Csl Behring Lengnau Ag

Steve Dower

Michael Wilson

Dallas Hartman

Con Panousis

Matthew Hardy

Arna Andrews

Kerstin Emmrich

Stefan Schulte

Hubert Metzner

Thomas Weimer

Sabine Pestel

Mathew Hardy

The invention pertains to a polypeptide comprising a truncated von Willebrand Factor (VWF) and a half-life extending moiety, for use in the treatment of a blood coagulation disorder, said treatment comprising administering the polypeptide to a subject having a blood coagulation disorder and having endogenous Factor VIII (FVIII), wherein the activity level of endogenous FVIII in said subject before treatment with said polypeptide is reduced relative to the activity level of FVIII in normal human plasma (NHP) provided that the activity level of endogenous FVIII in said subject is at least 0.5% of the activity level of endogenous FVIII in normal human plasma (NHP), wherein the polypeptide is capable of binding to endogenous FVIII and wherein the endogenous FVIII level is increased following administration of said polypeptide.

Truncated von Willebrand Factor polypeptides for treating hemophilia

The present invention provides a modified polypeptide which binds Factor VIII. The polypeptide comprises truncated von Willebrand Factor (VWF) which comprises a sequence as shown in SEQ ID NO:3 or a fragment thereof or a sequence 90% identical thereto, wherein the truncated VWF comprises at least one modification in comparison to SEQ ID NO: 3 in at least one position selected from the group consisting of SI, S3, LI 8, V42, S43, K149, N248, S279, V320, T325, Q395 and K418.

Mutated truncated von Willebrand Factor

The present invention provides a modified polypeptide which binds Factor VIII. The modified polypeptide comprises a sequence as shown in SEQ ID NO:3 in which the sequence comprises at least one modification at a position selected from the group consisting of L18, V42, K149, N248, S279, V320, T325, Q395 and K418 such that the modified polypeptide binds to Factor VIII with an off rate lower than a reference polypeptide comprising an unmodified SEQ ID NO:3.

Mutated von Willebrand factor

The present invention provides a modified polypeptide which binds Factor VIII. The modified polypeptide comprises a sequence as shown in SEQ ID NO:3 in which the sequence comprises at least a modification at position 1 or 3 such that the modified polypeptide binds to Factor VIII with an off rate at least 5 fold lower than a reference polypeptide comprising an unmodified SEQ ID NO:3.

Modified von Willebrand Factor

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Fitzroy North, Australia

Steve Dower