Increase in Solubility of Monoclonal Antibodies - Formulation Perspective and the “Magic” of Arginine

Abstract

Monoclonal antibodies (mAb) intended for use in prophylactic therapy often require formulation at concentrations of ≥ 100 mg/mL, due to limit in the volume for administration via the subcutaneous injection. This poses challenges for the mAb formulation field in general, but especially for mAbs where protein engineering options are limited due to unique functional characteristics. The work presented will be a case study of a monoclonal antibody (mAb1) developed by the Vaccine Research Center (NIAID/NIH). mAb1 is an exciting candidate for prophylactic HIV therapy based on its capability to neutralize >95% of circulating HIV-1 strains (based on a 208-virus panel). With a range of molecular and structural biology approaches a selection of sequential variants of mAb1 were identified that retained or improved the biological activity of the native strain. mAb1 in the wild-type form has very poor solubility (<5 mg/mL); although solubility was increased in the selected variants, it was insufficient for manufacturing and clinical used. Here we present an exploration of a myriad of formulation options to identify solution conditions that will support the clinical manufacturing of the 10E8 mAb. Specifically, we discuss the critical role that Arginine played in achieving a high concentration formulation.