Government-Owned Inventions; Availability for Licensing, 23727-23729 [E9-11706]
Download as PDF
<![CDATA[
Federal Register / Vol. 74, No. 96 / Wednesday, May 20, 2009 / Notices
FDA received 146,274 mandatory
reports to CDRH during 2007. Based on
this experience, FDA estimates that
CDRH will receive 146,274 mandatory
reports annually from 1,665 users of the
electronic reporting system (a group
comprised of facilities, importers, and
manufacturers). FDA estimates the
maximum reporting burden for a
mandatory report to be 1 hour, for a
total burden of 146,274 hours (146,274
reports x 1 hour = 146,274 hours) or a
minimum burden of 99,466 hours with
((146,274 reports x 80% x 0.60 hour) +
(146,274 reports x 20% x 1 hour) =
99,466.32 hours). FDA received 5,000
voluntary reports to CFSAN during
2007. Based on this experience, FDA
estimates that CFSAN will receive 5,000
voluntary reports annually from 5,000
users of the electronic reporting system.
FDA estimates the reporting burden for
a voluntary report to be 0.6 hours, for
a total burden of 3,000 hours (5,000
reports x 0.6 hours = 3,000 hours).
FDA received 214 mandatory dietary
supplement reports to CFSAN from
January 1, 2008, to April 15, 2008.
Based on this experience, FDA estimates
that CFSAN will receive 856 mandatory
reports annually from 150 users of the
electronic reporting system. FDA
estimates the maximum reporting
burden for a mandatory report to be 1
hour, for a total burden of 856 hours
(856 reports x 1 hour = 856 hours) or a
minimum burden of 582 hours with
((856 reports x 80% x 0.60 hour) + (856
reports x 20% x 1 hour) = 582.08 hours).
FDA received 163 voluntary reports to
CVM during 2007. Based on this
experience, FDA estimates that CVM
will receive 163 voluntary reports
annually from 163 users of the
electronic reporting system. FDA
estimates the reporting burden for a
voluntary report to be 0.6 hours for a
total burden of 98 hours (163 reports x
0.6 hours = 97.8 hours).
FDA received 35,765 mandatory
reports to CVM during 2007. Based on
this experience, FDA estimates that
CVM will receive 35,765 mandatory
reports annually from 808 users of the
electronic reporting system. FDA
estimates the maximum reporting
burden for a mandatory report to be 1
hour, for a total burden of 35,765 hours
(35,765 reports x 1 hour = 35,765 hours)
or a minimum burden of 24,320 hours
with ((35,765 reports x 80% x 0.6 hour)
+ (35,765 reports x 20% x 1 hour) =
24,320.20 hours).
FDA received 5,000 voluntary reports
to ORA during 2007. Based on this
experience, FDA estimates that ORA
will receive 5,000 voluntary reports
annually from 5,000 users of the
electronic reporting system. FDA
VerDate Nov<24>2008
15:27 May 19, 2009
Jkt 217001
estimates the reporting burden for a
voluntary report to be 0.6 hours, for a
total burden of 3,000 hours (5,000
reports x 0.6 hours = 3,000 hours). ORA
does not receive mandatory reports.
FDAAA, Section 1005, the Reportable
Food Registry, established new
electronic mandatory and voluntary
reporting requirements for instances of
‘‘reportable’’ food, meaning an article of
food (other than infant formula) for
which there is a reasonable probability
that the use of, or exposure to, such
article of food will cause serious adverse
health consequences or death to humans
or animals. FDA received 625 voluntary
food complaints leading to adverse
events from January 1, 2008, to June 30,
2008, and there were 206 and 182 Class
1 Recalls for human food in Fiscal Years
2006 and 2007, respectively. Based on
these experiences, FDA estimates that
FDA could receive 200 to 1,200
‘‘reportable’’ food reports annually from
200 to 1,200 mandatory and voluntary
users of the electronic reporting system.
FDA will utilize the upper-bound
estimate of 1,200 for these calculations.
FDA estimates the reporting burden for
a mandatory ‘‘reportable’’ food report to
be 0.6 hours, for a total burden of 720
hours (1,200 reports x 0.6 hours = 720
hours). FDA estimates the reporting
burden for a voluntary ‘‘reportable’’
food report to be 0.6 hours, for a total
burden of 720 hours (1,200 reports x 0.6
hours = 720 hours).
FDAAA, Section 1002, Early Warning
Recall, mandated FDA establish a
system to receive voluntary pet food
complaint reports and provide an Early
Warning Recall system for the public.
FDA received 270 voluntary pet food
reports from January 1, 2008, to June 30,
2008. FDA received 10,740 and 99 pet
food complaints in FY 2007 and 2006,
respectively. Based on these
experiences, FDA estimates that FDA
could receive 540 voluntary pet food
reports annually from 540 users of the
electronic reporting system. FDA
estimates the reporting burden for a
voluntary ‘‘Early Warning Recall’’ report
to be 0.6 hours, for a total burden of 324
hours (540 reports x 0.6 hours = 324
hours).
Dated: May 13, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and
Planning.
[FR Doc. E9–11687 Filed 5–19–09; 8:45 am]
BILLING CODE 4160–01–S
PO 00000
Frm 00048
Fmt 4703
Sfmt 4703
23727
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.
A549 Cells: A Well-Characterized Lung
Carcinoma Cell Line Utilized for a
Variety of Scientific Studies, Including
Adenovirus Production and Testing
Description of Technology: Scientists
at the National Institutes of Health have
developed a cell line designated A549
that was derived from explanted
cultures of human lung cancer tissue.
The A549 cell line has been tested
under the guidance of the United States
Food and Drug Administration (FDA)
so, under current Good Manufacturing
Practices (GMP), these cells may be
suitable for use in manufacturing
constructs for use in clinical trials. The
A549 cell line has also been found to be
suitable for adenovirus production,
most notably replicating adenovirus
constructs that do not require
complementation by the viral oncogene,
early region 1A (E1A), which is
responsible for viral gene transcription.
This cell line is further utilized as a
negative control in assays to measure
the replication of adenoviruses that lack
E1A and as a target cell line to detect
replication competent adenoviruses
(RCA). A549 cells have been well
characterized through their use in a
wide variety of molecular studies, such
as anti-tumor drug permeability and
E:\FR\FM\20MYN1.SGM
20MYN1
23728
Federal Register / Vol. 74, No. 96 / Wednesday, May 20, 2009 / Notices
efficacy analysis, infection assays,
respiratory immunotoxicity tests, cell
senescence studies, and cytokine
expression profiling. These cells can
also be utilized to study a variety of
molecular characteristics for human
tumors in culture.
Application:
• Cell bank tested under cGMPcompliance regulations and used to
produce adenoviruses for use in clinical
trials.
• Research tool to analyze the efficacy
of potential anti-cancer agents to devise
better cancer treatments for
malignancies, such as non-small cell
lung cancer (NSCLC).
• Research tool to study the
infectivity of viruses that cause asthma
in order to develop better asthma
treatments.
• Standard research tool to analyze a
variety of molecular biology procedures,
for example, cell senescence, cytokine
induction, protein expression,
apoptosis, and receptor-ligand
interactions.
Advantages:
• A549 cells are a well-characterized
standard among the human lung
carcinoma/alveolar cell lines used in
molecular biology.
• The A549 cells stored at the NIH
were tested under the guidance of the
FDA’s cGMP regulations.
• The A549 cells stored at the NIH
may be suitable for producing
adenoviruses that can be used in
clinical trials and analyzing adenoviralbased therapies and vaccine strategies.
Inventors: Wade P. Parks, Donald J.
Giard, and Stuart Aaronson (all formerly
NCI).
Publication: DJ Giard et al. In vitro
cultivation of human tumors:
Establishment of cell lines derived from
a series of solid tumors. J Natl Cancer
Inst. 1973 Nov; 51(5):1417–1423.
Patent Status: HHS Reference No. E–
129–2009/0—Research Tool. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing under a Biological Materials
License Agreement.
Licensing Contact: Samuel E. Bish,
PhD; 301–435–5282;
bishse@mail.nih.gov.
Mobilizing the Body to Fight Cancer: T
Cell Receptors Specific for the Tumor
Antigen Survivin
Description of Technology: A major
drawback of current chemotherapybased cancer treatments is the harsh
side-effects associated with many cancer
drugs. Thus, there is an urgent need to
develop new therapeutic strategies
combining fewer side-effects and more
VerDate Nov<24>2008
15:27 May 19, 2009
Jkt 217001
specific anti-tumor activity.
Immunotherapy is a promising new
cancer therapeutic approach that directs
an individual’s innate and adaptive
immune system to fight against specific
diseases, including cancer.
T cell receptors (TCRs) are 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 two domains, one
variable domain that recognizes the
antigen and one constant region that
helps the TCR anchor to the membrane
and transmit recognition signals by
interacting with other proteins.
Scientists at the National Institutes of
Health (NIH) have developed genetically
modified T cells, which possess TCRs
that specifically recognize human
survivin, a tumor antigen expressed in
many adult and pediatric cancers that is
absent from most normal tissues. Nonhuman T cells that recognized human
survivin peptides with high affinity in
the context of human leukocyte antigen
(HLA) alleles were identified. Then,
using recombinant DNA technology, the
survivin-specific TCRs from the nonhuman T cells were fused to human
TCR backbones and expressed in human
T cells. The resulting survivin-specific
human T cells could prove to be
powerful new immunotherapeutic tools
for attacking survivin-expressing tumors
after infusion into patients.
Applications:
• Immunotherapeutics to treat and/or
prevent the reoccurrence of a variety of
human cancers that overexpress human
survivin by inserting survivin-specific
TCR sequences into patient T cells
• A drug component of a combination
immunotherapy regimen aimed at
targeting the specific tumor-associated
antigens expressed by cancer cells
within individual patients.
Advantages:
• Survivin is overexpressed in
virtually all cancers, including lung,
colon, breast, pancreatic, stomach, liver,
ovarian and prostate cancer, as well as
in melanoma and hematopoietic
malignancies, but this antigen is not
expressed on normal cells. Thus,
survivin is an ideal antigen for targeted
treatment. Anti-survivin TCR
immunotherapy could treat a host of
cancer types while reducing the sideeffects of treatment.
• The survivin-specific TCR
sequences can be derived in non-human
species in the context of a wide variety
of HLA molecules and, thus, TCRs
specific for each patient’s HLA profile
can be generated rapidly.
• The survivin-specific T cells should
not be rejected by a patient’s immune
PO 00000
Frm 00049
Fmt 4703
Sfmt 4703
system since the survivin-specific TCR
sequences are fused to a human TCR
backbone.
Development Status: This technology
is in the pre-clinical stage of
development. The inventors plan to
initiate a clinical trial in the next 6–12
months.
Market: Cancer continues to be a
medical and financial burden on U.S.
public health. According to U.S.
estimates, cancer is the second leading
cause of death with over 565,000 deaths
reported in 2008 and almost 1.5 million
new cases were reported (excluding
some skin cancers) in 2008. In 2007, the
NIH estimated that the overall cost of
cancer was $219.2 billion dollars and
$89 billion went to direct medical costs.
Despite our increasing knowledge of
oncology and cancer treatment methods,
the fight against cancer will continue to
benefit from the development of new
therapeutics aimed at treating
individual patients.
Inventors: Crystal L. Mackall et al.
(NCI).
Publications:
1. Manuscript in preparation.
2. CJ Cohen et al. Recognition of fresh
human tumor by human peripheral
blood lymphocytes transduced with a
bicistronic retroviral vector encoding a
murine anti-p53 TCR. J Immunol. 2005
Nov 1;175(9):5799–5808. (Erratum in: J
Immunol. 2006 Oct 15;177(8):5746.)
3. RA Morgan et al. Cancer regression
in patients after transfer of genetically
engineered lymphocytes. Science 2006
Oct 6;314(5796):126–129.
Patent Status: U.S. Provisional
Application No. 61/140,338 filed 23 Dec
2008 (HHS Reference No. E–325–2008/
0–US–01)
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 Pediatric
Oncology Branch is seeking statements
of capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize genetically engineered
lymphocytes with specificity for human
survivin. Please contact John D. Hewes,
PhD at 301–435–3121 or
hewesj@mail.nih.gov for more
information.
Fused Azepinone Cyclin Dependent
Kinase Inhibitors
Description of Technology: The
invention describes a class of cyclin
dependent kinase (CDK) inhibitors that
have anti-proliferative activity in human
tumor cell lines. CDKs are important in
E:\FR\FM\20MYN1.SGM
20MYN1
Federal Register / Vol. 74, No. 96 / Wednesday, May 20, 2009 / Notices
the control of the cell cycle and
alterations in CDK expression, function,
or regulation and are associated with
diseases characterized by cellular
proliferation. Increasing CDK activity
has been reported in many cancers.
Likewise, the loss of inhibitory activity
has been observed in a wide variety of
primary human tumors and human
tumor-derived cell lines, including lung,
breast, brain, bone, skin, bladder,
kidney, ovary, liver, colon, and pancreas
as well as in leukemia. These
compounds have also been found to
potently inhibit GSK3beta activity
which has recently been linked to a
variety of cellular processes and several
disparate areas of biology. In particular,
GSK3beta activity has been strongly
implicated in Alzheimer’s as well as
cardiac failure. Thus, the compounds of
this invention offer unique
opportunities for a variety of
indications.
Applications: CDK/GSK3beta
inhibitor therapeutics for the treatment
of several indications including various
cancers, neurodegenerative diseases,
and cardiac conditions.
Development: Pre-clinical stage of
development.
Inventors: Daniel W. Zaharevitz et al.
(NCI).
Publication: DW Zaharevitz et al.
Discovery and initial characterization of
the paullones, a novel class of smallmolecule inhibitors of cyclin-dependent
kinases. Cancer Res. 1999 Jun
1;59(11):2566–2569.
Patent Status: HHS Reference No. E–
025–1998/0—
• U.S. Patent No. 6,610,684, issued
August 26, 2003;
• Australian Patent Nos. 780528 and
778735, issued March 24, 2005 and
December 16, 2004;
• Canada Patent Application No.
2335115, filed June 16, 1999;
• Japanese Patent Application No.
2000–554735, filed June 16, 1999;
• United Kingdom Patent No.
1086105, validated March 01, 2006 ((E–
025–1998/0–GB–09);
• French Patent No. 1086105,
validated March 01, 2006 (E–025–1998/
0–FR–10); and
• German Patent No. 69930120.3,
validated March 16, 2006 (E–025–1998/
0–DE–11).
Licensing Status: Available for
licensing.
Licensing Contact: Whitney A.
Hastings; 301–451–7337;
hastingw@mail.nih.gov.
VerDate Nov<24>2008
15:27 May 19, 2009
Jkt 217001
Dated: May 13, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–11706 Filed 5–19–09; 8:45 am]
BILLING CODE 4140–01–P
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.
Antibody and Immunotoxin Treatments
for Mesothelin-Expressing Cancers
Description of Technology:
Mesothelin is a cell surface protein that
is highly expressed in aggressive
cancers such as malignant
mesothelioma, ovarian cancer and
pancreatic cancer. As a result,
mesothelin is an excellent candidate for
tumor targeted immunotherapeutics.
However, the antibodies against
mesothelin that are available for clinical
trials are of murine origin. These
antibodies have the potential to elicit
immune responses in patients, which
may adversely affect the ability to
provide patients with repeated doses.
Thus, the clinical application of the
antibodies may be limited.
In order to address the issue of
immunogenicity in patients, NIH
inventors have generated antimesothelin antibody variable fragments
(Fv) of human origin. These antibody
PO 00000
Frm 00050
Fmt 4703
Sfmt 4703
23729
fragments (HN1 and HN2) have the
ability to efficiently recognize
mesothelin on the surface of numerous
cancer cells. As a result, these antibody
fragments represent an attractive
therapeutic alternative to the murine
anti-mesothelin antibodies currently
being tested in clinical trials.
Application:
• Use as an antibody therapeutic for
mesotheliomas, pancreatic tumors and
ovarian tumors.
• Use in an immunotoxin therapeutic
for mesotheliomas, pancreatic tumors
and ovarian tumors.
• Diagnostic for the detection of
mesothelin positive tumors.
• Research agent for the detection of
mesothelin.
Advantages:
• Fully human antibody reduces
potential immunogenicity, thereby
allowing repeated dosing.
• Antibody specificity improves the
therapeutic efficacy of the agent.
Development Status: Preclinical stage
of development with some pre-clinical
data available.
Inventors: Mitchell Ho et al. (NCI).
Patent Status: U.S. Provisional
Application No. 61/162,778, filed 24
Mar 2009 (HHS Reference E–091–2009/
0–US–01)
Related Technologies/Publications:
• U.S. Patent 6,083,502 entitled
‘‘Mesothelium Antigen and Methods
and Kits For Targeting It.’’
• PCT Application PCT/US97/0224
entitled ‘‘Mesothelium Antigen and
Methods and Kits For Targeting It.’’
• U.S. Patent 6,809,184 entitled
‘‘Antibodies, Including Fv Molecules,
and Immunoconjugates Having High
Binding Affinity for Mesothelin and
Methods for Their Use.’’
• PCT Application PCT/US98/25270
entitled ‘‘Antibodies, Including Fv
Molecules, and Immunoconjugates
Having High Binding Affinity for
Mesothelin and Methods for Their Use.’’
• U.S. Patent 7,081,518 entitled
‘‘Anti-mesothelin antibodies having
high binding affinity.’’
• PCT Application PCT/US00/14829
entitled ‘‘Immunoconjugates Having
High Binding Affinity Improvement of
scFVsr Ab’s with Higher Affinity for
Mesothelin.’’
Licensing Status: Available for
licensing.
Licensing Contact: David A.
Lambertson, Ph.D.; 301–435–4632;
lambertsond@mail.nih.gov.
Collaborative Research Opportunity:
The National Cancer Institute
Laboratory of Molecular Biology is
seeking statements of capability or
interest from parties interested in
collaborative research to further
E:\FR\FM\20MYN1.SGM
20MYN1
]]>Agencies
[Federal Register Volume 74, Number 96 (Wednesday, May 20, 2009)]
[Notices]
[Pages 23727-23729]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-11706]
-----------------------------------------------------------------------
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.
A549 Cells: A Well-Characterized Lung Carcinoma Cell Line Utilized for
a Variety of Scientific Studies, Including Adenovirus Production and
Testing
Description of Technology: Scientists at the National Institutes of
Health have developed a cell line designated A549 that was derived from
explanted cultures of human lung cancer tissue. The A549 cell line has
been tested under the guidance of the United States Food and Drug
Administration (FDA) so, under current Good Manufacturing Practices
(GMP), these cells may be suitable for use in manufacturing constructs
for use in clinical trials. The A549 cell line has also been found to
be suitable for adenovirus production, most notably replicating
adenovirus constructs that do not require complementation by the viral
oncogene, early region 1A (E1A), which is responsible for viral gene
transcription. This cell line is further utilized as a negative control
in assays to measure the replication of adenoviruses that lack E1A and
as a target cell line to detect replication competent adenoviruses
(RCA). A549 cells have been well characterized through their use in a
wide variety of molecular studies, such as anti-tumor drug permeability
and
[[Page 23728]]
efficacy analysis, infection assays, respiratory immunotoxicity tests,
cell senescence studies, and cytokine expression profiling. These cells
can also be utilized to study a variety of molecular characteristics
for human tumors in culture.
Application:
Cell bank tested under cGMP-compliance regulations and
used to produce adenoviruses for use in clinical trials.
Research tool to analyze the efficacy of potential anti-
cancer agents to devise better cancer treatments for malignancies, such
as non-small cell lung cancer (NSCLC).
Research tool to study the infectivity of viruses that
cause asthma in order to develop better asthma treatments.
Standard research tool to analyze a variety of molecular
biology procedures, for example, cell senescence, cytokine induction,
protein expression, apoptosis, and receptor-ligand interactions.
Advantages:
A549 cells are a well-characterized standard among the
human lung carcinoma/alveolar cell lines used in molecular biology.
The A549 cells stored at the NIH were tested under the
guidance of the FDA's cGMP regulations.
The A549 cells stored at the NIH may be suitable for
producing adenoviruses that can be used in clinical trials and
analyzing adenoviral-based therapies and vaccine strategies.
Inventors: Wade P. Parks, Donald J. Giard, and Stuart Aaronson (all
formerly NCI).
Publication: DJ Giard et al. In vitro cultivation of human tumors:
Establishment of cell lines derived from a series of solid tumors. J
Natl Cancer Inst. 1973 Nov; 51(5):1417-1423.
Patent Status: HHS Reference No. E-129-2009/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a Biological
Materials License Agreement.
Licensing Contact: Samuel E. Bish, PhD; 301-435-5282;
bishse@mail.nih.gov.
Mobilizing the Body to Fight Cancer: T Cell Receptors Specific for the
Tumor Antigen Survivin
Description of Technology: A major drawback of current
chemotherapy-based cancer treatments is the harsh side-effects
associated with many cancer drugs. Thus, there is an urgent need to
develop new therapeutic strategies combining fewer side-effects and
more specific anti-tumor activity. Immunotherapy is a promising new
cancer therapeutic approach that directs an individual's innate and
adaptive immune system to fight against specific diseases, including
cancer.
T cell receptors (TCRs) are 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
two domains, one variable domain that recognizes the antigen and one
constant region that helps the TCR anchor to the membrane and transmit
recognition signals by interacting with other proteins.
Scientists at the National Institutes of Health (NIH) have
developed genetically modified T cells, which possess TCRs that
specifically recognize human survivin, a tumor antigen expressed in
many adult and pediatric cancers that is absent from most normal
tissues. Non-human T cells that recognized human survivin peptides with
high affinity in the context of human leukocyte antigen (HLA) alleles
were identified. Then, using recombinant DNA technology, the survivin-
specific TCRs from the non-human T cells were fused to human TCR
backbones and expressed in human T cells. The resulting survivin-
specific human T cells could prove to be powerful new immunotherapeutic
tools for attacking survivin-expressing tumors after infusion into
patients.
Applications:
Immunotherapeutics to treat and/or prevent the
reoccurrence of a variety of human cancers that overexpress human
survivin by inserting survivin-specific TCR sequences into patient T
cells
A drug component of a combination immunotherapy regimen
aimed at targeting the specific tumor-associated antigens expressed by
cancer cells within individual patients.
Advantages:
Survivin is overexpressed in virtually all cancers,
including lung, colon, breast, pancreatic, stomach, liver, ovarian and
prostate cancer, as well as in melanoma and hematopoietic malignancies,
but this antigen is not expressed on normal cells. Thus, survivin is an
ideal antigen for targeted treatment. Anti-survivin TCR immunotherapy
could treat a host of cancer types while reducing the side-effects of
treatment.
The survivin-specific TCR sequences can be derived in non-
human species in the context of a wide variety of HLA molecules and,
thus, TCRs specific for each patient's HLA profile can be generated
rapidly.
The survivin-specific T cells should not be rejected by a
patient's immune system since the survivin-specific TCR sequences are
fused to a human TCR backbone.
Development Status: This technology is in the pre-clinical stage of
development. The inventors plan to initiate a clinical trial in the
next 6-12 months.
Market: Cancer continues to be a medical and financial burden on
U.S. public health. According to U.S. estimates, cancer is the second
leading cause of death with over 565,000 deaths reported in 2008 and
almost 1.5 million new cases were reported (excluding some skin
cancers) in 2008. In 2007, the NIH estimated that the overall cost of
cancer was $219.2 billion dollars and $89 billion went to direct
medical costs. Despite our increasing knowledge of oncology and cancer
treatment methods, the fight against cancer will continue to benefit
from the development of new therapeutics aimed at treating individual
patients.
Inventors: Crystal L. Mackall et al. (NCI).
Publications:
1. Manuscript in preparation.
2. CJ Cohen et al. Recognition of fresh human tumor by human
peripheral blood lymphocytes transduced with a bicistronic retroviral
vector encoding a murine anti-p53 TCR. J Immunol. 2005 Nov
1;175(9):5799-5808. (Erratum in: J Immunol. 2006 Oct 15;177(8):5746.)
3. RA Morgan et al. Cancer regression in patients after transfer of
genetically engineered lymphocytes. Science 2006 Oct 6;314(5796):126-
129.
Patent Status: U.S. Provisional Application No. 61/140,338 filed 23
Dec 2008 (HHS Reference No. E-325-2008/0-US-01)
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
Pediatric Oncology Branch is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize genetically engineered lymphocytes
with specificity for human survivin. Please contact John D. Hewes, PhD
at 301-435-3121 or hewesj@mail.nih.gov for more information.
Fused Azepinone Cyclin Dependent Kinase Inhibitors
Description of Technology: The invention describes a class of
cyclin dependent kinase (CDK) inhibitors that have anti-proliferative
activity in human tumor cell lines. CDKs are important in
[[Page 23729]]
the control of the cell cycle and alterations in CDK expression,
function, or regulation and are associated with diseases characterized
by cellular proliferation. Increasing CDK activity has been reported in
many cancers. Likewise, the loss of inhibitory activity has been
observed in a wide variety of primary human tumors and human tumor-
derived cell lines, including lung, breast, brain, bone, skin, bladder,
kidney, ovary, liver, colon, and pancreas as well as in leukemia. These
compounds have also been found to potently inhibit GSK3beta activity
which has recently been linked to a variety of cellular processes and
several disparate areas of biology. In particular, GSK3beta activity
has been strongly implicated in Alzheimer's as well as cardiac failure.
Thus, the compounds of this invention offer unique opportunities for a
variety of indications.
Applications: CDK/GSK3beta inhibitor therapeutics for the treatment
of several indications including various cancers, neurodegenerative
diseases, and cardiac conditions.
Development: Pre-clinical stage of development.
Inventors: Daniel W. Zaharevitz et al. (NCI).
Publication: DW Zaharevitz et al. Discovery and initial
characterization of the paullones, a novel class of small-molecule
inhibitors of cyclin-dependent kinases. Cancer Res. 1999 Jun
1;59(11):2566-2569.
Patent Status: HHS Reference No. E-025-1998/0--
U.S. Patent No. 6,610,684, issued August 26, 2003;
Australian Patent Nos. 780528 and 778735, issued March 24,
2005 and December 16, 2004;
Canada Patent Application No. 2335115, filed June 16,
1999;
Japanese Patent Application No. 2000-554735, filed June
16, 1999;
United Kingdom Patent No. 1086105, validated March 01,
2006 ((E-025-1998/0-GB-09);
French Patent No. 1086105, validated March 01, 2006 (E-
025-1998/0-FR-10); and
German Patent No. 69930120.3, validated March 16, 2006 (E-
025-1998/0-DE-11).
Licensing Status: Available for licensing.
Licensing Contact: Whitney A. Hastings; 301-451-7337;
hastingw@mail.nih.gov.
Dated: May 13, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E9-11706 Filed 5-19-09; 8:45 am]
BILLING CODE 4140-01-P
