High affinity human antibodies to human il-4 receptor

Abstract

The present invention provides nucleic acid molecules that encode antibodies or antigen-binding fragments thereof, which specifically bind human interleukin-4 receptor (IL-4R). Also provided are expression vectors comprising nucleic acid molecule that encode anti-IL-4R antibodies, host cells comprising the expression vectors, and methods of producing anti-IL-4R antibodies or antigen-binding fragments thereof comprising growing the host cells under conditions permitting production of the antibody or fragment, and recovering the antibody or fragment so produced.

1 . An antibody or antigen-binding fragment thereof that specifically binds human IL-4R, comprising three heavy chain complementarity determining region (HCDR) sequences comprising SEQ ID NO:148, 150, and 152, respectively, and three light chain complementarity determining region (LCDR) sequences comprising SEQ ID No:156, 158, and 160, respectively. 
     
     
         2 . The antibody or antigen-binding fragment of  claim 1 , wherein the heavy and light chain CDR amino acid sequences (HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3) are encoded by nucleotide sequences of SEQ ID NO:147, 149, 151, 155, 157, and 159, respectively. 
     
     
         3 . The antibody or antigen-binding fragment of  claim 1 , wherein the antibody or antigen binding fragment comprises a heavy chain variable region (HCVR) having an amino acid sequence of SEQ ID NO:162 and a light chain variable region (LCVR) having an amino acid sequence of SEQ ID NO:164. 
     
     
         4 . The antibody or antigen-binding fragment of  claim 1 , characterized by an affinity for hIL-4R (K D ) of ≤300 pM. 
     
     
         5 . The antibody or antigen-binding fragment of  claim 1 , characterized by an affinity for hIL-4R (K D ) of ≤100 pM. 
     
     
         6 . The antibody or antigen-binding fragment of  claim 1 , characterized by an affinity for hIL-4R (K D ) of ≤50 pM. 
     
     
         7 . The antibody or antigen-binding fragment of  claim 1 , wherein the antibody or fragment thereof cross-reacts with monkey IL-4R. 
     
     
         8 . The antibody or antigen-binding fragment of  claim 1  for use in the treatment of asthma or atopic dermatitis. 
     
     
         9 . A nucleic acid molecule comprising a nucleic acid sequence encoding the antibody or antigen-binding fragment of  claim 1 . 
     
     
         10 . A vector comprising the nucleic acid sequence of  claim 9 . 
     
     
         11 . An isolated host cell comprising the vector of  claim 10 . 
     
     
         12 . A therapeutic composition comprising the antibody or antigen-binding fragment of  claim 1  and an acceptable carrier. 
     
     
         13 . The therapeutic composition of  claim 12 , further comprising a second therapeutic agent selected from montelukast, pranlukast, zafirlukast, and rilonacept. 
     
     
         14 . The antibody or antigen-binding fragment of  claim 1  for use in the treatment of asthma. 
     
     
         15 . The antibody or antigen-binding fragment of  claim 1  for use in the treatment of atopic dermatitis. 
     
     
         16 . The antibody or antigen-binding fragment of  claim 1 , wherein the antibody or antigen-binding fragment thereof is a human antibody, and wherein the antibody or antigen-binding fragment thereof is made in a transgenic mouse. 
     
     
         17 . The antibody or antigen-binding fragment of  claim 1 , wherein the antibody or antigen-binding fragment is a human antibody, and wherein the antibody or antigen-binding fragment thereof is isolated from a hybridoma that is derived from a B cell that is isolated from a transgenic mouse. 
     
     
         18 . A therapeutic composition comprising an antibody or antigen-binding fragment thereof that specifically binds human IL-4R, and a pharmaceutically acceptable carrier, wherein the antibody or antigen binding fragment comprises a heavy chain variable region (HCVR) having an amino acid sequence of SEQ ID NO:162 and a light chain variable region (LCVR) having an amino acid sequence of SEQ ID NO:164. 
     
     
         19 . A therapeutic composition comprising an antibody or antigen-binding fragment thereof that specifically binds human IL-4R, and a pharmaceutically acceptable carrier, wherein the antibody or antigen binding fragment comprises heavy and light chain CDR amino acid sequences (HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3) having the amino acid sequences of SEQ ID NO:148, 150, 152, 156, 158, and 160, respectively. 
     
     
         20 . The therapeutic composition of  claim 19  formulated for subcutaneous administration.