What is Charge Heterogeneity?
In general, many proteins, such as therapeutic monoclonal antibodies (mAbs), have charge heterogeneity. The formation of protein charge variants can be subject to various enzymatic post-translational modifications (PTMs) during manufacture, such as glycation, glycosylation, lysine truncation, asparagine/glutamine deamidation, iso-Asp modification, and methionine oxidation. Additionally, chemical modifications such as oxidation or deamination can occur during purification and storage.
These modifications can alter the surface charge distribution and conformation of proteins, forming charge variants with various isoelectric points (pIs). Charge variants have different structures, stabilities, binding affinities, and chemical properties, which directly determine their biological reactivity and pharmacological effects. Therefore, characterization of charge variants of protein drugs are critical quality attributes necessary to guarantee product safety, efficacy, and stability. Analysis of charged variants is also a regulatory requirement for biotherapeutic proteins.