Compositions comprising a p75 tumor necrosis factor receptor/ig fusion protein

Abstract

The present invention relates to an aqueous pharmaceutical composition suitable for long-term storage of polypeptides containing an Fc domain of an immunoglobulin, methods of manufacture, methods of administration and kits containing same.

1 .- 30 . (canceled) 
     
     
         31 . A method comprising
 (a) forming an aqueous pharmaceutical composition comprising etanercept, an excipient and a buffer, and   (b) storing the aqueous pharmaceutical composition as a liquid for three months at 2-8° C., wherein the excipient is lysine, the buffer is sodium citrate, and wherein the aqueous pharmaceutical composition does not comprise arginine.   
     
     
         32 . The method of  claim 31 , wherein the sodium citrate of the aqueous pharmaceutical composition of step (a) is present at a concentration of about 10 mM to about 200 mM. 
     
     
         33 . The method of  claim 31 , wherein the aqueous pharmaceutical composition of step (a) comprises from about 10 mg/mL to about 100 mg/mL etanercept. 
     
     
         34 . The method of  claim 33 , wherein the aqueous pharmaceutical composition of step (a) comprises about 50 mg/mL etanercept. 
     
     
         35 . The method of  claim 31 , wherein the aqueous pharmaceutical composition of step (a) further comprises sodium chloride at a concentration of about 10 mM to about 200 mM. 
     
     
         36 . The method of  claim 31 , wherein the aqueous pharmaceutical composition of step (a) further comprises sucrose at a concentration of about 10 mM to about 200 mM. 
     
     
         37 . The method of  claim 31 , wherein step (a) comprises forming an aqueous pharmaceutical composition comprising 50 mg/ml etanercept, lysine at a concentration of 0.1-2 wt %, sodium citrate at a concentration of about 10 mM to about 200 mM, sodium chloride at a concentration of about 10 mM to about 200 mM, and sucrose at a concentration of about 10 mM to about 200 mM. 
     
     
         38 . The method of  claim 31 , wherein the aqueous pharmaceutical composition of step (b) does not lose more than 5% of its TNF binding activity at three months stored at 2-8° C. relative to the binding activity of the composition at the beginning of storage. 
     
     
         39 . A method comprising
 (a) forming an aqueous pharmaceutical composition comprising etanercept, an excipient and a buffer,   (b) freezing the aqueous pharmaceutical composition of step (a), and   (c) thawing the composition of step (b),   wherein the excipient is lysine, the buffer is sodium citrate, and wherein the aqueous pharmaceutical composition does not comprise arginine.   
     
     
         40 . The method of  claim 39 , wherein step (b) comprises freezing the composition at a temperature of −20° C. or less for a period of three months or more. 
     
     
         41 . The method of  claim 39 , wherein the sodium citrate of the aqueous pharmaceutical composition of step (a) is present at a concentration of about 10 mM to about 200 mM. 
     
     
         42 . The method of  claim 39 , wherein the aqueous pharmaceutical composition of step (a) comprises from about 10 mg/mL to about 100 mg/mL etanercept. 
     
     
         43 . The method of  claim 42 , wherein the aqueous pharmaceutical composition of step (a) comprises about 50 mg/mL etanercept. 
     
     
         44 . The method of  claim 39 , wherein the aqueous pharmaceutical composition of step (a) further comprises sodium chloride at a concentration of about 10 mM to about 200 mM. 
     
     
         45 . The method of  claim 39 , wherein the aqueous pharmaceutical composition of step (a) further comprises sucrose at a concentration of about 10 mM to about 200 mM. 
     
     
         46 . The method of  claim 39 , wherein step (a) comprises forming an aqueous pharmaceutical composition comprising 50 mg/ml etanercept, lysine at a concentration of about 0.1-2 wt %, sodium citrate at a concentration of about 10 mM to about 200 mM, sodium chloride at a concentration of about 10 mM to about 200 mM, and sucrose at a concentration of about 10 mM to about 200 mM. 
     
     
         47 . The method of  claim 39 , wherein the thawed composition of step (c) does not lose more than 5% of its TNF binding activity relative to the TNF binding activity of the aqueous pharmaceutical composition of step (a). 
     
     
         48 . The method of  claim 39 , further comprising (d) storing the thawed composition of step (c) for three months at 2-8° C. 
     
     
         49 . The method of  claim 39 , wherein the composition of step (d) does not lose more than 5% of its TNF binding activity relative to the TNF binding activity of the thawed composition of step (c). 
     
     
         50 . The method of  claim 39 , further comprising loading the thawed composition of step (c) into a syringe or injector pen, wherein etanercept is present at a concentration of 50 mg/ml.