Pharmaceutical Formulations

Abstract

A stable pharmaceutical formulation is provided that comprises a biologically active protein and an excipient selected from caritine, creatine or creatinine.

What is claimed is: 
     
         1 . A method for reducing the viscosity of a liquid pharmaceutical formulation comprising a therapeutic protein at a concentration of at least 70 mg/ml, comprising the step of combining the therapeutic protein with a viscosity-reducing concentration of an excipient selected from the group consisting of creatine, creatinine, carnitine and mixtures thereof. 
     
     
         2 . The method of  claim 1  wherein viscosity of the formulation is reduced by at least 10%. 
     
     
         3 . The method of  claim 1  wherein viscosity of the formulation is reduced by at least 30%. 
     
     
         4 . A pharmaceutical formulation produced by the method of any of  claims 1 - 3 . 
     
     
         5 . A pharmaceutical composition comprising a therapeutic protein at a concentration of at least 70 mg/mL, and an excipient selected from the group consisting of creatine, creatinine, carnitine and mixtures thereof. 
     
     
         6 . A pharmaceutical composition of  claim 5 , wherein the excipient is creatine, creatinine or a mixture thereof, and the concentration of creatine/creatinine is from about 0.002 mM to about 750 mM. 
     
     
         7 . A pharmaceutical composition of  claim 6 , wherein the concentration of creatine/creatinine is from about 0.01 mM to about 50 mM. 
     
     
         8 . A pharmaceutical composition of  claim 5 , wherein the excipient is camitine at a concentration between about 1 mM and about 3 M. 
     
     
         9 . A pharmaceutical composition of  claim 8 , wherein the carnitine is present at a concentration between about 5 mM and 300 mM. 
     
     
         10 . A pharmaceutical composition of any of  claims 1 - 9  having a pH between about 4.0 to about 6.0. 
     
     
         11 . A pharmaceutical composition of  claim 10  having a pH of about 5.0-5.5. 
     
     
         12 . A method of preparing a lyophilized powder comprising the step of lyophilizing a pharmaceutical formulation of any of  claims 1 - 11 . 
     
     
         13 . A lyophilized powder comprising a therapeutic protein and an excipient selected from the group consisting of creatine, creatinine, carnitine and mixtures thereof, wherein the excipient is present at a weight:weight concentration effective to reduce viscosity upon reconstitution with a diluent. 
     
     
         14 . A lyophilized powder of  claim 13  wherein the excipient is creatine, creatinine or a mixture thereof, present at a concentration of creatine/creatinine between about 4 ng per mg therapeutic protein to about 1.25 mg per mg therapeutic protein. 
     
     
         15 . A lyophilized powder of  claim 13  wherein the excipient is carnitine at a concentration between about 2 μg to about 7 mg per mg therapeutic protein. 
     
     
         16 . A method for reconstituting a lyophilized powder of any of  claims 13 - 15 , comprising the step of adding a sterile aqueous diluent. 
     
     
         17 . The method of any one of  claims 1 - 3 ,  12  or  16  wherein the therapeutic protein is an antibody. 
     
     
         18 . A formulation or composition of any of  claims 4 - 11  wherein the therapeutic protein is an antibody. 
     
     
         19 . A lyophilized powder of any of  claims 13 - 15  wherein the therapeutic protein is an antibody.