Vascular endothelial growth factor D(VEGF-D) antibodies and vectors, and methods of use
AssigneeLudwig Institute for Cancer Research and Helsinki University Licensing Ltd. OY
InventorsMarc G. Achen, Andrew F. Wilks, Steven A. Stacker, Kari Alitalo
Life of this patent
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Abstract
VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.
Claims76
An isolated nucleic acid molecule comprising a nucleic acid sequence which encodes a polypeptide comprising a sequence of amino acids substantially corresponding to the amino acid sequence set out in SEQ ID NO.3, SEQ ID NO.5, SEQ ID NO.8 or SEQ ID NO. 9, said polypeptide having the ability to stimulate vascular permeability or proliferation of endothelial cells, or a fragment or analogue thereof which has the ability to stimulate at least one biological activity selected from the group consisting of angiogenesis, vascular permeability, endothelial cell proliferation, differentiation, migration or survival, or which has the ability to bind to endothelial cells, but is unable to stimulate at least one of said biological activities.
An isolated polypeptide which comprises a sequence of amino acids substantially corresponding to the amino acid sequence set out in SEQ ID NO.3, SEQ ID NO.5, SEQ ID NO.8 or SEQ ID NO. 9, said polypeptide having the ability to stimulate vascular permeability or proliferation of endothelial cells, or a fragment or analogue thereof which has the ability to stimulate at least one endothelial cell biological activity selected from the group consisting of cell proliferation, cell differentiation, cell migration, cell survival and vascular permeability, or which has the ability to bind to endothelial cells but is unable to stimulate at least one of said biological activities.
A vector comprising an anti-sense nucleotide sequence, said anti-sense nucleotide sequence being complementary to at least a part of a VEGF-D genomic DNA sequence or a VEGF-D RNA sequence or a cDNA sequence which encodes VEGF-D or a fragment or analogue thereof which promotes at least one bioactivity selected from vascular permeability, proliferation of endothelial cells and endothelial cell differentiation, whereby said vector can be used to inhibit said at least one bioactivity.
A method of inhibiting a bioactivity selected from angiogenesis and neovascularization in a mammal, said method comprising the step of administering to said mammal an effective angiogenesis or neovascularization inhibiting amount of a VEGF-D antagonist according to claim 70.
A VEGF-D antagonist having the capability to inhibit at least one biological activity induced by VEGF-D selected from vascular permeability, endothelial cell proliferation and endothelial cell differentiation, said antagonist binding to VEGF-D or to a VEGF-D receptor, but being less able than VEGF-D to stimulate said at least one biological activity.
Dependencies are inferred from the claim text.