Patent ID: 6361946
Filing Date: 2002-03-26
Classification: A61K,A61P,C07K

Abstract:
A method for modulating myelopoiesis in a mammalian subject comprising the step of administering to a mammalian subject in need of modulation of myelopoiesis a polypeptide that binds to at least one endothelial cell surface receptor selected from the group consisting of Flt-1 receptor tyrosine kinase (VEGFR-1), KDR receptor tyrosine kinase (VEGFR-2) and Flt4 receptor tyrosine kinase (VEGFR-3), said polypeptide selected from the group consisting of:(a) a VEGF-C &Dgr;C156 polypeptide having an amino acid sequence comprising a portion of SEQ ID NO: 8 effective to permit binding to human Flt4 receptor tyrosine kinase (VEGFR-3), wherein the cysteine residue at position 156 of SEQ ID NO: 8 has been deleted or replaced by another amino acid; (b) a VEGF-C &Dgr;R226&Dgr;R227 polypeptide having an amino acid sequence comprising a portion of SEQ ID NO: 8 effective to permit binding to human Flt4 receptor tyrosine kinase (VEGFR-3), wherein the arginine residues at positions 226 and 227 of SEQ ID NO: 8 have been deleted or replaced by other amino acids; (c) a VEGF-Cbasic polypeptide having an amino acid sequence comprising amino acids 131 to 211 of SEQ ID NO: 8, with the proviso that from one to three of residues 187-191 of SEQ ID NO: 8 are substituted for by a basic amino acid selected from the group consisting of arginine, lysine, and histidine; and (d) a polypeptide analog of human VEGF that binds to at least one of VEGFR-1, VEGFR-2, and VEGFR-3, wherein a cysteine residue is introduced in the VEGF amino acid sequence at a position selected from residues 53 to 63 of the human VEGF165 precursor amino acid sequence set forth in SEQ ID NO: 56, and wherein the analog otherwise has amino acid sequence identity to the amino acid sequence of a human VEGF isoform or human VEGF precursor, wherein said polypeptide is administered in an amount effective to modulate myelopoiesis.