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.
Claims21
A variant of factor IX or activated factor IX selected from:
- a) a variant of factor IX (F.IX) or activated factor IX (F.IXa), which is characterized in that it has clotting activity in absence of its cofactor, wherein the cofactor is factor VIII (F.VIII) or activated factor VIII (F.VIIIa), comprising at least one amino acid substitution in a position selected from the group of 255 to 269, 383, 181, 290, 388, 34, 25, 353, 358, 338, 377, 4, 86, 217, 277, and[[/or]] a modification of the 99-loop, and
- b) a variant of factor IX (F.IX), which is characterized in that it has increased clotting activity in presence of its cofactor compared to wild type, wherein the cofactor is factor VIII (F.VIII) or activated factor VIII (F.VIIIa) comprising at least one amino acid substitution in a position selected from the group of 338, 377, 4, 86, 217 and 277.
Dependencies are inferred from the claim text.