Antibody molecules to a proliferation-inducing ligand (APRIL)
Antibody molecules that specifically bind to APRIL are disclosed. The antibody molecules can be used to treat, prevent, and/or diagnose disorders, such as IgA nephropathy.
1. An anti-A PRoliferation Inducing Ligand (APRIL) antibody molecule, comprising a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and a light chain variable region (VH) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3),
wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16; or
wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.
2. The antibody molecule of claim 1 , wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 11; an HCDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.
3. The antibody molecule of claim 1 , wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 17; an HCDR2 comprising the amino acid sequence of SEQ ID NO: 282, and an HCDR3 comprising the amino acid sequence of SEQ ID NO: 13; and the VL comprises an LCDR1 comprising the amino acid sequence of SEQ ID NO: 280; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 285, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 16.
4. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 296, or an amino acid sequence that is at least 85% identical thereto.
5. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 296.
6. The antibody molecule of claim 1 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 286, or an amino acid sequence that is at least 85% identical thereto.
7. The antibody molecule of claim 1 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 286.
8. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 296, and wherein the VL comprises the amino acid sequence of SEQ ID NO: 286.
9. The antibody molecule of claim 1 , which is a synthetic antibody molecule.
10. The antibody molecule of claim 1 , which is an isolated antibody molecule.
11. The antibody molecule of claim 1 , which is a humanized antibody molecule.
12. The antibody molecule of claim 1 , which comprises a heavy chain constant region of IgG1, IgG2, IgG3, or IgG4.
13. The antibody molecule of claim 1 , which comprises a heavy chain constant region of IgG2.
14. The antibody molecule of claim 1 , which comprises a light chain constant region of kappa or lambda light chain.
15. The antibody molecule of claim 1 , which comprises an Fc region.
16. The antibody molecule of claim 15 , wherein the Fc region comprises one or more mutations located at the interface between the CH2 and CH3 domains.
17. The antibody molecule of claim 1 , which comprises two VHs and two VLs.
18. The antibody molecule of claim 1 , which comprises a Fab, F(ab′)2, Fv, or single chain Fv (scFv) fragment.
19. The antibody molecule of claim 1 , wherein the VH is encoded by a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 313.
20. The antibody molecule of claim 1 , wherein the VL is encoded by a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 306.
21. A pharmaceutical composition comprising the antibody molecule of claim 1 and a pharmaceutically acceptable carrier.
22. A pharmaceutical composition comprising the antibody molecule of claim 2 and a pharmaceutically acceptable carrier.
23. A pharmaceutical composition comprising the antibody molecule of claim 3 and a pharmaceutically acceptable carrier.
24. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of any of SEQ ID NOs: 19, 283, 288, 289, 291, 292, 294, 296, or 317.
25. The antibody molecule of claim 24 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 286.
26. A pharmaceutical composition comprising the antibody molecule of claim 25 and a pharmaceutically acceptable carrier.
27. An anti-APRIL antibody molecule, comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence of SEQ ID NO: 296, and wherein the VL comprises the amino acid sequence of SEQ ID NO: 286.
28. The antibody molecule of claim 27 , which comprises a heavy chain constant region of IgG2.
29. The antibody molecule of claim 27 , which comprises a light chain constant region of kappa light chain.
30. A pharmaceutical composition comprising the antibody molecule of claim 27 and a pharmaceutically acceptable carrier.