An unstructured kinetic model of macromolecular metabolism in batch and fed-batch cultures of hybridoma cells producing monoclonal antibody

Growth profiles of the batch and fed-batch culture of hybridoma cells produ cing monoclonal antibody were simulated using an unstructured model. The mo del describes the production of cellular macromolecules and monoclonal anti body, the metabolism of glucose and glutamine with the production of lactat e and ammonia, and the profiles of cell growth in batch and fed-batch cultu re. Equations describing the cells arrested in G1 phase [T.I. Linardos, N. Kalogerakis, L.A. Behie, Biotechnol. Bioeng. 40 (1992) 359-368; E. Suzuki, D.F Ollis, Biotechnol. Bioeng. 34 (1989) 1398-1402] were included in this m odel to describe the increase of the specific antibody productivity in the near-zero specific growth rate, which was observed in the recent experiment s in fed-batch cultures of this study and the semi-continuous culture of hy bridoma cells [S. Reuveny, D. Velez, L. Miller, J.D. Macmillan, J. Immnol. Methods 86 (1986) 61-69]. This model predicted the increase of specific ant ibody production rate and the decline of the specific production rate of ce llular macromolecules such as DNA, RNA, protein, and polysaccharide in the late exponential and decline phase of batch culture and at lower specific g rowth rates in the fed-batch culture. (C) 2000 Elsevier Science S.A. All ri ghts reserved.