Effective method for manufacturing antibody-drug conjugate

The present invention is: a method for manufacturing an antibody-drug conjugate in which a drug linker represented by formula (1) (A in the formula representing an antibody binding site) and an antibody are bonded by a thioether bond, the manufacturing method characterized by including (i) a step fo...

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Hauptverfasser: SAKURATANI KENJI, YAMAGUCHI TATSUYA
Format: Patent
Sprache:chi ; eng
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Zusammenfassung:The present invention is: a method for manufacturing an antibody-drug conjugate in which a drug linker represented by formula (1) (A in the formula representing an antibody binding site) and an antibody are bonded by a thioether bond, the manufacturing method characterized by including (i) a step for reducing an antibody with a reducing agent, (ii) a step for reacting a drug linker intermediate with the antibody reduced in step (i), (iii) a step for adding a reagent having a thiol group and reacting with the drug linker intermediate remaining from step (ii), and (iv) a step for then removing abyproduct derived from the drug linker intermediate by ultrafiltration using a buffer solution containing a salt comprising a strong acid and a strong base; and a method for manufacturing a pharmaceutical composition including the aforementioned antibody-drug conjugate. 本发明为:用于生产抗体-药物缀合物的方法,在所述抗体-药物缀合物中,由式(1)(其中A表示与抗体的连接位置)表示的药物-接头经由硫醚键与抗体缀合,其中该方法特征在于:(i)用还原剂还原抗体的步骤;(ii)使药物-接头中间产物与步骤(i)中还原的抗体反应的步骤;(iii)加入具有硫醇基的试剂,并与步骤(ii