PROBLEM TO BE SOLVED: To provide an antigen-binding molecule having &ge2 value of KD(pH 5.8)/KD(pH 7.4) which is the ratio of the KD (dissociation constant) toward the antigen at pH 5.8 to the KD toward the same at pH 7.4.SOLUTION: It has been found that the antibodies having weaker antigen-binding activity at an early endosome pH as compared with the antigen-binding activity at the pH of plasma can bind with multiple number of antigen molecules by the one molecule of the antibody, have long half lives in the plasma and have the improved duration of periods in which they can bind with the antigens. Here, by substituting at least one amino acid in the antigen-binding molecule with histidine or inserting at least one histidine, there are provided a method for increasing the number of bindings of the antigen-binding molecule with the antigens, a method for improving pharmacokinetics and a method for dissociating the antigens bonded with the antigen-binding molecule outside the cell, from the antigen-binding molecule inside the cell.COPYRIGHT: (C)2012,JPO&INPIT【課題】抗原に対するpH5.8でのKDとpH7.4でのKDの比であるKD(pH5.8)/KD(pH7.4)の値が2以上である抗原結合分子の提供。【解決手段】血漿中でのpHにおける抗原結合活性と比較して早期エンドソーム内でのpHにおける抗原結合活性が弱い抗体は1分子の抗体で複数分子の抗原に結合することが可能になり、血漿中半減期が長く、抗原に結合可能な期間が改善されることを見出した。ここでは、抗原結合分子の少なくとも1つのアミノ酸をヒスチジンで置換する又は少なくとも1つのヒスチジンを挿入することにより、抗原結合分子の抗原への結合回数を増やす方法、薬物動態を向上させる方法、細胞外で抗原結合分子に結合した抗原を細胞内で抗原結合分子から解離させる方法。【選択図】なし
