Method for increasing production yield of antibody-drug conjugate by using thiol-reactive additive

A method for manufacturing modified antibodies, wherein each modified antibody comprises a functional group, the method comprising:

• (a) contacting antibodies and compounds for transferring the functional group to induce reactions between the antibodies and the compounds for transferring the functional group, thereby manufacturing the modified antibodies,
• wherein the compound for transferring the functional group comprises a thioester group, a functional group (FG), and a Fc-binding peptide (FcBP),
• wherein reactions between the thioester group of the compound and a nucleophile of the antibody allow the modified antibodies to have the functional group, and also cause by-products to be produced, wherein the each by-products, derived from the compound, comprises a thiol group derived from the thioester group and the Fc-binding peptide;
• and
• (b) contacting the by-products and thiol reactive additives to induce reactions between the by-products and the thiol reactive additives, thereby removing a reaction inhibition effect which arises from the by-product inhibiting the reactions between the antibodies and the compounds for transferring the functional group,
• wherein the thiol reactive additives react with the thiol groups of the by-products such that the thiol groups of the by-products are capped, which allows undesired reactions between the thiol groups of the by-products and the antibodies to be blocked,
• thereby the reaction inhibition effect of the by-products can be reduced.