Humanized Anti-Epiregulin Antibody, and Cancer Therapeutic Agent Comprising Said Antibody as Active Ingredient

Abstract

The inventors successfully produced anti-Epiregulin antibodies showing cross-species reactivity between cynomolgus monkey (non-human animals) and human, anti-Epiregulin antibodies with suppressed chemical degradation, anti-Epiregulin antibodies with lowered isoelectric point, anti-Epiregulin antibodies with increased thermal denaturation midpoint temperature, and anti-Epiregulin antibodies with reduced amount of aggregate by performing appropriate amino acid residue substitutions in the variable-region sequences of the humanized EP27 antibody which inhibits growth of cancer cells by exhibiting cytotoxic activity and neutralizing activity against human Epiregulin-expressing cells.

1 .- 39 . (canceled) 
     
     
         40 . A method for treating cancer in a subject in recognized need thereof, the method comprising administering to the subject as an active ingredient an anti-Epiregulin antibody which is an antibody that binds to an epitope bound by an anti-Epiregulin antibody comprising heavy-chain variable region CDRs of SEQ ID NOs: 9, 10, and 11 and light chain variable region CDRs of SEQ ID NO: 12, 13, and 14, wherein the antibody is characterized in having a smaller ratio of the KD value for monkey Epiregulin of SEQ ID NO: 170 (cEREG KD) to the KD value for human Epiregulin of SEQ ID NO: 34 (hEREG KD) (cEREG KD/hEREG KD) than the cEREG KD/hEREG KD ratio of the anti-Epiregulin antibody comprising heavy-chain variable region CDRs of SEQ ID NOs: 9, 10, and 11 and light-chain variable region CDRs of SEQ ID NO: 12, 13, and 14. 
     
     
         41 . A method for preventing cancer in a subject in recognized need thereof, the method comprising administering to the subject as an active ingredient an anti-Epiregulin antibody which is an antibody that binds to an epitope bound by an anti-Epiregulin antibody comprising heavy-chain variable region CDRs of SEQ ID NOs: 9, 10, and 11 and light chain variable region CDRs of SEQ ID NO: 12, 13, and 14, wherein the antibody is characterized in having a smaller ratio of the KD value for monkey Epiregulin of SEQ ID NO: 170 (cEREG KD) to the KD value for human Epiregulin of SEQ ID NO: 34 (hEREG KD) (cEREG KD/hEREG KD) than the cEREG KD/hEREG KD ratio of the anti-Epiregulin antibody comprising heavy-chain variable region CDRs of SEQ ID NOs: 9, 10, and 11 and light-chain variable region CDRs of SEQ ID NO: 12, 13, and 14.