The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
May. 07, 2019

Filed:

Mar. 30, 2018
Applicant:

Wave Life Sciences Ltd., Singapore, SG;

Inventors:

Gregory L. Verdine, Boston, MA (US);

Meena, Belmont, MA (US);

Naoki Iwamoto, Brighton, MA (US);

David Charles Donnell Butler, Medford, MA (US);

Assignee:

WAVE LIFE SCIENCES LTD., Singapore, SG;

Attorneys:
Primary Examiner:
Int. Cl.
CPC ...
A61K 31/66 (2006.01); A61K 31/70 (2006.01); C07H 13/04 (2006.01); C07H 21/04 (2006.01); C07C 309/66 (2006.01); C07D 295/108 (2006.01);
U.S. Cl.
CPC ...
C07H 21/04 (2013.01); A61K 31/66 (2013.01); A61K 31/70 (2013.01); C07C 309/66 (2013.01); C07D 295/108 (2013.01); C07H 13/04 (2013.01);
Abstract

The present application, among other things, provides technologies, e.g., reagents, methods, etc. for preparing oligonucleotides comprising phosphorothiotriesters linkages. In some embodiments, provided methods comprise reacting an H-phosphonate of structure Ia or Ib with a silylating reagent to provide a silyloxyphosphonate, and reacting the silyloxyphosphonate with a thiosulfonate reagent of structure IIa or IIb to provide an oligonucleotide of structure IIIa or IIIb. In some embodiments, provided methods comprise reacting an H-phosphonate of structure Ic with a silylating reagent to provide a silyloxyphosphonate, reacting the silyloxyphosphonate with a bis(thiosulfonate) reagent of structure IVc to provide a phosphorothiotriester comprising a thiosulfonate group of structure Vc, and then reacting the phosphorothiotriester comprising a thiosulfonate group of structure Vc with a nucleophile of structure VIc to provide an oligonucleotide of structure IIIc. In some embodiments, the present application provides a thiosulfonate reagent of structure IIa:


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