Purification of Modified Therapeutic Proteins Available on the Market: An Analysis of Chromatography-Based Strategies.
Purification of Modified Therapeutic Proteins Available on the Market: An Analysis of Chromatography-Based Strategies.
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DOI：
10.3389/fbioe.2021.717326
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发表时间：
2021
影响因子：
5.7
通讯作者：
Mayolo-Deloisa K
中科院分区：
文献类型：
--
作者：
Sánchez-Trasviña C;Flores-Gatica M;Enriquez-Ochoa D;Rito-Palomares M;Mayolo-Deloisa K
蛋白质具有固有的生物识别特性，长期以来一直被用作治疗各种临床适应症的治疗剂。通过与不同部分的共价附着对蛋白质进行修饰，改善了治疗药物的药代动力学特性、亲和力、稳定性，提供了防止蛋白质水解降解的保护，并延长了循环半衰期。目前，一些修饰的治疗性蛋白，包括聚乙二醇化、fc融合、脂化、白蛋白融合和糖基化蛋白，已经获得了监管部门的商业化批准。在其制造过程中，治疗剂的纯化步骤是决定性的，以确保最终产品的质量，有效性，效力和安全性。由于色谱方法的稳健性、选择性和高分辨率，这些方法被认为是治疗性蛋白质下游加工的金标准。此外，根据不同的修饰策略，蛋白质将遭受不同的物理化学变化，必须考虑确定纯化方法。本综述旨在深入分析目前市场上用于修饰治疗性蛋白的纯化方法，以了解所选策略成功的原因。重点放在色谱方法上，因为它们控制着制药行业的纯化过程。此外，为了讨论修饰类型如何强烈影响纯化策略，对比了三种不同修饰版本的凝血因子IX的纯化过程。
Proteins, which have inherent biorecognition properties, have long been used as therapeutic agents for the treatment of a wide variety of clinical indications. Protein modification through covalent attachment to different moieties improves the therapeutic’s pharmacokinetic properties, affinity, stability, confers protection against proteolytic degradation, and increases circulation half-life. Nowadays, several modified therapeutic proteins, including PEGylated, Fc-fused, lipidated, albumin-fused, and glycosylated proteins have obtained regulatory approval for commercialization. During its manufacturing, the purification steps of the therapeutic agent are decisive to ensure the quality, effectiveness, potency, and safety of the final product. Due to the robustness, selectivity, and high resolution of chromatographic methods, these are recognized as the gold standard in the downstream processing of therapeutic proteins. Moreover, depending on the modification strategy, the protein will suffer different physicochemical changes, which must be considered to define a purification approach. This review aims to deeply analyze the purification methods employed for modified therapeutic proteins that are currently available on the market, to understand why the selected strategies were successful. Emphasis is placed on chromatographic methods since they govern the purification processes within the pharmaceutical industry. Furthermore, to discuss how the modification type strongly influences the purification strategy, the purification processes of three different modified versions of coagulation factor IX are contrasted.
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