Compositions for inhibiting thrombin-induced coagulation and methods of use

Abstract

A method of achieving safe and effective treatment or prevention of potentially harmful blood clots, or in inhibiting the coagulation of blood when so desired such as during a wide array of disease conditions including stroke, myocardial infarction, sickle-cell crisis and venous thrombosis, is provided by the administration of a fibrinogen-binding protein capable of binding at the N-terminal Bβ chain of fibrinogen, such as SdrG or Fbe, or their respective binding regions such as the A domain. In addition, compositions comprising effective amounts of the fibrinogen-binding proteins are also provided. The present anti-coagulation compositions have been shown to inhibit thrombin-induced fibrin clot formation by interfering with the release of fibrinopeptide B and the resulting anti-coagulation effects can be achieved without potential for causing or exacerbating unwanted side effects such as thrombocytopenia associated with prior art anticoagulants such as heparin.

1 . A therapeutic composition for inhibiting thrombin-induced coagulation of blood in a human or animal patient in need thereof comprising an SdrG serine-aspartate repeat protein in an amount effective to inhibit thrombin-induced coagulation, and a pharmaceutically acceptable vehicle, carrier or excipient.  
     
     
         2 . A method of inhibiting thrombin-induced coagulation comprising administering to a human or animal patient in need thereof the composition of  claim 1  in an amount effective to inhibit thrombin-induced coagulation.  
     
     
         3 . A method for treating a disease condition selected from the group consisting of stroke, myocardial infarction, sickle-cell crisis and venous thrombosis comprising administering to a human or animal patient in need thereof an effective amount of the composition of  claim 1 .  
     
     
         4 . A method for reducing plasma fibrinogen concentration in blood comprising administering to a human or animal an effective amount of the composition according to  claim 1 .  
     
     
         5 . A therapeutic composition for inhibiting thrombin-induced coagulation comprising a fibrinogen-binding protein from  S. epidermidis  which can bind to the Bβ chain of fibrinogen in an amount effective to inhibit thrombin-induced coagulation, and a pharmaceutically acceptable vehicle, carrier or excipient.  
     
     
         6 . The therapeutic composition according to  claim 5  wherein the fibrinogen-binding protein is selected from the group consisting of SdrG, Fbe and their respective A regions.  
     
     
         7 . The therapeutic composition according to  claim 5  wherein the SdrG A region has the sequence of residues 50-597 of SdrG.  
     
     
         8 . The therapeutic composition according to  claim 5  wherein the fibrinogen-binding protein is a recombinant protein.  
     
     
         9 . The therapeutic composition according to  claim 5  wherein the fibrinogen-binding protein binds at the site of residues 6-20 of the fibrinogen Bβ chain  
     
     
         10 . A method of inhibiting thrombin-induced coagulation comprising administering to a human or animal patient in need thereof the composition of  claim 5  in an amount effective to inhibit thrombin-induced coagulation.  
     
     
         11 . A method for treating a disease condition selected from the group consisting of stroke, myocardial infarction, sickle-cell crisis and venous thrombosis comprising administering to a human or animal patient in need thereof an effective amount of the composition of  claim 5 .  
     
     
         12 . A method for reducing plasma fibrinogen concentration in blood comprising administering to a human or animal an effective amount of the composition according to  claim 5.