WO2020093061A1 - Therapeutic methods - Google Patents
Therapeutic methods Download PDFInfo
- Publication number
- WO2020093061A1 WO2020093061A1 PCT/US2019/059711 US2019059711W WO2020093061A1 WO 2020093061 A1 WO2020093061 A1 WO 2020093061A1 US 2019059711 W US2019059711 W US 2019059711W WO 2020093061 A1 WO2020093061 A1 WO 2020093061A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alkyl
- group
- compound
- formula
- alkoxy
- Prior art date
Links
- 238000002560 therapeutic procedure Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 314
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- 108020004707 nucleic acids Proteins 0.000 claims abstract description 150
- 229920000642 polymer Polymers 0.000 claims abstract description 104
- 230000008685 targeting Effects 0.000 claims abstract description 78
- 210000004027 cell Anatomy 0.000 claims abstract description 63
- 239000003446 ligand Substances 0.000 claims abstract description 63
- 239000000203 mixture Substances 0.000 claims abstract description 49
- 210000000172 cytosol Anatomy 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 312
- 125000005843 halogen group Chemical group 0.000 claims description 119
- 125000004432 carbon atom Chemical group C* 0.000 claims description 109
- 229910052739 hydrogen Inorganic materials 0.000 claims description 107
- 239000001257 hydrogen Substances 0.000 claims description 105
- 125000005647 linker group Chemical group 0.000 claims description 93
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 92
- -1 2-methyl- Chemical group 0.000 claims description 90
- 125000003118 aryl group Chemical group 0.000 claims description 86
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 81
- 108020004459 Small interfering RNA Proteins 0.000 claims description 78
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 78
- 108090000623 proteins and genes Proteins 0.000 claims description 78
- 239000007787 solid Substances 0.000 claims description 74
- 125000001072 heteroaryl group Chemical group 0.000 claims description 59
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 56
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 55
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 51
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 44
- 229920006395 saturated elastomer Polymers 0.000 claims description 44
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 43
- 125000001424 substituent group Chemical group 0.000 claims description 43
- 125000004423 acyloxy group Chemical group 0.000 claims description 42
- 125000000623 heterocyclic group Chemical group 0.000 claims description 42
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 41
- 125000004043 oxo group Chemical group O=* 0.000 claims description 39
- 125000004429 atom Chemical group 0.000 claims description 37
- 125000000304 alkynyl group Chemical group 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 26
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 26
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 24
- 125000004104 aryloxy group Chemical group 0.000 claims description 24
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- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 24
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
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- 125000003342 alkenyl group Chemical group 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000006545 (C1-C9) alkyl group Chemical group 0.000 claims description 18
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 229920001223 polyethylene glycol Polymers 0.000 claims description 17
- 241001465754 Metazoa Species 0.000 claims description 16
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
- 125000001589 carboacyl group Chemical group 0.000 claims description 16
- 230000000368 destabilizing effect Effects 0.000 claims description 16
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 14
- 239000002202 Polyethylene glycol Substances 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
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- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 12
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 12
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
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- CERQOIWHTDAKMF-UHFFFAOYSA-M methacrylate group Chemical group C(C(=C)C)(=O)[O-] CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 12
- 239000000693 micelle Substances 0.000 claims description 12
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- 125000006239 protecting group Chemical group 0.000 claims description 12
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- SOGAXMICEFXMKE-UHFFFAOYSA-N alpha-Methyl-n-butyl acrylate Chemical group CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 claims description 11
- 230000000692 anti-sense effect Effects 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
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- 201000010099 disease Diseases 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 11
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- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 10
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 claims description 10
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- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
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- HEBDGRTWECSNNT-UHFFFAOYSA-N 2-methylidenepentanoic acid Chemical group CCCC(=C)C(O)=O HEBDGRTWECSNNT-UHFFFAOYSA-N 0.000 claims description 9
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- 150000003839 salts Chemical class 0.000 claims description 9
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- ZHNSYNYLKYUVAH-GTPODGLVSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] 2-methylprop-2-enoate Chemical group C1C=C2C[C@@H](OC(=O)C(C)=C)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 ZHNSYNYLKYUVAH-GTPODGLVSA-N 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
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- 125000006648 (C1-C8) haloalkyl group Chemical group 0.000 claims description 7
- 108091081021 Sense strand Proteins 0.000 claims description 7
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- 210000004185 liver Anatomy 0.000 claims description 7
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- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 6
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 6
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- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 6
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- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 6
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- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 claims description 4
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
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- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
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- VIEHKBXCWMMOOU-UHFFFAOYSA-N 2,2,3,3,4,4,4-heptafluorobutyl 2-methylprop-2-enoate Chemical group CC(=C)C(=O)OCC(F)(F)C(F)(F)C(F)(F)F VIEHKBXCWMMOOU-UHFFFAOYSA-N 0.000 claims description 3
- RUEKTOVLVIXOHT-UHFFFAOYSA-N 2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl 2-methylprop-2-enoate Chemical group CC(=C)C(=O)OCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F RUEKTOVLVIXOHT-UHFFFAOYSA-N 0.000 claims description 3
- OOHZIRUJZFRULE-UHFFFAOYSA-N 2,2-dimethylpropyl 2-methylprop-2-enoate Chemical group CC(=C)C(=O)OCC(C)(C)C OOHZIRUJZFRULE-UHFFFAOYSA-N 0.000 claims description 3
- BEWCNXNIQCLWHP-UHFFFAOYSA-N 2-(tert-butylamino)ethyl 2-methylprop-2-enoate Chemical group CC(=C)C(=O)OCCNC(C)(C)C BEWCNXNIQCLWHP-UHFFFAOYSA-N 0.000 claims description 3
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- IINPCRFUGZHHAO-UHFFFAOYSA-N 2-hexyldecyl 2-methylprop-2-enoate Chemical group CCCCCCCCC(COC(=O)C(C)=C)CCCCCC IINPCRFUGZHHAO-UHFFFAOYSA-N 0.000 claims description 3
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- ULYIFEQRRINMJQ-UHFFFAOYSA-N 3-methylbutyl 2-methylprop-2-enoate Chemical group CC(C)CCOC(=O)C(C)=C ULYIFEQRRINMJQ-UHFFFAOYSA-N 0.000 claims description 3
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- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- 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
- A61P31/20—Antivirals for DNA viruses
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- 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
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
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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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
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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
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- 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 N.A.
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/31—Chemical structure of the backbone
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
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- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
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- C—CHEMISTRY; METALLURGY
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- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
Abstract
Description
Claims
Priority Applications (12)
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CN201980087524.XA CN113365662A (en) | 2018-11-02 | 2019-11-04 | Method of treatment |
EA202191210A EA202191210A1 (en) | 2018-11-02 | 2019-11-04 | TREATMENT METHODS |
KR1020217016674A KR20210120988A (en) | 2018-11-02 | 2019-11-04 | treatment method |
SG11202104461XA SG11202104461XA (en) | 2018-11-02 | 2019-11-04 | Therapeutic methods |
BR112021008449-5A BR112021008449A2 (en) | 2018-11-02 | 2019-11-04 | METHODS TO DELIVER A NUCLEIC ACID TO A CELL, TO DELIVER A NUCLEIC ACID TO THE CYTOSOL OF A CELL, COMPOSITION, TO TREAT A DISEASE, TO DELIVER A SIRNA TO THE LIVER OF AN ANIMAL, AND TO TREAT A VIRAL HEPATITIS B INFECTION IN AN ANIMAL, KITS, MEMBRANE DESTABILIZING POLYMER, FORMULA (X) NUCLEIC ACID CONJUGATES, USE OF A CONJUGATE AND PHARMACEUTICAL COMPOSITION |
AU2019370563A AU2019370563A1 (en) | 2018-11-02 | 2019-11-04 | Therapeutic methods |
JP2021525039A JP2022512965A (en) | 2018-11-02 | 2019-11-04 | Method of treatment |
US17/290,549 US20220031847A1 (en) | 2018-11-02 | 2019-11-04 | Therapeutic methods |
MX2021005130A MX2021005130A (en) | 2018-11-02 | 2019-11-04 | Therapeutic methods. |
CA3118142A CA3118142A1 (en) | 2018-11-02 | 2019-11-04 | Therapeutic methods |
EP19880313.2A EP3873530A4 (en) | 2018-11-02 | 2019-11-04 | Therapeutic methods |
IL282794A IL282794A (en) | 2018-11-02 | 2021-04-29 | Therapeutic methods |
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US201862755196P | 2018-11-02 | 2018-11-02 | |
US62/755,196 | 2018-11-02 |
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WO2020093061A1 true WO2020093061A1 (en) | 2020-05-07 |
Family
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PCT/US2019/059711 WO2020093061A1 (en) | 2018-11-02 | 2019-11-04 | Therapeutic methods |
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US (1) | US20220031847A1 (en) |
EP (1) | EP3873530A4 (en) |
JP (1) | JP2022512965A (en) |
KR (1) | KR20210120988A (en) |
CN (1) | CN113365662A (en) |
AU (1) | AU2019370563A1 (en) |
BR (1) | BR112021008449A2 (en) |
CA (1) | CA3118142A1 (en) |
EA (1) | EA202191210A1 (en) |
IL (1) | IL282794A (en) |
MX (1) | MX2021005130A (en) |
SG (1) | SG11202104461XA (en) |
WO (1) | WO2020093061A1 (en) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2021113820A1 (en) * | 2019-12-06 | 2021-06-10 | Genevant Sciences Gmbh | Conjugates and methods for treating liver fibrosis |
WO2021123332A1 (en) | 2019-12-20 | 2021-06-24 | Curevac Ag | Lipid nanoparticles for delivery of nucleic acids |
EP3873486A4 (en) * | 2018-11-02 | 2022-10-19 | Arbutus Biopharma Corporation | Bivalent targeted conjugates |
WO2023031392A2 (en) | 2021-09-03 | 2023-03-09 | CureVac SE | Novel lipid nanoparticles for delivery of nucleic acids comprising phosphatidylserine |
US11649260B2 (en) | 2021-06-18 | 2023-05-16 | Hongene Biotech Corporation | Functionalized N-acetylgalactosamine nucleosides |
WO2023097186A1 (en) * | 2021-11-24 | 2023-06-01 | The Regents Of The University Of California | Compositions and methods for enhancing visual function |
US11692001B2 (en) | 2021-08-30 | 2023-07-04 | Hongene Biotech Corporation | Functionalized n-acetylgalactosamine analogs |
WO2023179773A1 (en) * | 2022-03-25 | 2023-09-28 | Hansoh Bio Llc | Bicyclic heterocycles and their ligands for targeted delivery of therapeutic agents |
WO2023187760A1 (en) * | 2022-04-01 | 2023-10-05 | Genevant Sciences Gmbh | Mannose-targeted compositions |
EP4342460A1 (en) | 2022-09-21 | 2024-03-27 | NovoArc GmbH | Lipid nanoparticle with nucleic acid cargo |
EP4077473A4 (en) * | 2019-12-20 | 2024-05-01 | Arbutus Biopharma Corp | Synthetic processes and intermediates |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MA45478A (en) * | 2016-04-11 | 2019-02-20 | Arbutus Biopharma Corp | TARGETED NUCLEIC ACID CONJUGATE COMPOSITIONS |
WO2023143374A1 (en) * | 2022-01-30 | 2023-08-03 | 成都凌泰氪生物技术有限公司 | Ligand, method for preparing same, and use thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160206750A1 (en) * | 2013-07-30 | 2016-07-21 | Phaserx, Inic. | Block copolymers |
US9415113B2 (en) * | 2009-11-18 | 2016-08-16 | University Of Washington | Targeting monomers and polymers having targeting blocks |
US20180221402A1 (en) * | 2015-01-21 | 2018-08-09 | Phaserx, Inc. | Methods, compositions, and systems for delivering therapeutic and diagnostic agents into cells |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MA45478A (en) * | 2016-04-11 | 2019-02-20 | Arbutus Biopharma Corp | TARGETED NUCLEIC ACID CONJUGATE COMPOSITIONS |
US11684584B2 (en) * | 2016-12-30 | 2023-06-27 | Genevant Sciences Gmbh | Branched peg molecules and related compositions and methods |
MX2019012280A (en) * | 2017-04-11 | 2020-01-23 | Arbutus Biopharma Corp | Targeted compositions. |
-
2019
- 2019-11-04 CA CA3118142A patent/CA3118142A1/en active Pending
- 2019-11-04 BR BR112021008449-5A patent/BR112021008449A2/en unknown
- 2019-11-04 MX MX2021005130A patent/MX2021005130A/en unknown
- 2019-11-04 SG SG11202104461XA patent/SG11202104461XA/en unknown
- 2019-11-04 US US17/290,549 patent/US20220031847A1/en active Pending
- 2019-11-04 JP JP2021525039A patent/JP2022512965A/en active Pending
- 2019-11-04 EP EP19880313.2A patent/EP3873530A4/en active Pending
- 2019-11-04 EA EA202191210A patent/EA202191210A1/en unknown
- 2019-11-04 WO PCT/US2019/059711 patent/WO2020093061A1/en unknown
- 2019-11-04 CN CN201980087524.XA patent/CN113365662A/en active Pending
- 2019-11-04 KR KR1020217016674A patent/KR20210120988A/en unknown
- 2019-11-04 AU AU2019370563A patent/AU2019370563A1/en active Pending
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2021
- 2021-04-29 IL IL282794A patent/IL282794A/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9415113B2 (en) * | 2009-11-18 | 2016-08-16 | University Of Washington | Targeting monomers and polymers having targeting blocks |
US20160206750A1 (en) * | 2013-07-30 | 2016-07-21 | Phaserx, Inic. | Block copolymers |
US20180221402A1 (en) * | 2015-01-21 | 2018-08-09 | Phaserx, Inc. | Methods, compositions, and systems for delivering therapeutic and diagnostic agents into cells |
Non-Patent Citations (1)
Title |
---|
See also references of EP3873530A4 * |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3873486A4 (en) * | 2018-11-02 | 2022-10-19 | Arbutus Biopharma Corporation | Bivalent targeted conjugates |
WO2021113820A1 (en) * | 2019-12-06 | 2021-06-10 | Genevant Sciences Gmbh | Conjugates and methods for treating liver fibrosis |
WO2021123332A1 (en) | 2019-12-20 | 2021-06-24 | Curevac Ag | Lipid nanoparticles for delivery of nucleic acids |
EP4077473A4 (en) * | 2019-12-20 | 2024-05-01 | Arbutus Biopharma Corp | Synthetic processes and intermediates |
US11649260B2 (en) | 2021-06-18 | 2023-05-16 | Hongene Biotech Corporation | Functionalized N-acetylgalactosamine nucleosides |
US11884691B2 (en) | 2021-08-30 | 2024-01-30 | Hongene Biotech Corporation | Functionalized n-acetylgalactosamine analogs |
US11692001B2 (en) | 2021-08-30 | 2023-07-04 | Hongene Biotech Corporation | Functionalized n-acetylgalactosamine analogs |
WO2023031392A2 (en) | 2021-09-03 | 2023-03-09 | CureVac SE | Novel lipid nanoparticles for delivery of nucleic acids comprising phosphatidylserine |
WO2023097186A1 (en) * | 2021-11-24 | 2023-06-01 | The Regents Of The University Of California | Compositions and methods for enhancing visual function |
WO2023179773A1 (en) * | 2022-03-25 | 2023-09-28 | Hansoh Bio Llc | Bicyclic heterocycles and their ligands for targeted delivery of therapeutic agents |
WO2023187760A1 (en) * | 2022-04-01 | 2023-10-05 | Genevant Sciences Gmbh | Mannose-targeted compositions |
EP4342460A1 (en) | 2022-09-21 | 2024-03-27 | NovoArc GmbH | Lipid nanoparticle with nucleic acid cargo |
WO2024062001A1 (en) | 2022-09-21 | 2024-03-28 | Novoarc Gmbh | Lipid nanoparticle with nucleic acid cargo |
Also Published As
Publication number | Publication date |
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CA3118142A1 (en) | 2020-05-07 |
US20220031847A1 (en) | 2022-02-03 |
BR112021008449A2 (en) | 2021-10-26 |
KR20210120988A (en) | 2021-10-07 |
IL282794A (en) | 2021-06-30 |
SG11202104461XA (en) | 2021-05-28 |
EA202191210A1 (en) | 2022-01-25 |
EP3873530A1 (en) | 2021-09-08 |
JP2022512965A (en) | 2022-02-07 |
EP3873530A4 (en) | 2022-11-09 |
CN113365662A (en) | 2021-09-07 |
MX2021005130A (en) | 2021-11-04 |
AU2019370563A1 (en) | 2021-05-27 |
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