IL-8 antibodies
One nonexclusive aspect provides molecules further improved from antibodies that can bind to antigens in an ion concentration-dependent manner. An alternative nonexclusive aspect provides safe and more advantageous Fc region variants that have decreased binding to pre-existing ADA. An alternative nonexclusive aspect provides novel IL-8 antibodies that are superior as pharmaceuticals.
1. An isolated anti-IL-8 antibody which comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:67, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:73, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:74, (d) HVR-LI comprising the amino acid sequence of SEQ ID NO:70, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:75, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:76.
2. The anti-IL-8 antibody of claim 1 , which is an IgG antibody.
3. The anti-IL-8 antibody of claim 2 , wherein the IgG antibody is IgG1, IgG2, IgG3 or IgG4.
4. The anti-IL-8 antibody of claim 3 , wherein the IgG antibody is IgG1.
5. The anti-IL-8 antibody of claim 1 , which comprises one or more amino acid substitutions selected from the group consisting of: L235R, G236R, S239K, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.
6. The anti-IL-8 antibody of claim 5 , which comprises amino acid substitution N434A according to EU numbering.
7. The anti-IL-8 antibody of claim 6 , which comprises amino acid substitutions of L235R, G236R, S239K, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.
8. The anti-IL-8 antibody of claim 6 , which comprises amino acid substitutions of L235R, G236R, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.
9. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 1 and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 5 and a pharmaceutically acceptable carrier.
11. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 6 and a pharmaceutically acceptable carrier.
12. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 7 and a pharmaceutically acceptable carrier.
13. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 8 and a pharmaceutically acceptable carrier.
14. An isolated anti-IL-8 antibody which comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:78 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:79.
15. The anti-IL-8 antibody of claim 14 , which is an IgG antibody.
16. The anti-IL-8 antibody of claim 15 , wherein the IgG antibody is IgG1, IgG2, IgG3 or IgG4.
17. The anti-IL-8 antibody of claim 16 , wherein the IgG antibody is IgG1.
18. The anti-IL-8 antibody of claim 14 , which comprises one or more amino acid substitutions selected from the group consisting of: L235R, G236R, S239K, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.
19. The anti-IL-8 antibody of claim 18 , which comprises amino acid substitution N434A according to EU numbering.
20. The anti-IL-8 antibody of claim 19 , which comprises amino acid substitutions of L235R, G236R, S239K, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.
21. The anti-IL-8 antibody of claim 19 , which comprises amino acid substitutions of L235R, G236R, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.
22. The anti-IL-8 antibody of claim 14 , which comprises a heavy chain comprising an amino acid sequence selected from the group consisting of:
(a) SEQ ID NO:80;
(b) SEQ ID NO:81;
(c) SEQ ID NO:92; and
(d) SEQ ID NO:93.
23. The anti-IL-8 antibody of claim 14 , which comprises a light chain comprising the amino acid sequence of SEQ ID NO:82.
24. The anti-IL-8 antibody of claim 14 , which comprises a light chain comprising the amino acid sequence of SEQ ID NO:82 and a heavy chain comprising an amino acid sequence selected from the group consisting of:
(a) SEQ ID NO:80;
(b) SEQ ID NO:81;
(c) SEQ ID NO:92; and
(d) SEQ ID NO:93.
25. The anti-IL-8 antibody of claim 24 , which comprises a light chain comprising the amino acid sequence of SEQ ID NO:82 and a heavy chain comprising the amino acid sequence of SEQ ID NO:80.
26. The anti-IL-8 antibody of claim 24 , which comprises a light chain comprising the amino acid sequence of SEQ ID NO:82 and a heavy chain comprising the amino acid sequence of SEQ ID NO:81.
27. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 14 and a pharmaceutically acceptable carrier.
28. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 18 and a pharmaceutically acceptable carrier.
29. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 19 and a pharmaceutically acceptable carrier.
30. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 20 and a pharmaceutically acceptable carrier.
31. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 21 and a pharmaceutically acceptable carrier.
32. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 22 and a pharmaceutically acceptable carrier.
33. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 23 and a pharmaceutically acceptable carrier.
34. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 24 and a pharmaceutically acceptable carrier.
35. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 25 and a pharmaceutically acceptable carrier.
36. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 26 and a pharmaceutically acceptable carrier.