Physicochemical characterization of Remsima.
Physicochemical characterization of Remsima.
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作者：
Jung SK;Lee KH;Jeon JW;Lee JW;Kwon BO;Kim YJ;Bae JS;Kim DI;Lee SY;Chang SJ
Remsima®（英夫利昔单抗）最近在欧盟和韩国被批准为世界上第一个生物仿制药单克隆抗体（mAb）。为了实现这一目标，我们对 Remsima® 与 Remicade® 进行了广泛的物理化学表征，以证明两种分子之间高度相似的特性。大量最先进的分析表明，与原始产品相比，Remsima® 具有相同的初级结构以及无法区分的高阶结构。 Remsima® 的单体和骨料含量也与 Remicade® 相当。就电荷异构体而言，尽管观察到 Remsima® 含有比原始抗体略少的碱性变体，但差异主要是由于 C 端赖氨酸的存在。另一方面，这种赖氨酸被发现在体外和体内的血清中被快速剪切，表明它对药物的生物效力或安全性没有影响。对抗体聚糖含量的分析显示了可比较的聚糖类型和分布。近期临床研究结果进一步证实两种抗体产品高度相似。基于这项研究以及之前的临床和非临床可比性研究，Remsima®在理化性质、功效和安全性方面可以被认为是与Remicade®高度相似的分子，最终被批准作为Remicade®的生物仿制药产品。
Remsima® (infliximab) was recently approved as the world's first biosimilar monoclonal antibody (mAb) in both the European Union and Korea. To achieve this, extensive physicochemical characterization of Remsima® in relation to Remicade® was conducted in order to demonstrate the highly similar properties between the two molecules. A multitude of state-of-the-art analyses revealed that Remsima® has identical primary as well as indistinguishable higher order structures compared with the original product. Monomer and aggregate contents of Remsima® were also found to be comparable with those of Remicade®. In terms of charge isoforms, although Remsima® was observed to contain slightly less basic variants than the original antibody, the difference was shown to be largely due to the presence of C-terminal lysine. On the other hand, this lysine was found to be rapidly clipped inside serum in vitro and in vivo, suggesting it has no effect on the biological potency or safety of the drug. Analysis of the glycan contents of the antibodies showed comparable glycan types and distributions. Recent results of clinical studies have further confirmed that the two antibody products are highly similar to each other. Based on this research as well as previous clinical and non-clinical comparability studies, Remsima® can be considered as a highly similar molecule to Remicade® in terms of physicochemical properties, efficacy, and safety for its final approval as a biosimilar product to Remicade®.