Government-Owned Inventions; Availability for Licensing, 10375-10378 [2011-4170]
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Federal Register / Vol. 76, No. 37 / Thursday, February 24, 2011 / Notices
Licensing Contacts
• Uri Reichman, PhD, MBA; 301–
435–4616; UR7a@nih.gov.
• John Stansberry, PhD; 301–435–
5236; Stansbej@mail.nih.gov.
emcdonald on DSK2BSOYB1PROD with NOTICES
Meningococcal and Pneumococcal
Conjugate Vaccine and Method of Using
Same
Description of Invention:
Pneumococcal diseases are a major
public health problem all over the
world. The etiological agent,
Streptococcus pneumoniae (the
pneumococcus) is surrounded by a
polysaccharide capsule. Differences in
the composition of this capsule permit
serological differentiation between
about 90 capsular types, some of which
are frequently associated with
pneumococcal disease, others rarely.
Invasive pneumococcal infections
include pneumonia, meningitis and
febrile bacteremia; among the common
non-invasive manifestations are otitis
media, sinusitis and bronchitis. At least
1 million children die of pneumococcal
disease every year, most of these being
young children in developing countries.
Vaccination is the only available tool to
prevent pneumococcal disease. The
recent development of widespread
microbial resistance to essential
antibiotics underlines the urgent need
for more efficient pneumococcal
vaccines.
Meningococcal disease is a contagious
bacterial disease caused by the
meningococcus (Neisseria meningitidis).
It is spread by person-to-person contact
through respiratory droplets of infected
people. There are 3 main clinical forms
of the disease: the meningeal syndrome,
the septic form and pneumonia. The
onset of symptoms is sudden and death
can follow within hours. In as many as
10–15% of survivors, there are
persistent neurological defects,
including hearing loss, speech
disorders, loss of limbs, mental
retardation and paralysis. Up to 5–10%
of a population may be asymptomatic
carriers. These carriers are crucial to the
spread of the disease as most cases are
acquired through exposure to
asymptomatic carriers. Waning
immunity among the population against
a particular strain favors epidemics, as
do overcrowding and climatic
conditions such as dry seasons or
prolonged drought and dust storms. The
disease mainly affects young children,
but is also common in older children
and young adults. The disease occurs
sporadically throughout the world with
seasonal variations and accounts for a
proportion of endemic bacterial
meningitis. However, the highest
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burden of the disease is due to the
cyclic epidemics occurring in the
African meningitis belt.
With the burden of S. pneumoniae
and N. meningitidis infection on the
public health system at a global scale, it
is desirable to have a single vaccine that
is effective to prevent disease resulting
from the infection of both pathogens.
This application claims immunogenic
compositions for inducing an immune
response to two different
microorganisms, S. pneumoniae and N.
meningitidis. The application also
claims conjugate vaccines comprising at
least one N. meningitidis capsular
polysaccharide conjugated to a
recombinant pneumococcal protein.
Applications: Conjugate vaccine for
the prevention and/or therapy of
meningococcal and pneumococcal
infections.
Advantages
• Rapid production time.
• Higher-yielding manufacturing
method.
• Low manufacturing cost.
Development Status: Preclinical
studies have been conducted by the
inventors.
Inventors
• Stanley S. Tai (Howard University).
• Che-Hung Robert Lee (FDA).
Patent Status: HHS Reference No. E–
030–2010/0—
• U.S. Patent Application No. 12/
425,232 filed 16 Apr 2009.
• PCT/US2010/031083 filed 14 Apr
2010.
Licensing Status: Available for
licensing.
Licensing Contact: Daniel G. McCabe;
Associate General Counsel for Business
Transactions; Howard University, Office
of the General Counsel; 2400 6th Street,
NW., Suite 321; Washington, DC 20059;
Office: (202) 806–2650; Fax: (202) 806–
6357; E-mail: dmccabe@howard.edu.
Dated: February 16, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–4171 Filed 2–23–11; 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.
AGENCY:
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ACTION:
10375
Notice.
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:
Terahertz Spatial Light Modulator
System for Adaptive Near-Field
Imaging
Description of Technology: The
invention offered for licensing is in the
field of imaging microscopes and relates
to a terahertz light modulator system,
and in particular to a terahertz spatial
light modulator system for adaptive
near-field imaging.
More specifically, the invention
relates to a spatial light modulator
system for adaptive near-field imaging
having an optical source for transmitting
an optical beam through a filter which
is controlled to convert the optical light
beam into a filtered optical light beam
to define one or more transmission
pathways through a photoconductive
material. The system further includes a
terahertz light source for transmitting a
terahertz beam through one or more
transmission pathways defined by the
filtered optical light beam through the
photoconductive material for
illuminating and scanning the sample
without the use of moving structural
components. The device would allow
micron-scale spatial resolution, would
remove the need to mechanically scan a
sample, and would allow automatic
adjustment of image resolution and
transmitted terahertz power. The nearfield terahertz microscope of the
invention could have a compact, fibercoupled sensor head with no moving
parts—ideal for scientific, medical, and
industrial applications like crystal
growth optimization, skin cancer
diagnosis, and semiconductor chip
inspection. In one application, such as
‘‘one-cut’’ surgery, the compact sensor
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head of the terahertz imaging system has
the capability of distinguishing healthy
cells from cancerous cells with micronscale spatial resolution by immediately
identifying a skin cancer margin
without the need for laboratory work or
additional surgery. In another
application, the terahertz imaging
system may be used in nondestructive
semiconductor chip inspection since the
terahertz imaging system provides
micron-scale spatial resolution.
Applications:
• Biomedical research applications
(living tissues have distinctive terahertz
absorption signals)
• Clinical applications like
diagnostics of skin cancer (skin cancer
and normal skin reflect terahertz
radiation differently)
• Industrial applications like crystal
growth optimization
• Industrial applications like
semiconductor chip inspection.
Advantages: The system provides
micron-scale spatial resolution, while
removing any need to mechanically
scan samples (it is equipped with a
fiber-coupled sensor head), and at the
same time allows automatic adjustment
of image resolution and transmitted
terahertz power.
Development Status: In development.
Prototype is being built.
Inventors: Hari Shroff et al. (NIBIB).
Relevant Publications:
1. Mair S, Gompf B, Dressel M.
Microspectroscopy and imaging in the
THz range using coherent CW radiation.
Phys Med Biol. 2002 Nov
7;47(21):3719–3725. [PubMed:
12452559]
2. Chen Q, Jiang Z, Xu GX, Zhang XC.
Near-field terahertz imaging with a
dynamic aperture. Opt Lett. 2000 Aug
1;25(15):1122–1124. [PubMed:
18064291]
3. Wallace VP, Fitzgerald AJ, Shankar
S, Flanagan N, Pye R, Cluff J, Arnone
DD. Terahertz pulsed imaging of basal
cell carcinoma ex vivo and in vivo. Br
J Dermatol. 2004 Aug;151(2):424–432.
[PubMed: 15327550]
4. Hu BB, Nuss MC. Imaging with
terahertz waves. Opt Lett. 1995 Aug
15;20(16):1716–1718.
Patent Status: U.S. Provisional
Application No. 61/425,007 filed 20 Dec
2010 (HHS Reference No. E–243–2010/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact:
• Uri Reichman, PhD, MBA; 301–
435–4616; UR7a@nih.gov.
• Michael Shmilovich, Esq.; 301–
435–5019; ShmilovichM@mail.nih.gov.
Collaborative Research Opportunity:
The National Institute of Biomedical
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Imaging and Bioengineering is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize this technology. Please
contact Hari Shroff at
hari.shroff@nih.gov or 301–435–1995 for
more information.
Versatile Melanoma Antigen Family A3
(MAGE–A3) Specific Human T Cell
Receptors To Treat Cancer That Also
Recognize Other MAGE–A Antigen
Superfamily Members
Description of Technology: Current
approaches for treating cancer can also
generate harsh side effects in patients
and many cancer patients do not
respond to generalized chemotherapy
and radiation. New and improved
therapeutic strategies need to be
characterized by reduced side-effects
and enhancements in specific antitumor activity in individual patients.
Adoptive immunotherapy is a
promising new approach to cancer
treatment that engineers an individual’s
innate and adaptive immune system to
fight against specific diseases, such as
cancer. Scientists are aiming to improve
cell transfer therapies by targeting an
increasing collection of tumor antigens
with more effective immune cell
cultures.
T cell receptors (TCRs) are specialized
proteins that recognize antigens in the
context of infected or transformed cells
and activate T cells to mediate an
immune response and destroy abnormal
cells. TCRs consist of a variable domain
that recognizes the antigen and a
constant region that anchors the TCR to
the membrane and transmits recognition
signals by interacting with other
proteins. When a TCR is activated by
recognizing its antigen, such as a tumor
antigen, signaling pathways are
triggered in the cell to produce
cytokines that mediate the immune
response.
Scientists at the National Institutes of
Health (NIH) have developed T cells
genetically engineered to recognize
melanoma antigen family A3 (MAGE–
A3) peptide antigens. MAGE–A
superfamily antigens, including MAGE–
A3, are expressed primarily by tumor
cells from a variety of cancers. Other
than germ cells of the testis, normal
cells do not express MAGE–A3 and
other MAGE–A proteins, which makes
these antigens ideal targets for
developing cancer immunotherapies.
There are twelve (12) known MAGE–A
genes designated A1–A12. The normal
function of MAGE–A3 is not completely
known, but in cancerous cells it appears
to mediate fibronectin-controlled tumor
growth and spreading. MAGE–A3 is one
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of the most widely expressed cancer
testis antigens (CTAs) on human tumors
and its expression increases as the
cancer progresses to more advanced
stages. The T cell receptors (TCRs)
developed by these NIH scientists have
specificity for MAGE–A3 and MAGE–
A12 and deliver a robust immune
response when they encounter tumor
cells expressing these antigens. These
TCRs also recognize MAGE–A2 and/or
MAGE–A6, but to a lesser extent that
MAGE–A3 and MAGE–A12. The ability
to recognize antigens from multiple
MAGE–A family members could allow
these TCRs to be utilized in the
treatment of multiple types of cancer in
a wide array of cancer patients. Infusing
cancer patients with MAGE–A3 specific
T cells via adoptive immunotherapy
could prove to be a powerful approach
for selectively attacking tumors without
generating toxicity against
noncancerous cells.
Applications:
• Immunotherapeutics to treat and/or
prevent the recurrence of a variety of
human cancers, including melanoma,
lung cancers, head and neck cancers,
liver cancers, and multiple myeloma, by
adoptively transferring the genemodified T cells into patients whose
tumors express a MAGE–A family
member protein recognized by this TCR.
• A drug component of a combination
immunotherapy regimen aimed at
targeting specific tumor-associated
antigens, including MAGE–A3, MAGE–
A12, and MAGE–A2 and/or MAGE–A6
expressed by cancer cells within
individual patients.
• A research tool to investigate
signaling pathways in MAGE–A antigen
expressing cancer cells.
• An in vitro diagnostic tool to screen
for cells expressing a MAGE–A antigens.
Advantages:
• Selective toxicity for tumor cells—
MAGE–A3 and other MAGE–A proteins
are only expressed on testis germ cells
and tumor cells. Thus, infused cells
expressing an anti-MAGE–A3 TCR
should target MAGE–A3-expressing
tumor cells with little or no toxicity to
normal cells. Immunotherapy with these
T cells should yield little or no harsh
side effects to patients.
• Ability to recognize multiple
MAGE–A antigens—Since these MAGE–
A3 directed TCRs can also recognize up
to three (3) additional MAGE–A
antigens (MAGE–A12, A2, and A6),
cells expressing these TCRs are
expected to be able to fight a larger
range of tumor types. During treatment,
if an infused anti-MAGE–A3 T cell
culture encounters tumor cells
expressing other recognized MAGE–A
antigens, these T cells would not only
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be capable of eliminating the MAGE–A3
expressing tumor cells, but MAGE–A12,
MAGE–A2, and MAGE–A6 expressing
cells as well. This versatility should
allow these TCRs to be utilized to treat
a broader range of cancer patients.
• Expression on a majority of tumors
—MAGE–A3 is one of the most highly
expressed cancer testis antigens (CTAs)
on human tumors. For example, over
half of melanoma tumors and non-small
cell lung cancer cells express MAGE–
A3. A large spectrum of cancer patients
should be eligible for treatment with
these MAGE–A3 TCRs should they
prove successful in clinical studies.
Development Status: This technology
is in an early clinical stage of
development.
Inventors: Richard A. Morgan, et al.
(NCI).
Publications:
1. N Chinnasamy et al. A TCR
Targeting the HLA–A*0201–Restricted
Epitope of MAGE–A3 Recognizes
Multiple Epitopes of the MAGE–A
Antigen Superfamily in Several Types
of Cancer. J Immunol. 2011 Jan
15;186(2):685–696. [PubMed: 21149604]
2. V Cesson et al. MAGE–A3 and
MAGE–A4 specific CD4(+) T cells in
head and neck cancer patients:
Detection of naturally acquired
responses and identification of new
epitopes. Cancer Immunol Immunother.
2010 Sept. 21, E-pub ahead of print, doi:
10.1007/s00262–010–0916-z. [PubMed:
20857101]
Patent Status: U.S. Provisional
Application No. 61/405,668 filed 22
October 2010 (HHS Reference No. E–
236–2010/0–US–01).
Related Technologies: T cell receptor
technologies developed against other
CTAs: E–304–2006/0 and E–312–2007/1
(anti-NY–ESO–1) and E–269–2010/0
(anti-SSX–2).
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 the use of anti-MAGE–A
T-cell receptors for the adoptive
immunotherapy of cancer. Please
contact John Hewes, PhD at 301–435–
3121 or hewesj@mail.nih.gov for more
information.
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Selective 12–Human Lipoxygenase
Inhibitors for the Treatment of Diabetes
and Clotting
Description of Technology: This
invention discloses small molecule
inhibitors of human 12-lipoxygenase
(12-hLO). 12-lipoxygenase expression,
activation, and lipid metabolites have
been implicated in type 1 and type 2
diabetes, cardiovascular disease,
hypertension, Alzheimer’s, and
Parkinson’s disease. The development
of 12-hLO inhibitors may be a potent
intracellular approach to decreasing the
ability of platelets to form large clots in
response to vessel injury or activation of
the coagulation pathway. Thus, 12-hLO
inhibition has the potential to attenuate
platelet-mediated clot formation caused
by diabetes and/or cardiovascular
disease and significantly decrease the
occurrence of myocardial infarction and
death. Moreover, Type 1 and Type 2
diabetes are serious disorders that can
lead to major complications and
reduced lifespan. An unmet medical
need is to identify new ways to protect
beta cells in these metabolic disorders.
A selective 12-hLO inhibitor could
provide a new therapeutic approach to
prevent or treat either form of diabetes.
Applications:
• Therapeutic developments (blood
clots; Type 1 and Type 2 diabetes,
cardiovascular disease, and
neurodegenerative diseases)
• Inflammatory responses
Advantages:
• Small molecule (series of analogs
can be derived in search of improved
performances and/or different
functions)
• Selective inhibitor of human 12lipoxygenase
Market:
• Metabolic disorders
• Neurodegeneration
• Research tool—screening for 12lipoxygenase-mediated responses in
various human cell lines
Development Status: Pre-clinical; no
animal data.
Inventors: David J Maloney (NHGRI);
Ajit Jadhav (NHGRI); Ganesha Rai
(NHGRI); Anton Simeonov (NHGRI);
Theodore Holman (University California
Santa Cruz); Jerry Nadler (Eastern
Virginia Medical School); Michael
Holinstat (Thomas Jefferson University).
Patent Status: U.S. Provisional
Application No. 61/345,708 filled 18
May 2010 (HHS Reference No. E–134–
2010/0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Steven H.
Standley, PhD 301–435–4074;
sstand@mail.nih.gov.
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10377
Gene Expressed in Prostate Cancer and
Methods of Use
Description of Technology: Prostate
cancer is the second leading cause of
cancer-related deaths among males in
the United States. There are
approximately two hundred and fifteen
thousand (215,000) newly diagnosed
cases of prostate cancer and thirty
thousand (30,000) prostate cancerrelated deaths each year, underscoring
the importance of addressing this
deadly disease. Although there are
diagnostic tests in place for identifying
the potential for developing prostate
cancer, even the most widely accepted
diagnostic for detecting cancer (prostatespecific antigen or PSA) is capable of
producing a false negative result.
Furthermore, current treatments are
invasive and may produce deleterious
side-effects. Therefore, there is a clear
need to identify and develop new and
effective diagnostics and treatments for
prostate cancer.
This technology concerns the
identification of a novel protein that is
specifically expressed on prostate
tissue: Novel Gene Expressed in Prostate
(NGEP). Because of its selective
expression on prostate tissue, NGEP
represents a potential target in the fight
against prostate cancer. Monoclonal
antibodies that specifically recognize
NGEP have been developed in
conjunction with the identification of
the protein. These antibodies can be
used as both diagnostic agents and
therapeutic agents.
Applications:
• Antibodies to NGEP can be used as
diagnostic agents to identify metastatic
prostate tissue, either alone or in
combination with other diagnostic
antibodies
• Antibodies to NGEP can also be
used therapeutically to specifically
target cytotoxic agents to prostate cancer
cells or to induce antibody-dependent
cell-mediated cytotoxicity (ADCC)
• Antibodies to NGEP can be used as
research reagents for identifying
prostate tissue, including cancerous
tissue
Advantages:
• The selective expression of NGEP
allows the specific detection and
recognition of prostate tissue, which is
useful in both diagnostic and
therapeutic applications
• Combining the detection of NGEP
with other prostate cancer diagnostic
agents may reduce the incidence of a
false negative diagnosis
• The use of NGEP antibodies in
targeted therapy can decrease the nonspecific killing of non-cancerous cells,
thereby decreasing side-effects
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associated with current prostate cancer
therapies
Development Status: Preclinical stage
of development.
Inventors: Pastan (NCI) et al.
Patent Status:
• US Patent 7,816,087 (E–005–2002/
0–US–03)—Issued
• US Patent Application 12/193,604
(E–005–2002/0–US–05)—Allowed
• EP Patent Application 02795643.2
(E–005–2002/0–EP–04)—Pending
For more information, see:
• Das et al. ‘‘Topology of NGEP, a
prostate-specific cell:cell junction
protein widely expressed in many
cancers of different grade level.’’ Cancer
Res. 2008 Aug 1; 68(15):6306–12
• Das et al. ‘‘NGEP, a prostate-specific
plasma membrane protein that promotes
the association of LNCaP cells.’’ Cancer
Res. 2007 Feb 15; 67(4):1594–601
• Bera et al. ‘‘NGEP, a gene encoding
a membrane protein detected only in
prostate cancer and normal prostate.’’
Proc Natl Acad Sci U S A. 2004 Mar 2;
101(9):3059–64.
Licensing Status: Available for
licensing
Licensing Contact: David A.
Lambertson, PhD; 301–435–4632;
lambertsond@mail.nih.gov.
Stem Cells That Transform To Beating
Cardiomyocytes
Description of Technology: Many
people die each year of congestive heart
failure occurring from a variety of
causes including cardiomyopathy,
myocardial ischemia, congenital heart
disease and valvular heart disease
resulting in cardiac cell death and
myocardial dysfunction. When
cardiomyocytes are not replaced in
adult myocardial tissue, physiologic
demands on existing, healthy
cardiomyocytes can lead to
hypertrophy. Heart transplants have
been the only recourse for patients in
end-stage heart disease however this is
complicated by lack of donors, tissue
incompatibility and high cost.
An alternative approach to heart
transplantation is to generate
cardiomyocytes from stem cells in vitro
that can be used in the treatment of
cardiac diseases characterized by
myocardial cell death or dysfunction.
This invention discloses a novel
isolated population of stem cells, called
spoc cells, isolated from skeletal
muscle, that can be induced, either in
vivo or in vitro, to differentiate into
cardiomyocytes. Spoc cells may be
differentiated and utilized for screening
agents that affect cardiomyocytes and as
therapeutic agents in the treatment of
cardiac MI.
Potential Applications and
Advantages: This invention is an
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alternative approach to heart
transplantation which is typically
complicated by lack of donors, tissue
incompatibility and high cost.
Inventors: Neal D. Epstein (NHLBI), et
al.
Related Publication: SO Winitsky, et
al. Adult murine skeletal muscle
contains cells that can differentiate into
beating cardiomyocytes in vitro. PLoS
Biol. 2005 Apr;3(4):e87, doi:10.1371/
journal.pbio.0030087. [PubMed:
15757365]
Patent Status:
• Issued Australian Patent No.
2002337949 (HHS Ref. No. E–329–2001/
0–AU–03)
• Issued Japanese Patent No. 4377690
(HHS Ref. No. E–329–2001/0–JP–04)
• Allowed Canadian Patent Appl. No.
2464088 (HHS Ref. No. E–329–2001/0–
CA–05)
Licensing Status: Available for
licensing.
Licensing Contact: Fatima Sayyid,
M.H.P.M.; 301–435–4521;
Fatima.Sayyid@nih.hhs.gov.
Dated: February 16, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 2011–4170 Filed 2–23–11; 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
SUMMARY:
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Confidential Disclosure Agreement will
be required to receive copies of the
patent applications.
Recombinant BoCPB: An Enzymatic
Reagent for Removing Disordered,
Positively Charged C-terminal Residues
From Recombinant Proteins
Description of Technology: Affinity
tags are commonly used to facilitate the
purification of recombinant proteins,
but concerns about the potential impact
of the tags on the biological activity of
the target proteins makes it necessary to
remove them in most cases. Proteases
with high sequence specificity, such as
tobacco etch virus (TEV) protease, are
typically used for this purpose. Affinity
tags on the amino-terminus (N-terminal
tag) can be cleaved by TEV protease to
yield a recombinant protein product
with only one nonnative residues on its
C-terminus (usually G or S). In contrast,
removal by TEV protease of tags added
to the carboxy-terminus (C-terminal tag)
of proteins has proven to be somewhat
problematic, yielding a recombinant
protein product with six nonnative
residues on its C-terminus (ENLYFQ).
Since C-terminal affinity tags are
potentially very useful, particularly
when used in combination with Nterminal tags in an ‘‘affinity sandwich’’
format, it would be very desirable to
have a reagent to remove the C-terminal
affinity tags without leaving extra
nonnative residues behind.
Previously, the NIH inventors created
a tagged version of a fungal
carboxypeptidase from Metarhizium
anisopliae (MeCPA) that is capable of
removing histidine residues and many
other types of amino acids from the Ctermini of recombinant proteins. The
only limitation of the MeCPA enzyme is
that it does not remove positively
charged residues (arginine and lysine).
To overcome this drawback of MeCPA,
the NIH inventors have now cloned,
expressed and purified bovine
carboxypeptidase B (BoCPB), which is
specific for the removal of these
positively charged residues. Like the
genetically engineered MeCPA, the
recombinant BoCPB has a C-terminal
polyhistidine tag. This feature facilitates
the purification of the enzyme, and,
because this His-tag as been engineered
to be immune to the action of MeCPA
and BoCPB, it can be used to separate
the enzymes from the products of a
carboxypeptidase digest. By using a
mixture of MeCPA and BoCPB, it should
be possible to remove any short affinity
tag along with disordered C-terminal
residues of a recombinant protein with
the exception of proline, which can be
used as a ‘‘stop sign’’ to facilitate the
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Agencies
[Federal Register Volume 76, Number 37 (Thursday, February 24, 2011)]
[Notices]
[Pages 10375-10378]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-4170]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
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SUMMARY: The inventions listed below are owned by an agency of the U.S.
Government and are available for licensing in the U.S. in accordance
with 35 U.S.C. 207 to achieve expeditious commercialization of results
of federally-funded research and development. Foreign patent
applications are filed on selected inventions to extend market coverage
for companies and may also be available for licensing.
ADDRESSES: Licensing information and copies of the U.S. patent
applications listed below may be obtained by writing to the indicated
licensing contact at the Office of Technology Transfer, National
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville,
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A
signed Confidential Disclosure Agreement will be required to receive
copies of the patent applications.
Terahertz Spatial Light Modulator System for Adaptive Near-Field
Imaging
Description of Technology: The invention offered for licensing is
in the field of imaging microscopes and relates to a terahertz light
modulator system, and in particular to a terahertz spatial light
modulator system for adaptive near-field imaging.
More specifically, the invention relates to a spatial light
modulator system for adaptive near-field imaging having an optical
source for transmitting an optical beam through a filter which is
controlled to convert the optical light beam into a filtered optical
light beam to define one or more transmission pathways through a
photoconductive material. The system further includes a terahertz light
source for transmitting a terahertz beam through one or more
transmission pathways defined by the filtered optical light beam
through the photoconductive material for illuminating and scanning the
sample without the use of moving structural components. The device
would allow micron-scale spatial resolution, would remove the need to
mechanically scan a sample, and would allow automatic adjustment of
image resolution and transmitted terahertz power. The near-field
terahertz microscope of the invention could have a compact, fiber-
coupled sensor head with no moving parts--ideal for scientific,
medical, and industrial applications like crystal growth optimization,
skin cancer diagnosis, and semiconductor chip inspection. In one
application, such as ``one-cut'' surgery, the compact sensor
[[Page 10376]]
head of the terahertz imaging system has the capability of
distinguishing healthy cells from cancerous cells with micron-scale
spatial resolution by immediately identifying a skin cancer margin
without the need for laboratory work or additional surgery. In another
application, the terahertz imaging system may be used in nondestructive
semiconductor chip inspection since the terahertz imaging system
provides micron-scale spatial resolution.
Applications:
Biomedical research applications (living tissues have
distinctive terahertz absorption signals)
Clinical applications like diagnostics of skin cancer
(skin cancer and normal skin reflect terahertz radiation differently)
Industrial applications like crystal growth optimization
Industrial applications like semiconductor chip
inspection.
Advantages: The system provides micron-scale spatial resolution,
while removing any need to mechanically scan samples (it is equipped
with a fiber-coupled sensor head), and at the same time allows
automatic adjustment of image resolution and transmitted terahertz
power.
Development Status: In development. Prototype is being built.
Inventors: Hari Shroff et al. (NIBIB).
Relevant Publications:
1. Mair S, Gompf B, Dressel M. Microspectroscopy and imaging in the
THz range using coherent CW radiation. Phys Med Biol. 2002 Nov
7;47(21):3719-3725. [PubMed: 12452559]
2. Chen Q, Jiang Z, Xu GX, Zhang XC. Near-field terahertz imaging
with a dynamic aperture. Opt Lett. 2000 Aug 1;25(15):1122-1124.
[PubMed: 18064291]
3. Wallace VP, Fitzgerald AJ, Shankar S, Flanagan N, Pye R, Cluff
J, Arnone DD. Terahertz pulsed imaging of basal cell carcinoma ex vivo
and in vivo. Br J Dermatol. 2004 Aug;151(2):424-432. [PubMed: 15327550]
4. Hu BB, Nuss MC. Imaging with terahertz waves. Opt Lett. 1995 Aug
15;20(16):1716-1718.
Patent Status: U.S. Provisional Application No. 61/425,007 filed 20
Dec 2010 (HHS Reference No. E-243-2010/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact:
Uri Reichman, PhD, MBA; 301-435-4616; UR7a@nih.gov.
Michael Shmilovich, Esq.; 301-435-5019;
ShmilovichM@mail.nih.gov.
Collaborative Research Opportunity: The National Institute of
Biomedical Imaging and Bioengineering is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate, or commercialize this
technology. Please contact Hari Shroff at hari.shroff@nih.gov or 301-
435-1995 for more information.
Versatile Melanoma Antigen Family A3 (MAGE-A3) Specific Human T Cell
Receptors To Treat Cancer That Also Recognize Other MAGE-A Antigen
Superfamily Members
Description of Technology: Current approaches for treating cancer
can also generate harsh side effects in patients and many cancer
patients do not respond to generalized chemotherapy and radiation. New
and improved therapeutic strategies need to be characterized by reduced
side-effects and enhancements in specific anti-tumor activity in
individual patients. Adoptive immunotherapy is a promising new approach
to cancer treatment that engineers an individual's innate and adaptive
immune system to fight against specific diseases, such as cancer.
Scientists are aiming to improve cell transfer therapies by targeting
an increasing collection of tumor antigens with more effective immune
cell cultures.
T cell receptors (TCRs) are specialized proteins that recognize
antigens in the context of infected or transformed cells and activate T
cells to mediate an immune response and destroy abnormal cells. TCRs
consist of a variable domain that recognizes the antigen and a constant
region that anchors the TCR to the membrane and transmits recognition
signals by interacting with other proteins. When a TCR is activated by
recognizing its antigen, such as a tumor antigen, signaling pathways
are triggered in the cell to produce cytokines that mediate the immune
response.
Scientists at the National Institutes of Health (NIH) have
developed T cells genetically engineered to recognize melanoma antigen
family A3 (MAGE-A3) peptide antigens. MAGE-A superfamily antigens,
including MAGE-A3, are expressed primarily by tumor cells from a
variety of cancers. Other than germ cells of the testis, normal cells
do not express MAGE-A3 and other MAGE-A proteins, which makes these
antigens ideal targets for developing cancer immunotherapies. There are
twelve (12) known MAGE-A genes designated A1-A12. The normal function
of MAGE-A3 is not completely known, but in cancerous cells it appears
to mediate fibronectin-controlled tumor growth and spreading. MAGE-A3
is one of the most widely expressed cancer testis antigens (CTAs) on
human tumors and its expression increases as the cancer progresses to
more advanced stages. The T cell receptors (TCRs) developed by these
NIH scientists have specificity for MAGE-A3 and MAGE-A12 and deliver a
robust immune response when they encounter tumor cells expressing these
antigens. These TCRs also recognize MAGE-A2 and/or MAGE-A6, but to a
lesser extent that MAGE-A3 and MAGE-A12. The ability to recognize
antigens from multiple MAGE-A family members could allow these TCRs to
be utilized in the treatment of multiple types of cancer in a wide
array of cancer patients. Infusing cancer patients with MAGE-A3
specific T cells via adoptive immunotherapy could prove to be a
powerful approach for selectively attacking tumors without generating
toxicity against noncancerous cells.
Applications:
Immunotherapeutics to treat and/or prevent the recurrence
of a variety of human cancers, including melanoma, lung cancers, head
and neck cancers, liver cancers, and multiple myeloma, by adoptively
transferring the gene-modified T cells into patients whose tumors
express a MAGE-A family member protein recognized by this TCR.
A drug component of a combination immunotherapy regimen
aimed at targeting specific tumor-associated antigens, including MAGE-
A3, MAGE-A12, and MAGE-A2 and/or MAGE-A6 expressed by cancer cells
within individual patients.
A research tool to investigate signaling pathways in MAGE-
A antigen expressing cancer cells.
An in vitro diagnostic tool to screen for cells expressing
a MAGE-A antigens.
Advantages:
Selective toxicity for tumor cells--MAGE-A3 and other
MAGE-A proteins are only expressed on testis germ cells and tumor
cells. Thus, infused cells expressing an anti-MAGE-A3 TCR should target
MAGE-A3-expressing tumor cells with little or no toxicity to normal
cells. Immunotherapy with these T cells should yield little or no harsh
side effects to patients.
Ability to recognize multiple MAGE-A antigens--Since these
MAGE-A3 directed TCRs can also recognize up to three (3) additional
MAGE-A antigens (MAGE-A12, A2, and A6), cells expressing these TCRs are
expected to be able to fight a larger range of tumor types. During
treatment, if an infused anti-MAGE-A3 T cell culture encounters tumor
cells expressing other recognized MAGE-A antigens, these T cells would
not only
[[Page 10377]]
be capable of eliminating the MAGE-A3 expressing tumor cells, but MAGE-
A12, MAGE-A2, and MAGE-A6 expressing cells as well. This versatility
should allow these TCRs to be utilized to treat a broader range of
cancer patients.
Expression on a majority of tumors --MAGE-A3 is one of the
most highly expressed cancer testis antigens (CTAs) on human tumors.
For example, over half of melanoma tumors and non-small cell lung
cancer cells express MAGE-A3. A large spectrum of cancer patients
should be eligible for treatment with these MAGE-A3 TCRs should they
prove successful in clinical studies.
Development Status: This technology is in an early clinical stage
of development.
Inventors: Richard A. Morgan, et al. (NCI).
Publications:
1. N Chinnasamy et al. A TCR Targeting the HLA-A*0201-Restricted
Epitope of MAGE-A3 Recognizes Multiple Epitopes of the MAGE-A Antigen
Superfamily in Several Types of Cancer. J Immunol. 2011 Jan
15;186(2):685-696. [PubMed: 21149604]
2. V Cesson et al. MAGE-A3 and MAGE-A4 specific CD4(+) T cells in
head and neck cancer patients: Detection of naturally acquired
responses and identification of new epitopes. Cancer Immunol
Immunother. 2010 Sept. 21, E-pub ahead of print, doi: 10.1007/s00262-
010-0916-z. [PubMed: 20857101]
Patent Status: U.S. Provisional Application No. 61/405,668 filed 22
October 2010 (HHS Reference No. E-236-2010/0-US-01).
Related Technologies: T cell receptor technologies developed
against other CTAs: E-304-2006/0 and E-312-2007/1 (anti-NY-ESO-1) and
E-269-2010/0 (anti-SSX-2).
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 the use of anti-MAGE-A T-cell receptors for
the adoptive immunotherapy of cancer. Please contact John Hewes, PhD at
301-435-3121 or hewesj@mail.nih.gov for more information.
Selective 12-Human Lipoxygenase Inhibitors for the Treatment of
Diabetes and Clotting
Description of Technology: This invention discloses small molecule
inhibitors of human 12-lipoxygenase (12-hLO). 12-lipoxygenase
expression, activation, and lipid metabolites have been implicated in
type 1 and type 2 diabetes, cardiovascular disease, hypertension,
Alzheimer's, and Parkinson's disease. The development of 12-hLO
inhibitors may be a potent intracellular approach to decreasing the
ability of platelets to form large clots in response to vessel injury
or activation of the coagulation pathway. Thus, 12-hLO inhibition has
the potential to attenuate platelet-mediated clot formation caused by
diabetes and/or cardiovascular disease and significantly decrease the
occurrence of myocardial infarction and death. Moreover, Type 1 and
Type 2 diabetes are serious disorders that can lead to major
complications and reduced lifespan. An unmet medical need is to
identify new ways to protect beta cells in these metabolic disorders. A
selective 12-hLO inhibitor could provide a new therapeutic approach to
prevent or treat either form of diabetes.
Applications:
Therapeutic developments (blood clots; Type 1 and Type 2
diabetes, cardiovascular disease, and neurodegenerative diseases)
Inflammatory responses
Advantages:
Small molecule (series of analogs can be derived in search
of improved performances and/or different functions)
Selective inhibitor of human 12-lipoxygenase
Market:
Metabolic disorders
Neurodegeneration
Research tool--screening for 12-lipoxygenase-mediated
responses in various human cell lines
Development Status: Pre-clinical; no animal data.
Inventors: David J Maloney (NHGRI); Ajit Jadhav (NHGRI); Ganesha
Rai (NHGRI); Anton Simeonov (NHGRI); Theodore Holman (University
California Santa Cruz); Jerry Nadler (Eastern Virginia Medical School);
Michael Holinstat (Thomas Jefferson University).
Patent Status: U.S. Provisional Application No. 61/345,708 filled
18 May 2010 (HHS Reference No. E-134-2010/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Steven H. Standley, PhD 301-435-4074;
sstand@mail.nih.gov.
Gene Expressed in Prostate Cancer and Methods of Use
Description of Technology: Prostate cancer is the second leading
cause of cancer-related deaths among males in the United States. There
are approximately two hundred and fifteen thousand (215,000) newly
diagnosed cases of prostate cancer and thirty thousand (30,000)
prostate cancer-related deaths each year, underscoring the importance
of addressing this deadly disease. Although there are diagnostic tests
in place for identifying the potential for developing prostate cancer,
even the most widely accepted diagnostic for detecting cancer
(prostate-specific antigen or PSA) is capable of producing a false
negative result. Furthermore, current treatments are invasive and may
produce deleterious side-effects. Therefore, there is a clear need to
identify and develop new and effective diagnostics and treatments for
prostate cancer.
This technology concerns the identification of a novel protein that
is specifically expressed on prostate tissue: Novel Gene Expressed in
Prostate (NGEP). Because of its selective expression on prostate
tissue, NGEP represents a potential target in the fight against
prostate cancer. Monoclonal antibodies that specifically recognize NGEP
have been developed in conjunction with the identification of the
protein. These antibodies can be used as both diagnostic agents and
therapeutic agents.
Applications:
Antibodies to NGEP can be used as diagnostic agents to
identify metastatic prostate tissue, either alone or in combination
with other diagnostic antibodies
Antibodies to NGEP can also be used therapeutically to
specifically target cytotoxic agents to prostate cancer cells or to
induce antibody-dependent cell-mediated cytotoxicity (ADCC)
Antibodies to NGEP can be used as research reagents for
identifying prostate tissue, including cancerous tissue
Advantages:
The selective expression of NGEP allows the specific
detection and recognition of prostate tissue, which is useful in both
diagnostic and therapeutic applications
Combining the detection of NGEP with other prostate cancer
diagnostic agents may reduce the incidence of a false negative
diagnosis
The use of NGEP antibodies in targeted therapy can
decrease the non-specific killing of non-cancerous cells, thereby
decreasing side-effects
[[Page 10378]]
associated with current prostate cancer therapies
Development Status: Preclinical stage of development.
Inventors: Pastan (NCI) et al.
Patent Status:
US Patent 7,816,087 (E-005-2002/0-US-03)--Issued
US Patent Application 12/193,604 (E-005-2002/0-US-05)--
Allowed
EP Patent Application 02795643.2 (E-005-2002/0-EP-04)--
Pending
For more information, see:
Das et al. ``Topology of NGEP, a prostate-specific
cell:cell junction protein widely expressed in many cancers of
different grade level.'' Cancer Res. 2008 Aug 1; 68(15):6306-12
Das et al. ``NGEP, a prostate-specific plasma membrane
protein that promotes the association of LNCaP cells.'' Cancer Res.
2007 Feb 15; 67(4):1594-601
Bera et al. ``NGEP, a gene encoding a membrane protein
detected only in prostate cancer and normal prostate.'' Proc Natl Acad
Sci U S A. 2004 Mar 2; 101(9):3059-64.
Licensing Status: Available for licensing
Licensing Contact: David A. Lambertson, PhD; 301-435-4632;
lambertsond@mail.nih.gov.
Stem Cells That Transform To Beating Cardiomyocytes
Description of Technology: Many people die each year of congestive
heart failure occurring from a variety of causes including
cardiomyopathy, myocardial ischemia, congenital heart disease and
valvular heart disease resulting in cardiac cell death and myocardial
dysfunction. When cardiomyocytes are not replaced in adult myocardial
tissue, physiologic demands on existing, healthy cardiomyocytes can
lead to hypertrophy. Heart transplants have been the only recourse for
patients in end-stage heart disease however this is complicated by lack
of donors, tissue incompatibility and high cost.
An alternative approach to heart transplantation is to generate
cardiomyocytes from stem cells in vitro that can be used in the
treatment of cardiac diseases characterized by myocardial cell death or
dysfunction.
This invention discloses a novel isolated population of stem cells,
called spoc cells, isolated from skeletal muscle, that can be induced,
either in vivo or in vitro, to differentiate into cardiomyocytes. Spoc
cells may be differentiated and utilized for screening agents that
affect cardiomyocytes and as therapeutic agents in the treatment of
cardiac MI.
Potential Applications and Advantages: This invention is an
alternative approach to heart transplantation which is typically
complicated by lack of donors, tissue incompatibility and high cost.
Inventors: Neal D. Epstein (NHLBI), et al.
Related Publication: SO Winitsky, et al. Adult murine skeletal
muscle contains cells that can differentiate into beating
cardiomyocytes in vitro. PLoS Biol. 2005 Apr;3(4):e87, doi:10.1371/
journal.pbio.0030087. [PubMed: 15757365]
Patent Status:
Issued Australian Patent No. 2002337949 (HHS Ref. No. E-
329-2001/0-AU-03)
Issued Japanese Patent No. 4377690 (HHS Ref. No. E-329-
2001/0-JP-04)
Allowed Canadian Patent Appl. No. 2464088 (HHS Ref. No. E-
329-2001/0-CA-05)
Licensing Status: Available for licensing.
Licensing Contact: Fatima Sayyid, M.H.P.M.; 301-435-4521;
Fatima.Sayyid@nih.hhs.gov.
Dated: February 16, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-4170 Filed 2-23-11; 8:45 am]
BILLING CODE 4140-01-P