Humanized pan-her antibody compositions

Abstract

The invention relates to humanized recombinant antibodies targeting the EGFR family receptors EGFR, HER2 and HER3, compositions comprising at least one humanized anti-EGFR antibody, at least one humanized anti-HER2 antibody and at least one humanized anti-HER3 antibody, and use of the antibody compositions for treatment of cancer. The invention also relates to the use of antibodies targeting multiple EGFR-family receptors to treat cancer (e.g., pancreatic cancer) and cancer that has acquired resistance to previous therapies.

What is claimed is: 
     
         1 . An antibody composition comprising:
 a) a humanized anti-EGFR antibody or an antigen-binding fragment thereof;   b) a humanized anti-HER2 antibody or an antigen-binding fragment thereof, comprising the heavy chain CDR1-3 amino acid sequences in SEQ ID NO: 52 and the light chain CDR1-3 amino acid sequences in SEQ ID NO: 53;   c) a first humanized anti-HER3 antibody or an antigen-binding fragment thereof, comprising the heavy chain CDR1-3 amino acid sequences in SEQ ID NO: 54 and the light chain CDR1-3 amino acid sequences in SEQ ID NO: 55; and   d) a second humanized anti-HER3 antibody or an antigen-binding fragment thereof, comprising the heavy chain CDR1-3 amino acid sequences in SEQ ID NO: 60 and the light chain CDR1-3 amino acid sequences in SEQ ID NO: 61.   
     
     
         2 . The antibody composition of  claim 1 , wherein
 is the humanized anti-HER2 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 52 and a light chain comprising the amino acid sequence of SEQ ID NO: 53,   the first humanized anti-HER3 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 54 and a light chain comprising the amino acid sequence of SEQ ID NO: 55, and   the second humanized anti-HER3 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 60 and a light chain comprising the amino acid sequence of SEQ ID NO: 61.   
     
     
         3 . The antibody composition of  claim 2 , wherein said antibodies are IgG1 molecules. 
     
     
         4 . The antibody composition of  claim 1 , wherein at least one antibody in the composition is an immunoconjugate wherein the antibody is conjugated to an anti-cancer agent. 
     
     
         5 . The method of  claim 4 , wherein the anti-cancer agent is a cytotoxic agent, a cytokine, a toxin, or a radionuclide. 
     
     
         6 . An antibody composition comprising:
 a) two humanized anti-EGFR antibodies or antigen-binding fragments thereof;   b) a first humanized anti-HER2 antibody or an antigen-binding fragment thereof, comprising the heavy chain CDR1-3 amino acid sequences in SEQ ID NO: 52 and the light chain CDR1-3 amino acid sequences in SEQ ID NO: 53;   c) a second humanized anti-HER2 antibody;   d) a first humanized anti-HER3 antibody or an antigen-binding fragment thereof, comprising the heavy chain CDR1-3 amino acid sequences in SEQ ID NO: 54 and the light chain CDR1-3 amino acid sequences in SEQ ID NO: 55; and   e) a second humanized anti-HER3 antibody or an antigen-binding fragment thereof, comprising the heavy chain CDR1-3 amino acid sequences in SEQ ID NO: 60 and the light chain CDR1-3 amino acid sequences in SEQ ID NO: 61;   wherein each pair of antibodies that bind the same receptor bind to distinct and non-overlapping epitopes of that receptor.   
     
     
         7 . The antibody composition of  claim 6 , wherein
 the first humanized anti-HER2 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 52 and a light chain comprising the amino acid sequence of SEQ ID NO: 53,   the first humanized anti-HER3 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 54 and a light chain comprising the amino acid sequence of SEQ ID NO: 55, and   the second humanized anti-HER3 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 60 and a light chain comprising the amino acid sequence of SEQ ID NO: 61.   
     
     
         8 . The antibody composition of  claim 7 , wherein said antibodies are IgG1 molecules. 
     
     
         9 . The antibody composition of  claim 6 , wherein at least one antibody in the composition is an immunoconjugate wherein the antibody is conjugated to an anti-cancer agent. 
     
     
         10 . The method of  claim 9 , wherein the anti-cancer agent is a cytotoxic agent, a cytokine, a toxin, or a radionuclide. 
     
     
         11 . A pharmaceutical composition comprising the antibody composition of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         12 . A pharmaceutical composition comprising the antibody composition of  claim 6  and a pharmaceutically acceptable excipient. 
     
     
         13 . A method for treating cancer in a human patient, the method comprising administering to said patient an effective amount of the antibody composition of  claim 1 . 
     
     
         14 . The method of  claim 13 , wherein the antibody composition inhibits cancer growth in the patient. 
     
     
         15 . The method of  claim 13 , wherein the patient has pancreatic cancer or colon cancer. 
     
     
         16 . The method of  claim 13 , wherein said patient has acquired resistance to treatment with an antibody and/or a tyrosine kinase inhibitor. 
     
     
         17 . A method for treating cancer in a human patient, the method comprising administering to said patient an effective amount of the antibody composition of  claim 6 . 
     
     
         18 . The method of  claim 17 , wherein the antibody composition inhibits cancer growth in the patient. 
     
     
         19 . The method of  claim 17 , wherein the patient has pancreatic cancer or colon cancer. 
     
     
         20 . The method of  claim 17 , wherein said patient has acquired resistance to treatment with an antibody and/or a tyrosine kinase inhibitor.