Methods of treating comprising administering anti-OX40L antibodies
The present invention relates to anti-human OX40L antibodies, new medical uses and methods.
1. A method of treating an autoimmune disease or condition, a systemic inflammatory disease or condition, or transplant rejection in a human subject, comprising administering to the subject an anti-OX40L antibody or antibody fragment that specifically binds to an hOX40L epitope and comprises a heavy chain and a light chain wherein:
a. the heavy chain comprises:
i. a V H region having at least 90% identity to the amino acid sequence of SEQ ID NO: 34; and
ii. a heavy chain constant region having the amino acid sequence of SEQ ID NO: 128; and
b. the light chain comprises:
i. a V L region having at least 90% identity to the amino acid sequence of SEQ ID NO: 48; and
ii. a light chain constant region;
wherein the anti-OX40L antibody or antibody fragment is administered intravenously or subcutaneously to said subject in an amount effective to decrease secretion of IL-2.
2. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment specifically binds to hOX40L with a Kd from 1 nM to 10 pM, as determined by surface plasmon resonance (SPR).
3. The method of claim 1 , wherein the IL-2 secretion is reduced by at least 50% as compared to IL-2 secretion in the absence of the anti-OX40L antibody or antibody fragment, wherein IL-2 secretion is measured in an allogeneic mixed lymphocyte reaction (MLR) assay.
4. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment specifically binds to a rhesus monkey OX40L epitope with a Kd of from 1 nM to 10 pM, as determined by SPR.
5. The method of claim 1 , wherein the IL-2 secretion is decreased by at least 60% compared to the production of IL-2 in a human peripheral blood mononuclear cell (PBMC) MLR assay in the absence of an antibody that is specific for hOX40L.
6. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment comprises a V H domain which comprises the HCDR1 sequence of SEQ ID NO: 36 or 42.
7. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment comprises a V H domain which comprises the HCDR2 sequence of SEQ ID NO: 38 or 44.
8. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment comprises a V H domain which comprises the HCDR3 sequence of SEQ ID NO: 40 or 46.
9. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment comprises a VH domain comprising an amino acid sequence of SEQ ID NO: 34.
10. The method of claim 9 , wherein the anti-OX40L antibody or antibody fragment comprises first and second copies of the V H domain.
11. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment comprises a V L domain which comprises the LCDR1 sequence of SEQ ID NO: 50 or 56.
12. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment comprises a V L domain which comprises the LCDR2 sequence of SEQ ID NO: 52 or 58.
13. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment comprises a V L domain which comprises the LCDR3 sequence of SEQ ID NO: 54 or 60.
14. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment comprises a V L domain comprising an amino acid sequence of SEQ ID NO: 48.
15. The method of claim 14 , wherein the anti-OX40L antibody or antibody fragment comprises first and second copies of the V L domain.
16. The method of claim 1 , wherein the light chain is a kappa light chain.
17. The method of claim 16 , wherein the light chain constant region is selected from the group consisting of the kappa light chain constant region amino acid sequences of SEQ ID NOs: 136, 138, 140, 142, and 144.
18. The method of claim 16 , wherein the light chain constant region is a kappa light chain constant region comprising the amino acid sequence of SEQ ID NO: 136.
19. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment is fully human.
20. The method of claim 1 , wherein the heavy chain amino acid sequence of the anti-OX40L antibody or antibody fragment comprises the amino acid sequence of SEQ ID NO: 62 and the light chain amino acid sequence of the anti-OX40L antibody or antibody fragment comprises the amino acid sequence of SEQ ID NO: 64.
21. The method of claim 1 , wherein the heavy chain amino acid sequence of the anti-OX40L antibody or antibody fragment comprises the amino acid sequence of SEQ ID NO: 2 and the light chain amino acid sequence of the anti-OX40L antibody or antibody fragment comprises the amino acid sequence of SEQ ID NO: 16.
22. The method of claim 1 , wherein the anti-OX40L antibody or antibody fragment competes for binding to the hOX40L epitope with the antibody 2D10, wherein the antibody 2D10 comprises a V H domain comprising the amino acid sequence consisting of the sequence of SEQ ID NO: 34 and a V L domain comprising the amino acid sequence consisting of the sequence of SEQ ID NO: 48.
23. The method of claim 1 , wherein percent identity is determined by aligning the amino acid sequences for optimal comparison purposes.
24. The method of claim 23 , wherein percent identity is calculated using a mathematical algorithm in the ALIGN program using a PAM120 weight residue table.
25. The method of claim 1 , wherein percent identity is calculated using a mathematical algorithm in the ALIGN program using a PAM120 weight residue table.
26. The method of claim 1 , wherein the subject has or is at risk of rheumatoid arthritis, transplant rejection, allogenic transplant rejection, graft-versus-host disease (GvHD), diabetes, uveitis, ankylosing spondylitis, or contact hypersensitivity.
27. The method of claim 26 , wherein the subject has or is at risk of GvHD.
28. A method of treating an autoimmune disease or condition, a systemic inflammatory disease or condition, or transplant rejection in a human subject, comprising administering to the subject an anti-OX40L antibody or antibody fragment that specifically binds to an hOX40L epitope and comprises a heavy chain and a light chain and wherein:
a. the heavy chain comprises a V H region having at least 95% identity to the amino acid sequence of SEQ ID NO: 34; and
b. the light chain comprises a V L region having at least 95% identity to the amino acid sequence of SEQ ID NO: 48;
wherein the anti-OX40L antibody or antibody fragment is administered intravenously or subcutaneously to said subject in an amount effective to decrease secretion of IL-2.
29. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment specifically binds to hOX40L with a Kd from 1 nM to 10 pM, as determined by surface plasmon resonance (SPR).
30. The method of claim 28 , wherein the IL-2 secretion is reduced by at least 50% as compared to IL-2 secretion in the absence of the anti-OX40L antibody or antibody fragment, wherein IL-2 secretion is measured in an allogeneic mixed lymphocyte reaction (MLR) assay.
31. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment specifically binds to a rhesus monkey OX40L epitope with a Kd of from 1 nM to 10 pM, as determined by SPR.
32. The method of claim 28 , wherein the IL-2 secretion is decreased by at least 60% compared to the production of IL-2 in a human peripheral blood mononuclear cell (PBMC) MLR assay in the absence of an antibody that is specific for hOX40L.
33. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment comprises a VH domain which comprises the HCDR1 sequence of SEQ ID NO: 36 or 42.
34. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment comprises a VH domain which comprises the HCDR2 sequence of SEQ ID NO: 38 or 44.
35. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment comprises a VH domain which comprises the HCDR3 sequence of SEQ ID NO: 40 or 46.
36. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment comprises a VH domain comprising an amino acid sequence of SEQ ID NO: 34.
37. The method of claim 36 , wherein the anti-OX40L antibody or antibody fragment comprises first and second copies of the V H domain.
38. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment comprises a V L domain which comprises the LCDR1 sequence of SEQ ID NO: 50 or 56.
39. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment comprises a V L domain which comprises the LCDR2 sequence of SEQ ID NO: 52 or 58.
40. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment comprises a V L domain which comprises the LCDR3 sequence of SEQ ID NO: 54 or 60.
41. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment comprises a V L domain comprising an amino acid sequence of SEQ ID NO: 48.
42. The method of claim 41 , wherein the anti-OX40L antibody or antibody fragment comprises first and second copies of the V L domain.
43. The method of claim 28 , wherein the light chain is a kappa light chain.
44. The method of claim 43 , wherein the light chain constant region is selected from the group consisting of the kappa light chain constant region amino acid sequences of SEQ ID NOs: 136, 138, 140, 142, and 144.
45. The method of claim 43 , wherein the light chain constant region is a kappa light chain constant region comprising the amino acid sequence of SEQ ID NO: 136.
46. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment is fully human.
47. The method of claim 28 , wherein the heavy chain amino acid sequence of the anti-OX40L antibody or antibody fragment comprises the amino acid sequence of SEQ ID NO: 62 and the light chain amino acid sequence of the anti-OX40L antibody or antibody fragment comprises the amino acid sequence of SEQ ID NO: 64.
48. The method of claim 28 , wherein the heavy chain amino acid sequence of the anti-OX40L antibody or antibody fragment comprises the amino acid sequence of SEQ ID NO: 2 and the light chain amino acid sequence of the anti-OX40L antibody or antibody fragment comprises the amino acid sequence of SEQ ID NO: 16.
49. The method of claim 28 , wherein the anti-OX40L antibody or antibody fragment competes for binding to the hOX40L epitope with the antibody 2D10, wherein the antibody 2D10 comprises a V H domain comprising the amino acid sequence consisting of the sequence of SEQ ID NO: 34 and a V L domain comprising the amino acid sequence consisting of the sequence of SEQ ID NO: 48.
50. The method of claim 28 , wherein percent identity is determined by aligning the amino acid sequences for optimal comparison purposes.
51. The method of claim 50 , wherein percent identity is calculated using a mathematical algorithm in the ALIGN program using a PAM120 weight residue table.
52. The method of claim 28 , wherein percent identity is calculated using a mathematical algorithm in the ALIGN program using a PAM120 weight residue table.
53. The method of claim 28 , wherein the subject has or is at risk of rheumatoid arthritis, transplant rejection, allogenic transplant rejection, graft-versus-host disease (GvHD), diabetes, uveitis, ankylosing spondylitis, or contact hypersensitivity.
54. The method of claim 53 , wherein the subject has or is at risk of GvHD.