CN118339309A - 分析方法 - Google Patents
分析方法 Download PDFInfo
- Publication number
- CN118339309A CN118339309A CN202280079150.9A CN202280079150A CN118339309A CN 118339309 A CN118339309 A CN 118339309A CN 202280079150 A CN202280079150 A CN 202280079150A CN 118339309 A CN118339309 A CN 118339309A
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- China
- Prior art keywords
- nucleic acid
- target substance
- substance
- acid region
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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.)
- Pending
Links
- 238000004458 analytical method Methods 0.000 title claims abstract description 38
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 163
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 163
- 150000007523 nucleic acids Chemical group 0.000 claims abstract description 163
- 239000013076 target substance Substances 0.000 claims abstract description 84
- 239000000126 substance Substances 0.000 claims abstract description 79
- 230000027455 binding Effects 0.000 claims abstract description 76
- 230000000694 effects Effects 0.000 claims abstract description 11
- 230000000295 complement effect Effects 0.000 claims abstract description 7
- 102000004190 Enzymes Human genes 0.000 claims abstract description 6
- 108090000790 Enzymes Proteins 0.000 claims abstract description 6
- 230000009471 action Effects 0.000 claims abstract description 6
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 82
- 230000003321 amplification Effects 0.000 claims description 80
- 239000000243 solution Substances 0.000 claims description 57
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 238000000034 method Methods 0.000 claims description 21
- 230000008859 change Effects 0.000 claims description 17
- 102000004169 proteins and genes Human genes 0.000 claims description 17
- 108090000623 proteins and genes Proteins 0.000 claims description 17
- 238000005096 rolling process Methods 0.000 claims description 17
- 235000011180 diphosphates Nutrition 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- -1 hydrogen ions Chemical class 0.000 claims description 10
- 239000002773 nucleotide Substances 0.000 claims description 8
- 125000003729 nucleotide group Chemical group 0.000 claims description 8
- 238000010523 cascade reaction Methods 0.000 claims description 5
- 239000007983 Tris buffer Substances 0.000 claims description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 claims 3
- 229940048084 pyrophosphate Drugs 0.000 claims 2
- 238000003556 assay Methods 0.000 claims 1
- 239000012295 chemical reaction liquid Substances 0.000 claims 1
- 230000001351 cycling effect Effects 0.000 claims 1
- 230000033116 oxidation-reduction process Effects 0.000 claims 1
- 229940005657 pyrophosphoric acid Drugs 0.000 claims 1
- 239000011259 mixed solution Substances 0.000 description 28
- 108091008102 DNA aptamers Proteins 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 21
- 230000004927 fusion Effects 0.000 description 18
- 108091008104 nucleic acid aptamers Proteins 0.000 description 18
- 108091028043 Nucleic acid sequence Proteins 0.000 description 14
- 108020004638 Circular DNA Proteins 0.000 description 13
- 108020004414 DNA Proteins 0.000 description 12
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 9
- 102000004139 alpha-Amylases Human genes 0.000 description 9
- 108090000637 alpha-Amylases Proteins 0.000 description 9
- 229940024171 alpha-amylase Drugs 0.000 description 9
- 230000007423 decrease Effects 0.000 description 9
- 238000004020 luminiscence type Methods 0.000 description 9
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 8
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000006073 displacement reaction Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 5
- CGNLCCVKSWNSDG-UHFFFAOYSA-N SYBR Green I Chemical compound CN(C)CCCN(CCC)C1=CC(C=C2N(C3=CC=CC=C3S2)C)=C2C=CC=CC2=[N+]1C1=CC=CC=C1 CGNLCCVKSWNSDG-UHFFFAOYSA-N 0.000 description 5
- 108020004682 Single-Stranded DNA Proteins 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 101100012902 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) FIG2 gene Proteins 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
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- 238000010586 diagram Methods 0.000 description 3
- 238000005755 formation reaction Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000012410 DNA Ligases Human genes 0.000 description 2
- 108010061982 DNA Ligases Proteins 0.000 description 2
- 101001121408 Homo sapiens L-amino-acid oxidase Proteins 0.000 description 2
- 102100026388 L-amino-acid oxidase Human genes 0.000 description 2
- 238000007397 LAMP assay Methods 0.000 description 2
- 108091008103 RNA aptamers Proteins 0.000 description 2
- 101100233916 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR5 gene Proteins 0.000 description 2
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 229920001342 Bakelite® Polymers 0.000 description 1
- ZUHQCDZJPTXVCU-UHFFFAOYSA-N C1#CCCC2=CC=CC=C2C2=CC=CC=C21 Chemical compound C1#CCCC2=CC=CC=C2C2=CC=CC=C21 ZUHQCDZJPTXVCU-UHFFFAOYSA-N 0.000 description 1
- 241001678559 COVID-19 virus Species 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 108010007577 Exodeoxyribonuclease I Proteins 0.000 description 1
- 102100029075 Exonuclease 1 Human genes 0.000 description 1
- 101710114810 Glycoprotein Proteins 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 101710147059 Nicking endonuclease Proteins 0.000 description 1
- 108010079855 Peptide Aptamers Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 101710167605 Spike glycoprotein Proteins 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 101000865057 Thermococcus litoralis DNA polymerase Proteins 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000004637 bakelite Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229940079920 digestives acid preparations Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000013412 genome amplification Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 108010087904 neutravidin Proteins 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
-
- 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
- C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6804—Nucleic acid analysis using immunogens
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
- C12Q1/682—Signal amplification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/84—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving inorganic compounds or pH
-
- 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
- C12N2310/16—Aptamers
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021196186 | 2021-12-02 | ||
| JP2021-196186 | 2021-12-02 | ||
| PCT/JP2022/038105 WO2023100486A1 (ja) | 2021-12-02 | 2022-10-12 | 分析方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118339309A true CN118339309A (zh) | 2024-07-12 |
Family
ID=86611967
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202280079150.9A Pending CN118339309A (zh) | 2021-12-02 | 2022-10-12 | 分析方法 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20240301476A1 (https=) |
| EP (1) | EP4442837A4 (https=) |
| JP (1) | JPWO2023100486A1 (https=) |
| CN (1) | CN118339309A (https=) |
| WO (1) | WO2023100486A1 (https=) |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009222514A (ja) * | 2008-03-14 | 2009-10-01 | Toyobo Co Ltd | ピロリン酸濃度の測定方法およびそれを用いる核酸合成反応の測定方法 |
| US9586987B2 (en) * | 2011-09-08 | 2017-03-07 | Kabushiki Kaisha Dnaform | Primer set for isothermal amplication of a target nucleic acid sequence |
| EP4170031A1 (en) | 2012-10-23 | 2023-04-26 | Caris Science, Inc. | Aptamers and uses thereof |
| DK3430378T3 (da) * | 2016-03-14 | 2022-10-24 | Lucira Health Inc | Indretninger og fremgangsmåder til modifikation af optiske egenskaber |
| EP3429752A4 (en) * | 2016-03-14 | 2019-10-30 | Lucira Health, Inc. | SYSTEMS AND METHOD FOR IMPLEMENTING BIOLOGICAL TESTS |
| EP4477316A3 (en) * | 2016-03-14 | 2025-02-19 | Pfizer Inc. | Selectively vented biological assay devices and associated methods |
| CN109385426B (zh) * | 2018-09-10 | 2020-11-27 | 四川大学 | 识别增强型亚稳态核酸适配体探针及在目标物质计数分析中的应用 |
| JP7670166B2 (ja) * | 2021-12-02 | 2025-04-30 | 株式会社デンソー | 分析方法 |
-
2022
- 2022-10-12 EP EP22900920.4A patent/EP4442837A4/en not_active Withdrawn
- 2022-10-12 JP JP2023564773A patent/JPWO2023100486A1/ja active Pending
- 2022-10-12 CN CN202280079150.9A patent/CN118339309A/zh active Pending
- 2022-10-12 WO PCT/JP2022/038105 patent/WO2023100486A1/ja not_active Ceased
-
2024
- 2024-05-29 US US18/677,250 patent/US20240301476A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20240301476A1 (en) | 2024-09-12 |
| JPWO2023100486A1 (https=) | 2023-06-08 |
| EP4442837A4 (en) | 2025-04-30 |
| WO2023100486A1 (ja) | 2023-06-08 |
| EP4442837A1 (en) | 2024-10-09 |
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| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |