Antagonist anti-CD40 antibody pharmaceutical compositions
AssigneesNovartis AG, Xoma Technology Ltd.
InventorsXiaofeng Lu, Bao-Lu Chen, Kidisti Araya, Augustus Okhamafe
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Abstract
Stable liquid pharmaceutical compositions comprising an antagonist anti-CD40 antibody as a therapeutically or prophylactically active component and methods useful in their preparation are provided. These compositions comprise the antagonist anti-CD40 antibody, a buffering agent to maintain the pH of the composition between about pH 5.0 and about pH 7.0, and an amount of arginine-HCl sufficient to render the liquid composition near isotonic. The stable liquid antagonist anti-CD40 antibody-containing pharmaceutical compositions of the invention find use in methods for treating proliferative diseases and diseases having an autoimmune and/or inflammatory component.
Claims37
A stable liquid pharmaceutical composition comprising:
- a) an antagonist anti-CD40 monoclonal antibody as a therapeutically or prophylactically active component, wherein said monoclonal antibody is capable of specifically binding to a human CD40 antigen expressed on the surface of a human B cell, said monoclonal antibody being free of significant agonist activity when bound to the CD40 antigen expressed on the surface of said B cell;
- b) an amount of an isotonizing agent sufficient to render said composition as having an osmolality of about 240 mmol/kg to about 360 mmol/kg, wherein said isotonizing agent is arginine in its acidic form (arginine-HCl), and wherein said composition does not include NaCl as an additional isotonizing agent;
- and
- c) a buffering agent to maintain the pH of said composition within a range from about pH 5.0 to about pH 7.0, wherein said buffering agent is a citrate/citric acid buffer;
- wherein said antagonist anti-CD40 monoclonal antibody is present in said composition at a concentration of about 0.1 mg/ml to about 50.0 mg/ml and is selected from the group consisting of:
- i) a monoclonal antibody comprising the variable and constant region sequences shown in SEQ ID NO:2 and the variable and constant region sequences shown in SEQ ID NO:4;
- ii) a monoclonal antibody comprising the variable and constant region sequences shown in SEQ ID NO:2 and the variable and constant region sequences shown in SEQ ID NO:5;
- iii) a monoclonal antibody comprising the leader, variable and constant region sequences shown in SEQ ID NO:2 and the leader, variable and constant region sequences shown in SEQ ID NO:4;
- and
- iv) a monoclonal antibody comprising the leader, variable and constant region sequences shown in SEQ ID NO:2 and the leader, variable and constant region sequences shown in SEQ ID NO:5;
- wherein the concentration of said buffering agent is about 5 mM to about 100 mM, and wherein said composition comprises arginine-HCl at a concentration of about 50 mM to about 200 mM.
A method for increasing stability of an anti-CD40 monoclonal antibody in a liquid pharmaceutical composition, said method comprising formulating said composition by combining said anti-CD40 monoclonal antibody, an amount of an isotonizing agent sufficient to render to said composition as having an osmolality of about 240 mmol/kg to about 360 mmol/kg, wherein said isotonizing agent is arginine in its acidic form (arginine-HCl) and wherein said composition does not include NaCl as an additional isotonizing agent, and a buffering agent to maintain the pH of said composition between about pH 5.0 and about pH 7.0, wherein said buffering agent is a citrate/citric acid buffer, and wherein said anti-CD40 monoclonal antibody is present in said composition at a concentration of about 0.1 mg/ml to about 50.0 mg/ml and is selected from the group consisting of:
- i) a monoclonal antibody comprising the variable and constant region sequences shown in SEQ ID NO:2 and the variable and constant region sequences shown in SEQ ID NO:4;
- ii) a monoclonal antibody comprising the variable and constant region sequences shown in SEQ ID NO:2 and the variable and constant region sequences shown in SEQ ID NO:5;
- iii) a monoclonal antibody comprising the leader, variable and constant region sequences shown in SEQ ID NO:2 and the leader, variable and constant region sequences shown in SEQ ID NO:4;
- and
- iv) a monoclonal antibody comprising the leader, variable and constant region sequences shown in SEQ ID NO:2 and the leader, variable and constant region sequences shown in SEQ ID NO:5;
- wherein the concentration of said buffering agent is about 5 mM to about 100 mM, and wherein said composition comprises arginine-HCl at a concentration of about 50 mM to about 200 mM.
A method for preparing a liquid pharmaceutical composition comprising an anti-CD40 monoclonal antibody, said method comprising formulating said composition by combining said anti-CD40 monoclonal antibody, an amount of an isotonizing agent sufficient to render to said composition as having an osmolality of about 240 mmol/kg to about 360 mmol/kg, wherein said isotonizing agent is arginine in its acidic form (arginine-HCl) and wherein said composition does not include NaCl as an additional isotonizing agent, and a buffering agent to maintain the pH of said composition between about pH 5.0 and about pH 7.0, wherein said buffering agent is a citrate/citric acid buffer, wherein said anti-CD40 monoclonal antibody is present in said composition at a concentration of about 0.1 mg/ml to about 50.0 mg/ml and is selected from the group consisting of:
- i) a monoclonal antibody comprising the variable and constant region sequences shown in SEQ ID NO:2 and the variable and constant region sequences shown in SEQ ID NO:4;
- ii) a monoclonal antibody comprising the variable and constant region sequences shown in SEQ ID NO:2 and the variable and constant region sequences shown in SEQ ID NO:5;
- iii) a monoclonal antibody comprising the leader, variable and constant region sequences shown in SEQ ID NO:2 and the leader, variable and constant region sequences shown in SEQ ID NO:4;
- and
- iv) a monoclonal antibody comprising the leader, variable and constant region sequences shown in SEQ ID NO:2 and the leader, variable and constant region sequences shown in SEQ ID NO:5;
- wherein the concentration of said buffering agent is about 5 mM to about 100 mM, and wherein said composition comprises arginine-HCl at a concentration of about 50 mM to about 200 mM.
Dependencies are inferred from the claim text.