Bioconjugates of synthetic apelin polypeptides

US9340582B2 · kind B2 · utility

Assignee

• Novartis AG · CH

Inventors

• Jun Yuan · Guilford, US
• Frederic Zecri · Cambridge, US
• Philipp Grosche · Inzlingen, DE
• Hongjuan Zhao · Lexington, US
• Eric Peters · San Diego, US
• Shari Lynn Caplan · Lunenburg, US
• Changgang LOU · Portage, US

Key dates

• Filing date: Jul 21, 2014
• Grant date: May 17, 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 bioconjugates comprising a synthetic polypeptide of Formula I′ (SEQ ID NO: 1):or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein and a half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the 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 agent…