a Institute of Cell Biology and Immunology , University of Stuttgart , Stuttgart , Germany.
Expert Opin Biol Ther. 2016 Jul;16(7):903-15. doi: 10.1517/14712598.2016.1165661. Epub 2016 Apr 18.
Many of the biotherapeutics approved or under development suffer from a short half-life necessitating frequent applications in order to maintain a therapeutic concentration over an extended period of time. The implementation of half-life extension strategies allows the generation of long-lasting therapeutics with improved pharmacokinetic and pharmacodynamic properties.
This review gives an overview of the different half-life extension strategies developed over the past years and their application to generate next-generation biotherapeutics. It focuses on srategies already used in approved drugs and drugs that are in clinical development. These strategies include those aimed at increasing the hydrodynamic radius of the biotherapeutic and strategies which further implement recycling by the neonatal Fc receptor (FcRn).
Half-life extension strategies have become an integral part of development for many biotherapeutics. A diverse set of these strategies is available for the fine-tuning of half-life and adaption to the intended treatment modality and disease. Currently, half-life extension is dominated by strategies utilizing albumin binding or fusion, fusion to an immunoglobulin Fc region and PEGylation. However, a variety of alternative strategies, such as fusion of flexible polypeptide chains as PEG mimetic substitute, have reached advanced stages and offer further alternatives for half-life extension.
许多已批准或正在开发的生物治疗药物半衰期较短，需要频繁应用才能在较长时间内维持治疗浓度。实施半衰期延长策略可以生成半衰期更长、药代动力学和药效学特性改善的长效治疗药物。
本文综述了过去几年开发的不同半衰期延长策略及其在生成下一代生物治疗药物中的应用。重点介绍了已在批准药物和临床开发药物中应用的策略。这些策略包括旨在增加生物治疗药物流体力学半径的策略以及进一步利用新生 Fc 受体（FcRn）进行循环利用的策略。
半衰期延长策略已成为许多生物治疗药物开发的重要组成部分。有多种半衰期延长策略可用于微调半衰期并适应预期的治疗方式和疾病。目前，半衰期延长主要依赖于利用白蛋白结合或融合、与免疫球蛋白 Fcγ 区融合和聚乙二醇化的策略。然而，各种替代策略，如融合柔性多肽链作为聚乙二醇模拟物替代物，已经进入高级阶段，为半衰期延长提供了更多选择。
