Stabilized Formulations Containing Anti-PCSK9 Antibodies

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) 5±0.75 mM to 50±7.5 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 liquid pharmaceutical formulation of claim 1 , wherein the histidine concentration is selected from the group consisting of:

(i) 5±0.75 mM to 15±2.25 mM;

(ii) 6±0.9 mM to 14±2.1 mM;

(iii) 7±1.05 mM to 13±1.95 mM;

(iv) 8±1.2 mM to 12±1.8 mM;

(v) 9±1.35 mM to 11±1.65 mM; and

(vi) 10±1.5 mM.

3 . 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.

4 . The liquid pharmaceutical formulation of claim 2 , 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.

5 . The liquid pharmaceutical formulation of claim 1 , wherein the formulation comprises about 175 mg/mL of the antibody or antigen-binding fragment thereof.

6 . The liquid pharmaceutical formulation of claim 1 , wherein the formulation comprises about 150 mg/mL of the antibody or antigen-binding fragment thereof.

7 . The liquid pharmaceutical formulation of claim 1 , wherein the formulation comprises about 100 mg/mL of the antibody or antigen-binding fragment thereof.

8 . The liquid pharmaceutical formulation of claim 1 , wherein the formulation comprises about 75 mg/mL of the antibody or antigen-binding fragment thereof.

9 . The liquid pharmaceutical formulation of claim 1 , wherein the formulation comprises about 50 mg/mL of the antibody or antigen-binding fragment thereof.

10 . A liquid pharmaceutical formulation comprising:

(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 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) histidine (pH 6.0±0.3), at a concentration selected from the group consisting of:

(i) 5±0.75 mM to 15±2.25 mM;

(ii) 6±0.9 mM to 14±2.1 mM;

(iii) 7±1.05 mM to 13±1.95 mM;

(iv) 8±1.2 mM to 12±1.8 mM;

(v) 9±1.35 mM to 11±1.65 mM; and

(vi) 10±1.5 mM;

(c) 0.01±0.0015% w/v polysorbate 20; and

(d) 10±1.5% w/v sucrose.

11 . The liquid pharmaceutical formulation of claim 10 , 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.

12 . The liquid pharmaceutical formulation of claim 10 , wherein the histidine concentration is 8±1.2 mM.

13 . A liquid pharmaceutical formulation comprising:

(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 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) histidine (pH 6.0±0.3), at a concentration selected from the group consisting of:

(i) 5±0.75 mM to 15±2.25 mM;

(ii) 6±0.9 mM to 14±2.1 mM;

(iii) 7±1.05 mM to 13±1.95 mM;

(iv) 8±1.2 mM to 12±1.8 mM;

(v) 9±1.35 mM to 11±1.65 mM; and

(vi) 10±1.5 mM;

(c) 0.01±0.0015% w/v polysorbate 20; and

(d) 10±1.5% w/v sucrose.

14 . The liquid pharmaceutical formulation of claim 13 , 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.

15 . The liquid pharmaceutical formulation of claim 13 , wherein the histidine concentration is 6±0.9 mM.

16 . A liquid pharmaceutical formulation comprising:

(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 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) histidine (pH 6.0±0.3), at a concentration selected from the group consisting of:

(i) 5±0.75 mM to 15±2.25 mM;

(ii) 6±0.9 mM to 14±2.1 mM;

(iii) 7±1.05 mM to 13±1.95 mM;

(iv) 8±1.2 mM to 12±1.8 mM;

(v) 9±1.35 mM to 11±1.65 mM; and

(vi) 10±1.5 mM;

(c) 0.01±0.0015% w/v polysorbate 20; and

(d) 10±1.5% w/v sucrose.

17 . The liquid pharmaceutical formulation of claim 16 , wherein the histidine concentration is 8±1.2 mM.

18 . A liquid pharmaceutical formulation comprising:

(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 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) histidine (pH 6.0±0.3), at a concentration selected from the group consisting of:

(i) 5±0.75 mM to 15±2.25 mM;

(ii) 6±0.9 mM to 14±2.1 mM;

(iii) 7±1.05 mM to 13±1.95 mM;

(iv) 8±1.2 mM to 12±1.8 mM;

(v) 9±1.35 mM to 11±1.65 mM; and

(vi) 10±1.5 mM;

(c) 0.01±0.0015% w/v polysorbate 20; and

(d) 10±1.5% w/v sucrose.

19 . The liquid pharmaceutical formulation of claim 13 , wherein the histidine concentration is 6±0.9 mM.