Assessment of analytical techniques for characterization of crystalline clopidogrel forms in patent applications

The aim of this study was to evaluate two important aspects of patent applications of crystalline forms of drugs: (i) the physicochemical characterization of the crystalline forms; and (ii) the procedure for preparing crystals of the blockbuster drug clopidogrel. To this end, searches were conducted using online patent databases. The results showed that: (i) the majority of patent applications for clopidogrel crystalline forms failed to comply with proposed Brazilian Patent Office guidelines. This was primarily due to insufficient number of analytical techniques evaluating the crystalline phase. In addition, some patent applications lacked assessment of chemical/crystallography purity; (ii) use of more than two analytical techniques is important; and (iii) the crystallization procedure for clopidogrel bisulfate form II were irreproducible based on the procedure given in the patent application.

本研究旨在评估药物晶型专利申请的两项关键要点：一是药物晶型的理化表征；二是重磅药物氯吡格雷（clopidogrel）的晶体制备流程。为此，本研究通过在线专利数据库开展了检索工作。研究结果显示：(i) 绝大多数氯吡格雷晶型专利申请未能符合巴西专利局（Brazilian Patent Office）提出的相关指南要求，主要原因是用于表征晶相的分析技术数量不足；此外，部分专利申请未对化学/晶体学纯度进行评估；(ii) 采用两种及以上分析技术进行表征至关重要；(iii) 根据专利申请中记载的制备流程，硫酸氢氯吡格雷晶型II（clopidogrel bisulfate form II）的结晶步骤无法实现重复制备。