(IN201717037933) Compositions and methods for correcting limb girdle muscular dystrophy type 2c using exon skipping 机翻标题: 暂无翻译,请尝试点击翻译按钮。

源语言标题
Compositions and methods for correcting limb girdle muscular dystrophy type 2c using exon skipping
公开号/公开日
IN201717037933 A 2017-12-29 [IN201717037933] / 2017-12-29
申请号/申请日
2017IN-17037933 / 2017-10-26
发明人
Elizabeth MCNALLY;Eugene WYATT;
申请人
NORTHWESTERN UNIVERSITY;UNIVERSITY OF CHICAGO;
主分类号
IPC分类号
C07H-021/00C12N-015/11C12N-015/113
摘要
(IN201717037933) The invention is directed to one or more antisense polynucleotides and their use in pharmaceutical compositions in a strategy to induce exon skipping in the ? sarcoglycan gene in patients suffering from Limb Girdle Muscular Dystrophy 2C (LGMD2C) or in patients at risk of such a disease.  The invention also provides methods of preventing or treating muscular dystrophy e.g.  LGMD2C by exon skipping in the gamma sarcoglycan gene using antisense polynucleotides.  Accordingly in some aspects the invention provides an isolated antisense oligonucleotide wherein the oligonucleotide specifically hybridizes to an exon target region of a ? sarcoglycan RNA.  In another aspect the the invention provides a method of inducing exon skipping of a gamma sarcoglycan RNA comprising delivering an antisense oligonucleotide or a composition to a cell.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2015US-62144712 2015-04-08
主权利要求
(IN201717037933)  1. An isolated antisense oligonucleotide (AON) selected from the group consisting of oligonucleotides listed in Table 2. 2. The antisense oligonucleotide of claim 1, wherein the oligonucleotide cannot form an RNase H substrate. 3. The antisense oligonucleotide of claim 1 or claim 2, comprising a modified oligonucleotide backbone. 4. The antisense oligonucleotide of claim 3, wherein the modified oligonucleotide backbone comprises a modified moiety substituted for the sugar of at least one of the oligonucleotides. 5. The antisense oligonucleotide of claim 4, wherein the modified moiety is a Morpholino. 6. The antisense oligonucleotide of any one of claims 3-5, wherein the modified oligonucleotide backbone of at least one of the oligonucleotides comprises at least one modified internucleotide linkage. 7. The antisense oligonucleotide of claim 6, wherein the modified internucleotide linkage is a tricyclo-DNA (tc-DNA) modification. 8. The antisense oligonucleotide of claim 6, wherein the modified internucleotide linkage comprises a modified phosphate. 9. The antisense oligonucleotide of claim 8, wherein the modified phosphate is selected from the group consisting of a methyl phosphonate, a methyl phosphorothioate, a phosphoromorpholidate, a phosphoropiperazidate and a phosphoroamidate. 10. The antisense oligonucleotide of any one of claims 3-9, wherein the Oligonucleotide is a 2'-0-methyl-oligoribonucleotide. 11. The antisense oligonucleotide of any one of claims 1-10, wherein the oligonucleotide comprises a peptide nucleic acid. 12. The antisense oligonucleotide of any one of claims 1-11, wherein the oligonucleotide is chemically linked to one or more conjugates that enhance the activity, cellular distribution, or cellular uptake of the antisense oligonucleotide. 13. The antisense oligonucleotide of claim 12, wherein the oligonucleotide is chemically linked to a polyethylene glycol molecule. 14. The antisense oligonucleotide of claim 12 or claim 13 wherein the conjugate is a peptide that enhances cellular uptake. 15. The antisense oligonucleotide of claim 14 wherein the peptide is selected from the group consisting of a nuclear localization signal (NLS), HIV-1 TAT protein, a peptide comprising an integrin binding domain, oligolysine, adenovirus fiber protein and a peptide comprising a receptor-mediated endocytosis (RME) domain. 16. A pharmaceutical composition, comprising the antisense oligonucleotide of any one of claims 1-15 and a physiologically compatible buffer. 17. A method of inducing exon-skipping of a gamma sarcoglycan RNA, comprising delivering to a cell the antisense oligonucleotide of any one of claims 1-14 or the composition of claim 15, thereby inducing exon-skipping of the gamma sarcoglycan RNA. 18. The method of claim 17, wherein the cell is a human muscle cell. 19. The method of claim 18, wherein the human muscle cell is in a patient. 20. The method of claim 19, wherein the patient has muscular dystrophy. 21. The method of claim 20, wherein the muscular dystrophy is Limb Girdle Muscular Dystrophy type 2C (LGMD2C). 22. A method of ameliorating Limb Girdle Muscular Dystrophy type 2C (LGMD2C) in a patient in need thereof comprising the step of administering to the patient a therapeutically effective amount of the composition of claim 16, thereby ameliorating LGMD2C. 23. A method of inhibiting the progression of dystrophic pathology associated with LGMD2C in a patient in need thereof comprising the step of administering to the patient a therapeutically effective amount of the composition of claim 16, thereby inhibiting the progression of dystrophic pathology. 24. A method of improving muscle function in a patient suffering from Limb Girdle Muscular Dystrophy type 2C (LGMD2C) comprising the step of administering to the patient a therapeutically effective amount of the composition of claim 16, thereby improving muscle function. 25. The method of claim 24 wherein the muscle is a cardiac muscle. 26. The method of claim 24 or claim 25 wherein the improvement in muscle function is an improvement in muscle strength. 27. The method of claim 26 wherein the improvement in muscle strength is an improvement in respiratory muscle strength. 28. The method of claim 24 or claim 25 wherein the improvement in muscle function is an improvement in motor stability, improved upper limb strength, or improved cardiac function. 29. The method of claim 28 wherein the improvement in motor stability results in an improved six-minute walk test by the patient relative to a previously measured six-minute walk test by that patient. 30. A kit comprising the antisense oligonucleotide of any one of claims 1-15, optionally in a container, and a package insert, package label, instructions or other labeling. 31. The kit of claim 30, further comprising an additional oligonucleotide, wherein the additional oligonucleotide specifically hybridizes to an exon in a gamma sarcoglycan RNA.
法律状态
(IN201717037933) LEGAL DETAILS FOR IN201717037933  Actual or expected expiration date=2037-10-26    Legal state=ALIVE    Status=PENDING     Event publication date=2017-10-26  Event code=IN/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=IN IN201717037933  Application date=2017-10-26  Standardized application number=2017IN-17037933     Event publication date=2017-12-29  Event code=IN/A  Event indicator=Pos  Event type=Examination events  Application laid open  Publication country=IN  Publication number=IN201717037933  Publication stage Code=A  Publication date=2017-12-29  Standardized publication number=IN201717037933
专利类型码
A
国别省市代码
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