US 12,460,015 B2
Pharmaceutical formulation comprising aqueous solution of antibody
Kohei Soeda, Tokyo (JP); Masakazu Fukuda, Tokyo (JP); Masaya Takahashi, Tokyo (JP); Hirotaka Imai, Tokyo (JP); Satoshi Saitoh, Tokyo (JP); Jeremy Duboeuf, Basel (CH); Kishore Ravuri, Basel (CH); Robert Kopf, Basel (CH); Wei Chen, Basel (CH); and Nuria Sancho Oltra, Basel (CH)
Assigned to Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP); and Hoffmann-La Roche Inc., Little Falls, NJ (US)
Appl. No. 18/715,020
Filed by Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP); and Hoffmann-La Roche Inc., Little Falls, NJ (US)
PCT Filed Dec. 1, 2022, PCT No. PCT/JP2022/044355
§ 371(c)(1), (2) Date May 30, 2024,
PCT Pub. No. WO2023/100975, PCT Pub. Date Jun. 8, 2023.
Claims priority of application No. 2021-195788 (JP), filed on Dec. 1, 2021.
Prior Publication US 2025/0136716 A1, May 1, 2025
Int. Cl. C07K 16/36 (2006.01); A61K 39/00 (2006.01); C07K 16/28 (2006.01)
CPC C07K 16/36 (2013.01) [A61K 39/0005 (2013.01); C07K 16/2866 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01)] 11 Claims
 
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(C2H4O)a(C3H6O)b(C2H4O)cH  (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.