Ionis Pharmaceuticals, Inc.

Isis Pharmaceuticals, Inc.

Guillermo Vasquez

Eric E Swayze

Punit P Seth

Thazha P Prakash

Michael T Migawa

Garth A Kinberger

W Brad Wan

Jinghua Yu

Balkrishen Bhat

Charles Allerson

Jie Xia

Sayten P Patel

Satyen P Patel

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 compounds and methods of using them for preparing bicyclic nucleosides. The bicyclic nucleosides are useful for preparing chemically modified oligomeric compounds. Oligomeric compounds comprising these bicyclic nucleosides have enhanced properties such as increased nuclease resistance.

Compounds and methods for synthesis of bicyclic nucleic acid analogs

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Oceanside, CA, United States of America

Guillermo Vasquez