WO2026080442A2 - Compositions et méthodes de traitement de maladies fibrotiques et inflammatoires - Google Patents

Compositions et méthodes de traitement de maladies fibrotiques et inflammatoires

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Publication number
WO2026080442A2
WO2026080442A2 PCT/US2025/049791 US2025049791W WO2026080442A2 WO 2026080442 A2 WO2026080442 A2 WO 2026080442A2 US 2025049791 W US2025049791 W US 2025049791W WO 2026080442 A2 WO2026080442 A2 WO 2026080442A2
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WO
WIPO (PCT)
Prior art keywords
seq
inhibitory compound
certain aspects
fibrosis
consist
Prior art date
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Pending
Application number
PCT/US2025/049791
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English (en)
Inventor
Resat CINAR
Lenny POMMEROLLE
Muhammad Arif
Abhishek Basu
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US Department of Health and Human Services
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US Department of Health and Human Services
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Application filed by US Department of Health and Human Services filed Critical US Department of Health and Human Services
Publication of WO2026080442A2 publication Critical patent/WO2026080442A2/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • 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
    • C12N15/1137—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 against enzymes
    • 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
    • C12N15/1138—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 against receptors or cell surface proteins
    • 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
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • 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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • 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
    • C12N2310/341—Gapmers, i.e. of the type ===---===

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical 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)
  • Virology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente divulgation concerne, en partie, des méthodes de traitement de maladies fibrotiques et inflammatoires, de maladies à remodelage stromal et de maladies prolifératives telles que des maladies fibrotiques et le cancer. Plus particulièrement, la divulgation concerne des compositions pour inhiber l'expression de gènes, ou les protéines qu'elles codent, qui sont impliquées dans des voies fibrotiques et/ou inflammatoires. La divulgation concerne plus précisément des composés pour inhiber l'expression du gène ABHD14B, soit indépendamment, soit en combinaison avec des composés qui inhibent CB1R et/ou MGLUR5. Des oligonucléotides antisens particuliers comprenant des ARNsi et des gapmères pour inhiber l'expression du gène ABHD14B sont divulgués. Sont également divulgués un procédé de traitement d'individus à l'aide des composés divulgués ainsi que des kits comprenant les composés divulgués.
PCT/US2025/049791 2024-10-07 2025-10-07 Compositions et méthodes de traitement de maladies fibrotiques et inflammatoires Pending WO2026080442A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202463704345P 2024-10-07 2024-10-07
US63/704,345 2024-10-07

Publications (1)

Publication Number Publication Date
WO2026080442A2 true WO2026080442A2 (fr) 2026-04-16

Family

ID=97677011

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2025/049791 Pending WO2026080442A2 (fr) 2024-10-07 2025-10-07 Compositions et méthodes de traitement de maladies fibrotiques et inflammatoires

Country Status (1)

Country Link
WO (1) WO2026080442A2 (fr)

Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
US5491133A (en) 1987-11-30 1996-02-13 University Of Iowa Research Foundation Methods for blocking the expression of specifically targeted genes
US5565350A (en) 1993-12-09 1996-10-15 Thomas Jefferson University Compounds and methods for site directed mutations in eukaryotic cells
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US20090286969A1 (en) 2003-07-31 2009-11-19 Regulus Therapeutics, Llc. Oligomeric Compounds And Compositions For Use In Modulation Of Small Non-Coding RNAs
US20100197762A1 (en) 2006-10-18 2010-08-05 Swayze Eric E Antisense compounds
US20110112170A1 (en) 2008-04-04 2011-05-12 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity
WO2023244530A1 (fr) 2022-06-15 2023-12-21 The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services Traitement de troubles fibrotiques à l'aide d'antagonistes de récepteur glutamate métabotropique 5 ou/et d'antagonistes de récepteur des cannabinoïdes 1
US20250304710A1 (en) 2018-08-02 2025-10-02 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating muscular dystrophy

Patent Citations (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5013830A (en) 1986-09-08 1991-05-07 Ajinomoto Co., Inc. Compounds for the cleavage at a specific position of RNA, oligomers employed for the formation of said compounds, and starting materials for the synthesis of said oligomers
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
US5491133A (en) 1987-11-30 1996-02-13 University Of Iowa Research Foundation Methods for blocking the expression of specifically targeted genes
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5366878A (en) 1990-02-15 1994-11-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
US5565350A (en) 1993-12-09 1996-10-15 Thomas Jefferson University Compounds and methods for site directed mutations in eukaryotic cells
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US7432250B2 (en) 1996-06-06 2008-10-07 Isis Pharmaceuticals, Inc. Oligoribonucleotides and ribonucleases for cleaving RNA
US20090286969A1 (en) 2003-07-31 2009-11-19 Regulus Therapeutics, Llc. Oligomeric Compounds And Compositions For Use In Modulation Of Small Non-Coding RNAs
US7683036B2 (en) 2003-07-31 2010-03-23 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of small non-coding RNAs
US20100197762A1 (en) 2006-10-18 2010-08-05 Swayze Eric E Antisense compounds
US20110112170A1 (en) 2008-04-04 2011-05-12 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity
US20250304710A1 (en) 2018-08-02 2025-10-02 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating muscular dystrophy
WO2023244530A1 (fr) 2022-06-15 2023-12-21 The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services Traitement de troubles fibrotiques à l'aide d'antagonistes de récepteur glutamate métabotropique 5 ou/et d'antagonistes de récepteur des cannabinoïdes 1

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* Cited by examiner, † Cited by third party
Title
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F. C. DEVOS ET AL.: "Forced expiration measurements in mouse models of obstructive and restrictive lung diseases", RESPIR RES, vol. 18, 2017, pages 123
J. K. PARK ET AL.: "Bleomycin Induces Drug Efflux in Lungs. A Pitfall for Pharmacological Studies of Pulmonary Fibrosis", AM J RESPIR CELL MOL BIOL, vol. 62, 2020, pages 178 - 190
M. ARIF ET AL.: "An Integrative Multiomics Framework for Identification of Therapeutic Targets in Pulmonary Fibrosis", ADV SCI, 2023, pages 2207454
M. ARIF ET AL.: "Integrative transcriptomic analysis of tissue-specific metabolic crosstalk after myocardial infarction", ELIFE, vol. 10, 2021
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P. VIRTANEN ET AL.: "SciPy 1.0: fundamental algorithms for scientific computing in Python", NATURE METHODS, vol. 17, 2020, pages 261 - 272
T. K. MCGOVERN: "Evaluation of respiratory system mechanics in mice using the forced oscillation technique", J VIS EXP, 2013, pages 50172

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