LIQUID PHARMACEUTICAL COMPOSITION OF ADALIMUMAB

Abstract

A liquid pharmaceutical composition comprising adalimumab; zwitterionic histidine; and a sugar stabilizer, wherein the composition is either free from amino acids other than histidine or comprises one or more amino acids other than histidine in a combined concentration of at most 0.1 mM; wherein the zwitterionic histidine is present in a concentration between 0.77 mg / ml and 2.2 mg / ml or in a concentration between 5 and 14 mM.

Claims

[1] A liquid pharmaceutical composition comprising adalimumab; zwitterionic histidine; and a sugar stabilizer, wherein the composition is either free from amino acids other than histidine or comprises one or more amino acids other than histidine in a combined concentration of at most 0.1 mM; wherein the zwitterionic histidine is present in a concentration between 0.77 mg / ml and 2.2 mg / ml or in a concentration between 5 and 14 mM. [2] The liquid pharmaceutical composition according to claim 1, further comprising a surfactant. [3] A liquid pharmaceutical composition according to claim 1 or claim 2, further comprising a toning agent. [4] A liquid pharmaceutical composition according to any one of the preceding claims, wherein the sugar stabilizer is a sugar polyol or a disaccharide. [5] A liquid pharmaceutical composition according to claim 4, wherein the sugar stabilizer is trehalose or mannitol. [6] A liquid pharmaceutical composition according to claim 2 or any preceding claim dependent thereon, wherein the surfactant is polysorbate 80 or polysorbate 20. [7] A liquid pharmaceutical composition according to claim 3 or any preceding claim dependent thereon, wherein the toning agent is non-buffering. [8] A liquid pharmaceutical composition according to claim 3 or any preceding claim dependent thereon, wherein the toning agent is or comprises a metal salt. [9] A liquid pharmaceutical composition according to claim 8, wherein the toning agent is or comprises sodium chloride. [10] A liquid pharmaceutical composition according to any one of the preceding claims, wherein the liquid pharmaceutical composition comprises: - Adalimumab; - 5 to 14 mM zwitterionic histidine; - 100 to 300 mM of a sugar stabilizer (e.g. trehalose); - 10 to 200 mM of a toning agent (e.g. sodium chloride); and - Water (for injections); - where the composition: o has a pH value between 6.3 and 6.7 (e.g. pH 6.4) o is (substantially or completely) free of arginine; comprises arginine in a concentration of not more than 0.1 mM; o is (substantially or completely) free from amino acids other than histidine or comprises one or more amino acids other than histidine in a (combined) concentration of not more than 0.1 mM; o is (substantially or completely) free from surfactants with the optional exception of polysorbate 80 or comprises one or more of the same surfactants (optionally excluding polysorbate 80) in a (combined) concentration of not more than 1 mM; and / or ◯ is (substantially or completely) free from phosphate buffers (e.g. sodium dihydrogen phosphate, disodium hydrogen phosphate) or comprises a phosphate buffer system in a concentration of not more than 0.1 mM. [11] A process for the preparation of a liquid pharmaceutical composition comprising adalimumab, zwitterionic histidine and a sugar stabilizer; wherein the composition is either free from amino acids other than histidine or comprises one or more amino acids other than histidine in a combined concentration of at most 0.1 mM; and the composition comprises between 0.77 mg / ml and 2.2 mg / ml zwitterionic histidine or between 5 and 14 mM zwitterionic histidine; the process comprising mixing the adalimumab, the zwitterionic histidine and the sugar stabilizer in water. [12] The method of claim 11, wherein the method comprises forming a histidine buffer system comprising the zwitterionic histidine, wherein forming the histidine buffer system comprises mixing the zwitterionic histidine with histidine hydrochloride. [13] A method according to claim 11 or claim 12, wherein the liquid pharmaceutical composition corresponds to one of the compositions according to claims 1 to 10. [14] A liquid pharmaceutical composition according to any one of claims 1 to 10, or a liquid pharmaceutical composition prepared according to the process of any one of claims 11 to 13, for use in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, moderate to severe chronic psoriasis and / or juvenile idiopathic arthritis. [15] A liquid pharmaceutical composition for use according to claim 14, wherein the treatment is psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, moderate to severe chronic psoriasis and / or juvenile idiopathic arthritis.