BIOCONJUGADOS DE POLIPÉPTIDOS DE APELINA SINTÉTICA

• Main Authors: CAPLAN, SHARI L, YASOSHIMA, KAYO, GROSCHE, PHILIPP, LOU, CHANGGANG, GOLOSOV, ANDREI, USERA, AIMEE RICHARDSON, ZECRI, FREDERIC, ZHAO, HONGJUAN, GUAIMARAES, CARLA, PARKER, DAVID THOMAS, KANTER, AARON, PETERS, ERIC C, YUAN, JUN
• Format: Patent
• Language: Spanish
• Published: 31.08.2016
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

La invención proporciona un bioconjugado que comprende un polipéptido sintético de la Fórmula I´: ESPACIO PARA FÓRMULA I´ o una amida, un éster o una sal del mismo, en donde X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 Y X13 se definen en el presente documento y una fracción de extensión de vida media en donde el péptido y la fracción de extensión de vida media se une o fusiona covalentemente, opcionalmente a través de un enlazador. Los polipéptidos son agonistas del receptor APJ. La presente invención además proporciona una combinación de agentes farmacológicamente activos y una composición farmacéutica. 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.