Viscosity-reducing excipient compounds for protein formulations

Abstract

The invention encompasses formulations and methods for the production thereof that permit the delivery of concentrated protein solutions. The inventive methods can yield a lower viscosity liquid formulation or a higher concentration of therapeutic or nontherapeutic proteins in the liquid formulation, as compared to traditional protein solutions.

1 .- 58 . (canceled) 
     
     
         59 . A liquid pharmaceutical formulation comprising a therapeutic antibody and a viscosity reducing amount of caffeine, wherein:
 (i) viscosity of the liquid pharmaceutical formulation is at least about 10% less than viscosity of a control formulation and is less than about 90 cP,   (ii) the liquid pharmaceutical formulation comprising at least about 100 mg/mL of the therapeutic antibody, and   (iii) the viscosity reducing amount of caffeine is about 22 mg/ml or less,   wherein the control formulation does not contain the viscosity reducing amount of caffeine.   
     
     
         60 . The liquid pharmaceutical formulation of  claim 59 , wherein the viscosity of the liquid pharmaceutical formulation is reduced at least about 20% as compared to the control formulation. 
     
     
         61 . The liquid pharmaceutical formulation of  claim 59 , wherein the viscosity of the liquid pharmaceutical formulation is reduced at least about 30% as compared to the control formulation. 
     
     
         62 . The liquid pharmaceutical formulation of  claim 59 , wherein the viscosity of the liquid pharmaceutical formulation is less than about 70 cP. 
     
     
         63 . The liquid pharmaceutical formulation of  claim 59 , wherein the viscosity of the liquid pharmaceutical formulation is less than about 20 cP. 
     
     
         64 . The liquid pharmaceutical formulation of  claim 59 , wherein the viscosity of the liquid pharmaceutical formulation is less than about 10 cP. 
     
     
         65 . The liquid pharmaceutical formulation of  claim 59 , wherein the viscosity reducing amount of caffeine is about 20 mg/ml or less. 
     
     
         66 . The liquid pharmaceutical formulation of  claim 59 , wherein the viscosity reducing amount of caffeine is about 10 mg/ml or less. 
     
     
         67 . The liquid pharmaceutical formulation of  claim 59 , wherein the liquid pharmaceutical formulation comprises at least about 200 mg/ml of the therapeutic antibody. 
     
     
         68 . The liquid pharmaceutical formulation of  claim 59 , wherein the liquid pharmaceutical formulation further comprises arginine. 
     
     
         69 . The liquid pharmaceutical formulation of  claim 68 , wherein an amount of arginine is at least about 25 mg/ml or less. 
     
     
         70 . A liquid pharmaceutical formulation comprising a therapeutic antibody and a viscosity reducing amount of caffeine, wherein:
 (i) viscosity of the liquid pharmaceutical formulation is at least about 50% less than viscosity of a control formulation and is less than about 90 cP,
 (ii) the liquid pharmaceutical formulation comprising at least about 100 mg/mL of the therapeutic antibody, and 
   (iii) the viscosity reducing amount of caffeine is about 22 mg/ml or less;   wherein the control formulation does not contain caffeine.   
     
     
         71 . The liquid pharmaceutical formulation of  claim 70 , where the viscosity of the liquid pharmaceutical formulation is at least about 70% less than viscosity of the control formulation. 
     
     
         72 . The liquid pharmaceutical formulation of  claim 70 , wherein the viscosity of the liquid pharmaceutical formulation is less than about 70 cP. 
     
     
         73 . The liquid pharmaceutical formulation of  claim 70 , wherein the liquid pharmaceutical formulation comprises at least about 200 mg/ml of the therapeutic antibody. 
     
     
         74 . The liquid pharmaceutical formulation of  claim 70 , wherein the viscosity reducing amount of caffeine is about 20 mg/ml or less. 
     
     
         75 . The liquid pharmaceutical formulation of  claim 70 , wherein the viscosity reducing amount of caffeine is about 15 mg/ml or less. 
     
     
         76 . The liquid pharmaceutical formulation of  claim 70 , wherein the viscosity reducing amount of caffeine is about 10 mg/ml or less. 
     
     
         77 . The liquid pharmaceutical formulation of  claim 70 , wherein the liquid pharmaceutical formulation further comprises arginine. 
     
     
         78 . The liquid pharmaceutical formulation of  claim 77 , wherein an amount of arginine is at least about 25 mg/ml or less.