Stabilized formulations containing anti-interleukin-6 receptor (IL-6R) antibodies
The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human interleukin-6 receptor (hIL-6R). The formulations may contain, in addition to an anti-hIL-6R antibody, at least one amino acid, at least one sugar, and/or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.
1. A stable pharmaceutical formulation comprising: (i) 5 mg/mL 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) histidine at a concentration of from 25 mM to 100 mM; (iii) arginine at a concentration of from 25 mM to 50 mM; (iv) sucrose in an amount of from 3% to 10% w/v; and (v) polysorbate 20 in an amount of from 0.1% to 0.2%, 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 pharmaceutical formulation of claim 1 , comprising: (i) about 150 mg/mL of the antibody; (ii) about 25 mM histidine; (iii) about 5% sucrose; (iv) about 0.2% polysorbate 20; and (v) about 25 mM arginine.
3. The pharmaceutical formulation of claim 1 , comprising: (i) about 175 mg/mL of the antibody; (ii) about 25 mM histidine; (iii) about 5% sucrose; (iv) about 0.2% polysorbate 20; and (v) about 50 mM arginine.
4. The pharmaceutical formulation of claim 3 contained in a glass vial.
5. The pharmaceutical formulation of claim 3 contained in a syringe.
6. The pharmaceutical formulation of claim 3 contained in a microinfusor.
7. The pharmaceutical formulation of claim 5 , wherein said syringe comprises a fluorocarbon-coated plunger.
8. The pharmaceutical formulation of claim 5 , wherein said syringe is a low tungsten syringe.
9. The pharmaceutical formulation of claim 8 , wherein said syringe comprises a fluorocarbon-coated plunger.
10. The pharmaceutical formulation of claim 3 , wherein at least 90% of native form of said antibody is recovered after nine months of storage at 5° C., as determined by size exclusion-high performance liquid chromatography (SE-HPLC).
11. The pharmaceutical formulation of claim 10 , wherein at least 95% of native form of said antibody is recovered after nine months of storage at 5° C., as determined by size exclusion-high performance liquid chromatography (SE-HPLC).
12. The pharmaceutical formulation of claim 11 , wherein at least 96% of native form of said antibody is recovered after nine months of storage at 5° C., as determined by size exclusion-high performance liquid chromatography (SE-HPLC).
13. The pharmaceutical formulation of claim 3 , wherein the formulation exhibits a viscosity of less than about 15 cPoise.
14. The pharmaceutical formulation of claim 13 , wherein the formulation exhibits a viscosity of less than about 12 cPoise.
15. The pharmaceutical formulation of claim 14 , wherein the formulation exhibits a viscosity of less than about 9 cPoise.
16. 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 25 mM histidine; (iii) about 5% sucrose; (iv) about 0.2% polysorbate 20; and (v) about 50 mM arginine, wherein the formulation has a pH of about 6.0 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.
17. A stable pharmaceutical formulation comprising: (i) 25 mg/mL 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 25 mM histidine; (iii) about 25 mM or about 50 mM arginine; (iv) about 5% w/v sucrose; and (v) about 0.2% w/v polysorbate 20, 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.