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 anti-human Epiregulin-expressing cancer cells.本案發明人等藉由將對於表現人類表皮調節素(Epireglulin)之癌細胞發揮細胞毒性及中和活性而抑制癌細胞之增殖之人型化EP27抗體之可變區序列中之胺基酸殘基予以適當取代，而成功地製作顯示非人類動物食蟹猴及人類動物間之種交叉反應性之抗表皮調節素抗體、化學性分解受抑制之抗表皮調節素抗體、等電點下降之抗表皮調節素抗體、熱改性中間溫度為上昇之抗表皮調節素抗體、組合體量減少的抗表皮調節素抗體。
