Stable aqueous antibody formulation

Abstract

The present invention relates 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 an aqueous formulation of an anti-vascular endothelial growth factor (VEGF) antibody.

1 - 18 . (canceled) 
     
     
         19 . A method for treating or inhibiting cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an aqueous formulation comprising: about 25 mg/ml to about 150 mg/ml of an anti-vascular endothelial growth factor (VEGF) antibody; a buffer; a polyol; a surfactant; a chelating agent; and wherein the formulation has a pH at about 5.0 to about 6.0. 
     
     
         20 . The method of claim  0 , wherein the cancer is selected from the group consisting of colorectal cancer, rectal cancer, non-squamous non-small cell lung cancer (NSCLC), non-Hodgkins lymphoma (NHL), metastatic renal cell cancer (mRCC), prostate cancer, liver cancer, pancreatic cancer, soft-tissue sarcoma, kaposi's sarcoma, carcinoid carcinoma, head and neck cancer, melanoma, ovarian cancer, mesothelioma, glioblastoma, cervical cancer, breast cancer, and multiple myeloma. 
     
     
         21 . The method of claim  0 , wherein the formulation is administered to the subject subcutaneously or intravenously. 
     
     
         22 . The method of  claim 19 , wherein the subject is human. 
     
     
         23 - 24 . (canceled) 
     
     
         25 . The method of  claim 19 , wherein the buffer is a succinate or histidine buffer. 
     
     
         26 . The method of  claim 19 , wherein the concentration of the buffer is about 1 mM to about 100 mM. 
     
     
         27 . The method of  claim 19 , wherein the surfactant is a polysorbate. 
     
     
         28 . The method of  claim 27 , wherein the polysorbate is polysorbate 80 (PS80). 
     
     
         29 . The method of  claim 19 , wherein the concentration of the surfactant is about 0.01 mg/ml to about 10 mg/ml. 
     
     
         30 . The method of  claim 19 , wherein the chelating agent is EDTA (ethylenediaminetetraacetic acid). 
     
     
         31 . The method of  claim 19 , wherein the concentration of the chelating agent is about 0.01 mg/ml to about 1.0 mg/ml. 
     
     
         32 . The method of  claim 19 , wherein the antibody comprises a heavy chain variable region (VH) complementary determining region one (CDR1) having the amino acid sequence shown in SEQ ID NO: 1, a VH CDR2 having the amino acid sequence shown in SEQ ID NO: 2, a VH CDR3 having the amino acid sequence shown in SEQ ID NO: 3, and a light chain variable region (VL) CDR1 having the amino acid sequence shown in SEQ ID NO: 4, a VL CDR2 having the amino acid sequence shown in SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence shown in SEQ ID NO: 6. 
     
     
         33 . The method of  claim 19 , wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH region comprises the amino acid sequence of SEQ ID NO: 7, and the VL region comprises the amino acid sequence of SEQ ID NO: 8. 
     
     
         34 . The method of  claim 19 , wherein the formulation has a shelf life of at least about 36 months. 
     
     
         35 . A method for treating or inhibiting cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of aqueous formulation comprising:
 about 15 mg/ml to about 150 mg/ml of an anti-vascular endothelial growth factor (VEGF) antibody;   about 1 mM to about 100 mM of a buffer;   about 1 mg/mL to about 300 mg/mL of a polyol;   about 0.01 mg/ml to about 10 mg/ml of a surfactant;   about 0.01 mg/ml to about 1.0 mg/ml of a chelating agent;   wherein the formulation has a pH at about 5.0 to about 6.0; and wherein the antibody comprises a heavy chain variable region (VH) complementary determining region one (CDR1) having the amino acid sequence shown in SEQ ID NO: 1, a VH CDR2 having the amino acid sequence shown in SEQ ID NO: 2, a VH CDR3 having the amino acid sequence shown in SEQ ID NO: 3, and a light chain variable region (VL) CDR1 having the amino acid sequence shown in SEQ ID NO: 4, a VL CDR2 having the amino acid sequence shown in SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence shown in SEQ ID NO: 6.   
     
     
         36 . The method of  claim 35 , wherein the concentration of the antibody is about 15 mg/mL to about 30 mg/mL, about 22.5 mg/mL to about 27.5 mg/mL, or about 90 mg/mL to about 160 mg/mL. 
     
     
         37 . A method for treating or inhibiting cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of aqueous formulation comprising:
 about 25 mg/ml of an anti-vascular endothelial growth factor (VEGF) antibody;   about 20 mM histidine or succinate buffer;   about 85 mg/mL sucrose;   about 0.2 mg/ml polysorbate 80;   about 0.05 mg/ml EDTA;   wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8; and   wherein the formulation has pH at about 5.5 or 5.8.