Patent ID: 8728483

Claim:
A polypeptide comprising: (a) an N-terminal domain comprising a first fibronectin type III tenth domain ( 10 Fn3), wherein the 10 Fn3 domain (i) comprises a loop, AB; a loop, BC; a loop, CD; a loop, DE; a loop EF; and a loop FG; (ii) has at least one loop selected from loop BC, DE, and FG with an altered amino acid sequence relative to the sequence of the corresponding loop of the human 10 Fn3 domain (SEQ ID NO: 1), and (iii) binds to insulin-like growth factor-I receptor (IGF-IR) with a K D of less than 500 nM; and (b) a C-terminal domain comprising a second fibronectin type III tenth domain ( 10 Fn3), wherein the 10 Fn3 domain (i) comprises a loop, AB; a loop, BC; a loop, CD; a loop, DE; a loop EF; and a loop FG; (ii) has at least one loop selected from loop BC, DE, and FG with an altered amino acid sequence relative to the sequence of the corresponding loop of the human 10 Fn3 domain (SEQ ID NO: 1), and (iii) binds to vascular endothelial growth factor receptor 2 (VEGFR2) with a K D of less than 500 nM; wherein the first and second 10 Fn3 domains are linked via a polypeptide selected from a glycine-serine based linker, a glycine-proline based linker, a proline-alanine based linker or the amino acid sequence of SEQ ID NO: 20, wherein the polypeptide comprises an amino acid sequence at least 85% identical to the amino acid sequence of any one of SEQ ID NOs: 8-11, 29-31, and 63-70.