[Federal Register Volume 75, Number 231 (Thursday, December 2, 2010)]
[Notices]
[Pages 75179-75182]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-30278]
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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.
Mouse Monoclonal Antibody for CEACAM
Abstract: The following biological material is a hybridoma cell
line generated from mice lymphocytes immunized with human mammary
carcinomas and fused to a myeloma cell line. The resulting mouse
monoclonal antibody (MAb, clone B1.1) is directed against
carcinoembryonic antigen (CEA). CEA are glyco-proteins whose expression
levels are increased on the surface of metastatic cancer cells.
Therefore, antibodies generated from the hybridoma clone B1.1 can be
used to detect cancer cells. MAb B1.1 binds to the surface of human
breast and melanoma cell lines and cells associated with colon
carcinomas and adenomas. The antibody has been tested to work
effectively in several techniques such as Immunofluorescence, Western
Blot, Fluorescent Activated Cell Sorting (FACS), and
Immunohistochemistry (IHC).
Commercial Applications
Developing cancer biomarker.
Developing cell sorting assays (e.g. FACS).
Immunofluorescence, Western Blotting, and
Immunohistochemistry for CEA.
Developing prognostic assays for cancer.
Competitive Advantages: Tested to bind CEA and can be used in
different Immunological Techniques such as Immunofluorescence, Western
Blot, Fluorescent Activated Cell Sorting (FACS), and
Immunohistochemistry (IHC).
Materials Available: 1 vial of Hybridoma cell line (B1.1).
Inventors: Jeffrey Schlom and David Colcher (NCI).
Related Publications
1. D. Colcher et al. (1983) [PubMed: 6365268].
2. D. Stramignoni et al. (1983) [PubMed: 6852972].
Patent Status: ``The Generation of Monoclonal Antibody (MAb) B1.1
and Its Reactivity to Human Tumors,'' HHS Reference No. E-272-2010/0--
Research Material. Patent protection is not being pursued for this
technology.
Licensing Status: Available for licensing under a Biological
Materials License Agreement.
Licensing Contact: Sabarni Chatterjee, Ph.D.; 301-435-5587;
[email protected].
Novel Compounds That Specifically Kill Multi-Drug Resistant Cancer
Cells
Description of Technology: One of the major hindrances to
successful cancer chemotherapy is the development of multi-drug
resistance (MDR) in cancer cells. MDR is frequently caused by the
increased expression or activity of ABC transporter proteins in
response to the toxic agents used in chemotherapy. The increased
expression or activity of the ABC transporter proteins causes the toxic
agents to be removed from cells before they can act to kill the cell.
As a result, research has generally been directed to overcoming MDR by
inhibiting the activity of ABC transporters, thus causing the
chemotherapeutic agents to remain in the cell long enough to exert
their effects. However, compounds that inhibit ABC transporter activity
often elicit strong and undesirable side-effects due to the inhibition
of ABC transporter function in normal cells, thereby restricting their
usefulness as therapeutics.
[[Page 75180]]
Investigators at the NIH previously identified novel compounds with
the ability to kill multi-drug resistant cancer cells while leaving
normal cells relatively unharmed. These ``MDR-selective compounds''
were not inhibitors of ABC transporters because they killed multi-drug
resistant cells without affecting the activity of ABC transporters.
Furthermore, their activity was dependent directly on the level of
expression of ABC transporters, thus increasing their selectivity for
diseased cells. As a result, the undesirable side-effects that have
prevented the use of inhibitors of ABC transporters as therapeutics
should not affect the therapeutic application of the MDR-selective
compounds.
The inventors have now generated third generation MDR-selective
compounds with further improved solubility, selectivity and killing
activity toward MDR cells. The new MDR-selective compounds selectively
kill MDR cancer cells, and their efficacy correlates directly with the
level of ABC transporter expression. This suggests that the third
generation MDR-selective compounds represent a powerful strategy for
treating MDR cancers.
Applications:
Treatment of cancers associated with MDR, either alone or
in combination with other therapeutics.
Development of a pharmacophore for improved MDR-selective
compounds.
Advantages:
MDR-selective compounds capitalize on one of the most
common drawbacks to cancer therapies (MDR) by using it as an advantage
for treating cancer.
The compositions do not inhibit the activity of ABC
transporters, thereby reducing the chance of undesired side-effects
during treatment.
The effects of MDR-selective compounds correlate with the
level of ABC transporter expression, allowing healthy cells to better
survive treatments.
Increased specificity and solubility of the new MDR-
inverse compounds allows greater access to MDR cells, thereby
increasing therapeutic effectiveness.
Development Status: Preclinical stage of development, in vitro
data.
Inventors: Hall (NCI) et al.
U.S. Patent Status: U.S. Provisional Application 61/375,672 (E-249-
2010/0-US-01).
For more information, see:
Hall, MD et al. (2009) ``Synthesis, activity, and
pharmacophore development for isatin-beta-thiosemicarbazones with
selective activity toward multidrug-resistant cells'' J Med Chem.
52(10):3191-204.
PCT Publication WO 2009/102433 (PCT Patent Application
PCT/US2009/000861).
Licensing Status: Available for licensing.
Licensing Contact: David A. Lambertson, Ph.D.; 301-435-4632;
[email protected].
Collaborative Research Opportunity: The Center for Cancer Research,
Laboratory of Cell Biology, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize this technology. Please contact
John Hewes, Ph.D. at 301-435-3121 or [email protected] for more
information.
Isocitrate Dehydrogenase 1 (IDH1) R132 Mutation Human Melanoma
Metastasis Cell Line
Description of Technology: Isocitrate dehydrogenase 1 (IDH1) plays
an important role in glucose metabolism in the cytoplasm, converting
isocitrate to [alpha]-ketoglutarate while reducing nicotinamide adenine
dinucleotide phosphate (NADP+ to NADPH). However, when IDH1 harbors a
R132 mutation it results in the accumulation of 2-hydroxyglutarate and
has a corresponding association with cancer. This mutation in IDH1 has
previously been identified in approximately 80% of progressive gliomas
and 10% acute myeloid leukemias (AML). In contrast, this mutation is
very rare in other cancers. Therefore, additional research on the IDH1
R132 mutation could be useful for diagnostic, prognostic, and
therapeutic purposes.
The researchers at the NIH have developed a human melanoma cell
line designated 2633, which harbors the IDH1 R132C mutation. The
inventors used low passage cell lines derived from a panel of confirmed
metastatic melanoma tumor resections, paired with apheresis-collected
peripheral blood mononuclear cells to identify IDH1 mutations.
Sequencing of IDH1 in this panel allowed them to discover a melanoma
cell line with the IDH1 R132C mutation. Until now no such cell line has
been found and this has hindered the understanding of the effects
mutated IDH1 has on cancer progression as well as the development of
drugs that would be specific for cells that harbor this mutation. Use
of this cell line will allow researchers to decipher the biology of
this gene as well as aid in the development of specific inhibitors of
its mutated form.
Applications:
In vitro and in vivo cell model for the IDH1 R132C
mutation in melanoma. This would be an extremely useful research tool
for investigating the underlying biology of IDH1 phenotypes, including
effects on growth, motility, invasion, and metabolite production.
Research tool for testing the activity of inhibitors to
IDH1, where such inhibitors could be used as a therapeutic drug to
treat particular cancers including potentially glioma, AML and
melanoma.
Research tool to generate cell lines where the R132C
mutation is knocked out or the wild type gene is knocked in using an
adeno-associated virus. These resulting cells can be used to understand
the underlying biology of IDH1 phenotypes or to identify candidate
small molecule and other therapeutic drugs.
Advantages:
Cell line is derived from a melanoma patient: This cell
line likely retains many features of primary melanoma samples. For
example novel melanoma antigens identified from this cell would be
expected to correlate with antigens expressed on human melanoma tumors.
Studies performed using this cell line could be used to elucidate to
the biological basis of the initiation and progression of melanoma in
humans as well as aid in the identification and/or testing of IDH1
R132-targeted inhibitors.
Expresses the R132 IDH1 mutation in melanoma: IDH1 R132
mutations frequently occur in advanced gliomas, however this is the
first identification of an IDH1 mutation in melanoma. Therefore, the
2633 cell line represents a tool that can be utilized to study the
impact of this IDH1 gene and the R132C mutation on melanoma and other
cancers.
Inventors: Yardena Samuels (NHGRI) and Steven Rosenberg (NCI).
Publication: Lopez GY, Reitman ZJ, Solomon D, Waldman T, Bigner DD,
McLendon RE, Rosenberg SA, Samuels Y, Yan H. IDH1(R132) mutation
identified in one human melanoma metastasis, but not correlated with
metastases to the brain. Biochem Biophys Res Commun. 2010 Jul
30;398(3):585-587. [PubMed: 20603105]
Patent Status: HHS Reference No. E-232-2010/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing.
Licensing Contact: Whitney Hastings; 301-451-7337;
[email protected].
Collaborative Research Opportunity: The National Human Genome
Research Institute's Cancer Genetics Branch is seeking statements of
capability or
[[Page 75181]]
interest from parties interested in collaborative research to further
develop, evaluate and/or commercialize this newly identified melanoma-
associated gene as a diagnostic marker as well as utilize the IDH1 R132
cell line to identify and test IDH1 inhibitors as possible therapeutic
drug candidates to treat melanoma and other cancers. Please contact Dr.
Yardena Samuels at [email protected] for more information.
ERBB4 Mutations Mutation Identified in Human Melanoma Metastasis Cell
Lines (2690, 2379, 2197, 2183, 2535, 2645, 1770, 2359, 2238, 2319,
2190)
Description of Technology: Protein tyrosine kinases (PTKs) have
been associated with a wide variety of cancers, including melanoma.
Using high-throughput gene sequencing, the NIH has analyzed PTKs in
melanoma and identified several novel somatic alterations, including
alterations in ERBB4 (also called HER4). These mutations were found to
increase the sensitivity of cells in which they reside to small
molecule inhibitors, such as lapatinib.
Available for licensing are several melanoma cell lines that harbor
ERBB4 mutations. These cell lines provide methods of identifying
specific inhibitors to ERBB4 that could be used to treat patients with
ERBB4 mutations as well as methods to further understand the role of
ERBB4 mutations in melanoma. Given the recent success of small molecule
protein kinase inhibitors and specifically inhibitors to epidermal
growth factor receptor (EGFR) (such as gefinitib and erlotinib), these
reagents could be used to further the development of specific
inhibitors to ERBB4 and improve existing melanoma treatments for
patients with these mutations.
Applications:
In vitro and in vivo cell model for understanding the
biology of ERBB4, including growth, motility, invasion, and metabolite
production.
High throughput drug screening to test for ERBB4
inhibitors that could be used to treat particular cancers, such as
melanoma.
Diagnostic array for the detection of ERBB4 mutations.
Research tool to generate cell lines where the ERBB4
mutation is knocked out or the wild type gene is knocked in using an
adeno-associated virus. These resulting cells can be used to understand
the underlying biology of ERBB4 phenotypes or to identify candidate
small molecule and other therapeutic drugs.
Advantages:
Cell lines are derived from melanoma patients: These cell
lines are likely to retain many features of primary melanoma samples.
For example novel melanoma antigens identified from this cell line
would be expected to correlate with antigens expressed on human
melanoma tumors. Studies performed using these cell lines could be used
to elucidate the biological basis of initiation and progression of
melanoma in humans as well as aid in the identification and/or testing
of ERBB4 inhibitors.
Expresses the ERBB4 mutation in melanoma: ERBB4 is a
highly mutated gene in melanoma, suggesting its important functional
role in the disease. Therefore, these cell lines represent a tool that
can be utilized to study the impact of the ERBB4 gene and the
associated mutations on melanoma, and possible other cancers since
mutations in ERBB family members such as EGRF and ERBB2 are prevalent
in lung cancer, glioblastoma and gastric cancer.
Inventors: Yardena Samuels (NHGRI), Steven Rosenberg (NCI), and
Todd Prickett (NHGRI).
Publication: Prickett TD, Agrawal NS, Wei X, Yates KE, Lin JC,
Wunderlich JR, Cronin JC, Cruz P, Rosenberg SA, Samuels Y. Analysis of
the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4.
Nature Genet. 2009 October; 41(10):1127-1132. [PubMed: 19718025]
Patent Status: HHS Reference No. E-229-2010/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing.
Licensing Contact: Whitney Hastings; 301-451-7337;
[email protected].
Collaborative Research Opportunity: The National Human Genome
Research Institute's Cancer Genetics Branch is seeking statements of
capability or interest from parties interested in collaborative
research to further develop, evaluate and/or commercialize these newly
characterized ERBB4 mutant cell lines as well as to identify and test
ERBB4 inhibitors as possible therapeutic drug candidates to treat
melanoma and other cancers. Please contact Dr. Yardena Samuels at
[email protected] for more information.
Synthetic Analogs of RGD and NGR Cyclic Peptides
Description of Technology: Cell surface biomolecules such as
integrins ([alpha]v[beta]3, [alpha]v[beta]5,
[alpha]v[beta]8, [alpha]6[beta]4), folate
receptors, and CD13 are highly expressed in cancer cells and are
involved in angiogenesis, invasion and metastasis. Consequently, this
has made these cellular biomolecules attractive targets for delivery of
drugs that can bind to them selectively. The peptide motifs RGD (Arg-
Gly-Asp) and NGR (Asn-Gly-Arg), in particular, are recognized by
integrins [alpha]v[beta]3 and
[alpha]v[beta]5 and CD13 with high affinity.
Further, short peptide sequences of RGD and NGR are commercially useful
because they are amenable to large scale synthesis, chemical
modification and are non-immunogenic. Therefore, there is a need for
cyclic compounds having the NGR peptide motif to target CD13 or having
the RGD peptide motif to target [alpha]v[beta]3
and [alpha]v[beta]5 integrins.
Accordingly, the researchers at the NIH have developed cyclic NGR
and RGD pentapeptide analogs efficiently synthesized on resin via click
chemistry. These cyclic peptides are potentially useful in targeted
delivery of drugs, antibodies, or nanoparticles to the site of
angiogenic blood vessels and tumors. By allowing for targeted drug
delivery, these peptides can minimize general cytotoxicity and improve
bioavailability. The cyclic peptides described are novel, synthetic
analogs of RGD and NGR cyclic peptides. Therefore, their inherent
cyclic structure and the cyclization strategy will make these compounds
stable from hydrolytic degradation, thereby prolonging their half life
in circulation.
Applications: Targeted drug delivery and medical imaging of cancer
tissues expressing CD13 or [alpha]v[beta]3 and
[alpha]v[beta]5 integrins.
Advantages:
These cyclic peptides contain a triazole unit that would
be less likely to be attacked by hydrolytic enzymes and esterases, thus
making them ideal candidates for in vivo targeted delivery and imaging.
The RGD and NGR cyclic peptides are amenable to large
scale synthesis, chemical modification and are non-immunogenic, while
the linear RGD peptide counterparts are prone to protease degradation
making them much less stable and limiting their use in in vivo
applications.
Both linear and disulfide-bridged cyclic peptides
containing the NGR motif have been used to deliver various anti-tumor
compounds and viral particles to tumor vessels, with the cyclic
versions showing more than a 10 fold higher binding affinity than their
linear counterparts.
Development Status: Pre-clinical proof of principle.
Inventors: Belhu B. Metaferia and Javed Khan (NCI).
Publications: B Metaferia et al. Synthesis of novel cyclic NGR/RGD
[[Page 75182]]
peptide analogs via on resin click chemistry. In preparation.
Patent Status: U.S. Provisional Application No. 61/347,038 filed 21
May 2010 (HHS Reference No. E-130-2010/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Whitney Hastings; 301-451-7337;
[email protected].
Novel Therapeutic Compounds for Treatment of Cancer and Immune
Disorders
Description of Invention: The global market for cancer therapeutics
is over $40 billion and is anticipated to continue to rise in the
future. There remains a significant unmet need for therapeutics for
cancers that affect blood, bone marrow, and lymph nodes and the immune
system, such as leukemia, multiple myeloma, and lymphoma. The
proteasome inhibitor bortezomib, which may prevent degradation of pro-
apoptotic factors permitting activation of programmed cell death in
neoplastic cells dependent upon suppression of pro-apoptotic pathways,
has been a successful mode of treatment for such cancers. However, some
patient's cancers have been found to be resistant to the drug.
Researchers at the National Institutes of Health have developed
novel hydrazone and diacyl hydrazine compounds that are inhibitors of
the endoplasmic reticulum-associated protein degradation (ERAD)
pathway. These compounds preferentially target the proteasome assistant
ATPase p97/VCP at a site independent of nucleotide binding. The
researchers have shown that these ERAD inhibitors can induce cancer
cell death and can also synergize with bortezomib in cytotoxic
activity. In addition to treating diseases or disorders in which
inhibition of the ERAD pathway is an effective therapy, these novel
compounds may also be useful in the study of protein degradation.
Advantages:
Development of therapies against tumors that are resistant
to bortezomib.
Use in therapies in combination with proteasome
inhibitors.
Development of immunosuppressive therapies that target the
ubiquitin proteasome system.
Studies of the mechanism of protein degradation and other
biological processes that involve the p97 ATPase.
Bioprobes to detect endoplasmic reticulum (ER) structures
in live cells.
Advantages:
Potent anti-tumor activity.
Simpler chemical structure makes synthesis easier and more
cost-effective than previous ERAD inhibitors.
Retain activity against bortezomib-resistant cells and can
synergize with bortezomib.
Fluorescent.
High affinity for the ER.
Development Status: Pre-clinical.
Inventors: Adrian Wiestner (NHLBI), William Trenkle (NIDDK), Yihong
Ye (NIDDK) et al.
Relevant Publications:
1. Qiuyan Wang et al. ERAD inhibitors integrate ER stress with an
epigenetic mechanism to activate BH3-only protein NOXA in cancer cells.
Proc Natl Acad Sci USA 2009 Feb 17;106(7):2200-2205. [PubMed: 19164757]
2. Qiuyan Wang et al. The ERAD inhibitor Eeyarestatin I is a
bifunctional compound with a membrane-binding domain and a p97/VCP
inhibitory group. PloS ONE 2010, in press.
Patent Status: U.S. Provisional Application No. 61/266,760 filed 04
Dec 2009 (HHS Reference No. E-291-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Surekha Vathyam, Ph.D.; 301-435-4076;
[email protected].
Targeted Anti-Cancer Compounds for Treating Chromosomal Instability
Syndromes
Description of Invention: At $47 billion, cancer is one of the
largest, fastest growing markets in the pharmaceutical industry. There
remains a significant unmet need for new therapeutics that target
cancer cells while sparing normal cells. Cancer cells show higher
levels of DNA damage than normal cells, and therefore rely more heavily
than normal cells on DNA repair mechanisms for survival. There is a
particular need for cancer therapies for cancer-prone chromosomal
instability syndromes such as Ataxia Telangiectasia, Nijmegen Breakage,
Bloom, and Fanconi's anemia, which result from dysfunctional DNA repair
systems.
Researchers at Columbia University and the National Cancer
Institute (NCI) have developed compositions and methods of useful in
the treatment of cancer and in the sensitization of cancer cells to
cancer therapy. The compositions target the MRE11-RAD50-NBS1 (MRN)
complex, a DNA repair complex essential for sensing and responding to
DNA damage.
Given the dependency of cancer cells on DNA repair systems, they
are susceptible to compositions that inhibit DNA damage repair. Thus,
cancers that already have one or more defects in DNA repair systems,
such as those from patients with chromosomal instability syndromes, are
effectively treated with the present compositions.
Applications: Development of treatments for cancer.
Development Status: Pre-clinical.
Inventors: Levy Kopelovich (NCI) et al.
Relevant Publication: A Dupr[eacute] et al. A forward chemical
genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex.
Nat Chem Biol. 2008;4(2):119-125. [PubMed: 18176557]
Patent Status:
U.S. Provisional Application No. 61/203,377 filed 22 Dec
2008 (HHS Reference No. E-154-2009/0-US-01).
International Application No. PCT/US09/69171 filed 22 Dec
2009, which published as WO 2010/075372 on 01 Jul 2010 (HHS Reference
No. E-154-2009/0-PCT-02).
Licensing Status: Available for licensing.
Licensing Contact: Patrick P. McCue, Ph.D.; 301-435-5560;
[email protected].
Collaborative Research Opportunity: The National Cancer Institute,
Division of Cancer Prevention, Chemopreventive Agent Development
Research Group, is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize agents for the prevention and treatment of
cancer. Please contact John Hewes, Ph.D. at 301-435-3121 or
[email protected] for more information.
Dated: November 24, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-30278 Filed 12-1-10; 8:45 am]
BILLING CODE 4140-01-P