Plasma kallikrein binding proteins

Abstract

Plasma kallikrein binding proteins and methods of using such proteins are described.

1 .- 24 . (canceled) 
     
     
         25 . An isolated monoclonal antibody, which binds human plasma kallikrein (pKal), wherein the monoclonal antibody binds at or near the active site of the catalytic domain of the pKal, or binds an epitope that overlaps with the active site of the catalytic domain of the pKal. 
     
     
         26 . The isolated monoclonal antibody of  claim 25 , wherein the antibody binds an epitope comprising one or more amino acids of His434, Asp483, and Ser578 of SEQ ID NO:2. 
     
     
         27 . The isolated monoclonal antibody of  claim 25 , wherein the antibody binds human plasma prekallikrein less effectively relative to human pKal by a factor of at least 10 fold. 
     
     
         28 . The isolated monoclonal antibody of  claim 27 , which binds human plasma prekallikrein less effectively relative to the human pKal by a factor of at least 100 fold. 
     
     
         29 . The isolated monoclonal antibody of  claim 28 , which binds human plasma prekallikrein less effectively relative to the human pKal by a factor of at least 1000 fold. 
     
     
         30 . The isolated monoclonal antibody of  claim 25 , which competes with epi-Kal2 for binding to the human pKal. 
     
     
         31 . The isolated monoclonal antibody of  claim 25 , which competes with AEBSF for binding to the human pKal. 
     
     
         32 . The isolated monoclonal antibody of  claim 25 , which decreases the catalytic activity of the human pKal as compared to the catalytic activity of the human pKal in the absence of the monoclonal antibody and under the same conditions. 
     
     
         33 . The isolated monoclonal antibody of  claim 30 , wherein the monoclonal antibody decreases the production of Factor XIIa or bradykinin by at least 50% as compared to the production of Factor XIIa or bradykinin in the absence of the monoclonal antibody and under the same conditions. 
     
     
         34 . The isolated monoclonal antibody of  claim 33 , wherein the monoclonal antibody decreases the production of Factor XIIa or bradykinin by at least 75% as compared to the production of Factor XIIa or bradykinin in the absence of the monoclonal antibody and under the same conditions. 
     
     
         35 . The isolated monoclonal antibody of  claim 34 , wherein the monoclonal antibody decreases the production of Factor XIIa or bradykinin by at least 90% as compared to the production of Factor XIIa or bradykinin in the absence of the monoclonal antibody and under the same conditions. 
     
     
         36 . The isolated monoclonal antibody of  claim 25 , which is a human antibody. 
     
     
         37 . The isolated monoclonal antibody of  claim 25 , which is an IgG molecule. 
     
     
         38 . The isolated monoclonal antibody of  claim 37 , which is an IgG1 molecule. 
     
     
         39 . The isolated monoclonal antibody of  claim 25 , which is substantially a full-length antibody. 
     
     
         40 . The isolated monoclonal antibody of  claim 25 , which comprises an antigen-binding fragment of a full-length antibody. 
     
     
         41 . The isolated monoclonal antibody of  claim 25 , which comprises a heavy chain variable region and a light chain variable region. 
     
     
         42 . The isolated monoclonal antibody of  claim 38 , which is a germlined antibody. 
     
     
         43 . A pharmaceutical composition, comprising the monoclonal antibody of  claim 25  and a pharmaceutically acceptable carrier. 
     
     
         44 . A method for treating hereditary angioedema, comprising administering to a subject in need thereof an effective amount of the monoclonal antibody of  claim 25 .