Pharmaceutical products and stable liquid compositions of IL-17 antibodies
The disclosure is directed to pharmaceutical products and stable liquid compositions of IL-17 antibodies and antigen-binding fragments thereof, e.g., AIN457 (secukinumab), and processes of making these pharmaceutical products and compositions. The disclosure is also directed to the use of these pharmaceutical products and liquid compositions (e.g., as part of a kit having instructions for use) for the treatment of various IL-17-mediated disorders (e.g., autoimmune disorders, such as psoriasis, ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis).
1 . A liquid pharmaceutical composition comprising:
(i) about 150 mg/mL secukinumab;
(ii) 2.5 mM to 134 mM methionine;
(iii) a non-ionic stabilizer; and
(iv) a surfactant;
wherein the composition has a pH of about 5.2 to about 6.4; and
wherein upon storage of the liquid pharmaceutical composition at 2-8° C. for about 24 months, at least one of the following criteria is met:
(a) no more than 5% of secukinumab main variant is degraded as measured by reverse phase-high performance liquid chromatography (RP-HPLC); and
(b) no more than 5% of secukinumab pre-main peak variant is formed as measured by RP-HPLC.
2 . The composition of claim 1 , wherein upon storage of the liquid pharmaceutical composition at 2-8° C. for about 24 months, at least one of the following criteria is additionally met:
(a) no more than 5% of secukinumab main variant is degraded as measured by cation exchange chromatography (CEX);
(b) no more than 5% of secukinumab basic variants are formed as measured by CEX; and
(c) no more than 5% of secukinumab acidic variants are formed as measured by CEX.
3 . The composition of claim 2 , wherein upon storage of the liquid pharmaceutical composition at 2-8° C. for about 24 months, at least one of the following criteria is additionally met:
(a) no more than 5% of secukinumab monomer is degraded as measured by size exclusion chromatography (SEC);
(b) no more than 5% secukinumab aggregates are formed as measured by SEC; and
(c) no more than 5% secukinumab degradation products are formed as measured by SEC.
4 . The composition of claim 1 , wherein the composition comprises a buffer selected from gluconate, histidine, citrate, phosphate, succinate, acetate, Tris, glycine, arginine, and a combination thereof.
5 . The composition of claim 2 , wherein the composition comprises a buffer selected from gluconate, histidine, citrate, phosphate, succinate, acetate, Tris, glycine, arginine, and a combination thereof.
6 . The composition of claim 3 , wherein the composition comprises a buffer selected from gluconate, histidine, citrate, phosphate, succinate, acetate, Tris, glycine, arginine, and a combination thereof.
7 . The composition of claim 4 , wherein the non-ionic stabilizer is mannitol, trehalose, raffinose, maltose, sorbitol, or a combination thereof.
8 . The composition of claim 5 , wherein the non-ionic stabilizer is mannitol, trehalose, raffinose, maltose, sorbitol, or a combination thereof.
9 . The composition of claim 6 , wherein the non-ionic stabilizer is mannitol, trehalose, raffinose, maltose, sorbitol, or a combination thereof.
10 . The composition of claim 7 , wherein the surfactant is polysorbate 20 or polysorbate 80.
11 . The composition of claim 8 , wherein the surfactant is a polysorbate 20 or polysorbate 80.
12 . The composition of claim 9 , wherein the surfactant is a polysorbate 20 or polysorbate 80.
13 . The composition of claim 10 , wherein:
(a) the buffer is at a concentration of 10 mM to 30 mM;
(b) the non-ionic stabilizer is at a concentration of about 175 mM to about 350 mM; and
(c) the surfactant is at a concentration of 0.01% (w/v) to 0.1% (w/v).
14 . The composition of claim 11 , wherein:
(a) the buffer is at a concentration of 10 mM to 30 mM;
(b) the non-ionic stabilizer is at a concentration of about 175 mM to about 350 mM; and
(c) the surfactant is at a concentration of 0.01% (w/v) to 0.1% (w/v).
15 . The composition of claim 12 , wherein:
(a) the buffer is at a concentration of 10 mM to 30 mM;
(b) the non-ionic stabilizer is at a concentration of about 175 mM to about 350 mM; and
(c) the surfactant is at a concentration of 0.01% (w/v) to 0.1% (w/V).
16 . The composition of claim 13 , wherein:
(a) the buffer comprises citrate;
(b) the non-ionic stabilizer is sorbitol; and
(c) the surfactant is polysorbate 80.
17 . The composition of claim 14 , wherein:
(a) the buffer comprises citrate;
(b) the non-ionic stabilizer is sorbitol; and
(c) the surfactant is polysorbate 80.
18 . The composition of claim 15 , wherein:
(a) the buffer comprises citrate;
(b) the non-ionic stabilizer is sorbitol; and
(c) the surfactant is polysorbate 80.
19 . The composition of claim 13 , wherein:
(a) the buffer comprises histidine;
(b) the non-ionic stabilizer is trehalose; and
(c) the surfactant is polysorbate 80.
20 . The composition of claim 14 , wherein:
(a) the buffer comprises histidine;
(b) the non-ionic stabilizer is trehalose; and
(c) the surfactant is polysorbate 80.
21 . The composition of claim 15 , wherein:
(a) the buffer comprises histidine;
(b) the non-ionic stabilizer is trehalose; and
(c) the surfactant is polysorbate 80.
22 . The composition of claim 16 , wherein the methionine is at a concentration from about 10 mM to about 67 mM.
23 . The composition of claim 17 , wherein the methionine is at a concentration from about 10 mM to about 67 mM.
24 . The composition of claim 18 , wherein the methionine is at a concentration from about 10 mM to about 67 mM.
25 . The composition of claim 19 , wherein the methionine is at a concentration from about 10 mM to about 67 mM.
26 . The composition of claim 20 , wherein the methionine is at a concentration from about 10 mM to about 67 mM.
27 . The composition of claim 21 , wherein the methionine is at a concentration from about 10 mM to about 67 mM.
28 . The composition of claim 3 , wherein the secukinumab has at least 2.0 mol free thiol (SH) per mol secukinumab upon storage the liquid pharmaceutical composition at 2-8° C. for about 24 months.
29 . The composition of claim 12 , wherein the secukinumab has at least 2.0 mol free thiol (SH) per mol secukinumab upon storage the liquid pharmaceutical composition at 2-8° C. for about 24 months.
30 . The composition of claim 15 , wherein the secukinumab has at least 2.0 mol free thiol (SH) per mol secukinumab upon storage the liquid pharmaceutical composition at 2-8° C. for about 24 months.