Antibody formulations

Abstract

Formulations of VLA-4 binding antibody are described.

1 . An aqueous pharmaceutical composition comprising natalizumab at a concentration of about 125 mg/mL to about 175 mg/mL, sodium phosphate buffer at about 1 mM to about 100 mM; sodium chloride at about 50 mM to about 200 mM, polysorbate 80 at about 0.01% to 0.12% and having pH 6±1.0. 
     
     
         2 . The composition of  claim 1 , wherein the composition comprises about 150 mg/mL natalizumab. 
     
     
         3 . The composition of  claim 1 , wherein the composition comprises about 10 mM sodium phosphate buffer. 
     
     
         4 . The composition of  claim 1 , wherein the composition comprises about 140 mM sodium chloride. 
     
     
         5 . The composition of  claim 1 , wherein the composition comprises about 0.04% (w/v) polysorbate 80. 
     
     
         6 . The composition of  claim 1 , wherein the composition comprises about 0.02% (w/v) polysorbate 80. 
     
     
         7 . The composition of  claim 1 , wherein the composition is at pH 6.0±0.5. 
     
     
         8 . The composition of  claim 1 , wherein the composition is suitable for subcutaneous administration. 
     
     
         9 . The composition of  claim 1 , wherein the composition is suitable for intramuscular administration. 
     
     
         10 . The composition of  claim 1 , wherein the composition is stable for at least 18 months at a temperature of about 2° C. to about 8° C. 
     
     
         11 . The composition of  claim 1 , wherein the composition is stable for at least 2 days at ambient temperature. 
     
     
         12 . A delivery device designed for or suitable for subcutaneous administration, wherein the delivery device is packaged with or contains a unit dose of the composition of  claim 1 . 
     
     
         13 . The delivery device of  claim 12 , wherein administration of the unit dose to a human delivers between about 1.4 mg/kg and about 3.0 mg/kg natalizumab per kg of body weight to the human. 
     
     
         14 . The delivery device of  claim 13 , wherein the unit dose is about 1 mL. 
     
     
         15 . The delivery device of  claim 13 , wherein the unit dose is about 150 mg. 
     
     
         16 . A method of instructing a patient in need of a VLA-4 binding antibody therapy to treat herself or himself, the method comprising (i) providing the patient with at least one unit dose of the composition of  claim 1 ; and (ii) instructing the patient to self-administer the at least one unit dose subcutaneously. 
     
     
         17 . The method of  claim 16 , wherein the patient has an inflammatory disorder. 
     
     
         18 . The method of  claim 16 , wherein the patient has a disorder selected from the group consisting of multiple sclerosis, asthma, arthritis, diabetes, fibrosis, and inflammatory bowel disease. 
     
     
         19 . A unit dose of the composition of  claim 1 , wherein the unit dose is about 0.25 mL to 1.5 mL 
     
     
         20 . The unit dose of  claim 19 , wherein the unit dose is about 1 mL. 
     
     
         21 . A unit dose of the composition of  claim 1 , wherein administration of the unit dose to a human will deliver between about 1.4 mg and about 3.0 mg natalizumab per kg of body weight to the human. 
     
     
         22 . A method of treating a patient having a VLA-4-mediated condition, the method comprising administering to said patient the composition of  claim 1 . 
     
     
         23 . The method of  claim 22 , wherein the patient has an inflammatory disorder. 
     
     
         24 . The method of  claim 22 , wherein the patient has a disorder selected from the group consisting of multiple sclerosis, asthma, rheumatoid arthritis, diabetes, or Crohn's disease. 
     
     
         25 . The method of  claim 22 , wherein the composition is administered as a regimen. 
     
     
         26 . The method of  claim 22 , further comprising selecting a patient suitable for treatment with the composition. 
     
     
         27 . The method of  claim 26 , wherein the selecting comprises identifying a patient that has multiple sclerosis and has demonstrated an inadequate or undesirable response to a prior treatment for multiple sclerosis that did not include administration of natalizumab. 
     
     
         28 . The method of  claim 22 , further comprising administering to the patient a therapeutic agent selected from the group consisting of a thrombolytic agent, a neuroprotective agent, an anti-inflammatory agent, a steroid, a cytokine, or a growth factor. 
     
     
         29 . A method of evaluating a patient comprising (i) determining if the patient meets a preselected criterion, and (ii) if the patient meets said preselected criterion, approving, providing, prescribing, or administering a composition of  claim 1  to said patient. 
     
     
         30 . The method of  claim 29 , wherein the patient has multiple sclerosis, and the patient has had an inadequate or undesirable response to a prior alternate treatment for multiple sclerosis. 
     
     
         31 . An aqueous pharmaceutical composition comprising about 150 mg/mL natalizumab, about 10 mM sodium phosphate buffer, about 140 mM sodium chloride, and about 0.04% (w/v) polysorbate 80, at about pH 6±0.5. 
     
     
         32 . A method of preparing an aqueous composition comprising about 120 to 175 mg/mL natalizumab and polysorbate in a phosphate buffer comprising:
 (i) expressing the natalizumab in cell culture,   (ii) passing the natalizumab through at least one chromatography purification step,   (iii) passing the antibody through at least two ultrafiltration/diafiltration steps in phosphate buffer,   (iv) passing the natalizumab through at least one ultrafiltration step in phosphate buffer, and   (v) adjusting the concentration of the natalizumab to about 120 mg/mL to 175 mg/mL by adding polysorbate 80 and phosphate buffer.   
     
     
         33 . A method of evaluating the quality of a composition of  claim 1 , comprising evaluating the composition for a solution parameter, determining whether the solution parameter meets at least one preselected criterion, and if the solution parameter meets the preselected criterion, then determining that the quality of the composition is suitable for use. 
     
     
         34 . The method of  claim 33 , wherein the solution parameter is color, clarity or viscosity.