Random Heteropolymer Excipients Improve the Colloidal Stability of a Monoclonal Antibody for Subcutaneous Administration.

Purpose: Developing stable high concentration monoclonal antibody (mAb) formulations is increasingly important to move toward subcutaneous (SC) administration for better patient experience. Challenges stemming from protein-protein interactions in these crowded solutions, such as colloidal instability, limit the feasibility of some formulations because of concerns of safety, product quality, and/or manufacturability. Herein, we report novel random heteropolymer excipients that improve the colloidal stability of a high concentration mAb formulation for SC administration.

Methods: A library of polymers was synthesized and screened by a high-throughput, absorbance-based assay. The lead polymers were selected and characterized for their ability to alter the precipitation kinetics of a mAb in physiologically relevant conditions using two model systems.

Results: Biophysical testing via surface tension measurements, isothermal titration calorimetry (ITC), microscale thermophoresis (MST), and intrinsic fluorescence quenching indicated that the polymers delayed onset of mAb precipitation from a combination of surfactant behaviour and interactions with the protein to prevent protein-protein interactions leading to colloidal instability.

Conclusions: The random heteropolymers described are a new class of excipients that may enable development of SC mAb formulations previously inaccessible to patients.