Cyclic polypeptides for the treatment of heart failure

US9266925B2 · kind B2 · utility

Assignee

• Novartis AG · CH

Inventors

• Frederic Zecri · Cambridge, US
• Philipp Grosche · Inzlingen, DE
• Kayo Yasoshima · Cambridge, US
• Hongjuan Zhao · Lexington, US
• Jun Yuan · Guilford, US
• Aimee Richardson USERA · Winchester, US
• Changgang LOU · Portage, US
• Aaron KANTER · Somerville, US
• Alexandra Marshall BRUCE · Cambridge, US
• Carla Giumaraes · Boston, US

Key dates

• Filing date: Jul 21, 2014
• Grant date: Feb 23, 2016
• Expiry date: Jul 21, 2034

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/31
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention provides a cyclic polypeptide of Formula I (SEQ ID NO: 1):X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13  Ior an amide, an ester or a salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides of the invention or bioconjugates thereof, and their therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.