Stabilized Formulations Containing Anti-IL-33 Antibodies

Abstract

The present invention provides pharmaceutical formulations comprising an antibody that specifically binds to human interleukin-33 (hlL-33). The formulations may contain, in addition to an anti-IL-33 antibody, a buffer, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months and after being subjected to thermal and other physical stresses.

What is claimed is: 
     
         1 - 69 . (canceled) 
     
     
         70 . A stable liquid pharmaceutical formulation comprising:
 (i) a human antibody that specifically binds to human interleukin-33 (hIL-33), wherein the antibody comprises the complementarity determining regions (HCDR1-HCDR2-HCDR3) of a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2, and the complementarity determining regions (LCDR1-LCDR2-LCDR3) of a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 10, and wherein the antibody is present at a concentration of from 1 mg/ml to 200 mg/ml;   (ii) a buffer;   (iii) a surfactant;   (iv) a thermal stabilizer; and   (v) a viscosity modifier, wherein the viscosity modifier comprises arginine or a combination of arginine and glutamic acid, and wherein the viscosity modifier is present at a concentration of at least 50 mM;   wherein the formulation has a pH from 5 to 5.6, and wherein the formulation exhibits a viscosity of less than about 15 cPoise when measured at 20° C.   
     
     
         71 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the viscosity modifier is present at a concentration of from 50 mM to 100 mM. 
     
     
         72 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the viscosity modifier comprises arginine. 
     
     
         73 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the viscosity modifier comprises a combination of arginine and glutamic acid. 
     
     
         74 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the antibody is present at a concentration of from 100 mg/ml to 200 mg/ml. 
     
     
         75 . The stable liquid pharmaceutical formulation of  claim 74 , wherein the antibody is present at a concentration of from 135 mg/ml to 165 mg/ml. 
     
     
         76 . The stable liquid pharmaceutical formulation of  claim 74 , wherein the antibody is present at a concentration of about 150 mg/ml. 
     
     
         77 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the antibody comprises HCDR1-HCDR2-HCDR3 regions comprising the amino acid sequences of SEQ ID NOs: 4-6-8, respectively, and LCDR1-LCDR2-LCDR3 regions comprising the amino acid sequences of SEQ ID NOs: 12-14-16, respectively. 
     
     
         78 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the antibody comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2, and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 10. 
     
     
         79 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 18 and a light chain comprising the amino acid sequence of SEQ ID NO: 20. 
     
     
         80 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the pH of the formulation is from 5.2 to 5.4. 
     
     
         81 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the buffer comprises acetate or histidine at a concentration of from 1 mM to 40 mM. 
     
     
         82 . The stable liquid pharmaceutical formulation of  claim 81 , wherein the buffer comprises acetate at a concentration of from 1 mM to 20 mM. 
     
     
         83 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the surfactant is a non-ionic surfactant. 
     
     
         84 . The stable liquid pharmaceutical formulation of  claim 83 , wherein the non-ionic surfactant is a polysorbate, a poloxamer, polyethylene-polypropylene glycol, or polyethylene glycol. 
     
     
         85 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the surfactant is present at a concentration of from 0.01% w/v to 0.15% w/v. 
     
     
         86 . The stable liquid pharmaceutical formulation of  claim 70 , wherein the thermal stabilizer is sucrose at a concentration of from 1% w/v to 10% w/v. 
     
     
         87 . The stable liquid pharmaceutical formulation of  claim 70  contained in a glass vial. 
     
     
         88 . The stable liquid pharmaceutical formulation of  claim 70  contained in a syringe. 
     
     
         89 . The stable liquid pharmaceutical formulation of  claim 88 , wherein the syringe is a prefilled syringe. 
     
     
         90 . The stable liquid pharmaceutical formulation of  claim 70  contained in a large volume device or bolus injector. 
     
     
         91 . The stable liquid pharmaceutical formulation of  claim 70  contained in a pen or autoinjector delivery device.