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:
Nov. 14, 2023

Filed:

Jun. 26, 2018
Applicant:

Roche Innovation Center Copenhagen A/s, Horsholm, DK;

Inventors:

Dennis Jul Hansen, Farum, DK;

Erik Daa Funder, Hilleroed, DK;

Attorneys:
Primary Examiner:
Int. Cl.
CPC ...
C07H 21/00 (2006.01); C07H 21/02 (2006.01); C07H 21/04 (2006.01); C07H 1/00 (2006.01);
U.S. Cl.
CPC ...
C07H 1/00 (2013.01); C07H 21/00 (2013.01); C07H 21/02 (2013.01); C07H 21/04 (2013.01);
Abstract

The present invention relates to methods of synthesis of stereodefined oligonucleotides wherein the protected 5'-hydroxy terminus of a nucleoside or oligonucleotide attached to a solid support is first unprotected, followed by coupling an oxazaphospholidine phosphoramidite monomer to the now deprotected 5′-hydroxy terminus, oxidizing the resultant phosphite triester intermediate with a sulfurizing reagent, and optionally washing the product. The method of synthesis of the present invention described above may be repeated to optionally elongate the stereodefined oligonucleotide being synthesized until the elongation cycle is intentionally terminated via deprotecting and cleavaging the resulting stereodefined oligonucleotide from the solid support. The oxazaphospholidine phosphoramidite monomer to be coupled in the present invention may optionally be chosen from Formula 1a and 1b. Generally, the present invention relates to enhanced synthesis methods wherein a single elongation cycle, optionally comprising repeated coupling and oxidation steps, results in an enhanced yield and higher purity of stereodefined phosphorothioate oligonucleotides.


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