Feasibility of Antibody–Poly(Glutamic Acid) Complexes: Preparation of High-Concentration Antibody Formulations and Their Pharmaceutical Properties

摘要

Development of high-concentration antibody formulations for subcutaneous administration remains challenging. Recently, a precipitation–redissolution method was proposed to prepare suspensions or precipitates of salt-dissociable protein–poly(amino acid) complexes. To elucidate the utility of this method for protein therapy, we investigated the feasibility of a precipitation–redissolution method using poly(amino acid) for high-concentration antibody formulation. Omalizumab and adalimumab formulations of 150 mg/mL could be prepared using poly-l-glutamic acid (polyE) from low-concentration stock solutions. Enzyme-linked immunosorbent assay, circular dichroism, and size-exclusion chromatography revealed that the formation of antibody–polyE complex and precipitation–redissolution process did not significantly affect the immunoreactivity or secondary structure of the antibodies. The precipitation–redissolution method was less time-consuming and more effective than lyophilization–redissolution, evaporation–redissolution, and ultrafiltration from the viewpoint of final yield. Scalability was confirmed from 400 μL to 1.0 L. The general toxicity and pharmacokinetic profiles of the antibody–polyE complex formulations were similar to those of conventional antibody formulations. These results suggested that the precipitation–redissolution method using poly(amino acid) has great potential as a concentration method for antibody formulation and medicinal use.