用于延长生物制品半衰期的融合蛋白作为制造生物改良药的一种策略。
Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters.
作者信息
Strohl William R
机构信息
Janssen BioTherapeutics, Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson & Johnson, SH31-21757, 1400 Welsh and McKean Roads, PO Box 776, Spring House, PA, 19477, USA,
出版信息
BioDrugs. 2015 Aug;29(4):215-39. doi: 10.1007/s40259-015-0133-6.
Abstract
The purpose of making a "biobetter" biologic is to improve on the salient characteristics of a known biologic for which there is, minimally, clinical proof of concept or, maximally, marketed product data. There already are several examples in which second-generation or biobetter biologics have been generated by improving the pharmacokinetic properties of an innovative drug, including Neulasta(®) [a PEGylated, longer-half-life version of Neupogen(®) (filgrastim)] and Aranesp(®) [a longer-half-life version of Epogen(®) (epoetin-α)]. This review describes the use of protein fusion technologies such as Fc fusion proteins, fusion to human serum albumin, fusion to carboxy-terminal peptide, and other polypeptide fusion approaches to make biobetter drugs with more desirable pharmacokinetic profiles.
摘要
制造“生物优化药”生物制剂的目的是改进已知生物制剂的显著特性，对于这些特性，至少有临床概念验证，至多有上市产品数据。已经有几个例子表明，通过改善创新药物的药代动力学特性产生了第二代或生物优化药生物制剂，包括优保津（Neulasta）[重组人粒细胞刺激因子聚乙二醇化长效剂型，即新特罗（Neupogen，重组人粒细胞刺激因子）的长效剂型]和阿法达贝泊汀（Aranesp）[促红细胞生成素α（Epogen）的长效剂型]。本综述描述了蛋白质融合技术的应用，如Fc融合蛋白、与人血清白蛋白融合、与羧基末端肽融合以及其他多肽融合方法，以制造具有更理想药代动力学特征的生物优化药。
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