Methods of treatment using human antibody molecules for IL-13
Specific binding members, in particular human anti-IL-13 antibody molecules and especially those which neutralise IL-13 activity. Methods for using anti-IL-13 antibody molecules in diagnosis or treatment of IL-13 related disorders, including asthma, atopic dermatitis, allergic rhinitis, fibrosis, inflammatory bowel disease and Hodgkin's lymphoma.
1. A method of treatment of a disease or disorder selected from the group consisting of asthma, atopic dermatitis, allergic rhinitis, fibrosis and Hodgkin's lymphoma, the method comprising administering a specific binding member to a patient with the disease or disorder, wherein the specific binding member binds interleukin-13 (IL-13) and comprises an antibody antigen-binding site which is composed of a human antibody heavy chain variable region (VH) and a human antibody light chain variable region (VL) comprising a set of complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the VH comprises HCDR1, HCDR2 and HCDR3 and the VL comprises LCDR1, LCDR2 and LCDR3, wherein:
HCDR1 comprises SEQ ID NO:7;
HCDR2 comprises SEQ ID NO:8;
HCDR3 comprises SEQ ID NO:9;
LCDR1 comprises SEQ ID NO:10;
LCDR2 comprises SEQ ID NO:11; and
LCDR3 comprises SEQ ID NO:12.
2. The method of claim 1 , wherein the specific binding member is an antibody.
3. The method of claim 2 , wherein the antibody is a monoclonal antibody, a human antibody, a humanized antibody, a chimeric antibody, a synthetic antibody, a bi-specific antibody, a multi-specific antibody, or an antibody fragment thereof.
4. The method of claim 3 , wherein the antibody fragment is a Fab fragment, a Fd fragment, a Fv fragment, a F(ab′) 2 fragment, a single chain Fv molecule, or a diabody.
5. The method of claim 3 , wherein the antibody further comprises a heavy chain immunoglobulin constant region selected from the group consisting of:
(a) an IgA constant region;
(b) an IgE constant region;
(c) an IgG1 constant region;
(d) an IgG2 constant region;
(e) an IgG3 constant region;
(f) an IgG4 constant region; and
(g) an IgM constant region.
6. The method of claim 3 , wherein the antibody further comprises a light chain immunoglobulin constant region selected from the group consisting of:
(a) a kappa constant domain; and
(b) a lambda constant domain.
7. The method of claim 3 , wherein the antibody further comprises a human IgG4 constant region and a human lambda constant domain.
8. The method of claim 7 , wherein the disease or disorder is asthma.
9. The method of claim 7 , wherein the disease or disorder is atopic dermatitis.
10. The method of claim 7 , wherein the disease or disorder is allergic rhinitis.
11. The method of claim 7 , wherein the disease or disorder is fibrosis.
12. The method of claim 7 , wherein the disease or disorder is Hodgkin's lymphoma.
13. The method of claim 1 , wherein the specific binding member comprises the BAK502G9 VH domain (SEQ ID NO:15).
14. The method of claim 1 , wherein the specific binding member comprises the BAK502G9 VL domain (SEQ ID NO:16).
15. The method of claim 1 , wherein the specific binding member comprises the BAK502G9 VH domain (SEQ ID NO:15) and the BAK502G9 VL domain (SEQ ID NO:16).
16. The method of claim 15 , wherein the specific binding member is an antibody.
17. The method of claim 16 , wherein the antibody is a monoclonal antibody, a human antibody, a humanized antibody, a chimeric antibody, a synthetic antibody, a bi-specific antibody, a multi-specific antibody, or an antibody fragment thereof.
18. The method of claim 17 , wherein the antibody fragment is a Fab fragment, a Fd fragment, a Fv fragment, a F(ab′) 2 fragment, a single chain Fv molecule, or a diabody.
19. The method of claim 17 , wherein the antibody further comprises a heavy chain immunoglobulin constant region selected from the group consisting of:
(a) an IgA constant region;
(b) an IgE constant region;
(c) an IgG1 constant region;
(d) an IgG2 constant region;
(e) an IgG3 constant region;
(f) an IgG4 constant region; and
(g) an IgM constant region.
20. The method of claim 17 , wherein the antibody further comprises a light chain immunoglobulin constant region selected from the group consisting of:
(a) a kappa constant domain; and
(b) a lambda constant domain.
21. The method of claim 17 , wherein the antibody further comprises a human IgG4 constant region and a human lambda constant domain.
22. The method of claim 21 , wherein the disease or disorder is asthma.
23. The method of claim 21 , wherein the disease or disorder is atopic dermatitis.
24. The method of claim 21 , wherein the disease or disorder is allergic rhinitis.
25. The method of claim 21 , wherein the disease or disorder is fibrosis.
26. The method of claim 21 , wherein the disease or disorder is Hodgkin's lymphoma.
27. A method of treating an interleukin-13 (IL-13) related disorder in a patient comprising administering to the patient an antibody or antibody fragment thereof comprising:
(a) a set of complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises SEQ ID NO:7;
HCDR2 comprises SEQ ID NO:8;
HCDR3 comprises SEQ ID NO:9;
LCDR1 comprises SEQ ID NO:10;
LCDR2 comprises SEQ ID NO:11; and
LCDR3 comprises SEQ ID NO:12;
or
(b) a heavy chain variable region (VH) comprising SEQ ID NO:15 and a light chain variable region (VL) comprising SEQ ID NO:16:,
wherein the IL-13 related disorder is selected from the group consisting of: asthma, atopic dermatitis, allergic rhinitis, chronic obstructive pulmonary disease (COPD), fibrosis, scleroderma, and Hodgkin's lymphoma.
28. The method of claim 27 , wherein the antibody is a monoclonal antibody, a human antibody, a humanized antibody, a chimeric antibody, a synthetic antibody, a bi-specific antibody, a multi-specific antibody, or an antibody fragment thereof.
29. The method of claim 27 , wherein the antibody fragment is a Fab fragment, a Fd fragment, a Fv fragment, a F(ab′) 2 fragment, a single chain Fv molecule, or a diabody.
30. The method of claim 27 , wherein the antibody further comprises a heavy chain immunoglobulin constant region selected from the group consisting of:
(a) an IgA constant region;
(b) an IgE constant region;
(c) an IgG1 constant region;
(d) an IgG2 constant region;
(e) an IgG3 constant region;
(f) an IgG4 constant region; and
(g) an IgM constant region.
31. The method of claim 27 , wherein the antibody or antibody fragment thereof further comprises a light chain immunoglobulin constant region selected from the group consisting of:
(a) a kappa constant domain; and
(b) a lambda constant domain.
32. The method of claim 27 , wherein the antibody further comprises a human IgG4 constant region and a human lambda constant domain.
33. The method of claim 27 , wherein the antibody or antibody fragment thereof comprises (a).
34. The method of claim 27 , wherein the antibody or antibody fragment thereof comprises (b).
35. The method of claim 27 , wherein the IL-13 related disorder is asthma.
36. The method of claim 27 , wherein the IL-13 related disorder is atopic dermatitis.
37. The method of claim 27 , wherein the IL-13 related disorder is allergic rhinitis.
38. The method of claim 27 , wherein the IL-13 related disorder is fibrosis.
39. The method of claim 27 , wherein the IL-13 related disorder is Hodgkin's lymphoma.
40. The method of claim 27 , wherein the IL-13 related disorder is COPD.
41. The method of claim 27 , wherein the IL-13 related disorder is scleroderma.
42. A method of inhibiting or neutralizing interleukin-13 (IL-13) in a patient comprising administering to the patient an antibody or antibody fragment thereof comprising:
(a) a set of complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein
HCDR1 comprises SEQ ID NO:7;
HCDR2 comprises SEQ ID NO:8;
HCDR3 comprises SEQ ID NO:9;
LCDR1 comprises SEQ ID NO:10;
LCDR2 comprises SEQ ID NO:11; and
LCDR3 comprises SEQ ID NO:12;
or
(b) a heavy chain variable region (VH) comprising SEQ ID NO:15 and a light
chain variable region (VL) comprising SEQ ID NO:16;
wherein the patient has a disease or condition selected from the group consisting of: asthma, atopic dermatitis, allergic rhinitis, chronic obstructive pulmonary disease (COPD), fibrosis, scleroderma, and Hodgkin's lymphoma.
43. The method of claim 42 , wherein the antibody is a monoclonal antibody, a human antibody, a humanized antibody, a chimeric antibody, a synthetic antibody, a bi-specific antibody, a multi-specific antibody, or an antibody fragment thereof.
44. The method of claim 42 , wherein the antibody fragment is a Fab fragment, a Fd fragment, a Fv fragment, a F(ab′) 2 fragment, a single chain Fv molecule, or a diabody.
45. The method of claim 42 , wherein the antibody further comprises a heavy chain immunoglobulin constant region selected from the group consisting of:
(a) an IgA constant region;
(b) an IgE constant region;
(c) an IgG1 constant region;
(d) an IgG2 constant region;
(e) an IgG3 constant region;
(f) an IgG4 constant region; and
(g) an IgM constant region.
46. The method of claim 42 , wherein the antibody or antibody fragment thereof further comprises a light chain immunoglobulin constant region selected from the group consisting of:
(a) a kappa constant domain; and
(b) a lambda constant domain.
47. The method of claim 42 , wherein the antibody further comprises a human IgG4 constant region and a human lambda constant domain.
48. The method of claim 42 , wherein the antibody or antibody fragment thereof comprises (a).
49. The method of claim 42 , wherein the antibody or antibody fragment thereof comprises (b).
50. The method of claim 42 , wherein the disease or condition is asthma.
51. The method of claim 42 , wherein the disease or condition is atopic dermatitis.
52. The method of claim 42 , wherein the disease or condition is allergic rhinitis.
53. The method of claim 42 , wherein the disease or condition is fibrosis.
54. . The method of claim 42 , wherein the disease or condition is Hodgkin's lymphoma.
55. The method of claim 42 , wherein the disease or condition is COPD.
56. The method of claim 42 , wherein the disease or condition is scleroderma.
57. A method of treating asthma in a patient comprising administering to the patient an effective amount of an anti-IL-13 antibody or antibody fragment thereof, wherein the anti-IL-13 antibody or antibody fragment thereof comprises:
(a) a set of complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3,
LCDR1, LCDR2 and LCDR3, wherein
HCDR1 comprises SEQ ID NO:7;
HCDR2 comprises SEQ ID NO:8;
HCDR3 comprises SEQ ID NO:9;
LCDR1 comprises SEQ ID NO:10;
LCDR2 comprises SEQ ID NO:11; and
LCDR3 comprises SEQ ID NO:12;
or
(b) a heavy chain variable region (VH) comprising SEQ ID NO:15 and a light chain variable region (VL) comprising SEQ ID NO:16.
58. The method of claim 57 , wherein the antibody is a monoclonal antibody, a human antibody, a humanized antibody, a chimeric antibody, a synthetic antibody, a bi-specific antibody, a multi-specific antibody, or an antibody fragment thereof.
59. The method of claim 57 , wherein the antibody fragment is a Fab fragment, a Fd fragment, a Fv fragment, a F(ab′) 2 fragment, a single chain Fv molecule, or a diabody.
60. The method of claim 57 , wherein the antibody further comprises a heavy chain immunoglobulin constant region selected from the group consisting of:
(a) an IgA constant region;
(b) an IgE constant region;
(c) an IgG1 constant region;
(d) an IgG2 constant region;
(e) an IgG3 constant region;
(f) an IgG4 constant region; and
(g) an IgM constant region.
61. The method of claim 57 , wherein the antibody or antibody fragment thereof further comprises a light chain immunoglobulin constant region selected from the group consisting of:
(a) a kappa constant domain; and
(b) a lambda constant domain.
62. The method of claim 57 , wherein the antibody further comprises a human IgG4 constant region and a human lambda constant domain.
63. The method of claim 57 , wherein the antibody or antibody fragment thereof comprises (a).
64. The method of claim 57 , wherein the antibody or antibody fragment thereof comprises (b).
65. A method of treating atopic dermatitis in a patient comprising administering to the patient an effective amount of an anti-IL-13 antibody or antibody fragment thereof, wherein the anti-IL-13 antibody or antibody fragment thereof comprises:
(a) a set of complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3,
LCDR1, LCDR2 and LCDR3, wherein
HCDR1 comprises SEQ ID NO:7;
HCDR2 comprises SEQ ID NO:8;
HCDR3 comprises SEQ ID NO:9;
LCDR1 comprises SEQ ID NO:10;
LCDR2 comprises SEQ ID NO:11; and
LCDR3 comprises SEQ ID NO:12;
or
(b) a heavy chain variable region (VH) comprising SEQ ID NO:15 and a light chain variable region (VL) comprising SEQ ID NO:16.
66. The method of claim 65 , wherein the antibody is a monoclonal antibody, a human antibody, a humanized antibody, a chimeric antibody, a synthetic antibody, a bi-specific antibody, a multi-specific antibody, or an antibody fragment thereof.
67. The method of claim 65 , wherein the antibody fragment is a Fab fragment, a Fd fragment, a Fv fragment, a F(ab′) 2 fragment, a single chain Fv molecule, or a diabody.
68. The method of claim 65 , wherein the antibody further comprises a heavy chain immunoglobulin constant region selected from the group consisting of:
(a) an IgA constant region;
(b) an IgE constant region;
(c) an IgG1 constant region;
(d) an IgG2 constant region;
(e) an IgG3 constant region;
(f) an IgG4 constant region; and
(g) an IgM constant region.
69. The method of claim 65 , wherein the antibody or antibody fragment thereof further comprises a light chain immunoglobulin constant region selected from the group consisting of:
(a) a kappa constant domain; and
(b) a lambda constant domain.
70. The method of claim 65 , wherein the antibody further comprises a human IgG4 constant region and a human lambda constant domain.
71. The method of claim 65 , wherein the antibody or antibody fragment thereof comprises (a).
72. The method of claim 65 , wherein the antibody or antibody fragment thereof comprises (b).