| abstract |
The invention provides a biological conjugate comprising a synthetic polypeptide of Formula I':nOr a guanamine, ester or salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are as defined herein and a half-life extending moiety, wherein the peptide This half-life extension is optionally covalently linked or fused via a linker. The polypeptide is an agonist of the APJ receptor. The invention also relates to a method for the manufacture of a bioconjugate of the invention, and to its therapeutic use, such as for the treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, cloth Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular disease, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including Gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accident, transient ischemic attack, traumatic brain injury, amyotrophic lateral sclerosis, burns (including sunburn), and pre-eclampsia. The invention further provides combinations and pharmaceutical compositions of pharmacologically active agents. |