Heterodimeric proteins
In one aspect, the present invention provides heterodimeric antibodies comprising a first monomer comprising a first heavy chain constant domain comprising a first variant Fc domain and a first antigen binding domain and a second monomer comprising a second heavy chain constant domain comprising a second variant Fc domain and a second antigen binding domain. In an additional aspect the heterodimeric antibody comprises a first monomer comprising a heavy chain comprising a first Fc domain and a single chain Fv region (scFv) that binds a first antigen, wherein the scFv comprises a charged scFv linker. The heterodimeric antibody further comprises a second monomer comprising a first heavy chain comprising a second Fc domain and a first variable heavy chain and a first light chain.
1. A heterodimeric antibody comprising:
a) a first monomer comprising:
i) scFv means for binding human CD3;
ii) a first variant Fc domain; and
b) a second monomer comprising VH-CH1-hinge-CH2-CH3, wherein CH2-CH3 is a second variant Fc domain; and
c) a light chain comprising VL-CL;
wherein said second variant Fc domain comprises amino acid substitutions N208D/Q295E/N384D/Q418E/N421D, wherein said first and second variant Fc domains each comprise amino acid substitutions E233P/L234V/L235A/G236del/S267K; and wherein said first variant Fc domain comprises amino acid substitutions S364K/E357Q and second variant Fc domain comprises amino acid substitutions L368D/K370S, wherein numbering is according to the EU index as in Kabat.
2. A heterodimeric antibody according to claim 1 wherein said first and second variant Fc domains further comprise the amino acid substitutions M428L/N434S.
3. A heterodimeric antibody according to claim 1 wherein said first and second variant Fc domains further comprise the amino acid substitutions M428L/N434A.