CN112888785A - 包含非规范碱基对的rna分子 - Google Patents
包含非规范碱基对的rna分子 Download PDFInfo
- Publication number
- CN112888785A CN112888785A CN201980065254.2A CN201980065254A CN112888785A CN 112888785 A CN112888785 A CN 112888785A CN 201980065254 A CN201980065254 A CN 201980065254A CN 112888785 A CN112888785 A CN 112888785A
- Authority
- CN
- China
- Prior art keywords
- sequence
- rna molecule
- ribonucleotide
- base pairs
- antisense
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- 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.)
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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
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- 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
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
- A01N63/60—Isolated nucleic acids
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- C—CHEMISTRY; METALLURGY
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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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
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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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8216—Methods for controlling, regulating or enhancing expression of transgenes in plant cells
- C12N15/8218—Antisense, co-suppression, viral induced gene silencing [VIGS], post-transcriptional induced gene silencing [PTGS]
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
- C12N15/8261—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield
- C12N15/8271—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance
- C12N15/8279—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance for biotic stress resistance, pathogen resistance, disease resistance
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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
- 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
- C12N2310/11—Antisense
- C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
-
- 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
- C12N2310/33—Chemical structure of the base
-
- 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
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/531—Stem-loop; Hairpin
-
- 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
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/532—Closed or circular
-
- 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
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/533—Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Virology (AREA)
- Mycology (AREA)
- Dentistry (AREA)
- Pest Control & Pesticides (AREA)
- Environmental Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Catching Or Destruction (AREA)
- Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2018902840A AU2018902840A0 (en) | 2018-08-03 | RNA molecules | |
| AU2018902840 | 2018-08-03 | ||
| AU2018902896A AU2018902896A0 (en) | 2018-08-08 | RNA molecules | |
| AU2018902896 | 2018-08-08 | ||
| AUPCT/AU2018/051015 | 2018-09-17 | ||
| PCT/AU2018/051015 WO2019051563A1 (en) | 2017-09-15 | 2018-09-17 | Rna molecules |
| AU2019900941 | 2019-03-20 | ||
| AU2019900941A AU2019900941A0 (en) | 2019-03-20 | RNA molecules | |
| PCT/AU2019/050814 WO2020024019A1 (en) | 2018-08-03 | 2019-08-02 | Rna molecules comprising non-canonical base pairs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112888785A true CN112888785A (zh) | 2021-06-01 |
Family
ID=69230474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980065254.2A Pending CN112888785A (zh) | 2018-08-03 | 2019-08-02 | 包含非规范碱基对的rna分子 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20210269800A1 (https=) |
| EP (1) | EP3830268A4 (https=) |
| JP (2) | JP2021533812A (https=) |
| KR (2) | KR20210054518A (https=) |
| CN (1) | CN112888785A (https=) |
| AU (2) | AU2019313162B2 (https=) |
| BR (1) | BR112021001978A2 (https=) |
| CA (1) | CA3108536A1 (https=) |
| IL (1) | IL280562A (https=) |
| MX (1) | MX2021001360A (https=) |
| MY (1) | MY210286A (https=) |
| PH (1) | PH12021500009A1 (https=) |
| SG (1) | SG11202101059WA (https=) |
| UA (1) | UA129911C2 (https=) |
| WO (1) | WO2020024019A1 (https=) |
| ZA (1) | ZA202101256B (https=) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115011609A (zh) * | 2022-06-06 | 2022-09-06 | 江苏大学 | BnaFANCM基因、应用及获得油菜雄性不育突变体的方法 |
| CN115029349A (zh) * | 2022-06-09 | 2022-09-09 | 中国农业大学 | 与植物抗病性相关的circRNA、来源基因及其应用 |
| CN116478262A (zh) * | 2022-09-28 | 2023-07-25 | 西南大学 | RACK1在抗家蚕核型多角体病毒BmNPV中的应用 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2022001439A (es) * | 2019-08-02 | 2022-05-06 | Commw Scient Ind Res Org | Moléculas de arn para modular el florecimiento en plantas. |
| US20230090706A1 (en) * | 2020-02-28 | 2023-03-23 | The University Of Chicago | Methods and compositions comprising trans-acting translational activators |
| CA3185762A1 (en) * | 2020-07-15 | 2022-01-20 | Steve Whyard | Use of paperclip rna structure to inhibit target gene expression |
| CN111979210A (zh) * | 2020-08-31 | 2020-11-24 | 中国农业大学 | 辣椒疫霉纤维素合酶蛋白及其编码基因与应用 |
| WO2023215782A2 (en) * | 2022-05-04 | 2023-11-09 | University Of Maryland, College Park | Rna vectors with hairpin-like inserts |
| WO2024164008A1 (en) * | 2023-02-03 | 2024-08-08 | Sirnaomics, Inc. | Products and compositions |
| WO2026000033A1 (en) * | 2024-06-28 | 2026-01-02 | Commonwealth Scientific And Industrial Research Organisation | Double stranded rna molecules with a to g substitutions |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040053876A1 (en) * | 2002-03-26 | 2004-03-18 | The Regents Of The University Of Michigan | siRNAs and uses therof |
| CN101370940A (zh) * | 2006-01-12 | 2009-02-18 | 德福根有限公司 | 作为昆虫防治剂的dsRNA |
| WO2009150431A1 (en) * | 2008-06-13 | 2009-12-17 | Institute For Animal Health | Vector |
| CN102352360A (zh) * | 2011-11-11 | 2012-02-15 | 南开大学 | 抑制hiv-1的双长发卡结构rna表达原件的构建及功能检测 |
| WO2012051152A2 (en) * | 2010-10-12 | 2012-04-19 | Kevin Ryan | Novel dna templates for small rna production in mammalian cells |
| WO2016100333A1 (en) * | 2014-12-15 | 2016-06-23 | Syngenta Participations Ag | Pesticidal microrna carriers and use thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2008211580B2 (en) * | 2007-01-29 | 2013-08-29 | University Of The Witwatersrand Johannesburg | Use of double stranded RNA hairpin duplexes in gene silencing |
| US8841437B2 (en) * | 2008-06-20 | 2014-09-23 | The Board Of Trustees Of The Leland Stanford Junior University | Precursor miRNA loop-modulated target regulation |
| EP2542247A4 (en) * | 2010-03-01 | 2014-05-07 | Philadelphia Children Hospital | NUCLEIC ACID FOR ADDRESSING MULTIPLE REGIONS OF THE HCV GENOM |
-
2019
- 2019-08-02 KR KR1020217006457A patent/KR20210054518A/ko active Pending
- 2019-08-02 BR BR112021001978-2A patent/BR112021001978A2/pt unknown
- 2019-08-02 SG SG11202101059WA patent/SG11202101059WA/en unknown
- 2019-08-02 MY MYPI2021000568A patent/MY210286A/en unknown
- 2019-08-02 JP JP2021529494A patent/JP2021533812A/ja active Pending
- 2019-08-02 MX MX2021001360A patent/MX2021001360A/es unknown
- 2019-08-02 CA CA3108536A patent/CA3108536A1/en active Pending
- 2019-08-02 WO PCT/AU2019/050814 patent/WO2020024019A1/en not_active Ceased
- 2019-08-02 CN CN201980065254.2A patent/CN112888785A/zh active Pending
- 2019-08-02 KR KR1020267002946A patent/KR20260036292A/ko active Pending
- 2019-08-02 EP EP19844044.8A patent/EP3830268A4/en active Pending
- 2019-08-02 US US17/265,713 patent/US20210269800A1/en active Pending
- 2019-08-02 UA UAA202101024A patent/UA129911C2/uk unknown
- 2019-08-02 AU AU2019313162A patent/AU2019313162B2/en active Active
-
2021
- 2021-02-01 IL IL280562A patent/IL280562A/en unknown
- 2021-02-02 PH PH12021500009A patent/PH12021500009A1/en unknown
- 2021-02-24 ZA ZA2021/01256A patent/ZA202101256B/en unknown
-
2024
- 2024-05-22 AU AU2024203407A patent/AU2024203407A1/en active Pending
- 2024-06-26 JP JP2024102981A patent/JP2024133533A/ja active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040053876A1 (en) * | 2002-03-26 | 2004-03-18 | The Regents Of The University Of Michigan | siRNAs and uses therof |
| CN101370940A (zh) * | 2006-01-12 | 2009-02-18 | 德福根有限公司 | 作为昆虫防治剂的dsRNA |
| WO2009150431A1 (en) * | 2008-06-13 | 2009-12-17 | Institute For Animal Health | Vector |
| US20120076823A1 (en) * | 2008-06-13 | 2012-03-29 | Institute For Animal Health | Vector |
| WO2012051152A2 (en) * | 2010-10-12 | 2012-04-19 | Kevin Ryan | Novel dna templates for small rna production in mammalian cells |
| CN102352360A (zh) * | 2011-11-11 | 2012-02-15 | 南开大学 | 抑制hiv-1的双长发卡结构rna表达原件的构建及功能检测 |
| WO2016100333A1 (en) * | 2014-12-15 | 2016-06-23 | Syngenta Participations Ag | Pesticidal microrna carriers and use thereof |
Non-Patent Citations (5)
| Title |
|---|
| CHANG LIU 等: "Efficacy Analysis of Combinatorial siRNAs against HIV Derived from One Double Hairpin RNA Precursor", FRONT MICROBIOL., vol. 8, pages 2 * |
| HERRERA-CARRILLO等: "Probing the shRNA characteristics that hinder Dicer recognition and consequently allow Ago-mediated processing and AgoshRNA activity", RNA, vol. 20, pages 1410, XP055488337, DOI: 10.1261/rna.043950.113 * |
| MASAYUKI SANO等: "Expression of long anti-HIV-1 Hairpin RNAs for the Generation of Multiple siRNAs:advantages and limitations", MOLECULAR THERAPY, vol. 16, no. 1, pages 1, XP093052077, DOI: 10.1038/sj.mt.6300298 * |
| TARRYN BOURHILL等: "Successful disabling of the 5’UTR of HCV using adeno-associated viral vectors modular multimeric primary microRNA mimics", JOURNAL OF VIROLOGICAL METHODS, vol. 235, pages 26 - 33, XP029689268, DOI: 10.1016/j.jviromet.2016.05.008 * |
| 梁之聘: "多靶位RNA干扰对HIV-1抑制作用的研究", 中国博士学位论文全文数据库(电子期刊)医药卫生科技, no. 4, pages 061 - 23 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115011609A (zh) * | 2022-06-06 | 2022-09-06 | 江苏大学 | BnaFANCM基因、应用及获得油菜雄性不育突变体的方法 |
| CN115011609B (zh) * | 2022-06-06 | 2024-03-19 | 江苏大学 | BnaFANCM基因、应用及获得油菜雄性不育突变体的方法 |
| CN115029349A (zh) * | 2022-06-09 | 2022-09-09 | 中国农业大学 | 与植物抗病性相关的circRNA、来源基因及其应用 |
| CN116478262A (zh) * | 2022-09-28 | 2023-07-25 | 西南大学 | RACK1在抗家蚕核型多角体病毒BmNPV中的应用 |
| CN116478262B (zh) * | 2022-09-28 | 2024-03-22 | 西南大学 | RACK1在抗家蚕核型多角体病毒BmNPV中的应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| PH12021500009A1 (en) | 2021-09-13 |
| UA129911C2 (uk) | 2025-09-10 |
| CA3108536A1 (en) | 2020-02-06 |
| KR20260036292A (ko) | 2026-03-16 |
| JP2024133533A (ja) | 2024-10-02 |
| AU2019313162A1 (en) | 2021-03-18 |
| KR20210054518A (ko) | 2021-05-13 |
| EP3830268A1 (en) | 2021-06-09 |
| ZA202101256B (en) | 2022-09-28 |
| MX2021001360A (es) | 2021-07-16 |
| US20210269800A1 (en) | 2021-09-02 |
| SG11202101059WA (en) | 2021-02-25 |
| AU2024203407A1 (en) | 2024-08-01 |
| IL280562A (en) | 2021-03-25 |
| BR112021001978A2 (pt) | 2021-05-04 |
| AU2019313162B2 (en) | 2024-02-22 |
| EP3830268A4 (en) | 2023-12-13 |
| WO2020024019A1 (en) | 2020-02-06 |
| MY210286A (en) | 2025-09-08 |
| JP2021533812A (ja) | 2021-12-09 |
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