Factor VIII-XTEN fusions and uses thereof
First Claim
1. A chimeric protein comprising (i) a Factor VIII (FVIII) polypeptide and (ii) four XTENs wherein the FVIII polypeptide has reduced affinity for von Willebrand Factor (VWF), and wherein the FVIII polypeptide lacks amino acids 746-1685 corresponding to the mature human FVIII polypeptide (SEQ ID NO:
- 4).
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Abstract
The present invention provides chimeric proteins comprising a Factor VIII (FVIII) polypeptide and XTEN polypeptides. The FVIII polypeptide can have a reduced affinity for von Willebrand Factor (VWF). XTEN polypeptides of appropriate sizes are inserted into the FVIII polypeptide at particular locations in order to extend the half-life of the FVIII polypeptide. The invention also includes nucleotides, vectors, host cells, and methods of using the chimeric proteins, e.g., to treat bleeding diseases and disorders.
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Citations
17 Claims
- 1. A chimeric protein comprising (i) a Factor VIII (FVIII) polypeptide and (ii) four XTENs wherein the FVIII polypeptide has reduced affinity for von Willebrand Factor (VWF), and wherein the FVIII polypeptide lacks amino acids 746-1685 corresponding to the mature human FVIII polypeptide (SEQ ID NO:
Specification