浅谈跟随性药物的创制

On the innovation of follow-on drugs

跟随性药物是首创性药物的后续与补充,是新药创制的一个重要方面。如今首创性药物优化的比较充分,专利覆盖的也比较广泛,致使研发跟随性药物的空间变小,加之药监部门要求新药的品质优于或不劣于同类已有的药物,风险大且后置于市场。研制跟随性药物可从两方面入手,一是从小分子化合物切入,有针对性地进行骨架变换和修饰,并在安全、疗效或方便使用等方面进行优化,以优于已有药物;另一是从大分子靶标入手,根据对作用机制的深化认识或靶标的变异而构建新结构,从微观的互补性特征或反应机制研发小分子。本文以成功的实例阐述跟随性药物的研制特征。

Follow-on drug approach is to follow-up and make-up of the innovation of pioneering drugs. Since the millennium new molecular entities（NME） have experienced ample optimization, and the patents have claimed in wide ranges, as well as the drug administration requires NME being superior or non-inferior to the existing drugs of the same class. These situations have made the space of follow-on drug innovation narrow and smaller than before. The follow-on drug approach can be concisely differentiated into two aspects： one is to start from the chemistry of small molecules, which are performed with a niche-targeting manipulation to optimize the safety, efficacy and（or） convenience for dose superior to the existing drugs; another proceeds with the macromolecule targets. Based on the knowledge of the mechanism of action or of target mutation, active compounds are constructed through complementary binding or by the reaction mechanism. In this article successful examples are briefly described to illustrate the features of follow-on drug approach.