WO2026080323A1 - Traitement de maladies neurologiques à l'aide de modulateurs de transcrits de gènes unc13a - Google Patents

Traitement de maladies neurologiques à l'aide de modulateurs de transcrits de gènes unc13a

Info

Publication number
WO2026080323A1
WO2026080323A1 PCT/US2025/049415 US2025049415W WO2026080323A1 WO 2026080323 A1 WO2026080323 A1 WO 2026080323A1 US 2025049415 W US2025049415 W US 2025049415W WO 2026080323 A1 WO2026080323 A1 WO 2026080323A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
unc13a
oligonucleotide
modified oligonucleotide
linkage
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2025/049415
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English (en)
Inventor
Daniel Elbaum
Marisa Elizabeth KAMELGARN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Quralis Corp
Original Assignee
Quralis Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Quralis Corp filed Critical Quralis Corp
Publication of WO2026080323A1 publication Critical patent/WO2026080323A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/332—Abasic residue
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/33—Alteration of splicing

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des oligonucléotides antisens UNC13A ayant des structures de squelette modifiées. Les oligonucléotides UNC13A décrits permettent de réduire la quantité de transcrits UNC13A mal épissés et d'augmenter la quantité de transcrits UNC13A pleine longueur, conférant ainsi une efficacité thérapeutique contre des maladies neurologiques telles que la sclérose latérale amyotrophique (SLA), la démence fronto-temporale (FTD) ou la maladie d'Alzheimer (AD).
PCT/US2025/049415 2024-10-09 2025-10-03 Traitement de maladies neurologiques à l'aide de modulateurs de transcrits de gènes unc13a Pending WO2026080323A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202463705254P 2024-10-09 2024-10-09
US63/705,254 2024-10-09

Publications (1)

Publication Number Publication Date
WO2026080323A1 true WO2026080323A1 (fr) 2026-04-16

Family

ID=97677158

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2025/049415 Pending WO2026080323A1 (fr) 2024-10-09 2025-10-03 Traitement de maladies neurologiques à l'aide de modulateurs de transcrits de gènes unc13a

Country Status (1)

Country Link
WO (1) WO2026080323A1 (fr)

Citations (31)

* Cited by examiner, † Cited by third party
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WO1999014226A2 (fr) 1997-09-12 1999-03-25 Exiqon A/S Analogues d'oligonucleotides
US6268490B1 (en) 1997-03-07 2001-07-31 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogues
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
US6670461B1 (en) 1997-09-12 2003-12-30 Exiqon A/S Oligonucleotide analogues
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
WO2004106356A1 (fr) 2003-05-27 2004-12-09 Syddansk Universitet Derives de nucleotides fonctionnalises
WO2005021570A1 (fr) 2003-08-28 2005-03-10 Gene Design, Inc. Nouveaux acides nucleiques artificiels de type a liaison n-o reticulee
US20050130923A1 (en) 2003-09-18 2005-06-16 Balkrishen Bhat 4'-thionucleosides and oligomeric compounds
US7053207B2 (en) 1999-05-04 2006-05-30 Exiqon A/S L-ribo-LNA analogues
WO2007134181A2 (fr) 2006-05-11 2007-11-22 Isis Pharmaceuticals, Inc. Analogues d'acides nucléiques bicycliques modifiés en 5'
US20080039618A1 (en) 2002-11-05 2008-02-14 Charles Allerson Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
US7399845B2 (en) 2006-01-27 2008-07-15 Isis Pharmaceuticals, Inc. 6-modified bicyclic nucleic acid analogs
WO2008101157A1 (fr) 2007-02-15 2008-08-21 Isis Pharmaceuticals, Inc. Nucléosides modifiés 5'-substitués-2'-f et composés oligomères préparés à partir de ceux-ci
WO2008150729A2 (fr) 2007-05-30 2008-12-11 Isis Pharmaceuticals, Inc. Analogues d'acides nucléiques bicycliques pontés par aminométhylène n-substitué
WO2008154401A2 (fr) 2007-06-08 2008-12-18 Isis Pharmaceuticals, Inc. Analogues d'acide nucléique bicyclique carbocylique
WO2009006478A2 (fr) 2007-07-05 2009-01-08 Isis Pharmaceuticals, Inc. Analogues d'acides nucléiques bicycliques disubstitués en position 6
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WO2014039493A1 (fr) 2012-09-04 2014-03-13 Lauren Sciences Llc Composés bolaamphiphiles, compositions de ceux-ci et leurs utilisations
WO2014039502A1 (fr) 2012-09-04 2014-03-13 Lauren Sciences Llc Composés bolaamphiphiles, compositions et leurs utilisations
WO2014039503A1 (fr) 2012-09-04 2014-03-13 Lauren Sciences Llc Composés bolaamphiphiles, compositions et leurs utilisations
WO2014179620A1 (fr) 2013-05-01 2014-11-06 Isis Pharmaceuticals, Inc. Composés antisens conjugués et leur utilisation
WO2016028187A1 (fr) 2014-08-22 2016-02-25 Noogen Llc Oligonucléotides modifiés et leurs procédés de synthèse
WO2020118246A1 (fr) 2018-12-06 2020-06-11 Wave Life Sciences Ltd. Compositions d'oligonucléotides et procédés associés
WO2021247800A2 (fr) 2020-06-03 2021-12-09 Quralis Corporation Traitement de maladies neurologiques à l'aide de modulateurs de transcrits de gènes
WO2022246251A2 (fr) * 2021-05-21 2022-11-24 Ionis Pharmaceuticals, Inc. Composés pour moduler l'expression d'unc13a
WO2023102225A2 (fr) 2021-12-03 2023-06-08 Quralis Corporation Traitement de maladies neurologiques à l'aide de modulateurs de transcrits du gène d'unc13a
WO2023104964A1 (fr) * 2021-12-09 2023-06-15 Ucl Business Ltd Agents thérapeutiques pour le traitement de troubles neurodégénératifs

Patent Citations (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994014226A1 (fr) 1992-12-14 1994-06-23 Honeywell Inc. Systeme de moteur a tolerance de pannes
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
US6268490B1 (en) 1997-03-07 2001-07-31 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogues
US7034133B2 (en) 1997-09-12 2006-04-25 Exiqon A/S Oligonucleotide analogues
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
WO1999014226A2 (fr) 1997-09-12 1999-03-25 Exiqon A/S Analogues d'oligonucleotides
US6670461B1 (en) 1997-09-12 2003-12-30 Exiqon A/S Oligonucleotide analogues
US7053207B2 (en) 1999-05-04 2006-05-30 Exiqon A/S L-ribo-LNA analogues
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
US20080039618A1 (en) 2002-11-05 2008-02-14 Charles Allerson Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
US7696345B2 (en) 2002-11-05 2010-04-13 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
WO2004106356A1 (fr) 2003-05-27 2004-12-09 Syddansk Universitet Derives de nucleotides fonctionnalises
US7427672B2 (en) 2003-08-28 2008-09-23 Takeshi Imanishi Artificial nucleic acids of n-o bond crosslinkage type
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WO2007134181A2 (fr) 2006-05-11 2007-11-22 Isis Pharmaceuticals, Inc. Analogues d'acides nucléiques bicycliques modifiés en 5'
US7547684B2 (en) 2006-05-11 2009-06-16 Isis Pharmaceuticals, Inc. 5′-modified bicyclic nucleic acid analogs
WO2008101157A1 (fr) 2007-02-15 2008-08-21 Isis Pharmaceuticals, Inc. Nucléosides modifiés 5'-substitués-2'-f et composés oligomères préparés à partir de ceux-ci
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WO2008154401A2 (fr) 2007-06-08 2008-12-18 Isis Pharmaceuticals, Inc. Analogues d'acide nucléique bicyclique carbocylique
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WO2010054826A1 (fr) 2008-11-13 2010-05-20 Giuliani International Limited Compositions antisens et procédés de préparation et d’utilisation de celles-ci
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WO2014039504A1 (fr) 2012-09-04 2014-03-13 Lauren Sciences Llc Composés bolaamphiphiles, compositions et leurs utilisations
WO2014039493A1 (fr) 2012-09-04 2014-03-13 Lauren Sciences Llc Composés bolaamphiphiles, compositions de ceux-ci et leurs utilisations
WO2014039502A1 (fr) 2012-09-04 2014-03-13 Lauren Sciences Llc Composés bolaamphiphiles, compositions et leurs utilisations
WO2014039503A1 (fr) 2012-09-04 2014-03-13 Lauren Sciences Llc Composés bolaamphiphiles, compositions et leurs utilisations
WO2014179620A1 (fr) 2013-05-01 2014-11-06 Isis Pharmaceuticals, Inc. Composés antisens conjugués et leur utilisation
WO2016028187A1 (fr) 2014-08-22 2016-02-25 Noogen Llc Oligonucléotides modifiés et leurs procédés de synthèse
WO2020118246A1 (fr) 2018-12-06 2020-06-11 Wave Life Sciences Ltd. Compositions d'oligonucléotides et procédés associés
WO2021247800A2 (fr) 2020-06-03 2021-12-09 Quralis Corporation Traitement de maladies neurologiques à l'aide de modulateurs de transcrits de gènes
WO2022246251A2 (fr) * 2021-05-21 2022-11-24 Ionis Pharmaceuticals, Inc. Composés pour moduler l'expression d'unc13a
WO2023102225A2 (fr) 2021-12-03 2023-06-08 Quralis Corporation Traitement de maladies neurologiques à l'aide de modulateurs de transcrits du gène d'unc13a
WO2023104964A1 (fr) * 2021-12-09 2023-06-15 Ucl Business Ltd Agents thérapeutiques pour le traitement de troubles neurodégénératifs

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