Heterodimeric proteins
The invention provides novel heterodimeric proteins including heterodimeric antibodies.
1. A heterodimeric antibody comprising:
a) a first heavy chain comprising:
i) a first variant Fc domain; and
ii) a single chain Fv region (scFv) that binds a first antigen, wherein said scFv region comprises a first variable heavy chain, a variable light chain and a charged scFv linker, wherein said charged scFv linker covalently attaches said first variable heavy chain and said variable light chain; and
b) a second heavy chain comprising a VH-CH1-hinge-CH2-CH3 monomer, wherein VH is a second variable heavy chain and CH2-CH3 is a second variant Fc domain; and
c) a light chain;
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. The heterodimeric antibody of claim 1 , wherein the charged linker is a positive charged linker.
3. The heterodimeric antibody of claim 1 , wherein the charged linker has the amino acid sequence SEQ ID NO: 450.
4. The heterodimeric antibody of claim 1 , wherein said first and second variant Fc domains are selected from the group consisting of variant human IgG1, IgG2 and IgG4 variant Fc domains.
5. The heterodimeric antibody of claim 2 , wherein said first and second variant Fc domains are selected from the group consisting of variant human IgG1, IgG2 and IgG4 variant Fc domains.
6. The heterodimeric antibody of claim 3 , wherein said first and second variant Fc domains are selected from the group consisting of variant human IgG1, IgG2 and IgG4 variant Fc domains.
7. The heterodimeric antibody of claim 1 wherein said first and second variant Fc domains are variant human IgG1 Fc domains.
8. The heterodimeric antibody of claim 2 wherein said first and second variant Fc domains are variant human IgG1 Fc domains.
9. The heterodimeric antibody of claim 3 wherein said first and second variant Fc domains are variant human IgG1 Fc domains.