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.