Government-Owned Inventions; Availability for Licensing, 47840-47842 [05-16136]
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47840
Federal Register / Vol. 70, No. 156 / Monday, August 15, 2005 / Notices
includes whether the acquisition of the
nonbanking company complies with the
standards in section 4 of the BHC Act
(12 U.S.C. 1843). Unless otherwise
noted, nonbanking activities will be
conducted throughout the United States.
Additional information on all bank
holding companies may be obtained
from the National Information Center
website at www.ffiec.gov/nic/.
Unless otherwise noted, comments
regarding each of these applications
must be received at the Reserve Bank
indicated or the offices of the Board of
Governors not later than September 18,
2005.
A. Federal Reserve Bank of Cleveland
(Cindy West, Manager) 1455 East Sixth
Street, Cleveland, Ohio 44101-2566:
1. Rurban Financial Corp., Defiance,
Ohio; to merge with Exchange
Bancshares, Inc., and thereby acquire
The Exchange Bank, both of Luckey,
Ohio.
Board of Governors of the Federal Reserve
System, August 9, 2005.
Robert deV. Frierson,
Deputy Secretary of the Board.
[FR Doc. 05–16089 Filed 8–12–05; 8:45 am]
BILLING CODE 6210–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Proposed Collection; Comment
Request; Field Test of the Discovering
the Science of Alcohol Curriculum
Summary: In compliance with the
requirement of Section 3506(c)(2)(A) of
the Paperwork Reduction Act of 1995,
regarding the opportunity for public
comment on proposed data collection
projects, the National institute on
Alcohol Abuse and Alcoholism
(NIAAA), the National Institutes of
Health (NIH) will publish periodic
summaries of proposed projects
submitted to the Office of Management
and Budget (OMB) for review and
approval.
Proposed Collection: Title: Field Test
of the Discovering the Science of
Alcohol Curriculum. Type of
Information Collection Request: New.
Need and Use of Information Collection:
The Discovering the Science of Alcohol
curriculum (DSA) was developed with a
Phase II SBIR grant to bring accurate,
research-based information to high
school students in biology and science
classrooms. The curriculum includes
standards-based content objectives and
assessment activities. Curriculum
materials include a teacher’s guide and
website. The field test is necessary to
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estimate the DSA curriculum’s
effectiveness in conveying information
to students and teachers. Specifically,
the field study is designed to enable
NIAAA to determine whether teachers
and students who complete the DSA
curriculum demonstrate significantly
greater knowledge of the topics covered
in the curriculum than teachers and
students who do not use the DSA
curriculum. In addition, the study is
designed to enable NIAAA to determine
whether the students who are exposed
to the curriculum components selfreport different beliefs, attitudes, and
intentions regarding alcohol use than
their counterparts who are not exposed
to the curriculum at their schools.
Participating in this field test will be
an experimental group of 30 high school
biology classrooms with a total of
approximately 400 to 500 students and
a control group of 30 high school
biology classrooms with approximately
400 to 500 students. Teachers and
students from grades 9, 10, 11, and 12
will comprise both groups. The field test
will include two surveys: (1) An online,
computerized survey that measures
teachers’ knowledge of the DSA
curriculum components and teacher
satisfaction with the DSA curriculum
components. (2) For students, an
anonymous, online, computerized
survey that measures three factors: (a)
student knowledge of the DSA
components, (b) student attitudes,
beliefs, and intentions, and (c) student
satisfaction with the DSA curriculum
components. Frequency of response:
Once per respondent. Affected Public:
Individuals. Type of Respondents:
Biology/Science teachers and high
school students.
The reporting burden is as follows:
Estimated Number of Respondents: It is
estimated that we will be able to recruit
approximately 60 teachers and
approximately 1000 students. Estimated
Number of Responses per Respondent:
One response per respondent. Average
Burden Hours per Response: 15 minutes
per individual in the control group and
30 minutes per individual in the
experimental group, for a total
respondent burden of 662.5 hours.
Estimated Total Annual Burden Hours
Requested: 662.5 hours. Estimated Costs
to Respondents: Assuming an hourly
rate of $22 for teachers, we estimate the
total costs to be $825. There are no
Capital Costs to report. There are no
Operating or Maintenance costs to
report.
Request for Comments: Written
comments and suggestions from the
public and affected agencies are invited
on the following points: (1) Whether the
data collection is necessary for the
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proper performance of the function of
the agency, including whether the
information will have practical utility;
(2) the accuracy of the agency’s estimate
of the burden of the proposed collection
of information, including the validity of
the methodology and assumptions; (3)
ways to enhance the quality, utility, and
clarity of the information to be
collected; and (4) ways to minimize the
burden of the collection of information
on those who are to respond, including
the use of appropriate automated,
electronic, mechanical, or other
technological collection techniques or
other forms of information technology.
For further information contact: To
request more information on the
proposed project or to obtain a copy of
the data collection plans and
instruments, contact Jason Lazarow,
M.Ed., NIH/NIAAA/ORTC/HSEB, 5635
Fishers Lane, Room 3101, MSC 9304,
Bethesda, MD 20892–9304, or e-mail
your request to: jlazarow@mail.nih.gov.
Mr. Lazarow can be contacted by
telephone at 301–435–8043.
Comments Due Date: Comments
regarding this information collection are
best assured of having their full effect if
received within 60 days of the date of
this publication.
Dated: August 8, 2005.
Stephen Long,
Executive Officer, NIAAA.
[FR Doc. 05–16139 Filed 8–12–05; 8:45 am]
BILLING CODE 4140–01–M
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, DHHS.
ACTION: Notice.
AGENCY:
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
E:\FR\FM\15AUN1.SGM
15AUN1
Federal Register / Vol. 70, No. 156 / Monday, August 15, 2005 / Notices
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.
Transgenic Mice in which the Gene for
MCP–1 is Deleted
Teizo Yoshimura (NCI).
HHS Reference No. E–241–2005/0—
Research Tool.
Licensing Contact: Susan S. Rucker;
301/435–4478;
ruckersu@mail.nih.gov.
Dr. Yoshimura has developed a
transgenic mouse which does not
express the chemokine MCP–1 due to a
deletion of the gene for MCP–1. MCP–
1 is a CC chemokine which is
responsible for recruiting monocytes
into sites of inflammation and cancer.
Using a thioglycollate challenge as a
measure of the impact of the deletion of
MCP–1, MCP–1 deficient mice exhibit a
60% reduction in the number of
monocytes/macrophages at 96 hours
compared to wild type mice. Although
the gene for MCP–1 has been deleted the
expression of the neighboring gene for
MCP–3 is unaffected. This mouse may
be useful as an in vivo model for
evaluating the role of MCP–1 in cancer
or other diseases associated with
inflammation due to the accumulation
of monocytes.
This work has not yet been published.
These mice are not the subject of any
patent or patent application filed by the
NIH and are available under a biological
materials license.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
Monoclonal Antibody to the Protein
NCOA6 (Also Called ASC–2, AIB–3)
Paul S. Meltzer (NHGRI).
HHS Reference No. E–168–2005/0—
Research Tool.
Licensing Contact: Mojdeh Bahar; 301/
435–2950; baharm@mail.nih.gov.
The invention relates to monoclonal
antibodies that bind to the transcription
factor NCOA6 (ASC–2, AIB–3, TRB,
TRAP250, NRC). The antibodies have
proven successful reagents for Western
blotting and for purifying complexes
containing NCOA6. The Western blot
experiments revealed that NCOA6 is
over-expressed in several breast cancer
cell lines, and the purification
experiments identified a protein
complex containing NCOA6 (the
ASCOM complex). The monoclonal
antibodies may be useful reagents for
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13:17 Aug 12, 2005
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studying the role of NCOA6 in
transcription and for studying the
ASCOM complex. Additional
information on the antibodies can be
found in Goo et al. (2003) Mol Cell Biol
23:140–9 and Lee et al. (1999) J Biol
Chem 274:34283–93.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
An Enzymatic Reagent for Removing CTerminal Polyhistidine Tags From
Recombinant Proteins
David S. Waugh (NCI).
HHS Reference No. E–162–2005/0—
Research Tool.
Licensing Contact: Mojdeh Bahar; 301/
435–2950; baharm@mail.nih.gov.
The technology is a new method for
removing affinity tags from fusion
proteins. Affinity tags are commonly
used to purify recombinant proteins, but
the tag’s influence on the protein is
usually unknown. Accordingly, removal
of the affinity tag is often desired prior
to functional or structural studies.
In contrast to tags added to the aminoterminus (N-terminal tag), removal of
tags added to the carboxy-terminus (Cterminal tag) of proteins is problematic.
A new carboxypeptidase capable of
removing C-terminal tags has been
discovered. This enzyme, MeCPA, can
remove histidines and other amino
acids from the C-terminus of proteins
and could be used to remove affinity
tags. Because MeCPA will only digest
disordered/unstructured residues, it
could also be used to remove native
amino acids from the C-terminus of
proteins to facilitate crystallization.
The inventors have cloned the gene
that encodes MeCPA and over-produced
the enzyme. A tagged version of MeCPA
has been produced to facilitate removal
of MeCPA from the products of the
cleavage reaction. Background
information for this invention is
described in Joshi and Leger (1999) JBC
274: 9803–9811.
Induction of C/EBPalpha and Uses
Thereof
Robert H. Shoemaker (NCI) et al.
U.S. Provisional Application filed 15 Jul
2005 (HHS Reference No. E–140–
2005/0–US–01).
Licensing Contact: Michelle A. Booden;
301/451–7337;
boodenm@mail.nih.gov.
CCAAT/enhancer binding protein
alpha (C/EBPalpha) is a leucine-zipper
structure transcription factor that plays
a key role in regulating the
differentiation and proliferation of a
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47841
variety of cell types. For example,
conditional expression of C/EBPalpha is
sufficient to trigger neutrophilic
differentiation. In addition,
administration of antisense molecules
against C/EBPalpha has been shown to
interfere with proliferation of the late
myeloblast and promyelocytic leukemic
cell lines HL60 and NB4.
Dominant negative mutations of the
CEBPA gene have been identified in a
large percentage of subjects with t(8;21)
acute myeloid leukemia (AML),
subtypes M1 and M2. AML is a cancer
of the blood and bone marrow
characterized by rapid and uncontrolled
growth of myelocytes and a lack of
myeloid cell differentiation.
Approximately 8% of all AML cases are
of the t(8;21) variety. Therefore,
pharmacologic modulators of C/
EBPalpha may be useful as a means to
induce cell differentiation, and thus
limit proliferation of AML cells.
The present invention describes
methods for treating various leukemic
disorders by administrating compounds.
Additional embodiments describe the
mechanism of action of these sterol
mesylate compounds through their
ability to modulate C/EBPalpha. This
disclosure also provides methods for
screening for C/EBPalpha inducing
compounds. Sterol mesylate compounds
and derivatives thereof have the
potential to result in more effective
therapeutics for the treatment of
leukemia and lymphoma.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
Use of Discoidin Domain Receptor 1
(DDR1) and Agents That Affect the
DDR1/Collagen Pathway
Teizo Yoshimura (NCI).
U.S. Patent Application No. 10/507,385
filed 09 Sep 2004 (HHS Reference No.
E–083–2002/2–US–02).
Licensing Contact: Jesse Kindra; 301/
435–5559; kindraj@mail.nih.gov.
Dendritic cells (DCs) are pivotal
antigen-presenting cells for initiation of
an immune response. Indeed, dendritic
cells provide the basis for the
production of an effective immune
response to a vaccine, particularly for
antigens wherein conventional
vaccination is inadequate. DCs are also
important in the production on an
immune response to tumor antigens.
The present invention discloses
methods of using the receptor tyrosine
kinase discoidin domain receptor 1
(DDR1) to facilitate the maturation/
differentiation of DCs or macrophages.
Activating agents of DDR1 may be
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47842
Federal Register / Vol. 70, No. 156 / Monday, August 15, 2005 / Notices
useful in the induction of highly potent,
mature DCs or highly differentiated
macrophages from DC precursors, such
as monocytes. Use of this method may
enhance the antigen presenting
capabilities of the immune system,
leading to a more effective overall
immune response.
This research is further described in
H. Kamohara et al., FASEB J. (October
15, 2001) 10.1096/fj.01–0359fje; and W.
Matsuyama et al., FASEB J. (May 8,
2003) 10.1096/fj.02–0320fje.
Methods for Reducing Tumor Growth
and Metastasis by Inhibiting MCP–1
Activity
William J. Murphy et al. (NCI).
PCT Patent Application No. PCT/US01/
16058, filed May 18, 2001 [HHS Ref.
No. E–131–2000/0–PCT–02];
Australian Patent Application No.
2001261743, filed May 18, 2001 [HHS
Ref. No. E–131–2000/0–AU–03];
Canadian Patent Application No.
2409298, filed May 18, 2001 [HHS
Ref. No. E–131–2000/0–CA–04];
European Patent Application No.
01935670.8–24, filed May 18, 2001
[HHS Ref. No. E–131–2000/0–EP–05];
and U.S. Patent Application No. 10/
276,644, filed March 10, 2003 [HHS
Ref. No. E–131–2000/0–US–06].
Licensing Contact: Jesse S. Kindra; 301/
435–5559; kindraj@mail.nih.gov.
Monocyte Chemotactic Protein 1
(MCP–1) is a chemokine that is
abundantly produced in a variety of
inflammatory diseases. Consistent with
its role in inflammation, MCP–1 is
known to be chemotactic for monocytes,
T lymphocytes, basophiles and NK
cells.
Based on its chemotactic effect on
monocytes, MCP–1 has been observed to
have an anti-tumor effect in certain
mouse/tumor experimental designs. In
those mouse systems, MCP–1
production by tumor cells was
positively correlated with the number of
intratumoral macrophages and inversely
correlated with tumor growth. These
studies have led to the hypothesis that
MCP–1 possesses anti-tumorigenic
activity.
The present invention is based on the
surprising discovery that inhibition of
MCP–1 activity inhibits tumor
metastasis and prolongs survival.
Accordingly, this invention generally
relates to methods of inhibiting tumor
growth and/or metastasis in a subject,
and methods of treating cancer and/or
increasing survival of a subject with a
tumor, by inhibiting MCP–1 activity in
the subject.
In addition to licensing, the
technology is available for further
development through collaborative
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Jkt 205001
research opportunities with the
inventors.
Methods of Delivering Agents to Target
Cells
Novel DNA Liposome Complexes for
Increased Systemic Delivery and Gene
Expression
Andrew J. George et al. (NCI).
U.S. Patent No. 5,861,156 issued 19 Jan
1999 (HHS Reference No. E–130–
1993/0–US–01).
Licensing Contact: George G. Pipia; 301/
435–5560; pipiag@mail.nih.gov.
Nancy Smyth-Templeton and George N.
Pavlakis (NCI).
U.S. Patent No. 6,413,544 issued 02
Jul 2002 (HHS Reference No. E–143–
1996/0–US–03); U.S. Patent No.
6,770,291 issued 03 Aug 2004 (HHS
Reference No. E–143–1996/0–US–04);
U.S. Patent Application No. 10/825,803
filed 15 Apr 2004 (HHS Reference No.
E–143–1996/0–US–16).
Licensing Contact: John Stansberry; 301/
435–5236; stansbej@mail.nih.gov.
Improved liposomes have been
created that could increase the efficacy
of treatments for cancer, cardiovascular
diseases, and HIV–1 related diseases in
small and large animal models. These
liposomes efficiently condense nucleic
acids, proteins, viruses, drugs, and
mixtures of these agents on the interior
of bilamellar invaginated structures
produced by a novel extrusion
procedure. This technology is an
improved delivery system for all
biologically active reagents. By using
extruded DOTAP:Cholesterol liposomes
to form complexes with DNA encoding
specific proteins, expression has been
improved dramatically. These nucleic
acid:liposome complexes have extended
half-life in the circulation, are stable in
serum, have broad biodistribution,
efficiently encapsulate various sizes of
nucleic acids and other molecules
including viruses and drugs, are
targetable to specific organs and cell
types, penetrate through tight barriers in
several organs, are fusogenic with cell
membranes and avoid endosomes, are
optimized for nucleic acid:lipid ratio
and colloidal suspension in vivo, can be
size fractionated to produce a totally
homogenous population of complexes
prior to injection; are non-toxic, nonimmunogenic and can be repeatedly
administered, and liquid suspensions
and freeze-dried formulations are stable.
These complexes have been injected
into mice, rats, rabbits, pigs, nonhuman
primates, and humans. Currently, these
complexes are injected intravenously
into patients in clinical trials to treat
lung cancer and will be used in
upcoming trials to treat breast,
pancreatic, head and neck cancers; and
Hepatitis B and C.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
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The present invention relates to
methods of delivering agents to target
cells. The target cells are modified by
one or more monospecific binding
proteins reactive with one or more
consistent naturally occurring target cell
surface markers. The monospecific
binding protein reactive with the cell
surface marker is tagged, fused to, or
labeled with a chemical moiety which is
recognized by, and binds to a site on a
multivalent antibody, which also binds
an agent to be delivered. The agent is
bound to the multivalent antibody,
which in turn, is also bound to a tagged
monospecific binding protein which is
bound to a cell surface marker on a
target cell. Thus, the agent is delivered,
or directed, to the target cells.
Chemical moiety, as used herein,
includes a genetically fused or
otherwise coupled peptide, one or more
peptides within the sequence of a monoor bispecific binding protein, a
posttranslationally or chemically
modified peptide, a chemical
substituent such as biotin, incorporated
into the protein, or any non-natural
amino acid incorporated into the
binding protein. Chemical moiety also
includes any protein or parts thereof, or
peptide comprising an amino acid
sequence that is reactive with a
recognition site, including a linker
connecting variable regions of a singlechain Fv (sFv) or sFv fusion protein, or
an epitope of the monospecific binding
protein.
The present invention further relates
to a method of immunotherapy in a host
whereby target cells are destroyed with
enhanced selectivity using target celldirected cytotoxic agents. This method
of immunotherapy involves two
concepts: the specific modification of
the target cell with chemical moietylabeled monospecific binding proteins
and the targeting of cytotoxic agents to
the modified target cells.
Dated: August 5, 2005.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 05–16136 Filed 8–12–05; 8:45 am]
BILLING CODE 4140–01–P
E:\FR\FM\15AUN1.SGM
15AUN1
]]>Agencies
[Federal Register Volume 70, Number 156 (Monday, August 15, 2005)]
[Notices]
[Pages 47840-47842]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-16136]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, DHHS.
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
[[Page 47841]]
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.
Transgenic Mice in which the Gene for MCP-1 is Deleted
Teizo Yoshimura (NCI).
HHS Reference No. E-241-2005/0--Research Tool.
Licensing Contact: Susan S. Rucker; 301/435-4478;
ruckersu@mail.nih.gov.
Dr. Yoshimura has developed a transgenic mouse which does not
express the chemokine MCP-1 due to a deletion of the gene for MCP-1.
MCP-1 is a CC chemokine which is responsible for recruiting monocytes
into sites of inflammation and cancer. Using a thioglycollate challenge
as a measure of the impact of the deletion of MCP-1, MCP-1 deficient
mice exhibit a 60% reduction in the number of monocytes/macrophages at
96 hours compared to wild type mice. Although the gene for MCP-1 has
been deleted the expression of the neighboring gene for MCP-3 is
unaffected. This mouse may be useful as an in vivo model for evaluating
the role of MCP-1 in cancer or other diseases associated with
inflammation due to the accumulation of monocytes.
This work has not yet been published. These mice are not the
subject of any patent or patent application filed by the NIH and are
available under a biological materials license.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Monoclonal Antibody to the Protein NCOA6 (Also Called ASC-2, AIB-3)
Paul S. Meltzer (NHGRI).
HHS Reference No. E-168-2005/0--Research Tool.
Licensing Contact: Mojdeh Bahar; 301/435-2950; baharm@mail.nih.gov.
The invention relates to monoclonal antibodies that bind to the
transcription factor NCOA6 (ASC-2, AIB-3, TRB, TRAP250, NRC). The
antibodies have proven successful reagents for Western blotting and for
purifying complexes containing NCOA6. The Western blot experiments
revealed that NCOA6 is over-expressed in several breast cancer cell
lines, and the purification experiments identified a protein complex
containing NCOA6 (the ASCOM complex). The monoclonal antibodies may be
useful reagents for studying the role of NCOA6 in transcription and for
studying the ASCOM complex. Additional information on the antibodies
can be found in Goo et al. (2003) Mol Cell Biol 23:140-9 and Lee et al.
(1999) J Biol Chem 274:34283-93.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
An Enzymatic Reagent for Removing C-Terminal Polyhistidine Tags From
Recombinant Proteins
David S. Waugh (NCI).
HHS Reference No. E-162-2005/0--Research Tool.
Licensing Contact: Mojdeh Bahar; 301/435-2950; baharm@mail.nih.gov.
The technology is a new method for removing affinity tags from
fusion proteins. Affinity tags are commonly used to purify recombinant
proteins, but the tag's influence on the protein is usually unknown.
Accordingly, removal of the affinity tag is often desired prior to
functional or structural studies.
In contrast to tags added to the amino-terminus (N-terminal tag),
removal of tags added to the carboxy-terminus (C-terminal tag) of
proteins is problematic. A new carboxypeptidase capable of removing C-
terminal tags has been discovered. This enzyme, MeCPA, can remove
histidines and other amino acids from the C-terminus of proteins and
could be used to remove affinity tags. Because MeCPA will only digest
disordered/unstructured residues, it could also be used to remove
native amino acids from the C-terminus of proteins to facilitate
crystallization.
The inventors have cloned the gene that encodes MeCPA and over-
produced the enzyme. A tagged version of MeCPA has been produced to
facilitate removal of MeCPA from the products of the cleavage reaction.
Background information for this invention is described in Joshi and
Leger (1999) JBC 274: 9803-9811.
Induction of C/EBPalpha and Uses Thereof
Robert H. Shoemaker (NCI) et al.
U.S. Provisional Application filed 15 Jul 2005 (HHS Reference No. E-
140-2005/0-US-01).
Licensing Contact: Michelle A. Booden; 301/451-7337;
boodenm@mail.nih.gov.
CCAAT/enhancer binding protein alpha (C/EBPalpha) is a leucine-
zipper structure transcription factor that plays a key role in
regulating the differentiation and proliferation of a variety of cell
types. For example, conditional expression of C/EBPalpha is sufficient
to trigger neutrophilic differentiation. In addition, administration of
antisense molecules against C/EBPalpha has been shown to interfere with
proliferation of the late myeloblast and promyelocytic leukemic cell
lines HL60 and NB4.
Dominant negative mutations of the CEBPA gene have been identified
in a large percentage of subjects with t(8;21) acute myeloid leukemia
(AML), subtypes M1 and M2. AML is a cancer of the blood and bone marrow
characterized by rapid and uncontrolled growth of myelocytes and a lack
of myeloid cell differentiation. Approximately 8% of all AML cases are
of the t(8;21) variety. Therefore, pharmacologic modulators of C/
EBPalpha may be useful as a means to induce cell differentiation, and
thus limit proliferation of AML cells.
The present invention describes methods for treating various
leukemic disorders by administrating compounds. Additional embodiments
describe the mechanism of action of these sterol mesylate compounds
through their ability to modulate C/EBPalpha. This disclosure also
provides methods for screening for C/EBPalpha inducing compounds.
Sterol mesylate compounds and derivatives thereof have the potential to
result in more effective therapeutics for the treatment of leukemia and
lymphoma.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Use of Discoidin Domain Receptor 1 (DDR1) and Agents That Affect the
DDR1/Collagen Pathway
Teizo Yoshimura (NCI).
U.S. Patent Application No. 10/507,385 filed 09 Sep 2004 (HHS Reference
No. E-083-2002/2-US-02).
Licensing Contact: Jesse Kindra; 301/435-5559; kindraj@mail.nih.gov.
Dendritic cells (DCs) are pivotal antigen-presenting cells for
initiation of an immune response. Indeed, dendritic cells provide the
basis for the production of an effective immune response to a vaccine,
particularly for antigens wherein conventional vaccination is
inadequate. DCs are also important in the production on an immune
response to tumor antigens.
The present invention discloses methods of using the receptor
tyrosine kinase discoidin domain receptor 1 (DDR1) to facilitate the
maturation/differentiation of DCs or macrophages. Activating agents of
DDR1 may be
[[Page 47842]]
useful in the induction of highly potent, mature DCs or highly
differentiated macrophages from DC precursors, such as monocytes. Use
of this method may enhance the antigen presenting capabilities of the
immune system, leading to a more effective overall immune response.
This research is further described in H. Kamohara et al., FASEB J.
(October 15, 2001) 10.1096/fj.01-0359fje; and W. Matsuyama et al.,
FASEB J. (May 8, 2003) 10.1096/fj.02-0320fje.
Methods for Reducing Tumor Growth and Metastasis by Inhibiting MCP-1
Activity
William J. Murphy et al. (NCI).
PCT Patent Application No. PCT/US01/16058, filed May 18, 2001 [HHS Ref.
No. E-131-2000/0-PCT-02]; Australian Patent Application No. 2001261743,
filed May 18, 2001 [HHS Ref. No. E-131-2000/0-AU-03]; Canadian Patent
Application No. 2409298, filed May 18, 2001 [HHS Ref. No. E-131-2000/0-
CA-04]; European Patent Application No. 01935670.8-24, filed May 18,
2001 [HHS Ref. No. E-131-2000/0-EP-05]; and U.S. Patent Application No.
10/276,644, filed March 10, 2003 [HHS Ref. No. E-131-2000/0-US-06].
Licensing Contact: Jesse S. Kindra; 301/435-5559; kindraj@mail.nih.gov.
Monocyte Chemotactic Protein 1 (MCP-1) is a chemokine that is
abundantly produced in a variety of inflammatory diseases. Consistent
with its role in inflammation, MCP-1 is known to be chemotactic for
monocytes, T lymphocytes, basophiles and NK cells.
Based on its chemotactic effect on monocytes, MCP-1 has been
observed to have an anti-tumor effect in certain mouse/tumor
experimental designs. In those mouse systems, MCP-1 production by tumor
cells was positively correlated with the number of intratumoral
macrophages and inversely correlated with tumor growth. These studies
have led to the hypothesis that MCP-1 possesses anti-tumorigenic
activity.
The present invention is based on the surprising discovery that
inhibition of MCP-1 activity inhibits tumor metastasis and prolongs
survival. Accordingly, this invention generally relates to methods of
inhibiting tumor growth and/or metastasis in a subject, and methods of
treating cancer and/or increasing survival of a subject with a tumor,
by inhibiting MCP-1 activity in the subject.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Novel DNA Liposome Complexes for Increased Systemic Delivery and Gene
Expression
Nancy Smyth-Templeton and George N. Pavlakis (NCI).
U.S. Patent No. 6,413,544 issued 02 Jul 2002 (HHS Reference No. E-
143-1996/0-US-03); U.S. Patent No. 6,770,291 issued 03 Aug 2004 (HHS
Reference No. E-143-1996/0-US-04); U.S. Patent Application No. 10/
825,803 filed 15 Apr 2004 (HHS Reference No. E-143-1996/0-US-16).
Licensing Contact: John Stansberry; 301/435-5236;
stansbej@mail.nih.gov.
Improved liposomes have been created that could increase the
efficacy of treatments for cancer, cardiovascular diseases, and HIV-1
related diseases in small and large animal models. These liposomes
efficiently condense nucleic acids, proteins, viruses, drugs, and
mixtures of these agents on the interior of bilamellar invaginated
structures produced by a novel extrusion procedure. This technology is
an improved delivery system for all biologically active reagents. By
using extruded DOTAP:Cholesterol liposomes to form complexes with DNA
encoding specific proteins, expression has been improved dramatically.
These nucleic acid:liposome complexes have extended half-life in the
circulation, are stable in serum, have broad biodistribution,
efficiently encapsulate various sizes of nucleic acids and other
molecules including viruses and drugs, are targetable to specific
organs and cell types, penetrate through tight barriers in several
organs, are fusogenic with cell membranes and avoid endosomes, are
optimized for nucleic acid:lipid ratio and colloidal suspension in
vivo, can be size fractionated to produce a totally homogenous
population of complexes prior to injection; are non-toxic, non-
immunogenic and can be repeatedly administered, and liquid suspensions
and freeze-dried formulations are stable. These complexes have been
injected into mice, rats, rabbits, pigs, nonhuman primates, and humans.
Currently, these complexes are injected intravenously into patients in
clinical trials to treat lung cancer and will be used in upcoming
trials to treat breast, pancreatic, head and neck cancers; and
Hepatitis B and C.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Methods of Delivering Agents to Target Cells
Andrew J. George et al. (NCI).
U.S. Patent No. 5,861,156 issued 19 Jan 1999 (HHS Reference No. E-130-
1993/0-US-01).
Licensing Contact: George G. Pipia; 301/435-5560; pipiag@mail.nih.gov.
The present invention relates to methods of delivering agents to
target cells. The target cells are modified by one or more monospecific
binding proteins reactive with one or more consistent naturally
occurring target cell surface markers. The monospecific binding protein
reactive with the cell surface marker is tagged, fused to, or labeled
with a chemical moiety which is recognized by, and binds to a site on a
multivalent antibody, which also binds an agent to be delivered. The
agent is bound to the multivalent antibody, which in turn, is also
bound to a tagged monospecific binding protein which is bound to a cell
surface marker on a target cell. Thus, the agent is delivered, or
directed, to the target cells.
Chemical moiety, as used herein, includes a genetically fused or
otherwise coupled peptide, one or more peptides within the sequence of
a mono-or bispecific binding protein, a posttranslationally or
chemically modified peptide, a chemical substituent such as biotin,
incorporated into the protein, or any non-natural amino acid
incorporated into the binding protein. Chemical moiety also includes
any protein or parts thereof, or peptide comprising an amino acid
sequence that is reactive with a recognition site, including a linker
connecting variable regions of a single-chain Fv (sFv) or sFv fusion
protein, or an epitope of the monospecific binding protein.
The present invention further relates to a method of immunotherapy
in a host whereby target cells are destroyed with enhanced selectivity
using target cell-directed cytotoxic agents. This method of
immunotherapy involves two concepts: the specific modification of the
target cell with chemical moiety-labeled monospecific binding proteins
and the targeting of cytotoxic agents to the modified target cells.
Dated: August 5, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 05-16136 Filed 8-12-05; 8:45 am]
BILLING CODE 4140-01-P
