Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Genzyme Corporation

Mark J Graham

Rosanne M Crooke

Susan M Freier

Punit P Seth

Eric E Swayze

Thazha P Prakash

Kenneth W Dobie

Sanjay Bhanot

Kristina M Lemonidis

Andrew T Watt

Diane Tribble

Brett P Monia

Richard Theodore Lee

Marc Lim

Andrew Dibble

Pamela S Nero

Loren J Miraglia

Adam Mullick

Kristina Lemonidis Tarbet

Kristina L Lemonidis

Lex M Cowsert

Thomas A Bell

John G Geisler

Roseanne M Crooke

Steven Mah

Richard Lee

Kristina M Lemonidis Tarbet

Kristina Lemonidis-Tarbet

COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION

Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein (a) [apo(a)]. In certain embodiments, the apo(a) targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting apo(a) for use in decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) and/or Lp(a). Certain diseases, disorders or conditions related to apo(a) and/or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Compositions and methods for modulating apolipoprotein (a) expression

Disclosed herein are antisense compounds and methods for decreasing apo(a) to treat, prevent, or ameliorate diseases, disorders or conditions related to apo(a) or Lp(a). Certain diseases, disorders or conditions related to apo(a) or Lp(a) include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The antisense compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Methods and compositions for modulating apolipoprotein (a) expression

Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and/or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides.

Methods for treating hypercholesterolemia

Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing plasma lipids, plasma glucose and atherosclerotic plaques in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease or metabolic disease, or a symptom thereof.

Modulation of angiopoietin-like 3 expression

Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof.

Provided herein are oligomeric compounds with conjugate groups targeting apolipoprotein C-III (ApoCIII). In certain embodiments, the ApoCIII targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting ApoCIII for use in decreasing ApoCIII to treat, prevent, or ameliorate diseases, disorders or conditions related to ApoCIII. Certain diseases, disorders or conditions related to ApoCIII include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Compositions and methods for modulating apolipoprotein C-III expression

Disclosed herein are compositions and compounds comprising modified oligonucleotides for modulating AGT and modulating a RAAS pathway related disease, disorder and/or condition in an individual in need thereof. A RAAS pathway related disease, disorder and/or condition in an individual such as hypertension can be treated, ameliorated, delayed or prevented with the administration of antisense compounds targeted to AGT.

Compounds and methods for modulating angiotensinogen expression

Compositions and methods for modulating angiopoietin-like 3 expression

Methods and compositions for modlating apolipoprotein (A) expression

Growing community of inventors

San Clemente, CA, United States of America

Mark J Graham