Abstract
This patent describes the generation of a recombinant monoclonal antibody (mAb) with specificity for human E-selectin. The novelty lies in the modification of the immunoglobulin to a 'neutral isotype' which is unable to bind IgG-Fc receptors (FcR) or activate complement. Furthermore, the engineered immunoglobulin contains a modified hinge region which results in more stable dimeric antibody molecules with prolonged duration of circulation in vivo. These modifications are considered to be beneficial for the intended use of the anti-E-selectin mAb as a therapeutic agent to inhibit leukocyte adhesion to endothelium in inflamed tissues. The principles of the approach could be extended to other antibodies for which neutral effector function and prolonged circulation time are desirable.