Stable, Aqueous Antibody Formulations

Abstract

The present invention relates to stable, aqueous antibody formulations. In some embodiments, the stable, aqueous formulations comprise about 2 mg/mL to about 100 mg/mL of an anti-IL5R antibody, and about 0.002% to about 0.01% polysorbate-20. Also provided are methods of making and methods of using such antibody formulations.

1 . A stable, aqueous antibody formulation comprising:
 a. about 2 mg/mL to about 100 mg/mL of an antibody, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the Kabat-defined CDR1, CDR2, and CDR3 sequences of SEQ ID NOs: 5-7, and wherein the light chain variable region comprises the Kabat-defined CDR1, CDR2, and CDR3 sequences of SEQ ID NOs: 8-10, and   b. about 0.002% to about 0.01% polysorbate-20.   
     
     
         2 . The antibody formulation of  claim 1 , further comprising an uncharged excipient. 
     
     
         3 . The antibody formulation of  claim 2 , wherein the uncharged excipient is trehalose. 
     
     
         4 . (canceled) 
     
     
         5 . The antibody formulation of  claim 1 , comprising about 20 to about 100 mg/ml of the antibody. 
     
     
         6 . (canceled) 
     
     
         7 . The antibody formulation of  claim 5 , wherein the uncharged excipient concentration is about 200 mM to about 400 mM. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . The antibody formulation of  claim 1 , further comprising histidine. 
     
     
         13 . The antibody formulation of  claim 12 , wherein the histidine concentration is about 15 mM to about 30 mM. 
     
     
         14 . (canceled) 
     
     
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         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The antibody formulation of  claim 1 , wherein the formulation is stable upon storage at about 25° C. for at least 3 months. 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . The antibody formulation of  claim 1 , wherein the formulation is substantially free from particles upon storage at about 40° C. for at least 1 month as determined by visual inspection. 
     
     
         30 . (canceled) 
     
     
         31 . The antibody formulation of  claim 1 , wherein the formulation is an injectable formulation. 
     
     
         32 . (canceled) 
     
     
         33 . A sealed container containing the antibody formulation of  claim 1 . 
     
     
         34 . A pharmaceutical unit dosage form suitable for parenteral administration to a human which comprises the antibody formulation of  claim 1  in a suitable container. 
     
     
         35 . (canceled) 
     
     
         36 . The pharmaceutical unit dosage form of  claim 34 , wherein the suitable container is a pre-filled syringe. 
     
     
         37 . The pharmaceutical unit dosage form of  claim 36 , wherein the pre-filled syringe comprises a needle. 
     
     
         38 . The pharmaceutical unit dosage form of  claim 37 , wherein the needle is a 29 G thin wall needle. 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . A pre-filled syringe comprising:
 a. about 20 mg/mL to about 100 mg/mL of an antibody, wherein the antibody comprises an amino acid sequence of SEQ ID NO:1,   b. about 0.002% to about 0.01% polysorbate-20.   
     
     
         46 . (canceled) 
     
     
         47 . (canceled) 
     
     
         48 . (canceled) 
     
     
         49 . (canceled) 
     
     
         50 . (canceled) 
     
     
         51 . (canceled) 
     
     
         52 . (canceled) 
     
     
         53 . A kit comprising the formulation of  claim 1 . 
     
     
         54 . A method of producing a stable, aqueous antibody formulation, the method comprising:
 a. purifying an antibody to about 1 mg/mL to about 400 mg/mL, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the Kabat-defined CDR1, CDR2, and CDR3 sequences of SEQ ID NOs: 5-7, and wherein the light chain variable region comprises the Kabat-defined CDR1, CDR2, and CDR3 sequences of SEQ ID NOs: 8-10;   b. placing the isolated antibody in a stabilizing formulation to form the stable, aqueous antibody formulation, wherein the resulting stable, aqueous antibody formulation comprises:
 i. about 2 mg/mL to about 100 mg/mL of the antibody, and 
 ii. about 0.002% to about 0.01% polysorbate-20. 
   
     
     
         55 . (canceled) 
     
     
         56 . (canceled) 
     
     
         57 . (canceled) 
     
     
         58 . An antibody formulation comprising an antibody wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the Kabat-defined CDR1, CDR2, and CDR3 sequences of SEQ ID NOs: 5-7, and wherein the light chain variable region comprises the Kabat-defined CDR1, CDR2, and CDR3 sequences of SEQ ID NOs: 8-10, wherein the antibody formulation is essentially free of particles. 
     
     
         59 . An antibody formulation comprising an antibody wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the Kabat-defined CDR1, CDR2, and CDR3 sequences of SEQ ID NOs: 5-7, and wherein the light chain variable region comprises the Kabat-defined CDR1, CDR2, and CDR3 sequences of SEQ ID NOs: 8-10, wherein the antibody formulation is essentially free of active glutathione S-transferase (GST). 
     
     
         60 . (canceled) 
     
     
         61 . (canceled) 
     
     
         62 . (canceled) 
     
     
         63 . (canceled) 
     
     
         64 . (canceled) 
     
     
         65 . (canceled) 
     
     
         66 . A method of treating a pulmonary disease or disorder in a subject, the method comprising administering a therapeutically effective amount of the antibody formulation of  claim 1 . 
     
     
         67 . (canceled) 
     
     
         68 . The method of  claim 66 , wherein the pulmonary disease or disorder is asthma, COPD, eosinophilic asthma, combined eosinophilic and neutrophilic asthma, aspirin sensitive asthma, allergic bronchopulmonary aspergillosis, acute and chronic eosinophilic bronchitis, acute and chronic eosinophilic pneumonia, Churg-Strauss syndrome, hypereosinophilic syndrome, drug, irritant and radiation-induced pulmonary eosinophilia, infection-induced pulmonary eosinophilia (fungi, tuberculosis, parasites), autoimmune-related pulmonary eosinophilia, eosinophilic esophagitis, Crohn's disease, or combination thereof. 
     
     
         69 . (canceled) 
     
     
         70 . (canceled)