Optimized anti-CD3 variable regions
The present invention is directed to optimized anti-CD3 variable sequences for use in a variety of bispecific formats, including those that utilize scFv components. The invention further relates to nucleic acids encoding for the polypeptide, to vectors comprising the same and to host cells comprising the vector. In another aspect, the invention provides for a pharmaceutical composition comprising the mentioned polypeptide and medical uses of the polypeptide.
1. A composition comprising an anti-CD3 binding domain, said anti-CD3 binding domain comprising:
a) a variable heavy chain comprising 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
b) a variable light chain comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 420; a vlCDR2 having the amino acid sequence of SEQ ID NO: 425; and avlCDR3 having the amino acid sequence of SEQ ID NO: 433.
2. A composition comprising an anti-CD3 binding domain, said anti-CD3 binding domain comprising a variable heavy chain having the amino acid sequence of SEQ ID NO: 397 and a variable light chain having the amino acid sequence of SEQ ID NO: 398.
3. A composition comprising an anti-CD3 binding domain, said anti-CD3 binding domain comprising:
a) a variable heavy chain comprising a vhCDR1, vhCDR2 and vhCDR3 of a variable heavy chain having the amino acid sequence SEQ ID NO:397; and
b) a variable light chain comprising a vlCDR1, vlCDR2 and vlCDR3 of a variable light chain having the amino acid sequence of SEQ ID NO:398.
4. A composition according to claim 1 , wherein said anti-CD3 binding domain further comprises a scFv linker that covalently attaches said variable heavy chain and variable light chain to form an scFv domain.
5. A composition according to claim 2 , wherein said anti-CD3 binding domain further comprises a scFv linker that covalently attaches said variable heavy chain and variable light chain to form an scFv domain.
6. A composition according to claim 3 , wherein said anti-CD3 binding domain further comprises a scFv linker that covalently attaches said variable heavy chain and variable light chain to form an scFv domain.
7. A composition according to claim 4 , wherein said composition further comprises an Fc domain selected from the group consisting of a human IgG1, IgG2 and IgG4 Fc domain.
8. A composition according to claim 7 , wherein said Fc domain is a variant Fc domain selected from the group consisting of a human IgG1, IgG2 and IgG4 variant Fc domain.
9. A composition according to claim 5 , wherein said composition further comprises an Fc domain selected from the group consisting of a human IgG1, IgG2 and IgG4 Fc domain.
10. A composition according to claim 9 , wherein said Fc domain is a variant Fc domain selected from the group consisting of a human IgG1, IgG2 and IgG4 variant Fc domain.
11. A composition according to claim 6 , wherein said composition further comprises an Fc domain selected from the group consisting of a human IgG1, IgG2 and IgG4 Fc domain.
12. A composition according to claim 11 , wherein said Fc domain is a variant Fc domain selected from the group consisting of a human IgG1, IgG2 and IgG4 variant Fc domain.
13. A composition according to claim 1 , wherein said anti-CD3 binding domain is a fragment antigen binding (Fab) domain.
14. A composition according to claim 2 , wherein said anti-CD3 binding domain is a fragment antigen binding (Fab) domain.
15. A composition according to claim 3 , wherein said anti-CD3 binding domain is a fragment antigen binding (Fab) domain.
16. A composition according to claim 1 , wherein said composition is an antibody comprising said anti-CD3 binding domain.
17. A composition according to claim 2 , wherein said composition is an antibody comprising said anti-CD3 binding domain.
18. A composition according to claim 3 , wherein said composition is an antibody comprising said anti-CD3 binding domain.