Antibodies to interleukin-6
The present invention provides an isolated IL-6 antagonist including an antibody variable region that prevents IL-6 from binding to gp130. The present invention also provides compositions and methods for treating IL-6 related diseases based on the IL-6 antagonists of the invention.
1. An isolated antibody specific for a complex of IL-6 and IL-6Ralpha, wherein the antibody comprises an antibody variable region, wherein the antibody variable region binds to an epitope on IL-6 such that the binding sterically blocks the interaction between IL-6 and gp130, wherein the antibody variable region does not sterically block an interaction between IL-6 and IL-6Ralpha.
2. The antibody of claim 1 , wherein the antibody variable region comprises a heavy chain CDR1 comprising an amino acid sequence selected from the group consisting of FTFSNYWMN (SEQ ID NO:2), FSFSNYWMN (SEQ ID NO:3), and FTFSDAWMD (SEQ ID NO:4).
3. The antibody of claim 1 , wherein the antibody variable region comprises a heavy chain CDR2 comprising an amino acid sequence selected from the group consisting of EIRLKSNNYATHYAESVKG (SEQ ID NO:6), EIRLKSNKGATHYAESVKG (SEQ ID NO:7), EIRLTSNKQAIYYAESVKG (SEQ ID NO:8), and EIRSKANNHATYYAESVKG (SEQ ID NO:9).
4. The antibody of claim 1 , wherein the antibody variable region comprises a heavy chain CDR3 comprising an amino acid sequence selected from the group consisting of EDYYGYPDY (SEQ ID NO:11), LLYDGYLH (SEQ ID NO:12), LFYDGYLH (SEQ ID NO:13), and PTLYGAMDY (SEQ ID NO:14).
5. The antibody of claim 1 , wherein the antibody variable region comprises a light chain CDR1 comprising an amino acid sequence selected from the group consisting of RASESVDNFGISFM (SEQ ID NO:16), RASESVGNFGISFM (SEQ ID NO:17), RASESVHNFGISFM (SEQ ID NO:18), and RASESVDNYGISFM (SEQ ID NO:19).
6. The antibody of claim 1 , wherein the antibody variable region comprises a light chain CDR2 comprising an amino acid sequence selected from the group consisting of TASNQGS (SEQ ID NO:21), VASNQGS (SEQ ID NO:22), and AASNQGS (SEQ ID NO:23).
7. The antibody of claim 1 , wherein the antibody variable region comprises a light chain CDR3 comprising an amino acid sequence selected from the group consisting of QQSKEVPWT (SEQ ID NO:25), QQSKEVPYT (SEQ ID NO:26), QQSKEIPWT (SEQ ID NO:27), and QQGKEVPWT (SEQ ID NO:28).
8. The antibody of claim 1 , wherein the antibody comprises a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, and SEQ ID NO:36.
9. The antibody of claim 1 , wherein the antibody comprises a heavy chain comprising an amino acid sequence at least 90% identical to SEQ ID NO:35, wherein the heavy chain comprises a CDR1 comprising SEQ ID NO:3, a CDR2 comprising SEQ ID NO:8, and a CDR3 comprising SEQ ID NO:13.