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US 12,195,774 B2Granted
Antidotes to factor XA inhibitors
AssigneeAlexion Pharmaceuticals, Inc.
InventorsPamela B. Conley, Genmin Lu, Leonard G. Presta, John T. Curnutte
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Abstract
The present disclosure relates to antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. In one embodiment, the derivatives described herein lack or have reduced intrinsic coagulant activity.
Claims4
An isolated two-chain polypeptide comprising the amino acid sequence of SEQ ID NO. 13 which further comprises at least one mutation, as compared to SEQ ID NO. 13, selected from the group consisting of:
- (i) D12E, D29E, N59Q, N71Q, N71S, N71A, N86Q, N86S, D114E, D114S, N163S, N163Q, N259Q, N259S, and N259A,
- (ii) V232I, D284M, D284Q, D284S, V308S, G311H, G311K, G311N, G311Q, and G311S, and
- (iii) A290N, A290Q, A290K, H147S, H147T, H147N, H147Q, and D193N.
Dependencies are inferred from the claim text.