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 KD of about 500 pM or less and blocks IL-6 activity with an IC50 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 .- 17 . (canceled) 
     
     
         18 . An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a heavy chain variable region (HCVR) of an antibody or antibody fragment which specifically binds human interleukin-6 receptor (hIL-6R), wherein the HCRV comprises:
 three heavy chain complementarity determining region (CDR) sequences; and   three light chain CDR sequences;   wherein the three heavy chain CDR sequences are SEQ ID NO:181, 183 and 185; and   wherein the three light chain CDR sequences are SEQ ID NO:189, 191 and 193.   
     
     
         19 . The nucleic acid molecule of  claim 18 , wherein the antibody or antibody fragment comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:179. 
     
     
         20 . The nucleic acid molecule of  claim 18 , wherein the antibody or antibody fragment comprises a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:187. 
     
     
         21 . A recombinant expression vector comprising the nucleic acid molecule of  claim 18 . 
     
     
         22 . An isolated host cell comprising the expression vector of  claim 21 . 
     
     
         23 . The host cell of  claim 22  being a prokaryotic cell or an eukaryotic cell. 
     
     
         24 . The host cell of  claim 22 , wherein the prokaryotic cell is an  E. coli  cell and the eukaryotic cell is a CHO cell. 
     
     
         25 . 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 22  under conditions permitting production of the antibody or fragment thereof, and recovering the antibody or fragment thereof so produced. 
     
     
         26 . An isolated nucleic acid molecule encoding a heavy chain variable region and light chain variable region pair (HCVR/LCVR) SEQ ID NO:179/187. 
     
     
         27 . An isolated nucleic acid molecule encoding a heavy chain variable region and light chain variable region pair (HCVR/LCVR) SEQ ID NO:178/186. 
     
     
         28 . A recombinant expression vector comprising the nucleic acid molecule of  claim 26 . 
     
     
         29 . An isolated host cell comprising the expression vector of  claim 28 . 
     
     
         30 . The host cell of  claim 29  being a prokaryotic cell or a eukaryotic cell. 
     
     
         31 . The host cell of  claim 30 , wherein the prokaryotic cell is an  E. coli  cell and the eukaryotic cell is a CHO cell. 
     
     
         32 . 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 29  under conditions permitting production of the antibody or fragment thereof, and recovering the antibody or fragment thereof so produced. 
     
     
         33 . A recombinant expression vector comprising the nucleic acid molecule of  claim 27 . 
     
     
         34 . An isolated host cell comprising the expression vector of  claim 33 . 
     
     
         35 . The host cell of  claim 34  being a prokaryotic cell or a eukaryotic cell. 
     
     
         36 . The host cell of  claim 35 , wherein the prokaryotic cell is an  E. coli  cell and the eukaryotic cell is a CHO cell. 
     
     
         37 . 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 36  under conditions permitting production of the antibody or fragment thereof, and recovering the antibody or fragment thereof so produced.