Monoclonal antibodies against activated protein c

Abstract

The present invention provides monoclonal antibodies that selectively bind to and inhibit activated protein C without binding to or inhibiting unactivated protein C. Other antibodies inhibit both activated protein C and activation of unactivated protein C. Methods of treatment employing these antibodies are described herein as are methods of screening for and detecting these antibodies.

1 . (canceled) 
     
     
         2 . The monoclonal antibody of  claim 22 , wherein said binding to activated protein C occurs at the active site of activated protein C and does not inhibit the cytoprotective effects of activated protein C. 
     
     
         3 . The monoclonal antibody of  claim 22 , further defined as HAPC1573. 
     
     
         4 . The monoclonal antibody of  claim 22 , wherein said inhibition of activated or unactivated protein C is in vivo. 
     
     
         5 . The monoclonal antibody of  claim 22 , wherein said inhibition of activated or unactivated protein C is in vitro. 
     
     
         6 . The monoclonal antibody of  claim 22 , wherein the antibody is a murine antibody. 
     
     
         7 . The monoclonal antibody of  claim 22 , wherein the antibody is a human antibody. 
     
     
         8 . The monoclonal antibody of  claim 22 , wherein the antibody is a humanized antibody. 
     
     
         9 . The monoclonal antibody of  claim 22 , wherein the antibody is an antibody fragment. 
     
     
         10 . The monoclonal antibody of  claim 9 , wherein the antibody fragment is further defined as Fab′, Fab, F(ab′) 2 , a single domain antibody, Fv, or scFv. 
     
     
         11 - 21 . (canceled) 
     
     
         22 . A method of inhibiting activated protein C anticoagulant activity in a subject, comprising administering an effective amount of a monoclonal antibody that binds to activated protein C and inhibits anticoagulant activity but does not bind to or inhibit activation of unactivated protein C to said subject. 
     
     
         23 . The method of  claim 22 , wherein the cytoprotective effects of activated protein C are not decreased by said monoclonal antibody. 
     
     
         24 . A method of inhibiting activated protein C amidolytic activity in a subject comprising administering an effective amount of an antibody that binds to activated protein C and inhibits anticoagulant activity but does not bind to or inhibit activation of unactivated protein C to said subject. 
     
     
         25 . A method of treating a subject in need of blood coagulation comprising administering an effective amount of an antibody that binds to activated protein C and inhibits anticoagulant activity but does not bind to or inhibit activation of unactivated protein C to said subject. 
     
     
         26 . (canceled) 
     
     
         27 . A method of treating a subject suffering from sepsis comprising administrating an effective amount of an antibody that binds to activated protein C and inhibits anticoagulant activity but does not bind to or inhibit activation of unactivated protein C to said subject. 
     
     
         28 . The method of  claim 27 , further comprising administration of activated protein C. 
     
     
         29 - 32 . (canceled) 
     
     
         33 . A method of modulating hemostasis in a subject, comprising administrating an effective amount of an antibody that binds to activated protein C and inhibits anticoagulant activity but does not bind to or inhibit activation of unactivated protein C to said subject. 
     
     
         34 . The method of  claim 33 , wherein the subject is a trauma patient. 
     
     
         35 - 36 . (canceled) 
     
     
         37 . A method of modulating thrombosis in a subject, comprising administrating an effective amount of an antibody that binds to activated protein C and inhibits anticoagulant activity but does not bind to or inhibit activation of unactivated protein C to said subject. 
     
     
         38 - 39 . (canceled)