Growth Factor Binding Constructs Materials and Methods
AssigneeVegenics Limited
InventorsKari Alitalo, Markku Michael Jeltsch
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Abstract
The present invention provides materials and methods for antagonizing the function of vascular endothelial growth factor receptors, platelet derived growth factor receptors and other receptors. Soluble binding constructs able to bind vascular endothelial growth factors, platelet derived growth factors, and other ligands are provided.
Claims62
1-14. (canceled)
A purified or isolated polynucleotide comprising a nucleotide sequence encoding the polypeptide of claim 1.
A purified polypeptide comprising an amino acid sequence at least 95% identical to a VEGFR-2 fragment, wherein the VEGFR-2 fragment comprises an amino acid sequence consisting of a portion of SEQ ID NO:
- 4, wherein the amino terminal amino acid of the VEGFR-2 fragment is selected from the group consisting of positions 106-145 of SEQ ID NO:
- 4, wherein the carboxy terminal amino acid of the VEGFR-2 fragment is selected from the group consisting of positions 203 to 240 of SEQ ID NO:
- 4, and wherein the VEGFR-2 fragment and the polypeptide bind VEGF-C or VEGF-D.
(canceled)
40-41. (canceled)
43-45. (canceled)
A binding construct comprising a first polypeptide operatively connected to a second polypeptide,
- wherein the first and second polypeptides each binds at least one growth factor selected from the group consisting of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, PlGF, PDGF-A, PDGF-B, PDGF-C, and PDGF-D polypeptides;
- wherein the amino acid sequence of the first polypeptide differs from the amino acid sequence of the second polypeptide;
- and wherein the first and second polypeptides comprise members independently selected from the group consisting of:
- (a) a polypeptide comprising an amino acid sequence at least 90% identical to the VEGFR-1 extracellular domain amino acid sequence comprising positions 27-758 of SEQ ID NO:
- 2;
- (b) a fragment of (a) that binds VEGF-A, VEGF-B, or PlGF;
- (c) a polypeptide comprising an amino acid sequence at least 90% identical to the VEGFR-2 extracellular domain amino acid sequence comprising positions 20-764 of SEQ ID NO:
- 4;
- (d) a fragment of (c) that binds VEGF-A, VEGF-C, VEGF-E or VEGF-D;
- (e) a polypeptide comprising an amino acid sequence at least 90% identical to the VEGFR-3 extracellular domain amino acid sequence comprising residues 24-775 of SEQ ID NO:
- 6;
- (f) a fragment of (e) that binds VEGF-C or VEGF-D;
- (g) a polypeptide comprising an amino acid sequence at least 90% identical to the neuropilin-1 extracellular domain amino acid sequence comprising residues 22-856 of SEQ ID NO:
- 113;
- (h) a fragment of (g) that binds VEGF-A, VEGF-B, VEGF-C, VEGF-E, or PlGF;
- (i) a polypeptide comprising an amino acid sequence at least 90% identical to the neuropilin-2 extracellular domain amino acid sequence comprising residues 21-864 of SEQ ID NO:
- 115;
- (j) a fragment of (i) that binds VEGF-A, VEGF-C, or PlGF;
- (k) a polypeptide comprising an amino acid sequence at least 90% identical to the platelet derived growth factor receptor alpha extracellular domain amino acid sequence comprising residues 24-524 of SEQ ID NO:
- 117;
- (l) a fragment of (k) that binds PDGF-A, PDGF-B, or PDGF-C;
- (m) a polypeptide comprising an amino acid sequence at least 90% identical to the platelet derived growth factor beta extracellular domain amino acid sequence comprising residues 33 to 531 of SEQ ID NO:
- 119;
- (n) a fragment of (m) that binds PDGF-B or PDGF-D;
- and
- (o) a polypeptide comprising an antigen binding fragment of an antibody that binds to at least one growth factor selected from the group consisting of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, PlGF, PDGF-A, PDGF-B, PDGF-C, and PDGF-D;
- wherein the resulting binding construct does not constitute a bispecific antibody.
A binding construct comprising:
- a) a first amino acid sequence at least 90% identical to a fragment of the VEGFR-3 extracellular domain, wherein said fragment comprises VEGFR-3 immunoglobulin-like domain 1 amino acid sequence;
- (b) a second amino acid sequence at least 90% identical to a fragment of the VEGFR-2 extracellular domain, wherein the fragment comprises immunoglobulin-like domain 2 amino acid sequence;
- and,
- (c) a third amino acid sequence at least 90% identical to a fragment of the VEGFR-1 extracellular domain, wherein the fragment comprises immunoglobulin-like domain 3 amino acid sequence;
- wherein the first, second, and third amino acid sequences are operatively connected, and
- wherein the binding construct binds to at least VEGF-A and VEGF-C.
57-59. (canceled)
61-62. (canceled)
64-67. (canceled)
70-71. (canceled)
73-78. (canceled)
80-84. (canceled)
A purified polynucleotide encoding a polypeptide comprising an amino acid sequence of a VEGFR-3 fragment, said VEGFR-3 fragment consisting of a portion of SEQ ID NO:
- 6, wherein the carboxy-terminal residue of the VEGFR-3 fragment is selected from the group consisting of positions 211 to 247 of SEQ ID NO:
- 6, and wherein the VEGFR-3 fragment and the purified polypeptide bind human VEGF-C.
Dependencies are inferred from the claim text.