Concentrated protein formulations and uses thereof
Described are low viscosity, hypotonic formulations containing one or more proteins, e.g., antibodies, at high concentration, uses of the formulations, and articles of manufacture. In particular, the formulations are useful and beneficial for the subcutaneous administration or delivery of a high concentration of a protein drug, such as an antibody, to a subject who is afflicted with a disease or condition that is treatable by the protein drug.
1. A formulation comprising a concentrated protein consisting of PRO 140 or antigen binding fragment thereof in an amount greater than about 100 mg/mL and less than about 200 mg/mL, a tonicifier of a sodium salt and a histidine and glycine buffer consisting of a combined total amount of less than 110 mM, wherein the formulation has a total salt concentration of less than about 100 mM, a buffer in a concentration of about 10 mM to 25 mM, and an osmolality of less than about 290 mOs/kg.
2. The formulation of claim 1 , wherein the formulation is stable at a temperature of about 2° C. to about 8° C. for at least two months.
3. The formulation of claim 2 , wherein the formulation is substantially free of at least one of aggregates and degradation products.
4. The formulation of claim 2 , wherein at least one of about 90% of the concentrated PRO 140 or antigen binding fragment thereof activity is maintained at or about 90% of the concentrated PRO 140 or antigen binding fragment thereof is intact.
5. The formulation of claim 1 , wherein the concentrated PRO 140 or antigen binding fragment thereof is present in an amount of about 120 mg/mL to about 185 mg/mL.
6. The formulation of claim 1 , wherein the concentrated PRO 140 or antigen binding fragment thereof is an antibody, or a fragment of the antibody.
7. The formulation of claim 1 , wherein the concentrated PRO 140 or fragment thereof is directed against CCR5 chemokine receptor.
8. The formulation of claim 1 , wherein the salt comprises sodium acetate, sodium chloride, sodium gluconate, sodium lactate, sodium thiocyanate, or any combination thereof.
9. The formulation of claim 1 , wherein the buffer comprises a nonpolar neutral amino acid.
10. The formulation of claim 1 , wherein the formulation is at least one of ultrafiltrated and diafiltrated.
11. The formulation of claim 1 , further comprising a surfactant present in an amount of about 0.001% w/v to about 0.2% w/v.
12. The formulation of claim 1 , further comprising a stabilizing agent or a non-salt tonicifier.
13. The formulation of claim 1 , wherein the formulation has a viscosity less than or equal to about 40 cps.
14. The formulation of claim 1 , wherein the formulation has a density of between about 1.04 g/mL to about 1.07 g/mL.
15. The formulation of claim 1 , wherein the formulation is in a liquid form that is manipulable through a 25 g syringe needle or a 27 g syringe needle.
16. The formulation of claim 1 , wherein the formulation has a pH of from about 5.4 to about 6.4.
17. The formulation of claim 1 , wherein the concentrated PRO 140 or antigen binding fragment thereof is formulated for administration via a syringe needle, a pen, a pump, a cartridge, a two-chambered cartridge, a multishot needle syringe, a multidose needle syringe, a multidose pen, a jet injector, a syrette, an autoinjector, or a pre-filled syringe needle.
18. A formulation comprising:
a concentrated protein consisting of PRO 140 or antigen binding fragment thereof in an amount greater than about 100 mg/mL and less than about 200 mg/mL;
a sodium salt in an amount less than about 100 mM;
a histidine and glycine buffer in an amount greater than about 10 mM and less than about 25 mM;
a tonicifier of a sodium salt and a buffer consisting of a combined total amount of less than 110 mM; and
wherein the formulation has a total salt concentration of less than about 100 mM and a viscosity less than or equal to about 40 cps.
19. An article of manufacture comprising a container and a stable concentrated protein consisting of PRO 140 or antigen binding fragment thereof formulation having a concentration of greater than 100 mg/mL and less than 200 mg/mL, and a tonicifier of a sodium salt and a histidine and glycine buffer consisting of a combined total amount of less than 110 mM, a buffer in a concentration of about 10 mM to 25 mM, and a total salt concentration of less than about 100 mM.