Process for the manufacture of oligonucleotides
AssigneeGirindus America, Inc.
InventorsTadeusz Krzysztof Wyrzykiewicz, Hagen Cramer, Huihe Zhu, Kevin James Finn
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Abstract
A process for manufacturing an oligonucleotide which comprises removing β-eliminating phosphorus-protecting groups, in particular β-cyanoethyl protective groups from a protected oligonucleotide, wherein said removing comprises contacting the protected oligonucleotide with an amine solution in a solvent which preferably does not consist of pyridine, wherein the conjugate acid of the amine has preferably a pKa of greater than 11.5, and wherein the concentration of the amine in the solution is less than 0.5 mole/liters.
Claims22
A process for manufacturing an oligonucleotide which comprises removing β-eliminating phosphorus-protecting group from a protected oligonucleotide, wherein said removing comprises contacting the protected oligonucleotide with an amine solution in a solvent which does not consist of pyridine, wherein the amine has a conjugate acid with a pKa greater than 11.5, and wherein the concentration of the amine in the solution is less than 0.5 mole/liters.
A process for manufacturing an oligonucleotide selected from the group consisting of BNA, LNA, ENA, UNA, and derivatives thereof, which comprises at least a step of removing β-eliminating phosphorus-protecting group from a protected BNA-, LNA-, ENA- or UNA-oligonucleotide, wherein said removing comprises contacting the protected oligonucleotide with an amine solution in a solvent which does not consist of pyridine, wherein the amine has a the conjugate acid with a pKa greater than 11.5.
canceled
A process for manufacturing an oligonucleotide which comprises removing β-eliminating phosphorus-protecting groups from a protected oligonucleotide, wherein said removing comprises contacting the protected oligonucleotide with an amine solution in a solvent which does not consist of pyridine, wherein the amine has a conjugate acid with a pKa from 8 to 11.5, and wherein the concentration of the amine in the solution is less than 0.5 mole/liters.
Dependencies are inferred from the claim text.