Inhibitors of type 2 vascular endothelial growth factor receptors

摘要

The present disclosure relates to novel vascular endothelial growth factor receptor (VEGFR)-binding polypeptides and methods for using these polypeptides to inhibit biological activities mediated by vascular endothelial growth factors (VEGFs). The present disclosure also provides various improvements relating to single domain binding polypeptides.

主权项

1. A polypeptide comprising a modified fibronectin type III tenth (10Fn3) domain, wherein the modified 10Fn3 domain (i) comprises a modified amino acid sequence in one or more of the AB, BC, CD, DE, EF and FG loops relative to the wild-type 10Fn3 domain set forth in SEQ ID NO: 5, (ii) comprises an amino acid sequence that is at least 60% identical to SEQ ID NO: 5, (iii) binds to a target molecule not bound by the wild-type 10Fn3 domain, and (iv) comprises a C-terminal tail comprising the amino acid sequence EIDKPSQ (residues 88-94 of SEQ ID NO: 184) or EIDKPCQ (residues 88-94 of SEQ ID NO: 194).