The Sweeping Antibody® is a recycling antibody that has been further engineered to bind to FcRn at neutral pH. When conventional antibodies against a soluble antigen are administered, a stable antigen-antibody complex is formed which often persists in plasma. This is because the soluble antigen remains tightly bound to the antibody after internalisation, and the antigen-antibody complex is recycled into circulation by the neonatal FcRn receptor in the endosome. As the recycled antigen does not reach the lysosome for degradation, this leads to an accumulation of the antigen in antibody bound form in the plasma, and in some cases, the concentration of antigen-antibody complexes can accumulate more than 1000-fold. A large amount of antibody is therefore required to ensure complete blockade of highly accumulated antigen.
This problem can be overcome by Chugai’s proprietary SMART-Ig sweeping Antibody technology. This enhances the uptake of antibody-bound soluble antigen into cells, accelerating antigen degradation by ‘sweeping’ the antigen from plasma. With these characteristics, a sweeping antibody can be administered in smaller doses with a longer dosing interval and can eliminate antigens present in large amounts in plasma that cannot be antagonised by conventional antibodies. Furthermore, even if sweeping antibodies do not completely block an antigen’s activity, they can still be effective by directly eliminating antigens from plasma. Moreover, by modulating the binding affinity for FcRn, the rate of antigen clearance by the sweeping antibody can be tailored to meet the therapeutic requirements of disease treatment. These properties confer the SMART-Ig technology with tremendous potential in a wide range of applications.