ABSTRACT:The IgG4 isotype antibody is a potential candidate for immunotherapy when reduced effector functions are desirable. However, antigen binding fragment (Fab) arm exchange leads to functional monovalency with potentially reduced therapeutic efficacy. Mutagenesis studies suggested that the CH3 domain and not the core hinge is dominantly involved in in vivo molecular processing. This work investigated whether stabilization of the core hinge of a therapeutic IgG4 antibody by mutation of Ser228 to Pro ( Since the first approval of a therapeutic monoclonal antibody in 1986, more than 20 therapeutic antibodies were approved in the United States, and over 200 therapeutic monoclonal antibodies (mAb) were undergoing clinical evaluation in (Reichert, 2008. Therapeutic mAbs have become an increasingly important class of therapeutic compounds in a variety of diseases. A number of technologies have been successfully used to engineer mAbs (Lonberg, 2008). Of the 21 approved therapeutic mAbs, the majority (15) are of the IgG1 isotype, whereas three mAbs are IgG2 antibodies and three are IgG4 or hybrid IgG2/4 antibodies (Reichert, 2008).

No abstract

No abstract

No abstract

No abstract

The IC assay allows a reliable ADA detection in matrices with high drug concentrations, such as ocular fluids.

No abstract

The hsFcγRI-based ADA assay can serve as alternative screening assay or as orthogonal confirmation method for preclinical and clinical immunogenicity testing of IgG therapeutics lacking Fc effector functions.