Antagonistic human LIGHT-specific human monoclonal antibodies
View Patent ↗Provided herein are antibodies, such as fully human antibodies that immunospecifically bind to an hLIGHT polypeptide. Also provided are isolated nucleic acids encoding antibodies, such as fully human antibodies, that immunospecifically bind to a hLIGHT polypeptide. Further provided are vectors and host cells comprising nucleic acids encoding antibodies, such as fully human antibodies, that immunospecifically bind to a hLIGHT polypeptide. Also provided are methods of making antibodies, such as fully human antibodies, that immunospecifically bind to a hLIGHT polypeptide. Also provided herein is a method of treating a hLIGHT-mediated disease in a subject comprising administering to the subject an antibody, such as a fully human antibody, that immunospecifically binds to a hLIGHT polypeptide. In preferred embodiments, that anti-hLIGHT antibodies provided herein will ameliorate, neutralize or otherwise inhibit hLIGHT biological activity in vivo (e.g., the hLIGHT-mediated production or secretion of CCL20, IL-8 or RANTES from a cell expressing a hLIGHT receptor). Also provided herein is a method for the detection of hLIGHT in a sample as well as a method for ameliorating, neutralizing or otherwise inhibiting hLIGHT activity, e.g., in a human subject suffering from a disorder in which hLIGHT activity is detrimental.
1. An isolated antibody that immunospecifically binds to a human LIGHT (hLIGHT), wherein the antibody comprises:
a variable heavy (VH) complementarity determining region (CDR) 1 comprising the amino acid sequence of GYNWH (SEQ ID NO:20); a VH CDR2 comprising the amino acid sequence of EITHSGSTNYNPSLKS (SEQ ID NO:21); and a VH CDR3 comprising the amino acid sequence of EIAVAGTGYYGMDV (SEQ ID NO:22); and
a variable light (VL) CDR1 comprising the amino acid sequence of RASQGINSAFA (SEQ ID NO:35); a VL CDR2 comprising the amino acid sequence of DASSLES (SEQ ID NO:36); and a VL CDR3 comprising the amino acid sequence of QQFNSYPLT (SEQ ID NO:37).
2. An isolated antibody that immunospecifically binds to a hLIGHT, wherein the antibody comprises a VH domain comprising the amino acid sequence of SEQ ID NO:4.
3. The antibody of claim 2 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:4.
4. The antibody of claim 2 , wherein the antibody further comprises a VL domain comprising a VL CDR1 comprising the amino acid sequence of RASQGINSAFA (SEQ ID NO:35); a VL CDR2 comprising the amino acid sequence of DASSLES (SEQ ID NO:36); and a VL CDR3 comprising the amino acid sequence of QQFNSYPLT (SEQ ID NO:37).
5. The antibody of claim 4 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO:9.
6. The antibody of claim 2 , wherein the antibody further comprises a light chain comprising a VL CDR1 comprising the amino acid sequence of RASQGINSAFA (SEQ ID NO:35); a VL CDR2 comprising the amino acid sequence of DASSLES (SEQ ID NO:36); and a VL CDR3 comprising the amino acid sequence of QQFNSYPLT (SEQ ID NO:37).
7. The antibody of claim 6 , wherein the light chain comprises the amino acid sequence of SEQ ID NO:9.
8. The antibody of claim 3 , wherein the antibody further comprises a VL domain comprising a VL CDR1 comprising the amino acid sequence of RASQGINSAFA (SEQ ID NO:35); a VL CDR2 comprising the amino acid sequence of DASSLES (SEQ ID NO:36); and a VL CDR3 comprising the amino acid sequence of QQFNSYPLT (SEQ ID NO:37).
9. The antibody of claim 8 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO:9.
10. The antibody of claim 3 , wherein the antibody further comprises a light chain comprising a VL CDR1 comprising the amino acid sequence of RASQGINSAFA (SEQ ID NO:35); a VL CDR2 comprising the amino acid sequence of DASSLES (SEQ ID NO:36); and a VL CDR3 comprising the amino acid sequence of QQFNSYPLT (SEQ ID NO:37).
11. The antibody of claim 10 , wherein the light chain comprises the amino acid sequence of SEQ ID NO:9.
12. An isolated antibody that immunospecifically binds to a hLIGHT, wherein the antibody comprises a VL domain comprising the amino acid sequence of SEQ ID NO:9.
13. The antibody of claim 12 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:9.
14. The antibody of claim 12 , wherein the antibody further comprises a VH domain comprising a VH CDR1 comprising the amino acid sequence of GYNWH (SEQ ID NO:20); a VH CDR2 comprising the amino acid sequence of EITHSGSTNYNPSLKS (SEQ ID NO:21); and a VH CDR3 comprising the amino acid sequence of EIAVAGTGYYGMDV (SEQ ID NO:22).
15. The antibody of claim 12 , wherein the antibody further comprises a heavy chain comprising a VH CDR1 comprising the amino acid sequence of GYNWH (SEQ ID NO:20); a VH CDR2 comprising the amino acid sequence of EITHSGSTNYNPSLKS (SEQ ID NO:21); and a VH CDR3 comprising the amino acid sequence of EIAVAGTGYYGMDV (SEQ ID NO:22).
16. The antibody of claim 13 , wherein the antibody further comprises a VH domain comprising a VH CDR1 comprising the amino acid sequence of GYNWH (SEQ ID NO:20); a VH CDR2 comprising the amino acid sequence of EITHSGSTNYNPSLKS (SEQ ID NO:21); and a VH CDR3 comprising the amino acid sequence of EIAVAGTGYYGMDV (SEQ ID NO:22).
17. The antibody of claim 13 , wherein the antibody further comprises a heavy chain comprising a VH CDR1 comprising the amino acid sequence of GYNWH (SEQ ID NO:20); a VH CDR2 comprising the amino acid sequence of EITHSGSTNYNPSLKS (SEQ ID NO:21); and a VH CDR3 comprising the amino acid sequence of EIAVAGTGYYGMDV (SEQ ID NO:22).
18. The antibody of claim 1 , wherein the antibody is a fully human antibody.
19. The antibody of claim 1 , wherein the antibody is a chimeric antibody.
20. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
21. The antibody of claim 1 , wherein the antibody is a recombinant antibody.
22. The antibody of claim 1 , wherein the antibody is an antigen binding fragment.
23. The antibody of claim 1 , wherein the antibody is a Fab fragment, F(ab′) 2 fragment, single chain Fv (sFv), diabody, or triabody.
24. A composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
25. The antibody of claim 2 , wherein the antibody is a fully human antibody.
26. The antibody of claim 2 , wherein the antibody is a chimeric antibody.
27. The antibody of claim 2 , wherein the antibody is a monoclonal antibody.
28. The antibody of claim 2 , wherein the antibody is a recombinant antibody
29. The antibody of claim 2 , wherein the antibody is an antigen binding fragment.
30. The antibody of claim 2 , wherein the antibody is a Fab fragment, F(ab′) 2 fragment, single chain Fv (sFv), diabody, or triabody.
31. A composition comprising the antibody of claim 2 and a pharmaceutically acceptable carrier.
32. The antibody of claim 12 , wherein the antibody is a fully human antibody.
33. The antibody of claim 12 , wherein the antibody is a chimeric antibody.
34. The antibody of claim 12 , wherein the antibody is a monoclonal antibody.
35. The antibody of claim 12 , wherein the antibody is a recombinant antibody.
36. The antibody of claim 12 , wherein the antibody is an antigen binding fragment.
37. The antibody of claim 12 , wherein the antibody is a Fab fragment, F(ab′) 2 fragment, single chain Fv (sFv), diabody, or triabody.
38. A composition comprising the antibody of claim 12 and a pharmaceutically acceptable carrier.