Anti-CD79b antibodies and methods of use
The invention provides anti-CD79b antibodies and methods of using the same.
1. An isolated anti-CD79b antibody, wherein the antibody comprises a CD79b binding domain comprising the following six hypervariable regions (HVRs):
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 5;
(b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 8;
(c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9;
(d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10;
(e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11; and
(f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 12.
2. The anti-CD79b antibody of claim 1 , wherein the CD79b binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 3;
(b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 6;
(c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9;
(d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10;
(e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11; and
(f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 12.
3. The anti-CD79b antibody of claim 1 , wherein the CD79b binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SEQ ID NO: 4;
(b) an HVR-H2 comprising the amino acid sequence of SEQ ID NO: 7;
(c) an HVR-H3 comprising the amino acid sequence of SEQ ID NO: 9;
(d) an HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10;
(e) an HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11; and
(f) an HVR-L3 comprising the amino acid sequence of SEQ ID NO: 12.
4. The anti-CD79b antibody of claim 2 , comprising (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:17, 21, 23, 25, 27 or 29; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:18, 22, 24, 26, 28, or 30; or (c) a VH sequence as in (a) and a VL sequence as in (b).
5. The anti-CD79b antibody of claim 3 , comprising a VH sequence of SEQ ID NO: 17, 21, 23, 25, 27 or 29.
6. The anti-CD79b antibody of claim 3 , comprising a VL sequence of SEQ ID NO: 18, 22, 24, 26, 28, or 30.
7. The anti-CD79b antibody of claim 3 , comprising (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:19; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:20; or (c) a VH sequence as in (a) and a VL sequence as in (b).
8. The anti-CD79b antibody of claim 3 , comprising a VH sequence of SEQ ID NO:19.
9. The anti-CD79b antibody of claim 8 , comprising a VL sequence of SEQ ID NO:20.
10. The anti-CD79b antibody of claim 1 , wherein the CD79b binding domain binds to SEQ ID NO:63.
11. The anti-CD79b antibody of claim 10 , wherein the CD79b binding domain binds human CD79b with a Kd as a dual arm, bivalent IgG antibody of less than about 25 nM less than about 10 nM or less than about 5 nM.
12. The antibody of claim 11 wherein the CD79b binding domain binds human CD79b binds a B cell at an EC 50 in a monovalent format of less than about 1.5 ug/mL, less than about 1 ug/mL, less than about 0.75 ug/mL, less than about 0.5 ug/mL or less than 0.25 ug/mL.
13. The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody is a monoclonal, human, humanized, or chimeric antibody.
14. The anti-CD79b antibody of claim 13 , wherein the anti-CD79b antibody is an IgG antibody.
15. The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody is an antibody fragment that binds CD79b.
16. The anti-CD79b antibody of claim 15 , wherein the anti-CD79b antibody fragment is a Fab, Fab′-SH, Fv, scFv, and/or (Fab′) 2 fragment.
17. The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody is a full-length antibody.
18. The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody comprises an aglycosylation site mutation.
19. The anti-CD79b antibody of claim 18 , wherein the aglycosylation site mutation is a substitution mutation.
20. The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody comprises reduced effector function.
21. The anti-CD79b antibody of claim 1 , wherein the anti-CD79b antibody comprises a substitution mutation is at amino acid residue N297, L234, L235, and/or D265 according to EU numbering.
22. The anti-CD79b antibody of claim 21 , wherein the substitution mutation is selected from the group consisting of N297G, N297A, L234A, L235A, and D265A according to EU numbering.
23. The anti-CD79b antibody of claim 21 , wherein the antibody comprises an N297G substitution mutation at amino acid residue 297 according to EU numbering.
24. An isolated nucleic acid encoding the anti-CD79b antibody of claim 1 .
25. A vector comprising the isolated nucleic acid of claim 24 .
26. A host cell comprising the vector of claim 25 .
27. A method of producing an anti-CD79b antibody, the method comprising culturing the host cell of claim 26 in a culture medium.
28. An immunoconjugate comprising the anti-CD79b antibody of claim 1 and a cytotoxic agent.
29. A pharmaceutical composition comprising the anti-CD79b antibody of claim 1 .
30. A method of treating or delaying the progression of a cell proliferative disorder comprising cells that express CD79b or an autoimmune disorder comprising cells that express CD79b in a subject in need thereof, the method comprising administering to the subject the anti-CD79b antibody of claim 1 .
31. A method of enhancing immune function in a subject having a cell proliferative disorder comprising cells that express CD79b or an autoimmune disorder comprising cells that express CD79b, the method comprising administering to the subject an effective amount of the anti-CD79b antibody of claim 1 .