Application of mathemtical model for production recombinant antibody 14D9 by Nicotiana tabacum cel suspension culture

PATRICIA MARCONI

Jornada; Progreso en fermentaciones procariotas; 2013

Fundación Cassará, CONICET, Lobov SA

One of the bottlenecks in biopharming is the scalability and modeling of batch cultures at bench scale, largely because bioreactors and mathematical models were originally designed for microbe cultures. Thus, a mathematical model that acknowledges kinetic and growth processes, basic aspect of cell structure, and physiology and productivity is needed. We proposed a new combination of structured and unstructured mathematical models for cell cultivation in fed-batch and chemostat. In the model, the ratio of maintenance energy to energy consumed for biomass growth or the precise rate of accumulation of stable or nondividing cells is taken into account. The model is based on separating the biomass into two main groups: dividing and nondividing cells (using a combination of statistical data and qualitative causal assumptions). The age structure of cell population varies and characterizing these variations are fundamental for the structured model. We have scaled the full antibody Ab-KDEL expressed in N. tabacum cell suspension from a 225 mL-Erlenmeyer flask to 2L-bioreactor and applied the above mentioned mathematical model in order to estimate and predict the growth rate of cell cultures and the expression of the recombinant protein. Under the proposed model two inoculum sizes were used in order to obtain experimental data, specific growth rates and productivity, which allow the analysis of the prediction under different conditions.