Factor IX variants with clotting activity in absence of their cofactor and their use for treating bleeding disorders
AssigneeDrk Blutspendedienst Baden-WüRttemberg-Hessen Ggmbh
InventorsErhard Seifried, Jörg Schüttrumpf
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Abstract
The present invention relates to variants of a vitamin K-dependent serine protease of the coagulation cascade, preferably variants of factor IX (F.IX), wherein the variant is characterized in that it has clotting activity in absence of its cofactor. The present invention furthermore relates to the use of these variants for the treatment and/or prophylaxis of bleeding disorders, in particular hemophilia A and/or hemophilia B or hemophilia caused or complicated by inhibitory antibodies to F.VIII. The present invention also relates to further variants of factor IX (F.IX) which have desired properties and can, thus be tailored for respective specific therapeutic applications.
Claims12
A variant of factor IX (F.IX) or activated factor IX (F.IXa), which is characterized in that it has clotting activity in the absence of its cofactor and/or that it has increased clotting activity in the presence of its cofactor compared to wildtype F.IX or F.IXa,
- wherein the cofactor is factor VIII (F.VIII) or activated factor VIII (F.VIIIa),
- comprising an amino acid substitution in position 338 selected from R338A and R338L and further comprising an amino acid substitution S377W,
- and wherein said amino acid substitutions are made at positions in reference to amino acids 47 to 461 of the amino acid sequence of SEQ ID NO:
- 2,
- and wherein when the variant of factor IX (F.IX) or activated factor IX (F.IXa) has clotting activity in the absence of its cofactor, the variant of factor IX (F.IX) or activated factor IX (F.IXa) further comprises an amino acid substitution K265T.
Dependencies are inferred from the claim text.