Therapeutic Antibodies

Abstract

The present invention concerns human antibodies recognising the human C5a receptor. By binding to C5aR the antibodies inhibit C5a signalling, whereby the pro-inflammatory signal is inhibited. Based on the role of C5a and its receptor in stimulation of inflammation the invention further relates to therapeutic use of said human anti-C5aR antibodies and in particular in relation to treatment of immunological disorders.

1 - 15 . (canceled) 
     
     
         16 . An antibody that specifically binds C5aR, comprising an Fc region, wherein the Fc region has been modified to include one or more point mutations compared to a reference Fc region. 
     
     
         17 . The antibody of  claim 16 , wherein the reference Fc region comprises IgG1 (SEQ ID NO:33), IgG2 (SEQ ID NO:34), IgG4 (SEQ ID NO:35) or IgG4/G2 (SEQ ID NO:36) isotypes. 
     
     
         18 . The antibody of  claim 17 , wherein the antibody has a decreased binding affinity to one or more Fc gamma receptors (FcγR) compared to the binding affinity of IgG1, IgG2, IgG3 or IgG4/G2 Fc reference sequences. 
     
     
         19 . The antibody of  claim 16 , wherein the antibody binds the 2nd extracellular loop of C5aR. 
     
     
         20 . The antibody of  claim 16 , wherein the antibody has an Fc hinge region of the IgG1 isotype. 
     
     
         21 . The antibody of  claim 16 , wherein the antibody has an Fc region of the IgG1 isotype. 
     
     
         22 . The antibody of  claim 16 , wherein the Fc region of the antibody is IgG1 (SEQ ID NO: 33), IgG2 (SEQ ID NO: 34), IgG2/4 (SEQ ID NO: 35), or IgG4 (SEQ ID NO: 36), with one or more of the following point mutations:
 a. E233P;   b. L234A or V234A or F234L or F234V;   c. L235E or L235A;   d. G236R or G236A;   e. G237A;   f. N297Q;   g. L328R;   h. A330S;   i. P331S.   
     
     
         23 . The antibody of  claim 16 , wherein the antibody is a human antibody. 
     
     
         24 . The antibody of  claim 16 , wherein said antibody binds human C5aR and preferably the 2nd extracellular loop of human C5aR. 
     
     
         25 . The antibody of  claim 16 , wherein the affinity of the antibody as measured by competition ligand binding assay on neutrophils is below 0.80 nM. 
     
     
         26 . The antibody of  claim 16 , wherein the antibody significantly inhibits or reduces binding of C5a to C5aR. 
     
     
         27 . The antibody of  claim 16 , wherein the antibody significantly inhibits migration of human neutrophils in vitro. 
     
     
         28 . The antibody of  claim 16 , wherein the antibody does not significantly induce ADCC, CDC and/or phagocytosis of neutrophils in vitro.