Government-Owned Inventions; Availability for Licensing, 36551-36553 [2011-15492]
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Federal Register / Vol. 76, No. 120 / Wednesday, June 22, 2011 / Notices
expression is significantly increased in
the brain of PD patients, while
expression of miR–205 is specifically
down-regulated in the same patients.
Also, the NIH inventors have discovered
that the expression levels of LRRK2 and
miR–205 are dynamically regulated and
reversely correlated in multiple brain
regions and at different ages in mouse
brains, indicating that miR–205 plays a
regulatory role in LRRK2 protein
expression.
Based on these novel findings, the
present technology provides for novel
methods of treatment of patients
suffering from PD disease by modulating
the amount of miR–205 in patients by
administration of a miR–205 gene
product, a vector encoding a miR–205
gene product or an agent that increases
expression of miR–205. The present
technology also provides for methods of
determining the effectiveness of
different candidate drugs for the
treatment of PD, methods of diagnosing
PD, or having an increased
susceptibility to developing PD, and an
in vitro process for identifying a
therapeutic agent for the treatment of
PD.
Applications: Therapeutics and
diagnostics for PD.
Development Status: Early-stage.
Inventors: Huaibin Cai and Hyun J.
Cho (NIA).
Patent Status: U.S. Provisional
Application No. 61/430,626 filed 07 Jan
2011 (HHS Reference No. E–209–2010/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Suryanarayana
Vepa, PhD, J.D.; 301–435–5020;
vepas@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute on Aging,
Transgenics Section, is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize microRNA–205 or other
reagents for the treatment and diagnosis
of Parkinson Disease. Please contact
Nicole Guyton, PhD at 301–435–3101 or
darackn@mail.nih.gov for more
information.
Dated: June 14, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–15467 Filed 6–21–11; 8:45 am]
BILLING CODE 4140–01–P
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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.
SUMMARY:
Monoclonal Antibodies to Glypican-3
Protein and Heparin Sulfate for
Treatment of Cancer
Description of Technology:
Hepatocellular carcinoma (HCC) is the
most common form of liver cancer, and
is among the more deadly cancers in the
world due to its late detection and poor
prognosis. HCC is often associated with
liver disease, curtailing traditional
chemotherapy as a treatment option.
While surgical resection offers the best
method for long term treatment of the
disease, only a small portion of HCC
patients are eligible for this procedure.
As a result, there is a need for new
treatments that can be successfully
applied to a large population of HCC
patients.
Glypican-3 (GPC3) is a cell surface
protein that is preferentially expressed
on HCC cells. Evidence has
demonstrated that a soluble form of
GPC3 that is incapable of cell signaling
has the ability to inhibit the growth of
HCC cells. This suggested that blocking
GPC3 signaling could serve as a
therapeutic approach for treating HCC.
This invention concerns monoclonal
antibodies against GPC3 and their use,
either by themselves or as the targeting
domain for an immunotoxin, for the
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treatment of GPC3-expressing cancers
such as HCC. Specifically, the inventors
have generated two distinct monoclonal
antibodies to GPC3. The first
monoclonal antibody (HN3) binds to a
conformational epitope on the cell
surface domain of GPC3. The second
monoclonal antibody (HS20) binds
specifically to heparin sulfate chains on
GPC3.
By blocking GPC3 function, these
antibodies can inhibit the growth of
HCC cells, thereby decreasing the ability
of tumors to grow and metastasize.
Furthermore, by using the antibodies to
target a toxin to only those cells that
express GPC3, cancer cells can be
eliminated while allowing healthy,
essential cells to remain unharmed.
Thus, monoclonal antibodies to GPC3
(and corresponding immunotoxins)
represent a novel therapeutic candidate
for treatment of HCC, as well as other
cancers associated with the differential
expression of GPC3.
Applications:
• Therapeutic candidates against
cancers that overexpress GPC3;
• Antibodies for killing cancer cells
by inhibiting GPC3-based cell signaling,
thereby inhibiting tumor cell growth;
• Immunotoxins for killing cancer
cells through the action of a toxic agent;
• Diagnostics for detecting cancers
associated with GPC3 overexpression;
• Specific cancers include
hepatocellular cancer (HCC), melanoma,
thyroid cancer, lung squamous cell
carcinoma, Wilms’ tumor,
neuroblastoma, hepatoblastoma, and
testicular germ-cell tumors.
Advantages:
• Monoclonal antibodies create a
level of specificity that can reduce
deleterious side-effects;
• Multiple treatment strategies
available including the killing of cancer
cells with a toxic agent or by inhibiting
cell signaling;
• Non-invasive and potentially nonliver toxic alternative to current HCC
treatment strategies.
Development Status: Preclinical stage
of development; cell culture data with
HCC cells.
Inventors: Mitchell Ho (NCI) et al.
Patent Status: U.S. provisional
application 61/477,020 (HHS
technology reference E–130–2011/0–
US–01).
For more information, see:
• M Feng et al. Recombinant soluble
glypican 3 protein inhibits the growth of
hepatocellular carcinoma in vitro. Int J
Cancer 2011 May1;128(9):2246–2247,
doi 10.1002/ijc.25549. [PMID:
20617511].
• SI Zitterman et al. Soluble glypican
3 inhibits the growth of hepatocellular
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carcinoma in vitro and in vivo. Int J
Cancer 2010 Mar 15;126(6):1291–1301.
[PMID: 19816934].
Licensing Status: Available for
licensing.
Licensing Contact: David A.
Lambertson, PhD; 301–435–4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity:
The Center for Cancer Research,
Laboratory of Molecular Biology, is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
human monoclonal antibodies or
immunoconjugates such as
immunotoxins and antibody-drug
conjugates against GPC3, soluble GPC3
and its immunoconjugates such as Fc
fusion proteins, large scale antibody
production, and HCC xenograft mouse
models. Please contact John Hewes, PhD
at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
mstockstill on DSK4VPTVN1PROD with NOTICES
Mouse Xenograft Model for
Mesothelioma
Description of Technology: Malignant
mesothelioma is a cancer that presents
itself in the protective lining of several
organs (e.g., lung, heart, testis, etc.). The
primary cause for mesothelioma is
direct or indirect exposure to asbestos,
although the disease can present
without any prior exposure.
Mesothelioma is relatively rare, but the
prognosis for patients is poor, indicating
a need to better understand and treat the
disease. Current treatments often
involve chemotherapy and radiation
therapy, although recent studies have
employed the use of therapeutic
antibodies and antibody-targeted toxins.
This invention involves the creation
of a new mouse model for
mesothelioma. By creating xenografts
with mesothelioma cells that express
GFP-Luciferase fusion proteins, the
xenografts can be detected to a high
degree of sensitivity, and monitored for
several months following implantation.
The high level of detection sensitivity
improves the ability to monitor disease
progression in response to therapeutic
candidates, thereby allowing more
efficient drug screening and evaluation.
This has already been demonstrated by
using the mouse to evaluate an antimesothelioma immunotoxin known as
SS1P, a drug candidate that is currently
being evaluated for clinical
effectiveness.
Applications:
• Animal model for screening
compounds as potential therapeutics for
mesothelioma;
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• Animal model for studying the
effectiveness of potential therapeutics
for mesothelioma;
• Animal model for studying the
pathology of mesothelioma.
Advantages:
• The model is created using well
characterized, art-accepted
mesothelioma cells;
• The model exhibits the classical
clinical progression of mesothelioma,
demonstrating its accuracy as a model;
• The use of GFP-Luciferase fusion
proteins allow for non-invasive
evaluation of mesothelioma progression
and response to drug candidates;
• The use of GFP-Luciferase fusion
proteins allow the use of highly
sensitive detection systems such as
bioluminescence.
Benefits:
• The convenient and efficient
identification and evaluation of
mesothelioma drug candidates.
Inventor: Mitchell Ho (NCI).
Patent Status: HHS Reference No. E–
302–2009/0 — Research Tool. Patent
protection is not being pursued for this
technology.
For more information, see:
• M. Feng et al. In vivo imaging of
human malignant mesothelioma grown
orthotopically in the peritoneal cavity of
nude mice. J Cancer. 2011 Mar 1;2:123–
131. [PMID: 21479131];
• PCT Patent Application WO 2010/
065044 (HHS technology reference E–
336–2008/0–PCT–02);
• U.S. Patent 7,081,518 (HHS
technology reference E–139–1999/0–
US–07).
Licensing Status: The technology is
available for non-exclusive licensing as
a Biological material/Research tool.
Licensing Contact: David A.
Lambertson, PhD; 301–435–4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity:
The Center for Cancer Research,
Laboratory of Molecular Biology, is
seeking statements of capability or
interest from parties interested in
collaborative research to further
develop, evaluate, or commercialize
monoclonal antibodies and
immunoconjugates targeting malignant
mesotheliomas. Please contact John
Hewes, PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
Increased Therapeutic Effectiveness of
Immunotoxins Through the Use of Less
Immunogenic Toxin Domains
Description of Technology: Targeted
toxins (e.g., immunotoxins) are
therapeutics that have at least two
important components: (1) A toxin
domain that is capable of killing cells
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and (2) a targeting domain that is
capable of selectively localizing the
toxic domain to only those cells which
should be killed. By selecting a targeting
domain that binds only to certain
diseased cells (e.g., a cell which only
expresses a cell surface receptor when
in a diseased state), targeted toxins can
kill the diseased cells while allowing
healthy, essential cells to survive. As a
result, patients receiving a targeted
toxin are less likely to experience the
deleterious side-effects associated with
non-discriminate therapies such as
chemotherapy or radiation therapy.
A particular toxin that has been used
in targeted toxins is Pseudomonas
exotoxin A (PE). The effectiveness of
PE-containing targeted toxins has been
demonstrated against various forms of
cancer, including hairy cell leukemia
(HCL) and pediatric acute lymphocytic
leukemia (pALL). Although early
variations these targeted toxins have
demonstrated efficacy upon first
administration, the continued
administration of a targeted toxin often
leads to a reduced patient response. The
primary cause of the reduced response
is the formation of neutralizing
antibodies against PE by the patient.
Several variations of PE have been
created to reduce the immunogenicity of
PE as a means of increasing the
therapeutic effectiveness of targeted
toxins through multiple rounds of drug
administration. This technology
involves the identification of two
important B-cell epitopes on PE, and the
elimination of those epitopes by
mutation. These new PE variants retain
a sufficient cell killing activity while
increasing their therapeutic
effectiveness toward patients that
receive multiple administrations. By
further combining these new mutations
with previously identified modifications
that also improve the efficacy of PEbased targeted toxins, it may be possible
to treat any disease characterized by
cells that express a particular cell
surface receptor when in a disease state.
Applications:
• Essential component of a targeted
toxin, such as an immunotoxin
(antibody-targeted toxin) or ligandtargeted toxin;
• Treatment of diseases that are
associated with the increased
expression of a cell surface receptor;
• Applicable to any disease
associated with cells that preferentially
express a specific cell surface receptor;
• Relevant diseases include various
cancers, including lung, ovarian, breast,
head and neck, and hematological
cancers.
Advantages:
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Federal Register / Vol. 76, No. 120 / Wednesday, June 22, 2011 / Notices
• Less immunogenic targeted toxin
results in improved efficacy during
multiple administrations;
• Targeted therapy decreases nonspecific killing of healthy, essential
cells, resulting in fewer side-effects and
healthier patients.
Development Status: Preclinical stage
of development.
Inventors: Pastan (NCI) et al.
Patent Status:
• U.S. provisional application 61/
241,620 (HHS technology reference E–
269–2009/0–US–01);
• PCT patent application PCT/
US2010/048504 (HHS technology
reference E–269–2009/0–PCT–02).
For more information, see:
• U.S. Patent Publication US
20100215656 A1 (HHS technology
reference E–292–2007/0–US–06);
• U.S. Patent Publication US
20090142341 A1 (HHS technology
reference E–262–2005/0–US–06);
• U.S. Patent 7,777,019 (HHS
technology reference E–129–2001/0–
US–07).
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,
Molecular Biology Section, 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, PhD at 301–435–
3121 or hewesj@mail.nih.gov for more
information.
Dated: June 15, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–15492 Filed 6–21–11; 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.
mstockstill on DSK4VPTVN1PROD with NOTICES
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
SUMMARY:
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16:40 Jun 21, 2011
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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.
Mouse Model for Cerebral Cavernous
Malformation, an Inherited Brain
Disorder
Description of Technology: Cerebral
Cavernous Malformation (CCM) is a
brain disease affecting up to 0.5% of the
worldwide population. CCM is
characterized by grossly dilated vessels
prone to leaking and hemorrhage which
result in severe headaches, seizures, and
strokes. Inherited forms of the disease
are due to mutations in one of three loci,
CCM1, CCM2, and CCM3. Prior efforts
to develop mice with targeted null
mutations in Ccm1, Ccm2, or Ccm3
have been unsuccessful, as such
mutations result in embryonic death.
The inventors have developed the
first mouse model available for the
study of CCM, in which mouse Ccm2
can be conditionally deleted in bloodaccessible and endothelial cells,
resulting in neurological defects, ataxia,
and brain hemorrhages consistent with
the human disease. The model was
generated through a cross of C57BL/6
Ccm2-floxed mice with C57BL/6 MX–1–
Cre mice, which permits inducible
ablation by polyinosinic:polycytidylic
acid (pIpC).
Inventors: Ulrich Siebenlist (NIAID)
and Yoh-suke Mukoyama (NHLBI).
Related Publications: In preparation.
Patent Status: HHS Reference No. E–
158–2011/0—Research Material. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing under a Biological Materials
License Agreement.
Licensing Contact: Tara L. Kirby, PhD;
301–435–4426; tarak@mail.nih.gov.
System to Increase Consistency and
Reduce Variations in Contrast and
Sensitivity in MRI Imaging
Description of Technology: The
technology relates to the field of MRI.
More specifically, the invention
describes and claims system and
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36553
methods related to the use of non-linear
B0 shims to improve excitation flip
angle uniformity in high field MRI. The
disclosed system and methods can be
used in conjunction with existing multidimension excitation methods,
including those that use parallel
excitation to improve contrast and
sensitivity in gradient echo magnetic
resonance imaging. The technology is
designed to overcome shortcomings
associated with high field MRI, namely
RF flip angle inhomogeneity due to
wavelength effects that can lead to
spatial variations in contrast and
sensitivity.
Applications: High field MRI.
Advantages: The present system and
methods will improve performance of
high field MRI:
• Improve the transmit profile
homogeneity, and therefore the
uniformity of MRI images.
• The method is applicable to all MRI
scanning with poor B1 uniformity. This
includes situations when B1 variations
are caused by the coil B1 profile, by the
dielectric properties of the object
(wavelength effects), or by a
combination of both.
• The method is applicable with
currently available single or multichannel B1 coils.
Development Status:
• Proof of principle has been
demonstrated on a prototype device.
• Demonstration of the application to
human imaging is currently underway.
Inventors: Jeff Duyn (NINDS).
Relevant Publication: Duan Q, van
Gelderen P, Duyn J. B0 based shimming
of RF flip angle in MRI. Submitted to
Magnetic Resonance in Medicine.
Patent Status: U.S. Provisional
Application No. 61/473,610 filed 08 Apr
2011 (HHS Reference No. E–129–2011/
0–US–01).
Licensing Status: Available for
licensing and commercial development.
Licensing Contacts:
• Uri Reichman, PhD, MBA; 301–
435–4616; UR7a@nih.gov.
• John Stansberry, PhD; 301–435–
5236; js852e@nih.gov.
Polyclonal Antibodies Against RGS7, a
Regulator of G Protein Signaling, for
Research and Diagnostic Use
Description of Technology:
Investigators at the National Institutes of
Health have generated a polyclonal
antibody against the Regulator of G
protein Signaling Protein 7 (RGS7). The
RGS7 protein regulates neuronal G
protein signaling pathways and inhibits
signal transduction by increasing the
GTPase activity of G protein alpha.
RGS7 may play an important role in
synaptic vesicle exocytosis and in the
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]]>Agencies
[Federal Register Volume 76, Number 120 (Wednesday, June 22, 2011)]
[Notices]
[Pages 36551-36553]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-15492]
-----------------------------------------------------------------------
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.
Monoclonal Antibodies to Glypican-3 Protein and Heparin Sulfate for
Treatment of Cancer
Description of Technology: Hepatocellular carcinoma (HCC) is the
most common form of liver cancer, and is among the more deadly cancers
in the world due to its late detection and poor prognosis. HCC is often
associated with liver disease, curtailing traditional chemotherapy as a
treatment option. While surgical resection offers the best method for
long term treatment of the disease, only a small portion of HCC
patients are eligible for this procedure. As a result, there is a need
for new treatments that can be successfully applied to a large
population of HCC patients.
Glypican-3 (GPC3) is a cell surface protein that is preferentially
expressed on HCC cells. Evidence has demonstrated that a soluble form
of GPC3 that is incapable of cell signaling has the ability to inhibit
the growth of HCC cells. This suggested that blocking GPC3 signaling
could serve as a therapeutic approach for treating HCC.
This invention concerns monoclonal antibodies against GPC3 and
their use, either by themselves or as the targeting domain for an
immunotoxin, for the treatment of GPC3-expressing cancers such as HCC.
Specifically, the inventors have generated two distinct monoclonal
antibodies to GPC3. The first monoclonal antibody (HN3) binds to a
conformational epitope on the cell surface domain of GPC3. The second
monoclonal antibody (HS20) binds specifically to heparin sulfate chains
on GPC3.
By blocking GPC3 function, these antibodies can inhibit the growth
of HCC cells, thereby decreasing the ability of tumors to grow and
metastasize. Furthermore, by using the antibodies to target a toxin to
only those cells that express GPC3, cancer cells can be eliminated
while allowing healthy, essential cells to remain unharmed. Thus,
monoclonal antibodies to GPC3 (and corresponding immunotoxins)
represent a novel therapeutic candidate for treatment of HCC, as well
as other cancers associated with the differential expression of GPC3.
Applications:
Therapeutic candidates against cancers that overexpress
GPC3;
Antibodies for killing cancer cells by inhibiting GPC3-
based cell signaling, thereby inhibiting tumor cell growth;
Immunotoxins for killing cancer cells through the action
of a toxic agent;
Diagnostics for detecting cancers associated with GPC3
overexpression;
Specific cancers include hepatocellular cancer (HCC),
melanoma, thyroid cancer, lung squamous cell carcinoma, Wilms' tumor,
neuroblastoma, hepatoblastoma, and testicular germ-cell tumors.
Advantages:
Monoclonal antibodies create a level of specificity that
can reduce deleterious side-effects;
Multiple treatment strategies available including the
killing of cancer cells with a toxic agent or by inhibiting cell
signaling;
Non-invasive and potentially non-liver toxic alternative
to current HCC treatment strategies.
Development Status: Preclinical stage of development; cell culture
data with HCC cells.
Inventors: Mitchell Ho (NCI) et al.
Patent Status: U.S. provisional application 61/477,020 (HHS
technology reference E-130-2011/0-US-01).
For more information, see:
M Feng et al. Recombinant soluble glypican 3 protein
inhibits the growth of hepatocellular carcinoma in vitro. Int J Cancer
2011 May1;128(9):2246-2247, doi 10.1002/ijc.25549. [PMID: 20617511].
SI Zitterman et al. Soluble glypican 3 inhibits the growth
of hepatocellular
[[Page 36552]]
carcinoma in vitro and in vivo. Int J Cancer 2010 Mar 15;126(6):1291-
1301. [PMID: 19816934].
Licensing Status: Available for licensing.
Licensing Contact: David A. Lambertson, PhD; 301-435-4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity: The Center for Cancer Research,
Laboratory of Molecular Biology, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize human monoclonal antibodies or
immunoconjugates such as immunotoxins and antibody-drug conjugates
against GPC3, soluble GPC3 and its immunoconjugates such as Fc fusion
proteins, large scale antibody production, and HCC xenograft mouse
models. Please contact John Hewes, PhD at 301-435-3121 or
hewesj@mail.nih.gov for more information.
Mouse Xenograft Model for Mesothelioma
Description of Technology: Malignant mesothelioma is a cancer that
presents itself in the protective lining of several organs (e.g., lung,
heart, testis, etc.). The primary cause for mesothelioma is direct or
indirect exposure to asbestos, although the disease can present without
any prior exposure. Mesothelioma is relatively rare, but the prognosis
for patients is poor, indicating a need to better understand and treat
the disease. Current treatments often involve chemotherapy and
radiation therapy, although recent studies have employed the use of
therapeutic antibodies and antibody-targeted toxins.
This invention involves the creation of a new mouse model for
mesothelioma. By creating xenografts with mesothelioma cells that
express GFP-Luciferase fusion proteins, the xenografts can be detected
to a high degree of sensitivity, and monitored for several months
following implantation. The high level of detection sensitivity
improves the ability to monitor disease progression in response to
therapeutic candidates, thereby allowing more efficient drug screening
and evaluation. This has already been demonstrated by using the mouse
to evaluate an anti-mesothelioma immunotoxin known as SS1P, a drug
candidate that is currently being evaluated for clinical effectiveness.
Applications:
Animal model for screening compounds as potential
therapeutics for mesothelioma;
Animal model for studying the effectiveness of potential
therapeutics for mesothelioma;
Animal model for studying the pathology of mesothelioma.
Advantages:
The model is created using well characterized, art-
accepted mesothelioma cells;
The model exhibits the classical clinical progression of
mesothelioma, demonstrating its accuracy as a model;
The use of GFP-Luciferase fusion proteins allow for non-
invasive evaluation of mesothelioma progression and response to drug
candidates;
The use of GFP-Luciferase fusion proteins allow the use of
highly sensitive detection systems such as bioluminescence.
Benefits:
The convenient and efficient identification and evaluation
of mesothelioma drug candidates.
Inventor: Mitchell Ho (NCI).
Patent Status: HHS Reference No. E-302-2009/0 -- Research Tool.
Patent protection is not being pursued for this technology.
For more information, see:
M. Feng et al. In vivo imaging of human malignant
mesothelioma grown orthotopically in the peritoneal cavity of nude
mice. J Cancer. 2011 Mar 1;2:123-131. [PMID: 21479131];
PCT Patent Application WO 2010/065044 (HHS technology
reference E-336-2008/0-PCT-02);
U.S. Patent 7,081,518 (HHS technology reference E-139-
1999/0-US-07).
Licensing Status: The technology is available for non-exclusive
licensing as a Biological material/Research tool.
Licensing Contact: David A. Lambertson, PhD; 301-435-4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity: The Center for Cancer Research,
Laboratory of Molecular Biology, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize monoclonal antibodies and
immunoconjugates targeting malignant mesotheliomas. Please contact John
Hewes, PhD at 301-435-3121 or hewesj@mail.nih.gov for more information.
Increased Therapeutic Effectiveness of Immunotoxins Through the Use of
Less Immunogenic Toxin Domains
Description of Technology: Targeted toxins (e.g., immunotoxins) are
therapeutics that have at least two important components: (1) A toxin
domain that is capable of killing cells and (2) a targeting domain that
is capable of selectively localizing the toxic domain to only those
cells which should be killed. By selecting a targeting domain that
binds only to certain diseased cells (e.g., a cell which only expresses
a cell surface receptor when in a diseased state), targeted toxins can
kill the diseased cells while allowing healthy, essential cells to
survive. As a result, patients receiving a targeted toxin are less
likely to experience the deleterious side-effects associated with non-
discriminate therapies such as chemotherapy or radiation therapy.
A particular toxin that has been used in targeted toxins is
Pseudomonas exotoxin A (PE). The effectiveness of PE-containing
targeted toxins has been demonstrated against various forms of cancer,
including hairy cell leukemia (HCL) and pediatric acute lymphocytic
leukemia (pALL). Although early variations these targeted toxins have
demonstrated efficacy upon first administration, the continued
administration of a targeted toxin often leads to a reduced patient
response. The primary cause of the reduced response is the formation of
neutralizing antibodies against PE by the patient.
Several variations of PE have been created to reduce the
immunogenicity of PE as a means of increasing the therapeutic
effectiveness of targeted toxins through multiple rounds of drug
administration. This technology involves the identification of two
important B-cell epitopes on PE, and the elimination of those epitopes
by mutation. These new PE variants retain a sufficient cell killing
activity while increasing their therapeutic effectiveness toward
patients that receive multiple administrations. By further combining
these new mutations with previously identified modifications that also
improve the efficacy of PE-based targeted toxins, it may be possible to
treat any disease characterized by cells that express a particular cell
surface receptor when in a disease state.
Applications:
Essential component of a targeted toxin, such as an
immunotoxin (antibody-targeted toxin) or ligand-targeted toxin;
Treatment of diseases that are associated with the
increased expression of a cell surface receptor;
Applicable to any disease associated with cells that
preferentially express a specific cell surface receptor;
Relevant diseases include various cancers, including lung,
ovarian, breast, head and neck, and hematological cancers.
Advantages:
[[Page 36553]]
Less immunogenic targeted toxin results in improved
efficacy during multiple administrations;
Targeted therapy decreases non-specific killing of
healthy, essential cells, resulting in fewer side-effects and healthier
patients.
Development Status: Preclinical stage of development.
Inventors: Pastan (NCI) et al.
Patent Status:
U.S. provisional application 61/241,620 (HHS technology
reference E-269-2009/0-US-01);
PCT patent application PCT/US2010/048504 (HHS technology
reference E-269-2009/0-PCT-02).
For more information, see:
U.S. Patent Publication US 20100215656 A1 (HHS technology
reference E-292-2007/0-US-06);
U.S. Patent Publication US 20090142341 A1 (HHS technology
reference E-262-2005/0-US-06);
U.S. Patent 7,777,019 (HHS technology reference E-129-
2001/0-US-07).
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,
Molecular Biology Section, 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, PhD at 301-435-3121 or hewesj@mail.nih.gov for more
information.
Dated: June 15, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-15492 Filed 6-21-11; 8:45 am]
BILLING CODE 4140-01-P
