Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Antisense Therapeutics Limited

Jeffrey R Crosby

Susan M Freier

C Frank Bennett

Brett P Monia

Chenguang Zhao

Hong Zhang

Andrew M Siwkowski

James G Karras

Susan Gregory

Kenneth W Dobie

Richard Theodore Lee

Huynh-Hoa Bui

Robert A MacLeod

George Tachas

Mausumee Guha

Frank C Bennett

David Tung

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of FXII RNA in a cell or subject, and in certain instances reducing the amount of FXII protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to prevent, treat, or ameliorate at least one symptom of a thromboembolic condition. Such thromboembolic conditions include deep vein thrombosis, venous or arterial thrombosis, pulmonary embolism, myocardial infarction, and stroke. Such symptoms include pain, shortness of breath, heart burn, cold sweat, fatigue, lightheadedness, dizziness, swelling, cramping, and death. Such compounds, methods, and pharmaceutical compositions are useful to prevent, treat, or ameliorate at least one symptom of hereditary angioedema.

Compounds and methods for modulating factor XII

Disclosed herein are antisense compounds and methods for decreasing Factor 11 and treating or preventing thromboembolic complications in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 11 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Antisense compounds targeting Factor 11 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism.

Modulation of factor 11 expression

Provided herein are methods, compounds, and compositions for reducing expression of KEAP1 in animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate oxidative stress or a disease, disorder or condition related to oxidative stress an animal in need. Diseases, disorders or conditions related to oxidative stress include NASH, NAFLD, asthma and insulin resistance.

Methods of modulating KEAP1

Disclosed herein are methods for decreasing Factor 12 and treating or preventing thromboembolic conditions in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 12 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, and mesenteric thrombosis. Methods for inhibiting Factor 12 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism.

Methods for modulating factor 12 expression

Disclosed herein are antisense compounds and methods for decreasing Factor 7 and treating or preventing thromboembolic complications, hyperproliferative disorders, or inflammatory conditions in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 7 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, cancer, rheumatoid arthritis, and fibrosis.

Modulation of factor 7 expression

A method for the treatment and/or prophylaxis of an animal having a respiratory disease or condition associated with airway hyperresponsiveness, eosinophilia, neutrophilia, leukocytes or overproduction of mucus and/or with the expression of integrin &#x3b1;4 comprising administering to the animal a composition comprising from. 0.001 to 1000 &#x3bc;g per kg body weight of the animal of an antisense compound targeted to a nucleic acid molecule encoding integrin &#x3b1;4.

Topical administrations of antisense compounds to VLA-4 for the treatment of respiratory conditions

Disclosed herein are compounds, compositions and methods for modulating the expression of IL-4R alpha in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders related to expression of IL 4R-&#x3b1;, airway hyperresponsiveness, and/or pulmonary inflammation.

Growing community of inventors

Carlsbad, CA, United States of America

Jeffrey R Crosby