Formulation for anti-alpha4beta7 antibody

Abstract

Antibody formulations are described comprising a mixture of an anti-a4b7 antibody, an antioxidant or chelator, and at least one free amino acid. The disclosed formulations may have improved stability, reduced aggregate formation, or both. The present invention further provides a safe dosing regimen of these antibody formulations that is easy to follow, and which results in a therapeutically effective amount of the anti-a4b7 antibody in vivo.

1 . A stable liquid pharmaceutical formulation comprising a mixture of an anti-α4β7 antibody, an antioxidant or chelator, and at least one free amino acid, wherein the formulation is in liquid form. 
     
     
         2 . The stable liquid pharmaceutical formulation of  claim 1 , wherein the molar ratio of the anti-α4β7 antibody to the antioxidant or chelator is about 1:4 to about 1:100. 
     
     
         3 - 4 . (canceled) 
     
     
         5 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said antioxidant or chelator is citrate. 
     
     
         6 . (canceled) 
     
     
         7 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said free amino acid is selected from the group consisting of histidine, alanine, arginine, glycine, glutamic acid and combinations thereof. 
     
     
         8 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said formulation further comprises a surfactant. 
     
     
         9 . The stable liquid pharmaceutical formulation of  claim 8 , wherein the molar ratio of the antioxidant or chelator to the surfactant is about 3:1 to about 156:1. 
     
     
         10 - 14 . (canceled) 
     
     
         15 . A stable liquid pharmaceutical formulation comprising at least about 60 mg/ml to about 160 mg/ml anti-α4β7 antibody, a buffering agent and at least about 5 mM citrate, wherein said formulation is a liquid formulation. 
     
     
         16 - 18 . (canceled) 
     
     
         19 . A stable liquid pharmaceutical formulation comprising a mixture of an anti-α4β7 antibody, citrate, histidine, arginine, and polysorbate 80, wherein the formulation is in liquid form. 
     
     
         20 . The stable liquid pharmaceutical formulation of  claim 19 , wherein said formulation is present in a container selected from the group consisting of a vial, cartridge, syringe and autoinjector. 
     
     
         21 . (canceled) 
     
     
         22 . The stable liquid pharmaceutical formulation of  claim 1 , wherein said antibody is vedolizumab. 
     
     
         23 . (canceled) 
     
     
         24 . A method of treating inflammatory bowel disease, comprising administering to a patient in need thereof the pharmaceutical formulation of  claim 1 . 
     
     
         25 . The method of  claim 24 , wherein said administering is subcutaneous or intramuscular administering. 
     
     
         26 . The method of  claim 24 , wherein said administering is self-administering. 
     
     
         27 .- 28 . (canceled) 
     
     
         29 . A method for treating a human patient suffering from inflammatory bowel disease, wherein the method comprises the step of:
 administering to a patient suffering from inflammatory bowel disease, a humanized immunoglobulin or antigen-binding fragment thereof having binding specificity for human α4β7 integrin,   wherein the humanized immunoglobulin or antigen-binding fragment thereof is administered to the patient according to the following dosing regimen:   (a) initial doses of 165 mg of the humanized immunoglobulin or antigen-binding fragment thereof as a subcutaneous injection every other day for six doses;   (b) followed by a seventh and subsequent doses of 165 mg of the humanized immunoglobulin or antigen-binding fragment thereof as a subcutaneous injection every two weeks or every four weeks as needed;   wherein the dosing regimen induces a clinical response and clinical remission in the inflammatory bowel disease of the patient;
 further wherein the humanized immunoglobulin or antigen-binding fragment thereof comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin, wherein the humanized immunoglobulin or antigen-binding fragment thereof has binding specificity for the α4β7 complex, wherein the antigen-binding region comprises the CDRs: 
 Light chain: CDR1 SEQ ID NO: 11
 CDR2 SEQ ID NO:12 and 
 CDR3 SEQ ID NO: 13; and 
 
 Heavy chain: CDR1 SEQ ID NO:8
 CDR2 SEQ ID NO:9 and 
 CDR3 SEQ ID NO:10. 
 
   
     
     
         30 . The method of  claim 29 , wherein the patient had a lack of an adequate response with, loss response to, or was intolerant to treatment with at least one of an immunomodulator, a tumor necrosis factor-alpha antagonist or combinations thereof. 
     
     
         31 . The method of  claim 29 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis. 
     
     
         32 .- 33 . (canceled) 
     
     
         34 . The method of  claim 29 , wherein the dosing regimen results in mucosal healing in patients suffering from moderate to severely active ulcerative colitis. 
     
     
         35 . The method of  claim 29 , wherein the dosing regimen results in a reduction, elimination or reduction and elimination of corticosteroids use by the patient. 
     
     
         36 - 63 . (canceled) 
     
     
         64 . The stable liquid pharmaceutical formulation of  claim 19 , wherein the anti-α4β7 antibody is vedolizumab. 
     
     
         65 . The method of  claim 24 , wherein the anti-α4β7 antibody is vedolizumab.