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 Fc domain; and
ii) a single chain FIT region (scFv) that binds CD3 comprising 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;
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 Fc domain; and
c) a light chain,
wherein said first variable heavy chain comprises a vhCDR1 having the amino acid sequence of SEQ ID NO:411; a vhCDR2 having the amino acid sequence of SEQ ID NO: 413; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 417, and
wherein said variable light chain comprises a v1CDR1 having the amino acid sequence of SEQ ID NO: 420; a v1CDR2 having the amino acid sequence of SEQ ID NO: 425; and a v1CDR3 having the amino acid sequence of SEQ ID NO: 433.
2. The heterodimeric antibody according to claim 1 , wherein said first variable heavy chain has the amino acid sequence of SEQ ID NO: 397 and said variable light chain has the amino acid sequence of SEQ ID NO: 398.
3. The heterodimeric antibody according to claim 1 , wherein said charged scFv linker is a positive charged linker.
4. The heterodimeric antibody according to claim 2 , wherein said charged scFv linker is a positive charged linker.
5. The heterodimeric antibody according to claim 1 , wherein said charged scFv linker is a negatively charged linker.
6. The heterodimeric antibody according to claim 2 , wherein said charged scFv linker is a negatively charged linker.
7. The heterodimeric antibody of claim 1 , wherein said first and second Fc domains are variant Fc domains as compared to a parent Fc polypeptide.
8. The heterodimeric antibody of claim 7 , wherein said parent Fc polypeptide is selected from the group consisting of a human IgG1, IgG2 and IgG4 Fc polypeptide.
9. The heterodimeric antibody of claim 2 , wherein said first and second Fc domains are variant Fc domains as compared to a parent Fc polypeptide.
10. The heterodimeric antibody of claim 9 , wherein said parent Fc polypeptide is selected from the group consisting of a human IgG1, IgG2 and IgG4 Fc polypeptide.
11. The heterodimeric antibody of claim 1 , wherein said charged scFv linker comprises SEQ ID NO: 472.
12. The heterodimeric antibody of claim 2 , wherein said charged scFv linker comprises SEQ ID NO: 472.
13. 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 CD3 comprising a first variable heavy chain comprising SEQ ID NO: 397, a variable light chain comprising SEQ ID NO: 398 and a charged scFv linker comprising SEQ ID NO: 472, wherein said charged scFv linker covalently attaches said first variable heavy chain and said variable light chain;
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.
14. The heterodimeric antibody of claim 13 , wherein said first and second Fc domains are variant Fc domains as compared to a parent Fc polypeptide.
15. The heterodimeric antibody of claim 14 , wherein said parent Fc polypeptide is selected from the group consisting of a human IgG1, IgG2 and IgG4 Fc polypeptide.