Stabilized formulations containing anti-interleukin-4 receptor (IL-4R) antibodies
The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human interleukin-4 receptor (hIL-4R). The formulations may contain, in addition to an anti-hIL-4R antibody, at least one amino acid, at least one sugar, 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 pre-filled syringe composition comprising a liquid pharmaceutical formulation, wherein the liquid pharmaceutical formulation comprises:
(a) 100±10 mg/mL to 200±20 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human interleukin-4 receptor alpha (hIL-4Rα), wherein the antibody comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1, and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO:5;
(b) 10 mM to 15 mM acetate;
(c) 15 mM to 25 mM histidine;
(d) 2.5% w/v to 10% w/v sucrose;
(e) 0.1% w/v to 0.3% w/v polysorbate; and
(f) 20 mM to 100 mM arginine;
wherein said liquid pharmaceutical formulation has a pH of from 5.6 to 6.2 and is contained within a syringe.
2. The pre-filled syringe composition of claim 1 , wherein the syringe is a normal tungsten syringe.
3. The pre-filled syringe composition of claim 1 , wherein the syringe is a low tungsten syringe.
4. The pre-filled syringe composition of claim 1 , wherein the syringe comprises a coated plunger.
5. The pre-filled syringe composition of claim 4 , wherein the coated plunger is coated with a fluorocarbon film.
6. The pre-filled syringe composition of claim 1 , wherein the syringe is a low tungsten syringe, and wherein the syringe comprises a coated plunger.
7. The pre-filled syringe composition of claim 1 , wherein at least 90% of the antibody has native conformation after eight weeks of storage at 45° C.
8. The pre-filled syringe composition of claim 1 , wherein less than 45% of the antibody is an acidic form of the antibody after eight weeks of storage at 45° C.
9. The pre-filled syringe composition of claim 1 , wherein at least 98% of the antibody has native conformation after six months of storage at 5° C.
10. The pre-filled syringe composition of claim 1 , wherein less than 4% of the antibody recovered after six months of storage at 25° C. is aggregated.
11. The pre-filled syringe composition of claim 1 , wherein the formulation comprises about 175 mg/mL of the antibody.
12. The pre-filled syringe composition of claim 1 , wherein the formulation comprises about 150 mg/mL of the antibody.
13. The pre-filled syringe composition of claim 1 , wherein the formulation comprises about 100 mg/mL of the antibody.
14. The pre-filled syringe composition of claim 1 , wherein the polysorbate is polysorbate 20.
15. The pre-filled syringe composition of claim 1 , wherein the polysorbate is polysorbate 80.
16. The pre-filled syringe composition of claim 1 , wherein the polysorbate is present at a concentration of 0.2%±0.03% w/v.
17. The pre-filled syringe composition of claim 1 , wherein the arginine is present at a concentration of 25 mM±3.75 mM.
18. The pre-filled syringe composition of claim 1 , wherein the arginine is present at a concentration of 50 mM±7.5 mM.
19. The pre-filled syringe composition of claim 1 , wherein the formulation comprises:
(a) 150±50.0 mg/mL of the antibody;
(b) 12.5 mM±2 mM acetate;
(c) 20 mM±3 mM histidine;
(d) 5%±0.75% w/v sucrose;
(e) 0.2% w/v±0.03% w/v polysorbate 20; and
(f) 25 mM±3.75 mM arginine;
wherein said liquid pharmaceutical formulation has a pH of 5.9±0.5.
20. The pre-filled syringe composition of claim 1 , wherein the formulation comprises:
(a) 150±50.0 mg/mL of the antibody;
(b) 12.5 mM±2 mM acetate;
(c) 20 mM±3 mM histidine;
(d) 5%±0.75% w/v sucrose;
(e) 0.2% w/v±0.03% w/v polysorbate 80; and
(f) 25 mM±3.75 mM arginine;
wherein said liquid pharmaceutical formulation has a pH of 5.9±0.5.
21. The pre-filled syringe composition of claim 1 , wherein the formulation comprises:
(a) 175 mg/mL of the antibody;
(b) 12.5 mM±2 mM acetate;
(c) 20 mM±3 mM histidine;
(d) 5%±0.75% w/v sucrose;
(e) 0.2% w/v±0.03% w/v polysorbate 20; and
(f) 50 mM±7.5 mM arginine;
wherein said liquid pharmaceutical formulation has a pH of 5.9±0.5.
22. The pre-filled syringe composition of claim 1 , wherein the formulation comprises:
(a) 175 mg/mL of the antibody;
(b) 12.5 mM±2 mM acetate;
(c) 20 mM±3 mM histidine;
(d) 5%±0.75% w/v sucrose;
(e) 0.2% w/v±0.03% w/v polysorbate 80; and
(f) 50 mM±7.5 mM arginine;
wherein said liquid pharmaceutical formulation has a pH of 5.9±0.5.