Complex-specific antibodies and antibody fragments and its use

Abstract

The present invention provides antibodies and fragments thereof that specifically detect the complex of a specific cognate antigen-binding moiety, in particular antibodies, and its antigen. The antibodies of the present disclosure do not bind either said cognate antigen binding moiety or said antigen alone and thus can be used e.g. to directly detect antigen-bound antigen-binding moieties. Further disclosed are methods for use of said antibodies and antibody fragments.

1 . An isolated monoclonal antibody or fragment thereof, which specifically binds to the complex of a specific cognate antibody and its antigen. 
     
     
         2 . The isolated monoclonal antibody or fragment thereof of  claim 1 , which specifically binds to the complex of a specific cognate antibody and its antigen and does not bind either said specific cognate antibody or said antigen alone. 
     
     
         3 . The isolated monoclonal antibody or fragment thereof of  claim 1 , wherein the epitope of said isolated monoclonal antibody or fragment thereof includes one or more amino acids of a variable region of the specific cognate antibody. 
     
     
         4 . The isolated monoclonal antibody or fragment thereof of  claim 1 , wherein said isolated monoclonal antibody or fragment thereof is a humanized or human monoclonal antibody or fragment. 
     
     
         5 . The isolated monoclonal antibody or fragment thereof of  claim 1 , wherein said specific cognate antibody is a murine, chimeric, humanized of human monoclonal antibody or fragment thereof. 
     
     
         6 . The isolated monoclonal antibody or fragment thereof of  claim 5 , wherein the specific cognate antibody or fragment thereof is selected from a list that consists but is not limited to Adalimumab, MOR103, Rituximab, Trastuzumab, Alemtuzumab, Bevacizumab, Cetuximab, Gemtuzumab, Infliximab, Ranibizumab, Ustekinumab, Golimumab, Natalizumab, Ofatumumab, Omalizumab, Panitumumab. 
     
     
         7 . The isolated monoclonal antibody or fragment thereof of  claim 1 , wherein the antigen is a cytokine or a receptor. 
     
     
         8 . Use of an isolated antibody or fragment thereof of  claim 1  for the detection of a complex of a specific cognate antibody and its antigen in a sample. 
     
     
         9 . A method of detecting the complex of a specific cognate antibody and its antigen in a sample, the method comprising the steps of
 a) contacting said sample with an isolated antibody or fragment of  claim 1  and   b) detecting said isolated antibody or fragment bound to said complex.   
     
     
         10 . The method of  claim 9 , wherein said complex is detected using EIA, ELISA, RIA, indirect competitive immunoassay, direct competitive immunoassay, noncompetitive immunoassay, sandwich immunoassay, agglutination assay or MSD. 
     
     
         11 . The method of  claim 9 , wherein said complex of a specific cognate antibody and its antigen is selected from a group that consists but is not limited to Adalimumab/TNF-α, MOR103/GM-CSF, Trastuzumab/Her2/c-neu, Alemtuzumab/CD52, Bevacizumab/VEGF-A, Cetuximab/EGF-R, Gemtuzumab/CD33, Infliximab/TNF-a, Ranibizumab/VEGF-A, Ustekinumab/IL-12, Ustekinumab/IL-23, Golimumab/TNF-α, Natalizumab/a4-integrin, Ofatumumab/CD20, Rituximab/CD20, Omalizumab/lgE (Fc region), Panitumumab/EGFR. 
     
     
         12 . A method to identify an isolated monoclonal antibody, or fragment thereof, of  claim 1 , said method comprising
 (a) screening a library of antibodies or antibody fragments against a complex of a specific cognate antibody and its antigen in the presence of the unbound antigen and an antibody that has the same isotype as the specific cognate antibody,   (b) isolating said complex of a specific cognate antibody and its antigen and the bound antibodies or antibody fragments, and   (c) identifying and isolating said antibodies or antibody fragments.   
     
     
         13 . An isolated monoclonal antibody of fragment thereof obtainable by the method according to  claim 12 . 
     
     
         14 . A kit comprising one or more antibodies, or fragments thereof, according to  claim 1  and at least one reagent or device necessary for the detection of a complex of a specific cognate antibody and its antigen. 
     
     
         15 . The kit of  claim 14 , wherein said one or more antibodies are selected from the group of antibodies or fragments thereof which bind to one of the complexes selected from a group that consists but is not limited to Adalimumab/TNF-a, MOR103/GM-CSF, Trastuzumab/Her2/c-neu, Alemtuzumab/CD52, BevacizumabA EGF-A, Cetuximab/EGF-R, Gemtuzumab/CD33, Infliximab TNF-a, RanibizumabA/EGF-A, Ustekinumab/IL-12, Ustekinumab/IL-23, Golimumab/TNF-a, Natalizumab/a4-integrin, Ofatumumab/CD20, Rituximab/CD20, Omalizumab/lgE (Fc region), Panitumumab/EGFR.