Use of anti-factor xi antibodies for prevention of thrombus formation

Abstract

The present invention relates to binding molecules such as antibodies that specifically bind plasma coagulation factor XI and that inhibit factor XI activation and/or activity. The factor XI-binding molecules of the invention may used in methods for preventing or treating diseases, disorders and/or conditions that are mediated by factor XI activation and/or wherein inhibition of factor XI has a beneficial effect.

What is claimed is: 
     
         1 . An antibody or a factor XI-binding fragment thereof that binds factor XI at or near the active site located in the light chain region of activated factor XI and inhibits factor XI activity,
 wherein, when administered to a subject in an effective amount, said antibody or fragment treats or attenuates a disease, disorder or condition for which inhibition of factor XI has a beneficial effect.   
     
     
         2 . The antibody or fragment according to  claim 1  that preferentially binds to the activated form of factor XI. 
     
     
         3 . The antibody or fragment according to  claim 1  that prevents activation of substrate factor IX by factor XIa. 
     
     
         4 . The antibody or fragment according to  claim 1  that prevents activation of substrate factor XI by factor XIa. 
     
     
         5 . The antibody or fragment according to  claim 1  that prevents the conversion of a chromogenic substrate to a colored product by factor XIa. 
     
     
         6 . The antibody or fragment according to  claim 1 , that is a monoclonal antibody or a factor XI-binding fragment thereof. 
     
     
         7 . The antibody or fragment according to  claim 1 , that treats or attenuates said disease, disorder or condition when administered at a dosage equivalent to 0.5-20 mg of IgG per kg body weight of the subject. 
     
     
         8 . The antibody or fragment according to  claim 1 , that treats or attenuates said disease, disorder or condition when administered at a dosage that yields a molar ratio in serum that is less than or equal to 4 moles of factor XI binding sites of antibody or fragment to 1 mole of factor XI,
 wherein the antibody or fragment has an affinity for factor XI characterized by a Kd that is less than or equal to 1 nM.   
     
     
         9 . The antibody or fragment according to  claim 1 , wherein the disease, disorder or condition is a thrombo-embolic disease. 
     
     
         10 . The antibody or fragment according to  claim 9 , wherein the thrombo-embolic disease is ischemic stroke, cardio-embolism, vascular access thrombosis, deep venous thrombosis, diffuse intravascular coagulation, sepsis, or septic shock. 
     
     
         11 . The antibody or fragment according to  claim 1 , that treats or attenuates said disease, disorder or condition when administered intravenously, intramuscularly or subcutaneously. 
     
     
         12 . The antibody or fragment according to  claim 11 , that treats or attenuates said disease, disorder or condition when administered intravenously as a bolus infusion or as a continuous infusion over up to 24 hours. 
     
     
         13 . The antibody or fragment according to  claim 1 , that has a half life of at least 6 days when administered to the subject and an affinity for factor XI characterized by a Kd that is less than 1 nM.