Antibody formulation

Abstract

The invention provides a stable aqueous pharmaceutical formulation comprising a therapeutically effective amount of an antibody, optionally, not subjected to prior lyophilization, a buffer maintaining the pH in the range from about 4.0 to about 6.0, and an optional surfactant, methods for making such a formulation, and methods of using such a formulation.

1 - 56 . (canceled) 
     
     
         57 . A method of treating a disease or disorder in a subject comprising administering an effective amount of a pharmaceutical formulation to the subject, wherein the pharmaceutical formulation comprises an antibody that binds to VEGF in an arginine acetate buffer at a pH from about 4.5 to about 6.0, and a surfactant, wherein the antibody is bevacizumab. 
     
     
         58 - 70 . (canceled) 
     
     
         71 . The method of  claim 57 , wherein the disease or disorder is cancer. 
     
     
         72 . The method of  claim 71 , wherein the cancer is colorectal cancer, lung cancer, breast cancer, renal cancer, or glioblastoma. 
     
     
         73 . The method of  claim 57 , wherein the arginine acetate buffer is at a pH from about 4.5 to about 5.5. 
     
     
         74 . The method of  claim 57 , wherein the arginine acetate buffer is at a pH from about 4.8 to about 5.4. 
     
     
         75 . The method of  claim 57 , wherein the arginine acetate buffer is at pH about 5.2. 
     
     
         76 . The method of  claim 57 , wherein the arginine acetate concentration in the buffer is from about 25 mM to about 250 mM. 
     
     
         77 . The method of  claim 57 , wherein the arginine acetate concentration in the buffer is from about 50 mM to about 250 mM. 
     
     
         78 . The method of  claim 57 , wherein the arginine acetate concentration in the buffer is from about 75 mM to about 250 mM. 
     
     
         79 . The method of  claim 57 , wherein the arginine acetate concentration in the buffer is from about 100 mM to about 250 mM. 
     
     
         80 . The method of  claim 57 , wherein the arginine acetate concentration in the buffer is from about 120 mM to about 240 mM. 
     
     
         81 . The method of  claim 57 , wherein the arginine acetate concentration in the buffer is from about 150 mM to about 225 mM. 
     
     
         82 . The method of  claim 57 , wherein the arginine acetate concentration in the buffer is about 200 mM. 
     
     
         83 . The method of  claim 57 , wherein the surfactant is polysorbate. 
     
     
         84 . The method of  claim 83 , wherein the polysorbate is polysorbate 20. 
     
     
         85 . The method of  claim 57 , wherein the surfactant concentration is from about 0.0001% v/v to about 1.0%0/v/v. 
     
     
         86 . The method of  claim 57 , wherein the surfactant concentration is from about 0.01% v/v to about 0.05% v/v. 
     
     
         87 . The method of  claim 57 , wherein the surfactant concentration is about 0.04% v/v. 
     
     
         88 . The method of  claim 57 , wherein the antibody concentration is from about 10 mg/ml to about 250 mg/ml. 
     
     
         89 . The method of  claim 57 , wherein the antibody concentration is from about 25 mg/ml to about 200 mg/ml. 
     
     
         90 . The method of  claim 57 , wherein the antibody concentration is from about 50 mg/ml to about 150 mg/ml. 
     
     
         91 . The method of  claim 57 , wherein the antibody concentration is from about 75 mg/ml to about 125 mg/ml. 
     
     
         92 . The method of  claim 57 , wherein the antibody concentration is about 100 mg/ml. 
     
     
         93 . The method of  claim 57 , wherein the antibody is not subject to prior lyophilization. 
     
     
         94 . The method of  claim 57 , wherein the antibody is susceptible to aggregation. 
     
     
         95 . The method of  claim 57 , wherein the antibody concentration is about 75 mg/ml to about 125 mg/ml, the arginine acetate buffer is at a pH from about 4.8 to about 5.4, the arginine acetate concentration in the buffer is from about 150 mM to about 225 mM, and the surfactant is polysorbate in an amount of about 0.01% v/v to about 0.05% v/v. 
     
     
         96 . The method of  claim 95 , wherein the antibody concentration is about 100 mg/ml, the arginine acetate buffer is at pH about 5.2, the arginine acetate concentration in the buffer is about 200 mM, and the surfactant is polysorbate in an amount of about 0.04% v/v. 
     
     
         97 . The method of  claim 57 , wherein the pharmaceutical formulation is sterile. 
     
     
         98 . The method of  claim 57 , wherein the pharmaceutical formulation is stable upon storage at about 40° C. for at least 28 days. 
     
     
         99 . The method of  claim 57 , wherein the pharmaceutical formulation is aqueous and is administered to a subject. 
     
     
         100 . The method of  claim 99 , wherein the pharmaceutical formulation is for intravenous (IV), subcutaneous (SQ), or intramuscular (IM) administration. 
     
     
         101 . The method of  claim 100 , wherein the pharmaceutical formulation is for IV administration and the antibody concentration is from about 10 mg/ml to about 250 mg/ml. 
     
     
         102 . The method of  claim 100 , wherein the pharmaceutical formulation is for IV administration and the antibody concentration is from about 50 mg/ml to about 150 mg/ml. 
     
     
         103 . The method of  claim 100 , wherein the pharmaceutical formulation is for SQ administration and the antibody concentration is from about 25 mg/ml to about 250 mg/ml. 
     
     
         104 . The method of  claim 100 , wherein the pharmaceutical formulation is for SQ administration and the antibody concentration is from about 50 mg/ml to about 150 mg/ml.