IP Library Granted Patent US 7,476,709
Granted Patent B2
US 7,476,709 · App. 10/512,138 · Granted Jan 13, 2009

Process for preparing oligonucleotides

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Quick Facts
Patent No.
US 7,476,709
App. No.
10/512,138
Granted
Jan 13, 2009
Kind
B2
Abstract

A process for the preparation of an oligonucleotide is provided. The process comprises the assembly of an oligonucleotide attached to a solid support, wherein the solid support is prepared by a process comprising polymerisation of a monomer which comprises a protected hydroxypolyC 2-4 alkyleneoxy chain attached to a polymerisable unit wherein the protected hydroxypolyC 2-4 alkyleneoxy chain contains from 2 to 10 C 2-4 alkyleneoxy groups and wherein the hydroxypolyC 2-4 alkyleneoxy chain is protected with an acid-labile protecting group, preferably an optionally substituted trityl group.

Claims (26)

1. In a process for the preparation of an oligonucleotide by assembly of the oligonucleotide attached to a solid support, the improvement wherein the solid support is prepared by polymerisation of a monomer which comprises a protected hydroxypolyC 2-4 alkyleneoxy chain attached to a polymerisable unit wherein the protected hydroxypolyC 2-4 alkyleneoxy chain contains from 2 to 10 C 2-4 alkyleneoxy groups and wherein the hydroxypolyC 2-4 alkyleneoxy chain is protected with a poly-aryl methane protecting group.

2. A process according to claim 1 , wherein the solid support is prepared by a polymerisation of a monomer of the following formula

wherein

R 1 is an optionally substituted ethylene group;

R 2-4 are independently hydrogen, hydrocarbyl, halogen, or hydrocarbyloxy;

R 5 is an optionally substituted trityl group; and

n is 2 to 10.

3. A process according to claim 2 , wherein R 1 is para to the group of formula R 5 —O—[C 2-4 alkylene-O]—, R 1 is an unsubstituted ethylene group, R 2-4 are each H, the C 2-4 alkylene group is —CH 2 CH 2 —and n is 4.

4. A process according to claim 1 , wherein the support is crosslinked.

5. A process according to claim 1 , wherein the oligonucleotide is assembled by phosphoramidite chemistry.

6. A process according to claim 1 , wherein the oligonucleotide is attached to the solid support via a cleavable linker.

7. A process according to claim 6 , wherein the cleavable linker is a succinyl, oxalyl or trityl linker.

8. A process according to claim 1 , further comprising cleaving the oligonucleotide from the solid support.

9. A process according to claim 8 , wherein the oligonucleotide is deprotected prior to, concomitant with, or after, cleavage from the solid support.

10. A composition of matter having the formula:

Ps-Z-Q

wherein

Ps represents a polymer obtained by polymerisation of a monomer which comprises a protected hydroxypolyC 2-4 alkyleneoxy chain attached to a polymerisable unit wherein the protected hydroxypolyC 2-4 alkyleneoxy chain contains from 2 to 10 C 2-4 alkyleneoxy groups and is protected with a poly-aryl methane protecting group;

Z represents a single bond or a cleavable linker; and

Q represents H, a nucleoside or an oligonucleotide, provided that Q is not H when Z represents a single bond.

11. A composition of matter according to claim 10 , wherein Z is a group of the formula —Y 2 -L-Y 3 , wherein Y 2 represents a single bond, —C(O)—, —C(O)NR 17 — or —C(O)O—, Y 3 represents a single bond, —C(O)—, —C(O)NR 17 —, —NR 17 —C(O)—, —C(O)O—,—O—C(O)—, —NR 17 — or —O—, R 17 is —H, a substituted or unsubstituted aliphatic group or a substituted or unsubstituted aromatic group and L is a bridging group.

12. A composition of matter according to claim 11 , wherein L is a C 2-4 alkylene group.

13. A composition of matter according to claim 12 of the formula:

wherein R X is an acid labile protecting group, R y is H, F, allyl, OMe, OCH 2 CH 2 OMe, or hydroxy protected by a base labile or silyl-protecting group, and B is H, a protected adenine, guanine, or cytosine moiety or an optionally protected thymine, uracil or hypoxanthine moiety.

14. The process of claim 1 wherein the protecting group is a trityl group, a dimethoxytrityl group or a 2-chlorotrityl group.

15. The composition of matter of claim 10 wherein the protecting group is a trityl group, a dimethoxytrityl group or a 2-chlorotrityl group.

Assignments (3)
CHANGE OF NAME Recorded Jul 12, 2012
From: AVECIA BIOTECHNOLOGY INC
To: NITTO DENKO AVECIA, INC.
Reel/Frame 028549/0910 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2007
From: AVECIA LIMITED
To: AVECIA BIOTECHNOLOGY INC.
Reel/Frame 019050/0453 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 14, 2005
From: MOODY, DAVID JOHN; WELLINGS, DONALD ALFRED; MCCORMAC, PAUL
To: AVECIA LIMITED
Reel/Frame 016916/0911 →