Chemistry: molecular biology and microbiology – Vector – per se
Reexamination Certificate
2001-10-04
2003-08-26
Nguyen, Dave T. (Department: 1635)
Chemistry: molecular biology and microbiology
Vector, per se
C435S252300, C514S04400A, C536S023100, C536S023500, C536S023400
Reexamination Certificate
active
06610534
ABSTRACT:
This invention relates to the induction of blood vessel formation. More particularly, this invention relates to the induction of blood vessel formation in an animal by administering to the animal a sphingosine kinase, or an analogue, fragment, or derivative thereof. Preferably, the sphingosine kinase, or analogue, fragment, or derivative thereof is administered by administering to the animal a polynucleotide encoding a sphingosine kinase, or an analogue, fragment, or derivative thereof. The polynucleotide encoding the sphingosine kinase may be contained in an appropriate expression vehicle or expression vector, such as an adenoviral vector.
BACKGROUND OF THE INVENTION
Vascular endothelial cells undergo morphogenesis into capillary networks in response to angiogenic factors. It was shown previously that sphingosine-1-phosphate, or SPP, a platelet-derived bioactive lipid, is an important sphingolipid-derived second messenger in mammalian cells that acts to promote proliferation and to inhibit apoptosis. (Olivera, et al.,
Nature,
Vol. 365, pgs. 557-560 (Oct. 7, 1993); Spiegel, et al.,
J. Leukoc. Biol.,
Vol. 65, No. 3, pgs. 341-344 (March 1999).) Recently, SPP was defined as a novel regulator of angiogenesis. (Lee, et al.,
Cell,
Vol. 99, No. 3, pgs. 301-312 (Oct. 29, 1999).) SPP activates the endothelial cell differentiation genes (EDG) EDG-1 and EDG-3 subtypes of G protein-coupled receptors on endothelial cells. Both EDG-1 and EDG-3 regulated signaling pathways are required for endothelial cell morphogenesis into capillary-like networks. SPP induces the Gi/mitogen-activated protein kinase cell survival pathway and enhances small GTPase Rho and Rac coupled adherens junction assembly. (Lee, 1999.) The level of SPP is regulated potentially by the enzyme that catalyzes the phosporylation of sphingosine to SPP. The cloning and characterization of the first mammalian sphingosine kinases (murine SPHK1&agr; and SPHK1&bgr;) has been reported. (Kohama, et al.,
J. Biol. Chem.,
Vol. 273, No. 37, pgs. 23722-23728 (Sep. 11, 1998)). Human sphingosine kinases (SPHK1 and SPHK2) have also been reported. (Nava, et al.,
FEBS,
473:81-84 (2000) and Liu, et al., J. Biol. Chem., 275:19513-19520 (2000).)
SUMMARY OF THE INVENTION
Applicants have discovered that the administration of sphingosine kinase, and in particular, that vector-mediated expression of sphingosine kinase enhances the formation of new blood vessels. Thus, the present invention is directed to inducing blood vessel formation in an animal by administering to the animal a sphingosine kinase, preferably by administering to the animal a polynucleotide encoding a sphingosine kinase or an analogue, fragment, or derivative thereof. The sphingosine kinase, or analogue, fragment, or derivative thereof, or polynucleotide encoding sphingosine kinase or an analogue, fragment, or derivative thereof, may be administered in combination with other angiogenic proteins or polynucleotides encoding other angiogenic proteins such as, but not limited to, VEGF, FGF, IGF, angiopoietins, PD-EGF, TGF&bgr;, HIF1-&agr;, nitric oxide synthase, MCP-1, Interleukin-8, ephrins, NAP-2, ENA-78, GROW-2, and fragments of tyrosyl-tRNA synthetase that have angiogenic activity as disclosed in U.S. patent applications Ser. Nos. 60/193,471 filed Mar. 31, 2000, and 09/813,718, filed Mar. 21, 2001. The polynucleotide encoding the sphingosine kinase may be contained in an appropriate expression vehicle or expression vector, such as a viral vector. The administration of a polynucleotide encoding a sphingosine kinase to an animal is a method by which SPP can be delivered at elevated levels to a local site, and such method provides for the formation of larger vessels containing a well-defined structure that is supported by mural cells such as pericytes and smooth-muscle cells.
REFERENCES:
patent: 5932540 (1999-08-01), Hu et al.
patent: WO 99/61581 (1999-12-01), None
patent: WO 00/70028 (2000-11-01), None
Boguslawski, et al., “Sphingosylphosphorylcholine Induces Endothelial Cell Migration and Morphogenesis,”Biochemical and Biophysical Research Communications, 272:603-609 (Jun. 7, 2000).
Hla, et al., “Sphingosine-1-phosphate: Extracellular Mediator or Intracellular Second Messenger?”Biochemical Pharmacology, 58:201-207 (1999).
Kohama, et al., “Molecular Cloning and Functional Characterization of Murine Sphingosine Kinase,”The Journal of Biological Chemistry, 273(37):23722-23728 (Sep. 11, 1998).
Lee, et al., “Sphingosine-1-Phosphate as a Ligand for the G Protein-Coupled Receptor EDG-1,”Science, 279:1552-1555 (Mar. 6, 1998).
Lee, et al., “Vascular Endothelial Cell Adherens Junction Assembly and Morphogenesis Induced by Sphingosine-1-Phosphate,”Cell, 99:301-312 (Oct. 29, 1999).
Lee, et al., “Sphingosine 1-Phosphate Induces Angiogenesis: Its Angiogenic Action and Signaling Mechanism in Human Umbilical Vein Endothelial Cells,”Biochemical and Biophysical Research Communications, 264:743-750 (1999).
Liau, G., “A Gene Therapy Approach toward the Modulation of Angiogenesis,” International Business Communications Sixth Annual International Conference on Angiogenesis, Oct. 5-6, 2000.
Liu, et al., “Molecular Cloning and Functional Characterization of a Novel Mammalian Sphingosine Kinase Type 2 Isoform,”The Journal of Biological Chemistry, 275(26):19513-19520 (Jun. 30, 2000).
Liu, et al., “Edg-1, the G Protein-Coupled Receptor for Sphingosine-1-Phosphate, is Essential for Vascular Maturation,”The Journal of Clinical Investigation, 106(8):951-961 (Oct. 2000).
Nava, et al., “Functional Characterization of Human Sphingosine Kinase-1,”FEBS Letters, 473:81-84 (May 4, 2000).
Olivera, et al., “Sphingosine-1-Phosphate as Second Messenger in Cell Proliferation Induced by PDGF and FCS Mitogens,”Nature, 365:557-560 (Oct. 7, 1993).
Panetti, et al., “Sphingosine-1-Phosphate and Lysophosphatidic Acid Stimulate Endothelial Cell Migration,”Arterioscler. Thromb. Vasc. Biol., pp. 1013-1019 (1999).
Passaniti, et al., “Methods in Laboratory Investigation,”Laboratory Investigation, 67(4):519-528 (1992).
Pyne, et al., “Sphingosine 1-Phosphate Signalling in Mammalian Cells,”Biochem., J., 349:385-402 (Jul. 15, 2000).
Spiegel, S., “Sphingosine 1-Phosphate: A Prototype of a New Class of Second Messengers,”Journal of Leukocyte Biology, 65:341-344 (Mar. 1999).
Wang, et al., “Sphingosine 1-Phosphate Stimulates Cell Migration Through a Gl-Coupled Cell Surface Receptor,”The Journal of Biological Chemistry, 274(50):35343-35350 (Dec. 10, 1999).
Ylä-Herttuala, et al., “Cardiovascular Gene Therapy,”The Lancet, 355:213-222 (Jan. 15, 2000).
Zhang, et al., “Comparative Analysis of Three Murine G-Protein Coupled Receptors Activated by Sphingosine-1-Phosphate,”Gene, 227:89-99 (1999).
Banno, et al., “Evidence for the Presence of Multiple Forms of Sph Kinase in Human Platelets,”J. Biochem., 335:301-304 (1998).
Liau Gene
Stefansson Steingrimur
Su Joseph
Angell J Eric
Golightly Douglas A.
Karny Geoffrey M.
Meigs J. Timothy
Nguyen Dave T.
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