Observation of Heavy-Chain C-Terminal Des-GK Truncation in Recombinant and Human Endogenous IgG4
Bhavana Shah1, YaXing Zhu2, Jette Wypych1
1Process Development, Amgen Inc. One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
Therapeutic IgG mAbs have shown presence of three variations of their heavy chain C-termini, including the unprocessed C-terminal lysine, the processed C-terminal lysine, and C-terminal amidation. These variants are also present in endogenous human IgGs, although the level of unprocessed C-terminal lysine is very low. Here we report a new heavy-chain C-terminal variant, i.e., the des-GK truncation, which exists in both recombinant and endogenous human IgG4. The des-GK truncation was found in negligible amount in IgG1, IgG2 and IgG3 subclasses. Observation of a significant level of heavy-chain C-terminal des-GK truncation in endogenous human IgG4 suggests that low level of this variant present in therapeutic IgG4 is unlikely to be a safety concern.
Therapeutic IgG mAbs have shown presence of three variations of their heavy chain C-termini, including the unprocessed C-terminal lysine, the processed C-terminal lysine, and C-terminal amidation. These variants are also present in endogenous human IgGs, although the level of unprocessed C-terminal lysine is very low. Here we report a new heavy-chain C-terminal variant, i.e., the des-GK truncation, which exists in both recombinant and endogenous human IgG4. The des-GK truncation was found in negligible amount in IgG1, IgG2 and IgG3 subclasses. Observation of a significant level of heavy-chain C-terminal des-GK truncation in endogenous human IgG4 suggests that low level of this variant present in therapeutic IgG4 is unlikely to be a safety concern.
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