Compositions comprising PCSK9-binding molecules and methods of use
The present disclosure provides pharmaceutical compositions comprising fibronectin based scaffold domain proteins that bind, for example, proprotein convertase subtilisin kexin-9 (PCSK9).
1. A composition comprising one or more unit doses of a PCSK9-binding fusion protein having the amino acid sequence of SEQ ID NO:3, the unit dose containing from 250 mg to 350 mg of the PCSK9-binding fusion protein formulated at a concentration of at least 200 mg/mL; and a pharmaceutically-acceptable carrier.
2. The composition of claim 1 , wherein the unit dose has a concentration of at least 250 mg/mL of the PCSK9-binding fusion protein.
3. The composition of claim 1 , wherein the unit dose has a concentration of at least 300 mg/mL of the PCSK9-binding fusion protein.
4. The composition of claim 1 , wherein the pharmaceutically-acceptable carrier comprises a buffering agent, an isotonicity agent, a solvent, and optionally a surfactant.
5. The composition of claim 4 , wherein the buffering agent comprises one or more of an amino acid buffer, citrate buffer, a phosphate buffer, an acetate buffer, succinate buffer, and a bicarbonate buffer.
6. The composition of claim 5 , wherein the buffering agent comprises L-Histidine/L-Histidine monohydrochloride.
7. The composition of claim 5 , wherein the isotonicity agent comprises one or more of sodium chloride, dextrose, sucrose, glycerin, mannitol, sorbitol, arginine, and potassium chloride.
8. The composition of claim 7 , wherein the isotonicity agent comprises sodium chloride.
9. The composition of claim 4 , wherein the pharmaceutically-acceptable carrier comprises polysorbate-80.
10. The composition of claim 4 , wherein the composition does not comprise a surfactant.
11. The composition of claim 4 , wherein the solvent is water.
12. An injection pen comprising the composition of claim 1 .
13. The injection pen of claim 12 , wherein the injection pen contains from 1 to 10 unit doses.
14. The injection pen of claim 13 , wherein the unit doses are no more than 1.5 mL in volume.
15. The injection pen of claim 14 , wherein the unit doses are no more than 1 mL in volume.
16. A method for treating a PCSK9-related disorder, comprising:
administering to a subject in need, a unit dose of a PCSK9-binding fusion protein having the amino acid sequence of SEQ ID NO:3, the unit dose containing from 250 mg to 350 mg of the PCSK9-binding fusion protein formulated at a concentration of at least 200 mg/mL in a pharmaceutically-acceptable carrier; wherein the unit dose is administered subcutaneously every 4 weeks.
17. The method of claim 16 , wherein the unit dose has a concentration of at least 250 mg/mL of the PCSK9-binding fusion protein.
18. The method of claim 16 , wherein the pharmaceutically-acceptable carrier comprises a buffering agent, an isotonicity agent, a solvent, and optionally a surfactant.
19. The method of claim 18 , wherein the buffering agent comprises one or more of an amino acid buffer, citrate buffer, a phosphate buffer, an acetate buffer, succinate buffer, and a bicarbonate buffer.
20. The method of claim 19 , wherein the buffering agent comprises L-Histidine/L-Histidine monohydrochloride.
21. The method of claim 18 , wherein the isotonicity agent comprises one or more of sodium chloride, dextrose, sucrose, glycerin, mannitol, sorbitol, arginine, and potassium chloride.
22. The method of claim 18 , wherein the pharmaceutically-acceptable carrier comprises polysorbate-80.
23. The method of claim 18 , wherein the solvent is water.
24. The method of claim 16 , wherein the unit dose is no more than 1.5 mL in volume.
25. The method of claim 16 , wherein the subject is a human, having a condition selected from a lipid disorder, hypercholesterolemia, dyslipidemia, coronary heart disease, atherosclerosis, high blood pressure, Type 2 diabetes mellitus, and cholestatic liver disease.
26. The method of claim 25 , wherein the subject has hypercholesterolemia.
27. The method of claim 26 , wherein the subject has familial hypercholesterolemia.
28. The method of claim 16 , wherein the subject has atherosclerotic cardiovascular disease (ASCVD) or is at high risk of ASCVD.
29. The method of claim 16 , wherein the subject is not undergoing therapy with a statin, or is not undergoing therapy with a lipid-lowering oral therapy.
30. The method of claim 16 , wherein the subject is undergoing therapy with a statin, or another lipid-lowering oral therapy.