The present invention provides: a modified FcRn-binding domain having an enhanced affinity for the Fc Receptor neonatal (FcRn) at neutral pH； an antigen-binding molecule comprising said FcRn-binding domain, which has low immunogenicity, high stability and form only a few aggregates； a modified antigen-binding molecule having an increased FcRn-binding activity at neutral or acidic pH without an increased binding activity at neutral pH for a pre-existing anti-drug antibody； use of the antigen-binding molecules for improving antigen-binding molecule-mediated antigen uptake into cells； use of the antigen-binding molecules for reducing the plasma concentration of a specific antigen； use of the modified FcRn-binding domain for increasing the total number of antigens to which a single antigen-binding molecule can bind before its degradation； use of the modified FcRn-binding domain for improving pharmacokinetics of an antigen-binding molecule； methods for decreasing the binding activity for a pre-existing anti-drug antibody； and methods for producing said antigen-binding molecules.本發明提供：於中性pH對於Fc新生兒受體(FcRn)具有增強的親和性之經改質FcRn結合域；包含上述FcRn結合域之抗原結合分子，其具有低免疫原性、高安定性以及僅形成少數凝集物；於中性或酸性pH具有增加的FcRn結合活性而於中性pH對於預存在之抗藥物抗體無增加的結合活性之經改質之抗原結合分子；上述抗原結合分子用於改良抗原結合分子媒介之抗原攝入至細胞的用途；上述抗原分子用於減少特定抗原之血漿濃度的用途；上述經改質之FcRn結合域用於增加抗原對可於其降解之前結合之單一抗原結合分子的總數的用途；上述經改質FcRn結合域用於改良抗原結合分子之藥物動力學的用途；用於降低對於預存在之抗藥抗體的結合活性的方法；以及用於製造上述抗原結合分子的方法。
