title: C-terminal modification of monoclonal antibody drugs: amidated species as a general product-related substance.
abstract: Twelve therapeutic mAbs, comprising 10 IgG1s and 2 IgG4s, were analyzed by a peptide mapping technique to detect and quantify C-terminal modifications. C-terminal amidated structures were found in 8 out of the 12 mAbs. An in vitro study using a commercially available peptidylglycine alpha-amidating monooxygenase (PAM) revealed that both IgG1 and IgG4 can be substrates for PAM. This study showed that C-terminal amidation is a general C-terminal modification on the heavy chains of therapeutic mAbs and that C-terminal amidation of mAbs can be catalyzed by a certain PAM(s) in the Chinese hamster ovary (CHO) cells that are widely used for manufacturing therapeutic mAbs.
authors.affiliation: Analytical Technology, CMC Development Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsubaki
authors.forename: Isamu
authors.initials: I
authors.lastname: Terashima
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Kamata
authors.forename: Akiko
authors.initials: A
authors.lastname: Koga
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011994:Recombinant Proteins