colitis
patients were also shown to contain
increased numbers of nonclassical NKT
cells that produce markedly increased
amounts of IL–13 and that in keeping
with epithelial damage being a key
factor in UC, these NKT cells are
cytotoxic for epithelial cells. Building
on their previous work, scientists at
NIAID and FDA have shown that an Il13 chimeric fusion protein linked to an
effector molecule was able to prevent
colitis in a mouse model of ulcerative
colitis.
Available for licensing are methods
for treating or preventing the
inflammatory response of IBD by
inhibiting the binding of IL–13 to IL–13
receptors on NKT cells. Additionally,
these mutant and chimeric Il-13
molecules are able to block the chronic
E:\FR\FM\27OCN1.SGM
27OCN1
srobinson on DSKHWCL6B1PROD with NOTICES
66110
Federal Register / Vol. 75, No. 207 / Wednesday, October 27, 2010 / Notices
inflammatory response that results in
fibrosis as seen in Crohn’s disease.
Preventing the inflammatory response of
colitis by either modulating or blocking
IL–13 and NKT cell activity continues to
be an effective therapeutic approach in
animal models of colitis with
implications for the treatment of human
ulcerative colitis and for the treatment
of fibrosis associated with Crohn’s
disease.
Inventors: Warren Strober (NIAID),
Ivan J. Fuss (NIAID), Peter Mannon
(NIAID), Jan Preiss (NIAID), Raj Puri
(FDA), Koji Kawakami (FDA), Stefan
Fichtner-Feigl (NIAID), Atsushi Kitani
(NIAID).
Related Publications:
1. F Heller, IJ Fuss, EW Nieuwenhuis,
RS Blumberg, W Strober. Oxazolone
colitis, a Th2 colitis model resembling
ulcerative colitis, is mediated by IL–13producing NK–T cells. Immunity 2002
Nov;17(5):629–628. [PubMed:
12433369].
2. IJ Fuss, F Heller, M Boirivant, F
Leon, M Yoshida, S Fichtner-Feigl, Z
Yang, M Exley, A Kitani, RS Blumberg,
P Mannon, W Strober. Nonclassical
CD1d-restricted NK T cells that produce
IL–13 characterize an atypical Th2
response in ulcerative colitis. J Clin
Invest. 2004 May 15;113(10):1490–1497.
[PubMed: 15146247].
Patent Status: U.S. Patent Application
No. 11/918,711 filed 14 Apr 2006 (HHS
Reference No. E–003–2005/0–US–03)
and related international filings.
Related Technologies:
• IL–13 modulators and inhibitors—
U.S. Patent No. 7,666,411 issued 23 Feb
2010 (HHS Reference No. 131–2002/0–
US–02), U.S. Patent Application No. 12/
709,029 filed 19 Feb 2010 (HHS
Reference No. E–131–2002/0–US–10),
and related international filings.
• NF-kappa B decoy
oligonucleotides—U.S. Patent
Application No. 11/920,214 filed 09
Nov 2007 (HHS Reference No. E–108–
2005/0–US–03).
Licensing Status: Available for
licensing.
Licensing Contact: Betty B. Tong,
Ph.D.; 301–594–6565;
tongb@mail.nih.gov.
Dated: October 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2010–27177 Filed 10–26–10; 8:45 am]
BILLING CODE 4140–01–P
VerDate Mar<15>2010
17:00 Oct 26, 2010
Jkt 223001
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Guidelines for Use of Stored
Specimens and Access to Ancillary
Data and Proposed Cost Schedule:
Stored Biologic Specimens and
Ancillary Data From the Collaborative
Perinatal Project (CPP)
Notice and request for
comments.
ACTION:
The Division of
Epidemiology, Statistics and Prevention
Research (hereafter, Division) of the
Eunice Kennedy Shriver National
Institute of Child Health and Human
Development (NICHD) maintains an
extensive repository of datasets from
completed studies, biospecimens, and
ancillary data. The Division intends to
make datasets and biospecimens more
widely available to the research
community for use by qualified
researchers and to establish procedures
for access consistent with the National
Institutes of Health (NIH) Data Sharing
Policy. The Division has established an
internal committee, the Biospecimen
Repository Access and Data Sharing
Committee (BRADSC), to oversee the
repository access and data sharing
program. The purpose of this notice is
to request comments on this program
and present the initial proposed cost
schedule. After full consideration of
comments submitted in response to this
notice, the BRADSC will finalize
proposal guidelines and procedures,
publish the cost schedule to the
Division Web site, and begin to accept
proposals for use of the stored biologic
samples and for access to ancillary data
that may not be available electronically.
The first specimens and ancillary data
that will be made available under this
program are those from the national
Collaborative Perinatal Project (CPP).
The CPP is a large, prospective cohort
study, conducted by the National
Institute of Neurological Diseases and
Stroke (NINDS) of the National
Institutes of Health (NIH), which
recruited and enrolled 48,197 women
who contributed 54,390 pregnancies
that were prospectively followed from
1959–1966 at twelve academic medical
centers across the United States.
Custody for disposition of the CPP
serum specimens was transferred to the
Division from the NINDS in 1993 and
for the microfiche archives in 1999.
However, under the Federal Privacy Act
of 1974 the samples and archive still
belong to NINDS. Since 1992, the
specimens have had limited public
SUMMARY:
PO 00000
Frm 00051
Fmt 4703
Sfmt 4703
availability through Division
investigators. Going forward, the
Biospecimen Repository Access and
Data Sharing Committee (BRADSC) will
oversee the repository access and data
sharing program. Access to other
Division resources will be announced
on the Division Web site. The BRADSC
reserves the right to amend the
procedures and costs schedules as
necessary to maintain the integrity of
the program and to suit the conditions
under which other specimens were
collected. Announcements and current
proposal guidelines will be available
under the Research link at https://
despr.nichd.nih.gov, and interested
researchers should consult the Division
Web site for resources available, the
most recent guidelines for proposal
submission and evaluation, and cost
schedules. Procedures may vary
depending on the age and nature of the
samples and original institutional
review board (IRB) approval, although
the general outline of the procedures
should remain the same. Cost schedules
may vary depending on the nature and
complexity of the request.
No funding is provided as part of this
notice nor will any be available as part
of the program either to support
laboratory analyses or data management.
Samples will only be provided to
approved projects upon receipt of
evidence of necessary IRB approval(s),
funding and payment of repository costs
and shipping. Approved projects that do
not obtain funding will be canceled
within one year of their approval date.
A more complete description of this
program follows. Comments or requests
for clarification on all aspects of the
program are welcome.
DATES:
• Comment Receipt Date: December
15, 2010.
• Invitation to Submit Proposal:
Proposals can be submitted on an
ongoing basis.
• Scientific Review Dates: Technical
Panels for reviews will be assembled
beginning on January 1, May 1, or
September 1 of the calendar year so that
proposals can be evaluated well in
advance of Federal funding deadlines.
• Anticipated Distribution of
Samples: Within one month of
demonstrable proof of applicant IRB
approval and receipt of payment to
cover repository costs and shipping.
ADDRESSES: To send comments and to
request information, contact: Dr. Mary
L. Hediger, Division of Epidemiology,
Statistics and Prevention Research,
Eunice Kennedy Shriver National
Institute of Child Health and Human
Development, 6100 Executive Blvd,
E:\FR\FM\27OCN1.SGM
27OCN1
]]>Agencies
[Federal Register Volume 75, Number 207 (Wednesday, October 27, 2010)]
[Notices]
[Pages 66108-66110]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-27177]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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.
Photosensitizing Antibody-Fluorophore Conjugate for Photo-Immunotherapy
Description of Invention: A major goal of targeted cancer therapy
is to improve the sensitivity and specificity of the therapy so that
cancer cells can be detected and targeted for elimination, while normal
cells in the surrounding area remain largely intact. Photodynamic
therapy (PDT) is a treatment for cancer and non-cancerous lesions
involving light and a photosensitizer. The photosensitizer can be
targeted to a specific cell using antibodies specific for proteins
expressed on the target cell surface, the target cells will then be
destroyed after being exposed to light at appropriate wavelength.
The NIH technology describes a method of photosensitizing cancerous
cells by irradiating an antibody fluorophore conjugate. The NIH
investigators have conducted in vitro studies using a proprietary IRDye
700DX NHS Ester. The IR700 dye was conjugated to a proprietary
humanized anti-HER1 or anti-HER2 or anti-PSMA antibody, Panitumumab or
Trastuzumab or huJ591. Subsequent irradiation of non-ionizing near
infrared light showed rapid cell death of tumor cells, while normal
cells were not noticeably killed. The studies were repeated in mice
with similar results.
Applications and Market:
Photodynamic therapy for cancer by selective targeting and
killing of cells without suffering normal tissue side effects.
Cancer was responsible for about 13% of all human deaths
in 2007. There remains a need for therapies that effectively kill the
tumor cells while not harming non-cancerous cells.
Development Status: Both in vitro and in vivo data available.
Inventors: Hisataka Kobayashi, Peter L. Choyke, Makoto Mitsunaga
(NCI)
Publications: Manuscript in submission.
Patent Status: U.S. Provisional Patent Application No. 61/363,079,
filed July 9, 2010 (HHS Reference No. E-205-2010/0-US-01)
Licensing Status: Available for licensing.
Licensing Contact: Betty B. Tong, PhD; 301-594-6565;
tongb@mail.nih.gov.
Soluble Glypican-3 Protein for Treatment of Cancer
Description of Technology: Hepatocellular carcinoma (HCC) is a form
of liver cancer that is among the more deadly cancers in the world. HCC
is typically only detected at the later stages of cancer development,
which is always associated with poor prognosis. Because HCC is often
associated with liver disease, traditional chemotherapy is not an
option, making surgery the most common form of treatment. As a result,
there is a need for new treatments.
Glypican-3 (GPC3) is a cell surface protein that is normally
involved in cell growth and differentiation. GPC3 has been shown to act
through the Wnt-signaling pathway, a pathway that is often activated in
a number of different cancer cell types. Significantly, the ability of
GPC3 to activate signaling through Wnt requires that GPC3 be bound to
the cell membrane. GPC3 is also preferentially expressed on HCC cells,
suggesting it could play a particularly important role in tumorigenesis
in HCC.
This invention concerns a soluble form of GPC3 that lacks its cell
membrane anchoring domain. This soluble form of GPC3 maintains its
ability to interact with the Wnt signaling pathway, but cannot induce
the activation of the pathway because it is not bound to the cell
membrane. By competing with fully functional GPC3, the soluble GPC3 is
able to inhibit the growth of HCC cells, thereby decreasing the ability
of tumors to grow and metastasize. This suggests that soluble GPC3
represents a possible therapeutic for HCC.
Applications:
Soluble GPC3 represents a potential therapeutic for
patients with cancer with hyperactivated Wnt-signaling pathways.
Specific cancers include hepatocellular cancer (HCC),
melanoma, thyroid cancer, lung squamous cell carcinoma, Wilms' tumor,
neuroblastoma, hepatoblastoma, and testicular germ-cell tumors.
Advantages:
Removal of the glycosyl-phosphatidylinositol (GPI) anchor
results in a soluble form of GPC3 that can interrupt Wnt-signaling.
Soluble GPC3 maintains the ability to compete with fully
functional GPC3 despite its inability to activate signaling.
For treatment of HCC, offers a non-invasive, potentially
non-liver toxic alternative to current strategies.
Development Status: Preclinical stage of development; cell culture
data with HCC cells
Inventors: Ho (NCI) et al.
For more information, see:
``Recombinant soluble glypican 3 protein inhibits the
growth of hepatocellular carcinoma in vitro'' Feng et al. Int. J.
Cancer: E-pub (8 July 2010).
``Soluble Glypican 3 inhibits the growth of Hepatocellular
Carcinoma in vitro and in vivo'' Zitterman et al. Int. J. Cancer: 126,
1291-1301 (2010).
Patent Status: U.S. provisional applications 61/334,135 (E-176-
2010/0-US-01) and 61/350,722 (E-176-2010/1-US-01).
Licensing Status: Available for licensing.
Licensing Contact: David A. Lambertson, PhD; 301-435-4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute,
Laboratory of 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 Hewes,
[[Page 66109]]
PhD, at 301-435-3121 or hewesj@mail.nih.gov for more information.
Drug Combination of DNA Topoisomerase I (TOP1) Inhibitors and
Extracellular ATP Produces a Significant Increase in Beneficial Anti-
Carcinoma Cytotoxicity
Description of Invention: DNA Topoisomerase inhibitors are a
category of drugs used for cancer therapy. DNA topoisomerase 1 (TOP1)
inhibitors, such as Camptothecin (CPT) and its structurally related
analogues, bind to the TOP1 complex and prevent the religation of the
single strand DNA molecules, ultimately leading to cell death. CPT and
close analogues show anticancer activity in clinical trials treating
ovarian, small-cell lung, and colorectal cancers, but also adverse drug
reaction. By reducing the cytotoxic dose in the thousands of folds, the
NIH scientists are able to target the tumor and reduce the cytotoxicity
to normal cells. The instant invention discloses that the drug
combination of DNA topoisomerase 1 (TOP1) inhibitors, such as the anti-
cancer drug Camptothecin (CPT), and extracellular ATP produces a
significant increase in beneficial anti-carcinoma cytotoxicity.
Applications and Market:
This invention may provide a new combination of drug with
extracellular ATP to target various cancers for treatment.
Cancer is the second leading cause of death in the U.S.
The National Cancer Institute estimate the overall annual costs for
cancer in the U.S. at $107 billion; development of more effective
therapies with less adverse drug reaction is always in high demand.
Development Status: Pre-clinical stage of development.
Inventors: Joseph Riss, Glenn Merlino, J. Carl Barrett (NCI).
Publications: Manuscript in preparation.
Patent Status: U.S. Provisional Application No. 61/350,660 filed 02
Jun 2010 (HHS Reference No. E-098-2010/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Betty B. Tong, PhD; 301-594-6565;
tongb@mail.nih.gov.
Novel Prognostic and Therapeutic Biomarker for Cancer and Inflammatory
Diseases
Description of Invention: There remains a significant unmet need
for diagnostics, prognostics, and therapeutics for conditions that
involve inflammation and the formation of blood clots such as bleeding
disorders, trauma, and diseases such as sepsis, cardiovascular disease,
stroke, and cancer. The global market for such products is varied and
competitive, and is forecast to be over $40 billion by 2010.
Researchers at the National Cancer Institute (NCI) have identified
that levels of a novel soluble protein involved in the repair mechanism
for damaged blood vessels correlate with outcome in sepsis and with the
diagnosis of disseminated intravascular coagulation, a contributing
factor to the morbidity and mortality associated with sepsis.
Further, the NCI researchers have demonstrated that a recombinant
version of this novel protein facilitates the clotting of blood,
suggesting a potentially significant therapeutic benefit for the
treatment of bleeding disorders or trauma.
Applications:
Diagnostic and prognostic biomarker for diseases that
involve inflammation and blood clot formation (i.e., sepsis,
cardiovascular disease, stroke, cancer).
Treatment of bleeding disorders or trauma.
Treatment of cerebral bleeding associated with aneurism or
stroke.
Therapy for patients with low platelet counts.
Therapy for women suffering from preeclampsia or
thrombotic episodes.
Advantages:
High specificity.
Protein levels correlate with disease state/outcome.
Administration of recombinant protein accelerates the
formation of blood clots.
Development Status: Pre-clinical.
Inventors: Daniel McVicar et al. (NCI).
Relevant Publications:
1. Washington AV et al. TREM-like transcript-1 protects against
inflammation-associated hemorrhage by facilitating platelet aggregation
in mice and humans. J Clin Invest. 2009 Jun;119(6):1489-1501. [PubMed:
19436112].
2. Ford JW, McVicar DW. TREM and TREM-like receptors in
inflammation and disease. Curr Opin Immunol. 2009 Feb;21(1):38-46.
[PubMed: 19230638].
Patent Status:
U.S. Provisional Application No. 61/177,242 filed 11 May
2009 (HHS Reference No. E-197-2009/0-US-01).
PCT Application No. PCT/US10/34263 filed 10 May 2010 (HHS
Reference No. E-197-2009/0-PCT-02).
Licensing Status: Available for licensing.
Licensing Contact: Patrick P. McCue, PhD; 301-435-5560;
mccuepat@mail.nih.gov.
Treatment and Prevention of Inflammatory Bowel Disease (IBD) Using
Mutant and Chimeric IL-13 Molecules
Description of Invention: Ulcerative colitis (UC) is a chronic
inflammatory disease of the colorectum and affects approximately
400,000 people in the United States. The cause of UC is not known,
although an abnormal immunological response to bacterial antigens in
the gut microflora is thought to be involved. Present treatments for UC
include anti-inflammatory therapy using aminosalicylates or
corticosteroids, as well as immunomodulators and diet. However, 25-40%
of ulcerative colitis patients must eventually have their colons
removed due to massive bleeding, severe illness, rupture of the colon,
risk of cancer or due to side effects of corticosteroids and novel
treatments are still actively being sought. NIH scientists and their
collaborators have used a mouse model of experimental colitis
(oxazolone colitis, OC) to show that IL-13, a Th2 cytokine, is a
significant pathologic factor in OC and that neutralizing IL-13 in
these animals effectively prevents colitis.
OC is a colitis induced by intrarectal administration of a
relatively low dose of the haptenating agent oxazolone subsequent to
skin sensitization with oxazolone. A highly reproducible and chronic
colonic inflammation is obtained that is histologically similar to
human ulcerative colitis. Studies show that Natural Killer T (NKT)
cells, rather than conventional CD4+T cells, mediate oxazolone colitis
and are the source of IL-13 as well as being activated by CD1-
expressing intestinal epithelial cells. Tissue removed from ulcerative
colitis patients were also shown to contain increased numbers of
nonclassical NKT cells that produce markedly increased amounts of IL-13
and that in keeping with epithelial damage being a key factor in UC,
these NKT cells are cytotoxic for epithelial cells. Building on their
previous work, scientists at NIAID and FDA have shown that an Il-13
chimeric fusion protein linked to an effector molecule was able to
prevent colitis in a mouse model of ulcerative colitis.
Available for licensing are methods for treating or preventing the
inflammatory response of IBD by inhibiting the binding of IL-13 to IL-
13 receptors on NKT cells. Additionally, these mutant and chimeric Il-
13 molecules are able to block the chronic
[[Page 66110]]
inflammatory response that results in fibrosis as seen in Crohn's
disease. Preventing the inflammatory response of colitis by either
modulating or blocking IL-13 and NKT cell activity continues to be an
effective therapeutic approach in animal models of colitis with
implications for the treatment of human ulcerative colitis and for the
treatment of fibrosis associated with Crohn's disease.
Inventors: Warren Strober (NIAID), Ivan J. Fuss (NIAID), Peter
Mannon (NIAID), Jan Preiss (NIAID), Raj Puri (FDA), Koji Kawakami
(FDA), Stefan Fichtner-Feigl (NIAID), Atsushi Kitani (NIAID).
Related Publications:
1. F Heller, IJ Fuss, EW Nieuwenhuis, RS Blumberg, W Strober.
Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis,
is mediated by IL-13-producing NK-T cells. Immunity 2002 Nov;17(5):629-
628. [PubMed: 12433369].
2. IJ Fuss, F Heller, M Boirivant, F Leon, M Yoshida, S Fichtner-
Feigl, Z Yang, M Exley, A Kitani, RS Blumberg, P Mannon, W Strober.
Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize
an atypical Th2 response in ulcerative colitis. J Clin Invest. 2004 May
15;113(10):1490-1497. [PubMed: 15146247].
Patent Status: U.S. Patent Application No. 11/918,711 filed 14 Apr
2006 (HHS Reference No. E-003-2005/0-US-03) and related international
filings.
Related Technologies:
IL-13 modulators and inhibitors--U.S. Patent No. 7,666,411
issued 23 Feb 2010 (HHS Reference No. 131-2002/0-US-02), U.S. Patent
Application No. 12/709,029 filed 19 Feb 2010 (HHS Reference No. E-131-
2002/0-US-10), and related international filings.
NF-kappa B decoy oligonucleotides--U.S. Patent Application
No. 11/920,214 filed 09 Nov 2007 (HHS Reference No. E-108-2005/0-US-
03).
Licensing Status: Available for licensing.
Licensing Contact: Betty B. Tong, Ph.D.; 301-594-6565;
tongb@mail.nih.gov.
Dated: October 21, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-27177 Filed 10-26-10; 8:45 am]
BILLING CODE 4140-01-P
