Ionis Pharmaceuticals, Inc.

Isis Pharmaceuticals, Inc.

Astrazeneca Ab

Lonis Pharmaceuticals, Inc.

Garth A Kinberger

Eric E Swayze

Thazha P Prakash

Balkrishen Bhat

Walter F Lima

Punit P Seth

Christine Esau

Michael T Migawa

W Brad Wan

Guillermo Vasquez

Brett P Monia

Martin A Maier

Richard Holmes Griffey

Stanley T Crooke

Richard Theodore Lee

Eric G Marcusson

Charles Allerson

Jinghua Yu

Shalini Andersson

Eva Carina Ämmälä

Daniel Laurent Knerr

Maria Astrid Ölwegård-Halvarsson

Eric Valeur

Sayten P Patel

William John Drury, Iii

Satyen P Patel

Heather Murray

The present embodiments provide compounds and methods for targeting cells expressing GLP-1 receptor.

GLP-1 receptor ligand moiety conjugated oligonucleotides and uses thereof

Oligonucleotides, chemically-modified oligonucleotides, and oligonucleotide-conjugate complexes for use in research, diagnostics, and/or therapeutics are described herein. In some embodiments, oligonucleotides comprising a stabilized phosphate moiety covalently attached to the 5'-terminal nucleoside are provided.

Oligomer-conjugate complexes and their use

Provided herein are improved methods for the synthesis of reactive conjugate clusters and intermediates used in such methods. In particular, improvements are provided that enhance the synthesis of reactive conjugate clusters by reducing the number of synthetic steps required. The reactive conjugate clusters prepared using the improved methods don't include any transacylation impurities that are formed using existing methods. The improved methods also provide an increase in overall yield and a cost benefit over existing methods.

Method for synthesis of reactive conjugate clusters

The present invention provides oligomeric compounds and uses thereof. In certain embodiments, such oligomeric compounds are useful as antisense compounds. Certain such antisense compounds are useful as RNase H antisense compounds or as RNAi compounds.

Oligomeric compounds and methods

Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapeutic index. Further provided are methods for selectively modulating miRNA activating in a cell.

Oligomeric compounds and compositions for the use in modulation of micrornas

Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapeutic index. Further provided are methods for selectively modulating miRNA activing in a cell.

Oligomeric compounds and compositions for the use in modulation of target nucleic acids

Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapeutic index. Further provided are methods for selectively modulating miRNA activity in a cell.

Oligomeric compounds and compositions for the use in modulation of microRNAs

The activated oligomer compounds described herein are capable of forming bio-reversible covalent bonds with plasma proteins, in particular with human serum albumin. The plasma protein-oligomer complexes of the present invention exhibit enhanced cellular entry and significantly enhanced serum half-life.

Oligomers comprising activated disulfides which bind to plasma proteins and their use for delivery to cells

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San Diego, CA, United States of America

Garth A Kinberger