ES2689568T3 - Sondas de oligonucleótidos monocatenarias para la enumeración de copias de cromosomas o genes - Google Patents
Sondas de oligonucleótidos monocatenarias para la enumeración de copias de cromosomas o genes Download PDFInfo
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- ES2689568T3 ES2689568T3 ES15705997.3T ES15705997T ES2689568T3 ES 2689568 T3 ES2689568 T3 ES 2689568T3 ES 15705997 T ES15705997 T ES 15705997T ES 2689568 T3 ES2689568 T3 ES 2689568T3
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- 210000000349 chromosome Anatomy 0.000 title abstract description 3
- 108020005187 Oligonucleotide Probes Proteins 0.000 title description 13
- 239000002751 oligonucleotide probe Substances 0.000 title description 13
- 108090000623 proteins and genes Proteins 0.000 title 1
- 239000000523 sample Substances 0.000 abstract description 17
- 241000576133 Alphasatellites Species 0.000 abstract 1
- 238000001514 detection method Methods 0.000 abstract 1
- 210000003917 human chromosome Anatomy 0.000 abstract 1
- 238000011065 in-situ storage Methods 0.000 abstract 1
- 239000003550 marker Substances 0.000 abstract 1
- 239000000178 monomer Substances 0.000 abstract 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 35
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 35
- 101100495913 Arabidopsis thaliana CHR17 gene Proteins 0.000 description 18
- 230000009977 dual effect Effects 0.000 description 10
- 238000009396 hybridization Methods 0.000 description 10
- 108020003215 DNA Probes Proteins 0.000 description 9
- 239000003298 DNA probe Substances 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 8
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000002230 centromere Anatomy 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
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- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
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- 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
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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- 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
- C12Q1/6841—In situ hybridisation
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- 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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
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- 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
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
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- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Analytical Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Un sistema para la detección in situ de una región de control del cromosoma humano 17, comprendiendo dicho sistema: un conjunto de dos o más sondas de control monocatenarias específicas para X monómeros distintos de una región de control del satélite alfa del cromosoma humano 17, en el que X >= 2-14, las sondas de control están marcadas cada una con al menos un primer marcador, en el que cada sonda de control comprende: - una secuencia seleccionada del grupo que consiste en las SEQ ID NO: 3-16; o - una secuencia seleccionada del grupo que consiste en una versión truncada de las SEQ ID NO: 3-16, siendo la versión truncada al menos 40 pb contiguos de dichas SEQ ID NO: 3-16; o - una secuencia seleccionada del grupo que consiste en una secuencia que tiene al menos un 70 % de identidad de secuencia con una de las SEQ ID NO: 3-16, o complementos de la misma.
Description
La sonda bicatenaria de HER2 (sonda bc de HER2) se marcó con DNP con la misma plantilla de ADN de HER2 en la sonda INFORM HER2 DUAL ISH DNA. La sonda bc de HER2 se formuló con 4 mg/ml de ADN bloqueante humano en el tampón basado en formamida. La sonda bc de HER2 solo se usó en el ensayo de ISH simple.
5 El producto comercial INFORM HER2 DUAL ISH DNA mencionado anteriormente contiene un dispensador que contiene 0,75 μg/ml de una sonda del Chr17 marcada con DIG en un cóctel con el HER2 marcado con DNP.
Se preparó una sonda de oligonucleótidos monocatenaria del Chr17 (sonda de oligonucleótidos del Chr17) con un
10 conjunto de 14 oligonucleótidos con longitudes de 58 pb a 87 pb. Cada oligonucleótido se marcó con dos moléculas del hapteno DIG en una cola que no se une que tiene la secuencia TATTTTTATTTT en su extremo 5’ (véase la FIG. 2(A) -(C), en la que la FIG. 2(A) muestra una secuencia de sonda del Chr17 ejemplar (SEQ ID. NO: 2) que incluye la cola en el extremo 5’ y la FIG. 2(B) muestra una estructura más detallada de la región en negrita de aminoC6+Dig de la FIG. 2(A) y la FIG. 2(B) muestra una estructura más detallada de la región en negrita Am~Uni+Dig. Estos
15 oligonucleótidos se purificaron mediante PAGE y se analizaron con espectrometría de masas. La sonda de oligonucleótidos del Chr17 se formuló en un tampón basado en formamida sin ADN bloqueante humano. En el proceso de cribado inicial, se sometieron a prueba un total de 28 oligonucleótidos para determinar la especificidad por el centrómerodelcromosoma17.Seformularonindividualmente eneltampónbasado enformamidasinADNbloqueante humano para este cribado inicial como un conjunto para análisis como un ensayo de DISH. La sonda de
20 oligonucleótidos de HER2 (15 μg/ml) y la sonda de oligonucleótidos del CHR17 (0,5 μg/ml) se formularon en el tampón basado en formamida sin ADN bloqueante humano. En modos de realización ilustrativos, la sonda del Chr17 comprende una o más de las secuencias enumeradas en la TABLA 3.
TABLA 3. Secuencias de la sonda del cromosoma 17 25
- Nombre de oligo
- Secuencias Longitud
- CHR17_M1.1 SEQ ID. NO: 3
- 79
- CHR17M2.1 SEQ ID. NO: 4
- 79
- CHR17_M2.2 SEQ ID. NO: 5
- 79
- CHR17_M3.1 SEQ ID. NO: 6
- 79
- CHR17_M5.1 SEQ ID. NO: 7
- 83
- CHR17_M5.2 SEQ ID. NO: 8
- 87
- CHR17_M8.2 SEQ ID. NO: 9
- 71
- CHR17_M9.1 SEQ ID. NO: 10
- 58
- CHR17_M9.2 SEQ ID. NO: 11
- 65
- CHR17_M11.2 SEQ ID. NO: 12
- 71
- CHR17_M12.1 SEQ ID. NO: 13
- 80
- CHR17_M13.1 SEQ ID. NO: 14
- 80
- CHR17_M16.1 SEQ ID. NO: 15
- 80
- CHR17_M16.2 SEQ ID. NO: 16
- 80
26
TABLA 7. Número de portaobjetos a un nivel de intensidad de señal dado
- Nivel de intensidad
- Sonda INFORM HER2 DUAL ISH DNA (hib 6 h) DISH con sonda de oligonucleótidos de HER2/CHR17 (hib 1 h) Significación Sonda INFORM HER2 DUAL ISH DNA (hib 6 h) DISH con sonda de oligonucleótidos de HER2/CHR17 (hib 1 h) Significación
- Señal de HER2
- Señal de HER2
- Señal de CHR17 Señal de CHR17
- 3
- 0 5 0 0
- 2,5
- 10 28 4 16
- 2
- 47 40 29 36
- 1,5
- 16 2 11 9
- 1
- 3 10 4 7
- 0,5
- 8 4 21 18
- 0
- 11 6 26 9
- Núcleos de tejido totales
- 95 95 95 95
- Porcentaje de núcleos de tejido aptos
- 60,0 % (57/95) 76,8 % (73/95) p = 0,011 35/95 (36,8 %) 53/95 (55,8 %) p = 0,012
Puntuaciones de tinción de HER2 y CHR17
- Sonda INFORM HER2 DUAL ISH DNA (hib 6 h)
- DISH con sonda de oligonucleótidos de HER2/CHR17 (hib 1 h) Significación
- Intensidad de HER2
- 1,58 ± 0,78 1,89 ± 0,76 p = 0,005
- Fondo de HER2
- 0,04 ± 0,11 0,11 ± 0,18 p = 0,001
- Intensidad de CHR17
- 1,04 ± 0,87 1,49 ± 0,83 p = 0,000
- Fondo de CHR17
- 0 0 ND
Los datos sugieren que la DISH con sonda de oligonucleótidos de HER2/CHR17 con hibridación durante 1 hora tiene
10 una tinción más potente en tejidos difíciles que la sonda INFORM HER2 DUAL ISH DNA con hibridación durante 6 horas.
Además de someterse a prueba en tejidos de mama, también se demostró la viabilidad de DISH con sonda de oligonucleótidos de HER2/CHR17 con hibridación durante 1 h en tejidos de pulmón (FIG. 12(A) que muestra la sonda 15 monocatenaria y FIG. 12(B) que muestra la sonda bicatenaria) y gástricos (FIG. 13(A) que muestra la sonda monocatenaria y FIG. 13(B) que muestra la sonda bicatenaria). Además, se sometió a prueba la DISH con sonda de oligonucleótidos de HER2/CHR17 con hibridación durante 1 h en portaobjetos duplicados de 10 tejidos de pulmón y 10 tejidos gástricos. La DISH con sonda de oligonucleótidos de HER2/CHR17 con hibridación durante 1 h tiene un 65 % de aptos para HER2 y un 50 % de aptos para CHR17 (basado en criterios de intensidad ≥ 2), similar a un 55 % 20 de aptos para HER2 y un 50 % para CHR17 de la sonda INFORM HER2 DUAL ISH DNA con hibridación durante 6 h (p = 0,516 para HER2 y p = 1,000paraCHR17).LaFIG.12(A)-(B)es unejemplode tinciónenelCaso n.º F101411A1. La tinción en DISH con sonda de oligonucleótidos de HER2/CHR17 con hibridación durante 1 h tenía una intensidad de HER2 de 3, una cobertura de un 80 %, un fondo de 0; Chr17: intensidad 3.0, cobertura 80 %, fondo 0; mientras que la tinción con la sonda INFORM HER2 DUAL ISH DNA con hibridación durante 6 h tuvo una intensidad de HER2
25 de 3, una cobertura de un 80 %, un fondo de 0,5; intensidad de CHR17 de 3, cobertura de un 80 %, fondo de 0. Se observó algo de fondo de plata en el tejido teñido por la sonda INFORM HER2 DUAL ISH DNA con hibridación durante 6 h.
Elegimos 10 casos de tejido gástrico que se tiñeron adecuadamente con la sonda INFORM HER2 DUAL ISH DNA con 30 hibridación durante 6 horas. Los portaobjetos duplicados para cada caso se tiñeron con DISH con sonda de
32
TABLA 8. Secuencias
- SEQ ID. NO: 1
-
imagen31
- SEQ ID. NO: 2
-
imagen32
- SEQ ID. NO: 3 CHR17_M1.1
-
imagen33
- SEQ ID. NO: 4 CHR17_M2.1
-
imagen34
- SEQ ID. NO: 5 CHR17_M2.2
-
imagen35
- SEQ ID. NO: 6 CHR17_M3.1
-
imagen36
- SEQ ID. NO: 7 CHR17_M5.1
-
imagen37
- SEQ ID. NO: 8 CHR17_M5.2
-
imagen38
- SEQ ID. NO: 9 CHR17_M8.2
-
imagen39
- SEQ ID. NO: 10 CHR17_M9.1
-
imagen40
- SEQ ID. NO: 11 CHR17_M9.2
-
imagen41
- SEQ ID. NO: 12 CHR17_M11.2
-
imagen42
- SEQ ID. NO: 13 CHR17_M12.1
-
imagen43
- SEQ ID. NO: 14 CHR17_M13.1
-
imagen44
- SEQ ID. NO: 15 CHR17_M16.1
-
imagen45
- SEQ ID. NO: 16 CHR17_M16.2
-
imagen46
34
Claims (1)
-
imagen1 imagen2
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461943196P | 2014-02-21 | 2014-02-21 | |
| US201461943196P | 2014-02-21 | ||
| US201462094543P | 2014-12-19 | 2014-12-19 | |
| US201462094543P | 2014-12-19 | ||
| PCT/EP2015/053555 WO2015124702A1 (en) | 2014-02-21 | 2015-02-20 | Single-stranded oligonucleotide probes for chromosome or gene copy enumeration |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2689568T3 true ES2689568T3 (es) | 2018-11-14 |
Family
ID=52574155
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15705997.3T Active ES2689568T3 (es) | 2014-02-21 | 2015-02-20 | Sondas de oligonucleótidos monocatenarias para la enumeración de copias de cromosomas o genes |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US10752955B2 (es) |
| EP (1) | EP3108006B1 (es) |
| JP (2) | JP6982392B2 (es) |
| AU (1) | AU2015220749B2 (es) |
| CA (1) | CA2940111C (es) |
| DK (1) | DK3108006T3 (es) |
| ES (1) | ES2689568T3 (es) |
| WO (1) | WO2015124702A1 (es) |
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| AU2015326827B2 (en) * | 2014-10-02 | 2019-11-07 | Ventana Medical Systems, Inc. | Polymers and conjugates comprising the same |
| JP7038209B2 (ja) | 2017-11-13 | 2022-03-17 | エフ．ホフマン－ラ ロシュ アーゲー | エピタコ電気泳動を使用する試料分析のための装置 |
| EP3864403A1 (en) | 2018-10-12 | 2021-08-18 | F. Hoffmann-La Roche AG | Detection methods for epitachophoresis workflow automation |
| WO2020229437A1 (en) | 2019-05-14 | 2020-11-19 | F. Hoffmann-La Roche Ag | Devices and methods for sample analysis |
| CN111411146B (zh) * | 2020-03-31 | 2024-01-16 | 宜昌美光硅谷生命科技股份有限公司 | 一种检测和定量单拷贝染色体外dna或rna的方法 |
| CN112795649A (zh) * | 2021-01-05 | 2021-05-14 | 武汉友芝友医疗科技股份有限公司 | 一种用于检测her2基因扩增水平的探针组及其应用 |
| CN114214318A (zh) * | 2021-11-30 | 2022-03-22 | 广州康立明生物科技股份有限公司 | 一种染色体着丝粒探针 |
| WO2024215528A1 (en) | 2023-04-13 | 2024-10-17 | Ventana Medical Systems, Inc. | Proliferation assay for fixed solid tumors |
| WO2025193604A1 (en) | 2024-03-11 | 2025-09-18 | Ventana Medical Systems, Inc. | Non-enzymatic dissociation of ffpe tissue and generation of single cells with intact cell surface markers |
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| US5447841A (en) | 1986-01-16 | 1995-09-05 | The Regents Of The Univ. Of California | Methods for chromosome-specific staining |
| JPH0686697A (ja) * | 1991-04-09 | 1994-03-29 | Univ California | 反復配列染色体特異的核酸プローブ |
| US5750340A (en) * | 1995-04-07 | 1998-05-12 | University Of New Mexico | In situ hybridization solution and process |
| US6046004A (en) * | 1997-02-27 | 2000-04-04 | Lorne Park Research, Inc. | Solution hybridization of nucleic acids with antisense probes having modified backbones |
| US6573043B1 (en) * | 1998-10-07 | 2003-06-03 | Genentech, Inc. | Tissue analysis and kits therefor |
| GB2373500B (en) * | 2000-02-04 | 2004-12-15 | Aeomica Inc | Methods and apparatus for predicting, confirming, and displaying functional information derived from genomic sequence |
| US20030017491A1 (en) | 2000-09-14 | 2003-01-23 | Zuo-Rong Shi | Chromogenic in situ hybridization methods, kits, and compositions |
| JP2002296279A (ja) * | 2001-03-29 | 2002-10-09 | Hitachi Software Eng Co Ltd | バイオチップ及びプローブ設計方法 |
| US20020160401A1 (en) | 2001-03-29 | 2002-10-31 | Yasuyuki Nozaki | Biochip and method of designing probes |
| EP1989329A2 (en) * | 2006-01-25 | 2008-11-12 | Board of Regents, The University of Texas System | Detection and diagnosis of smoking related cancers |
| US7807356B2 (en) | 2006-03-09 | 2010-10-05 | Agilent Technologies, Inc. | Labeled nucleotide composition |
| JP5126644B2 (ja) * | 2006-05-31 | 2013-01-23 | 独立行政法人産業技術総合研究所 | 遺伝子発現プロファイルを用いた漢方薬の評価法 |
| US20080299555A1 (en) * | 2007-05-30 | 2008-12-04 | Hiroaki Nitta | Multicolor chromogenic detection of biomarkers |
| EP2335221B8 (en) * | 2008-09-16 | 2016-05-25 | Novartis AG | Reproducible quantification of biomarker expression |
| ES2645754T3 (es) | 2009-07-30 | 2017-12-07 | F. Hoffmann-La Roche Ag | Conjunto de sondas de oligonucleótidos así como métodos y usos relacionados con el mismo |
| EP2627780B1 (en) * | 2010-10-12 | 2018-02-21 | Universite Libre De Bruxelles | Bach2 repression in cells |
| CA2838736A1 (en) * | 2011-06-07 | 2012-12-13 | Caris Mpi, Inc. | Molecular profiling for cancer |
| US10510435B2 (en) * | 2013-04-30 | 2019-12-17 | California Institute Of Technology | Error correction of multiplex imaging analysis by sequential hybridization |
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2015
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- 2015-02-20 DK DK15705997.3T patent/DK3108006T3/en active
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- 2015-02-20 EP EP15705997.3A patent/EP3108006B1/en active Active
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| US11788149B2 (en) | 2023-10-17 |
| JP2020089374A (ja) | 2020-06-11 |
| AU2015220749A1 (en) | 2016-07-07 |
| CA2940111C (en) | 2022-03-15 |
| CA2940111A1 (en) | 2015-08-27 |
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| US20170009305A1 (en) | 2017-01-12 |
| EP3108006B1 (en) | 2018-08-01 |
| JP6982392B2 (ja) | 2021-12-17 |
| US10752955B2 (en) | 2020-08-25 |
| JP2017511698A (ja) | 2017-04-27 |
| US20240084395A1 (en) | 2024-03-14 |
| EP3108006A1 (en) | 2016-12-28 |
| WO2015124702A1 (en) | 2015-08-27 |
| AU2015220749B2 (en) | 2020-12-24 |
| US20210002726A1 (en) | 2021-01-07 |
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