IP Library › Granted Patent US 8,846,037
Granted Patent B2
US 8,846,037 · App. 13/857,867 · Granted Sep 30, 2014

Antibodies to IL-6 and their uses

Inventors: Arvind Rajpal (San Francisco, CA); Madhav Narasimha Devalaraja (Gaithersburg, MD); Kristopher Toy (San Jose, CA); Lan Yang (Morgan Hill, CA); Haichun Huang (Fremont, CA); Jun Zhang (Tracy, CA); Peter Brams (Sacramento, CA); Brigitte Devaux (Palo Alto, CA); David B. Passmore (San Carlos, CA)
Assignees: Pfizer Inc.; Bristol-Myers Squibb Company
C07K16/248C07K2317/565C07K2317/92C07K2317/567C07K2317/56
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 8,846,037
App. No.
13/857,867
Granted
Sep 30, 2014
Kind
B2
Abstract

Antibodies and antigen-binding portions thereof that bind to human IL-6 are provided. Also provided are nucleic acids encoding such antibodies and antigen binding portions, methods of making such antibodies and antigen binding portions, compositions comprising such antibodies or antigen binding portions, and uses of such antibodies or antigen binding portions.

Claims (105)

1. A method for treating or alleviating the symptoms of an IL-6 mediated disorder in a subject in need thereof, comprising administering to said subject an anti-IL-6 antibody or an antigen-binding portion thereof, wherein the antibody comprises a heavy chain and a light chain, and wherein

(a) the heavy chain comprises the CDR1, CDR2 and CDR3 of the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the light chain comprises the CDR1, CDR2 and CDR3 of the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016; or

(b) the heavy chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the light chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively.

2. The method of claim 1 , wherein the monoclonal antibody or antigen-binding portion comprises

heavy chain FR1, FR2, FR3, and FR4 comprising the amino acid sequences of (1) SEQ ID NOs: 8 or 38, (2) SEQ ID NO: 9, (3) SEQ ID NO: 10 or 30, and (4) SEQ ID NO: 11, respectively; and

light chain FR1, FR2, FR3, and FR4 comprising the amino acid sequences of (1) SEQ ID NO: 19, (2) SEQ ID NO: 20, (3) SEQ ID NO: 21, and (4) SEQ ID NO: 22, respectively.

3. The method of claim 1 , wherein the monoclonal antibody or antigen-binding portion comprises a V H domain and a V L domain comprising the amino acid sequences of:

(a) SEQ ID NOs: 4 and 15, respectively;

(b) SEQ ID NOs: 29 and 15, respectively;

(c) SEQ ID NOs: 37 and 15, respectively;

(d) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8013 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively;

(e) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016, respectively; or

(f) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8019 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively.

4. The method of claim 1 , wherein the heavy and light chains comprise the amino acid sequences of:

(a) SEQ ID NOs: 3 and 14, respectively;

(b) SEQ ID NOs: 24 and 26, respectively;

(c) SEQ ID NOs: 32 and 14, respectively;

(d) SEQ ID NOs: 28 and 26, respectively;

(e) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8013 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively;

(f) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016, respectively; or

(g) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8019 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively.

5. A method for treating or alleviating the symptoms of an IL-6 mediated disorder in a subject in need thereof, comprising administering to said subject a pharmaceutical composition comprising an anti-IL-6 monoclonal antibody or an antigen-binding portion thereof, and a pharmaceutically acceptable carrier, wherein the antibody comprises a heavy chain and a light chain, and wherein

(a) the heavy chain comprises the CDR1, CDR2 and CDR3 of the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the light chain comprises the CDR1, CDR2 and CDR3 of the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016; or

(b) the heavy chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the light chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively.

6. The method of claim 1 , wherein the IL-6 mediated disorder is selected from the group consisting of an inflammatory disorder, an allergic disorder, an autoimmune disorder, a graft rejection disorder, atherosclerosis, osteoporosis, neuropathic pain, type 2 diabetes mellitus, chronic obstructive pulmonary disease, multiple sclerosis, sepsis, cancer, Castleman's disease, and a fibrotic condition.

7. The method of claim 6 wherein said inflammatory disorder is selected from the group consisting of rheumatoid arthritis, juvenile idiopathic arthritis, osteoarthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis, Crohn's disease, and adult-onset Still's disease.

8. The method of claim 6 wherein said fibrotic condition is selected from the group consisting of liver fibrosis, renal fibrosis, and pulmonary fibrosis.

9. The method of claim 6 wherein said cancer is multiple myeloma or renal cell carcinoma.

10. The method of claim 5 , wherein the monoclonal antibody or antigen-binding portion comprises

heavy chain FR1, FR2, FR3, and FR4 comprising the amino acid sequences of (1) SEQ ID NOs: 8 or 38, (2) SEQ ID NO: 9, (3) SEQ ID NO: 10 or 30, and (4) SEQ ID NO: 11, respectively; and

light chain FR1, FR2, FR3, and FR4 comprising the amino acid sequences of (1) SEQ ID NO: 19, (2) SEQ ID NO: 20, (3) SEQ ID NO: 21, and (4) SEQ ID NO: 22, respectively.

11. The method of claim 5 , wherein the monoclonal antibody or antigen-binding portion comprises a V H domain and a V L domain comprising the amino acid sequences of:

(a) SEQ ID NOs: 4 and 15, respectively;

(b) SEQ ID NOs: 29 and 15, respectively;

(c) SEQ ID NOs: 37 and 15, respectively;

(d) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8013 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively;

(e) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016, respectively; or

(f) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8019 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively.

12. The method of claim 6 , wherein the heavy and light chains comprise:

(a) SEQ ID NOs: 3 and 14, respectively;

(b) SEQ ID NOs: 24 and 26, respectively;

(c) SEQ ID NOs: 32 and 14, respectively;

(d) SEQ ID NOs: 28 and 26, respectively;

(e) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8013 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively;

(f) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016, respectively; or

(g) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8019 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively.

13. The method of claim 6 , wherein the IL-6 mediated disorder is selected from the group consisting of an inflammatory disorder, an allergic disorder, an autoimmune disorder, a graft rejection disorder, atherosclerosis, osteoporosis, neuropathic pain, type 2 diabetes mellitus, chronic obstructive pulmonary disease, multiple sclerosis, sepsis, cancer, Castleman's disease, and a fibrotic condition.

14. The method of claim 13 wherein said inflammatory disorder is selected from the group consisting of rheumatoid arthritis, juvenile idiopathic arthritis, osteoarthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis, Crohn's disease, and adult-onset Still's disease.

15. The method of claim 13 wherein said fibrotic condition is selected from the group consisting of liver fibrosis, renal fibrosis, and pulmonary fibrosis.

16. The method of claim 13 wherein said cancer is multiple myeloma or renal cell carcinoma.

17. A method for treating or alleviating the symptoms of an IL-6 mediated disorder in a subject in need thereof, comprising administering to said subject an anti-IL-6 antibody comprising a heavy chain amino acid sequence of SEQ ID NO: 28 and a light chain amino acid sequence of SEQ ID NO: 26.

18. The method of claim 17 , wherein the IL-6 mediated disorder is selected from the group consisting of an inflammatory disorder, an allergic disorder, an autoimmune disorder, a graft rejection disorder, atherosclerosis, osteoporosis, neuropathic pain, type 2 diabetes mellitus, chronic obstructive pulmonary disease, multiple sclerosis, sepsis, cancer, Castleman's disease, and a fibrotic condition.

19. The method of claim 18 wherein said inflammatory disorder is selected from the group consisting of rheumatoid arthritis, juvenile idiopathic arthritis, osteoarthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis, Crohn's disease, and adult-onset Still's disease.

20. The method of claim 18 wherein said fibrotic condition is selected from the group consisting of liver fibrosis, renal fibrosis, and pulmonary fibrosis.

21. The method of claim 18 wherein said cancer is multiple myeloma or renal cell carcinoma.

22. A method for treating or alleviating the symptoms of Crohn's disease in a subject in need thereof, comprising administering to said subject an anti-IL-6 antibody or an antigen-binding portion thereof, wherein the antibody comprises a heavy chain and a light chain, and wherein

(a) the heavy chain comprises the CDR1, CDR2 and CDR3 of the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the light chain comprises the CDR1, CDR2 and CDR3 of the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016; or

(b) the heavy chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the light chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively.

23. A method for treating or alleviating the symptoms of Crohn's disease in a subject in need thereof, comprising administering to said subject a pharmaceutical composition comprising an anti-IL-6 antibody or an antigen-binding portion thereof, wherein the antibody comprises a heavy chain and a light chain, and wherein

(a) the heavy chain comprises the CDR1, CDR2 and CDR3 of the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the light chain comprises the CDR1, CDR2 and CDR3 of the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016; or

(b) the heavy chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the light chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively.

24. The method of claim 22 or 23 , wherein the monoclonal antibody or antigen-binding portion comprises

heavy chain FR1, FR2, FR3, and FR4 comprising the amino acid sequences of (1) SEQ ID NOs: 8 or 38, (2) SEQ ID NO: 9, (3) SEQ ID NO: 10 or 30, and (4) SEQ ID NO: 11, respectively; and

light chain FR1, FR2, FR3, and FR4 comprising the amino acid sequences of (1) SEQ ID NO: 19, (2) SEQ ID NO: 20, (3) SEQ ID NO: 21, and (4) SEQ ID NO: 22, respectively.

25. The method of claim 22 or 23 , wherein the monoclonal antibody or antigen-binding portion comprises a V H domain and a V L domain comprising the amino acid sequences of:

(a) SEQ ID NOs: 4 and 15, respectively;

(b) SEQ ID NOs: 29 and 15, respectively;

(c) SEQ ID NOs: 37 and 15, respectively;

(d) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8013 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively;

(e) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016, respectively; or

(f) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8019 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively.

26. The method of claim 22 or 23 , wherein the heavy and light chains comprise the amino acid sequences of:

(a) SEQ ID NOs: 3 and 14, respectively;

(b) SEQ ID NOs: 24 and 26, respectively;

(c) SEQ ID NOs: 32 and 14, respectively;

(d) SEQ ID NOs: 28 and 26, respectively;

(e) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8013 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively;

(f) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016, respectively; or

(g) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8019 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively.

27. A method for treating or alleviating the symptoms of Crohn's disease in a subject in need thereof, comprising administering to said subject an anti-IL-6 antibody comprising a heavy chain amino acid sequence of SEQ ID NO: 28 and a light chain amino acid sequence of SEQ ID NO: 26.

28. A method for treating or alleviating the symptoms of systemic lupus erythematosus in a subject in need thereof, comprising administering to said subject an anti-IL-6 antibody or an antigen-binding portion thereof, and a pharmaceutically acceptable carrier, wherein the antibody comprises a heavy chain and a light chain, and wherein

(a) the heavy chain comprises the CDR1, CDR2 and CDR3 of the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the light chain comprises the CDR1, CDR2 and CDR3 of the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016; or

(b) the heavy chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the light chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively.

29. A method for treating or alleviating the symptoms of systemic lupus erythematosus in a subject in need thereof, comprising administering to said subject a pharmaceutical composition comprising an anti-IL-6 monoclonal antibody or an antigen-binding portion thereof, and a pharmaceutically acceptable carrier, wherein the antibody comprises a heavy chain and a light chain, and wherein

(a) the heavy chain comprises the CDR1, CDR2 and CDR3 of the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the light chain comprises the CDR1, CDR2 and CDR3 of the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016; or

(b) the heavy chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 5, 6, and 7, respectively, and the light chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of SEQ ID NOs: 16, 17, and 18, respectively.

30. The method of claim 28 or 29 , wherein the monoclonal antibody or antigen-binding portion comprises

heavy chain FR1, FR2, FR3, and FR4 comprising the amino acid sequences of (1) SEQ ID NOs: 8 or 38, (2) SEQ ID NO: 9, (3) SEQ ID NO: 10 or 30, and (4) SEQ ID NO: 11, respectively; and

light chain FR1, FR2, FR3, and FR4 comprising the amino acid sequences of (1) SEQ ID NO: 19, (2) SEQ ID NO: 20, (3) SEQ ID NO: 21, and (4) SEQ ID NO: 22, respectively.

31. The method of claim 28 or 29 , wherein the monoclonal antibody or antigen-binding portion comprises a V H domain and a V L domain comprising the amino acid sequences of:

(a) SEQ ID NOs: 4 and 15, respectively;

(b) SEQ ID NOs: 29 and 15, respectively;

(c) SEQ ID NOs: 37 and 15, respectively;

(d) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8013 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively;

(e) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016, respectively; or

(f) the V H domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8019 and the V L domain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively.

32. The method of claim 28 or 29 , wherein the heavy and light chains comprise the amino acid sequences of:

(a) SEQ ID NOs: 3 and 14, respectively;

(b) SEQ ID NOs: 24 and 26, respectively;

(c) SEQ ID NOs: 32 and 14, respectively;

(d) SEQ ID NOs: 28 and 26, respectively;

(e) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8013 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively;

(f) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8015 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8016, respectively; or

(g) the heavy chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8019 and the light chain encoded by the cDNA insert of the plasmid deposited with the ATCC under accession number PTA-8014, respectively.

33. A method for treating or alleviating the symptoms of systemic lupus erythematosus in a subject in need thereof, comprising administering to said subject an anti-IL-6 antibody comprising a heavy chain amino acid sequence of SEQ ID NO: 28 and a light chain amino acid sequence of SEQ ID NO: 26.

Continuity (4)
Division 13454296 · Apr 24, 2012
Division 12480991 · Jun 9, 2009
Provisional Application 61073430 · Jun 18, 2008
Related Publication 20130280266A1 · Oct 24, 2013