Antibodies to IL-6 and use thereof
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 said 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. A method of producing an anti-interleukin 6 (IL-6) antibody or antibody fragment comprising:
(i) obtaining a cell comprising a nucleic acid sequence encoding a light chain polypeptide or variable light chain polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:2, 20, 702, 706 and 709; and further comprising a nucleic acid sequence encoding a heavy chain polypeptide or variable heavy chain polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:3, 18, 19, 657, 658, 704 and 708;
(ii) culturing said cell under conditions whereby an anti-IL-6 antibody or antibody fragment is expressed comprising a light chain polypeptide or variable light chain polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:2, 20, 702, 706 and 709 and a heavy chain polypeptide or variable heavy chain polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:3, 18, 19, 657, 658, 704 and 708.
2. The method of claim 1 , wherein said cell is a bacterial, yeast or mammalian cell.
3. The method of claim 1 , wherein said cell is a yeast cell.
4. The method of claim 3 , wherein said yeast cell is a Pichia cell.
5. The method of claim 3 , wherein said yeast cell is a Pichia pastoris cell.
6. The method of claim 3 , wherein said yeast cell is a diploid Pichia pastoris cell.
7. The method of claim 1 , wherein said cell is a mammalian cell.
8. The method of claim 7 , wherein said mammalian cell is a CHO cell.
9. The method of claim 1 , wherein said anti-IL6 antibody comprises a light chain polypeptide or variable heavy chain polypeptide comprising the amino acid sequence of SEQ ID NOS: 709; and a heavy chain polypeptide or a variable light chain polypeptide comprising an amino acid sequence of SEQ ID NO: 657.
10. The method of claim 1 , wherein said anti-IL6 antibody comprises a light chain polypeptide comprising the amino acid sequence of SEQ ID NOS: 702 and a heavy chain polypeptide comprising an amino acid sequence of SEQ ID NO: 704.
11. The method of claim 1 , wherein said light chain polypeptide is encoded by SEQ ID NO: 701 or SEQ ID NO: 705 and the heavy chain polypeptide is encoded by SEQ ID NO:703 or 707.
12. The method of claim 1 , wherein said light chain polypeptide is encoded by SEQ ID NO:701 and the heavy chain polypeptide is encoded by SEQ ID NO:703.
13. The method of claim 1 , wherein said light chain polypeptide is encoded by SEQ ID NO:705 and the heavy chain polypeptide is encoded by SEQ ID NO:707.
14. The method of claim 1 , wherein said light chain polypeptide is encoded by SEQ ID NO:705 and the heavy chain polypeptide is encoded by SEQ ID NO:703.
15. The method of claim 1 , wherein said light chain polypeptide is encoded by SEQ ID NO:701 and the heavy chain polypeptide is encoded by SEQ ID NO:707.
16. The method of claim 1 , which includes isolating the expressed antibody or antibody fragment from said cell.
17. The method of claim 1 , which includes isolating the expressed antibody or antibody fragment from a culture medium containing said cell.