Proprotein convertase subtilisin kexin type 9 (PCSK9) allosteric binding ligands to modulate serum low density lipoprotein (LDL) levels

US10287317B2 · kind B2 · utility

Assignee

• SRX Cardio, LLC · US

Inventors

• Michael M. Muehlemann · Liverpool, US
• Thomas E. Barta · Evanston, US
• Kyle D. Monroe · Pittsford, US
• Jonathan William Bourne · Fairport, US
• Margaret Thompson Reece · Springfield, US
• Vesa Nevalainen · Weymouth, US
• Eric T. Baldwin · Carmel, US

Key dates

• Filing date: Aug 13, 2015
• Grant date: May 14, 2019
• Expiry date: Aug 13, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K5/1016
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

This invention is related to the field of hypercholesterolemia. In particular, the invention provides compositions and methods to modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9 using synthetic ligands and/or synthetic ligand derivative sequences of 3-8 amino acids ranging between 350-2,000 Da. Altering the conformation of PCSK9 affects the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for ligands which can raise LDL levels.