Provided herein are heteromultimer constructs with reduced or silenced
effector function. In an embodiment is provided a heteromultimer construct comprising an IgG Fc construct having a first and a second Fc polypeptide, each Fc polypeptide comprising a modified lower
hinge region wherein: the modified lower
hinge region of said first Fc polypeptide comprises at least one
amino acid modification, the modified lower
hinge region of said second Fc polypeptide comprises at least one
amino acid modification which is different from at least one
amino acid modification of said first Fc polypeptide, and the IgG Fc construct displays reduced binding to all Fc Gamma receptors and to C1q
protein as compared to a corresponding parent IgG Fc construct. Also provided are methods of producing such heteromultimer constructs, and methods of reducing ADCC for an
antibody construct by reducing
effector function.