Pharmacokinetics of Bispecific Antibody

This article provides a brief overview of bispecific antibody (BsAb) mechanisms of action, structures, and pharmacokinetic (PK) properties, including absorption, distribution, and elimination. Recent trend in BsAb development is also introduced from a PK perspective. Advances in biotechnology have led to the development of diverse BsAb formats, which provide a wide range of options to tailor the design of BsAbs to match the proposed mechanisms of action and to optimize the intended therapies. Understanding the PK properties of BsAbs and the important factors influencing PK is critical for the rationale design and development of BsAb therapeutics. PK behavior of a BsAb is dependent on its format and could be governed by molecular weight, physicochemical properties, interaction with Fc receptors, and binding to target, etc. Due to their multi-binding properties, BsAbs may have superior target tissue deliveries (e.g., brain, solid tumors) and additional unique PK properties compared to conventional mAbs, which may offer therapeutic advantages. Despite the many unknowns about BsAb disposition, it is generally believed that an ideal BsAb should have a balance between favorable systemic exposure (typically a long half-life is preferred) and appropriate distribution and tissue penetration. BsAb has unique mechanisms of action, structures, and PK properties when compared to conventional monoclonal antibody (mAb) and also shares similar pathways that contribute to PK characteristics of conventional mAb. Understanding the PK of BsAbs and the important factors influencing the PK is critical for the rationale design and development of BsAb therapeutics.