Capped and uncapped antibody cysteines, and their use in antibody-drug conjugation

An antibody production process in mammalian cells in which engineered unpaired cysteine residues are post-translationally modified and capped with particular chemical entities, which capped antibodies are well suited to further site-specific conjugation steps to form antibody-drug conjugates (ADCs)...

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Bibliographische Detailangaben
Hauptverfasser: Somers, Will, Letendre, Leo Joseph, He, Tao, Kriz, Ronald William, Zhong, Xiaotian, Wang, Wenge, Prashad, Amarnauth Shastrie
Format: Patent
Sprache:eng
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Beschreibung
Zusammenfassung:An antibody production process in mammalian cells in which engineered unpaired cysteine residues are post-translationally modified and capped with particular chemical entities, which capped antibodies are well suited to further site-specific conjugation steps to form antibody-drug conjugates (ADCs) or protein drug conjugates; ADCs produced using these capped antibodies including in particular ADCs formed by the selective reduction of the capped antibodies' cysteine residues, and ADCs formed using chemical handles such as aldehyde/azide/alkyne biorthogonal groups, which permit additional drug conjugation chemistry; and uncapped antibodies produced by cells in low cysteine, cysteine and glutathione media, and ADCs produced via direct conjugation to these uncapped antibodies.