AU2018209934B2 - Endosomal cleavable linkers - Google Patents

Endosomal cleavable linkers Download PDF

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Publication number
AU2018209934B2
AU2018209934B2 AU2018209934A AU2018209934A AU2018209934B2 AU 2018209934 B2 AU2018209934 B2 AU 2018209934B2 AU 2018209934 A AU2018209934 A AU 2018209934A AU 2018209934 A AU2018209934 A AU 2018209934A AU 2018209934 B2 AU2018209934 B2 AU 2018209934B2
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Prior art keywords
achn
molecule
nhac
gene
sirna
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AU2018209934A1 (en
Inventor
Scott LENTINI
Martin Maier
Jayaprakash K. Nair
Kallanthottathil G. Rajeev
Christopher THEILE
Ivan Zlatev
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Alnylam Pharmaceuticals Inc
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Alnylam Pharmaceuticals Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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    • 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
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
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    • 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]
    • C12N2310/141—MicroRNAs, miRNAs
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/314—Phosphoramidates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
    • 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
    • C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
    • C12N2310/3183—Diol linkers, e.g. glycols or propanediols
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3519—Fusion with another nucleic acid
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/50—Physical structure
    • C12N2310/51—Physical structure in polymeric form, e.g. multimers, concatemers

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  • Health & Medical Sciences (AREA)
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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
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  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Communicable Diseases (AREA)
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  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
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  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
AU2018209934A 2017-01-18 2018-01-18 Endosomal cleavable linkers Active AU2018209934B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2024200743A AU2024200743B2 (en) 2017-01-18 2024-02-07 Endosomal cleavable linkers

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201762447786P 2017-01-18 2017-01-18
US62/447,786 2017-01-18
PCT/US2018/014213 WO2018136620A2 (en) 2017-01-18 2018-01-18 Endosomal cleavable linkers

Related Child Applications (1)

Application Number Title Priority Date Filing Date
AU2024200743A Division AU2024200743B2 (en) 2017-01-18 2024-02-07 Endosomal cleavable linkers

Publications (2)

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AU2018209934A1 AU2018209934A1 (en) 2019-08-15
AU2018209934B2 true AU2018209934B2 (en) 2023-11-09

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AU2018209934A Active AU2018209934B2 (en) 2017-01-18 2018-01-18 Endosomal cleavable linkers
AU2024200743A Active AU2024200743B2 (en) 2017-01-18 2024-02-07 Endosomal cleavable linkers

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AU2024200743A Active AU2024200743B2 (en) 2017-01-18 2024-02-07 Endosomal cleavable linkers

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US (2) US11286482B2 (enExample)
EP (1) EP3570892A4 (enExample)
JP (4) JP7244424B2 (enExample)
AU (2) AU2018209934B2 (enExample)
CA (1) CA3049133A1 (enExample)
WO (1) WO2018136620A2 (enExample)

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JP7244424B2 (ja) * 2017-01-18 2023-03-22 アルニラム ファーマスーティカルズ インコーポレイテッド エンドソーム切断可能なリンカー
CA3098623A1 (en) 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
JP7785543B2 (ja) * 2019-06-21 2025-12-15 アルナイラム ファーマシューティカルズ， インコーポレイテッド 構造的に明確なｓｉＲＮＡ－二重可変ドメイン免疫グロブリンコンジュゲート
IL291251B2 (en) * 2019-09-10 2026-06-01 Daiichi Sankyo Co Limited CONJUGATE OF GalNAC-OLIGONUCLEOTIDE FOR DELIVERY TO LIVER AND MANUFACTURING METHOD THEREOF
CA3174708A1 (en) 2020-03-04 2021-09-10 Verve Therapeutics, Inc. Compositions and methods for targeted rna delivery
EP4132951A4 (en) 2020-04-09 2025-06-11 Verve Therapeutics, Inc. CHEMICALLY MODIFIED GENE EDITING GUIDE RNAS WITH CAS12B
US20230257745A1 (en) 2020-07-10 2023-08-17 Alnylam Pharmaceuticals, Inc. Circular siRNAs
WO2023283403A2 (en) 2021-07-09 2023-01-12 Alnylam Pharmaceuticals, Inc. Bis-rnai compounds for cns delivery
EP4380576A4 (en) 2021-08-03 2026-04-29 Verve Therapeutics Inc RNA TARGETED COMPOSITIONS AND ADMINISTRATION METHODS
EP4522742A2 (en) 2022-05-13 2025-03-19 Alnylam Pharmaceuticals, Inc. Single-stranded loop oligonucleotides
WO2024238385A2 (en) 2023-05-12 2024-11-21 Alnylam Pharmaceuticals, Inc. Single-stranded loop oligonucleotides
WO2025242235A1 (zh) * 2024-05-21 2025-11-27 深圳信立泰药业股份有限公司 双链rna缀合物及其制备方法和用途
WO2025259743A1 (en) 2024-06-12 2025-12-18 Alnylam Pharmaceuticals, Inc. Dual conjugate compounds for extrahepatic delivery
TW202615058A (zh) 2024-06-12 2026-04-16 美商艾拉倫製藥股份有限公司 失養強直性肌肉蛋白質激酶（ｄｍｐｋ）ｉｒｎａ組成物及其使用方法
WO2026122478A1 (en) 2024-12-02 2026-06-11 Korro Bio, Inc. Extrahepatic delivery formulations and methods

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WO2010054266A2 (en) * 2008-11-06 2010-05-14 University Of Washington Multiblock copolymers
US20100330155A1 (en) * 2007-03-06 2010-12-30 Flagship Ventures METHODS AND COMPOSITIONS FOR IMPROVED THERAPEUTIC EFFECTS WITH siRNA
US20110123520A1 (en) * 2008-04-11 2011-05-26 Alnylam Pharmaceuticals, Inc. Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
WO2017015109A1 (en) * 2015-07-17 2017-01-26 Alnylam Pharmaceuticals, Inc. Multi-targeted single entity conjugates

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CA2580707C (en) * 2004-09-24 2014-07-08 Alnylam Pharmaceuticals, Inc. Rnai modulation of apob and uses thereof
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WO2010093788A2 (en) * 2009-02-11 2010-08-19 Dicerna Pharmaceuticals, Inc. Multiplex dicer substrate rna interference molecules having joining sequences
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EA201590622A1 (ru) * 2012-10-16 2015-10-30 Эндосайт, Инк. Конъюгаты для доставки лекарственного средства, содержащие не встречающиеся в природе аминокислоты, и способы применения
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JP7244424B2 (ja) * 2017-01-18 2023-03-22 アルニラム ファーマスーティカルズ インコーポレイテッド エンドソーム切断可能なリンカー

Patent Citations (4)

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US20100330155A1 (en) * 2007-03-06 2010-12-30 Flagship Ventures METHODS AND COMPOSITIONS FOR IMPROVED THERAPEUTIC EFFECTS WITH siRNA
US20110123520A1 (en) * 2008-04-11 2011-05-26 Alnylam Pharmaceuticals, Inc. Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
WO2010054266A2 (en) * 2008-11-06 2010-05-14 University Of Washington Multiblock copolymers
WO2017015109A1 (en) * 2015-07-17 2017-01-26 Alnylam Pharmaceuticals, Inc. Multi-targeted single entity conjugates

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JP2026020334A (ja) 2026-02-06
US11286482B2 (en) 2022-03-29
EP3570892A2 (en) 2019-11-27
US20190330630A1 (en) 2019-10-31
WO2018136620A2 (en) 2018-07-26
AU2024200743A1 (en) 2024-04-11
CA3049133A1 (en) 2018-07-26
US20220177885A1 (en) 2022-06-09
AU2018209934A1 (en) 2019-08-15
AU2024200743B2 (en) 2026-03-26
JP2024052946A (ja) 2024-04-12
JP7244424B2 (ja) 2023-03-22
JP2023010836A (ja) 2023-01-20
EP3570892A4 (en) 2020-11-25
JP7450008B2 (ja) 2024-03-14
JP2020505032A (ja) 2020-02-20
WO2018136620A3 (en) 2018-11-08

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