改变培养条件控制cho细胞中表达的igg1融合蛋白聚集.pdfVIP

Process Biochemistry 47 (2012) 69–75 Contents lists available at SciVerse ScienceDirect Process Biochemistry j o u r n a l h o m e p ag e: w w w. elsev /locate/proc bio Identification of cell culture conditions to control protein aggregation of IgG fusion proteins expressed in Chinese hamster ovary cells Ying Jing a , Michael Borys a , Samiksha Nayak b , Susan Egan a , Yueming Qian a , Shih-Hsie Pan a , Zheng Jian Li a,∗ a Biologics Process and Product Development, Technical Operations, Bristol-Myers Squibb Company, East Syracuse, NY 13057, USA b Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA a r t i c l e i n f o a b s t r a c t Article history: The presence of aggregated forms of proteins can be problematic for therapeutics due to the potential for Received 17 May 2011 immunogenic and pharmacokinetic issues. Although downstream processing can remove the aggregated Received in revised form forms, inhibiting aggregate formation upstream during the cell culture stage could reduce the burden on 18 September 2011 downstream processing and potentially improve process yields. This study first examined the effects of Accepted 10 October 2011 environmental factors (temperature, pH, and dissolved oxygen) and medium components (bivalent cop- Available online 18 October 2011 per ion, cysteine, and cystine) on the aggregation of two different recombinant fusion proteins expressed