Disulfide cyclic polypeptides for the treatment of heart failure

US9683018B2 · 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

Key dates

• Filing date: Jul 21, 2014
• Grant date: Jun 20, 2017
• Expiry date: Jul 21, 2034

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K14/47
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention provides a synthetic polypeptide of Formula I′: X1-R-P-R-X5-X6-X7-K-X9-P-X11-X12-X13 or an amide, an ester, a salt or a bioconjugate thereof, wherein X1, X5, X6, X7, X9 and X11 to X13 are defined herein. The polypeptides and bioconjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides or bioconjugates of the invention, and its 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.