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The structural patterns of IgG2 disulfide isoforms fundamentally influence a spectrum of critical attributes, from molecular properties such as surface charge distribution, hydrophobicity, and N-glycosylation to ultimate biological activity and potency. Evenity (romosozumab) is a humanized IgG2 monoclonal antibody targeting sclerostin, for the treatment of osteoporosis. During the development of a romosozumab biosimilar, difference in the disulfide isoform profiles of the biosimilar and the reference medicinal product (RMP) was identified. Compared with RMP, the biosimilar presented a reduced IgG2-B content, accompanied by elevated IgG2-A\/B and IgG2-A contents. The disulfide isoforms were fractionated via CEX-HPLC or enriched via a redox procedure, after which the key physicochemical properties, binding ability and potency were investigated. The analytical data revealed that, despite observed differences in specific physicochemical properties\u2014including surface charge distribution, hydrophobicity, and high mannose content\u2014the biosimilar\u2019s disulfide isoforms exhibited comparable potency to the RMP. 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