Driven by high doses and a growing market, pressure to improve productivity and reduce cost of monoclonal antibody manufacturing processes has fueled the development of alternative expressions systems such as bacteria, yeast, filamentous fungi and transgenics.

Therapeutic function of many therapeutic proteins is influenced by N-linked glycosylation, which is dictated by a combination the expression host and culture conditions. For example, all currently approved monoclonal antibodies are produced in mammalian cells with N-linked glycan structures similar but not identical to their human equivalents.

Here we will present some of the genetic and metabolic engineering approaches developed to re-engineer the secretory pathway of the methyltotrophic yeast P. pastoris.

For example, GlycoFi Inc. has established a glycoengineered yeast strain capable of producing greater than 1g/L of a fully assembled and functional monoclonal antibody in a readily scaleable process with highly uniform human N-linked glycans.

With the ability of yeast systems to express full length antibodies, cytokines, serum proteins and other therapeutically relevant proteins, we expect yeast-based therapeutic protein expression to become a serious contender in any manufacturing strategy. At present no other expression system allows for this degree of flexibility and control of glycosylation at the preclinical and discovery phase, while allowing cost effective scale-up and manufacturing during commercial development.

This paper demonstrates the ability of the GlycoFi technology to produce therapeutic glycoproteins at commercially viable expression levels, with competitive development timelines.

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