Humanized anti-CD79b antibodies and immunoconjugates and methods of use
The present invention is directed to anti-CD79b antibodies with specific hypervariable region sequences in the heavy and light chain variable domains as enumerated in the SEQ ID NOs described herein.
1. An anti-CD79b antibody comprising the following hypervariable region (HVR) sequences:
(i) HVR-L1 comprising sequence A1-A16, wherein A1-A16 is KSSQSLLDSDGKTYLN (SEQ ID NO: 59);
(ii) HVR-L2 comprising sequence B1-B7, wherein B1-B7 is LVSKLDS (SEQ ID NO: 60);
(iii) HVR-L3 comprising sequence C1-C9, wherein C1-C9 is FQGTHFPFT (SEQ ID NO: 79);
(iv) HVR-H1 comprising sequence D1-D10, wherein D1-D10 is GYTFTSYWMN (SEQ ID NO: 62);
(v) HVR-H2 comprising sequence E1-E18, wherein E1-E18 is GMIDPSDSETHYNHIFKD (SEQ ID NO: 63); and
(vi) HVR-H3 comprising sequence F1-F6, wherein F1-F6 is ARNLYL (SEQ ID NO: 64).
2. The antibody of claim 1 , wherein the antibody is humanized.
3. The antibody of claim 1 , wherein at least a portion of the framework sequence is a human consensus framework sequence.
4. The antibody of any one of claims 1 , and 2 - 3 comprising human κ subgroup 1 consensus framework sequence.
5. The antibody of any one of claims 1 , and 2 - 3 comprising heavy chain human subgroup III consensus framework sequence.
6. The antibody of claim 5 wherein the framework sequence comprises a substitution at position 71, 73 and/or 78.
7. The antibody of claim 6 wherein said substitution is R71A, N73T and/or L78A.
8. The antibody of claim 1 , wherein the antibody is monovalent and comprises an Fc region.
9. The antibody of claim 1 , wherein the antibody comprises a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 12.
10. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 16.
11. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable domain comprising one, two, three or four framework amino acid sequences selected from SEQ ID NOs: 69, 70, 71 and 72.
12. The antibody of claim 1 , wherein the antibody comprises a light chain variable domain comprising one, two, three or four framework amino acid sequences selected from SEQ ID NOs: 65, 66, 67 and 68.
13. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 12.
14. The antibody of claim 1 or 13 , wherein the antibody binds to an epitope within a region of CD79b from amino acid 29-39 of SEQ ID NO: 2 or amino acid 1-11 of SEQ ID NO: 78.
15. The antibody of claim 1 or 13 , wherein the CD79b is expressed on the surface of a cell.
16. The antibody of claim 15 , wherein the cell is a B cell.
17. The antibody of claim 15 , wherein the B cell is associated with a B cell proliferative disorder.
18. The antibody of claim 17 , wherein the B cell proliferative disorder is a cancer.
19. The antibody of claim 18 , wherein the B cell proliferative disorder is selected from lymphoma, non-Hodgkins lymphoma (NHL), aggressive NHL, relapsed aggressive NHL, relapsed indolent NHL, refractory NHL, refractory indolent NHL, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, leukemia, hairy cell leukemia (HCL), acute lymphocytic leukemia (ALL), and mantle cell lymphoma.
20. The antibody of claim 1 or 13 , wherein the antibody is a monoclonal antibody.
21. The antibody of claim 20 , wherein the antibody is humanized.
22. A composition comprising the antibody of any of one of claims 1 and 13 .
23. The composition of claim 22 , wherein the composition comprises a carrier.