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 pen delivery device 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. A pre-filled pen delivery device 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.
3. A pre-filled pen delivery device 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.