Stabilizing excipients for therapeutic protein formulations

Abstract

The invention encompasses therapeutic formulations comprising a protein active ingredient and a stabilizing excipient, methods of improving stability in a therapeutic formulation comprising a protein active ingredient by adding a stability-improving amount of a stabilizing excipient to the therapeutic formulation, and methods of reducing adverse infusion-related effects in a patient, comprising administering to a patient in need thereof a therapeutic formulation comprising a protein active ingredient and a stabilizing excipient.

1 . A therapeutic formulation comprising a protein active ingredient and a stabilizing excipient. 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The formulation of  claim 1 , wherein the formulation contains at least about 1 mg/mL of protein active ingredient. 
     
     
         5 . (canceled) 
     
     
         6 . The formulation of  claim 4 , wherein the formulation contains at least 100 mg/mL of protein active ingredient. 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The formulation of  claim 1 , wherein the protein active ingredient is selected from the group consisting of an antibody, an antibody-drug conjugate, an enzyme, a cytokine, a neurotoxin, a fusion protein, an immunogenic protein, a PEGylated protein, and an antibody fragment. 
     
     
         10 . The formulation of  claim 1 , wherein the formulation contains at least about 1 to about 5000 ppm of the stabilizing excipient. 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . The formulation of  claim 1 , wherein the stabilizing excipient excludes polypropylene block copolymers. 
     
     
         14 . The formulation of  claim 1 , wherein the stabilizing excipient is selected from the group consisting of polypropylene glycol, adducts of polypropylene glycol, and random copolymers comprising propylene oxide units. 
     
     
         15 . The formulation of  claim 14 , wherein the stabilizing excipient is a polypropylene glycol homopolymer. 
     
     
         16 . The formulation of  claim 15 , wherein the polypropylene glycol homopolymer has a number-average molecular weight between about 300 and 5000 Daltons. 
     
     
         17 . The formulation of  claim 16 , wherein the polypropylene glycol homopolymer has a number-average molecular weight of about 425 Daltons. 
     
     
         18 . The formulation of  claim 16 , wherein the polypropylene glycol homopolymer has a number-average molecular weight of about 1000 Daltons. 
     
     
         19 . (canceled) 
     
     
         20 . The formulation of  claim 15 , wherein the polypropylene glycol homopolymer is a linear polymer with at least two hydroxyl groups. 
     
     
         21 . The formulation of  claim 20 , wherein the linear polymer contains two or three hydroxyl groups. 
     
     
         22 . The formulation of  claim 14 , wherein the polypropylene glycol is a branched polymer. 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . The formulation of  claim 14 , wherein the stabilizing excipient is an adduct of polypropylene glycol. 
     
     
         26 . (canceled) 
     
     
         27 . The formulation of  claim 1 , wherein the stabilizing excipient is a hydrophobically modified cellulosic polymer. 
     
     
         28 . The formulation of  claim 27 , wherein the hydrophobically modified cellulosic polymer is selected from the group consisting of a methylcellulose, a hydroxypropyl methylcellulose, a hydroxypropyl cellulose, and a hydroxyethyl cellulose. 
     
     
         29 . The formulation of  claim 28 , wherein the hydrophobically modified cellulosic polymer is not a sodium carboxymethyl cellulose. 
     
     
         30 - 41 . (canceled) 
     
     
         42 . The formulation of  claim 1 , wherein the formulation further comprises a second stabilizing excipient. 
     
     
         43 . The formulation of  claim 1 , wherein the formulation excludes conventional surfactants. 
     
     
         44 - 49 . (canceled) 
     
     
         50 . A method of improving stability in a therapeutic formulation comprising a protein active ingredient by adding a stability-improving amount of a stabilizing excipient to the therapeutic formulation. 
     
     
         51 - 54 . (canceled) 
     
     
         55 . A method of reducing adverse infusion-related effects in a patient, comprising administering to a patient in need thereof a therapeutic formulation comprising a protein active ingredient and a stabilizing excipient, wherein infusing the therapeutic formulation into the patient results in fewer adverse infusion-related effects than infusing a control formulation into the patient, wherein the control formulation lacks the stabilizing excipient. 
     
     
         56 . (canceled)