EXCIPIENT COMPOUNDS FOR BIOPOLYMER FORMULATIONS
Disclosed herein are reduced viscosity liquid formulations comprising a protein and an excipient compounds. Further disclosed are methods of reducing the viscosity of a liquid formulation comprising a protein, methods of treatment, and methods of improving protein processing.
1 . A liquid formulation comprising a protein and an excipient compound wherein the excipient compound is a pyrimidine, and wherein the excipient compound is added in a viscosity-reducing amount.
2 . The liquid formulation of claim 1 , wherein the pyrimidine is a methyl-substituted pyrimidine.
3 . The liquid formulation of claim 1 , wherein the pyrimidine is selected from the group consisting of pyrimidine, pyrimidinone, triaminopyrimidine, 1,3-dimethyluracil, 1-methyluracil, 3-methyluracil, 1,3-diethyluracil, 5-methyluracil, 6-methyluracil, uracil, 1,3-dimethyl-tetrahydro pyrimidinone, thymine, 1-methylthymine, O-4-methylthymine, 1,3-dimethylthymine, dimethylthymine dimer, theacrine, cytosine, 5-methylcytosine, and 3-methylcytosine.
4 . The liquid formulation of claim 3 , wherein the pyrimidine is 1,3-dimethyluracil.
5 . The liquid formulation of claim 1 , wherein the formulation is a pharmaceutical composition and wherein the protein is a therapeutic protein and wherein the excipient compound is a pharmaceutically acceptable excipient compound.
6 . (canceled)
7 . The liquid formulation of claim 5 , wherein the therapeutic protein is a PEGylated protein.
8 . The liquid formulation of claim 5 , wherein the therapeutic protein is a therapeutic antibody.
9 . The liquid formulation of claim 8 , wherein the therapeutic antibody is selected from the group consisting of bevacizumab, trastuzumab, adalimumab, infliximab, etanercept, cetuximab, rituximab, ipilimumab, and omalizumab.
10 . The liquid formulation of claim 1 , wherein the viscosity-reducing amount of the excipient compound is about 250 mg/mL or less.
11 . The liquid formulation of claim 1 , wherein the viscosity-reducing amount of the excipient compound is between about 10 mg/mL and about 200 mg/mL.
12 . The liquid formulation of claim 11 , wherein the viscosity-reducing amount of the excipient compound is between about 10 mg/mL and about 120 mg/mL.
13 . The liquid formulation of claim 12 , wherein the viscosity-reducing amount of the excipient compound is between about 20 mg/mL and about 120 mg/mL.
14 . The liquid formulation of claim 1 , wherein the viscosity-reducing amount of the excipient compound is between about 1 mg/mL and about 100 mg/mL.
15 . The liquid formulation of claim 14 , wherein the viscosity-reducing amount of the excipient compound is between about 2 mg/mL and about 80 mg/mL.
16 . The liquid formulation of claim 15 , wherein the viscosity-reducing amount of the excipient compound is between about 5 mg/mL and about 50 mg/mL.
17 . (canceled)
18 . The liquid formulation of claim 1 , wherein the viscosity-reducing amount of the excipient compound is between about 1 mM and about 400 mM.
19 . The liquid formulation of claim 18 , wherein the viscosity-reducing amount of the excipient compound is between about 2 mM and about 150 mM.
20 . The liquid formulation of claim 19 , wherein the viscosity-reducing amount of the excipient compound is between about 5 mM and about 100 mM.
21 . The liquid formulation of claim 20 , wherein the viscosity-reducing amount of the excipient compound is between about 10 mM and about 75 mM.
22 . The liquid formulation of claim 21 , wherein the viscosity-reducing amount of the excipient compound is between about 15 mM and about 50 mM.
23 . The liquid formulation of claim 1 , wherein the viscosity-reducing amount reduces the viscosity of the formulation to a viscosity less than the viscosity of a control formulation, wherein the control formulation does not contain the excipient compound but is otherwise identical on a dry weight basis to the therapeutic formulation.
24 . The liquid formulation of claim 23 , wherein the viscosity of the liquid formulation is at least about 10% less than the viscosity of the control formulation.
25 . The liquid formulation of claim 24 , wherein the viscosity of the liquid formulation is at least about 30% less than the viscosity of the control formulation.
26 - 28 . (canceled)
29 . The liquid formulation of claim 23 , wherein the viscosity of the liquid formulation is less than about 100 cP.
30 - 32 . (canceled)
33 . The formulation of claim 1 , further comprising an additional agent selected from the group consisting of preservatives, surfactants, sugars, polysaccharides, arginine, proline, hyaluronidase, stabilizers, solubilizers, co-solvents, hydrotropes, and buffers.
34 . A liquid formulation comprising a protein and an excipient compound selected from the group consisting of 3-aminopyridine, dicyclomine, 1-methyl-2-pyrrolidone, phenylserine, DL-3-phenylserine, and cycloserine, wherein the excipient compound is added in a viscosity-reducing amount.
35 . (canceled)
36 . (canceled)