Antagonistic human LIGHT-specific human monoclonal antibodies
View Patent ↗Provided herein are antibodies that immunospecifically bind to an hLIGHT polypeptide; isolated nucleic acids encoding the antibodies; vectors and host cells comprising nucleic acids encoding the antibodies; methods of making the antibodies; and a method of treating a hLIGHT-mediated disease in a subject comprising administering to the subject the antibodies. In preferred embodiments, the 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 or a hLIGHT binding fragment thereof, that specifically binds to the native form of soluble hLIGHT but does not bind to denatured hLIGHT, wherein the antibody comprises a VH domain having the amino acid sequence of residues 27-143 of SEQ ID NO:5 and a VL domain having the amino acid sequence of residues 23-129 of SEQ ID NO:10.
2. An isolated antibody or a hLIGHT binding fragment thereof, that specifically binds to the native form of soluble hLIGHT but does not bind to denatured hLIGHT, wherein the antibody comprises:
(a) a heavy chain variable region comprising a VH CDR1 having the amino acid sequence of SEQ ID NO:23, a VH CDR2 having the amino acid sequence of SEQ ID NO:24, and a VH CDR3 having the amino acid sequence of SEQ ID NO:25; and
(b) a light chain variable region comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:38, a VL CDR2 having the amino acid sequence of SEQ ID NO:39, and a VL CDR3 having the amino acid sequence of SEQ ID NO:40.
3. The antibody or hLIGHT binding fragment thereof of claim 1 that specifically binds to a hLIGHT comprising the amino acid sequence of SEQ ID NO:52 and having a lysine or glutamic acid at amino acid position 214, and that inhibits RANTES secretion mediated by 214E or 214K hLIGHT SNP variant expressing cell line.
4. The antibody or hLIGHT binding fragment thereof of claim 2 that specifically binds to a hLIGHT comprising the amino acid sequence of SEQ ID NO:52 and having a lysine or glutamic acid at amino acid position 214, and that inhibits RANTES secretion mediated by 214E or 214K hLIGHT SNP variant expressing cell line.
5. The antibody or hLIGHT binding fragment thereof of claim 1 , wherein the antibody is an antagonist.
6. The antibody or hLIGHT binding fragment thereof of claim 2 , wherein the antibody is an antagonist.
7. The antibody or hLIGHT binding fragment thereof of claim 1 , wherein the antibody competes with HVEM, LTβR, or a fusion protein thereof, for binding to cell surface-expressed hLIGHT or soluble hLIGHT.
8. The antibody or hLIGHT binding fragment thereof of claim 2 , wherein the antibody competes with HVEM, LTβR, or a fusion protein thereof, for binding to cell surface-expressed hLIGHT or soluble hLIGHT.
9. An isolated antibody or a hLIGHT binding fragment thereof, that specifically binds to the native form of soluble hLIGHT but does not bind to denatured hLIGHT, wherein the antibody comprises (a) a VH of an antibody produced by a hybridoma having ATCC Accession No. PTA-7728; and (b) a VL of an antibody produced by the hybridoma having ATCC Accession No. PTA-7728.
10. The antibody or hLIGHT binding fragment thereof of claim 1 , wherein the antibody is produced by a hybridoma having ATCC Accession No. PTA-7728.
11. The antibody or hLIGHT binding fragment thereof of claim 2 , wherein the antibody is produced by a hybridoma having ATCC Accession No. PTA-7728.
12. The antibody or hLIGHT binding fragment thereof of claim 1 , wherein the antibody is a fully human antibody or a chimeric antibody.
13. The antibody or hLIGHT binding fragment thereof of claim 2 , wherein the antibody is a fully human antibody or a chimeric antibody.
14. The antibody or hLIGHT binding fragment thereof of claim 1 , wherein the antibody is a monoclonal antibody.
15. The antibody or hLIGHT binding fragment thereof of claim 2 , wherein the antibody is a monoclonal antibody.
16. The antibody or hLIGHT binding fragment thereof of claim 1 , wherein the antibody is a recombinant antibody.
17. The antibody or hLIGHT binding fragment thereof of claim 2 , wherein the antibody is a recombinant antibody.
18. The antibody or hLIGHT binding fragment thereof of claim 1 , wherein the antibody or the hLIGHT binding fragment thereof is a Fab fragment, F(ab′) 2 fragment, single chain Fv (scFv), diabody or triabody.
19. The antibody or hLIGHT binding fragment thereof of claim 2 , wherein the antibody or the hLIGHT binding fragment thereof is a Fab fragment, F(ab′) 2 fragment, single chain Fv (scFv), diabody or triabody.
20. A composition comprising the antibody or hLIGHT binding fragment thereof of claim 1 .
21. A composition comprising the antibody or hLIGHT binding fragment thereof of claim 2 .
22. A hybridoma having ATCC Accession No. PTA-7728 (124 F23).
23. A pharmaceutical composition comprising the antibody or hLIGHT binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
24. A pharmaceutical composition comprising the antibody or hLIGHT binding fragment thereof of claim 2 and a pharmaceutically acceptable carrier.
25. A kit which comprises the antibody or hLIGHT binding fragment thereof of claim 1 .
26. A kit which comprises the antibody or hLIGHT binding fragment thereof of claim 2 .
27. A kit which comprises the composition of claim 20 .
28. A kit which comprises the composition of claim 21 .