Excipient compounds for protein processing

Abstract

Disclosed herein are methods for improving a parameter of a protein-related process comprising providing a viscosity-reducing excipient compound selected from the group consisting of hindered amines, anionic aromatics, functionalized amino acids, oligopeptides, short-chain organic acids, and low molecular weight aliphatic polyacids, and adding a viscosity-reducing amount of the viscosity-reducing excipient compound to a carrier solution for the protein-related process, wherein the carrier solution contains a protein of interest, and carrier solutions comprising a liquid medium in which is dissolved a protein of interest, and a viscosity-reducing excipient, wherein the viscosity of the carrier solution has a lower viscosity that that of a control solution that is substantially similar to the carrier solution except for the presence of the viscosity-reducing excipient.

1 . A method of improving a parameter of a protein-related process, comprising:
 providing a viscosity-reducing excipient additive comprising at least one excipient compound selected from the group consisting of hindered amines, anionic aromatics, functionalized amino acids, oligopeptides, short-chain organic acids, low molecular weight aliphatic polyacids, and diones and sulfones, and   adding a viscosity-reducing amount of the at least one excipient compound to a carrier solution for the protein-related process, wherein the carrier solution contains a protein of interest,   thereby improving the parameter.   
     
     
         2 . The method of  claim 1 , wherein the parameter is selected from the group consisting of cost of protein production, amount of protein production, rate of protein production, and efficiency of protein production. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the protein-related process is an upstream processing process. 
     
     
         5 . The method of  claim 4 , wherein the carrier solution for the upstream processing process is a cell culture medium. 
     
     
         6 . The method of  claim 5 , wherein the step of adding the excipient additive to the carrier solution comprises a first substep of adding the excipient additive to a supplemental medium to form an excipient-containing supplemental medium, and a second substep of adding the excipient-containing supplemental medium to the cell culture medium. 
     
     
         7 . The method of  claim 1 , wherein the protein-related process is a downstream processing process. 
     
     
         8 . The method of  claim 7 , wherein the downstream processing process is a chromatography process. 
     
     
         9 . The method of  claim 8 , wherein the chromatography process is a Protein-A chromatography process. 
     
     
         10 . The method of  claim 8 , wherein the chromatography process recovers the protein of interest, and wherein the protein of interest is characterized by an improved protein-related parameter selected from the group consisting of improved purity, improved yield, fewer particles, less misfolding, or less aggregation, as compared to a control solution. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the protein-related process is a process selected from the group consisting of filtration, injection, syringing, pumping, mixing, centrifugation, membrane separation, and lyophilization. 
     
     
         13 . The method of  claim 12 , wherein the process requires less force than a control process. 
     
     
         14 . The method of  claim 1 , wherein the protein-related process is selected from the group consisting of a cell culture process, a cell culture harvesting process, a chromatography process, a viral inactivation process, and a filtration process. 
     
     
         15 . The method of  claim 14 , wherein the protein-related process is the viral inactivation process, and the viral inactivation process is conducted at a pH level of about 2.5 to about 5.0. 
     
     
         16 . The method of  claim 15 , wherein the protein-related process is the viral inactivation process, and the viral inactivation process is conducted at a higher pH than the control process. 
     
     
         17 . The method of  claim 14 , wherein the protein-related process is the filtration process. 
     
     
         18 . The method of  claim 17 , wherein the filtration process is a virus removal filtration process or an ultrafiltration/diafiltration process. 
     
     
         19 . The method of  claim 17 , wherein the filtration process is characterized by an improved filtration-related parameter. 
     
     
         20 . The method of  claim 19 , wherein the improved filtration-related parameter is a faster filtration rate than the filtration rate of the control solution, production of a smaller amount of aggregated protein than the amount of aggregated protein produced by a control filtration process, a higher mass transfer efficiency than the mass transfer efficiency of the control filtration process, or a higher concentration or a higher yield of the target protein than a concentration or yield of the target protein produced by the control filtration process. 
     
     
         21 - 23 . (canceled) 
     
     
         24 . The method of  claim 1 , wherein the viscosity-reducing excipient additive comprises two or more excipient compounds. 
     
     
         25 . The method of  claim 1 , wherein the at least one excipient compound is a hindered amine. 
     
     
         26 . The method of  claim 25 , wherein the at least one excipient compound is selected from the group consisting of caffeine, saccharin, acesulfame potassium, aspartame, theophylline, taurine, 1-methyl-2-pyrrolidone, 2-pyrrolidinone, niacinamide, and imidazole. 
     
     
         27 . The method of  claim 26 , wherein the at least one excipient compound is selected from the group consisting of caffeine, taurine, niacinamide, and imidazole. 
     
     
         28 . The method of  claim 1 , wherein the at least one excipient compound is an anionic aromatic excipient. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 1 , wherein the viscosity-reducing amount is between about 1 mg/mL to about 100 mg/mL of the at least one excipient compound. 
     
     
         31 . The method of  claim 1 , wherein the viscosity-reducing amount is between about 1 mM to about 400 mM of the at least one excipient compound. 
     
     
         32 . (canceled) 
     
     
         33 . The method of  claim 1 , wherein the carrier solution comprises an additional agent selected from the group consisting of preservatives, sugars, polysaccharides, arginine, proline, surfactants, stabilizers, and buffers. 
     
     
         34 . The method of  claim 1 , wherein the protein of interest is a therapeutic protein. 
     
     
         35 . The method of  claim 34 , wherein the therapeutic protein is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, an antibody fragment, a fusion protein, a PEGylated protein, an antibody-drug conjugate, a synthetic polypeptide, a protein fragment, a lipoprotein, an enzyme, and a structural peptide. 
     
     
         36 . The method of  claim 34 , wherein the therapeutic protein is a recombinant protein. 
     
     
         37 - 39 . (canceled)