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Improvement of pharmacokinetic properties of therapeutic antibodies by antibody engineering

期刊

DRUG METABOLISM AND PHARMACOKINETICS
卷 34, 期 1, 页码 25-41

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JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.1016/j.dmpk.2018.10.003

关键词

Therapeutic antibody; Pharmacokinetics; Antibody engineering; FcRn; Fc gamma R; pH-dependent target-antigen binding; TMDD; Isoelectric point; Charge

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Monoclonal antibodies ( mAbs) have become an important therapeutic option for several diseases. Since several mAbs have shown promising efficacy in clinic, the competition to develop mAbs has become severe. In efforts to gain a competitive advantage over other mAbs and provide significant benefits to patients, innovations in antibody engineering have aimed at improving the pharmacokinetic properties of mAbs. Because engineering can provide therapeutics that are more convenient, safer, and more efficacious for patients in several disease areas, it is an attractive approach to provide significant benefits to patients. Further advances in engineering mAbs to modulate their pharmacokinetics were driven by the increase of total soluble target antigen concentration that is often observed after injecting a mAb, which then requires a high dosage to antagonize. To decrease the required dosage, several antibody engineering techniques have been invented that reduce the total concentration of soluble target antigen. Here, we review the various ways that antibody engineering can improve the pharmacokinetic properties of mAbs. (c) 2018 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

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