Anti-OX40L antibodies and methods of treating graft versus host disease
The present invention relates to anti-human OX4OL antibodies, new medical uses and methods.
1. An antibody or a fragment thereof that specifically binds to hOX40L, comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, comprising:
(a) the HCDR1 sequences of SEQ ID NOs: 68 or 74, the HCDR2 sequences of SEQ ID NOs: 70 or 76, the HCDR3 sequences of SEQ ID NOs: 72 or 78, the LCDR1 sequences of SEQ ID NOs: 82 or 88, the LCDR2 sequences of SEQ ID NOs: 84 or 90, and the LCDR3 sequences of SEQ ID NOs: 86 or 92; or
(b) the HCDR1 sequences of SEQ ID NOs: 96 or 102, the HCDR2 sequences of SEQ ID NOs: 98 or 104, the HCDR3 sequences of SEQ ID NOs: 100 or 106; the LCDR1 sequences of SEQ ID NOs: 110 or 116, the LCDR2 sequences of SEQ ID NOs: 112 or 118, and the LCDR3 sequences of SEQ ID NOs: 114 or 120.
2. The antibody or fragment thereof according to claim 1 , wherein:
(a) the antibody or fragment thereof of (a) further comprises the VH domain amino acid sequence of SEQ ID NO:66; or
(b) the antibody or fragment thereof of (b) further comprises the VH domain amino acid sequence of SEQ ID NO: 94.
3. The antibody or fragment thereof according to claim 1 , comprising a first and a second copy of the VH domain.
4. The antibody or fragment thereof according to claim 1 , wherein:
(a) the antibody or fragment thereof of (a) further comprises the VL domain amino acid sequence of SEQ ID NO:80; or
(b) the antibody or fragment thereof of (b) further comprises the VL domain amino acid sequence of SEQ ID NO: 108.
5. The antibody or fragment thereof according to claim 1 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO:80 and the VH domain comprises the amino acid sequence of SEQ ID NO:66; or
wherein the VL domain comprises the amino acid sequence of SEQ ID NO:108 and the VH domain comprises the amino acid sequence of SEQ ID NO:94.
6. The antibody or fragment thereof according to claim 1 or claim 4 , comprising a first and a second copy of the VL domain.
7. The antibody or fragment thereof according to claim 1 , comprising a kappa light chain.
8. The antibody or fragment thereof according to claim 1 , comprising a constant region.
9. The antibody or fragment thereof according to claim 8 , comprising an IgG4-PE constant region of SEQ ID NO:128.
10. The antibody or fragment thereof according to 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 human IgG4 constant region.
11. A composition comprising the antibody or fragment thereof according to claim 1 and a pharmaceutically acceptable excipient, diluent, or carrier.
12. The composition according to claim 11 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO:80 and the VH domain comprises the amino acid sequence of SEQ ID NO:66; or
wherein the VL domain comprises the amino acid sequence of SEQ ID NO:108 and the VH domain comprises the amino acid sequence of SEQ ID NO:94.
13. A kit comprising the composition according to claim 11 and an IV or injection device.
14. A method of treating graft versus host disease (GvHD) or transplant rejection in a subject in need of treatment thereof, comprising administering to the subject the antibody or fragment thereof according to claim 1 the composition according to claim 11 .