Details for Patent: 9,528,109

Title:	Methods and means for efficient skipping of exon 45 in duchenne muscular dystrophy pre-mRNA
Abstract:	The invention relates to a method for inducing or promoting skipping of exon 45 of DMD pre-mRNA in a Duchenne Muscular Dystrophy patient, preferably in an isolated (muscle) cell, the method comprising providing an isolated muscle cell with a molecule that binds to a continuous stretch of at least 21 nucleotides within the exon. The invention further relates to such molecule used in the method.
Inventor(s):	De Kimpe; Josephus Johannes (Utrecht, NL), Rus; Adriana Marie (Hoofddorp, NL), Platenburg; Gerard Johannes (Voorschoten, NL), Van Deutekom; Judith Christina Theodora (Dordrecht, NL), Van Ommen; Garrit-Jan Boudewijn (Amsterdam, NL)
Assignee:	BioMarin Technologies B.V. (Leiden, NL) Academisch Ziekenhuis Leiden (Leiden, NL)
Filing Date:	Nov 14, 2014
Application Number:	14/542,183
Claims:	1. An antisense oligonucleotide whose base sequence consists of the base sequence of 5 'UUUGCCGCUGCCCAAUGCCAUCCUG-3' (SEQ ID: NO: 3), said oligonucleotide comprising a modification. 2. The oligonucleotide of claim 1, comprising a phosphorodiamidate morpholino oligomer (PMO). 3. The oligonucleotide of claim 1, wherein said oligonucleotide comprises a locked nucleic acid (LNA). 4. The antisense oligonucleotide of claim 1 wherein the oligonucleotide comprises a modified base. 5. The antisense oligonucleotide of claim 1 wherein the oligonucleotide comprises a modified sugar moiety. 6. The antisense oligonucleotide of claim 1 wherein the oligonucleotide comprises a modified internucleoside linkage. 7. The oligonucleotide of claim 1 wherein said oligonucleotide comprises a phosphorothioate internucleoside linkage and a 2'-O-alkyl substituted ribose moiety. 8. The oligonucleotide of claim 5, wherein the modified sugar moiety is selected from the group consisting of: a ribose that is mono- or di-substituted at the 2', 3', and/or 5' position. 9. The oligonucleotide of claim 8, wherein the ribose is a 2'-O-substituted ribose. 10. The oligonucleotide of claim 9, wherein the ribose is a 2'-O-methyl ribose. 11. The oligonucleotide of claim 6, said oligonucleotide comprising a modified backbone such that all of internucleoside linkages of said oligonucleotide are modified. 12. The oligonucleotide of claim 11, said internucleoside linkages comprising phosphorothioate. 13. The oligonucleotide of claim 11, said internucleoside linkages comprising a phosphorodiamidate morpholino oligomer (PMO). 14. The oligonucleotide of claim 1 said modification comprising a peptide nucleic acid, and/or locked nucleic acid. 15. The oligonucleotide of claim 11, wherein said backbone is selected from the group consisting of a morpholino backbone, a carbamate backbone, a siloxane backbone, a sulfide backbone, a sulfoxide backbone, a sulfone backbone, a formacetyl backbone, a thioformacetyl backbone, a methyleneformacetyl backbone, a riboacetyl backbone, an alkene containing backbone, a sulfamate backbone, a sulfonate backbone, a sulfonamide backbone, a methyleneimino backbone, a methylenehydrazino backbone and an amide backbone. 16. The antisense oligonucleotide of claim 1 wherein said oligonucleotide is capable of inducing skipping of exon 45 by at least 50%. 17. The antisense oligonucleotide of claim 16, wherein said oligonucleotide is capable of inducing skipping of exon 45 by at least 60%. 18. The antisense oligonucleotide of claim 17, wherein said oligonucleotide is capable of inducing skipping of exon 45 by at least 70%. 19. The antisense oligonucleotide of claim 18, wherein said oligonucleotide is capable of inducing skipping of exon 45 by at least 80%. 20. The antisense oligonucleotide of claim 19, wherein said oligonucleotide is capable of inducing skipping of exon 45 by at least 90%. 21. A viral-based vector comprising an expression cassette comprising a nucleotide sequence encoding the oligonucleotide of claim 1. 22. A pharmaceutical composition comprising the oligonucleotide of claim 1, and a pharmaceutically acceptable carrier. 23. The pharmaceutical composition of claim 1, further comprising an antisense oligonucleotide which induces or promotes skipping of exon 7, 44, 46, 51, 53, 59, or 67 of dystrophin pre-mRNA of a patient.