Protein Formulations Containing Amino Acids

Abstract

Provided are stable protein formulations that contain at least one amino acid. In certain embodiments, amino acid combinations either at least two, or three, or four, or more amino acids are included. By virtue of inclusion of the amino acids, the formulation has low viscosity and a protein in the formulations is physically, chemically, and biological stable even at high concentrations. In further embodiments, by virtue of inclusion of the amino acids, a protein in the formulations is physically, chemically, and biological stable even at high concentrations.

1 . A stable pharmaceutical formation comprising one or more amino acids to stabilize a protein in the pharmaceutical formulation and one or more amino acids to reduce the viscosity of the pharmaceutical formulation. 
     
     
         2 . The formulation of  claim 1 , wherein a first amino acid stabilizes the protein and a second different amino acid reduces the viscosity of the protein solution. 
     
     
         3 . The formulation of  claim 1 , wherein the same amino acid stabilizes the protein and reduces the viscosity of the protein solution. 
     
     
         4 . The formulation of  claim 1 , wherein the pharmaceutical formulation comprises two or more different amino acids to stabilize protein. 
     
     
         5 . The formulation of  claim 1 , wherein the pharmaceutical formulation comprises two or more different amino acids to reduce the viscosity of the pharmaceutical formulation. 
     
     
         6 . The formulation of  claim 1 , wherein the pharmaceutical formulation comprises two or more different amino acids to stabilize a protein in the pharmaceutical formulation and two or more different amino acids to reduce the viscosity of the pharmaceutical formulation, wherein the two or more different amino acids to stabilize a protein in the pharmaceutical formulation are the same as the two or more different amino acids to reduce the viscosity of the pharmaceutical formulation. 
     
     
         7 . The formulation of  claim 1 , wherein the pharmaceutical formulation comprises two or more different amino acids to stabilize a protein in the pharmaceutical formulation and two or more different amino acids to reduce the viscosity of the pharmaceutical formulation, wherein the two or more different amino acids to stabilize a protein in the pharmaceutical formulation are not the same as the two or more different amino acids to reduce the viscosity of the pharmaceutical formulation. 
     
     
         8 . The formulation of  claim 1 , wherein, the amino acid to stabilize the protein is selected from G, S, T, A, R, M, K, P and N. 
     
     
         9 . The formulation of  claim 1 , wherein the amino acid to reduce the viscosity of the formulation is Proline or Glycine. 
     
     
         10 . The formulation of  claim 9 , wherein the Proline is L-Proline. 
     
     
         11 . The formulation of  claim 1 , wherein at least one of the amino acids contains a positively charged side chain. 
     
     
         12 . The formulation of  claim 1 , wherein at least one of the amino acids contains a negatively charged side chain. 
     
     
         13 . The formulation of  claim 1 , wherein at least one of the amino acids contains a hydrophobic side chain. 
     
     
         14 . The formulation of  claim 1 , wherein at least one of the amino acids contains a polar uncharged side chain. 
     
     
         15 . The formulation of  claim 2 , wherein one of the two different amino acids contains a polar uncharged side chain and the one of the two different amino acids contains a hydrophobic side chain. 
     
     
         16 . The formulation of  claim 2 , wherein one of the two different amino acids contains a polar uncharged side chain and the other is selected from the group consisting of G and P. 
     
     
         17 . The formulation of  claim 1 , wherein the one or more amino acids is selected from the group consisting of I, M, P, S, R, K, E, and N, and wherein each is present at a concentration of greater than about 0.1 mg/mL. 
     
     
         18 . The formulation of  claim 1 , wherein the one or more amino acids is selected from the group consisting of S, T, N, G, A, K, F, V, L, H, I, and P, and wherein each is present at a concentration of greater than about 0.1 mg/mL. 
     
     
         19 . The formulation of  claim 1 , wherein the protein is selected from the group consisting of an enzyme, a cytokine, a neurotropic factor, an antibody, a peptide, a hormone, a DNA-binding protein, vaccine, toxin or an aptamer. 
     
     
         20 . The formulation of  claim 19 , wherein the protein is an antibody.