[Federal Register: April 16, 2003 (Volume 68, Number 73)]
[Notices]
[Page 18656-18658]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr16ap03-80]
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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 agencies 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.
Method and Materials for Promoting Migration of T Cells to the
Vasculature of a Tumor
Patrick Hwu and Mary Tschoi (NCI).
Serial No. 60/447,497 filed 14 Feb 2003.
Licensing Contact: Jonathan Dixon; (301) 435-5559; dixonj@od.nih.gov.
Adoptive immunotherapy with T cells is a promising therapeutic
modality for cancer. However, the effectiveness of this method of
treatment appears to be limited by the inefficient migration of T cells
to the tumor site. The present invention provides materials and methods
that promote the migration of T cells to the vasculature of a tumor.
This invention discloses a novel method of administering modified
autologous T cells, which bind to cell-surface molecules on endothelial
cells of the vasculature of a tumor. Using the disclosed method and
modified T cells, investigators were able to promote the migration of T
cells to molecules expressed on the vasculature of tumors. It is
anticipated that this method and these modified autologous T cells will
improve the effectiveness of adoptive immunotherapy for a variety of
tumors, including melanoma and many carcinomas and sarcomas.
This research has been described, in part, in Dudley et al.,
Science 298:850-854 (25 October 2002).
Amplification and Overexpression of Septin9 MLL Septin-Like Fusion
(MSF) and Methods Related Thereto
Cristina Montagna et al. (NCI).
DHHS Reference No. E-003-2003.
Licensing Contact: Matthew Kiser; (301) 435-5236; kiserm@od.nih.gov.
This invention pertains to methods of detecting cancer, a method of
inhibiting a protein, oligonucleotides for use therein, a method of
inducing apoptosis, methods of testing a candidate drug for efficacy as
an anti-cancer drug and methods for evaluating the progression of
cancer.
The inventors have demonstrated that the Septin9 gene in mice (MSF
gene in humans) is amplified in cancer models for breast cancer.
Furthermore, it has been shown that the product encoded by this gene is
overexpressed in cancer. In this regard, the present invention provides
methods of detecting cancer in a mammal. One method comprises
determining whether or not the mammal has an amplification of the
Septin9 (MSF) locus or an ortholog of the gene. In this method,
overexpression of the protein or of the nucleic acid molecule is
indicative of cancer. Another method
[[Page 18657]]
comprises determining whether or not the mammal has an overexpression
of a protein or of a nucleic acid molecule, wherein the protein or the
nucleic acid molecule is encoded by a MSF gene, a Septin9 gene, or an
ortholog. In this method, overexpression of the protein or the nucleic
acid molecule is indicative of cancer.
Additionally, the present invention also provides a method of
inhibiting a protein encoded by the Septin9 gene (MSF gene) or an
ortholog in a cell. The method comprises administering to the cell an
interference RNA in an amount sufficient to reduce mRNA stability and
inhibit protein synthesis. Isolated or purified oligonucleotides, which
are suitable for use in the above method, are also disclosed.
This research is described, in part, in Montagna et al., The septin
9 (MSF) gene is amplified and overexpressed in mouse mammary gland
adenocarcinomas and human breast cancer cell lines, Cancer Research, in
press.
Methods of Inhibiting Metastasis or Growth of a Tumor Cell
Sam Hwang (NCI).
Serial No. 60/425,472 filed 12 Nov 2002.
Licensing Contact: Jonathan Dixon; (301) 435-5559; e-mail:
dixonj@od.nih.gov.
Cancer metastasis is the primary mechanism of clinical morbidity
and mortality in patients from cancer. Recently, chemokine receptors
have been shown to potentially play a role in tumor metastasis. One
such receptor, CXC Chemokine Receptor-4 (CXCR-4), is expressed in many
cancer-derived cell lines, from breast carcinoma and melanoma.
The present invention discloses the use of polypeptides to block
CXCR-4-mediated metastasis. One such polypeptide, an 18 amino acid
peptide named T22, has been shown to block CXCR-4 in CXCR-4-expressing
melanoma cells. This invention shows that CXCR-4 can be blocked through
the use of the T22 peptide to prevent the spreading of melanoma tumor
cells in the lungs in a murine model of melanoma metastasis. By not
allowing cells to metastasize, this invention could potentially reduce
the morbidity and mortality that are normally associated with
metastatic melanoma.
Method of Distinguishing Epithelioid Melanoma from Fibroblastoid
Melanoma
Denise Simmons (NCI).
DHHS Reference No. E-233-2002 filed 31 Oct 2002.
Licensing Contact: Matthew Kiser; (301) 435-5236; kiserm@od.nih.gov.
The incidence of primary cutaneous malignant melanoma is increasing
such that, at the beginning of this century, the lifetime risk for
developing melanoma approached one in 75 in the United States. In
addition, the death rate from melanoma has doubled over the last 50
years.
Melanoma in humans can have epithelioid or fibroblastoid
morphology. The fibroblastoid morphology has been associated with
resistance to treatment and escape mechanisms. Therefore, there is a
need for a method of distinguishing epithelioid and fibroblastoid
melanoma. The ability to distinguish epithelioid and fibroblastoid
melanoma would be useful in diagnosis and determining treatment
protocols. It is an object of the present invention to provide such a
method.
The present invention provides a method of distinguishing
epithelioid melanoma from fibroblastoid melanoma. The method comprises
assaying a sample of melanoma cells for retinyl ester synthesis.
Retinyl ester synthesis is indicative of the melanoma cells being
epithelioid, whereas the absence of retinyl ester synthesis is
indicative of the melanoma cells being fibroblastoid.
This research is described, in part, in Simmons et al.,
Carcinogenesis, Vol. 23 No. 11, pp 1821-1830, November 2002.
Chondropsin-Class Antitumor V-ATPase Inhibitor Compounds, Compositions
and Methods of Use Thereof
Michael Boyd and Kirk Gustafson (NCI).
DHHS Reference No. E-191-2002 filed 24 Jul 2002.
Licensing Contact: George Pipia; (301) 435-5560; pipiag@od.nih.gov.
Vacuolar type (H+) ATPase (V-ATPase) has been described as ``a
universal proton pump of eukaryotes''. V-ATPase is responsible for
maintaining internal acidity and is important in myriad of
physiological functions, such as sorting of membrane proteins,
proinsulin conversion, neurotransmitter uptake, and cellular
degradation process. This new chondropsin, Poecillastrin-A, is a
cytotoxic, 33-member ring, macrolide lactam, isolated from the sponge
Poecillastra sp. It is structurally related to the chondropsin class of
macrolide lactams. However, it possesses unique patterns of methylation
and oxygenation, and it is the first member of this family of
polyketide derivatives with a 33-membered macrocyclic ring. Its in
vitro antitumor activity is comparable to that of the chondropsins,
however the new structural features found in Poecillastrin-A broaden
the known structural diversity of this family of potent
antiproliferative and cytotoxic macrolide lantams. The chondropsins and
poecillastrin A produce a distinctive pattern of differential
cytotoxicity in the NCI's 60 cell antitumor screen that directly
correlates with selective V-ATPase inhibitors. This compound and its
derivatives could be directed to any cancer types and may have
applicability as highly selective anticancer small molecule inhibitors.
This research is described, in part, in M. A. Rashid et al.,
Organic Letters 2002, 4, 3293-3296. Also, for a reference on selective
V-ATPase inhibitors see: M. R. Boyd et al., J. Pharmacol. Exp. Ther.
2001, 297, 114-120.
Scorpionate-Like Pendant Macrocyclic Ligands, Complexes and
Compositions Thereof, and Methods of Using Same
Martin Brechbiel and Hyun-soon Chong (NCI).
DHHS Reference No. E-063-2002/0 filed 03 Jun 2002.
Licensing Contact: Matthew Kiser; (301) 435-5236; kiserm@od.nih.gov.
Monoclonal antibodies (mAbs) have been employed as targeting
biomolecules for the delivery of radionuclides into tumor cells in
radioimmunotherapy (RIT). Numerous clinical trials have been performed
to validate this modality of cancer therapy. Several useful
B- emitting radionuclides, including 131I,
90Y, 177Lu, and 153Sm, have been
employed for labeling mAbs for RIT applications. The pure B-
emitting radionuclide 90Y has been extensively studied in
RIT due to its physical properties. The macrocyclic chelating agent
1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid
(``DOTA'') is well-known to be an effective chelator of Y(III) and
lanthanides. In general, DOTA conjugated to mAbs displays relatively
slow and inefficient radiolabeling with Y(III) isotopes under mild
conditions. This is contrary to the rapid and high-yield radiolabeling
( 90%) of mAbs conjugated with bifunctional derivatives of
the acyclic chelating agent diethylenetriaminepentaacetic acid (DTPA).
Thus, there is still a need for a compound that possesses complex
stability comparable to that of DOTA, the excellent practical
complexation kinetics of DTPA, and increased stability in vitro and in
vivo. The subject invention provides such a compound.
The invention provides substituted 1,4,7-triazacyclononane-
N,N',N''-triacetic acid compounds with a pendant donor amino group,
metal
[[Page 18658]]
complexes thereof, compositions thereof and methods of using same. The
compounds of the present invention possess the same octadentate
coordinating groups as DOTA and DTPA; however, these compounds have a
combined macrocyclic and acyclic character. The macrocyclic component
chosen is based upon 1,4,7-triazacyclononane-N,N',N''-triacetic acid
(``NOTA''), while the acyclic component is a pendant
bis(carboxymethyl)amino donor group that is connected by an alkylene
bridge that is optionally substituted with an aralkyl group. The
cooperative binding of the pendant donor groups coupled with the pre-
organization and macrocyclic effect of the NOTA sub-structure
accelerates complexation with metal ions and isotopes (e.g., Y(III),
Gd(III); etc.) while maintaining a high level of stability of the
complexes.
Compositions and Methods for Inhibiting Vascular Channels and Methods
of Inhibiting Proliferation
Myung Hee Park, Paul M.J. Clement, Hartmut M. Hanauske-Abel, Edith C.
Wolff, Hynda K. Kleinman, Bernadette M. Cracchiolo (NIDCR).
DHHS Reference No. E-320-2001/0 filed 23 Aug 2001 and PCT/US02/26909
filed 23 Aug 2002.
Licensing Contact: Matthew Kiser; (301) 435-5236; kiserm@od.nih.gov.
Angiogenesis, the recruitment of new blood vessels, is recognized
as an important factor in tumor proliferation in many types of cancer.
It is generally accepted that therapeutic approaches that inhibit
angiogenesis effectively limit, or even prevent, the formation of solid
tumors. It has also been shown that anti-angiogenic therapeutics allow
conventional radiation therapy and chemotherapy to be more effective.
This invention pertains to certain compounds that inhibit
angiogenesis in a previously unrecognized way. These compounds also
inhibit the proliferation of cells within intraepithelial neoplasias
(clusters of abnormally proliferating epithelial cells that are the
origin of cancers). The subject compounds specifically block the
formation of the amino acids hypusine and hydroxyproline. The former is
the critical residue of eukaryotic translation initiation factor 5A
(eIF5A), which is important in cell cycle progression, and
hydroxyproline constitutes the critical residue of the collagens. The
targeted enzymes are deoxyhypusine hydroxylase and prolyl 4-
hydroxylase, respectively.
This invention provides evidence for an important role of eIF-5A in
angiogenesis, and discloses a family of compounds with useful clinical
properties. Specifically, these compounds include the core structures
and potential derivatives of ciclopirox olamine, deferiprone,
deferoxamine, and 2,2'-dipyridyl.
Ciclopirox olamine has potential for treatment of oral-pharyngeal
cancer, and chemoprevention and treatment of cervical and vulvar
cancer. Notably, this drug is FDA-approved in the USA as a topical
medication against fungal infections while, in Europe, it is also
approved for the treatment of yeast infections of the genital tract.
The compound has a known clinical profile and lacks teratogenicity,
potentially expediting clinical trials for new cancer treatment
indications.
sFRP and Peptide Motifs That Interact With sFRP and Methods of Their
Use
Jeffrey Rubin, Aykut Uren (both of NCI), Matthew Gillespie, Nicole
Horwood, (both of St. Vincent's Institute of Medical Research), Brian
Kay and Bernard Weisblum
Serial No. PCT/US02/00869 filed 10 Jan 2002; Serial No. 60/260,908
filed 10 Jan 2001.
Licensing Contact: Susan S. Rucker; (301) 435-4478; email:
ruckers@od.nih.gov.
These patent applications describe and claim inventions related to
the protein sFRP-1 and methods of regulating signal transduction
pathways using sFRP-1. sFRP-1 is a member of a family of secreted
proteins (secreted Frizzled Related Proteins) that were originally
identified as being able to bind to Wnt proteins. When bound to Wnts,
sFRP-1 alters the ability of Wnt protein to bind its receptor
(Frizzled), typically acting as an antagonist of Wnt signaling.
More particularly, the patent applications and inventions claimed
therein relate to methods for influencing bone remodeling using sFRP-1.
In particular, the patent application and claimed inventions relate to
methods of inhibiting osteoclastogenesis with the sFRP-1 protein. The
ability to inhibit osteoclast formation may be of value in developing
treatments for diseases such as post menopausal osteoporosis, Paget's
disease, lytic bone metastases, multiple myeloma, hyperparathyroidism,
rheumatoid arthritis, periodontitis and hypercalcemia of malignancy.
In addition to describing the method of inhibiting osteoclast
formation, the patent applications disclose various peptides containing
a conserved motif that allows the peptide containing the motif to bind
to sFRP-1.
This work has been published as WO 02/055547 (July 10, 2002).
Dated: April 8, 2003.
Steven M. Ferguson,
Acting Director, Division of Technology Development and Transfer,
Office of Technology Transfer, National Institutes of Health.
[FR Doc. 03-9284 Filed 4-15-03; 8:45 am]
BILLING CODE 4140-01-P