Selective clearance of monoclonal antibodies via the mannose receptor is dependent on glycan pairing

The pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs) are influenced by N-glycosylation, a critical quality attribute (CQA) that affects serum half-life and receptor interactions. High-mannose N-glycans are known to accelerate mAb clearance, likely via the mannose receptor (MR). However, the impact of high-mannose glycan pairing - whether symmetrical or asymmetrical - on this process remains poorly understood. MAbs enriched in high-mannose N-glycans were fractionated using mannose receptor—affinity chromatography to isolate symmetrical and asymmetrical high-mannose glyco-pairs. These fractions were characterized for physicochemical properties and labeled for a cell-based internalization assay…