Granted Patent B2

US 12,599,664 · App. 18/481,213 · Granted Apr 14, 2026

Inventors: Susanne Joerg (Binningen, CH); Kathrin Serno-Schersch (Basel, CH)

Assignee: NOVARTIS AG

A61K39/39591C07K16/244H04L5/0016H04L5/0023H04L5/0051C07K2317/21

Abstract

Claims (58)

1 . A process for preventing secukinumab oxidation, comprising

a. preparing a liquid composition by combining secukinumab and methionine; and

b. disposing said liquid composition in a container thereby providing a container having the liquid composition and a headspace, the liquid composition

i. having a pH of about 5.2 to about 6.2,

ii. comprising about 20 mg/mL to about 175 mg/mL secukinumab, and

iii. comprising at least 2.5 mM methionine, wherein the container is adjusted to have a headspace oxygen level that is reduced relative to the oxygen level of air by introducing an inert gas into the headspace, by placing the container in a system and removing oxygen by applying a vacuum, or both.

2 . The process of claim 1 , wherein the container is adjusted to have a headspace oxygen level of less than about 12%.

3 . The process of claim 1 , wherein the container is adjusted to have a headspace oxygen level of less than about 10%.

4 . The process of claim 1 , wherein the process comprises adjusting the headspace oxygen level before filling the container with the liquid composition.

5 . The process of claim 1 , wherein the process comprises adjusting the headspace oxygen level during filling the container with the liquid composition.

6 . The process of claim 1 , wherein the process comprises adjusting the headspace oxygen level during sealing of the container containing the liquid composition.

7 . The process of claim 1 , wherein the container is a vial, a pen, a pre-filled syringe, or an autoinjector.

8 . The process of claim 7 , wherein the container is a vial and the concentration of secukinumab is about 25 mg/mL.

9 . The process of claim 7 , wherein the container is a pen, a pre-filled syringe, or an autoinjector, and the concentration of secukinumab is about 150 mg/mL.

10 . The process of claim 7 , wherein the container is a pen, a pre-filled syringe, or an autoinjector, and the concentration of secukinumab is about 175 mg/mL.

11 . The process of claim 1 , wherein the composition comprises a buffer at a concentration of about 10 mM to about 30 mM.

12 . The process of claim 11 , wherein the buffer is gluconate, histidine, citrate, phosphate, succinate, acetate, Tris, glycine, arginine, or a combination thereof.

13 . The process of claim 1 , wherein the composition comprises a non-ionic stabilizer at a concentration of about 175 mM to about 350 mM.

14 . The process of claim 13 , wherein the non-ionic stabilizer is mannitol, trehalose, raffinose, maltose, sorbitol, or a combination thereof.

15 . The process of claim 1 , wherein the composition comprises an amino acid stabilizer, or comprises an amino acid stabilizer at a concentration of about 175 mM to about 350 mM.

16 . The process of claim 15 , wherein the amino acid stabilizer is glycine and/or arginine.

17 . The process of claim 16 , wherein the glycine is at a concentration of about 270 mM.

18 . The process of claim 16 , wherein the arginine is at a concentration of about 160 mM.

19 . The process of claim 1 , wherein the composition comprises a surfactant wherein the surfactant is at a concentration of about 0.01% (w/v) to about 0.04% (w/v).

20 . The process of claim 19 , wherein the surfactant is a polysorbate, a poloxamer, or a combination thereof.

21 . The process of claim 20 , wherein the surfactant is polysorbate 20 or polysorbate 80.

22 . The process of claim 20 , wherein the surfactant is polysorbate 80.

23 . The process of claim 1 , wherein the methionine is at a concentration of less than about 134 mM.

24 . The process of claim 1 , wherein the methionine is at a concentration sufficient to maintain the amount of pre-main peak species below 10% as measured by reverse phase-high performance liquid chromatography (RH-HPLC) upon storage at 2-8° C. for about 6 months.

25 . The process of claim 1 , wherein the secukinumab is at a concentration of about 25 mg/mL.

26 . The process of claim 1 , wherein the secukinumab is at a concentration of about 150 mg/mL.

27 . The process of claim 1 , wherein the secukinumab is at a concentration of about 175 mg/mL.

28 . The process of claim 1 , wherein upon storage at 2-8° C. for about 24 months: (a) no more than 10% of secukinumab monomer is degraded as measured by size exclusion chromatography (SEC); (b) no more than 10% of secukinumab main variant is degraded as measured by cation exchange chromatography (CEX); or (c) no more than 10% of secukinumab main variant is degraded as measured by reverse phase-high performance liquid chromatography (RP-HPLC).

29 . The process of claim 1 , wherein upon storage at 2-8° C. for about 24 months: (a) no more than 10% of secukinumab monomer is degraded as measured by size exclusion chromatography (SEC); (b) no more than 10% of secukinumab main variant is degraded as measured by cation exchange chromatography (CEX); and (c) no more than 10% of secukinumab main variant is degraded as measured by reverse phase-high performance liquid chromatography (RP-HPLC).

30 . The process of claim 1 , wherein upon storage at 25° C. for about 6 months: (a) no more than 10% of secukinumab monomer is degraded as measured by size exclusion chromatography (SEC); (b) no more than 10% of secukinumab main variant is degraded as measured by cation exchange chromatography (CEX); or (c) no more than 10% of secukinumab main variant is degraded as measured by reverse phase-high performance liquid chromatography (RP-HPLC).

31 . The process of claim 1 , wherein upon storage at 25° C. for about 6 months: (a) no more than 10% of secukinumab monomer is degraded as measured by size exclusion chromatography (SEC); (b) no more than 10% of secukinumab main variant is degraded as measured by cation exchange chromatography (CEX); and (c) no more than 10% of secukinumab main variant is degraded as measured by reverse phase-high performance liquid chromatography (RP-HPLC).

32 . The process of claim 28 , wherein the relative biological activity of secukinumab in the composition is at least 80% of a reference standard as measured by the inhibition of interleukin-6 (IL-6) release from human chondrocytes upon storage at 2-8° C. for about 24 months.

33 . The process of claim 29 , wherein the relative biological activity of secukinumab in the composition is at least 80% of a reference standard as measured by the inhibition of interleukin-6 (IL-6) release from human chondrocytes upon storage at 2-8° C. for about 24 months.

34 . The process of claim 1 , wherein the container is adjusted to have a headspace oxygen level by introducing an inert gas into the headspace.

35 . The process of claim 34 , wherein the inert gas is nitrogen or argon.

36 . The process of claim 34 , wherein the inert gas is introduced prior to filling of the container.

37 . The process of claim 34 , wherein the inert gas is introduced during filling of the container.

38 . The process of claim 34 , wherein the inert gas is introduced during sealing of the container.

39 . The process of claim 1 , wherein the liquid composition:

i. comprises a buffer at a concentration of about 10 mM to about 30 mM;

1. wherein the buffer is selected from the group consisting of gluconate, histidine, citrate, phosphate, succinate, acetate, Tris, glycine, arginine, and a combination thereof;

ii. comprises a non-ionic stabilizer at a concentration of about 175 mM to about 350 mM;

1. wherein the non-ionic stabilizer is mannitol, trehalose, raffinose, maltose, sorbitol, or a combination thereof;

iii. comprises about 25 mg/mL to about 150 mg/mL secukinumab; and

iv. comprises from at least 2.5 mM methionine to about 67 mM methionine.

40 . The process of claim 39 , wherein the liquid composition comprises an amino acid stabilizer.

41 . The process of claim 40 , wherein the amino acid stabilizer is glycine and/or arginine.

42 . The process of claim 39 , wherein the liquid composition comprises a surfactant.

43 . The process of claim 42 , wherein the surfactant is a polysorbate, a poloxamer, or a combination thereof.

44 . The process of claim 43 , wherein the surfactant is a polyoxyethylene sorbitan fatty acid ester.

45 . The process of claim 43 , wherein the surfactant is polysorbate 20 or polysorbate 80.

46 . The process of claim 45 wherein the surfactant is polysorbate 80.

47 . The process of claim 46 , wherein the surfactant is polysorbate 80 at a concentration of about 0.01% to about 0.04% (w/v).

Assignments (4)

Continuity (3)

References Cited (400)