Isolated host cells expressing anti-IL-6 antibodies
The present invention is directed to antibodies and fragments thereof and humanized versions thereof having binding specificity for IL-6. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the V H , V L and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-IL-6 antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making the anti-IL-6 antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-IL-6 antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with IL-6. These antibodies may bind at least one of soluble IL-6, cell surface expressed IL-6, IL-6/IL-6R and/or prevent the association of IL-6 and IL-6R, the association of IL-6/IL-6R and gp130 and or the formation of IL-6/IL-6R/gp130 multimers and thereby inhibit a biological effect associated with any of the foregoing.
1. An isolated host cell which expresses an anti-human IL-6 antibody or antigen-binding fragment which comprises a variable light (V L ) region comprising complementarity region CDR1, CDR2 and CDR3 polypeptides, respectively having the sequences of SEQ ID NO:4, 5 and 6, and a variable heavy (V H ) region comprising complementarity region CDR1, CDR2 and CDR3 polypeptides, respectively having the sequences of SEQ ID NO:7, 8 or 120 and 9.
2. The host cell of claim 1 , wherein the V L region comprises CDR1, CDR2 and CDR3 polypeptides, respectively having the sequences of SEQ ID NO:4, 5 and 6, and the V H region comprises CDR1, CDR2 and CDR3 polypeptides, respectively having the sequences of SEQ ID NO:7, 120 and 9.
3. The host cell of claim 1 , wherein the V L chain comprises a polypeptide which is at least 90% identical to a polypeptide having the sequence of SEQ ID NO:20 and the V H chain comprises a polypeptide which is at least 90% identical to the to a polypeptide having the sequence of SEQ ID NO: 18 or 19.
4. The host cell of claim 1 , wherein the V H chain comprises a polypeptide having the sequence of SEQ ID NO: 18 or 19 and a V L chain which comprises a polypeptide having the sequence of SEQ ID NO: 20.
5. The host cell of claim 1 , wherein said anti-human IL-6 antibody or fragment is a human, humanized or chimeric anti-human IL-6 antibody or fragment thereof.
6. The host cell of claim 1 , wherein said anti-human IL-6 antibody or fragment contains a human Fc region.
7. The host cell of claim 6 wherein said Fc region is of the IgG1, IgG2, IgG3 or IgG4 isotype.
8. The host cell of claim 7 wherein said Fc region is of the IgG1 isotype.
9. The host cell of claim 8 wherein said IgG1 Fc region comprises a kappa light chain polypeptide having the sequence of SEQ ID NO:586 and a gamma-1 constant heavy chain polypeptide having the sequence of SEQ ID NO:588.
10. The host cell of claim 1 , wherein said anti-human IL-6 antibody or fragment contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.
11. The host cell of claim 1 , wherein said anti-human IL-6 antibody or fragment is a humanized antibody or antibody fragment.
12. The host cell of claim 1 which is a mammalian or yeast cell.
13. The host cell of claim 12 which is Pichia pastoris.
14. The host cell of claim 12 which is a CHO cell.