Government-Owned Inventions; Availability for Licensing, 40381-40383 [2011-17228]
Download as PDF
<![CDATA[
Federal Register / Vol. 76, No. 131 / Friday, July 8, 2011 / Notices
Dated: June 21, 2011.
Sarah L. Glavin,
Deputy Director, Office of Science Policy,
Analysis and Communications, National
Institute of Child Health and Human
Development.
reactivity and mediate an immune
response that promotes robust tumor
cell elimination.
Advantages
[FR Doc. 2011–17201 Filed 7–7–11; 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.
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.
mstockstill on DSK4VPTVN1PROD with NOTICES
SUMMARY:
Breakthrough Immunotherapy for
Brain Cancer: Epidermal Growth
Factor Receptor Variant III Chimeric
Antigen Receptors
Description of Technology: Scientists
at the National Institutes of Health (NIH)
have developed chimeric antigen
receptors (CARs) with high affinity for
the epidermal growth factor receptor
variant III (EGFRvIII) to use as a
promising immunotherapy for
aggressive brain cancer (glioblastoma) as
well as several other malignancies.
CARs are hybrid proteins consisting of
the portion of an antibody that
recognizes a cancer antigen, in this case
human monoclonal antibody 139 which
recognizes EGFRvIII, fused to protein
signaling domains that serve to activate
the CAR-expressing cell. Human cells
that express CARs, most notably T cells,
can recognize specific tumor antigens in
an MHC-unrestricted manner with high
VerDate Mar<15>2010
17:52 Jul 07, 2011
Jkt 223001
• EGFRvIII CAR immunotherapy is a
breakthrough treatment for
glioblastomas, a cancer with no other
effective treatment option.
• EGFRvIII CARs can cross the bloodbrain barrier, are expected to target only
tumor cells, and thus, generate fewer
side effects than other brain cancer
treatment approaches.
• With the advent of Provenge®,
personalized immunotherapy is
becoming more widely accepted as a
viable cancer treatment option.
Applications
• Immunotherapeutics to treat and/or
prevent the recurrence of a variety of
cancers that overexpress human
EGFRvIII, primarily glioblastoma
multiforme (GBM). About half of GBM
tumor cells express the EGFRvIII
antigen. Other cancers that overexpress
EGFRvIII include breast, ovarian,
prostate, bladder, colorectal, non-small
cell lung carcinomas, and head and
neck squamous cell carcinomas.
• A personalized cancer treatment
strategy for patients whose tumor cells
express EGFRvIII whereby the patient’s
own T cells are isolated, engineered to
express the EGFRvIII specific CAR, and
re-infused into the patient to attack the
tumor.
EGFRvIII is a rare antigen in that is
highly expressed by tumor cells, but not
expressed by other cells in the body.
This cancer antigen is expressed on
nearly 50% of GBM tumor cells and also
in other tumor types, such as other
nervous system cancers and head and
neck cancers. There exist very few, if
any, effective treatments for GBM, so the
expected clinical benefit of an antiEGFRvIII CAR to patients is expected to
be a therapeutic breakthrough for
treatment of this cancer. These CARs are
expected to combine high affinity
recognition of EGFRvIII provided by the
antibody portion with the target cell
killing activity of cytotoxic T cells.
Infusion of these EGFRvIII-specific
CARs into patients could prove to be a
powerful new immunotherapeutic tool
for treating brain cancers, a type of
cancer with a long-felt need for
breakthrough therapeutics.
Development Status: This technology
could soon be ready for clinical
development. A clinical protocol to
utilize an EGFRvIII CAR to treat GBM is
currently under review at NIH.
Inventors: Richard A. Morgan and
Steven A. Rosenberg (NCI).
PO 00000
Frm 00060
Fmt 4703
Sfmt 4703
40381
Patent Status: U.S. Provisional
Application No. 61/473,409 filed April
8, 2011 (HHS Reference No. E–148–
2011/0–US–01).
Related Technologies
• E–269–2010/0—U.S. Provisional
Application No. 61/384,931 filed
September 21, 2010.
• E–236–2010/0—U.S. Provisional
Application No. 61/405,931 filed
October 22, 2010.
• E–205–2009/0—PCT Application
No. PCT/US2010/048701 filed
September 14, 2010, which published as
WO2011/041093 on April 7, 2011.
Relevant Publications
1. Weber R, et al. U.S. Patent No.
7,628,986 issued December 8, 2009
entitled ‘‘Antibodies Directed to the
Deletion Mutants of Epidermal Growth
Factor Receptor and Uses Thereof’’.
2. Carter B.S., et al. U.S. Patent
Application No. 12/444,090 filed April
2, 2009 entitled ‘‘Chimeric T–Cell
Receptors and T–Cells Targeting
EGFRvIII on Tumors’’.
3. Bullian SS, et al. Genetically
engineered T cells to target EGFRvIII
expressing glioblastoma. J Neurooncol.
2009 Sept;94(3):373–382. [PMID:
19387557].
4. Ohno M, et al. Retrovirally
engineered T-cell based immunotherapy
targeting type III variant epidermal
growth factor receptor, a gliomaassociated antigen. Cancer Sci. 2010
Dec;101(12):2518–2524. [PMID:
20880333].
Licensing Status: Available for
licensing.
Licensing Contact: Samuel E. Bish,
PhD; 301–435–5282;
bishse@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute, Surgery
Branch, is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize cell-based
immunotherapies targeting EGFRvIII
expressing cancers. Please contact John
Hewes, PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
An Improved Anti-Mesothelin
Immunotoxin for Treatment of
Mesothelioma, Lung Cancer, Ovarian
Cancer and Pancreatic Cancer
Description of Technology:
Mesothelin is a cell surface glycoprotein
that is highly expressed in many cancers
(e.g., malignant mesothelioma, lung
cancer, ovarian cancer, and pancreatic
cancer). Because of its differential
expression, mesothelin is an excellent
E:\FR\FM\08JYN1.SGM
08JYN1
40382
Federal Register / Vol. 76, No. 131 / Friday, July 8, 2011 / Notices
mstockstill on DSK4VPTVN1PROD with NOTICES
target for the selective killing of cancer
cells. For instance, anti-mesothelin
monoclonal antibodies can carry
cellular toxins specifically to
mesothelin-expressing cancer cells,
resulting in their selective killing while
healthy, essential cells remain
unharmed.
A high affinity anti-mesothelin
antibody (SS1) was previously
combined with a functional fragment of
Pseudomonas Exotoxin A (PE),
producing the immunotoxin SS1P. SS1P
selectively killed mesothelin-expressing
cancer cells, suggesting it could be an
excellent therapeutic agent.
Unfortunately, PE-based immunotoxins
can lose therapeutic efficacy following
multiple administrations, due to the
formation of neutralizing antibodies
against the PE portion of the molecule.
As a result, less immunogenic variants
of PE have been created in order to
develop immunotoxins that do not
induce the formation of neutralizing
antibodies.
Improved PE variants have been
created which lack lysosomal protease
sites, a dominant T-cell epitope (PE–
LR), and several major B-cell epitopes
(PE–LR/8M). Although these new PE
variants demonstrate efficient cell
killing activity when used in
combination with certain antibodies,
their activity when using SS1 as the
targeting agent (SS1–LR and SS1–LR/
8M) was less impressive. Fortunately,
the inventors surprisingly discovered
that the addition of a small linker
peptide within these immunotoxins was
able to restore their cell killing activity
to the level of SS1P.
These new SS1-targeted
immunotoxins (e.g., SS1–LR/GGS and
SS1–LR/GGS/8M) have the cell-killing
activity of SS1P, but are less likely to
generate neutralizing antibodies. As a
result, these immunotoxins are
considered to be very promising
prospects for treating patients suffering
from mesothelin-expressing cancers.
Applications
• Treatment of mesothelin expressing
cancers, including mesothelioma,
pancreatic cancer, ovarian cancer and
lung adenocarcinoma.
• Treatment in combination with
standard chemotherapy.
• Diagnostic agent for the detection of
mesothelin-expressing cancers.
Advantages
• Immunotoxins are highly selective
for cancer cells, reducing side-effects
due to the non-specific killing of
essential, healthy cells.
• Less immunogenic PE variants
increase the efficacy of the
VerDate Mar<15>2010
17:52 Jul 07, 2011
Jkt 223001
immunotoxin by reducing the formation
and action of neutralizing antibodies.
• PE variants include the removal of
both B-cell and T-cell epitopes.
• Use of a small linker peptide offers
an unexpected advantage of strong cellkilling activity with reduced
immunogenicity.
Development Status: Preclinical stage
of development for anti-mesothelin
immunotoxins; immunotoxins directed
to other targets have some clinical data
to demonstrate proof-of-concept
Inventors: Ira Pastan (NCI) et al.
Patent Status
• U.S. provisional patent application
61/483,531 (HHS technology E–117–
2011/0–US–01).
• U.S. provisional patent application
61/495,085 (HHS technology E–174–
2011/0–US–01).
For More Information
• U.S. Patent 7,081,518 (HHS
technology E–139–1999/0–US–07).
• U.S. Patent Publication US
20090142341 A1 (HHS technology E–
262–2005/0–US–06).
• U.S. Patent Publication US
20100215656 A1 (HHS technology E–
292–2007/0–US–06).
• PCT Publication WO 2011/032022
(HHS technology E–269–2009/0–PCT–
02).
Licensing Status: Available for
licensing.
Licensing Contact: David A.
Lambertson, PhD; 301–435–4632;
lambertsond@mail.nih.gov.
Efficient Production of Functional
Recombinant Human Neonatal
Receptor (FcRn) Proteins
Description of Technology: Human
monoclonal antibodies are becoming
common therapeutics for numerous
diseases, including rheumatoid arthritis,
multiple sclerosis, and several different
types of cancers. To improve their halflife, antibodies are engineered to have a
high affinity to the Fc receptor (FcRn).
This requires a reliable method to
produce high yields of functional FcRn
which comprises a 1:1 molar ratio of the
alpha to the beta chain. Unfortunately,
current methods can be difficult to
implement and are not very efficient in
producing functional FcRns with the 1:1
molar ratio of the alpha to the beta
chain. Thus, there is a strong need for
quick and economical methods of
producing functional FcRn to aid in
antibody development and the
improvement of existing antibody
therapeutics.
This technology describes a new and
efficient method for producing
functional human FcRn at a 1:1 molar
PO 00000
Frm 00061
Fmt 4703
Sfmt 4703
ratio of the alpha to the beta chain. The
uniqueness of this invention is that the
expression of both the beta and the
alpha chains is under the control of a
single promoter and the correct 1:1
molar folding of the two chains is
facilitated by the intermediate flexible
linker. The method is easy to scale up
for producing large quantities of highly
pure FcRn. Further, the inventors have
recently developed a stable cell line for
large scale production.
Benefits: Improving the half-life of
existing monoclonal antibodies as well
as monoclonal antibodies still in
development.
Advantages
• Efficient method of producing high
yields of functional human FcRn at a 1:1
molar ratio of the alpha to the beta
chain.
• Stable cell line also available.
Market: The monoclonal antibodies
market generated over $40 billion in
sales for therapeutic uses last year and
is expected to grow significantly over
the next several years.
Publications: Feng Y, Gong R,
Dimitrov D.S. Design, expression and
characterization of a soluble singlechain functional human neonatal Fc
receptor. Protein Expr Purif. 2011 Mar
29, E-pub ahead of print. [PMID:
21453773]
Inventors: Dimiter S. Dimitrov and
Yang Feng (NCI).
Patent Status: HHS Reference No. E–
296–2010/0—Research Tool. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing.
Licensing Contact: Whitney A.
Hastings; 301–451–7337;
hastingw@mail.nih.gov.
Immunocompetent Mouse Model for
Tracking Cancer Progression
Description of Technology: The
technology is a transgenic mouse model
tolerized to firefly Luciferase (ffLuc)and enhanced green fluorescent protein
(eGFP)-labeled tissue whilst
maintaining normal immune function.
Luc and eGFP are the most frequently
used bioimaging markers to track cancer
progression in pre-clinical mouse
models. As these markers are
immunogenic, their reporter activity
becomes diminished over time and so
their use has largely been limited to
immunodeficient mice. However,
immune function is crucial for tumor
development and progression, making
the use of immunocompetent mice more
desirable.
The immunocompetent mouse model
described in this invention was
E:\FR\FM\08JYN1.SGM
08JYN1
Federal Register / Vol. 76, No. 131 / Friday, July 8, 2011 / Notices
generated using the rat growth hormone
gene promoter (rGH) to target ffLuceGFP fusion gene expression to the
pituitary gland, restricting any resulting
interfering reporter signal within the
head. This allows the tracking of cancer
progression throughout the body, where
the reporter activity of introduced ffLuc/
eGFP-labeled tumors is maintained,
despite normal immune function. These
immunocompetent rGH-ffLuc-eGFP
transgenic mice can be used as hosts in
cancer models, allowing long-term in
vivo monitoring of the progression of
ffLuc/eGFP-labeled tumor cells in the
body, which may lead to more clinically
relevant insights into cancer
progression, metastases and response to
therapies.
Applications
• In vivo model for studying tumor
progression and testing anti-cancer
therapeutics using ffLuc or eGFP
labeling for bioimaging.
• Since rGH-ffLuc-eGFP is also a
growth hormone-responsive reporter,
these rGH–Luc-GFP mice may also be
used to screen growth-hormone
stimulating drugs for treating
Achondroplasia (dwarf syndrome) or as
a test for illegal performance-enhancing
drugs.
Advantages
• This technology represents a more
clinically relevant in vivo model of
cancer progression for testing anticancer therapeutics.
• This immunocompetent mouse
model is more desirable as a pre-clinical
model over the currently used
immunodeficient mouse models as
immune function is crucial for tumor
development and progression.
• Early-stage.
• Pre-clinical.
• In vitro data available.
• In vivo data available (animal).
Inventors: Chi-Ping Day and Glenn
Merlino (NCI).
mstockstill on DSK4VPTVN1PROD with NOTICES
Jkt 223001
Patent Status: HHS Reference No. E–
173–2010/0—Research Tool. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing.
Licensing Contact: Sabarni K.
Chatterjee, PhD; 301–435–5587;
chatterjeesa@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute Center for
Cancer Research is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize immunocompetent rGHffLuc-eGFP transgenic mice. Please
contact John Hewes, PhD at 301–435–
3121 or hewesj@mail.nih.gov for more
information.
Description of Technology: Embryonic
stem cells (ESCs) are pluripotent cells
that can be cultured indefinitely, and
maintain their capability to differentiate
into all cell lineages. To maintain these
cells as well as various types of related
induced stem cells and progenitor cells
in culture, Mouse Embryonic
Fibroblasts (MEFs) are routinely used as
feeder cells, largely to serve as a source
of Leukemia Inhibitory Factor (LIF).
ESCs can also be cultured without
feeders if the medium is supplemented
with recombinant LIF and other factors.
However, these methods of culturing
ESCs suffer from certain drawbacks,
such as limited proliferation capacity
and variability of primary MEFs.
Therefore, finding improved conditions
that maintain ESC pluripotency is an
area of great interest.
Scientists at NIEHS have now
developed a knock-in (KI) mouse model
in which LIF is overproduced from its
endogenous locus because of increased
stability of its mRNA. MEFs and
presumably other cells derived from the
homozygous mice hypersecrete LIF
protein; lesser degrees of overexpression
would be expected from heterozygous
mice. These mice can be used to study
LIF function, including how LIF
contributes to various physiological and
pathological states. Cells derived from
these mice can be used to culture ESCs,
as well as other progenitor cells. Cells
or genetic material derived from these
mice can also be used as sources of LIF
for isolation and purification.
Dated: July 1, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–17228 Filed 7–7–11; 8:45 am]
BILLING CODE 4140–01–P
Government-Owned Inventions;
Availability for Licensing
Public Health Service, National
Institutes of Health, HHS.
ACTION: Notice.
AGENCY:
1. Day C.P., et al. Preclinical therapeutic
response of residual metastatic disease is
distinct from its primary tumor of origin. Int
J Cancer. 2011 Feb 10, doi: 10.1002/ijc.25978.
[Epub ahead of print].
2. Day C.P., et al. Lentivirus-mediated
bifunctional cell labeling for in vivo
melanoma study. Pigment Cell Melanoma
Res. 2009 Jun;22(3):283–295. [PMID:
19175523].
3. Luque R.M., et al. Reporter expression,
induced by a growth hormone promoterdriven Cre recombinase (rGHp-Cre)
transgene, questions the developmental
relationship between somatotropes and
17:52 Jul 07, 2011
ADDRESSES:
National Institutes of Health
Relevant Publications
VerDate Mar<15>2010
lactotropes in the adult mouse pituitary
gland. Endocrinology. 2007
May;148(5):1946–1953. [PMID: 17289844].
4. Latta-Mahieu M., et al. Gene transfer of
a chimeric trans-activator is immunogenic
and results in short-lived transgene
expression. Hum Gene Ther. 2002 Sep
1;13(13):1611–1620. [PMID: 12228016].
5. Stripecke R., et al. Immune response to
green fluorescent protein: implications for
gene therapy. Gene Ther. 1999 Jul;6(7):1305–
1312. [PMID: 10455440].
6. Liao C.P., et al. Mouse models of
prostate adenocarcinoma with the capacity to
monitor spontaneous carcinogenesis by
bioluminescence or fluorescence. Cancer Res.
2007 Aug 1;67(15):7525–7533. [PMID:
17671224].
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Development Status
40383
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.
SUMMARY:
PO 00000
Frm 00062
Fmt 4703
Sfmt 4703
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 and Derived Cells That
Hypersecrete Leukemia Inhibitory
Factor (LIF)
Applications
• Maintenance of ESCs and
progenitor cells.
• In vivo, cellular and cell-free
sources of LIF.
• Sources of LIF for isolation and
purification.
• Studies of LIF function in mice,
such as contribution of LIF to tumor
growth.
Inventors: Dr. Perry Blackshear
(NIEHS), et al.
E:\FR\FM\08JYN1.SGM
08JYN1
]]>Agencies
[Federal Register Volume 76, Number 131 (Friday, July 8, 2011)]
[Notices]
[Pages 40381-40383]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-17228]
-----------------------------------------------------------------------
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.
Breakthrough Immunotherapy for Brain Cancer: Epidermal Growth Factor
Receptor Variant III Chimeric Antigen Receptors
Description of Technology: Scientists at the National Institutes of
Health (NIH) have developed chimeric antigen receptors (CARs) with high
affinity for the epidermal growth factor receptor variant III
(EGFRvIII) to use as a promising immunotherapy for aggressive brain
cancer (glioblastoma) as well as several other malignancies. CARs are
hybrid proteins consisting of the portion of an antibody that
recognizes a cancer antigen, in this case human monoclonal antibody 139
which recognizes EGFRvIII, fused to protein signaling domains that
serve to activate the CAR-expressing cell. Human cells that express
CARs, most notably T cells, can recognize specific tumor antigens in an
MHC-unrestricted manner with high reactivity and mediate an immune
response that promotes robust tumor cell elimination.
Advantages
EGFRvIII CAR immunotherapy is a breakthrough treatment for
glioblastomas, a cancer with no other effective treatment option.
EGFRvIII CARs can cross the blood-brain barrier, are
expected to target only tumor cells, and thus, generate fewer side
effects than other brain cancer treatment approaches.
With the advent of Provenge[supreg], personalized
immunotherapy is becoming more widely accepted as a viable cancer
treatment option.
Applications
Immunotherapeutics to treat and/or prevent the recurrence
of a variety of cancers that overexpress human EGFRvIII, primarily
glioblastoma multiforme (GBM). About half of GBM tumor cells express
the EGFRvIII antigen. Other cancers that overexpress EGFRvIII include
breast, ovarian, prostate, bladder, colorectal, non-small cell lung
carcinomas, and head and neck squamous cell carcinomas.
A personalized cancer treatment strategy for patients
whose tumor cells express EGFRvIII whereby the patient's own T cells
are isolated, engineered to express the EGFRvIII specific CAR, and re-
infused into the patient to attack the tumor.
EGFRvIII is a rare antigen in that is highly expressed by tumor
cells, but not expressed by other cells in the body. This cancer
antigen is expressed on nearly 50% of GBM tumor cells and also in other
tumor types, such as other nervous system cancers and head and neck
cancers. There exist very few, if any, effective treatments for GBM, so
the expected clinical benefit of an anti-EGFRvIII CAR to patients is
expected to be a therapeutic breakthrough for treatment of this cancer.
These CARs are expected to combine high affinity recognition of
EGFRvIII provided by the antibody portion with the target cell killing
activity of cytotoxic T cells. Infusion of these EGFRvIII-specific CARs
into patients could prove to be a powerful new immunotherapeutic tool
for treating brain cancers, a type of cancer with a long-felt need for
breakthrough therapeutics.
Development Status: This technology could soon be ready for
clinical development. A clinical protocol to utilize an EGFRvIII CAR to
treat GBM is currently under review at NIH.
Inventors: Richard A. Morgan and Steven A. Rosenberg (NCI).
Patent Status: U.S. Provisional Application No. 61/473,409 filed
April 8, 2011 (HHS Reference No. E-148-2011/0-US-01).
Related Technologies
E-269-2010/0--U.S. Provisional Application No. 61/384,931
filed September 21, 2010.
E-236-2010/0--U.S. Provisional Application No. 61/405,931
filed October 22, 2010.
E-205-2009/0--PCT Application No. PCT/US2010/048701 filed
September 14, 2010, which published as WO2011/041093 on April 7, 2011.
Relevant Publications
1. Weber R, et al. U.S. Patent No. 7,628,986 issued December 8,
2009 entitled ``Antibodies Directed to the Deletion Mutants of
Epidermal Growth Factor Receptor and Uses Thereof''.
2. Carter B.S., et al. U.S. Patent Application No. 12/444,090 filed
April 2, 2009 entitled ``Chimeric T-Cell Receptors and T-Cells
Targeting EGFRvIII on Tumors''.
3. Bullian SS, et al. Genetically engineered T cells to target
EGFRvIII expressing glioblastoma. J Neurooncol. 2009 Sept;94(3):373-
382. [PMID: 19387557].
4. Ohno M, et al. Retrovirally engineered T-cell based
immunotherapy targeting type III variant epidermal growth factor
receptor, a glioma-associated antigen. Cancer Sci. 2010
Dec;101(12):2518-2524. [PMID: 20880333].
Licensing Status: Available for licensing.
Licensing Contact: Samuel E. Bish, PhD; 301-435-5282;
bishse@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute,
Surgery Branch, is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize cell-based immunotherapies targeting
EGFRvIII expressing cancers. Please contact John Hewes, PhD at 301-435-
3121 or hewesj@mail.nih.gov for more information.
An Improved Anti-Mesothelin Immunotoxin for Treatment of Mesothelioma,
Lung Cancer, Ovarian Cancer and Pancreatic Cancer
Description of Technology: Mesothelin is a cell surface
glycoprotein that is highly expressed in many cancers (e.g., malignant
mesothelioma, lung cancer, ovarian cancer, and pancreatic cancer).
Because of its differential expression, mesothelin is an excellent
[[Page 40382]]
target for the selective killing of cancer cells. For instance, anti-
mesothelin monoclonal antibodies can carry cellular toxins specifically
to mesothelin-expressing cancer cells, resulting in their selective
killing while healthy, essential cells remain unharmed.
A high affinity anti-mesothelin antibody (SS1) was previously
combined with a functional fragment of Pseudomonas Exotoxin A (PE),
producing the immunotoxin SS1P. SS1P selectively killed mesothelin-
expressing cancer cells, suggesting it could be an excellent
therapeutic agent. Unfortunately, PE-based immunotoxins can lose
therapeutic efficacy following multiple administrations, due to the
formation of neutralizing antibodies against the PE portion of the
molecule. As a result, less immunogenic variants of PE have been
created in order to develop immunotoxins that do not induce the
formation of neutralizing antibodies.
Improved PE variants have been created which lack lysosomal
protease sites, a dominant T-cell epitope (PE-LR), and several major B-
cell epitopes (PE-LR/8M). Although these new PE variants demonstrate
efficient cell killing activity when used in combination with certain
antibodies, their activity when using SS1 as the targeting agent (SS1-
LR and SS1-LR/8M) was less impressive. Fortunately, the inventors
surprisingly discovered that the addition of a small linker peptide
within these immunotoxins was able to restore their cell killing
activity to the level of SS1P.
These new SS1-targeted immunotoxins (e.g., SS1-LR/GGS and SS1-LR/
GGS/8M) have the cell-killing activity of SS1P, but are less likely to
generate neutralizing antibodies. As a result, these immunotoxins are
considered to be very promising prospects for treating patients
suffering from mesothelin-expressing cancers.
Applications
Treatment of mesothelin expressing cancers, including
mesothelioma, pancreatic cancer, ovarian cancer and lung
adenocarcinoma.
Treatment in combination with standard chemotherapy.
Diagnostic agent for the detection of mesothelin-
expressing cancers.
Advantages
Immunotoxins are highly selective for cancer cells,
reducing side-effects due to the non-specific killing of essential,
healthy cells.
Less immunogenic PE variants increase the efficacy of the
immunotoxin by reducing the formation and action of neutralizing
antibodies.
PE variants include the removal of both B-cell and T-cell
epitopes.
Use of a small linker peptide offers an unexpected
advantage of strong cell-killing activity with reduced immunogenicity.
Development Status: Preclinical stage of development for anti-
mesothelin immunotoxins; immunotoxins directed to other targets have
some clinical data to demonstrate proof-of-concept
Inventors: Ira Pastan (NCI) et al.
Patent Status
U.S. provisional patent application 61/483,531 (HHS
technology E-117-2011/0-US-01).
U.S. provisional patent application 61/495,085 (HHS
technology E-174-2011/0-US-01).
For More Information
U.S. Patent 7,081,518 (HHS technology E-139-1999/0-US-07).
U.S. Patent Publication US 20090142341 A1 (HHS technology
E-262-2005/0-US-06).
U.S. Patent Publication US 20100215656 A1 (HHS technology
E-292-2007/0-US-06).
PCT Publication WO 2011/032022 (HHS technology E-269-2009/
0-PCT-02).
Licensing Status: Available for licensing.
Licensing Contact: David A. Lambertson, PhD; 301-435-4632;
lambertsond@mail.nih.gov.
Efficient Production of Functional Recombinant Human Neonatal Receptor
(FcRn) Proteins
Description of Technology: Human monoclonal antibodies are becoming
common therapeutics for numerous diseases, including rheumatoid
arthritis, multiple sclerosis, and several different types of cancers.
To improve their half-life, antibodies are engineered to have a high
affinity to the Fc receptor (FcRn). This requires a reliable method to
produce high yields of functional FcRn which comprises a 1:1 molar
ratio of the alpha to the beta chain. Unfortunately, current methods
can be difficult to implement and are not very efficient in producing
functional FcRns with the 1:1 molar ratio of the alpha to the beta
chain. Thus, there is a strong need for quick and economical methods of
producing functional FcRn to aid in antibody development and the
improvement of existing antibody therapeutics.
This technology describes a new and efficient method for producing
functional human FcRn at a 1:1 molar ratio of the alpha to the beta
chain. The uniqueness of this invention is that the expression of both
the beta and the alpha chains is under the control of a single promoter
and the correct 1:1 molar folding of the two chains is facilitated by
the intermediate flexible linker. The method is easy to scale up for
producing large quantities of highly pure FcRn. Further, the inventors
have recently developed a stable cell line for large scale production.
Benefits: Improving the half-life of existing monoclonal antibodies
as well as monoclonal antibodies still in development.
Advantages
Efficient method of producing high yields of functional
human FcRn at a 1:1 molar ratio of the alpha to the beta chain.
Stable cell line also available.
Market: The monoclonal antibodies market generated over $40 billion
in sales for therapeutic uses last year and is expected to grow
significantly over the next several years.
Publications: Feng Y, Gong R, Dimitrov D.S. Design, expression and
characterization of a soluble single-chain functional human neonatal Fc
receptor. Protein Expr Purif. 2011 Mar 29, E-pub ahead of print. [PMID:
21453773]
Inventors: Dimiter S. Dimitrov and Yang Feng (NCI).
Patent Status: HHS Reference No. E-296-2010/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing.
Licensing Contact: Whitney A. Hastings; 301-451-7337;
hastingw@mail.nih.gov.
Immunocompetent Mouse Model for Tracking Cancer Progression
Description of Technology: The technology is a transgenic mouse
model tolerized to firefly Luciferase (ffLuc)- and enhanced green
fluorescent protein (eGFP)-labeled tissue whilst maintaining normal
immune function. Luc and eGFP are the most frequently used bioimaging
markers to track cancer progression in pre-clinical mouse models. As
these markers are immunogenic, their reporter activity becomes
diminished over time and so their use has largely been limited to
immunodeficient mice. However, immune function is crucial for tumor
development and progression, making the use of immunocompetent mice
more desirable.
The immunocompetent mouse model described in this invention was
[[Page 40383]]
generated using the rat growth hormone gene promoter (rGH) to target
ffLuc-eGFP fusion gene expression to the pituitary gland, restricting
any resulting interfering reporter signal within the head. This allows
the tracking of cancer progression throughout the body, where the
reporter activity of introduced ffLuc/eGFP-labeled tumors is
maintained, despite normal immune function. These immunocompetent rGH-
ffLuc-eGFP transgenic mice can be used as hosts in cancer models,
allowing long-term in vivo monitoring of the progression of ffLuc/eGFP-
labeled tumor cells in the body, which may lead to more clinically
relevant insights into cancer progression, metastases and response to
therapies.
Applications
In vivo model for studying tumor progression and testing
anti-cancer therapeutics using ffLuc or eGFP labeling for bioimaging.
Since rGH-ffLuc-eGFP is also a growth hormone-responsive
reporter, these rGH-Luc-GFP mice may also be used to screen growth-
hormone stimulating drugs for treating Achondroplasia (dwarf syndrome)
or as a test for illegal performance-enhancing drugs.
Advantages
This technology represents a more clinically relevant in
vivo model of cancer progression for testing anti-cancer therapeutics.
This immunocompetent mouse model is more desirable as a
pre-clinical model over the currently used immunodeficient mouse models
as immune function is crucial for tumor development and progression.
Development Status
Early-stage.
Pre-clinical.
In vitro data available.
In vivo data available (animal).
Inventors: Chi-Ping Day and Glenn Merlino (NCI).
Relevant Publications
1. Day C.P., et al. Preclinical therapeutic response of residual
metastatic disease is distinct from its primary tumor of origin. Int
J Cancer. 2011 Feb 10, doi: 10.1002/ijc.25978. [Epub ahead of
print].
2. Day C.P., et al. Lentivirus-mediated bifunctional cell
labeling for in vivo melanoma study. Pigment Cell Melanoma Res. 2009
Jun;22(3):283-295. [PMID: 19175523].
3. Luque R.M., et al. Reporter expression, induced by a growth
hormone promoter-driven Cre recombinase (rGHp-Cre) transgene,
questions the developmental relationship between somatotropes and
lactotropes in the adult mouse pituitary gland. Endocrinology. 2007
May;148(5):1946-1953. [PMID: 17289844].
4. Latta-Mahieu M., et al. Gene transfer of a chimeric trans-
activator is immunogenic and results in short-lived transgene
expression. Hum Gene Ther. 2002 Sep 1;13(13):1611-1620. [PMID:
12228016].
5. Stripecke R., et al. Immune response to green fluorescent
protein: implications for gene therapy. Gene Ther. 1999
Jul;6(7):1305-1312. [PMID: 10455440].
6. Liao C.P., et al. Mouse models of prostate adenocarcinoma
with the capacity to monitor spontaneous carcinogenesis by
bioluminescence or fluorescence. Cancer Res. 2007 Aug 1;67(15):7525-
7533. [PMID: 17671224].
Patent Status: HHS Reference No. E-173-2010/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing.
Licensing Contact: Sabarni K. Chatterjee, PhD; 301-435-5587;
chatterjeesa@mail.nih.gov.
Collaborative Research Opportunity: The National Cancer Institute
Center for Cancer Research is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize immunocompetent rGH-ffLuc-eGFP
transgenic mice. Please contact John Hewes, PhD at 301-435-3121 or
hewesj@mail.nih.gov for more information.
Dated: July 1, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-17228 Filed 7-7-11; 8:45 am]
BILLING CODE 4140-01-P
