生物仿制药BAT1806/BIIB800与参比Tocilizumab的构效关系比较

IF 5.4 2区医学 Q1 IMMUNOLOGY

BioDrugs Pub Date : 2025-03-01 Epub Date: 2025-03-06 DOI:10.1007/s40259-024-00698-7

Yujie Liu, Jianhua Xie, Zhuxiang Li, Xiong Mei, Di Cao, Shengfeng Li, Linda Engle, Suli Liu, Hans C Ebbers, Cuihua Liu

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引用次数: 0

摘要

背景：tocilizumab的生物类似药BAT1806/BIIB800 （tofidef™/tocilizumab- bai）在综合比较分析评估中显示出与参考tocilizumab （TCZ）高度的分析和功能相似性。在TCZ方面，观察到一些属性的微小差异，本研究通过结构活性关系表征评估了这些差异的潜在影响。方法：利用一系列调查技术，进行了结构活性关系研究，以评估糖基化、糖基化、电荷变异、疏水性、氧化和脱酰胺差异。除糖基化外，BAT1806/BIIB800和TCZ（仅来自欧盟）各有一批进行了结构活性关系研究，其中糖基化使用了来自中国和美国的额外批次。结果：BAT1806/BIIB800的平均总糖化蛋白含量高于TCZ (10.08% vs 1.19%)；然而，生物活性，包括目标结合和功能效力，不受影响。胁迫诱导的BAT1806/BIIB800和TCZ糖基化也不影响产品的生物活性，尽管糖基化总量高达60%。BAT1806/BIIB800和TCZ在糖基化、电荷变异、疏水性、氧化和脱酰胺方面存在微小差异，但对白细胞介素-6受体结合、fc受体结合和效应器功能没有影响。在强制降解研究中，氧化和脱酰胺趋势在两种产品之间具有可比性。结论：对比BAT1806/BIIB800与TCZ的结构活性关系表征表明，BAT1806/BIIB800与参比TCZ的质量属性无相关差异。观察到的BAT1806/BIIB800和TCZ之间的差异对BAT1806/BIIB800没有功能影响。结果支持BAT1806/BIIB800与TCZ相似的结论。

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Comparative Structure Activity Relationship Characterization of the Biosimilar BAT1806/BIIB800 to Reference Tocilizumab.

Background: BAT1806/BIIB800 (Tofidence™/tocilizumab-bavi), a biosimilar of tocilizumab, demonstrated a high degree of analytical and functional similarity to reference tocilizumab (TCZ) in a comprehensive comparative analytical assessment. Minor differences with respect to TCZ were observed for some attributes and this study assessed the potential impact of these differences through structure activity relationship characterization.

Methods: Structure activity relationship studies were conducted to assess glycation, glycosylation, charge variants, hydrophobicity, oxidation, and deamidation differences, using a range of investigative techniques. Structure activity relationship studies were performed on one lot each of BAT1806/BIIB800 and TCZ (European Union sourced only) except for glycation, where additional lots sourced from China and the USA were used.

Results: Average total glycated protein content of BAT1806/BIIB800 was higher than TCZ (10.08% vs 1.19%); however, biological activity, including target binding and functional potency, was unaffected. Stress-induced glycation of BAT1806/BIIB800 and TCZ also did not affect the biological activity of the products despite up to 60% total glycation content. Minor differences were observed between BAT1806/BIIB800 and TCZ in glycosylation, charge variants, hydrophobicity, oxidation, and deamidation without a relevant impact on interleukin-6 receptor binding, Fc-receptor binding, and effector functions. In forced degradation studies, oxidation and deamidation trends were comparable between the two products.

Conclusions: Comparative structure activity relationship characterization of BAT1806/BIIB800 and TCZ indicated that there are no relevant differences in quality attributes between BAT1806/BIIB800 and reference TCZ. Observed differences between BAT1806/BIIB800 and TCZ had no functional impact on BAT1806/BIIB800. The results support the conclusion that BAT1806/BIIB800 is similar to TCZ.

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来源期刊

BioDrugs 医学-免疫学

CiteScore

12.60

自引率

2.90%

发文量

审稿时长

>12 weeks

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