Challenge: Alpha1 AntiTrypsin (AAT) Production without human plasma
The therapeutic drug Alpha1 AntiTrypsin (AAT) is being used for replacement therapy for patients with AAT defiency. The AAT found in humans display a very specific bi-antennary non-fucosylated N-glycan profile, which is very different from the heterogenous N glycan profile from recombinant AAT produced in CHO cells. The recombinant AAT with non-natural glycosylation has a very short half-life in humans, and is therefore not suited for replacement therapy. As a consequence, all of the approved AAT therapies used for the treatment of AAT deficiency is derived from fractionated human plasma.
Solution: Stable CHO line with the right Glycan profile for production of AAT
Using our glycan engineered CHO cell lines, we have generated a stable clonal CHO cell line capable of expressing at least 1,4 g/L of AAT with the exact same glycan profile as the human derived AAT and as the approved therapeutic AAT. We have proven that the clone is stable over more than 60 generations and we have developed a scalable protein purification protocol and activity assays for the AAT. We have used the platform to generate a large number of AAT variants with improved oxidation and protease dependent degradation features.