Modified binding proteins inhibiting the VEGF-A receptor interaction
AssigneeMolecular Partners AG
InventorsHans Kaspar Binz, Patrik Forrer, Michael Tobias Stumpp
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Abstract
The present invention relates to binding proteins specific for VEGF-A, in particular to recombinant binding proteins comprising a polyethylene glycol moiety and a binding domain, which inhibits VEGF-Axxx binding to VEGFR-2. Examples of such recombinant binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity, and a polyethylene glycol moiety. The binding proteins are useful in the treatment of cancer and other pathological conditions, e.g. eye diseases such as age-related macular degeneration.
Claims19
A recombinant binding protein comprising an ankyrin repeat domain and a polyethylene glycol moiety, wherein said ankyrin repeat domain binds vascular endothelial growth factor-A165 (VEGF-A165) and inhibits VEGF-A165 binding to vascular endothelial growth factor receptor-2 (VEGFR-2), and wherein said ankyrin repeat domain is selected from the group consisting of (1) amino acids 1 to 159 of SEQ ID NO:1, (2) amino acids 1 to 159 of SEQ ID NO:2, (3) amino acids 1 to 126 of SEQ ID NO:3, (4) amino acids 1 to 126 of SEQ ID NO:4, (5) amino acids 1 to 126 of SEQ ID NO:5, (6) amino acids 1 to 126 of SEQ ID NO:6, and (7) amino acids 1 to 159 of SEQ ID NO:7.
A binding protein comprising an ankyrin repeat domain and a polyethylene glycol, wherein said ankyrin repeat domain binds vascular endothelial growth factor-A165 (VEGF-A165), and wherein said ankyrin repeat domain comprises the amino acids 1 to 126 of SEQ ID NO:
- 3.
A recombinant binding protein comprising an ankyrin repeat domain and a polyethylene glycol, wherein said ankyrin repeat domain binds vascular endothelial growth factor-A165 (VEGF-A165), wherein said binding protein comprises the amino acid sequence of SEQ ID NO:
- 3, wherein the thiol of the C-terminal Cys of said amino acid sequence of SEQ ID NO:
- 3 is conjugated to said polyethylene glycol, wherein said polyethylene glycol is a maleimide-coupled polyethylene glycol, wherein said maleimide-coupled polyethylene glycol is α-[3-(3-maleimido-1-oxopropyl)amino]propyl-ω-methoxy-polyoxyethylene, and wherein the polyethylene glycol has a molecular weight of about 20 kDa.
Dependencies are inferred from the claim text.