LC-MS对奥马珠单抗与其生物类似物CMAB007的分析与结构特征

Structural characterization and analysis of Omalizumab and its biosimilar CMAB007 by LC-MS

摘要:

哮喘是当今世界威胁公共健康的最主要的慢性肺部疾病，作为治疗中重度和难治性哮喘的特效药奥马珠单抗治疗费用相对昂贵，生物类似药CMAB007的研制可以降低治疗费用。本研究用质谱分析一种奥马珠单抗生物类似药CMAB007与原研药的一致性，分别从氨基酸分析、肽图、N/C端序列，还原质谱，寡糖含量，N 糖分析等层面对CMAB007和奥马珠单抗进行了系统的比对研究，为进一步临床研究打下基础。结果表明CMAB007和奥马珠单抗氨基酸序列一致，赖氨酸剪切也基本一致，带唾液酸修饰糖形和带核心岩藻糖形比例相近，高甘露糖形比例差异不大，CMAB007略低于奥马珠单抗。因此CMAB007满足生物类似药在结构比对上一致性的要求，有望成为国内首先上市的重组抗人IgE单克隆抗体药物。

Abstract:

We compared the similarity of Omalizumab (Xolair; a humanized anti-immunoglobulin E monoclonal antibody) and it’s biosimilar CMAB007. An in depth characterization of a candidate biosimilar was carried out using a systematic approach, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. CMAB007 and Omalizumab had the same primary structure and exhibited almost the same content of C-terminal lysine variants. The types of detected free oligosaccharides were very similar, such as sialylation, fucosylation and high mannose types. CMAB007 could be considered as a highly similar molecular to Omalizumab and expected to be the first humanized anti-immunoglobulin E monoclonal antibody drug in China.