# US 12,599,664 B2 · Pharmaceutical products and stable liquid compositions of IL-17 antibodies > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,599,664 B2 - Document ID: US12599664B2 - Status: Granted - Kind: B2 - Application number: 18/481,213 - Filed: 2023-10-04 - Published: 2024-05-30 - Granted: 2026-04-14 - Earliest claimed: 2014-12-22 - Assignees: Novartis AG - Applicants: Novartis AG - Inventors: Susanne Joerg; Kathrin Serno-Schersch - Web page: https://patentgrep.com/patent/US12599664B2 ## CPC - A61K 39/39591: {Stabilisation, fragmentation} - A61P 17/06: Antipsoriatics - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 37/02: Immunomodulators - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - C07K 16/244: {Interleukins [IL]} - H04L 5/0016: {Time-frequency-code} - H04L 5/0023: {Time-frequency-space} - H04L 5/0051: {of dedicated pilots, i.e. pilots destined for a single user or terminal} - C07K 2317/21: from primates, e.g. man - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - H04L: TRANSMISSION OF DIGITAL INFORMATION, e.g. TELEGRAPHIC COMMUNICATION (arrangements common to telegraphic and telephonic communication H04M) ## Abstract 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). ## Claims ### Claim 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. ### Claim 2 (depends on 1) The process of claim 1, wherein the container is adjusted to have a headspace oxygen level of less than about 12%. ### Claim 3 (depends on 1) The process of claim 1, wherein the container is adjusted to have a headspace oxygen level of less than about 10%. ### Claim 4 (depends on 1) The process of claim 1, wherein the process comprises adjusting the headspace oxygen level before filling the container with the liquid composition. ### Claim 5 (depends on 1) The process of claim 1, wherein the process comprises adjusting the headspace oxygen level during filling the container with the liquid composition. ### Claim 6 (depends on 1) The process of claim 1, wherein the process comprises adjusting the headspace oxygen level during sealing of the container containing the liquid composition. ### Claim 7 (depends on 1) The process of claim 1, wherein the container is a vial, a pen, a pre-filled syringe, or an autoinjector. ### Claim 8 (depends on 7) The process of claim 7, wherein the container is a vial and the concentration of secukinumab is about 25 mg/mL. ### Claim 9 (depends on 7) 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. ### Claim 10 (depends on 7) 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. ### Claim 11 (depends on 1) The process of claim 1, wherein the composition comprises a buffer at a concentration of about 10 mM to about 30 mM. ### Claim 12 (depends on 11) The process of claim 11, wherein the buffer is gluconate, histidine, citrate, phosphate, succinate, acetate, Tris, glycine, arginine, or a combination thereof. ### Claim 13 (depends on 1) The process of claim 1, wherein the composition comprises a non-ionic stabilizer at a concentration of about 175 mM to about 350 mM. ### Claim 14 (depends on 13) The process of claim 13, wherein the non-ionic stabilizer is mannitol, trehalose, raffinose, maltose, sorbitol, or a combination thereof. ### Claim 15 (depends on 1) 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. ### Claim 16 (depends on 15) The process of claim 15, wherein the amino acid stabilizer is glycine and/or arginine. ### Claim 17 (depends on 16) The process of claim 16, wherein the glycine is at a concentration of about 270 mM. ### Claim 18 (depends on 16) The process of claim 16, wherein the arginine is at a concentration of about 160 mM. ### Claim 19 (depends on 1) 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). ### Claim 20 (depends on 19) The process of claim 19, wherein the surfactant is a polysorbate, a poloxamer, or a combination thereof. ### Claim 21 (depends on 20) The process of claim 20, wherein the surfactant is polysorbate 20 or polysorbate 80. ### Claim 22 (depends on 20) The process of claim 20, wherein the surfactant is polysorbate 80. ### Claim 23 (depends on 1) The process of claim 1, wherein the methionine is at a concentration of less than about 134 mM. ### Claim 24 (depends on 1) 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. ### Claim 25 (depends on 1) The process of claim 1, wherein the secukinumab is at a concentration of about 25 mg/mL. ### Claim 26 (depends on 1) The process of claim 1, wherein the secukinumab is at a concentration of about 150 mg/mL. ### Claim 27 (depends on 1) The process of claim 1, wherein the secukinumab is at a concentration of about 175 mg/mL. ### Claim 28 (depends on 1) 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). ### Claim 29 (depends on 1) 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). ### Claim 30 (depends on 1) 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). ### Claim 31 (depends on 1) 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). ### Claim 32 (depends on 28) 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. ### Claim 33 (depends on 29) 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. ### Claim 34 (depends on 1) The process of claim 1, wherein the container is adjusted to have a headspace oxygen level by introducing an inert gas into the headspace. ### Claim 35 (depends on 34) The process of claim 34, wherein the inert gas is nitrogen or argon. ### Claim 36 (depends on 34) The process of claim 34, wherein the inert gas is introduced prior to filling of the container. ### Claim 37 (depends on 34) The process of claim 34, wherein the inert gas is introduced during filling of the container. ### Claim 38 (depends on 34) The process of claim 34, wherein the inert gas is introduced during sealing of the container. ### Claim 39 (depends on 1) 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. ### Claim 40 (depends on 39) The process of claim 39, wherein the liquid composition comprises an amino acid stabilizer. ### Claim 41 (depends on 40) The process of claim 40, wherein the amino acid stabilizer is glycine and/or arginine. ### Claim 42 (depends on 39) The process of claim 39, wherein the liquid composition comprises a surfactant. ### Claim 43 (depends on 42) The process of claim 42, wherein the surfactant is a polysorbate, a poloxamer, or a combination thereof. ### Claim 44 (depends on 43) The process of claim 43, wherein the surfactant is a polyoxyethylene sorbitan fatty acid ester. ### Claim 45 (depends on 43) The process of claim 43, wherein the surfactant is polysorbate 20 or polysorbate 80. ### Claim 46 (depends on 45) The process of claim 45 wherein the surfactant is polysorbate 80. ### Claim 47 (depends on 46) The process of claim 46, wherein the surfactant is polysorbate 80 at a concentration of about 0.01% to about 0.04% (w/v).