Title:
OLIGOMERIC NUCLEIC ACID MOLECULE AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2020/135677
Kind Code:
A1
Abstract:
Provided are a small-activating nucleic acid molecule for treating spinal muscular atrophy, and an application thereof. The small-activating nucleic acid molecule comprises a sense nucleic acid strand and an antisense nucleic acid strand, wherein the sense nucleic acid chain and the antisense nucleic acid chain are respectively oligonucleotide chains having the length of 16-35 nucleotides, and one of nucleotide chains has at least 75% base homology or complementarity with a target selected from a target-gene SMN2 promoter region. Also provided are a pharmaceutical composition comprising the small-activating nucleic acid molecule and an optional medicinal carrier, and a method for up-regulation of an expression of the target gene in a cell and treatment of a disease caused by underexpression of the target gene by using the small-activating nucleic acid molecule or the pharmaceutical composition comprising the small-activating nucleic acid molecule.
Inventors:
LI LONGCHENG (CN)
KANG MOORIM (CN)
KANG MOORIM (CN)
Application Number:
PCT/CN2019/129025
Publication Date:
July 02, 2020
Filing Date:
December 27, 2019
Export Citation:
Assignee:
RACTIGEN THERAPEUTICS (CN)
International Classes:
C12N15/113; A61K48/00; A61P21/00; C07H21/00
Domestic Patent References:
| WO2017087486A1 | 2017-05-26 | |||
| WO2018017991A1 | 2018-01-25 | |||
| WO2008095357A1 | 2008-08-14 |
Foreign References:
| CN104583398A | 2015-04-29 | |||
| US20070292408A1 | 2007-12-20 | |||
| CN104630219A | 2015-05-20 | |||
| CN106032532A | 2016-10-19 | |||
| US9669109B1 | 2017-06-06 |
Other References:
WOO, C.J.: "Gene activation of SMN by selective disruption of lncRNA-me- diated recruitment of PRC2 for the treatment of spinal muscular atrophy", PNAS, 13 February 2017 (2017-02-13), XP055355645
SAMBROOK ET AL.: "Molecular Cloning: Laboratory Manual", 1989, COLD SPRING HARBOR LABORATORY PRESS
HUA ET AL., PLOSBIOL, vol. 5, no. 4, 2007, pages e73
KOLB SJCOFFEY CSYANKEY JWKROSSCHELL KARNOLD WD ET AL.: "Natural history of infantile-onset spinal muscular atrophy", ANN NEUROL, vol. 82, 2017, pages 883 - 91
SUGARMAN EANAGAN NZHU HAKMAEV VRZHOU Z ET AL.: "Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens", EUR J HUM GENET, vol. 20, 2012, pages 27 - 32
ZHANG CLANG Q: "New Therapeutic medication for treating Spinal Muscular Atrophy— -SPINRAZA", JOURNAL OF CLINICAL PHAMACOLOGY, vol. 15, 2017, pages 83 - 4
LEFEBVRE SBURGLEN LREBOULLET SCLERMONT OBURLET P ET AL.: "Identification and characterization of a spinal muscular atrophy-determining gene", CELL, vol. 80, 1995, pages 155 - 65
LORSON CLHAHNEN EANDROPHY EJWIRTH B: "A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy", PROC NATL ACAD SCI USA, vol. 96, 1999, pages 6307 - 11, XP002153155, DOI: 10.1073/pnas.96.11.6307
MONANI URLORSON CLPARSONS DWPRIOR TWANDROPHY EJ ET AL.: "A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2", HUM MOL GENET, vol. 8, 1999, pages 1177 - 83, XP002542964, DOI: 10.1093/hmg/8.7.1177
HUA YSAHASHI KHUNG GRIGO FPASSINI MA ET AL.: "Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model", GENES DEV, vol. 24, 2010, pages 1634 - 44, XP055038360, DOI: 10.1101/gad.1941310
HUA YSAHASHI KRIGO FHUNG GHOREV G ET AL.: "Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model", NATURE, vol. 478, 2011, pages 123 - 6, XP055038358, DOI: 10.1038/nature10485
NARYSHKIN NAWEETALL MDAKKAANARASIMHAN JZHAO X ET AL.: "Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy", SCIENCE, vol. 345, 2014, pages 688 - 93, XP055809115, DOI: 10.1126/science.1250127
PALACINO JSWALLEY SESONG CCHEUNG AKSHU L ET AL.: "SMN2 splice modulators enhance Ul-pre-mRNA association and rescue SMA mice", NAT CHEM BIOL, vol. 11, 2015, pages 511 - 7, XP055520469, DOI: 10.1038/nchembio.1837
MICHELSON DCIAFALONI EASHWAL SLEWIS ENARAYANASWAMI P ET AL.: "Evidence in focus: Nusinersen use in spinal muscular atrophy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology", NEUROLOGY, 2018
AVILA AMBURNETT BGTAYE AAGABANELLA FKNIGHT MA ET AL.: "Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy", J CLIN INVEST, vol. 117, 2007, pages 659 - 71, XP055449735, DOI: 10.1172/JCI29562
SOMERS ERIESSLAND MSCHREML JWIRTH BGILLINGWATER THPARSON SH: "Increasing SMN levels using the histone deacetylase inhibitor SAHA ameliorates defects in skeletal muscle microvasculature in a mouse model of severe spinal muscular atrophy", NEUROSCI LETT, vol. 544, 2013, pages 100 - 4, XP028558009, DOI: 10.1016/j.neulet.2013.03.052
SWOBODA KJSCOTT CBCRAWFORD TOSIMARD LRREYNA SP ET AL.: "SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy", PLOS ONE, vol. 5, 2010, pages e 12140
KISSEL JTSCOTT CBREYNA SPCRAWFORD TOSIMARD LR ET AL.: "SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy", PLOS ONE, vol. 6, 2011, pages e21296o
See also references of EP 3904517A4
SAMBROOK ET AL.: "Molecular Cloning: Laboratory Manual", 1989, COLD SPRING HARBOR LABORATORY PRESS
HUA ET AL., PLOSBIOL, vol. 5, no. 4, 2007, pages e73
KOLB SJCOFFEY CSYANKEY JWKROSSCHELL KARNOLD WD ET AL.: "Natural history of infantile-onset spinal muscular atrophy", ANN NEUROL, vol. 82, 2017, pages 883 - 91
SUGARMAN EANAGAN NZHU HAKMAEV VRZHOU Z ET AL.: "Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens", EUR J HUM GENET, vol. 20, 2012, pages 27 - 32
ZHANG CLANG Q: "New Therapeutic medication for treating Spinal Muscular Atrophy— -SPINRAZA", JOURNAL OF CLINICAL PHAMACOLOGY, vol. 15, 2017, pages 83 - 4
LEFEBVRE SBURGLEN LREBOULLET SCLERMONT OBURLET P ET AL.: "Identification and characterization of a spinal muscular atrophy-determining gene", CELL, vol. 80, 1995, pages 155 - 65
LORSON CLHAHNEN EANDROPHY EJWIRTH B: "A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy", PROC NATL ACAD SCI USA, vol. 96, 1999, pages 6307 - 11, XP002153155, DOI: 10.1073/pnas.96.11.6307
MONANI URLORSON CLPARSONS DWPRIOR TWANDROPHY EJ ET AL.: "A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2", HUM MOL GENET, vol. 8, 1999, pages 1177 - 83, XP002542964, DOI: 10.1093/hmg/8.7.1177
HUA YSAHASHI KHUNG GRIGO FPASSINI MA ET AL.: "Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model", GENES DEV, vol. 24, 2010, pages 1634 - 44, XP055038360, DOI: 10.1101/gad.1941310
HUA YSAHASHI KRIGO FHUNG GHOREV G ET AL.: "Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model", NATURE, vol. 478, 2011, pages 123 - 6, XP055038358, DOI: 10.1038/nature10485
NARYSHKIN NAWEETALL MDAKKAANARASIMHAN JZHAO X ET AL.: "Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy", SCIENCE, vol. 345, 2014, pages 688 - 93, XP055809115, DOI: 10.1126/science.1250127
PALACINO JSWALLEY SESONG CCHEUNG AKSHU L ET AL.: "SMN2 splice modulators enhance Ul-pre-mRNA association and rescue SMA mice", NAT CHEM BIOL, vol. 11, 2015, pages 511 - 7, XP055520469, DOI: 10.1038/nchembio.1837
MICHELSON DCIAFALONI EASHWAL SLEWIS ENARAYANASWAMI P ET AL.: "Evidence in focus: Nusinersen use in spinal muscular atrophy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology", NEUROLOGY, 2018
AVILA AMBURNETT BGTAYE AAGABANELLA FKNIGHT MA ET AL.: "Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy", J CLIN INVEST, vol. 117, 2007, pages 659 - 71, XP055449735, DOI: 10.1172/JCI29562
SOMERS ERIESSLAND MSCHREML JWIRTH BGILLINGWATER THPARSON SH: "Increasing SMN levels using the histone deacetylase inhibitor SAHA ameliorates defects in skeletal muscle microvasculature in a mouse model of severe spinal muscular atrophy", NEUROSCI LETT, vol. 544, 2013, pages 100 - 4, XP028558009, DOI: 10.1016/j.neulet.2013.03.052
SWOBODA KJSCOTT CBCRAWFORD TOSIMARD LRREYNA SP ET AL.: "SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy", PLOS ONE, vol. 5, 2010, pages e 12140
KISSEL JTSCOTT CBREYNA SPCRAWFORD TOSIMARD LR ET AL.: "SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy", PLOS ONE, vol. 6, 2011, pages e21296o
See also references of EP 3904517A4
Attorney, Agent or Firm:
JEEKAI & PARTNERS (CN)
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