Isis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Sequenom, Inc.

Variagenics, Inc.

Charles Allerson

Eric E Swayze

Balkrishen Bhat

Thazha P Prakash

Richard Holmes Griffey

Muthiah Manoharan

Punit P Seth

Brenda F Baker

Andrew M Siwkowski

Prasad Dande

Gregory Lawrence Verdine

Eric G Marcusson

Anne Bettina Eldrup

Vincent P Stanton, Jr

Tomohiko Kawate

Jia Liu Wolfe

Michael T Migawa

Garth A Kinberger

Jie Xia

Guillermo Vasquez

Ann B Eldrup

Anne B Eldrup

The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.

Compositions comprising alternating 2'-modified nucleosides for use in gene modulation

Provided herein are novel 5'-(S)&#x2014;CHsubstituted bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, the furanose ring of each of the novel 5&#x2032;-(S)&#x2014;CHsubstituted bicyclic nucleosides includes a 2&#x2032; to 4&#x2032; bridging group. The 5&#x2032;-(S)&#x2014;CHsubstituted bicyclic nucleosides are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as for example increasing the binding affinity. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom

The present disclosure describes tetrahydropyran nucleoside analogs, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, tetrahydropyran nucleoside analogs are provided, having one or more chiral substituents, that are useful for enhancing properties of oligomeric compounds including nuclease resistance and binding affinity. In some embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

Tetrahydropyran nucleic acid analogs

Provided herein are novel base modified bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, novel pyrimidine bicyclic nucleosides are provided wherein each pyrimidine base is substituted at the 5 position with an optionally substituted, aromatic or heteroaromatic ring system comprising from 5 to 7 ring atoms selected from C, N, O and S. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

Base modified bicyclic nucleosides and oligomeric compounds prepared therefrom

The present invention provides oligomeric compounds having sufficient complementarity to hybridize to a nucleic acid target and methods for their use in modulating gene expression. In one embodiment the oligomeric compounds comprise double stranded constructs wherein one of the strands capable of hybridizing to a nucleic acid target, and has a plurality of modified ribofuranosyl nucleosides at defined locations. The presence of modifications at such defined positions greatly enhances the properties of the corresponding compositions.

Positionally modified siRNA constructs

Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modification comprising a polycyclic sugar surrogate. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleoside of the oligomer has a polycyclic sugar surrogate modification.

Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation

The present invention provides modified oligomeric compounds and compositions of oligomeric compounds for use in the RNA interference pathway of gene modulation. The modified oligomeric compounds include siRNA and asRNA having at least one affinity modification.

Oligomeric compounds comprising 4'-thionucleosides for use in gene modulation

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San Diego, CA, United States of America

Charles Allerson