Cdr-grafted anti-tissue factor antibodies and methods of use thereof

Abstract

The present invention provides CDR-grafted antibodies against human tissue factor that retain the high binding affinity of rodent monoclonal antibodies against tissue factor but have reduced immunogenicity. The present humanized antibodies are potent anticoagulants and are thus useful in the treatment and prophylaxis of human thrombotic disease. The invention also provides methods of making the CDR-grafted antibodies and pharmaceutical compositions for the attenuation or prevention of coagulation.

1 . A CDR-grafted antibody capable of inhibiting human tissue factor wherein the complementarity determining regions (CDRs) are derived from a non-human monoclonal antibody against tissue factor and the framework (FR) and constant (C) regions are derived from one or more human antibodies. 
     
     
         2 . The CDR-grafted antibody of  claim 1  wherein said non-human monoclonal antibody is a murine antibody. 
     
     
         3 . The CDR-grafted antibody of  claim 2  wherein said murine antibody is TF8-5G9. 
     
     
         4 . (canceled) 
     
     
         5 . The CDR-grafted antibody of  claim 1  wherein the FR of the heavy chain is derived from the human antibody KOL. 
     
     
         6 . The CDR-grafted antibody of  claim 1  wherein the FR of the light chain is derived from the human antibody REI. 
     
     
         7 .- 37 . (canceled)