Compositions and methods for counteracting Factor Xa inhibition
AssigneePfizer Inc.
InventorsDebra D. Pittman, Rodney M. Camire, Joachim Fruebis
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Abstract
The disclosure provides compositions and methods for counteracting the effects of direct activated Factor X (FXa) inhibitors in a subject by administering a variant of FXa.
Claims20
A method for reversing the anticoagulant effect of a direct Factor Xa inhibitor in a subject, comprising administering to said subject a Factor Xa variant that contains at least one modification selected from the group consisting of:
- a) the amino acid at the position corresponding to 235 in SEQ ID NO:1 is substituted with Thr, Leu, Phe, Asp or Gly;
- and
- b) the amino acid at the position corresponding to 236 in SEQ ID NO:1 is substituted with Leu, Ala, or Gly,
- wherein said subject has acute major bleeding and acquired coagulopathy due to FXa inhibition therapy using a direct FXa inhibitor,
- wherein reversal of the anticoagulant effect of the direct Factor Xa inhibitor effects the urgent reversal of the acquired coagulopathy due to FXa inhibition therapy in said subject with acute major bleeding;
- and
- wherein said Factor Xa variant is effective to reverse the anticoagulant effect of the direct Factor Xa inhibitor at a plasma concentration at least 250-fold lower than the plasma concentration of the direct Factor Xa inhibitor.
A method for reversing the anticoagulant effect of a direct Factor Xa inhibitor in a subject, comprising administering to said subject a Factor Xa variant comprising Leu at the position corresponding to 235 in SEQ ID NO:1,
- wherein said subject has acute major bleeding and acquired coagulopathy due to FXa inhibition therapy using a direct FXa inhibitor,
- wherein reversal of the anticoagulant effect of the direct Factor Xa inhibitor effects the urgent reversal of the acquired coagulopathy due to FXa inhibition therapy in said subject with acute major bleeding;
- and
- wherein said Factor Xa variant is effective to reverse the anticoagulant effect of the direct Factor Xa inhibitor at a plasma concentration at least 250-fold lower than the plasma concentration of the direct Factor Xa inhibitor.
Dependencies are inferred from the claim text.