Isis Pharmaceuticals, Inc.

William A Gaarde

Brett P Monia

Robert McKay

Pamela S Nero

Susan M Freier

Nicholas M Dean

Lex M Cowsert

Andrew T Watt

Donna T Ward

Edward Wancewicz

Mausumee Guha

C Frank Bennett

Jacqueline R Wyatt

James G Karras

Susan Gregory

Trisha Lockhart

Disclosed herein are compounds, compositions and methods for modulating the expression of hepcidin in a cell, tissue or animal or preventing, ameliorating or treating anemia. Also provided are methods for prevention, amelioration or treatment of anemia, and for increasing red blood cell count in an animal. Also provided are methods for the prevention, amelioration and/or treatment of low serum iron levels, low red blood cell count and other clinical endpoints of anemia in an animal. These methods may be achieved by administration of compounds or compositions including antisense compounds targeted to a nucleic acid that expresses hepcidin polypeptide combined with an erythropoiesis stimulating agent.

Compositions and their uses directed to hepcidin

Antisense compounds, compositions and methods are provided for modulating the expression of connective tissue growth factor. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding connective tissue growth factor. Methods of using these compounds for modulation of connective tissue growth factor expression and for treatment of diseases associated with expression of connective tissue growth factor are provided.

Antisense modulation of connective tissue growth factor expression

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.

Compositions and their uses directed to IL-4R alpha

Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase (JNK protein) are provided. Oligonucleotide are herein provided which are specifically hybridizable with nucleic acids encoding JNK1, JNK2 and JNK3, as well as other JNK proteins and specific isoforms thereof. Methods of treating animals suffering from diseases or disorders amenable to therapeutic intervention by modulating the expression of one or more JNK proteins with such oligonucleotide are also provided. Methods for the treatment and diagnosis of diseases or disorders associated with aberrant expression of one or more JNK proteins are also provided. Methods for inducing apoptosis and for treating diseases or conditions associated with a reduction in apoptosis are also provided.

Antisense oligonucleotide compositions and methods for the modulation of JNK proteins

Antisense compounds, compositions and methods are provided for modulating the expression of TERT. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding TERT. Methods of using these compounds for modulation of TERT expression and for treatment of diseases associated with expression of TERT are provided.

Antisense modulation of TERT expression

Compositions and methods for the treatment and diagnosis of diseases or conditions amenable to treatment through modulation of expression of a gene encoding a p38 mitogen-activated protein kinase (p38 MAPK) are provided. Methods for the treatment and diagnosis of diseases or conditions associated with aberrant expression of one or more p38 MAPKs are also provided.

Antisense modulation of p38 mitogen activated protein kinase expression

Antisense inhibition of tert expression

Antisense compounds, compositions and methods are provided for modulating the expression of MEKK2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding MEKK2. Methods of using these compounds for modulation of MEKK2 expression and for treatment of diseases associated with expression of MEKK2 are provided.

Antisense inhibition of MEKK2 expression

Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase (JNK protein) are provided. Oligonucleotide are herein provided which are specifically hybridizable with nucleic acids encoding JNK1, JNK2 and JNK3, as well as other JNK proteins and specific isoforms thereof. Methods of treating animals suffering from diseases or disorders amenable to therapeutic intervention by modulating the expression of one or more JNK proteins with such oligonucleotide are also provided. Methods for the treatment and diagnosis of diseases or disorders associated with aberrant expression of one or more JNK proteins are also provided. The invention is thus directed to compositions for modulating, diagnostic methods for detecting, and therapeutic methods for inhibiting, the hyperproliferation of cells and formation, development and maintenance of tumors.

Antisense compounds, compositions and methods are provided for modulating the expression of MEKK1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding MEKK1. Methods of using these compounds for modulation of MEKK1 expression and for treatment of diseases associated with expression of MEKK1 are provided.

Antisense modulation of MEKK1 expression

Antisense modulation of P38 mitogen activated protein kinase expression

Compounds, compositions and methods are provided for inhibiting FAK mediated signaling. The compositions comprise antisense compounds targeted to nucleic acids encoding FAK. Methods of using these antisense compounds for inhibition of FAK expression and for treatment of diseases, particularly cancers, associated with overexpression or constitutive activation of FAK are provided.

Antisense inhibition of focal adhesion kinase expression

Antisense oligonucleotide compositions and methods for the modulation of

Antisense compounds, compositions and methods are provided for modulating the expression of MEKK5. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding MEKK5. Methods of using these compounds for modulation of MEKK5 expression and for treatment of diseases associated with expression of MEKK5 are provided.

Growing community of inventors

Carlsbad, CA, United States of America

William A Gaarde