University of California

The Scripps Research Institute

Institut National De La Sante Et De La Recherche Medicale

Scripps Clinic and Research Foundation

Université Paris Diderot-Paris 7

Indiana University

Ionis Pharmaceuticals, Inc.

Inserm (institut National De La Sante Et De La Recherche Medicale)

Joseph L Witztum

Sotirios Tsimikas

Linda K Curtiss

Xuchu Que

Richard S Smith

Wulf Palinski

Alain Tedgui

Ziad Mallat

Steven Young

Peta-Maree Lamb

Stephen G Young

Peter X Shaw

Kanaka Raju Koduri

William W Turner

Nicholas J Viney

Michael S Van Nieuwenhze

Veronica J Alexander

Yury Miller

Karsten Hartvigsen

Elizabeth Miller

Doreen M Hogle

Linda K Curtis

Ayelet Gonen

Sotorios Tsimikas

Sohvi H&ouml;rkk&ouml;

Daniel Steinberg

Provided herein are new diagnostic biomarkers for cardiovascular disease, antibodies for detecting said diagnostic biomarkers, and immunoassays, imaging agents, and therapeutics based therefrom.

Compositions and methods for diagnosis of cardiovascular disease

The disclosure provides for single chain variable fragments to MAA-oxidized specific epitopes (OSEs). The disclosure also provides single chain variable fragments that bind to MDA-OSEs or MAA-OSEs on oxidized phospholipids and methods of use thereof, including the production of transgenic animal models and the use of the fragments as therapeutic agents.

Antibodies to oxidation-specific epitopes

The disclosure provides for single chain variable fragments to oxidized phospholipid epitopes and methods of use thereof, including the production of transgenic animal models and the use of the fragments as therapeutic agents for treating CAS.

Method of treating rheumatoid arthritis using antibodies to oxidized phospholipids

The disclosure provides for methods and treatments of ischemic injury, reperfusion injury, stroke and myocardial infarctions by administering within minutes to hours an antibody or antibody fragment that bind to and inhibits the biological activity of OxPL in an affected tissue.

Inhibition of oxidation-specific epitopes to treat ischemic reperfusion injury

Antibodies to oxidized phospholipids

The disclosure provides for methods and treatments of TLR2-mediated diseases and disorders comprising administering an antibody, antibody fragment, or polypeptide that binds to and inhibits the biological activity of oxidized phospholipids.

Therapies and methods to treat TLR2-mediated diseases and disorders

The disclosure provides for single chain variable fragments to MAA-oxidized specific epitopes (OSEs). The disclosure also provides single chain virable fragments that bind to MDA-OSEs or MAA-OSEs on oxidized phospholipids and methods of use thereof, including the production of transgenic animal models and the use of the fragments as therapeutic agents.

Provided are methods, compounds, and compositions for reducing expression of ApoCIII mRNA and protein for treating, preventing, delaying, or ameliorating Fredrickson Type I dyslipidemia/FCS/LPLD, in a patient. Such methods, compounds, and compositions increase HDL levels and/or improving the ratio of TG to HDL and reducing plasma lipids and plasma glucose in the patient, and are useful to treat, prevent, delay, or ameliorate any one or more of pancreatitis, cardiovascular disease, metabolic disorder, and associated symptoms.

Modulation of apolipoprotein C-III (ApoCIII) expression in lipoprotein lipase deficient (LPLD) populations

The present invention provides a peptide-phospholipid conjugate of Formula 1: wherein: X is selected from the group consisting of &#x2014;CRR&#x2014;, &#x2014;R&#x2014;, &#x2014;O&#x2014;, &#x2014;S&#x2014;, and S(R)&#x2014;; Y is selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, ether, cycloamino, cycloether, aryl heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl; Z is a peptide comprising 1 to 50 amino acids; Rand Reach independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl; and Ris selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, aminoalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl.

Peptide-phospholipid conjugates

Provided herein are compositions and methods for examining the progression, regression or risk of individuals for having a stroke, transient ischemic attack or peripheral artery disease.

Oxidative biomarkers in predicting risk of stroke, transient ischemic attack (TIA) and peripheral arterial disease (PAD)

The present invention provides methods to analyze oxidized phospholipids (OxPL) on apolipoprotein B-100 in patients at high risk or with documented coronary artery disease (CAD) or acute coronary syndromes (ACS) such as unstable angina and acute myocardial infarction or suspected of being at risk for ACS. Such methods are useful for diagnostic purposes and for monitoring the effects of dietary interventions or with drugs such as statins. More particularly, the disclosure provides methods for determining OxPL/apoB ratios as indices of atherosclerosis regression and plaque stability.

Methods for assessing atherogenesis by determining oxidized phospholipid to apolipoprotein B ratios

Provided herein are compositions and methods for examining the progression, regression or risk of individuals at risk for developing coronary artery disease (CAD).

Methods to determine atherosclerosis regression, plaque stabilization and cardiovascular risk

The present invention related to a method of identifying a subject having or at risk of having or developing a cardiovascular disease and/or a cardiovascular event, comprising: &#x2014;measuring, in a sample obtained from said subject, at least two cardiovascular risk factors: a) sPLA2 type HA mass and b) oxidized phospholipids on apolipoprotein B-IOO particles (OxPL/apoB), &#x2014;combining said measurements, the combined value of sPLA2 type HA mass and OxPL/apoB being indicative of having or a risk of having or developing a cardiovascular disease and/or cardiovascular event.

Growing community of inventors

Sand Diego, CA, United States of America

Joseph L Witztum