Receptor ligand VEGF-C
AssigneesHelsinki University Licensing, Ltd., Ludwig Institute for Cancer Research
InventorsKari Alitalo, Vladimir Joukov
Life of this patent
Estimating the term…
Abstract
Provided are polypeptide ligands for the receptor tyrosine kinase, Flt4. Also provided are cDNAs and vectors encoding the ligands, pharmaceutical compositions and diagnostic reagents comprising the ligands, and methods of making and using the ligands.
Claims46
A purified and isolated polypeptide that binds to the extracellular domain of human Flt4 receptor tyrosine kinase (Flt4EC), said polypeptide including a contiguous portion of SEQ ID NO:
- 33 that is sufficient to bind human Flt4EC,
- wherein said contiguous portion includes eight cysteine residues that are conserved in human vascular endothelial growth factor (VEGF), human platelet derived growth factor A (PDGF-A), and human platelet derived growth factor B (PDGF-B), and
- wherein said polypeptide lacks any portion of SEQ ID NO:
- 33 that has one or more cysteine motifs of a Balbiani ring 3 protein (BR3P).
A purified and isolated mammalian polypeptide that binds to the extracellular domain of human Flt4 receptor tyrosine kinase (Flt4EC),
- said polypeptide including a contiguous portion of a mammalian Flt4 ligand precursor polypeptide that is sufficient to bind human Flt4EC,
- wherein said mammalian Flt4 ligand precursor polypeptide is encoded by a DNA which hybridizes to a non-coding strand complementary to nucleotides 352 to 1611 of SEQ ID NO:
- 32 under the following hybridization conditions:
- hybridization at 42° C. in a hybridization solution comprising 50% formamide, 5×SSC, 20 mM Na.PO4, pH 6.8;
- and washing in 0.2×SSC at 55° C.,
- wherein said contiguous portion includes eight cysteine residues that are conserved in human vascular endothelial growth factor (VEGF), human platelet derived growth factors A and B (PDGF-A, PDGF-B), human placenta growth factor (PlGF-1), and human vascular endothelial growth factor B (VEGF-B),
- and wherein said polypeptide lacks any portion of the mammalian Flt4 ligand precursor polypeptide that has one or more cysteine motifs of a Balbiani ring 3 protein (BR3P).
A purified and isolated polypeptide that binds to the extracellular domain of human Flt4 receptor tyrosine kinase, said polypeptide being encoded by plasmid pFLT4-L, deposited as ATCC Accession Number 97231, said polypeptide lacking the carboxyl terminal portion of the amino acid sequence encoded by plasmid pFLT4-L that contains cysteine motifs of a Balbiani ring 3 protein (BR3P).
A purified and isolated polypeptide that binds to the extracellular domain of human Flt4 receptor tyrosine kinase, said polypeptide having an amino acid sequence consisting of a portion of the amino acid sequence set forth in SEQ ID NO:
- 33, said portion including from residue 161 of SEQ ID NO:
- 33 to residue 211 of SEQ ID NO:
- 33, said portion lacking at least carboxy-terminal residues of SEQ ID NO:
- 33 beyond residue 227.
A purified and isolated polypeptide that binds to the extracellular domain of human Flt4 receptor tyrosine kinase, said polypeptide comprising a portion of the amino acid sequence in SEQ ID NO:
- 33 effective to permit said binding, said polypeptide lacking at least carboxy-terminal residues of SEQ ID NO:
- 33 beyond residue 227.
A purified and isolated polypeptide that binds to the extracellular domain of human Flt4 receptor tyrosine kinase, said polypeptide comprising a portion of SEQ ID NO:
- 33 effective to permit said binding, said portion of SEQ ID NO:
- 33 lacking at least carboxy terminal residues of SEQ ID NO:
- 33 having cysteine motifs of a Balbiani ring 3 protein.
A purified polypeptide that binds to the extracellular domain of human Flt4 receptor tyrosine kinase, said polypeptide produced by a method comprising the steps of:
- (a) expressing a nucleic acid in a host cell;
- and
- (b) purifying a polypeptide that binds to the extracellular domain of human Flt4 receptor tyrosine kinase from said host cell or from a growth medium of said host cell;
- wherein said nucleic acid comprises a nucleotide sequence encoding a portion of the amino acid sequence in SEQ ID NO:
- 33 effective to permit such binding, and wherein said polypeptide lacks at least the carboxy-terminal portion of SEQ ID NO:
- 33 that is characterized by cysteine motifs of a Balbiani ring 3 protein.
A purified and isolated polypeptide having the amino acid sequence of residues 1 to 415 of SEQ ID NO:
- 41.
A purified and isolated polypeptide that binds to the extracellular domain of an Flt4 receptor tyrosine kinase, said polypeptide comprising a contiguous portion of the amino acid sequence of SEQ ID NO:
- 41 effective to permit such binding,
- said contiguous portion including eight cysteine residues of SEQ ID NO:
- 41 that are conserved in human vascular endothelial growth factor (VEGF), human platelet derived growth factors A and B (PDGF-A, PDGF-B), human placenta growth factor (PlGF-1), and human vascular endothelial growth factor B (VEGF-B).
A purified polypeptide that binds to the extracellular domain of human Flt4 receptor tyrosine kinase, said polypeptide produced by a method comprising the steps of:
- (a) expressing a nucleic acid in a host cell, said nucleic acid comprising a nucleotide sequence encoding a portion of the amino acid sequence in SEQ ID NO:
- 41 effective to permit such binding;
- and
- (b) purifying a polypeptide that binds to the extracellular domain of human Flt4 receptor tyrosine kinase from said host cell or from a growth medium of said host cell, wherein said polypeptide lacks at least the carboxy-terminal portion of SEQ ID NO:
- 41 that is characterized by cysteine motifs of a Balbiani ring 3 protein.
Dependencies are inferred from the claim text.