| abstract |
Provided herein are heavy chain constant regions (referred to as "modified heavy chain constant regions") or functionally equivalent fragments thereof relative to unmodified forms (i) of the same antibody enhances the biological properties of the antibody or (ii) reduces effector function. Exemplary modified heavy chain constant regions comprise one IgG2 hinge and three constant domains (i.e., CH1, CH2 and CH3 domains), wherein one or more of the constant region domains are of a non-IgG2 isotype (eg, IgG1, IgG3 or IgG4). The heavy chain constant region may comprise wild-type human IgG domain sequences or variants of these sequences. Also provided herein are methods for enhancing certain biological properties of an antibody comprising a non-IgG2 hinge, such as internalization, agonism, and antagonism, wherein the method comprises replacing the non-IgG2 hinge of the antibody with an IgG2 hinge. |