Isis Pharmaceuticals, Inc.

Excaliard Pharmaceuticals, Inc.

Gregory E Hardee

Phillip Dan Cook

David J Ecker

Lloyd G Tillman

Muthiah Manoharan

Rahul C Mehta

Ching-Leou Teng

Michael V Templin

Richard S Geary

Yali Jennifer Tsai

Nicholas M Dean

James G Karras

Niall O'Donnell

J Gordon Foulkes

Susan Weinbach

Leroy Young

Mark Jewell

Randy Howard

Arthur Levin

Lincoln Krochmal

Sujatha Dokka

Scott Cooper

Susan Kelly

Susan P Weinbach

This invention provides methods of preventing formation of, or treating, fibrotic lesions, including skin scars such as keloids and hypertrophic scars which comprise administering to the subject by one or more injection a compound which comprises a modified oligonucleotide, such as a modified antisense oligonucleotide, siRNA, or oligodeoxyribonucleotide, which inhibits expression of protein involved in fibrosis. Dosing of the antisense using an intradermal threading technique is also described.

Method of treating keloids or hypertrophic scars using antisense compounds targeting connective tissue growth factor (CTGF)

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

The present invention relates to compositions and methods which enhance the delivery of nucleic acids and other nucleosidic moieties via topical routes of administration. The invention relates to the use of an aqueous solution to preferentially deliver nucleic acids preferentially to hair follicles. The invention relates to a method of inhibiting hair growth comprising administration of a nucleic acid preferentially to a hair follicle.

Compositions and methods for topical delivery of oligonucleotides

The present invention relates to compositions and methods which enhance the delivery of oligonucleotides and other nucleosidic moieties via topical routes of administration. Preferred compositions include liposomes or penetration enhancers for the delivery of such moieties to dermal and/or epidermal tissue in an animal for investigative, therapeutic or prophylactic purposes.

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

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Rancho Sante Fe, CA, United States of America

Gregory E Hardee