Stable Multi-Dose Compositions Comprising an Antibody and a Preservative

Abstract

The invention relates to stable, multi-dose liquid compositions containing proteins, in particular, but not exclusively stable antibodies, and to the use of said compositions in therapy, in particular for the subcutaneous delivery of said stable protein.

1 . A stable, multi-dose liquid composition comprising an antibody and one or more preservatives. 
     
     
         2 . A composition according to  claim 1 , wherein the preservative is present within the composition in an amount of between 0.001 to 2% (w/v), such as 0.002 to 1% (w/v). 
     
     
         3 . A composition according to  claim 1 , wherein the one or more preservative is selected from the group consisting of phenol, m-cresol, benzyl alcohol, chlorobutanol, ethanol, phenoxyethanol, p-chlor-m-cresol, methyl paraben, propyl paraben, benzalkonium chloride, thiomersal or any combinations thereof, such as phenol, m-cresol, benzyl alcohol and chlorobutanol. 
     
     
         4 . A composition according to  claim 1 , which comprises a single preservative, selected from the group consisting of phenol, m-cresol, benzyl alcohol, chlorobutanol, ethanol, phenoxyethanol, p-chlor-m-cresol, methyl paraben, propyl paraben, benzalkonium chloride and thiomersal, such as phenol, m-cresol, benzyl alcohol and chlorobutanol. 
     
     
         5 . A composition according to  claim 1 , which comprises two or more preservatives selected from the group consisting of phenol, m-cresol, benzyl alcohol, chlorobutanol, ethanol, phenoxyethanol, p-chlor-m-cresol, methyl paraben, propyl paraben, benzalkonium chloride and thiomersal, such as phenol, m-cresol, benzyl alcohol and chlorobutanol, in particular: phenol and m-cresol; and benzyl alcohol and chlorobutanol. 
     
     
         6 . A composition according to  claim 1 , which is buffered to a pH of between 5 and 7, such as a pH of between 6.0 and 7.0, such as 6.0 or 6.5, in particular 6.5. 
     
     
         7 . A composition according to  claim 1 , which further comprises a tonicity modifying agent selected from the group consisting of sucrose and propylene glycol. 
     
     
         8 . A composition according to  claim 1 , wherein the antibody is present within the composition in a concentration selected from the group consisting of 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150, 200, 250, and 300 mg/ml. 
     
     
         9 . A composition according to  claim 1 , wherein no surfactant is present. 
     
     
         10 . A composition according to  claim 1  comprising:
 (a) 100 mg/ml antibody; 
 (b) 25 mM sodium chloride; 
 (c) 33 mM histidine buffer; 
 (d) 25 mM arginine; 
 (e) 0.001% polysorbate 80; 
 (f) 1.5 mg/ml phenol and 1.8 mg/ml m-cresol; and 
 (g) 120 mM sucrose; 
 
       buffered to a pH of 6.5. 
     
     
         11 . A composition according to  claim 1  comprising:
 (a) 100 mg/ml antibody; 
 (b) 25 mM sodium chloride; 
 (c) 33 mM histidine buffer; 
 (d) 25 mM arginine; 
 (e) 0.01% polysorbate  80 ; 
 (f) 1.5 mg/ml phenol and 1.8 mg/ml m-cresol; and 
 (g) 120 mM sucrose; 
 
       buffered to a pH of 6.5. 
     
     
         12 . A composition according to  claim 1  comprising:
 (a) 100 mg/ml antibody; 
 (b) 25 mM sodium chloride; 
 (c) 33 mM histidine buffer; 
 (d) 25 mM arginine; 
 (e) 0.01% polysorbate  80 ; 
 (f) 1.5 mg/ml phenol and 1.8 mg/ml m-cresol; and 
 (g) 120 mM sucrose; 
 
       buffered to a pH of 6. 
     
     
         13 - 15 . (canceled) 
     
     
         16 . A method of treating an inflammatory disease comprising administering a stable antibody composition according to  claim 1 . 
     
     
         17 . A method of treating a coagulopathy comprising administering a stable antibody composition according to  claim 1 .