Nucleic acids encoding anti-IL-6 antibodies of defined epitopic specificity
View Patent ↗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. An isolated nucleic acid molecule encoding a variable heavy (V H ) chain of an anti-human IL-6 antibody or anti-human IL-6 antibody fragment, wherein said V H chain is a humanized V H chain polypeptide having an amino acid sequence of SEQ ID NOs:652, 656, 657, or 658 or a V H chain polypeptide comprising the same CDRs as any of said humanized V H chain polypeptides having the amino acid sequence of SEQ ID NO:652, 656, 657, or 658.
2. A vector containing an isolated nucleic acid according to claim 1 .
3. An isolated host cell comprising a vector according to claim 2 .
4. An isolated nucleic acid molecule encoding a variable light (V L ) chain of an anti-human IL-6 antibody or anti-human IL-6 antibody fragment, wherein said V L chain is a humanized V L chain polypeptide having an amino acid sequence of SEQ ID NO: 647 or 651 or a V L chain polypeptide comprising the same CDRs as said humanized V L chain polypeptide having the amino acid sequence of SEQ ID NO: 647 or 651.
5. A vector containing an isolated nucleic acid according to claim 4 .
6. An isolated host cell comprising a vector according to claim 5 .
7. An isolated nucleic acid molecule encoding an anti-human IL-6 antibody or anti-human IL-6 antibody fragment, wherein the variable heavy (V H ) chain of said anti-human IL-6 antibody or anti-human IL-6 antibody fragment is a humanized V H chain polypeptide having an amino acid sequence of SEQ ID NOs:652, 656, 657, or 658 or a V H chain polypeptide comprising the same CDRs as any of said humanized V H chain polypeptides having the amino acid sequence of SEQ ID NOs:652, 656, 657, or 658-and the variable light (V L ) chain of said anti-human IL-6 antibody or anti-human IL-6 antibody fragment is a humanized V L chain polypeptide having an amino acid sequence of SEQ ID NO: 647 or 651 or a V L chain polypeptide comprising the same CDRs as said humanized V L chain polypeptide having the amino acid sequence of SEQ ID NO: 647 or 651.
8. A vector containing an isolated nucleic acid according to claim 7 .
9. A vector according to claim 8 , which further comprises nucleic acids that are operably linked to encode from the N-terminal V H chain and V L chain to C-terminal end of each chain, a nucleic acid sequence that encodes human antibody constant regions.
10. A vector according to claim 9 , wherein the nucleic acids encode a human IgG1 heavy constant region having an amino acid sequence of SEQ ID NO:588 and a human IgG1 light constant regions having an amino acid sequence of SEQ ID NO:586.
11. An isolated host cell comprising a vector according to claim 10 .
12. A Pichia or CHO host cell comprising a vector according to claim 10 .
13. An isolated host cell comprising a vector according to claim 9 .
14. A Pichia or CHO host cell comprising a vector according to claim 9 .
15. A vector according to claim 8 , which further comprises nucleic acids that are operably linked to encode from the N-terminal V H chain and V L chain to C-terminal end of each chain, a nucleic acid sequence that encodes human IgG1 constant regions.
16. An isolated host cell comprising a vector according to claim 15 .
17. A Pichia or CHO host cell comprising a vector according to claim 15 .
18. An isolated host cell comprising a vector according to claim 8 .
19. A Pichia or CHO host cell comprising a vector according to claim 8 .