Stabilized formulations containing anti-interleukin-6 receptor (IL-6R) antibodies

1. A prefilled syringe containing a stable pharmaceutical formulation comprising:

(i) a human antibody that specifically binds to human interleukin-6 receptor (hIL-6R), wherein the antibody is at a concentration of from about 5 mg/ml to about 200 mg/ml and comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO:18 and a light chain variable region having the amino acid sequence of SEQ ID NO:26;

(ii) histidine at a concentration of from about 10 mM to about 25 mM;

(iii) arginine at a concentration of from about 25 mM to about 50 mM;

(iv) sucrose in an amount of from about 5% to about 10% w/v; and

(v) polysorbate in an amount of from about 0.1% to about 0.2% w/v,

wherein the formulation has a pH of about 5.8, about 6.0, or about 6.2, and at least 90% of the native form of the antibody is recovered after 1 month of storage at 45° C., as determined by size exclusion chromatography.

2. The prefilled syringe of claim 1 , wherein the histidine is at a concentration of 21 mM.

3. The prefilled syringe of claim 2 , wherein the arginine is present at a concentration of 45 mM.

4. The prefilled syringe of claim 3 , wherein the sucrose is present in an amount of 5% w/v.

5. The prefilled syringe of claim 4 , wherein the polysorbate is present at a concentration of 0.2% w/v.

6. The prefilled syringe of claim 5 , wherein the polysorbate is polysorbate 20.

7. The prefilled syringe of claim 6 , wherein the formulation has a pH of 6.

8. The prefilled syringe of claim 1 , wherein the antibody is at a concentration of from 25 mg/ml to 200 mg/ml.

9. The prefilled syringe of claim 1 , wherein the antibody is at a concentration of from 50 mg/ml to 180 mg/ml.

10. The prefilled syringe of claim 9 , wherein the antibody is at a concentration of 150 mg/ml.

11. The prefilled syringe of claim 9 , wherein the antibody is at a concentration of 175 mg/ml.

12. The prefilled syringe of claim 11 , wherein at least 90% of the native form of the antibody is recovered after nine months of storage at 5° C., as determined by size exclusion-high performance liquid chromatography (SE-HPLC).

13. The prefilled syringe of claim 12 , wherein at least 95% of the native form of the antibody is recovered after nine months of storage at 5° C., as determined by size exclusion-high performance liquid chromatography (SE-HPLC).

14. The prefilled syringe of claim 13 , wherein at least 96% of the native form of the antibody is recovered after nine months of storage at 5° C., as determined by size exclusion-high performance liquid chromatography (SE-HPLC).

15. The prefilled syringe of claim 11 , wherein the formulation exhibits a viscosity of less than about 15 cPoise.

16. The prefilled syringe of claim 11 , wherein the formulation exhibits a viscosity of less than about 12 cPoise.

17. The prefilled syringe of claim 11 , wherein the formulation exhibits a viscosity of less than about 9 cPoise.

18. The prefilled syringe of claim 1 that comprises a fluorocarbon-coated plunger.

19. The prefilled syringe of claim 1 that is a low tungsten syringe.

20. The prefilled syringe of claim 1 that is a staked needle prefilled syringe.

21. The prefilled syringe of claim 1 , wherein the prefilled syringe is for use in an autoinjector delivery device.

22. The prefilled syringe of claim 1 , wherein the human antibody that specifically binds to hIL-6R consists of two heavy chains and two light chains, each heavy chain comprising the heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 18 and a heavy chain constant region, and each light chain comprising the light chain variable region comprising the amino acid sequence of SEQ ID NO: 26 and a light chain constant region.

23. The prefilled syringe of claim 1 , wherein the human antibody that specifically binds to hIL-6R comprises two heavy chains and two light chains, each heavy chain comprising the heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 18 and a heavy chain constant region, and each light chain comprising the light chain variable region comprising the amino acid sequence of SEQ ID NO: 26 and a light chain constant region.

24. A prefilled syringe containing a stable pharmaceutical formulation comprising:

(i) 25 to 200 mg/mL of a human antibody that specifically binds to human interleukin-6 receptor (hIL-6R), wherein the antibody comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO:18 and a light chain variable region having the amino acid sequence of SEQ ID NO:26;

(ii) about 21, 22, 23, 24 or 25 mM histidine;

(iii) about 3%, 4% or 5% w/v sucrose;

(iv) about 0.18%, 0.19% or 0.2% w/v polysorbate 20; and

(v) about 45 or 50 mM arginine,

wherein the formulation has a pH of about 6, and at least 90% of the native form of the antibody is recovered after 1 month of storage at 45° C., as determined by size exclusion chromatography.

25. A prefilled syringe containing a stable pharmaceutical formulation comprising:

(i) about 150 mg/mL of a human antibody that specifically binds to human interleukin-6 receptor (hIL-6R), wherein said antibody comprises a heavy chain and light chain variable region (HCVR/LCVR) amino acid sequence pair of SEQ ID NOs:18/26;

(ii) about 21 mM histidine;

(iii) about 5% sucrose;

(iv) about 0.2% polysorbate 20; and

(v) about 45 mM arginine,

wherein the formulation has a pH of about 6, and at least 90% of the native form of the antibody is recovered after 1 month of storage at 45° C., as determined by size exclusion chromatography.

26. A prefilled syringe containing a stable pharmaceutical formulation comprising:

(i) about 175 mg/mL of a human antibody that specifically binds to human interleukin-6 receptor (hIL-6R), wherein said antibody comprises a heavy chain and light chain variable region (HCVR/LCVR) amino acid sequence pair of SEQ ID NOs:18/26;

(ii) about 21 mM histidine;

(iii) about 5% sucrose;

(iv) about 0.2% polysorbate 20; and

(v) about 45 mM arginine,

wherein the formulation has a pH of about 6, and at least 90% of the native form of the antibody is recovered after 1 month of storage at 45° C., as determined by size exclusion chromatography.

27. The prefilled syringe of claim 1 , wherein the prefilled syringe is for use in a reusable or disposable pen delivery device.