[Federal Register Volume 70, Number 156 (Monday, August 15, 2005)]
[Notices]
[Pages 47840-47842]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-16136]


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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, DHHS.

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

[[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; 
[email protected].

    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; [email protected].

    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; [email protected].

    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; 
[email protected].

    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; [email protected].

    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; [email protected].

    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; 
[email protected].

    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; [email protected].

    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