Ionis Pharmaceuticals, Inc.

Dana Chreng

Michael T Migawa

Provided herein are methods for the synthesis of oligomeric compounds wherein removal of the 5'-terminal trityl group is performed at reduced temperature and lower pH relative to standard methods. In certain embodiments, the present methods provide detritylated oligomeric compounds having a reduced percentage of depurination relative to the same detritylated oligomeric compounds prepared using standard methods. In certain embodiments, the present methods provide detritylated oligomeric compounds with increased purity relative to the same detritylated oligomeric compounds prepared using standard methods. In certain embodiments, the present methods provide an increased rate of detritylation compared to standard methods.

Method for solution phase detritylation of oligomeric compounds

Provided herein are methods for removal of monomethoxytrityl groups from oligomeric compounds comprising terminally linked monomethoxytrityl protected amino groups. The present methods differ from standard methods for 5'-dimethoxytrityl removal from oligonucleotides in that the present methods are performed at elevated temperatures and higher pH. In certain embodiments, the present methods provide detritylated oligomeric compounds having a reduced percentage of depurination relative to the same detritylated oligomeric compounds prepared using standard methods. In certain embodiments, the present methods provide an increased rate of detritylation compared to standard methods. In certain embodiments, the modification of the final detritylation step results in an improved yield.

Provided herein are methods for the synthesis of oligomeric compounds wherein removal of the 5'-terminal trityl group is performed at reduced temperature and lower pH relative to standard methods. In certain embodiments, the present methods provide detritylated oligomeric compounds having a reduced percentage of depurination relative to the same detritylated oligomeric compounds prepared using standard methods. In certain embodiments, the present methods provide detritylated oligomeric compounds with increased purity relative to the same detritylated oligomeric compounds prepared using standard methods. In certain embodiments, the present method provide an increased rate of detritylation compared to standard methods.

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San Marcos, CA, United States of America

Dana Chreng