Stabilized formulations containing anti-PCSK9 antibodies
View Patent ↗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 liquid pharmaceutical formulation comprising:
(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 comprises a heavy chain complementarity determining region (HCDR) 1 of SEQ ID NO:2, an HCDR2 of SEQ ID NO:3, an HCDR3 of SEQ ID NO:4, a light chain complementarity determining region (LCDR) 1 of SEQ ID NO:6, an LCDR2 of SEQ ID NO:7, and an LCDR3 of SEQ ID NO:8;
(b) 10±1.5 mM histidine (pH 6.0±0.3);
(c) 0.01±0.0015% w/v polysorbate 20; and
(d) 10±1.5% sucrose.
2. The liquid pharmaceutical formulation of claim 1 , wherein the antibody comprises a heavy chain variable domain (HCVD) comprising SEQ ID NO:1, and a light chain variable domain (LCVD) comprising SEQ ID NO:5.
3. The liquid pharmaceutical formulation of claim 1 , wherein: over 90% of the antibodies have a molecular weight of 155 kpa±1 kpa; over 50% of the antibodies have an isoelectric point of about 8.5; and from 75% to 90% of the antibodies are fucosylated.
4. The liquid pharmaceutical formulation of claim 1 , wherein at least 91% of the antibody has native conformation after 28 days at 45° C.
5. The liquid pharmaceutical formulation of claim 1 , wherein at least 35% of the antibody is the main charge variant of the antibody after 28 days at 45° C.
6. The liquid pharmaceutical formulation of claim 1 , wherein at least 94% of the antibody has native conformation after six months at 25° C.
7. The liquid pharmaceutical formulation of claim 1 , wherein at least 45% of the antibody is the main charge variant of the antibody after six months at 25° C.
8. The liquid pharmaceutical formulation of claim 1 , wherein at least 96% of the antibody has native conformation after six months at 5° C.
9. The liquid pharmaceutical formulation of claim 1 , wherein at least 58% of the antibody is the main charge variant of the antibody after six months at 5° C.
10. The liquid pharmaceutical formulation of claim 1 , wherein at least 96% of the antibody is the main charge variant of the antibody after three months at −20° C., −30° C., or −80° C.
11. The liquid pharmaceutical formulation of claim 1 , wherein at least 56% of the antibody is the main charge variant of the antibody after three months at −20° C., −30° C., or −80° C.
12. The liquid formulation of claim 1 , wherein the formulation comprises about 175 mg/mL of the antibody.
13. The liquid formulation of claim 1 , wherein the formulation comprises about 150 mg/mL of the antibody.
14. The liquid formulation of claim 1 , wherein the formulation comprises about 100 mg/mL of the antibody.
15. The liquid formulation of claim 1 , wherein the formulation comprises about 75 mg/mL of the antibody.
16. The liquid formulation of claim 1 , wherein the formulation comprises about 50 mg/mL of the antibody.