Stable liquid antibody formulation

Abstract

The present invention relates generally to the field of pharmaceutical formulations of antibodies. Specifically, the present invention relates to a stable liquid antibody formulation and its pharmaceutical preparation and use. This invention is exemplified by a liquid formulation of a humanised anti-NGF antibody.

1 - 34 . (canceled) 
     
     
         35 . A method for treating pain in a mammal comprising administering an effective amount of a liquid composition to said mammal once every eight weeks, wherein the liquid composition comprises
 at least one antibody,   at least one tonicity agent,   at least one buffer,   at least one chelating agent,   at least one surfactant,   wherein the pH of said composition is from 5.8 to 6.8, and wherein the at least one antibody comprises an amino acid sequence that is at least 90% identical to a heavy chain variable region amino acid sequence shown in SEQ ID NO:1, and an amino acid sequence that is at least 90% identical to a light chain variable region amino acid sequence shown in SEQ ID NO: 2.   
     
     
         36 . The method according to  claim 35  wherein the volume of the effective amount of the liquid composition is less than or equal to about 2.5 ml. 
     
     
         37 . The method according to  claim 35  wherein the effective amount of the liquid composition contains less than or equal to 50 mg of antibody. 
     
     
         38 . The method according to  claim 35  wherein administration of the effective amount of the liquid composition is administered either intravenously or subcutaneously intravenously. 
     
     
         39 . The method according to  claim 35 , wherein the tonicity agent is a non reducing sugar. 
     
     
         40 . The method according to  claim 39 , wherein the non reducing sugar is trehalose dihydrate at a concentration of about 1 mg/ml to about 100 mg/ml. 
     
     
         41 . The method according to  claim 35  wherein the surfactant is a polysorbate, preferably polysorbate 20. 
     
     
         42 . The method according to  claim 41  wherein the concentration of polysorbate is from about 0.01 to about 0.15 mg/ml. 
     
     
         43 . The method according to  claim 35  wherein the buffer is histidine buffer. 
     
     
         44 . The method according to  claim 43  wherein the concentration of histidine buffer is from about 1.0 to about 15 mM. 
     
     
         45 . The method according to  claim 35  wherein the chelating agent is disodium EDTA, preferably of a concentration from about 0.01 to about 0.1 mg/ml. 
     
     
         46 . The method according to  claim 35  wherein the antibody concentration is less than or equal to about 50 mg/ml. 
     
     
         47 . The method according to  claim 46  wherein the antibody concentration is selected from about 2 mg/ml, about 2.5 mg/ml, about 5 mg/ml, about 10 mg/ml, about 20 mg/ml, about 22 mg/ml and about 50 mg/ml. 
     
     
         48 . The method according to  claim 35  wherein the liquid composition further comprises an antioxidant agent and/or a preservative agent. 
     
     
         49 . The method according to  claim 35  wherein the liquid composition does not comprise an antioxidant agent, a preservative agent or both. 
     
     
         50 . The method according to  claim 35 , wherein the liquid composition comprises:
 about 0.5 mg/ml to about 50 mg/ml of at least one antibody,   about 1.0 mM to about 15 mM histidine buffer,   about 1 mg/ml to about 100 mg/ml trehalose dihydrate,   about 0.01 to about 0.15 mg/ml PS20,   about 0.01 to about 0.1 mg/ml. disodium EDTA,   wherein said composition is of a pH from 5.8 to 6.8.   
     
     
         51 . The method according to  claim 50 , wherein the liquid composition consists of:
 about 0.5 mg/ml to about 50 mg/ml of at least one antibody,   about 1.0 mM to about 15 mM histidine buffer,   about 1 mg/ml to about 100 mg/ml trehalose dihydrate,   about 0.01 to about 0.15 mg/ml PS20,   about 0.01 to about 0.1 mg/ml. disodium EDTA,   wherein said composition is of a pH from 5.8 to 6.8.   
     
     
         52 . The method according to  claim 50 , wherein the liquid composition comprises:
 about 2.5 mg/ml, 5 mg/ml, 10 mg/ml, 20 mg/ml, 22 mg/ml or about 50 mg/ml of at least one antibody,   about 10 mM histidine buffer,   about 84 mg/ml trehalose dihydrate,   about 0.1 mg/ml PS20,   about 0.05 mg/ml. disodium EDTA,   wherein said composition is of a pH 6.0+/−0.2.   
     
     
         53 . The method according to  claim 50 , wherein the at least one antibody binds to human NGF with a Kd of less than or about 2 nM. 
     
     
         54 . The method according to  claim 35  wherein the at least one antibody comprises an amino acid sequence that is at least 90% identical to a heavy chain amino acid sequence shown in SEQ ID NO: 16, and an amino acid sequence that is at least 90% identical to a light chain amino acid sequence shown in SEQ ID NO: 17. 
     
     
         55 . The method according to  claim 35  wherein the antibody comprises a variable heavy chain sequence of SEQ ID NO. 1 and a variable light chain sequence of SEQ ID NO. 2. 
     
     
         56 . The method according to  claim 35  wherein the composition is not lyophilized.