title: Proprotein convertase subtilisin / kexin 9 (PCSK9) inhibitors and the future of dyslipidemia therapy: an updated patent review (2011-2015).
abstract: The identification by Abifadel et al. in 2003 of the first mutations of PCSK9 was the major breakthrough in the cholesterol field that led to a new therapeutic target. This discovery paved the way to new lipid lowering drugs reducing LDL-cholesterol levels through the inhibition of PCSK9. Two anti-PCSK9 monoclonal antibodies have received FDA and EMA approvals: Alirocumab and Evolocumab. Areas covered: This article reviews the different strategies that are pursued to modulate the functional activity of PCSK9 for lowering LDL-cholesterol levels. It also provides a brief overview of the patents related to PCSK9 from 2011 until the end of 2015. This review is addressed to researchers from academia and pharmaceutical companies who are engaged in PCSK9 research/cholesterol regulation. Readers will gain an up-to-date overview of the different strategies that have been investigated to reduce PCSK9, focusing on anti-PCSK9 monoclonal antibodies and the related clinical trials. Expert opinion: Anti-PCSK9 antibodies are a new class of lipid lowering drugs with promising results in reducing LDL-cholesterol. Long-term ongoing studies investigating on a large scale the efficacy and safety of the anti-PCSK9 antibodies and their cardiovascular outcomes are eagerly awaited.
authors.affiliation: a LVTS , INSERM U1148, Hôpital Xavier-Bichat , Paris , France.|b Laboratory of Biochemistry and Molecular Therapeutics, Faculty of Pharmacy, Pôle Technologie- Santé , Saint-Joseph University , Beirut , Lebanon.
authors.forename: Sandy
authors.initials: S
authors.lastname: Elbitar
authors.affiliation: a LVTS , INSERM U1148, Hôpital Xavier-Bichat , Paris , France.|b Laboratory of Biochemistry and Molecular Therapeutics, Faculty of Pharmacy, Pôle Technologie- Santé , Saint-Joseph University , Beirut , Lebanon.
authors.forename: Petra El
authors.initials: PE
authors.lastname: Khoury
authors.affiliation: a LVTS , INSERM U1148, Hôpital Xavier-Bichat , Paris , France.|b Laboratory of Biochemistry and Molecular Therapeutics, Faculty of Pharmacy, Pôle Technologie- Santé , Saint-Joseph University , Beirut , Lebanon.
authors.forename: Youmna
authors.initials: Y
authors.lastname: Ghaleb
authors.affiliation: c Service de Biochimie et Génétique Moléculaire , AP-HP, Hôpitaux Universitaires Paris Ile-de-France Ouest, Site Ambroise Paré , Boulogne-Billancourt , France.|d UFR des Sciences de la Santé Simone Veil , Université Versailles Saint-Quentin-en-Yvelines , Montigny-Le-Bretonneux , France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Rabès
authors.affiliation: a LVTS , INSERM U1148, Hôpital Xavier-Bichat , Paris , France.|e Faculté de Médecine Paris 7 , Université Denis Diderot , Paris , France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Varret
authors.affiliation: f Laboratory of Biochemical Neuroendocrinology, Institut de Recherches Cliniques de Montréal , Affiliated to the Université de Montréal , Montréal , Québec , Canada.
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.affiliation: a LVTS , INSERM U1148, Hôpital Xavier-Bichat , Paris , France.|e Faculté de Médecine Paris 7 , Université Denis Diderot , Paris , France.|g Département de Génétique , AP-HP, CHU Xavier Bichat , Paris , France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.affiliation: a LVTS , INSERM U1148, Hôpital Xavier-Bichat , Paris , France.|b Laboratory of Biochemistry and Molecular Therapeutics, Faculty of Pharmacy, Pôle Technologie- Santé , Saint-Joseph University , Beirut , Lebanon.
authors.forename: Marianne
authors.initials: M
authors.lastname: Abifadel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D008078:Cholesterol, LDL / Q000097:blood; D015195:Drug Design; D050171:Dyslipidemias / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D009154:Mutation; D000091362:PCSK9 Inhibitors; D010330:Patents as Topic; D000071449:Proprotein Convertase 9 / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab; C571059:alirocumab
keywords: Cholesterol; PCSK9; anti-PCSK9 antibodies; cholesterol lowering drugs; patents