Amgen Inc., Process Development, Cambridge, Massachusetts 02141.
Amgen Inc., Process Development, Thousand Oaks, California 91320.
J Pharm Sci. 2018 May;107(5):1282-1289. doi: 10.1016/j.xphs.2018.01.002. Epub 2018 Jan 8.
Methionine oxidation in therapeutic antibodies can impact the product's stability, clinical efficacy, and safety and hence it is desirable to address the methionine oxidation liability during antibody discovery and development phase. Although the current experimental approaches can identify the oxidation-labile methionine residues, their application is limited mostly to the development phase. We demonstrate an in silico method that can be used to predict oxidation-labile residues based solely on the antibody sequence and structure information. Since antibody sequence information is available in the discovery phase, the in silico method can be applied very early on to identify the oxidation-labile methionine residues and subsequently address the oxidation liability. We believe that the in silico method for methionine oxidation liability assessment can aid in antibody discovery and development phase to address the liability in a more rational way.
治疗性抗体中的蛋氨酸氧化会影响产品的稳定性、临床疗效和安全性，因此在抗体发现和开发阶段解决蛋氨酸氧化的问题是很有必要的。虽然目前的实验方法可以识别易氧化的蛋氨酸残基，但这些方法的应用主要局限在开发阶段。我们展示了一种基于抗体序列和结构信息的可以预测易氧化的蛋氨酸残基的计算方法。由于在发现阶段就可以获得抗体序列信息，因此可以在早期应用计算方法来识别易氧化的蛋氨酸残基，并随后解决氧化的问题。我们相信，这种用于蛋氨酸氧化易损性评估的计算方法可以帮助在抗体发现和开发阶段以更合理的方式解决易损性问题。
