Method for preparing oligonucleotides

US8304532B2 · kind B2 · utility

Assignees

• Girindus AG · DE
• CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE · FR
• Universite De Montpellier · FR

Inventors

• Ilaria Adamo · Udine, IT
• Cecile Dueymes · Rodez, FR
• Andreas Schönberger · Wolfsburg, DE
• Jean-Louis Imbach · Montpellier, FR
• Albert Meyer · Pérols, FR
• François Morvan · Castelnau-le-Lez, FR
• Francoise Debart · Juvignac, FR
• Jean-Jacques Vasseur · Juvignac, FR
• Meinolf Lange · Oslo, NO
• Fritz Link · Bensberg, DE

Key dates

• Filing date: May 25, 2011
• Grant date: Nov 6, 2012
• Expiry date: May 25, 2031

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/582
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A solution phase synthesis method for preparing an oligonucleotide, wherein at least some of the reagents are solid supported. The method suitable for large-scale synthesis comprises coupling a protected compound with a nucleotide derivative having a protection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond; optionally processing the elongated oligonucleotide by capping by reaction with a solid supported capping agent and/or by oxidizing or sulfurizing by reaction of the oligonucleotide with a solid supported oxidizing or sulfurization reagent; and removing the protection group. The coupling may include reacting a 3′-protected compound of formula:with a nucleotide derivative having a 5′-protection group, or reacting a 5′-protected compound of formulawith a nucleotide derivative having a 3′-protection group.