Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Regulus Therapeutics Inc.

Sanjay Bhanot

Susan M Freier

Brett P Monia

Kenneth W Dobie

Robert McKay

Eric E Swayze

Punit P Seth

Andrew M Siwkowski

Xing-Xian Yu

Richard S Geary

Edward Wancewicz

Mark J Graham

Ravi Jain

Rosanne M Crooke

Andrew T Watt

Diane Tribble

Sanjay K Pandey

Kristina M Lemonidis

Thazha P Prakash

Huynh-Hoa Bui

Lex M Cowsert

Jacqueline R Wyatt

Christine Esau

Murielle M Veniant-Ellison

Richard A Lindberg

Kristina L Lemonidis

John G Geisler

John R Shutter

Eric G Marcusson

Michael L McCaleb

Madeline M Butler

Susan F Murray

Lynnetta Watts

Xing Xian Yu

Madelline M Butler

Robert Mckay

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

The present embodiments provide methods, compounds, and compositions for treating, preventing, or ameliorating a disease associated with excess growth hormone using antisense compounds or oligonucleotides targeted to growth hormone receptor (GHR).

Compositions and methods for modulating growth hormone receptor expression

The present embodiments provide methods, compounds, and compositions useful for inhibiting DGAT2 expression, which may be useful for treating, preventing, or ameliorating a disease associated with DGAT2.

Modulators of diacyglycerol acyltransferase 2 (DGAT2)

Provided herein are methods, compounds, and compositions for reducing expression of PTP1B mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof.

Antisense modulation of PTP1B expression

The present embodiments provide methods, compounds, and compositions for treating, preventing, ameliorating a disease associated with excess growth hormone using antisense compounds oligonucleotides targeted to growth hormone receptor (GHR).

Methods are provided for the treatment of cardiovascular or metabolic diseases characterized by elevated serum total cholesterol, elevated serum LDL-cholesterol, or elevated serum triglycerides, through the administration of an oligomeric compound which modulates the levels or activity of miR-122a. Further provided are methods for reducing hepatic steatosis or liver tissue triglyceride accumulation through the administration of an oligomeric compound which modulates the levels or activity of miR-122a. Such methods employ oligomeric compounds which hybridize with or sterically interfere with nucleic acid molecules comprising or encoding miR-122a. Such oligomeric compounds may include one or more modifications thereon, which may improve the activity, stability, or nuclease resistance of the oligomeric compound. These modified oligomeric compounds are used as single compounds or in compositions, including pharmaceutical compositions, to modulate or mimic the targeted nucleic acid comprising or encoding miR-122a.

Methods for use in modulating miR-122A

The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.

Compounds and methods for modulating gene expression

Provided herein are methods, compounds, and compositions for reducing expression of GCCR mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof.

Antisense modulation of GCCR expression

Provided herein are methods, compounds, and compositions for reducing expression of GCGR mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof.

Antisense modulation of GCGR expression

Short antisense compounds with gapmer configuration

Growing community of inventors

Carlsbad, CA, United States of America

Sanjay Bhanot