JPWO2020088492A5

JPWO2020088492A5 -

Info

Publication number: JPWO2020088492A5
Application number: JP2021523466A
Authority: JP
Publication date: 2022-10-24

Claims

(a) a buffer;
(b) a stabilizer;
(c) HCDR1 having the amino acid sequence SEQ ID NO: 1;
HCDR2 having the amino acid sequence SEQ ID NO:2;
HCDR3 having the amino acid sequence SEQ ID NO:3;
LCDR1 having the amino acid sequence SEQ ID NO:4;
LCDR2 having the amino acid sequence SEQ ID NO:5;
an antibody or antigen-binding fragment thereof that specifically binds to human PCSK9, comprising LCDR3 having the amino acid sequence SEQ ID NO:6;
and having a pH value of 5.5-6.5.

Antibody formulation according to claim 1, characterized in that said buffer is acetate buffer or histidine buffer.

3. The antibody preparation of claim 2, wherein said buffer is a histidine buffer prepared with L-histidine and L-histidine monohydrochloride.

The histidine buffer contains 1-10 mM histidine and 10-20 mM histidine salt, preferably the molar ratio of the histidine and the histidine salt is in the range of 1:1 to 1:4. The antibody formulation according to claim 2.

Antibody preparation according to claim 1, characterized in that the concentration of said buffer is 15-25 mM.

2. The antibody formulation of claim 1, wherein the stabilizer is arginine or its salts, sorbitol, mannitol or sucrose, or a combination of arginine or its salts and sorbitol, mannitol or sucrose.

Said stabilizer is an arginine salt whose concentration in said formulation is 50 mM to 200 mM , preferably 130 mM to 160 mM, or said stabilizer is a mixture of arginine salt and mannitol or sorbitol, and said Antibody formulation according to claim 6, characterized in that it is 50-150 mM, the concentration of mannitol or sorbitol is 50-200 mM, and the total concentration of the two stabilizers is within the range of 50 mM-250 mM.

The antibody or antigen-binding fragment thereof is characterized by comprising a heavy chain variable region (VH) having the amino acid sequence SEQ ID NO:7 and a light chain variable region (VL) having the amino acid sequence SEQ ID NO:8. The antibody formulation according to claim 1.

10. The antibody or antigen-binding fragment thereof comprises a heavy chain (HC) having amino acid sequence SEQ ID NO:9 and a light chain (LC) having amino acid sequence SEQ ID NO:10. 1. The antibody formulation according to 1.

2. The antibody formulation of claim 1, wherein the antibody formulation further comprises polysorbate 20 or polysorbate 80 at a concentration of about 0.01% to about 0.05%.

(a) about 20 mM histidine buffer;
(b) about 100 mM to 200 mM , preferably 130 mM to 160 mM arginine salt;
(c) about 0.02% Polysorbate 20;
(d) about 100 mg/mL to about 200 mg/mL of an antibody or antigen-binding fragment that specifically binds to human PCSK9;
2. The antibody formulation of claim 1, comprising:

The antibody formulation is
(A) (1) about 100 mg/mL to about 200 mg/mL of an anti-PCSK9 antibody or antigen-binding fragment thereof; and (2) about 10-50 mM histidine at a pH value of about 5.5-6.5. (3) about 50 mM to about 200 mM arginine salt; (4) about 0% to about 0.1% nonionic detergent; or
(B) (1) about 150±10 mg/mL anti-PCSK9 antibody or antigen-binding fragment thereof; (2) about 20 mM histidine buffer having a pH value of about 5.5 to 6.5; 3) about 60±5 mM, 130±5 mM, or 160±5 mM arginine salt; and (4) about 0% to about 0.1% nonionic surfactant, or
(C) (1) about 150±10 mg/kg, comprising a heavy chain variable region (VH) having the amino acid sequence SEQ ID NO:7 and a light chain variable region (VL) having the amino acid sequence SEQ ID NO:8; mL of anti-PCSK9 antibody or antigen-binding fragment thereof, (2) about 20 mM histidine buffer with a pH value of about 5.5 to 6.5, (3) about 160±5 mM arginine, ( 4) about 0.02% Polysorbate 20; or
(D) (1) about 150 ± 10 mg/mL of an antibody that is a full-length antibody comprising a heavy chain with the amino acid sequence of SEQ ID NO: 9 and a light chain with the amino acid sequence of SEQ ID NO: 10; (2) about 20 mM histidine buffer with a pH value of about 5.5-6.5; (3) about 160±5 mM arginine; (4) about 0.02% Polysorbate 20; or
(E) (1) 150 mg/ml anti-PCSK9 antibody or antigen-binding fragment thereof, (2) 20 mM histidine buffer, (3) 160 mM arginine hydrochloride, (4) 0.02% polysorbate 20 with or
(F) (1) 150 mg/ml anti-PCSK9 antibody or antigen-binding fragment thereof, (2) 20 mM histidine buffer, (3) 120 mM arginine hydrochloride and 60 mM mannitol, (4) 0.02 % polysorbate 20, or
(G) (1) 150 mg/ml anti-PCSK9 antibody or antigen-binding fragment thereof, (2) 20 mM histidine buffer, (3) 60 mM arginine hydrochloride and 160 mM mannitol, (4) 0.02 % Polysorbate 20;
(H) (1) about 150 mg/ml anti-PCSK9 antibody or antigen-binding fragment thereof, (2) about 20 mM histidine buffer, (3) about 130-160 mM arginine hydrochloride, (4) about 0 .02% Polysorbate 20;
The antibody preparation according to claim 1, which is selected from antibody preparations comprising

A delivery device comprising the antibody formulation of any one of claims 1-12.

A pre-filled syringe containing the antibody formulation of any one of claims 1-12.

The antibody formulation of any one of claims 1-12, the delivery device of claim 13, or the pre-filled syringe of claim 14 for treatment, prevention of any disease associated with PCSK9 activity or use for improvement.