Antibody formulations

Abstract

Formulations of anti-VLA-1 antibodies are described.

1 . A histidine-containing aqueous pharmaceutical composition comprising
 (a) 165 to 190 mg/mL of an anti-VLA-1 antibody having a light chain sequence of SEQ ID NO:1 and a heavy chain sequence of SEQ ID NO:2;   (b) 25 to 35 mM histidine;   (c) 170 to 288 mM sorbitol; and   (d) 0.008 to 0.012% polysorbate 20; and   wherein the histidine-containing aqueous pharmaceutical composition has a pH of 5 to 7.   
     
     
         2 . The histidine-containing aqueous pharmaceutical composition of  claim 1 , wherein the aqueous pharmaceutical composition comprises
 (a) 180 mg/mL of an anti-VLA-1 antibody having a light chain sequence of SEQ ID NO:1 and a heavy chain sequence of SEQ ID NO:2;   (b) 30 mM histidine;   (c) 250 mM sorbitol; and   (d) 0.01% polysorbate 20; and   wherein the histidine-containing aqueous pharmaceutical composition has a pH of 6.0.   
     
     
         3 . An acetate-containing aqueous pharmaceutical composition comprising
 (a) 165 to 200 mg/mL of an anti-VLA-1 antibody having a light chain sequence of SEQ ID NO:1 and a heavy chain sequence of SEQ ID NO:2;   (b) 25 to 35 mM acetate;   (c) 170 to 253 mM sorbitol; and   (d) 0.008 to 0.012% polysorbate 80; and   wherein the acetate-containing aqueous pharmaceutical composition has a pH of 4.5 to 6.5.   
     
     
         4 . The acetate-containing aqueous pharmaceutical composition of  claim 3 , wherein the aqueous pharmaceutical composition comprises
 (a) 190 mg/mL of an anti-VLA-1 antibody having a light chain sequence of SEQ ID NO:1 and a heavy chain sequence of SEQ ID NO:2;   (b) 30 mM acetate;   (c) 220 mM sorbitol; and   (d) 0.01% polysorbate 80; and   wherein the acetate-containing aqueous pharmaceutical composition has a pH of 5.5.   
     
     
         5 . The histidine-containing aqueous pharmaceutical composition of  claim 1 , wherein the histidine-containing aqueous pharmaceutical composition has an osmolality of 270 mOsm/kg to 380 mOsm/kg. 
     
     
         6 . The histidine-containing aqueous pharmaceutical composition of  claim 1 , wherein the histidine-containing aqueous pharmaceutical composition is stable after storage at 2 to 8° C. for 12 months, as indicated by the presence of less than 1500 particles/mL as assessed by the cumulative counts/mL for ≧10 μM particles using a liquid particle counter. 
     
     
         7 . The histidine-containing aqueous pharmaceutical composition of  claim 1 , wherein the histidine-containing aqueous pharmaceutical composition is stable after storage at 2 to 8° C. for 12 months, as indicated by the presence of less than 50 particles/mL as assessed by the cumulative counts/mL for ≧25 μM particles using a liquid particle counter. 
     
     
         8 . The histidine-containing aqueous pharmaceutical composition of  claim 1 , wherein the histidine-containing aqueous pharmaceutical composition is stable after storage at 2 to 8° C. for 12 months, as indicated by less than 3% relative loss of intact IgG as assessed using reduced SDS-PAGE. 
     
     
         9 . The histidine-containing aqueous pharmaceutical composition of  claim 1 , wherein the histidine-containing aqueous pharmaceutical composition is stable after storage at 2 to 8° C. for 12 months, as indicated by less than 5% fragmentation as assessed using size exlusion chromatography. 
     
     
         10 . The histidine-containing aqueous pharmaceutical composition of  claim 1 , wherein the histidine-containing aqueous pharmaceutical composition has a viscosity of less than 15 cP. 
     
     
         11 . A method of treating a patient in need of anti-VLA-1 therapy, comprising administering to the patient an effective amount of the histidine-containing aqueous pharmaceutical composition of  claim 1 . 
     
     
         12 . The method of  claim 11 , wherein the patient has an inflammatory disorder and the method is effective to treat the disorder. 
     
     
         13 . The method of  claim 11 , wherein the patient has a disorder selected from the group consisting of arthritis, inflammatory bowel disease, lupus, transplant rejection, psoriasis, and sarcoidosis, and wherein the method is effective to treat the disorder. 
     
     
         14 . The method of  claim 12 , wherein the patient has rheumatoid arthritis and the method is effective to treat rheumatoid arthritis. 
     
     
         15 . The method of  claim 14 , wherein the rheumatoid arthritis is moderately to severely active rheumatoid arthritis. 
     
     
         16 . The method of  claim 11 , wherein the histidine-containing aqueous pharmaceutical composition is administered subcutaneously. 
     
     
         17 . The method of  claim 11 , wherein the histidine-containing aqueous pharmaceutical composition is administered weekly. 
     
     
         18 . The method of  claim 17 , wherein the histidine-containing aqueous pharmaceutical composition is administered for at least 6 weeks. 
     
     
         19 . The method of  claim 11 , wherein the histidine-containing aqueous pharmaceutical composition is administered at a dose of 0.5 mg/kg to 6 mg/kg. 
     
     
         20 . The method of  claim 19 , wherein the histidine-containing aqueous pharmaceutical composition is administered at a dose of 2.0 mg/kg to 6.0 mg/kg. 
     
     
         21 . The method of  claim 13 , wherein the method reduces a sign or symptom of the disorder, slows progression of structural damage associated with the disorder, or improves physical function. 
     
     
         22 . The method of  claim 14 , wherein the method reduces a sign or symptom of rheumatoid arthritis, slows progression of structural damage associated with rheumatoid arthritis, or improves physical function. 
     
     
         23 . The method of  claim 14 , wherein the patient has had a prior alternate treatment for rheumatoid arthritis. 
     
     
         24 . The method of  claim 23 , wherein the patient has had an inadequate response to the prior alternate treatment. 
     
     
         25 - 26 . (canceled) 
     
     
         27 . The method of  claim 23 , wherein the prior alternate treatment comprises a biologic agent. 
     
     
         28 . The method of  claim 23 , wherein the prior alternate treatment comprises an agent selected from infliximab, adalimumab, certolizumab pegol, golimumab, etanercept abatacept, rituximab, tocilizumab, tofacitinib, methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine. 
     
     
         29 . A method of treating a patient in need of anti-VLA-1 therapy, comprising administering to said patient an effective amount of the acetate-containing aqueous pharmaceutical composition of  claim 3 . 
     
     
         30 . A method of treating an adult patient with moderately to severely active rheumatoid arthritis who has had an inadequate response to a prior alternate treatment with a biologic agent, said method comprising subcutaneously administering once weekly to said patient a histidine-containing aqueous pharmaceutical composition comprising
 (a) 165 to 190 mg/mL of an anti-VLA-1 antibody having a light chain sequence of SEQ ID NO:1 and a heavy chain sequence of SEQ ID NO:2;   (b) 25 to 35 mM histidine;   (c) 170 to 288 mM sorbitol; and   (d) 0.008 to 0.012% polysorbate 20;   wherein said histidine-containing aqueous pharmaceutical composition has a pH of 5 to 7 and wherein said method reduces a sign or symptom of rheumatoid arthritis, slows progression of structural damage associated with rheumatoid arthritis, or improves physical function.   
     
     
         31 . The method of  claim 12 , wherein the patient has inflammatory bowel disease. 
     
     
         32 . The method of  claim 14 , wherein the histidine-containing aqueous pharmaceutical composition is administered subcutaneously.