Factor Xa based anticoagulant compositions

Details Factor Xa based anticoagulant compositions Factor Xa based anticoagulant compositions

1989-06-14

1992-06-09

Stone, Jacqueline

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

435 696, 435212, 435226, 530381, 514 2, 514 12, 514 21, A61K 37547, A61K 3702, C12N 1501, C07K 1300

Patent

active

051205378

ABSTRACT:
An anticoagulant composition containing an effective amount of factor Xa having the active serine site inactivated that functions rapidly and effectively in vivo to suppress coagulation. In a preferred embodiment, Factor Xa, a serine esterase that forms a complex with Factor Va, Ca++, and phospholipid to catalyze prothrombin activation, is first inactivated with an active site inhibitor, such as dansyl-glu- gly-arg-chloromethyl ketone, to form inactivated factor Xa. In another embodiment, Factor Xa is expressed from a gene sequence wherein the portion encoding the active serine region is modified. The inactivated protein retains the ability to bind to endogenous factor Va in vivo, and has a half-life of approximately ten hours. Administration of inactive factor Xa to the blood of a patient results in the formation of inactive factor Xa-Va complexes in vivo, thereby inhibiting coagulation.

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