Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Genzyme Corporation

Carlsbad

Ionis Pharmacueticals, Inc.

Kastle Therapeutics, LLC

Richard S Geary

Eric E Swayze

Brett P Monia

Punit P Seth

Sanjay Bhanot

Rosanne M Crooke

Robert McKay

Andrew M Siwkowski

Edward Wancewicz

Zhengrong Yu

Nicholas J Viney

Yanfeng Wang

Gregory E Hardee

Rahul C Mehta

Diane Tribble

Lloyd G Tillman

Mark K Wedel

Michael V Templin

Susan Weinbach

Randy Howard

Arthur Levin

Susan P Weinbach

Rudy Gunawan

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.

Modulating apolipoprotein (A) expression

Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein (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.

Modulating apolipoprotein (a) expression

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

Methods for long-term lowering of lipid levels in human subjects and for the treatment of conditions associated with elevated LDL-cholesterol and elevated ApoB are provided.

Administering antisense oligonucleotides complementary to human apolipoprotein B

Short antisense compounds with gapmer configuration

Compounds and methods for modulating expression of DGAT2

Compounds and methods for modulating expression ApoB

Compounds and methods for modulating expression of PTP1B

Compounds and methods for modulating expression of GCCR

Compounds and methods for modulating expression of SGLT2

Compounds and methods for modulating expression of GCGR

Compounds and methods for modulating expression of PCSK9

Delayed release oral pharmaceutical formulations and methods for enhanced intestinal drug absorption. The formulation comprises a first population of carrier particles comprising a drug and a penetration enhancer which are released at a first location in the intestine, and a second population of carrier particles comprising a penetration enhancer and a delayed release coating or matrix. This penetration enhancer is released at a second location in the intestine downstream from the first location and enhances absorption of the drug when it reaches the second location.

Pulsatile release compositions and methods for enhanced intestinal oligonucleotide drug absorption

Pharmaceutical compositions comprising sterically stabilized liposomes containing antisense oligonucleotides are provided for the modulation of expression of the human ras gene in both the normal (wildtype) and activated (mutant) forms.

Liposomal oligonucleotide compositions for modulating RAS gene expression

Growing community of inventors

Carlsbad, CA, United States of America

Richard S Geary