Formulation for anti-alpha4beta7 antibody

Abstract

Antibody formulations are described comprising a mixture of a non-reducing sugar, an anti-α4β7 antibody and at least one amino acid. The disclosed formulations have improved stability, reduced aggregate formation, and may retard degradation of the anti-α4β7 antibody therein or exhibit any combinations thereof The prese invention further provides a safe dosing r men of these antibody formulations that is easy to follow, and which results in a therapeutically effective amount of the anti-α4β7 antibody in vivo.

1 . A stable formulation comprising a mixture of a non-reducing sugar, an anti-α4β7 antibody and at least one free amino acid, wherein the formulation is in solid form, and the molar ratio of non-reducing sugar to anti-α4β7 antibody (mole:mole) is greater than 600:1. 
     
     
         2 . The formulation of  claim 1 , wherein said formulation further comprises a buffering agent. 
     
     
         3 . The formulation of  claim 1 , wherein said non-reducing sugar is selected from the group consisting of mannitol, sorbitol, sucrose, trehalose and combinations thereof. 
     
     
         4 . The 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. 
     
     
         5 .The formulation of  claim 1 , wherein said formulation further comprises a surfactant. 
     
     
         6 . (canceled) 
     
     
         7 . The formulation of  claim 1 , wherein said formulation is lyophilized and comprises at least about 5% to about 10% anti-α4β7 antibody before lyophilization. 
     
     
         8 .- 28 . (canceled) 
     
     
         29 . A stable formulation comprising a mixture of a non-reducing sugar, an anti-α4β7 antibody, histidine, arginine, and polysorbate 80, wherein the formulation is in solid form, and the molar ratio of non-reducing sugar to anti-α4β7 antibody (mole:mole) is greater than 600:1. 
     
     
         30 .- 31 . (canceled) 
     
     
         32 . The formulation of  claim 1 , wherein said antibody is vedolizumab. 
     
     
         33 . A method of making the formulation of any one of  claim 1 , said method comprising maintaining the product temperature below the collapse temperature during primary drying. 
     
     
         34 . The method of  claim 33 , further comprising an annealing step. 
     
     
         35 . The method of  claim 33 , further comprising determining the quality of the dried formulation, comprising inspecting the formulation for appearance; determining reconstitution time; determining moisture content; determining percentage of aggregates present; determining percentage of fragments present; and determining oxidation/deamidation levels. 
     
     
         36 .- 66 . (canceled) 
     
     
         67 . The formulation of  claim 1 , wherein the free amino acid to antibody molar ratio is at least 250:1. 
     
     
         68 . (canceled)