Altered APRIL binding antibodies
The invention relates to APRIL-binding antibodies, which bind the same epitope of human APRIL as an antibody having an antigen binding site of hAPRIL.01A. The antibodies of the present invention comprise specific selections of framework sequences of the V H and V L domains and have unexpected features in comparison to hAPRIL.01A. The invention further relates to compositions comprising an antibody of the invention and to the medical and diagnostic uses of the antibodies and compositions.
1. A humanized antibody comprising a heavy chain variable region/light chain variable region pair selected from the group consisting of VH11/VL15, VH12/VL15, VH13/VL15, VH14/VL15, VH14_1/VL15, VH14_1C/VL15, VH14_1D/VL15, VH14_1E/VL15, and VH14_1G/VL15, wherein the antibody binds to human “A proliferation-inducing ligand” (“APRIL”) protein.
2. A composition comprising an antibody of claim 1 and a pharmaceutically acceptable carrier or diluent.
3. A humanized antibody comprising a heavy chain variable region/light chain variable region pair, comprising:
heavy chain complementary determining regions consisting of SEQ ID NO: 5, SEQ ID NO: 6, and SEQ ID NO: 7;
light chain complementary determining regions consisting of SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10; and
framework regions having at least 90% sequence similarity to the framework regions of a heavy chain variable region/light chain variable region pair selected from the group consisting of VH11/VL15, VH12/VL15, VH13/VL15, VH14/VL15, VH14_1/VL15, VH14_1C/VL15, VH14_1D/VL15, VH14_1E/VL15, and VH14_1G/VL15 wherein the antibody binds to human “A proliferation-inducing ligand” (“APRIL”) protein.
4. An antibody according to claim 3 , wherein at least 90% sequence similarity is at least 90% sequence identity.
5. An antibody according to claim 3 , wherein at least 90% sequence similarity is at least 95% sequence similarity.
6. An antibody according to claim 5 , wherein at least 95% sequence similarity is at least 95% sequence identity.
7. An antibody according to claim 3 , wherein the amino acid at position 72 of the heavy chain variable region is S.
8. An antibody according to claim 3 , wherein the amino acid at position 67 of the heavy chain variable region is K and the amino acid at position 68 of the heavy chain variable region is A.
9. An antibody according to claim 4 , wherein the amino acid at position 72 of the heavy chain variable region is S.
10. An antibody according to claim 4 , wherein the amino acid at position 67 of the heavy chain variable region is K and the amino acid at position 68 of the heavy chain variable region is A.
11. An antibody according to claim 5 , wherein the amino acid at position 72 of the heavy chain variable region is S.
12. An antibody according to claim 5 , wherein the amino acid at position 67 of the heavy chain variable region is K and the amino acid at position 68 of the heavy chain variable region is A.
13. An antibody according to claim 6 , wherein the amino acid at position 72 of the heavy chain variable region is S.
14. An antibody according to claim 6 , wherein the amino acid at position 67 of the heavy chain variable region is K and the amino acid at position 68 of the heavy chain variable region is A.
15. A composition comprising an antibody according to claim 3 and a pharmaceutically acceptable carrier or diluent.
16. A composition comprising an antibody according to claim 4 and a pharmaceutically acceptable carrier or diluent.
17. A composition comprising an antibody according to claim 5 and a pharmaceutically acceptable carrier or diluent.
18. A composition comprising an antibody according to claim 6 and a pharmaceutically acceptable carrier or diluent.
19. A composition comprising an antibody according to claim 7 and a pharmaceutically acceptable carrier or diluent.
20. A composition comprising an antibody according to claim 8 and a pharmaceutically acceptable carrier or diluent.
21. A composition comprising an antibody according to claim 9 and a pharmaceutically acceptable carrier or diluent.
22. A composition comprising an antibody according to claim 10 and a pharmaceutically acceptable carrier or diluent.
23. A composition comprising an antibody according to claim 11 and a pharmaceutically acceptable carrier or diluent.
24. A composition comprising an antibody according to claim 12 and a pharmaceutically acceptable carrier or diluent.
25. A composition comprising an antibody according to claim 13 and a pharmaceutically acceptable carrier or diluent.
26. A composition comprising an antibody according to claim 14 and a pharmaceutically acceptable carrier or diluent.