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Lipidomic Biomarkers for Atherosclerosis and Cardiovascular Disease

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Lipidomic Biomarkers for Atherosclerosis and Cardiovascular Disease (19) TZZ ¥¥ T (11) EP 2 385 374 B2 (12) NEW EUROPEAN PATENT SPECIFICATION After opposition procedure (45) Date of publication and mention (51) Int Cl.: of the opposition decision: G01N 33/92 (2006.01) 28.02.2018 Bulletin 2018/09 (45) Mention of the grant of the patent: 08.01.2014 Bulletin 2014/02 (21) Application number: 10162066.4 (22) Date of filing: 05.05.2010 (54) Lipidomic biomarkers for atherosclerosis and cardiovascular disease Lipidomik-Biomarker für Atherosklerose und kardiovaskuläre Erkrankung Biomarqueurs lipidomiques pour l’athérosclérose et les maladies cardiovasculaires (84) Designated Contracting States: • EKROOS KIM ET AL: "Lipidomics: a tool for AL AT BE BG CH CY CZ DE DK EE ES FI FR GB studies of atherosclerosis." CURRENT GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO ATHEROSCLEROSIS REPORTS JUL 2010 LNKD- PL PT RO SE SI SK SM TR PUBMED:20425241, vol. 12, no. 4, July 2010 (2010-07), pages 273-281, XP008124463 ISSN: (43) Date of publication of application: 1534-6242 09.11.2011 Bulletin 2011/45 • KADDURAH-DAOUK RIMA ET AL: "Lipidomic analysis of variation in response to simvastatin (73) Proprietor: Zora Biosciences OY in the Cholesterol and Pharmacogenetics Study" 02150 Espoo (FI) METABOLOMICS, vol. 6, no. 2, June 2010 (2010-06), pages 191-201, XP002592438 (72) Inventors: • LAAKSONEN ET AL: "Lipidomics as a tool for • Laaksonen, Reijo atherosclerosis research" NEW 37500 Lempäälä (FI) BIOTECHNOLOGY, ELSEVIER BV, NL, vol. 27, 1 • Ekroos, Kim April 2010 (2010-04-01), pages S18-S19, 00200 Helsinki (FI) XP026965681 ISSN: 1871-6784 •Hurme,Reini • WATERMAN C L ET AL: "Metabolomic strategies 02180 Espoo (FI) to study lipotoxicity in cardiovascular disease" •Jänis,Minna BIOCHIMICA AND BIOPHYSICA ACTA. 02330 Espoo (FI) MOLECULAR AND CELL BIOLOGY OFLIPIDS, • Katainen, Riikka ELSEVIER, AMSTERDAM, NL LNKD- 00120 Helsinki (FI) DOI:10.1016/J.BBALIP.2009.11.004,vol. 1801, no. • Tarasov, Kirill 3, 1 March 2010 (2010-03-01), pages 230-234, 02230 Espoo (FI) XP026904840 ISSN: 1388-1981 • HU C ET AL: "Analytical strategies in lipidomics (74) Representative: Dörries, Hans Ulrich andapplications in disease biomarker discovery" df-mp Dörries Frank-Molnia & Pohlman JOURNAL OF CHROMATOGRAPHY B: Patentanwälte Rechtsanwälte PartG mbB BIOMEDICAL SCIENCES & APPLICATIONS, Theatinerstrasse 16 ELSEVIER, AMSTERDAM, NL, vol. 877, no. 26, 15 80333 München (DE) September 2009 (2009-09-15), pages 2836-2846, XP026422757 ISSN: 1570-0232 (56) References cited: WO-A1-2007/144467 WO-A1-2011/063470 WO-A2-2004/085610 WO-A2-2007/127192 CN-A- 101 522 910 US-A1- 2004 143 461 US-A1- 2009 029 473 US-A1- 2009 197 242 EP 2 385 374 B2 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 385 374 B2 • STAHLMAN M ET AL: "High-throughput shotgun • GRIBANOV G.A. ET AL: ’Blood lipid changes in lipidomics by quadrupole time-of-flight mass hipoxic rats’ SPACE BIOLOGY ARID spectrometry" JOURNAL OF AEROSPACE MEDICINE (RUSSIAN JOURNAL) CHROMATOGRAPHY B: BIOMEDICAL vol. 6, 1978, pages 67 - 71 SCIENCES & APPLICATIONS, ELSEVIER, • BERESEWICZ A. ET AL: ’Accumulation of AMSTERDAM, NL, vol. 877, no. 26, 15 September specific ceramides in ischemic/reperfused rat 2009 (2009-09-15), pages 2664-2672, hearth; Effect of ischemic preconditioning’ XP026422742 ISSN: 1570-0232 JOURNAL OF PHYSIOLOGY AND • JÄNIS MINNA T ET AL: "Metabolomic strategies PHARMACOLOGY vol. 53, no. 3, 2002, pages 371 to identify tissue-specific effects of - 382 cardiovascular drugs." EXPERT OPINION ON • Borinsk et al. (Russian) Voprosy medicinskoj DRUG METABOLISM & TOXICOLOGY JUN 2008 himii, 1993, 39(6), page 20-22, UDC 61 6. 1 LNKD- PUBMED:18611110, vol. 4, no. 6, June 27-005.8:61 6.1 53.91 5, ISSN: 0042 8809 2008 (2008-06), pages 665-680, XP008124464 • English translation of D16 ISSN: 1742-5255 • MIETTINEN T.A. ET AL: ’Fatty-acid composition • FELLSTROM ET AL: AMERICAN JOURNAL OF of serum lipids predicts myocardial infarction’ TRANSPLANATION, vol. 5, 2005, pages BRITISH MEDICAL JOURNAL (CLIN. RES. ED.) 1986-1991, vol. 285, 09 October 1982, pages 993 - 996 • PARISH ET AL: EUROPEAN HEART JOURNAL, • RAPP J.H. ET AL: ’Lipids and human vol. 30, 2009, pages 2137-2146, atherosclerotic plaques and xanthomas: clues to • HUANG ET AL: JOURNAL OF themechanism of plaque progression’ JOURNAL ATHEROSCLEROSIS AND THROMBOSIS, vol. OF LIPID RESEARCH vol. 24, 1983, pages 1329 - 17, no. 3, 2010, 1335 • STEGEMANN ET AL.: ’Comparative lipidomics • MCLAURIN J. ET AL: ’Reactivity of two profiling of human atherosclerotic plaques’ CIRE anti-galactosl ceramide antibodies towards CARDIOVASC GENET vol. 4, 2011, pages 232 - myelin basic protein’ JOURNAL OF THE 242 NEUROLOGICAL SCIENCES vol. 108, 1992, • GERTLER M. M.: ’The interrelationships of serum pages 73 - 79 cholesterol, cholesterol esters and • TARASOW K. ET AL: ’Molecular lipids identify phospholipids in health and in coronary artery cardiovascular risk and are efficiently lowered by disease’ CIRCULATION vol. 2, August 1950, simvastatin and PCSK9 deficiency’ J. CLIN pages 205 - 214 ENDOCRINOL METAB. vol. 99, January 2014, • MEIKLE P.J. ET AL: ’Plasma lipidomic analysis pages E45 - E52 of stable and unstable coronary artery disease’ • Laaksonen et al., Summary of the SPUM-ACS ARTERIOSCLER THROMB VASC BIOL. vol. 31, (Switzerland) and Corogene (Finland) studies 2011, pages 2723 - 2732 • LAAKSONEN R. ET AL: ’Plasma ceramides • SUGANO M. ET AL: ’Effects of diltiazem on predict cardiovascular death in patients with suppression and regression of experimental stable coronary artery disease and acute atherosclerosis’ BR. J. EXP. PATH. vol. 69, 1988, coronary syndromes beyond LDL-cholesterol’ pages 515 - 523 EUROPEAN HEARTH JOURNAL vol. 37, 2016, • Priority documents D7 (US prov. 61/264,767) pages 1967 - 1976 • Wikipedia Entry "Cholesterinester", Version of • Cheng et al., Summary of the Atheroremo-Ivus October 28, 2009 study (The Netherlands) • CHATTERJEC S. ET AL: ’Accumulation of • CHENG J.M. ET AL: ’Plasma concentrations of glycosphingolipids in human atherosclerotic molecular lipids species in relation to coronary plaque and unaffected aorta tissues’ plaque characteristics and cardiovascular GLYCOBIOLOGY vol. 7, no. 1, 1997, pages 57 - 65 outcome: Results of the Atheroremo-Ivus study’ • STEGEMANN C. ET AL: ’Lipidomics profiling and ATHEROSCLEROSIS vol. 243, 2015, pages 560 - risk of cardiovascular disease in the prospective 566 population-based Bruneck study’ CIRCULATION • Diagram showing the average % change of lipid vol. 129, 2014, pages 1821 - 1831 markers in the Corogene study, the Luric study • ICHI I. ET AL: ’Association of ceramides in human of the patent and the completed Luric study. plasma with risk factors of atherosclerosis’ • Structure database (LMSD): Cer(d18:1/18:0) LIPIDS vol. 41, no. 9, 2009, pages 859 - 863 • Structure database (LMSD): Cer(d18:1/20:0) • KRAMSCH D.M. ET AL: ’The protein and lipid • LLOYD-JONES D. ET AL: ’Heart disease and compositionof arterial elastin and its relationship stroke statistics - 2010 Update’ AHA to lipid accumulation in the atherosclerotic STATISTICAL UPDATE 2010, pages E46-E47 - plaque’ THE JOURNAL OF CLINICAL E86-E93 INVESTIGATION vol. 50, 1971, pages 1666 - 1677 • Mayo Clinic News; May 31, 2016 2 (Cont. next page) EP 2 385 374 B2 • JÜRGEN LUDWIG: ’Handbook of Autopsy’, vol. Remarks: 3RD. ED., 2002, SPRINGER SCIENCE+BUSINESS Thefile contains technical information submitted after MEDIA, LLC, NEW YORK page 114 the application was filed and not included in this • Declaration of Dr. Kaisa Koistinen + Annex1 (CV specification of Dr. Koistinen) + Annex2 (LIPID MAPS entries for Cer(d18:1/18:0), Cer(d18:1/20:0) and Cer(d18:2/20:0). • SHEPHERD J.: ’Does statin monotherapy address the multiple lipid abnormalities in type 2 diabetes? ’ATHEROSCLEROSIS SUPPLEMENTS vol. 6, 2005, pages 19 - 19 • AMBROSE J.A. ET AL: ’The Pathophysiology of cigarette smoking and cardiovascular disease’ JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY vol. 43, no. 10, 2004, pages 1731 - 1737 3 EP 2 385 374 B2 Description Field of the Invention 5 [0001] This invention relates to methods and uses involving lipid levels to diagnose, predict, prevent and/or treat atherosclerosis or cardiovascular disease (CVD) and their fatal and non-fatal complications including e.g. acute myo- cardial infarctionand death. The methods include analyzing lipid levels of abiological sample,and comparing it to acontrol. Background of the Invention 10 [0002] Worldwide, cardiovascular diseases are among the leading causes of mortality and morbidity with ever-increas- ing prevalence. Early targeted initiation of preventive measures would be of great benefit and can provide a major opportunity inreducing mortality andmorbidity. To this end, accurate identification ofindividuals who are stillasymptomatic but at elevated risk is essential. However, traditional risk assessment fails to recognize a substantial proportion of patients 15 at high risk while a large proportion of individuals are classified as having intermediate risk, leaving patient management uncertain. Additional strategies to further refine risk assessment are therefore highly needed. To this end, the inventors have evaluated the role of novel lipidomic biomarkers as diagnostic tool for atherosclerosis. These new biomarkers can be used to identify an individual at elevated risk for CVD events such as angina pectoris, myocardial infarction, stroke and cardiovascular death. 20 [0003] Plasma or serum total cholesterol, LDL-cholesterol or HDL-cholesterol concentrations have been used as gold standard biomarkers for CVD/CAD risk prediction.
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