Biological drugs or biopharmaceuticals off patent open a large market for biosimilars and biobetters, follow-on biologics. Biobetters, in particular, are new drugs designed from existing ones with improved properties such as higher selectivity, stability, half-life and/or lower toxicity/immunogenicity. Glycosylation is one of the most used strategies to improve biological drugs, nonetheless bioconjugation is an additional alternative and refers to the covalent attachment of polymers to biological drugs. Extensive research on novel polymers is underway, nonetheless PEGylation is still the best alternative with the longest clinical track record. Innovative trends based on genetic engineering techniques such as fusion proteins and PASylation are also promising. In this review, all these alternatives were explored as well as current market trends, legislation and future perspectives.

非专利生物药物或生物药物为生物仿制药和生物更好、后续生物制剂打开了巨大的市场。特别是，Biobetter 是从现有药物设计的新药物，具有更高的选择性、稳定性、半衰期和/或更低的毒性/免疫原性等特性。糖基化是改进生物药物最常用的策略之一，但生物偶联是另一种选择，是指聚合物与生物药物的共价连接。对新型聚合物的广泛研究正在进行中，但聚乙二醇化仍然是临床记录最长的最佳替代方案。基于融合蛋白和PASylation等基因工程技术的创新趋势也很有前景。在本次审查中，所有这些替代方案都是 探索以及当前的市场趋势、立法和未来前景。