Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Smithkline Beecham Corporation

Lloyd G Tillman

Gregory E Hardee

Muthiah Manoharan

Phillip Dan Cook

David J Ecker

Ching-Leou Teng

Bret A Coldren

Marc Lim

Andrew Dibble

Richard S Geary

Susan Weinbach

Arup K Roy

Susan P Weinbach

The present disclosure provides compositions comprising an antisense oligonucleotide and one or more excipients that modulates viscosity, turbidity or both viscosity and turbidity. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity are provided. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low turbidity are provided. In certain embodiments, pharmaceutical compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity and turbidity are provided.

Antisense oligonucleotide compositions

The present invention relates to compositions and methods which enhance the local and systemic uptake and delivery of oligonucleotides and nucleic acids via non-parenteral routes of administration. Pharmaceutical compositions comprising oligonucleotides disclosed herein include, for systemic delivery, emulsion and microemulsion formulations for a variety of applications and oral dosage formulations. It has also surprisingly been discovered that oligonucleotides may be locally delivered to colonic sites by rectal enemas and suppositories in simple solutions, e.g., neat or in saline. Such pharmaceutical compositions of oligonucleotides may further include one or more penetration enhancers for the transport of oligonucleotides and other nucleic acids across mucosal membranes. The compositions and methods of the invention are utilized to effect the oral, buccal, rectal or vaginal administration of an antisense oligonucleotide to an animal in order to modulate the expression of a gene in the animal for investigative, therapeutic, palliative or prophylactic purposes.

Compositions and methods for non-parenteral delivery of oligonucleotides

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 formulations containing HIV protease inhibitors, specifically including 3S-&lsqb;3R*(1R*,2S*)&rsqb;-&lsqb;3-&lsqb;&lsqb;(4-aminophenyl)sulphonyl&rsqb;(2-methylpropyl)-amino&rsqb;-2-hydroxy-1-phenylmethyl)propyl&rsqb;carbamic acid, tetrahydro-3-furanyl ester (alternatively known as VX 478 or 141W94), and a tocopherol, and their use in medical therapy are described.

Pharmaceutical formulations

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Oceanside, CA, United States of America

Lloyd G Tillman