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Strategies for proprotein convertase subtilisin kexin 9 modulation: a perspective on recent patents

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Pages 1547-1571 | Published online: 17 Sep 2010

Bibliography

  • Abifadel M, Varret M, Rabes JP, Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003;34(2):154-6
  • Institut National de la Sante et de la Recherche Medicale. Mutations in the human PCSK9 gene associated to hypercholesterolemia. WO097047; 2004
  • Goldstein JL, Brown MS. Familial hypercholesterolemia: pathogenesis of a receptor disease. Johns Hopkins Med J 1978;143:8-16
  • Innerarity TL, Weisgraber KH, Arnold KS, Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding. Proc Natl Acad Sci USA 1987;84(19):6919-23
  • Timms KM, Wagner S, Samuels ME, A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree. Hum Genet 2004;114(4):349-53
  • Allard D, Amsellem S, Abifadel M, Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia. Hum Mutat 2005;26(5):497
  • Bourbon M, Alves AC, Medeiros AM, On behalf of the investigators of the Portuguese FH study. Familial hypercholesterolaemia in Portugal. Atherosclerosis 2007;196(2):633-42
  • Cameron J, Holla OL, Laerdahl JK, Characterization of novel mutations in the catalytic domain of the PCSK9 gene. J Intern Med 2008;263(4):420-31
  • Homer VM, Marais AD, Charlton F, Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa. Atherosclerosis 2007;196(2):659-66
  • Cameron J, Holla OL, Ranheim T, Effect of mutations in the PCSK9 gene on the cell surface LDL receptors. Hum Mol Genet 2006;15(9):1551-8
  • Cohen J, Pertsemlidis A, Kotowski IK, Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 2005;37(2):161-5
  • Cohen J, Pertsemlidis A, Kotowski IK, Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 2005;37(2):161-5
  • Cohen JC, Boerwinkle E, Mosley TH Jr, Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006;354(12):1264-72
  • Kotowski IK, Pertsemlidis A, Luke A, A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am J Hum Genet 2006;78(3):410-22
  • Hooper AJ, Marais AD, Tanyanyiwa DM, The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis 2007;193(2):445-8
  • Humphries SE, Neely RD, Whittall RA, Healthy individuals carrying the PCSK9 p.R46L variant and familial hypercholesterolemia patients carrying PCSK9 p.D374Y exhibit lower plasma concentrations of PCSK9. Clin Chem 2009;55(12):2153-61
  • Benn M, Nordestgaard BG, Grande P, PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses. J Am Coll Cardiol 2010;55(25):2833-42
  • Abboud S, Karhunen PJ, Lutjohann D, Proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is a risk factor of large-vessel atherosclerosis stroke. PLoS One 2007;2(10):e1043
  • Guella I, Asselta R, Ardissino D, Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population. J Lipid Res 2010; doi:10.1194/jlr.M010009
  • Brown MS, Goldstein JL. Biomedicine. Lowering LDL – not only how low, but how long? Science 2006;311(5768):1721-3
  • Herbert B, Patel D, Waddington SN, Increased secretion of lipoproteins in transgenic mice expressing human D374Y PCSK9 under physiological genetic control. Arterioscler Thromb Vasc Biol 2010;30(7):1333-9
  • Abifadel M, Rabes JP, Devillers M, Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum Mutat 2009;30(4):520-9
  • Zhao Z, Tuakli-Wosornu Y, Lagace TA, Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet 2006;79(3):514-23
  • Rashid S, Curtis DE, Garuti R, Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci USA 2005;102(15):5374-9
  • Millenium Pharmaceuticals, Inc. NARC-1, subtilase-like homologs. WO057081; 2001
  • Eli Lilly and Co. Novel secreted proteins and their uses. WO014358; 2002
  • Seidah NG, Benjannet S, Wickham L, The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci USA 2003;100(3):928-33
  • Adaerata Limited partnership. Chimeric PCSK9 proteins, cells comprising same, and assay using same. WO128121; 2007
  • Benjannet S, Rhainds D, Hamelin J, The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications. J Biol Chem 2006;281(41):30561-72
  • Lagace TA, Curtis DE, Garuti R, Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest 2006;116(11):2995-3005
  • McNutt MC, Lagace TA, Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells. J Biol Chem 2007;282(29):20799-803
  • Poirier S, Mayer G, Poupon V, Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route. J Biol Chem 2009;284(42):28856-64
  • Zhang DW, Lagace TA, Garuti R, Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem 2007;282(25):18602-12
  • Zhang DW, Garuti R, Tang WJ, Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc Natl Acad Sci USA 2008;105(35):13045-50
  • Cunningham D, Danley DE, Geoghegan KF, Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol 2007;14(5):413-19
  • Piper DE, Jackson S, Liu Q, The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol. Structure 2007;15(5):545-52
  • Fischer TS, Lo Surdo P, Pandit S, Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation. J Biol Chem 2007;282(28):20502-12
  • Bottomley MJ, Cirillo A, Orsatti L, Structural and biochemical characterization of the wild type PCSK9-EGF(AB) complex and natural familial hypercholesterolemia mutants. J Biol Chem 2009;284(2):1313-23
  • Irm LLC. Crystal structure of proprotein convertase 9 (PCSK9) and uses thereof. WO109871; 2008
  • Shan L, Pang L, Zhang R, PCSK9 binds to multiple receptors and can be functionally inhibited by EGF-A peptide. Biochem Biophys Res Commun 2008;375(1):69-73
  • McNutt MC, Kwon HJ, Chen C, Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells. J Biol Chem 2009;284(16):10561-70
  • Mayer G, Poirier S, Seidah NG. Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels. J Biol Chem 2008;283(46):31791-801
  • Maxwell KN, Soccio RE, Duncan EM, Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. J Lipid Res 2003;44(11):2109-19
  • Dubuc G, Chamberland A, Wassef H, Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2004;24(8):1454-9
  • Li H, Dong B, Park SW, Hepatocyte nuclear factor 1 alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. J Biol Chem 2009;284(42):28885-95
  • Cameron J, Ranheim T, Kulseth MA, Berberine decreases PCSK9 expression in HepG2 cells. Atherosclerosis 2008;201(2):266-73
  • Persson L, Galman C, Angelin B, Importance of proprotein convertase subtilisin/kexin type 9 in the hormonal and dietary regulation of rat liver low-density lipoprotein receptors. Endocrinology 2009;150(3):1140-6
  • Langhi C, Le May C, Kourimate S, Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes. FEBS Lett 2008;582(6):949-55
  • Schmidt RJ, Ficorilli JV, Zhang Y, A 15-ketosterol is a liver X receptor ligand that suppresses sterol-responsive element binding protein-2 activity. J Lipid Res 2006;47(5):1037-44
  • Bell TA III, Brown JM, Graham MJ, Liver-specific inhibition of acyl-coenzyme a: cholesterol acyltransferase 2 with antisense oligonucleotides limits atherosclerosis development in apolipoprotein B100-only low-density lipoprotein receptor-/- mice. Arterioscler Thromb Vasc Biol 2006;26(8):1814-20
  • Graham MJ, Lemonidis KM, Whipple CP, Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J Lipid Res 2007;48(4):763-7
  • Isis Pharmaceuticals, Inc. Compounds and methods for modulatin expression of PCSK9. WO143315; 2007
  • Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia. WO066776; 2008
  • Yu RZ, Geary RS, Leeds JM, Comparison of pharmacokinetics and tissue disposition of an antisense phosphorothioate oligonucleotide targeting human Ha-ras mRNA in mouse and monkey. J Pharm Sci 2001;90(2)182-93
  • Yu RZ, Geary RS, Monteith DK, Tissue disposition of 2′-O-(2-methoxy-)ethyl modified antisense oligonucleotides in monkeys. J Pharm Sci 2004;93(1):48-59
  • Greeve JI, Altkemper J, Dieterich H, Apolipoprotein B mRNA editing in 12 different mammalian species: hepatic expression is reflected in low concentrations of apoB-containing plasma lipoproteins. J Lipid Res 1993;34:1367-83
  • Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia. WO148605; 2009
  • Frank-Kamenetsky M, Grefhorst A, Anderson NN, Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci USA 2008;105(33):11915-20
  • Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the PCSK9 gene. WO134161; 2007
  • Schwartz GG, Olsson AG, Ezekowitz MD, Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001;285(13):1711-18
  • Alnylam Pharmaceuticals, Inc. Optimized methods for delivery of dsRNA targeting the PCSK9 gene. WO134487; 2009
  • Alnylam Pharmaceuticals, Inc. Phosphorothioate oligonucleotides non- nucleosidic phosphorothiotes as delivery agents for iRNA agents. WO006237; 2010
  • Gupta N, Fisker N, Asselin MC, A locked nucleic acid antisens oligonucleotide (LNA) silences PCSk9 and enhances LDLR expression in vitro and in vivo. PLoS One 2010;5(5):e10682
  • Zaid A, Roubtova A, Essalmani R, Proprotein convertase subtilisin/kexin type 9 (PCSK9): Hepatocye-specific low density lipoprotein receptor degradation and critical role in mouse liver regeneration. Hepatology 2008;48:646-54
  • Elmen J, Lindow M, Silahtaroglu A, Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver. Nucleic Acids Res 2008;36:1153-62
  • Elmen J, Lindow M, Schutz S, LNA-mediated microRNA silencing in non-human primates. Nature 2008;452:896-99
  • Lanford RE, Hildebrandt-Eriksen ES, Petri A, Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 2010;327:198-201
  • Stenvang J, Silahtaroglu AN, Lindow M, The utility of LNA in microRNA-based cancer diagnostics and therapeutics. Semin Cancer Biol 2008;18(2):89-102
  • Sapra P, Wang M, Bandaru R, Down-modulation of survivin expression and inhibition of tumor growth in vivo by EZN-3042, a locked nucleic acid antisense oligonucleotide. Nucleosides Nucleotides Nucleic Acids 2010;29(2):97-112
  • Sirna Therapeutics, Inc. RNA interference mediated inhibition of proprotein convertases subtilisin kexin 9 (PCSK9) gene expression using short interfering nucleic acid (SINA). WO011431; 2008
  • Nastech Pharmaceutical Co., Inc. Nucleic acid compounds for inhibiting PCSK9 gene expression and uses thereof. WO109472; 2008
  • Santaris Pharma A/S. Pharmaceutical composition comprising anti PCSK9 oligomers. WO127680; 2009
  • Chan JC, Piper DE, Cao Q, A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci USA 2009;106(24):9820-5
  • Amgen, Inc. Antigen binding proteins to proprotein convertases subtilisin kexin type 9 (PCSK9). WO026558; 2009
  • Amgen, Inc. Neutralizing proprotein convertases subtilisin kexin 9 (PCSK9) variants and uses thereof. WO131740; 2009
  • Ni YG, Condra JH, Orsatti L, A proprotein convertase subtilisin/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake. J Biol Chem 2010;285(17):12882-91
  • Regeneron Pharmaceuticals, Inc. High affinity human antibodies to PCSK9. WO077854; 2010
  • Labonte P, Begley S, Guevin C, PCSK9 impedes hepatitis C virus infection in vitro and modulates liver CD81 expression. Hepatology 2009;50(1):17-24
  • Poirier S, Mayer G, Benjannet S, The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. J Biol Chem 2008;283(4):2363-72
  • Jonas MC, Costantini C, Puglielli L. PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1. EMBO Rep 2008;9(9):916-22
  • Liu M, Wu G, Baysarowich J, PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain. J Lipid Res 2010;51:2611-8
  • Shibata N, Ohnuma T, Higashi S, No genetic association between PCSK9 polymorphisms and Alzheimer's disease and plasma cholesterol level in Japanese patients. Psychiatr Genet 2005;15(4):239
  • Langhi C, Le May C, Gmyr V, PCSK9 is expressed in pancreatic delta-cells and does not alter insulin secretion. Biochem Biophys Res Commun 2009;390(4):1288-93
  • Mbikay M, Sirois F, Mayne J, PCSK9-deficient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities. FEBS Lett 2010;584(4):701-6
  • Regeneron Pharmaceuticals, Inc. 2010 PR Newswire. Available from: http://www.regeneron.com/pipeline.html
  • Careskey HE, Davis RA, Alborn WE, Atorvastatin increases human serum levels of proprotein convertase subtilisin kexin type 9 (PCSK9). J Lipid Res 2008;49(2):394-8
  • Welder G, Zineh I, Pacanowski MA, High dose atorvastatin causes a rapid, sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res 2010;51:2714-21
  • Fasano T, Cefalu AB, Di Leo E, A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol. Arterioscler Thromb Vasc Biol 2007;27(3):677-81
  • Merck Sharp & Dohme Corp. PCSK9 Immunoassay. WO068526; 2010
  • Alnylam Pharmaceuticals, Inc. Processes for preparing lipids. WO048536; 2010
  • Alnylam Pharmaceuticals, Inc. Lipids and compositions for the delivery of therapeutics. WO054384; 2010
  • Carolus Therapeutics, Inc. Methods of treating cardiovascular disorders. WO056910; 2010
  • Intradigm Corp. Copositions comprising human PCSK9 and apolipoproteinB siRNA and methods of use. WO114475; 2009
  • Isis Pharmaceuticals, Inc. Compounds and methods for modulating the GCCR. WO134014; 2007
  • Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of SGLT2. WO143316; 2007
  • Sanofi-Aventis. Use of substituted pyridinone carboxylic acid derivates for producing pharmaceuticals for the treatment of dyslipidemia. WO000401; 2010
  • Santaris Pharmaceuticals A/S. RNA antagonist compounds for the modulation of PCSK9. WO043753; 2008
  • Lambert G. Charlton F, Rye KA, et al. Molecular basis of PCSK9 function. Atherosclerosis 2009;203(1):1-7
  • Merck and Co., Inc. Antagonists of PCSK9. WO057457, 057458,057459 and 063382; 2008
  • Merck and Co., Inc. Antagonists of PCSK9. WO133647; 2008
  • Merck Sharp and Dohme Corp. 1B20 PCSK9 antagonists. WO100318; 2009
  • Merck Sharp and Dohme Corp. and Instituto di recherche di Biologia Molecolare SPA.1D05 PCSK9 antagonists. WO100297; 2009
  • Novartis AG. Molecules and methods for modulating PCSK9. WO125623; 2008
  • Rinat Neuroscience Corp. Pfizer, Inc. PCSK9 antagonists. WO029513; 2010
  • Schering Corp. Anti-PCSK9 and methods for treating lipid and cholesterol disorders. WO055783; 2009
  • Seidah NG. PCSK9 as a therapeutic target of dyslipidemia. Expert Opin Ther Targets 2009;13(1):19-28
  • Schering Corp. EGF-A domain-mediated modulation of PCSK9. WO143367; 2009
  • Hericks JA. Targeting PCSK9 for the treatment of hypercholesterolemia. Curr Opin Investig Drug 2009;10(9):938-46
  • Affiris AG. Vaccine. WO057242; 2010
  • Bristol-Myers Squibb Co. Polynucleotides encoding novel PCSK9 variants. WO105797; 2008
  • Institut de recherches cliniques de Montreal. PCSK9 inhibitors and methods of use thereof. WO143633; 2009
  • Merck and Co., Inc. Method for detecting autoprocessed, secreted PCSK9. WO118386; 2008
  • Odyssey Thera, Inc. High- content and high throughput assays for identification of lipid regulating pathways, and novel therapeutic agents for lipid disorders. WO111073; 2009
  • Partnership and Corp. Technology transfer. Synthetic peptides for use as inhibitors of neurotransmitter secretion and as inducers of muscle relaxation. WO071448; 2007
  • Kwon HJ, Lagace TA, McNutt MC, Molecular basis for LDL receptor recognition by PCSK9. Proc Natl Acad Sci USA 2008;105(6):1820-25

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