FACTOR IX VARIANTS WITH CLOTTING ACTIVITY IN ABSENCE OF THEIR COFACTOR AND/OR WITH INCREASED FACTOR IX CLOTTING ACTIVITY AND THEIR USE FOR TREATING BLEEDING DISORDERS
PROBLEM TO BE SOLVED: To provide variants of Factor IX (F.IX) or activated Factor IX (F.IXa) having clotting activity in absence of their cofactor, where the cofactor is Factor VIII (F.VIII) or activated Factor VIII (F.VIIIa).SOLUTION: Disclosed herein is a variant of Factor IX (F.IX) or activated Factor IX (F.IXa) having at least one amino acid substitution at position 265 in combination with amino acid substitution V181I and/or I383V, further having loop alteration at a certain position, and more preferably, further having an amino acid substitution at a position selected from the group consisting of 6, 102 and/or 185.SELECTED DRAWING: NoneCOPYRIGHT: (C)2020,JPO&INPIT【課題】補因子の非存在下で凝固活性を有する第IX因子(F.IX)又は活性化第IX因子(F.IXa)の変異体であって、該補因子は第VIII因子(F.VIII)又は活性化第VIII因子(F.VIIIa)である変異体の提供。【解決手段】変異第IX因子又は活性化第IX因子は、アミノ酸置換V181I及び/又はI383Vと組み合わせて265位に少なくとも1つのアミノ酸置換を含み、さらに特定部位におけるループの改変、より好ましくは6、102及び/又は185の群より選択された位置にアミノ酸置換をさらに含む、前記第IX因子(F.IX)又は活性化第IX因子(F.IXa)の変異体。【選択図】なし