Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases
by Honghui Zhou, Diane R. Mould
9Translational Considerations in Developing Bispecific Antibodies: What Can We Learn from Quantitative Pharmacology?
Pradeep B. Lukka Santosh Wagh and Bernd Meibohm
The University of Tennessee Health Science Center, Department of Pharmaceutical Sciences, Memphis, TN, 38163, USA
9.1 Introduction
Bispecific antibodies (BsAbs) exhibit dual functionality and are capable of binding to two different epitopes of the same or different antigens. BsAbs can be divided into “IgG‐like” or “non‐IgG‐like” formats based on their resemblance to the native IgG. “IgG‐like” BsAbs have so far been the predominant group and are produced by a variety of methods, including the Quadroma [1], Knobs‐into‐Holes [2], CrossMab [3], dock‐and‐lock [4], DuoBody [5], and dual‐variable‐domain immunoglobulin [6] approaches. “Non‐IgG‐like” BsAbs have a lower molecular weight and include formats such as bispecific T‐cell engagers (BiTEs), dual‐affinity retargeting molecules (DARTs), and tandem diabody (TandAb) systems. In “non‐IgG‐like” BsAbs, antibody fragments, such as antibody‐binding fragment (Fab), single‐chain fragment variable (scFv), or single‐domain antibodies (sdAbs), are used as building blocks connected by short flexible peptide linkers. A recent review by Kontermann and Brinkmann exhibits the versatility of BsAb designs demonstrated by over 60 different formats that have been produced to date, with over 30 BsAbs in clinical development (Figure 9.1) [7].
Figure 9.1 A selection of different BsAbs scaffolds ...