Methods of treating SLE with anti-OX40L antibodies
The present invention relates to anti-human OX40L antibodies, new medical uses and methods.
1. A method of treating systemic lupus erythematosus (SLE) in a human subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an anti-OX40L antibody or antibody fragment that antagonizes specific binding of OX40 to OX40L, wherein the antibody or antibody fragment comprises:
(a) a HCDR1 amino acid sequence of SEQ ID NO: 36 or 42;
(b) a HCDR2 amino acid sequence of SEQ ID NO: 38 or 44;
(c) a HCDR3 amino acid sequence of SEQ ID NO: 40 or 46;
(d) a LCDR1 amino acid sequence of SEQ ID NO: 50 or 56;
(e) a LCDR2 amino acid sequence of SEQ ID NO: 52 or 58; and
(f) a LCDR3 amino acid sequence of SEQ ID NO: 54 or 60.
2. The method of claim 1 , wherein the antibody or fragment thereof further comprises a VH domain, wherein the VH domain comprises the amino acid sequence of SEQ ID No:34.
3. The method of claim 2 , wherein the antibody or antibody fragment comprises a first and a second copy of the VH domain.
4. The method of claim 2 , wherein the antibody or fragment thereof further comprises a VL domain, wherein the VL domain comprises the amino acid sequence of SEQ ID No:48.
5. The method of claim 1 , wherein the antibody or fragment thereof further comprises a VL domain and a VH domain, wherein the VL domain comprises the amino acid sequence of SEQ ID No:48 and the VH domain comprises the amino acid sequence of SEQ ID No:34.
6. The method of claim 5 , wherein the antibody or antibody fragment comprises a first and a second copy of the VL domain.
7. The method of claim 5 , wherein the antibody or antibody fragment comprises a kappa light chain.
8. The method of claim 5 , wherein the antibody or antibody fragment comprises a constant region.
9. The method of claim 8 , wherein the constant region comprises an IgG4-PE constant region, wherein the IgG4-PE constant region comprises a Leu235Glu mutation and a Ser228Pro mutation relative to the wild-type IgG4 constant region.
10. The method of claim 5 , wherein the antibody or antibody fragment comprises a IgG4-PE constant region of SEQ ID No:128.
11. The method of claim 1 , wherein the antibody or antibody fragment specifically binds hOX40L with an affinity of less than 1 μM.
12. The method of claim 11 , wherein the affinity of the antibody or antibody fragment is determined by surface plasmon resonance (SPR).
13. The method of claim 1 , wherein the antibody or fragment thereof comprises:
(a) a heavy chain amino acid sequence of SEQ ID NO: 62; and
(b) a light chain amino acid sequence of SEQ ID NO: 64.