Liquid pharmaceutical composition

Abstract

The present invention relates to novel liquid pharmaceutical compositions of adalimumab, which include adalimumab or a biosimilar thereof, arginine and/or methionine, and a small polyol stabiliser such as glycerol. Such a combination of components furnishes formulations having a stability (e.g. on storage and when exposed to stress) which is comparable to or an improvement upon those known in the art, and with fewer ingredients. Such advances will help adalimumab treatments to become more widely available at lower cost, and prolong the viability of pre-loaded delivery devices (e.g. pre-filled syringes) to reduce unnecessary waste of the drug.

1 . A liquid pharmaceutical composition comprising:
 (a) adalimumab;   (b) arginine;   (c) methionine; and   (d) a C2-C6 polyol.   
     
     
         2 . The liquid pharmaceutical composition according to  claim 1 , wherein the polyol is a C2-C4 polyol, suitably glycerol. 
     
     
         3 . The liquid pharmaceutical composition according to  claim 1 , wherein the composition further comprises a buffer system, suitably an acetate buffer system, suitably an acetate buffer system formed without generating sodium chloride, suitably an acetate buffer system formed by basification of a quantity of acetic acid. 
     
     
         4 . The liquid pharmaceutical composition according to  claim 1 , comprising 25 to 125 mg/ml adalimumab. 
     
     
         5 . The liquid pharmaceutical composition according to  claim 1 , wherein the composition is free of, substantially free of, or comprises at most mM of a tonicifier, suitably where the tonicifier is sodium chloride. 
     
     
         6 . The liquid pharmaceutical composition according to  claim 1  comprising:
 (a) adalimumab; 
 (b) arginine; 
 (c) methionine; 
 (d) a C2-C6 polyol; 
 (e) a buffer system; and 
 (f) a surfactant; 
 wherein the composition has a pH between 4.0 and 6.0. 
 
     
     
         7 . The liquid pharmaceutical composition according to  claim 6  comprising:
 (a) adalimumab; 
 (b) arginine; 
 (c) methionine; 
 (d) a C2-C4 polyol; 
 (e) an acetate buffer system; 
 (f) sodium chloride; and 
 (g) a non-ionic surfactant; 
 wherein the composition has a pH between 4.8 and 5.2. 
 
     
     
         8 . The liquid pharmaceutical composition according to  claim 6  comprising:
 (a) adalimumab; 
 (b) arginine; 
 (c) methionine; 
 (d) a C2-C4 polyol; 
 (e) an acetate buffer system; 
 (f) a non-ionic surfactant; 
 wherein the composition has a pH between 4.9 and 5.4, and the composition is free or substantially free of sodium chloride. 
 
     
     
         9 . The liquid pharmaceutical composition according to  claim 6  consisting of:
 (a) 25-125 mg/ml adalimumab; 
 (b) 50-70 mM L-arginine; 
 (c) 20-40 mM L-methionine; 
 (d) 100-150 mM glycerol or propylene glycol; 
 (e) 5-10 mM acetate buffer system; 
 (f) 20-40 mM sodium chloride; and 
 (g) 0.5-2 mg/ml polysorbate 20 or poloxamer 188; 
 wherein the composition has a pH between 4.8 and 5.2; 
 
       or consisting of:
 (a) 25-125 mg/ml adalimumab; 
 (b) 50-70 mM L-arginine; 
 (c) 20-40 mM L-methionine; 
 (d) 100-150 mM glycerol or propylene glycol; 
 (e) 5-10 mM acetate buffer system; and 
 (f) 0.5-2 mg/ml polysorbate 20 or poloxamer 188; 
 wherein the composition has a pH between 5.0 and 5.4. 
 
     
     
         10 . The liquid pharmaceutical composition according to  claim 6  consisting of:
 (a) 100 mg/ml adalimumab; 
 (b) 60 mM L-arginine; 
 (c) 30 mM L-methionine; 
 (d) 130 mM glycerol or propylene glycol; 
 (e) 8 mM acetate buffer system, preferably sodium acetate buffer; 
 (f) 30 mM sodium chloride; and 
 (g) 1 mg/ml polysorbate 20 or poloxamer 188; 
 wherein the composition has a pH of 5.0 (suitably +/−0.3); 
 
       or consisting of:
 (a) 100 mg/ml adalimumab; 
 (b) 60 mM L-arginine; 
 (c) 30 mM L-methionine; 
 (d) 130 mM glycerol or propylene glycol; 
 (e) 8 mM of an acetate buffer system, preferably sodium acetate buffer; and 
 (f) 1 mg/ml polysorbate 20 or poloxamer 188; 
 wherein the composition has a pH of 5.2 (suitably +/−0.3). 
 
     
     
         11 . A drug delivery device comprising the liquid pharmaceutical composition according to  claim 1 . 
     
     
         12 . A method of treating a disease or disorder comprising administering an effective amount of the liquid pharmaceutical composition of  claim 1  to a mammal having the disease or disorder. 
     
     
         13 . The method of  claim 12 , wherein the disease or disorder is rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis, hidradenitis suppurativa, uveitis or juvenile idiopathic arthritis. 
     
     
         14 . A method of manufacturing a liquid pharmaceutical composition, the method comprising mixing together adalimumab, arginine, methionine and a C2-C6 polyol. 
     
     
         15 . A solid composition obtainable by freeze-drying a liquid pharmaceutical composition according to  claim 1 .