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 at least one unit dose of a PCSK9-binding fusion protein having the amino acid sequence of SEQ ID NO:3, the unit dose containing from about 250 mg to about 350 mg of the PCSK9-binding fusion protein formulated at a concentration of at least 200 mg/mL, and a pharmaceutically-acceptable carrier comprising from about 1 mg/mL to about 10 mg/mL L-Histidine/L-Histidine monohydrochloride maintaining a pH of about 6.8, and from about 6 mg/mL to about 12 mg/mL sodium chloride.
2. The composition of claim 1 , wherein the unit dose has a concentration of at least about 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 about 300 mg/mL of the PCSK9-binding fusion protein.
4. The composition of claim 1 , wherein the pharmaceutically-acceptable carrier comprises polysorbate-80.
5. The composition of claim 1 , wherein the composition does not comprise a surfactant.
6. The composition of claim 1 , wherein the pharmaceutically-acceptable carrier comprises water.
7. The composition of claim 1 , wherein the composition is an injection pen, syringe, or autoinjector comprising the at least one unit dose.
8. The composition of claim 7 , wherein the injection pen, syringe, or autoinjector contains from 1 to 10 unit doses.
9. The composition of claim 8 , wherein the unit doses are no more than about 1.5 mL in volume.
10. The composition of claim 9 , wherein the unit doses are no more than about 1 mL in volume.
11. 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 about 250 mg to about 350 mg of the PCSK9-binding fusion protein formulated at a concentration of at least 200 mg/mL in a pharmaceutically-acceptable carrier comprising from about 1 mg/mL to about 10 mg/mL L-Histidine/L-Histidine monohydrochloride maintaining a pH of about 6.8, and from about 6 mg/mL to about 12 mg/mL sodium chloride; wherein a unit dose is administered subcutaneously about every 4 weeks.
12. The method of claim 11 , wherein the unit dose has a concentration of at least about 250 mg/mL of the PCSK9-binding fusion protein.
13. The composition of claim 1 , wherein the pharmaceutically-acceptable carrier consists of about 1 mg/mL to about 10 mg/mL L-Histidine/L-Histidine monohydrochloride maintaining a pH of about 6.8, about 2 mg/mL to about 20 mg/mL sodium chloride, about 0.01 mg/mL to about 0.5 mg/mL polysorbate-80, and water.
14. The method of claim 11 , wherein the pharmaceutically-acceptable carrier consists of about 1 mg/mL to about 10 mg/mL L-Histidine/L-Histidine monohydrochloride maintaining a pH of about 6.8, about 2 mg/mL to about 20 mg/mL sodium chloride, about 0.01 mg/mL to about 0.5 mg/mL polysorbate-80, and water.
15. The method of claim 11 , wherein the PCSK9-related disorder is hypercholesterolemia.
16. The method of claim 15 , wherein the hypercholesterolemia is familial hypercholesterolemia.
17. The method of claim 11 , wherein the PCSK9-related disorder is atherosclerosis or atherosclerotic coronary heart disease (CHD).