Method for preparing antibody-containing formulation

Patent metadata

Field	Value
Publication number	US-2025136716-A1
Application number	US-202218715020-A
Country	US
Kind code	A1
Filing date	Dec 1, 2022
Priority date	Dec 1, 2021
Publication date	May 1, 2025
Grant date	—

Abstract

Provided is a pharmaceutical formulation with reduced particle formation, comprising an anti-coagulation factor IXa/X antibody (bispecific monoclonal antibody) that substitutes for coagulation factor VIII, or an anti-IL-6 receptor antibody that inhibits binding to the interleukin 6 receptor. Provided is a pharmaceutical formulation comprising an aqueous solution comprising a polyoxyethylene polyoxypropylene glycol (poloxamer),
wherein the poloxamer is represented by formula I:

HO(C 2 H 4 O) a (C 3 H 6 O) b (C 2 H 4 O) c H  (I)

wherein a and c are independently an integer selected from 75 to 85;
b is an integer selected from 22 to 33; and a, b and c are average values over the entire poloxamer, and, the poloxamer comprises poloxamer molecules comprising 34 or more (C 3 H 6 O) in the molecule at a ratio of 3% (w/w) or more of the total poloxamer.

First claim

1 . A pharmaceutical formulation comprising an aqueous solution comprising:
a monoclonal antibody selected from (i) an antibody comprising an H chain comprising SEQ ID NO: 1, an H chain comprising SEQ ID NO: 2, and two L chains, each comprising SEQ ID NO: 3, and (ii) an antibody comprising two H chains, each comprising SEQ ID NO: 4, and two L chains, each comprising SEQ ID NO: 5, and polyoxyethylene polyoxypropylene glycol (poloxamer),
wherein the poloxamer is represented by formula I:
HO(C 2 H 4 O) a (C 3 H 6 O) b (C 2 H 4 O) c H  (I)

wherein
a and c are independently a number selected from 75 to 85;
b is a number selected from 22 to 33; and
a, b and c are average values over the entire poloxamer, and
the peak area after an elution time of 17 minutes is 19% or more of the total peak area in high performance liquid chromatography of the poloxamer under the high-performance liquid chromatography conditions defined below:

(1) Column: HPLC column packed with macroporous styrene divinylbenzene (1000 Å, 5 μm, 50×2.1 mm)
(2) Mobile phase:
Mobile phase A: Ultrapure water
Mobile phase B: Acetonitrile

(3) Elution gradient program
From 0 minute to 16.0 minutes: Mobile phase B 58% to 64%
From 16.0 minutes to 18.5 minutes: Mobile phase B 64% to 90%
From 18.5 minutes to 21.5 minutes: Mobile phase B fixed at 90%
From 21.5 minutes to 23.5 minutes: Mobile phase B 90% to 100%
From 23.5 minutes to 30.0 minutes: Mobile phase B fixed at 100%
From 30.0 minutes to 30.1 minutes: Mobile phase B 100% to 58%
From 30.1 minutes to 40.0 minutes: Mobile phase B fixed at 58%

(4) Flow rate: 0.2 mL/min
(5) Detection method: Evaporative light scattering detection (drift tube temperature: 50±25° C., nebulizer heating power level: 75%, gain value: 250, gas pressure: 20 psi)
(6) Column temperature: 65±5° C.
(7) Poloxamer concentration (in ultrapure water) as applied to the column: 0.5 mg/mL.

2 - 17 . (canceled)

18 . The pharmaceutical formulation of claim 1 , wherein the peak area after an elution time of 17 minutes is 33% or more of the total peak area.

19 . The pharmaceutical formulation of claim 1 , wherein b is a number selected from 25 to 30.

20 . The pharmaceutical formulation of claim 1 , wherein the HPLC column packed with macroporous styrene divinylbenzene is a PLRP-S column.

21 . The pharmaceutical formulation of claim 1 , wherein the number-average molecular weight of the poloxamer is in the range of 7680 to 9510.

22 . The pharmaceutical formulation of claim 1 , wherein the concentration of the poloxamer in the aqueous solution is 0.001 to 100 mg/mL.

23 . The pharmaceutical formulation according to claim 1 , wherein the concentration of the antibody in the aqueous solution is 10 to 300 mg/mL.

24 . The pharmaceutical formulation according to claim 1 , wherein the aqueous solution comprises one or more pharmaceutically acceptable excipients selected from sugars, sugar alcohols, buffering agents, preservatives, carriers, antioxidants, chelating agents, natural polymers, synthetic polymers, cryoprotectants, extenders, and stabilizers.

25 . The pharmaceutical formulation according to claim 1 , wherein the poloxamer is poloxamer 188.

Assignees

• Chugai Pharmaceutical Co Ltd
• Hoffmann La Roche

Inventors

• Soeda Kohei
• Fukuda Masakazu
• Takahashi Masaya
• Imai Hirotaka
• Saitoh Satoshi
• Duboeuf Jeremy
• RAVURI Kishore
• Kopf Robert
• Chen Wei
• Oltra Nuria Sancho

Classifications

• A61K39/0005

  Vertebrate antigens (from snakes A61K39/38) · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2317/31

  multispecific · CPC title

• C07K16/2866

  against receptors for cytokines, lymphokines, interferons · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title