High affinity antibodies to human il-6 receptor

Abstract

A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a K D of about 500 pM or less and blocks IL-6 activity with an IC 50 of 200 pM or less, is provided. In preferred embodiments, the antibody the antibody or antigen-binding fragment binds hIL-6R with an affinity at least 2-fold higher relative to its binding monkey IL-6R.

1 . An isolated nucleic acid molecule encoding an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hIL-6R), wherein the antibody or antibody fragment comprises three heavy chain complementarity determining region (CDR) sequences and three light chain CDR sequences, wherein the three heavy chain CDR sequences comprise a combination selected from the group consisting of SEQ ID NO:149, 151 and 153; SEQ ID NO:5, 7 and 9; and SEQ ID NO:181, 183 and 185; and wherein the three light chain CDR sequences comprise a combination selected from the group consisting of SEQ ID NO:157, 159 and 161; SEQ ID N0:13, 15 and 17; and SEQ ID NO:189, 191 and 193. 
     
     
         2 . The nucleic acid molecule of  claim 1 , wherein the antibody or antibody fragment comprises a CDR sequence combination selected from the group consisting of SEQ ID NO:149, 151, 153, 157, 159 and 161; SEQ 1D NO:5, 7, 9, 13, 15 and 17; and SEQ ID N0:181, 183, 185, 189, 191 and 193. 
     
     
         3 . The nucleic acid molecule of  claim 1 , wherein the antibody or antibody fragment comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:147, 3 or 179. 
     
     
         4 . The nucleic acid molecule of  claim 1 , wherein the antibody or antibody fragment comprises a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:155, 11 or 187. 
     
     
         5 . A recombinant expression vector comprising the nucleic acid molecule of  claim 1 . 
     
     
         6 . An isolated host cell comprising the expression vector of  claim 5 . 
     
     
         7 . The host cell of  claim 6  being a prokaryotic cell or an eukaryotic cell. 
     
     
         8 . The host cell of  claim 7 , wherein the prokaryotic cell is an  E. coli  cell and the eukaryotic cell is a CHO cell. 
     
     
         9 . A method of producing an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hIL-6R), comprising growing the host cell of  claim 6  under conditions permitting production of the antibody or fragment thereof, and recovering the antibody or fragment thereof so produced. 
     
     
         10 . An isolated nucleic acid molecule encoding an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hIL-6R), wherein the antibody or antibody fragment comprises a heavy chain variable region (HCVR) comprising SEQ ID N0:147, 3 or 179. 
     
     
         11 . The nucleic acid molecule of  claim 10 , comprising the nucleotide sequence of SEQ ID N0:146, 2 or 178. 
     
     
         12 . The nucleic acid molecule of  claim 10 , wherein the antibody or antibody fragment further comprises a light chain variable region (LCVR) comprising SEQ ID NO:155, 11 or 187. 
     
     
         13 . The nucleic acid molecule of  claim 12 , wherein the antibody or antibody fragment comprises a HCVR/LCVR pair selected from the group consisting of SEQ ID NO:147/155, 3/11 and 179/187. 
     
     
         14 . A recombinant expression vector comprising the nucleic acid molecule of  claim 13 . 
     
     
         15 . An isolated host cell comprising the expression vector of  claim 14 . 
     
     
         16 . The host cell of  claim 15  being a prokaryotic cell or an eukaryotic cell. 
     
     
         17 . The host cell of  claim 16 , wherein the prokaryotic cell is an  E. coli  cell and the eukaryotic cell is a CHO cell. 
     
     
         18 . A method of producing an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hlL-6R), comprising growing the host cell of  claim 15  under conditions permitting production of the antibody or fragment thereof, and recovering the antibody or fragment thereof so produced. 
     
     
         19 . An isolated nucleic acid molecule encoding an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hIL-6R), wherein the antibody or antibody fragment comprises a light chain variable region (LCVR) comprising SEQ ID NO:155, 11 or 187. 
     
     
         20 . The nucleic acid molecule of  claim 19 , comprising the nucleotide sequence of SEQ ID NO:154, 10 or 186.