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 agents and a pharmaceutical composition.