abstract |
The present invention provides a VWF fragment comprising a D' domain and a D3 domain of VWF, a chimeric protein comprising the VWF fragment and a heterologous portion, or a chimeric protein comprising the VWF fragment and the 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 prevents or inhibits endogenous VWF from binding to the FVIII protein. The VWF fragment can induce an increase in the half-life of the FVIII protein by preventing or inhibiting the binding of endogenous VWF to FVIII, wherein the binding is a half-life limiting factor for FVIII. The invention also includes nucleotides, vectors, host cells, methods of using the VWF fragments or such chimeric proteins. |