Accelerating and de‐risking CMC development with transposon‐derived manufacturing cell lines
Sowmya Rajendran, Sowmya Balasubramanian, Lynn Webster, Maggie Lee, Divya Teja Vavilala, N.V. Kulikov, Jessica Choi, Calvin Tang, Molly Hunter, Rebecca Wang, Harpreet Kaur, Surya Karunakaran, Varsha Sitaraman, Jeremy Minshull, Ferenc Boldog
Abstract
The development of highly productive, genetically stable manufacturing cell lines is on the critical path to IND filing for protein-based biologic drugs. Here, we describe the Leap-In Transposase® platform, a novel transposon-based mammalian (e.g., Chinese hamster ovary) cell line development system that produces high-titer stable pools with productivity and product quality attributes that are highly comparable to clones that are subsequently derived therefrom. The productivity distributions of clones are strongly biased toward high producers, and genetic and expression stability is consistently high. By avoiding the poor integration rates, concatemer formation, detrimental transgene recombination, low average expression level, unpredictable product quality, and inconsistent genetic stability characteristic of nonhomologous recombination methods, Leap-In provides several opportunities to de-risk programs early and reduce timelines and resources.