Early prediction of formulation behaviour for new antibody products

新抗体产品配方行为的早期预测

• 批准号: 2367694
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2367694
• 关键词: Early; prediction; formulation; behaviour; new

Antibody-based biologics such as monoclonal antibodies (mAbs) are a fast-growing segment of the biopharmaceutical industry due to their distinctive therapeutic potential. The global market for antibody-based therapeutics is forecasted to reach $114.6 billion by 2022 growing at a compound annual growth rate (CAGR) of 6.3% from 2017 to 2022 (Dewan, 2017). In contrast to traditional small molecule drugs, mAbs have high levels of specificity with low toxicity profiles, which drives their success in targeting previously untreatable indications (Keizer et al, 2010). Consequently, there has been a rise in research interest in developing novel mAb therapies and biosimilars.Formulation development remains a major challenge in mAb production as there is a high demand to formulate therapeutics economically and effectively for safe delivery to patients. The increased complexity of these large molecule makes them more unstable and prone to chemical and/or physical degradation, therefore requiring special handling and storage. Lyophilisation, or freeze drying is a common method used in industry to preserve chemical and biological properties of mAbs to sustain long-term stability and improve shelf life (Carpenter et al, 2002). Protein aggregation is a common problem that can occur at any stage of the manufacturing process up until drug administration. Not only can aggregation affect protein function and decrease product yield, it can also reduce the therapeutic half-life and cause immunogenic reactions in patients (Wang et al, 2007).Previous work at SPEL have uncovered the relationship between the Osmotic second virial coefficient (B22) obtained from self-interaction chromatography (SIC) and propensity of mAb aggregation (Hedberg et al, 2018). The aim of the project is to further investigate aggregation propensity of liquid and lyophilised biotherapeutics and understand the mechanisms of aggregation to help predict aggregation tendencies of novel mAbs. In addition to extensive structural characterisation, functionality will be investigated to assess biological activity and immunogenicity.

单克隆抗体 (mAb) 等基于抗体的生物制剂因其独特的治疗潜力而成为生物制药行业快速增长的部分。预计到 2022 年，全球抗体治疗市场将达到 1146 亿美元，2017 年至 2022 年复合年增长率 (CAGR) 为 6.3%（Dewan，2017）。与传统的小分子药物相比，mAb 具有高特异性和低毒性，这推动了它们成功地针对以前无法治疗的适应症（Keizer 等人，2010）。因此，人们对开发新型单克隆抗体疗法和生物仿制药的研究兴趣不断增加。制剂开发仍然是单克隆抗体生产中的一个主要挑战，因为对经济有效地配制治疗药物以安全地交付给患者的需求很高。这些大分子的复杂性增加使得它们更加不稳定并且容易发生化学和/或物理降解，因此需要特殊的处理和储存。冻干或冷冻干燥是工业上常用的方法，用于保存单克隆抗体的化学和生物特性，以维持长期稳定性并延长保质期（Carpenter 等，2002）。蛋白质聚集是一个常见问题，可能发生在生产过程的任何阶段直至给药。聚集不仅会影响蛋白质功能并降低产物产量，还会缩短治疗半衰期并引起患者免疫原性反应 (Wang et al, 2007)。 SPEL 之前的工作揭示了从自相互作用色谱 (SIC) 获得的渗透第二维里系数 (B22) 与 mAb 聚集倾向之间的关系 (Hedberg et al, 2018)。该项目的目的是进一步研究液体和冻干生物治疗药物的聚集倾向，并了解聚集机制，以帮助预测新型单克隆抗体的聚集倾向。除了广泛的结构表征外，还将研究功能性以评估生物活性和免疫原性。