ANTIBODY CO-FORMULATION TOOLBOX AND CAPABILITIES ESTABLISHED IN WUXI BIOLOGICS

Abstract Introduction Co-formulation containing two or more antibodies (mAbs) is deemed to hold distinct merits such as better treatment efficacy, higher efficiency and extended intellectual property right, attracting the demands from both patients and pharmaceutical companies. However, there are only limited numbers of approved drug products, partially due to the technical challenges in formulation development and analytical methods. Herein, we present WuXi Biologics efforts to accelerate the development of co-formulation drug products. Methodology We have established an antibody co-formulation specific toolbox with a dedicated team for co-formulation product development addressing the formulation and analytical challenges. Our co-formulation analytical expertise includes size exclusion-high performance liquid chromatography (SE-HPLC), caliper-sodium dodecyl sulfate reduced and non-reduced (Caliper-SDS-R & NR), imaged capillary isoelectric focusing (iCIEF), ion-exchange chromatography (IEC), reverse phase-liquid chromatography (RP-LC), hydrophobic interaction chromatography (HIC), Composition-Gradient Multi-Angle Light Scattering (CG-MALS), differential scanning calorimetry (DSC), enzyme-linked immunosorbent assay (ELISA) based and/or cell based potency, and peptide mapping with mass spectrometry etc. Results Remarkably, couple of antibodies co-formulation cases have completed successfully. Take one co-formulation case for instance, specifically, no substantial molecular interactions were observed between the two antibodies according to the results of differential light scattering (DLS) and CG-MALS. Besides, the main peaks of two mAbs were co-eluted in SE-HPLC and Caliper-SDS-NR, respectively. SE-HPLC and Caliper-SDS-NR methods were optimized to evaluate the purity of this co-formulation. As a result, the purity of these two mAbs in this co-formulation was comparable with its individual antibody respectively. Given the isoelectric point of two mAbs in this co-formulation differs by 1.0, iCIEF has been developed to separate the peaks of two mAbs completely. In another case, the isoelectric point of two mAbs differed by just 0.4, CEX has been developed. iCIEF and CEX method were optimized to evaluate the charge variants and determine the concentration ratio of these two mAbs in co-formulation product.