194g Consistent Production of Immunoglycoproteins of Higher Adcc Activity by Controlling Fucosylation In Cho Cells

Vijay Yabannavar, Brian Albarran, Jackie McGourty, and Richard Lowe. Trubion Pharmaceuticals, 2401 4th Avenue, Suite 1050, Seattle, WA 98121

In many immunoglycoproteins (including antibodies) used as biopharmaceuticals, increased ADCC activity is highly desirable. The extent of fucosylation in N-linked glycosylation has a major influence on ADCC activity. Unfortunately, it is reported that the extent of fucosylation varies significantly in a typical cell culture process. Here we report our discovery of the factors that influence the fucosylation in the production of immunoglycoproteins. Using this knowledge, we demonstrate a new system to make more potent immunoglycoproteins consistently. With the use of LC-MS and ADCC (and CD16 binding) assays, we have correlated the structure-ADCC activity relationships for the immunoglycoproteins.