Viscosity-reducing excipient compounds for protein formulations
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. A method of reducing a viscosity of a liquid protein formulation, comprising:
preparing the liquid protein formulation comprising a therapeutic protein and a viscosity-reducing amount of caffeine, wherein (i) the liquid protein formulation contains at least about 100 mg/mL of the therapeutic protein, and (ii) the viscosity-reducing amount of caffeine is about 30 mg/ml or less,
wherein the viscosity of the liquid protein formulation is at least about 50% less than a viscosity of a control formulation, and wherein the control formulation does not contain caffeine but is otherwise identical on a dry weight basis to the liquid protein formulation.
2. The method of claim 1 , wherein the viscosity-reducing amount of caffeine is about 22 mg/ml or less.
3. The method of claim 1 , wherein the viscosity-reducing amount of caffeine is about 15 mg/ml or less.
4. The method of claim 1 , wherein the liquid protein formulation contains at least about 200 mg/ml of the therapeutic protein.
5. The method of claim 1 , wherein the liquid protein formulation contains at least about 300 mg/ml of the therapeutic protein.
6. The method of claim 1 , wherein the therapeutic protein is a therapeutic antibody.
7. The method of claim 6 , wherein the liquid protein formulation contains at least about 200 mg/ml of the therapeutic antibody.
8. The method of claim 7 , wherein the liquid protein formulation contains at least about 300 mg/ml of the therapeutic antibody.
9. The method of claim 1 , wherein the viscosity of the liquid protein formulation is at least about 70% less than the viscosity of the control formulation.
10. The method of claim 1 , wherein the viscosity of the liquid protein formulation is at least about 90% less than the viscosity of the control formulation.
11. The method of claim 1 , wherein the viscosity of the liquid protein formulation is less than about 20 cP.
12. The method of claim 11 , wherein the viscosity of the liquid protein formulation is less than about 10 cP.
13. The method of claim 1 , wherein the liquid protein formulation comprises a second viscosity-reducing excipient.
14. The method of claim 13 , wherein the second viscosity-reducing excipient is selected from the group consisting of theophylline, tyramine, procaine, lidocaine, imidazole, aspartame, saccharin, acesulfame potassium, niacinamide, and isonicotinamide.
15. The method of claim 1 , wherein the liquid protein formulation is an injectable formulation.
16. The method of claim 1 , wherein the liquid protein formulation is an aqueous formulation.
17. The method of claim 1 , wherein the viscosity-reducing amount of caffeine is about 5 mg/ml to about 15 mg/ml.