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Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases
book

Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases

by Honghui Zhou, Diane R. Mould
March 2019
Intermediate to advanced content levelIntermediate to advanced
496 pages
15h
English
Wiley
Content preview from Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases

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 ...

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Publisher Resources

ISBN: 9781119289197Purchase book