THROMBIN CLEAVABLE LINKER

摘要

The present invention provides a chimeric molecule comprising a VWF protein fused to a heterologous moiety via a VWF linker. The invention provides an efficient VWF linker that can be cleaved in the presence of thrombin. The chimeric molecule can further comprise a polypeptide chain comprising a FVIII protein and a second heterologous moiety, wherein the chain comprising the VWF protein and the chain comprising the FVIII protein are associated with each other. The invention also includes nucleotides, vectors, host cells, methods of using the VWF fragment, or the chimeric proteins.

主权项

1. A chimeric molecule comprising a Von Willebrand Factor (VWF) protein, a heterologous moiety (H1), and a VWF linker connecting the VWF protein with the heterologous moiety, wherein the VWF linker comprises a polypeptide selected from:
i. an a2 region from Factor VIII (FVIII); ii. an a1 region from FVIII; iii. an a3 region from FVIII; iv. a thrombin cleavage site which comprises X-V-P-R (SEQ ID NO: 3) and a PAR1 exosite interaction motif, wherein X is an aliphatic amino acid; or v. any combination thereof.