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关于PD-1/PD-L1抗剂的更新专利审查 (2022年至今)
Wiktor Uzar1,2, Beata Kaminska1,2, Hubert Rybka1,2
1Faculty of Chemistry, Jagiellonian University, Cracow, Poland.
Expert opinion on therapeutic patents
|June 21, 2024
概括
针对编程细胞死亡配体1 (PD-L1) 的小分子抑制剂为抗体疗法提供了替代方案. 研究正在迅速推进,新的抑制剂在癌症治疗临床试验中显示出有前途.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 药用化学 医学化学
背景情况:
- 编程细胞死亡配体1 (PD-L1) 是一个关键的免疫检查点,使癌细胞能够逃避免疫监测.
- 针对PD-1/PD-L1的单克隆抗体 (mAbs) 在癌症治疗中取得了成功,但具有局限性,并可能导致与免疫相关的不良事件 (iRAE).
- 这刺激了研究小分子抑制剂PD-L1作为替代治疗策略的研究.
研究的目的:
- 从2022年至2023年审查在专利中报告的PD-L1的小分子和宏环抑制剂.
- 提供这些抑制剂的景观,包括它们的化学结构,活性和发育阶段.
- 评估这些抑制剂作为替代品或补充当前基于mAb的疗法的潜力.
主要方法:
- 世界知识产权组织和欧洲专利局 (2022-2023) 专利的系统审查.
- 对PD-L1抑制剂报告的化学结构,生物活性和临床开发状态的分析.
- 小分子和宏环抑制剂作用机制的比较.
主要成果:
- 最近的专利报告显示,越来越多的小分子和宏环抑制剂向PD-L1.
- 大多数小分子抑制剂通过诱导PD-L1二分化和随后的内化来起作用.
- 宏环作为蛋白质-蛋白质相互作用抑制剂通过竞争PD-L1/PD-1结合而起作用.
结论:
- 小分子抑制剂是针对PD-1/PD-L1通路的mAbs的一个有希望的替代品.
- 小分子和宏循环抑制剂采用不同的作用机制 (分离与竞争性抑制).
- 目前正在进行的临床试验对于确定这些新型PD-L1抑制剂的治疗潜力和临床实用性至关重要.
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