| abstract |
The present invention provides VWF fragments comprising the D' and D3 domains of VWF, chimeric proteins comprising the VWF fragment and a heterologous portion, or chimeric proteins comprising the VWF fragment and a FVIII protein, and methods of use thereof. A polypeptide chain comprising a VWF fragment of the invention binds or associates with a polypeptide chain comprising a FVIII protein, and the polypeptide chain comprising the VWF fragment can prevent or inhibit the binding of endogenous VWF to the FVIII protein. By preventing or inhibiting the binding of endogenous VWF, which is the half-life limiting factor of FVIII, to the FVIII, the VWF fragment can induce the half-life extension of the FVIII protein. The invention also includes nucleotides, vectors, host cells, methods of using the VWF fragments or the chimeric proteins. |