Stabilized formulations containing anti-PCSK9 antibodies
The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human proprotein convertase subtilisin/kexin type 9 (PCSK9). The formulations may contain, in addition to an anti-PCSK9 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 consists of:
(a) 50±7.5 mg/mL to 250±37.5 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin kexin-9 (PCSK9), wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain (HCVD) comprising SEQ ID NO:1, and a light chain variable domain (LCVD) comprising SEQ ID NO:5;
(b) 5±0.75 mM to 10±1.5 mM histidine, pH 6.0±0.3;
(c) 0.01±0.0015% w/v polysorbate 20; and
(d) 10±1.5% w/v sucrose.
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 the syringe is a 1 mL long glass syringe comprising a 27 gauge thin wall needle, a fluorocarbon coated rubber plunger, and a rubber needle shield.
8. A pre-filled syringe composition comprising a liquid pharmaceutical formulation, wherein the liquid pharmaceutical formulation consists of:
(a) 75 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin kexin-9 (PCSK9), wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain (HCVD) comprising SEQ ID NO:1, and a light chain variable domain (LCVD) comprising SEQ ID NO:5;
(b) 8±1.2 mM histidine, pH 6.0±0.3;
(c) 0.01±0.0015% w/v polysorbate 20; and
(d) 10±1.5% w/v sucrose.
9. The pre-filled syringe composition of claim 8 , wherein the syringe is a normal tungsten syringe.
10. The pre-filled syringe composition of claim 8 , wherein the syringe is a low tungsten syringe.
11. The pre-filled syringe composition of claim 8 , wherein the syringe comprises a coated plunger.
12. The pre-filled syringe composition of claim 11 , wherein the coated plunger is coated with a fluorocarbon film.
13. The pre-filled syringe composition of claim 8 , wherein the syringe is a low tungsten syringe, and wherein the syringe comprises a coated plunger.
14. The pre-filled syringe composition of claim 8 , wherein the syringe is a 1 mL long glass syringe comprising a 27 gauge thin wall needle, a fluorocarbon coated rubber plunger, and a rubber needle shield.
15. A pre-filled syringe composition comprising a liquid pharmaceutical formulation, wherein the liquid pharmaceutical formulation consists of:
(a) 150 mg/mL of an antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin kexin-9 (PCSK9), wherein the antibody or antigen-binding fragment comprises a heavy chain variable domain (HCVD) comprising SEQ ID NO:1, and a light chain variable domain (LCVD) comprising SEQ ID NO:5;
(b) 6±0.9 mM histidine (pH 6.0±0.3);
(c) 0.01±0.0015% w/v polysorbate 20; and
(d) 10±1.5% w/v sucrose.
16. The pre-filled syringe composition of claim 15 , wherein the syringe is a normal tungsten syringe.
17. The pre-filled syringe composition of claim 15 , wherein the syringe is a low tungsten syringe.
18. The pre-filled syringe composition of claim 15 , wherein the syringe comprises a coated plunger.
19. The pre-filled syringe composition of claim 18 , wherein the coated plunger is coated with a fluorocarbon film.
20. The pre-filled syringe composition of claim 15 , wherein the syringe is a low tungsten syringe, and wherein the syringe comprises a coated plunger.
21. The pre-filled syringe composition of claim 15 , wherein the syringe is a 1 mL long glass syringe comprising a 27 gauge thin wall needle, a fluorocarbon coated rubber plunger, and a rubber needle shield.