Optimized antibodies that target CD19
Antibodies that target CD19, wherein the antibodies comprise at least one modification relative to a parent antibody, wherein the modification alters affinity to an FcyR or alters effector function as compared to the parent antibody, and methods of using the antibodies.
1. An antibody that binds CD19, said antibody comprising a heavy chain and a light chain, said heavy chain comprising a variable region having a CDR1 comprising SEQ ID NO: 132, a CDR2 comprising SEQ ID NO: 147, and a CDR3 comprising SEQ ID NO:116; and said light chain comprising a variable region having a CDR1 comprising SEQ ID NO: 120, a CDR2comprising SEQ ID NO:129, and a CDR3 comprising SEQ ID NO:130, wherein the heavy chain comprises an Fc domain comprising an amino acid substitution at position S239 and/or 1332, wherein the numbering is according to the EU index as in Kabat.
2. The antibody according to claim 1 , wherein said heavy chain variable region comprises SEQ ID NO: 40.
3. The antibody according to claim 1 , wherein said light chain variable region comprises SEQ ID NO: 58.
4. An antibody according to claim 1 , wherein said heavy chain comprises SEQ ID NO: 40 and said light chain sequence comprises SEQ ID NO: 58.
5. An antibody according to claim 1 , wherein the amino acid substitution is at position S239, wherein the numbering is according to the EU index as in Kabat.
6. An antibody according to claim 2 , wherein the amino acid substitution is at position S239, wherein the numbering is according to the EU index as in Kabat.
7. An antibody according to claim 3 , wherein the amino acid substitution is at position S239, wherein the numbering is according to the EU index as in Kabat.
8. An antibody according to claim 4 , wherein the amino acid substitution is at position S239, wherein the numbering is according to the EU index as in Kabat.
9. An antibody according to claim 5 , wherein the substitution is S239D.
10. An antibody according to claim 6 , wherein the substitution is S239D.
11. An antibody according to claim 7 , wherein the substitution is S239D.
12. An antibody according to claim 8 , wherein the substitution is S239D.
13. An antibody according to claim 1 , wherein the amino acid substitution is at position l332, wherein the numbering is according to the EU index as in Kabat.
14. An antibody according to claim 2 , wherein the amino acid substitution is at position l332, wherein the numbering is according to the EU index as in Kabat.
15. An antibody according to claim 3 , wherein the amino acid substitution is at position l332, wherein the numbering is according to the EU index as in Kabat.
16. An antibody according to claim 4 , wherein the amino acid substitution is at position l332, wherein the numbering is according to the EU index as in Kabat.
17. An antibody according to claim 13 , wherein the substitution is l332E.
18. An antibody according to claim 14 , wherein the substitution is l332E.
19. An antibody according to claim 15 , wherein the substitution is l332E.
20. An antibody according to claim 16 , wherein the substitution is l332E.
21. An antibody according to claim 1 , further comprising an Fc domain having amino acid substitutions S239D and l332E, wherein the numbering is according to the EU index as in Kabat.
22. An antibody according to claim 2 , further comprising an Fc domain comprising amino acid substitutions S239D and l332E, wherein the numbering is according to the EU index as in Kabat.
23. An antibody according to claim 3 , further comprising an Fc domain comprising amino acid substitutions S239D and l332E, wherein the numbering is according to the EU index as in Kabat.
24. An antibody according to claim 4 , further comprising an Fc domain comprising amino acid substitutions S239D and l332E, wherein the numbering is according to the EU index as in Kabat.
25. A composition comprising a plurality of glycosylated antibodies according to claim 1 , wherein about 80-100% of the glycosylated antibody in the composition comprises a mature core carbohydrate structure which lacks fucose.
26. A composition comprising a plurality of glycosylated antibodies according to claim 2 , wherein about 80-100% of the glycosylated antibody in the composition comprises a mature core carbohydrate structure which lacks fucose.
27. A composition comprising a plurality of glycosylated antibodies according to claim 3 , wherein about 80-100% of the glycosylated antibody in the composition comprises a mature core carbohydrate structure which lacks fucose.
28. A composition comprising a plurality of glycosylated antibodies according to claim 4 , wherein about 80-100% of the glycosylated antibody in the composition comprises a mature core carbohydrate structure which lacks fucose.
29. A pharmaceutical composition comprising an antibody according claim 1 and a pharmaceutically acceptable carrier.
30. A pharmaceutical composition comprising an antibody according claim 2 and a pharmaceutically acceptable carrier.
31. A pharmaceutical composition comprising an antibody according claim 3 and a pharmaceutically acceptable carrier.
32. A pharmaceutical composition comprising an antibody according claim 4 and a pharmaceutically acceptable carrier.