IP Library Patent Application 13094571
Patent Application
App. No. 13/094,571

METHODS AND MEANS FOR EFFICIENT SKIPPING OF AT LEAST ONE OF THE FOLLOWING EXONS OF THE HUMAN DUCHENNE MUSCULAR DYSTROPHY GENE: 43, 46, 50-53

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Patent No.
US None
App. No.
13/094,571
Abstract

The invention relates a method wherein a molecule is used for inducing and/or promoting skipping of at least one of exon 43, exon 46, exons 50-53 of the DMD pre-mRNA in a patient, preferably in an isolated cell of a patient, the method comprising providing said cell and/or said patient with a molecule. The invention also relates to said molecule as such.

Claims (37)

1 . A molecule, which binds to a continuous stretch of at least 8 nucleotides within one of the following nucleotide sequences selected from:

(SEQ ID NO: 4)

5′-GGCGGTAAACCGUUUACUUCAAGAGCUGAGGGCAAAGCAGCCUGA

CCUAGCUCCUGGACUGACCACUAUUGG-3′

for skipping of exon 50;

(SEQ ID NO: 2)

5′AGAUAGUCUACAACAAAGCUCAGGUCGGAUUGACAUUAUUCAUAGC

AAGAAGACAGCAGCAUUGCAAAGUGCAACGCCUGUGG-3′

for skipping of exon 43

(SEQ ID NO: 3)

5′UUAUGGUUGGAGGAAGCAGAUAACAUUGCUAGUAUCCCACUUGAAC

CUGGAAAAGAGCAGCAACUAAAAGAAAAGC-3′

for skipping of exon 46;

(SEQ ID NO: 5)

5′CUCCUACUCAGACUGUUACUCUGGUGACACAACCUGUGGUUACUAA

GGAAACUGCCAUCUCCAAACUAGAAAUGCCAUCUUCCUUGAUG UUGG

AGGUAC-3′

for skipping of exon 51;

(SEQ ID NO: 6)

5′AUGCAGGAUUUGGAACAGAGGCGUCCCCAGUUGGAAGAACUCAUUA

CCGCUGCCCAAAAUUUGAAAAACAAGACCAGCAAUCAAGAGGCU-3′

for skipping of exon 52,

and

(SEQ ID NO: 7)

5′AAAUGUUAAAGGAUUCAACACAAUGGCUGGAAGCUAAGGAAAA GC

UGAGCAGGUCUUAGGACAGGCCAGAG-3′

for skipping of exon 53.

2 . A molecule according to claim 1 , wherein the molecule comprises or consists of the antisense nucleotide sequence selected from SEQ ID NO: 8-358, and/or SEQ ID NO 529-535 as depicted in tables 1 to 6.

3 . A molecule according to claim 2 , wherein the molecule comprises or consists of the antisense nucleotide sequence selected from SEQ ID NO:16, SEQ ID NO:65, SEQ ID NO:70, SEQ ID NO:91, SEQ ID NO:110, SEQ ID NO:117, SEQ ID NO:127, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:246, SEQ ID NO:299 and SEQ ID NO:357.

4 . A molecule according to claim 1 , comprising a 2′-O-alkyl phosphorothioate antisense oligonucleotide.

5 . A molecule according to claim 4 , comprising a 2′-O methyl phosphorothioate ribose.

6 . A viral-based vector, comprising an expression cassette that drives expression of a molecule as defined in claim 1 .

7 . A molecule according to claim 1 for use as a medicament, preferably for modulating splicing of the DMD pre-mRNA of a DMD or BMD patient or for the treatment of a DMD or BMD patient.

8 . A pharmaceutical composition comprising a molecule as defined in claim 1 , a pharmaceutical acceptable carrier, and optionally combined with a molecule which is able to induce or promote skipping of at least one of exon 6, 7, 11, 17, 19, 21, 43, 44, 45, 50-53, 55, 57, 59, 62, 63, 65, 66, 69, or 75 of the DMD pre-mRNA of a patient.

9 . A method for inducing and/or promoting skipping of at least one of exon 43, exon 46, and exons 50-53 of the DMD pre-mRNA in a patient, preferably in an isolated cell of a patient, the method comprising providing said cell and/or said patient with a molecule as defined in claim 1 .

10 . A method according to claim 9 , wherein an additional molecule is used which is able to induce or promote skipping of at least one of exon 6, 7, 11, 17, 19, 21, 43, 44, 45, 50-53, 55, 57, 59, 62, 63, 65, 66, 69, or 75 of the DMD pre-mRNA of a patient.

11 . A method of treating a patient with DMD or BMD comprising administering the molecule of claim 1 , wherein following administration, splicing of the DMD pre-mRNA of said patient is modulated, thereby treating said patient.

Assignments (6)
CHANGE OF NAME Recorded Sep 30, 2015
From: PROSENSA TECHNOLOGIES B.V.
To: BIOMARIN TECHNOLOGIES B.V.
Reel/Frame 036732/0042 →
CHANGE OF ADDRESS OF ASSIGNEE Recorded Feb 5, 2015
From: PROSENSA TECHNOLOGIES B.V.
To: PROSENSA TECHNOLOGIES B.V.
Reel/Frame 034916/0132 →
CHANGE OF NAME Recorded Nov 2, 2014
From: PROSENSA B.V.
To: PROSENSA HOLDING B.V.
Reel/Frame 034115/0916 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 2, 2014
From: PROSENSA HOLDING N.V.
To: PROSENSA TECHNOLOGIES B.V.
Reel/Frame 034115/0924 →
CHANGE OF NAME Recorded Nov 2, 2014
From: PROSENSA HOLDING B.V.
To: PROSENSA HOLDING N.V.
Reel/Frame 034115/0965 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 7, 2011
From: DE KIMPE, JOSEPHUS JOHANNES; PLATENBURG, GERARDUS JOHANNES; VAN DEUTEKOM, JUDITH CHRISTINA THEODORA; AARTSMA-RUS, ANNEMIEKE; VAN OMMEN, GARRIT-JAN BOUDENWIJN
To: ACADEMISCH ZIEKENHUIS LEIDEN; PROSENSA B.V.; PROSENSA TECHNOLOGIES B.V.; PROSENSA HOLDING B.V.
Reel/Frame 026556/0428 →