Articles
From 1 g/L To 3 g/L: Rapid Process Development For Phase II Clinical Production Of XmAbTM2513
August 5, 2009
•Poster: From 1 g/L To 3 g/L: Rapid Process Development For Phase II Clinical Production Of XmAbTM2513
By Marie M. Zhu, Jianxin Chen, Efren Carmona, Chris OBrien, Becky Tanamachi, Min Zhang, Scott Ross, and Kerry Koskie
XmAbTM2513, a monoclonal antibody achieved by application of Xencor's XmAb™ technology, exhibits significantly enhanced potency and efficacy against target lymphomas relative to the unmodified antibody, and is currently being moved into Phase I clinical study. To support pre-clinical and Phase I clinical studies for XmAb2513, we developed a CHO cell line and an animal-component-free (ACF) cell culture process that produces a final titer of 1-1.3 gram/L within 6 months. This process has been successfully scaled up at 250L- and 1200L-scale bioreactors. At Xencor, a continuous effort was made to improve production of XmAb2513 in order to meet an increasing demand of XmAb2513 for Phase II clinical studies and beyond. The cell culture process was optimized from three directions: basal medium, feed composition, and timing for temperature shift. With collaboration with the SAFC Biosciences, a new animalcomponent- free medium was developed in less than 4 months using the SAFC Biosciences' high-throughput screening technology and statistical Design-of-Experiment method. The new basal medium enhanced XmAb2513 production by 2-fold compared to the old basal medium. The antibody titer was further increased >2-fold by applying an ACF feed that was developed at Xencor. Earlier temperature shift prior to reaching a peak viable cell density shows benefit to enhancing expression of XmAb2513 although peak viable cell density is lower. Optimization in these three areas has led to a new cell culture process that produces > 3 g/L of XmAb2513. This presentation will elucidate the strategies applied in the process development and will report results obtained.
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