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Pharmacokinetics of Bispecific Antibody

  • Molecular Drug Disposition (M Hu, Section Editor)
  • Published:
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Abstract

Purpose of Review

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.

Recent Findings

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.

Summary

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.

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Acknowledgements

The authors thank Tommy Li and Xin Miao for editorial contribution and helpful discussion.

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Authors and Affiliations

  1. Janssen R&D, LLC, 1400 Mckean Rd, Spring House, PA, 19477, USA

    Yang Chen & Yan Xu

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  1. Yang Chen
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Correspondence to Yang Chen.

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The authors received no financial support in the writing of this manuscript. Both authors are employees of Janssen Research & Development, LLC. The opinions expressed in this publication are those of the authors and do not necessarily reflect those of the company who employs them.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Molecular Drug Disposition

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Chen, Y., Xu, Y. Pharmacokinetics of Bispecific Antibody. Curr Pharmacol Rep 3, 126–137 (2017). https://doi.org/10.1007/s40495-017-0090-5

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