A First Insight into the Developability of an Immunoglobulin G3: A Combined Computational and Experimental Approach

• DOI: 10.1021/acsptsci.4c00271
• Publication Date: 2024-07-15T14:09:12Z
• Authors: Georgina B. Armst...; Alan Lewis; Vidhi Shah; Paul Taylor; Craig J. Jamieson; Glenn A. Burley; William Lewis; Zahra Rattray

Immunoglobulin G 3 (IgG3) monoclonal antibodies (mAbs) are high-value scaffolds for developing novel therapies. Despite their wide-ranging therapeutic potential, IgG3 physicochemical properties and developability characteristics remain largely under-characterized. Protein–protein interactions elevate solution viscosity in high-concentration formulations, impacting stability, manufacturability, the injectability of mAbs. Therefore, this manuscript, key molecular descriptors biophysical a model anti-IL-8 IgG1 its ortholog characterized. A computational experimental framework was applied to measure downstream developability. Findings from approach underpin detailed understanding mAbs as potential entities. This work is first report examining manufacturability mAb formulations. While poorer conformational colloidal stability elevated were observed IgG3, future efforts controlling surface through sequence-engineering solvent-accessible patches can be used improve parameters that dictate