Antibodies targeting c5ar

Abstract

The present invention provides novel antibodies or antibody fragments specifically binding to human C5aR. In particular, it relates to antibodies or antibody fragments that have combined beneficial properties and are therefore useful for the treatment of inflammatory or autoimmune diseases or cancer.

1 : An isolated antibody or antibody fragment specific for human C5aR, wherein said antibody or antibody fragment comprises
 a) the HCDR1 region of SEQ ID NO: 27, the HCDR2 region of SEQ ID NO: 28, the HCDR3 region of SEQ ID NO: 29, the LCDR1 region of SEQ ID NO: 32, the LCDR2 region of SEQ ID NO: 33 and the LCDR3 region of SEQ ID NO: 34, or   b) the HCDR1 region of SEQ ID NO: 27, the HCDR2 region of SEQ ID NO: 39, the HCDR3 region of SEQ ID NO: 40, the LCDR1 region of SEQ ID NO: 32, the LCDR2 region of SEQ ID NO: 33 and the LCDR3 region of SEQ ID NO: 34.   
     
     
         2 : The isolated antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment comprises
 a) the VH of SEQ ID NO: 35 and the VL of SEQ ID NO 36, or   b) the VH of SEQ ID NO: 42 and the VL of SEQ ID NO 43.   
     
     
         3 : The isolated antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment comprises
 a) the HC of SEQ ID NO: 37 and the LC of SEQ ID NO 38, or   b) the HC of SEQ ID NO: 44 and the LC of SEQ ID NO 45.   
     
     
         4 : The isolated antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment is of the human IgG1 class. 
     
     
         5 : The isolated antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment does not substantially induce effector function in vitro. 
     
     
         6 : The isolated antibody or antibody fragment according to  claim 1 , wherein said antibody or antibody fragment comprises one or more amino acid substitution selected from the group of: L234A, L235E, G237A, A330S and P331S, with numbering according to EU index. 
     
     
         7 : The isolated antibody or antibody fragment according to  claim 1 , wherein said isolated antibody or antibody fragment is specific for human C5aR and cynomolgus C5aR. 
     
     
         8 : The isolated antibody or antibody fragment according to  claim 1 , wherein said isolated antibody or antibody fragment inhibits human C5a induced CD11b expression in human granulocytes with an IC 50  concentration of 42 nM in the presence of 150 nM human C5a in vitro. 
     
     
         9 : The isolated antibody or antibody fragment according to  claim 1 , wherein said isolated antibody or antibody fragment is a monoclonal antibody or antibody fragment. 
     
     
         10 : The isolated antibody or antibody fragment according to  claim 1 , wherein said isolated antibody or antibody fragment is a human, humanized or chimeric antibody or antibody fragment. 
     
     
         11 : The A method for altering biological activity of human C5aR comprising administering the isolated antibody or antibody fragment of  claim 1 . 
     
     
         12 : A nucleic acid composition comprising a nucleic acid sequence or a plurality of nucleic acid sequences encoding the isolated antibody or antibody fragment according to  claim 1 . 
     
     
         13 : A vector composition comprising a vector or a plurality of vectors comprising the nucleic acid composition of  claim 12 . 
     
     
         14 : A host cell comprising the vector composition of  claim 13 . 
     
     
         15 : A pharmaceutical composition comprising the isolated antibody or antibody fragment according to  claim 1  and a pharmaceutically acceptable carrier or excipient. 
     
     
         16 : A host cell comprising the nucleic acid composition of  claim 12 . 
     
     
         17 : A method for treating a disease in a subject comprising administering to the subject the antibody or antibody fragment of  claim 1 . 
     
     
         18 : A method for detecting C5aR in a subject or a sample, said method comprising the step of contacting said subject or sample with the antibody or antibody fragment of  claim 1 .