Synthesis, purification and analysis of PEGylated proteins using membrane based techniques

蛋白质生物制药，如单克隆抗体和干扰素，正越来越多地被用于 广泛的医疗应用，如癌症治疗，心脏病，多发性硬化症和病毒感染的治疗。蛋白质药物具有主要的稳定性、治疗效果和免疫原性问题，其中一些可以通过PEG化来解决，PEG化是指将聚乙二醇（PEG）连接到蛋白质上。几种聚乙二醇化的生物制药蛋白质已被FDA等监管机构批准，并已进入市场。由蛋白质PEG化产生的改善包括生物半衰期的增加（并且因此注射频率的降低），以及蛋白水解降解、免疫原性、疏水性和聚集倾向的降低。因此，拟议项目的总体目标是开发具有成本效益的聚乙二醇化生物制药膜基制造方法。对于非专利产品，这将导致产品成本降低，从而使更多人能够获得救命药物。

Protein biopharmaceuticals such as monoclonal antibodies and interferons are increasingly being used for a range of medical applications such as cancer therapy, and the treatment of cardiac diseases, multiple sclerosis and viral infections. Protein drugs have major stability, therapeutic effectiveness and immunogenicity problems, some of which can be addressed through PEGylation, which refers to the attachment of polyethylene glycol (PEG) to proteins. Several PEGylated biopharmaceutical proteins have been approved by regulatory agencies like the FDA and these have entered the market. The improvements resulting from protein PEGylation include an increase in biological half-life (and thereby decrease in the frequency of injections), and decrease in proteolytic degradation, immunogenicity, hydrophobicity and tendency to aggregate. The overall objective of the proposed project is therefore the development of cost-effective membrane-based manufacturing methods for PEGylated biopharmaceuticals. For generic products, this would lead to lower product cost and therefore wider access to life saving drugs.