Preparation comprising anti-PCSK9 antibody and use thereof

A liquid antibody preparation, comprising:

• (i) an anti-proprotein convertase subtilisin/kexin type 9 (anti-PCSK9) antibody or an antigen-binding fragment thereof;
• (ii) a buffer, wherein the buffer is selected from the group consisting of histidine buffer, glutamate buffer, phosphate buffer, acetate buffer, citrate buffer, and tris(hydroxymethyl)aminomethane buffer;
• (iii) a viscosity inhibitor, wherein the viscosity inhibitor is a combination of (a) sorbitol, and (b) arginine or an arginine salt;
• and
• (iv) a surfactant,
• wherein said anti-PCSK9 antibody or an antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein said VH comprises complementary determinant regions (CDRs) HCDR1, HCDR2 and HCDR3 and said VL comprises CDRs LCDR1, LCDR2 and LCDR3:
• (a) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 20, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 21, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 22;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• (b) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 1, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 2, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 3;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• (c) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 1, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 2, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 18;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• (d) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 1, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 14, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 19;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• (e) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 7, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 15, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 18;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• (f) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 8, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 16, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 19;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• (g) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 9, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 17, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 19;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• (h) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 10, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 17, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 19;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• (i) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 11, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 17, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 18;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• (j) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 12, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 17, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 18;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• or
• (k) HCDR1 comprising the amino acid sequence of SEQ ID NO:
• 13, HCDR2 comprising the amino acid sequence of SEQ ID NO:
• 17, and HCDR3 comprising the amino acid sequence of SEQ ID NO:
• 18;
• and LCDR1 comprising the amino acid sequence of SEQ ID NO:
• 4, LCDR2 comprising the amino acid sequence of SEQ ID NO:
• 5, and LCDR3 comprising the amino acid sequence of SEQ ID NO:
• 6;
• wherein the concentration of the anti-PCSK9 antibody or the antigen-binding fragment thereof in the liquid antibody preparation is about 50 mg/mL to about 200 mg/ml;
• wherein the concentration of the buffer in the liquid antibody preparation is about 0.1-50 mg/mL;
• wherein the concentration of the sorbitol is about 1% to 6% (w/v), and the concentration of the arginine or arginine salt is about 50 mmol/L to 180 mmol/L;
• wherein the concentration of the surfactant is about 0.01 mg/mL to 5 mg/ml;
• and
• wherein the pH of the liquid preparation is about 5.0 to 6.0.