US 12,274,693 B2
Anti-proprotein convertase subtilisin kexin type 9 (anti-PCSK9) nano-formulation of compounds and methods of using the same
Shaker A. Mousa, Wynantskill, NY (US); Nabil A. Elshourbagy, West Chester, PA (US); Harold V. Meyers, Weston, MA (US); and Sherin Salaheldin Abdel-Meguid, Exton, PA (US)
Assigned to SHIFA BIOMEDICAL CORPORATION, Malvern, PA (US)
Appl. No. 17/276,543
Filed by SHIFA BIOMEDICAL CORPORATION, Malvern, PA (US)
PCT Filed Nov. 5, 2019, PCT No. PCT/US2019/059777
§ 371(c)(1), (2) Date Mar. 16, 2021,
PCT Pub. No. WO2020/097016, PCT Pub. Date May 14, 2020.
Claims priority of provisional application 62/755,709, filed on Nov. 5, 2018.
Prior Publication US 2022/0031665 A1, Feb. 3, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/422 (2006.01); A61K 9/51 (2006.01); A61K 45/06 (2006.01); A61K 47/55 (2017.01)
CPC A61K 31/422 (2013.01) [A61K 9/5138 (2013.01); A61K 9/5153 (2013.01); A61K 9/5161 (2013.01); A61K 45/06 (2013.01); A61K 47/55 (2017.08)] 30 Claims
 
1. A nanoparticle comprising at least one PCSK9 antagonist encapsulated within the nanoparticle, wherein said PCSK9 antagonist is a compound of Formula (I):

OG Complex Work Unit Chemistry
including pharmaceutically acceptable salts and stereoisomers of said compound,
wherein R1 is H or CH3; R2 and R3 are independently selected from the group consisting of H, halogen, (C1-C3)-alkyl and (C1-C3)-alkoxy; and R4 is selected from the group consisting of CO2R5, CONR5R6, aryl, and heteroaryl, wherein R5 and R6 are independently selected from the group consisting of H and (C1-C3)-alkyl, wherein said aryl and heteroaryl are independently substituted or unsubstituted,
wherein said nanoparticle comprises polyvinyl pyrrolidone (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMC-AS), and
wherein said nanoparticle comprises a liver targeting moiety on the exterior of the nanoparticle.