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 liquid pharmaceutical formulation comprising a therapeutic antibody and a viscosity-reducing amount of caffeine, wherein (i) the viscosity of the formulation is at least about 50% less than the viscosity of a control formulation and is less than about 50 cP, (ii) the formulation contains at least about 100 mg/mL of the antibody, and (iii) the viscosity reducing amount of caffeine is about 15 mg/ml or less;
wherein the control formulation does not contain the caffeine but is otherwise identical on a dry weight basis to the liquid pharmaceutical formulation.
2. The formulation of claim 1 , wherein the viscosity of the formulation is at least about 70% less than the viscosity of the control formulation.
3. The formulation of claim 1 , wherein the viscosity of the formulation is at least about 90% less than the viscosity of the control formulation.
4. The formulation of claim 1 , wherein the viscosity is less than about 20 cP.
5. The formulation of claim 1 , wherein the viscosity is less than about 10 cP.
6. The formulation of claim 1 , wherein the formulation contains at least about 200 mg/mL of the antibody.
7. The formulation of claim 1 , wherein the formulation contains at least about 300 mg/mL of the antibody.
8. The formulation of claim 1 , wherein the viscosity reducing amount of caffeine is between about 5 mg/mL to about 15 mg/mL caffeine.
9. The formulation of claim 1 , further comprising an additional agent selected from the group consisting of preservatives, surfactants, sugars, polysaccharides, arginine, proline, hyaluronidase, stabilizers, and buffers.
10. The formulation of claim 1 wherein the formulation is suitable for subcutaneous injection.
11. The formulation of claim 1 wherein the formulation is suitable for intramuscular injection.
12. The formulation of claim 1 wherein the formulation is suitable for intravenous injection.