Claims for Patent: 10,472,424

Summary for Patent: 10,472,424

Title:	Treatment with anti-PCSK9 antibodies
Abstract:	The present invention relates to therapeutic dosing regimens utilizing a dose reduction strategy for treating disorders characterized by marked elevations of low density protein cholesterol (LDL-C) in the plasma of a patient. The subject therapeutic dosing regimens involve delivering as a single administration or plurality of administrations of an anti-proprotein convertase subtilisin kexin type 9 (PCSK9) antagonist antibody as an initial dose of at least about 100 mg, and delivering as a single administration or plurality of administrations at a subsequent dose in an amount that is about the same as the initial dose, or at least half the initial dose after the patient has a LDL-C level at or below about 25, 20, 15 or 10 mg/dL, preferably at or below 10 mg/dL.
Inventor(s):	Cropp; Anne Barbara (Madison, CT), Kim; Albert (Newton, MA), Plowchalk; David Raymond (Waterford, CT), Sweeney; Kevin Richard (East Lyme, CT), Wang; Ellen Qiao (Brooklyn, NY)
Assignee:	Pfizer Inc. (New York, NY)
Application Number:	15/510,600
Patent Claims:	1. A method for treating a patient diagnosed with a disorder characterized by an elevated low-density lipoprotein cholesterol (LDL-C) level in the blood, comprising delivering to the patient as a single administration or plurality of administrations an initial dose of at least about 100 mg of a proprotein convertase subtilisin kexin type 9 (PCSK9) antagonist antibody, and delivering to the patient a single administration or plurality of administrations at a subsequent dose that is about the same as the initial dose, or at least half the initial dose after the patient has a LDL-C level at or below about 25, 20, 15 or 10 mg/dL, wherein all administrations are separated in time from each other by at least about two weeks. 2. The method of claim 1, wherein the subsequent dose is about two thirds of the initial dose. 3. The method of claim 1, wherein the subsequent dose is about one half the initial dose. 4. The method of claim 1, wherein the initial dose is 150 mg, and the subsequent dose is reduced below 150 mg every two weeks after the patient has a LDL-C level below about 25, 20, 15 or 10 mg/dL. 5. The method of claim 4, wherein the subsequent dose is reduced to 75 mg after the patient has a LDL-C at or below about 25, 20, 15 or 10 mg/dL. 6. The method of claim 4, wherein the subsequent dose is 100 mg after the patient has a LDL-C at or below about 25, 20, 15 or 10 mg/dL. 7. The method of claim 1, wherein the subsequent dose is administered to the patient after the patient has at least about two consecutive assessments of LDL-C at or below about 25, 20, 15 or 10 mg/dL. 8. The method of claim 3, wherein said subsequent dose is reduced to half the initial dose and is administered every two weeks after the patient has a LDL-C at or below 25, 20, 15 or 10 mg/dL, and wherein a second subsequent dose is administered every two weeks and is even further reduced to one third or one quarter the initial dose, delivered as a single or plurality of administrations, after the patient has a LDL-C again at or below about 25, 20, 15 or 10 mg/dL while on the subsequent dose. 9. The method of claim 2, wherein said subsequent dose is reduced to two thirds the initial dose and is administered every two weeks after the patient has a LDL-C at or below 25, 20, 15 or 10 mg/dL, and wherein a second subsequent dose is administered every two weeks and is then even further reduced to one third or one quarter the initial dose, delivered as a single or plurality of administrations, after the patient had a LDL-C again at or below about 25, 20, 15 or 10 mg/dL while on the subsequent dose. 10. The method of claim 1, wherein said subsequent dose is reduced to half the initial dose and is administered every two weeks after the patient has at least about two consecutive assessments of LDL-C level at or below 25, 20, 15 or 10 mg/dL, and said subsequent dose is then administered every four weeks after the patient has at least about another two consecutive assessments of LDL-C level again at or below 25, 20, 15 or 10 mg/dL while on the subsequent dose every two weeks. 11. The method of claim 1, wherein said subsequent dose is reduced to half the initial dose and is administered every two weeks after the patient has a LDL-C level at or below 25, 20, 15 or 10 mg/dL, and said subsequent dose is then administered every four weeks after the patient has a LDL-C level again at or below 25, 20, 15 or 10 mg/dL while on the subsequent dose every two weeks. 12. The method of claim 11, wherein the initial dose is 150 mg and the subsequent dose is 75 mg. 13. The method of claim 1, wherein a statin has been administered prior to the initial dose of the PCSK9 antagonist antibody. 14. The method of claim 13, wherein the statin is atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, or any pharmaceutically acceptable salts, or stereoisomers, thereof. 15. The method of claim 1, wherein the disorder is dyslipidemia, hyperlipidemia, hypercholesterolemia, atherosclerosis, cardiovascular disease, and/or coronary heart disease. 16. The method of claim 1, wherein the antibody blocks LDLR binding to the PCSK9 of SEQ ID NO: 1. 17. The method of claim 1, wherein the antibody is alirocumab, evolocumab, REGN728, LGT209, RG7652, LY3015014, J16, L1L3 (bococizumab), 31H4, 11F1, 12H11, 8A1, 8A3, 3C4, 300N, or 1D05. 18. The method of claim 1, wherein the antibody comprises a VH CDR1 having the amino acid sequence shown in SEQ ID NO: 4, 5, or 6, a VH CDR2 having the amino acid sequence shown in SEQ ID NO:7 or 8, a VH CDR3 having the amino acid sequence shown in SEQ ID NO: 9; and a VL CDR1 having the amino acid sequence shown in SEQ ID NO:10, a VL CDR2 having the amino acid sequence shown in SEQ ID NO:11, and a VL CDR3 having the amino acid sequence shown in SEQ ID NO: 12. 19. The method of claim 1, wherein the LDL-C level is at least about or lower than 65, 60, 55, 45, 40, 35, 30, 25, 20, or 15 mg/dL after administration of the initial dose or both the initial dose and the subsequent dose.

Details for Patent 10,472,424

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Amgen, Inc.	REPATHA	evolocumab	Injection	125522	08/27/2015		2034-09-23
Amgen, Inc.	REPATHA	evolocumab	Injection	125522	07/08/2016		2034-09-23
Regeneron Pharmaceuticals, Inc.	PRALUENT	alirocumab	Injection	125559	07/24/2015		2034-09-23