Ultra-high concentration low-viscosity subcutaneous antibody formulations using ionic liquids

Abstract

Monoclonal antibodies (mAbs) are the single largest class of therapeutics used in various indications including oncology, immunology, and neurology. Given their high prevalence, the development of subcutaneously administrable mAb formulations via conventional needles is an urgent and unmet need. Subcutaneous mAb formulations need to meet several stringent requirements, including high concentrations to enable the delivery of therapeutic doses through small volumes, low viscosity to allow self-administration, and high shelf stability, all of which are inherently linked to protein-protein interactions, which have collectively limited mAb concentrations in current commercial formulations to ~150 mg/ml. Here, we report the use of ionic liquids (ILs) to mitigate protein-protein interactions to formulate antibodies at an ultra-high concentration in excess of 200 mg/ml. In addition to solubilizing antibodies at such high concentrations, IgG-IL formulations maintained a viscosity below the injectable threshold of 20 cP, remained stable at even room temperature and 37 °C, and exhibited improved bioavailability compared to saline formulations upon subcutaneous administration.