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41. 发明申请

WO2018106741A1 IMPROVED METHODS OF TREATING LUNG CANCER USING MULTIPLEX PROTEOMIC ANALYSIS 审中-公开
公开(公告)号：WO2018106741A1
公开(公告)日：2018-06-14
申请号：PCT/US2017/064787
申请日：2017-12-05
申请人： EXPRESSION PATHOLOGY, INC.
发明人： HEMBROUGH, Todd , CECCHI, Fabiola , SORIA, Jean-charles
IPC分类号： G01N21/64 , G01N21/76 , G01N33/53 , G01N33/574 , G01N33/68
摘要： The present invention provides methods for treating cancer patients comprising assaying tumor tissue from patients and identifying those patients most likely to respond to treatment with a platinum-based agent, such as cisplatin, in combination with pemetrexed. Methods are provided for identifying those lung cancer patients most likely to respond to treatment with the combination of cisplatin + pemetrexed chemotherapy agents ("CDDP+PEM") by determining expression patterns of a set of 38 specific proteins directly in tumor cells derived from patient tumor tissue using SRM mass spectrometry. The method further comprising determining if the patient will respond to treatment with combination therapy, and when proteomic analysis of patient tissue indicates that the patient will respond to treatment with combination therapy, the patient is administered a regimen that includes the pemetrexed/p!atinum agent combination.

42. 发明申请

WO2017100789A1 SRM/MRM ASSAYS 审中-公开
标题翻译： SRM / MRM测定
公开(公告)号：WO2017100789A1
公开(公告)日：2017-06-15
申请号：PCT/US2016/066221
申请日：2016-12-12
申请人： EXPRESSION PATHOLOGY, INC.
发明人： KRIZMAN, David , HEMBROUGH, Todd , LIAO, Wei-Li , AN, Eunkyung , THYPARAMBIL, Sheeno , BLACKLER, Adele
IPC分类号： G01N33/48 , G01N33/68
CPC分类号： G01N33/5748 , B01D15/08 , B01D57/02 , G01N33/5091 , G01N33/574 , G01N33/6848 , G01N33/6851 , G01N2333/82 , G01N2496/00 , G01N2560/00 , H01J49/0031
摘要： Methods are provided for quantifying specific proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and can be tissues and cells treated with formaldehyde containing agents/fixatives including formalin- fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A designated protein is quantitated in the sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. The proteins that can be detected and/or quantitated are TLE3, XRCC1, E- cadherin, PTEN, Vimentin, HGF, MRP1, RFC1, SYP, IDO1, and DHFR.
摘要翻译：提供了用于通过选择性反应监测（SRM）质谱法或者也可以称为多反应监测（MRM）的方法直接定量已经在福尔马林中固定的生物样品中的特定蛋白质的方法）质谱。这些生物样品是化学保存和固定的，并且可以是用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋（FFPE）组织/细胞，FFPE组织块和来自那些块的细胞和福尔马林固定和/或石蜡包埋的组织培养细胞。通过SRM / MRM质谱法的方法，通过在蛋白质样品中定量描述的至少一种或多种肽，在样品中定量指定的蛋白质。可被检测和/或定量的蛋白质是TLE3，XRCC1，E-钙粘蛋白，PTEN，波形蛋白，HGF，MRP1，RFC1，SYP，IDO1和DHFR。

43. 发明申请

WO2016183597A1 SRM/MRM ASSAY FOR THE FIBROBLAST GROWTH FACTOR RECEPTOR 2 (FGFR2) PROTEIN 审中-公开
标题翻译：纤维母细胞生长因子受体2（FGFR2）蛋白的SRM / MRM测定
公开(公告)号：WO2016183597A1
公开(公告)日：2016-11-17
申请号：PCT/US2016/032794
申请日：2016-05-16
申请人： EXPRESSION PATHOLOGY, INC.
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno , LIAO, Wei-li
IPC分类号： G01N33/68 , G01N33/48 , G01N33/574
CPC分类号： G01N33/74 , G01N33/574 , G01N33/6848 , G01N33/6863 , G01N2333/71 , G01N2560/00 , G01N2800/56
摘要： Methods are provided for quantifying the fibroblast growth factor receptor 2 protein (FGFR2) directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. The biological sample may be selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells. A protein sample is prepared from the biological sample and the FGFR2 protein is quantitated in the sample using the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one fragment peptide derived from FGFR2.
摘要翻译：提供了通过选择反应监测（SRM）/多反应监测（MRM）质谱法的方法，在已经在福尔马林中固定的生物样品中直接定量成纤维细胞生长因子受体2蛋白（FGFR2）的方法。生物样品可以选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块和来自那些块的细胞）和组织培养物细胞。从生物样品制备蛋白质样品，并使用SRM / MRM质谱法在样品中定量FGFR2蛋白质，通过在蛋白质样品中定量至少一种衍生自FGFR2的片段肽。

44. 发明申请

WO2016183590A1 SRM/MRM ASSAY FOR THE MESOTHELIN (MSLN) PROTEIN 审中-公开
标题翻译：梅毒素（MSLN）蛋白质的SRM / MRM测定
公开(公告)号：WO2016183590A1
公开(公告)日：2016-11-17
申请号：PCT/US2016/032775
申请日：2016-05-16
申请人： EXPRESSION PATHOLOGY, INC.
发明人： KRIZMAN, David B. , HEMBROUGH, Todd , BLACKLER, Adele , THYPARAMBIL, Sheeno , AN, Eunkyung
IPC分类号： G01N33/68 , G01N33/574
CPC分类号： G01N33/6848 , G01N33/574 , G01N2333/47 , G01N2333/976 , G01N2800/56 , G01N2800/7028
摘要： The current disclosure provides methods for quantifying the MSLN protein directly in biological samples, including samples that have been fixed in formalin by Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Samples that can be assayed include tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. Methods to prepare a protein sample from such a biological sample are provided and MSLN protein is quantitated by SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described.
摘要翻译：本公开提供了在生物样品中直接定量MSLN蛋白的方法，包括通过选择反应监测/多反应监测（SRM / MRM）质谱法在福尔马林中固定的样品。可以测定的样品包括用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋（FFPE）组织/细胞，FFPE组织块和来自那些块的细胞）和组织培养细胞已被福尔马林固定和石蜡包埋。提供从这样的生物样品制备蛋白质样品的方法，并通过SRM / MRM质谱法定量蛋白质样品中至少一种或多种所述的肽定量MSLN蛋白质。

45. 发明申请

WO2015168484A8 SRM/MRM ASSAY FOR THE TYROSINE-PROTEIN KINASE RECEPTOR UFO (AXL) PROTEIN 审中-公开
标题翻译：酪氨酸蛋白激酶激酶受体UFO（AXL）蛋白的SRM / MRM测定
公开(公告)号：WO2015168484A8
公开(公告)日：2016-11-10
申请号：PCT/US2015028667
申请日：2015-04-30
申请人： EXPRESSION PATHOLOGY INC
发明人： KRIZMAN DAVID B , HEMBROUGH TODD , BLACKLER ADELE , LIAO WEI-LI
IPC分类号： C12Q1/68 , G01N33/48
CPC分类号： G01N33/6848 , G01N33/57492 , G01N33/68 , G01N2333/912 , G01N2333/91205 , G01N2800/56 , G01N2800/7028
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the tyrosine-protein kinase receptor UFO protein (AXL) that are particularly advantageous for quantifying the AXL protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue reagents and protocol and the AXL protein is quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an AXL peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：目前的公开内容提供了来自酪氨酸 - 蛋白激酶受体UFO蛋白（AXL）的特定肽和衍生的电离特征，其特别有利于通过方法固定在福尔马林中的生物样品中直接定量AXL蛋白的选择反应监测（SRM）质谱，或什么也可以称为多反应监测（MRM）质谱。这样的生物样品被化学保存和固定，其中所述生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块）和来自这些区块的细胞和已被福尔马林固定和石蜡包埋的组织培养细胞。使用液体组织试剂和方案从所述生物样品制备蛋白质样品，并且通过SRM / MRM质谱法的方法在液体组织样品中定量AXL蛋白质，通过在蛋白质样品中定量至少一种或多种肽描述。如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 AXL肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其他氨基酸残基的磷酸化。

46. 发明申请

WO2016007963A1 SRM/MRM ASSAY FOR THE GTPASE KRAS PROTEIN (KRAS) 审中-公开
标题翻译：用于KRAS蛋白（KRAS）的SRM / MRM测定
公开(公告)号：WO2016007963A1
公开(公告)日：2016-01-14
申请号：PCT/US2015/040208
申请日：2015-07-13
申请人： EXPRESSION PATHOLOGY, INC.
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno , LIAO, Wei-Li
IPC分类号： G01N33/68
CPC分类号： G01N33/5748 , G01N33/68 , G01N33/6848 , G01N2333/912 , G01N2333/914
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the GTPase KRas Protein (KRas) that are particulariy advantageous for quantifying the KRas protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells,
摘要翻译：目前的公开内容提供来自GTP酶KRas蛋白（KRas）的肽的特定肽和衍生的电离特征，其特别有利于通过选择反应监测方法直接在福尔马林中固定的生物样品中直接定量KRas蛋白（SRM）质谱，或什么也可以称为多反应监测（MRM）质谱。这样的生物样品被化学保存和固定，其中生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞）处理的组织和细胞，

47. 发明申请

WO2016004233A3 SRM ASSAYS TO CHEMOTHERAPY TARGETS 审中-公开
公开(公告)号：WO2016004233A3
公开(公告)日：2016-01-07
申请号：PCT/US2015/038874
申请日：2015-07-01
申请人： EXPRESSION PATHOLOGY, INC.
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno , LIAO, Wei-li , AN, Eunkyung
IPC分类号： G01N33/48 , G01N33/50 , G01N31/00 , H01J49/00
摘要： Quantitative analysis of proteins that are targets of chemotherapy by Selected reaction monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry, by measuring modified forms of disclosed specific peptides from the ENT1, ERCC1, FOLR1, RRM1, TUBB3, TOP01, and/or TOP02A proteins. These peptides can be quantified if a modified form thereof comprises a phosphorylated, tyrosine, threonine, serine, and/or other amino acid residues within their amino acid sequence. Biological samples that have been fixed in formalin are used for the analysis.

48. 发明申请

WO2013173627A1 SRM/MRM ASSAY FOR SUBTYPING LUNG HISTOLOGY 审中-公开
标题翻译：用于分组肺组织学的SRM / MRM测定
公开(公告)号：WO2013173627A1
公开(公告)日：2013-11-21
申请号：PCT/US2013/041424
申请日：2013-05-16
申请人： EXPRESSION PATHOLOGY, INC.
发明人： KRIZMAN, David B. , LIAO, Wei-Li , THYPARAMBIL, Sheeno , HEMBROUGH, Todd
IPC分类号： C40B30/10
CPC分类号： G01N33/57492 , G01N33/57423 , G01N33/57484 , G01N33/6848 , G01N2033/57453 , G01N2333/47 , G01N2333/4704 , G01N2333/4742 , G01N2333/70596 , G01N2333/96472 , G01N2458/15 , G01N2560/00
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the KRTS, KRT7, NapsinA, TTFI, TP63, and/or MUCI proteins that are particularly advantageous for quantifying the KRTS, KRT7, NapsinA, TTFI, TP63, and/or MUCI proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological' samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.
摘要翻译：目前的公开内容提供来自KRTS，KRT7，NapsinA，TTFI，TP63和/或MUCI蛋白质的特定肽和衍生的电离特征，其特别有利于定量KRTS，KRT7，NapsinA，TTFI，TP63，和/或MUCI蛋白直接在已经通过选择反应监测（SRM）质谱法的方法固定在福尔马林中的生物样品中，或者也可以称为多反应监测（MRM）质谱法。这种生物样品是化学保存和固定的，其中所述生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块和来自这些区块的细胞，以及已被福尔马林固定和石蜡包埋的组织培养细胞。

49. 发明申请

WO2013044265A3 MULTIPLEX MRM ASSAY FOR EVALUATION OF CANCER 审中-公开
标题翻译：多重MRM测定用于评估癌症
公开(公告)号：WO2013044265A3
公开(公告)日：2013-08-29
申请号：PCT/US2012056965
申请日：2012-09-24
申请人： EXPRESSION PATHOLOGY INC
发明人： KRIZMAN DAVID B , HEMBROUGH TODD , THYPARAMBIL SHEENO , LIAO WEI-LIAO
IPC分类号： C40B30/10 , C07K1/00 , C07K14/00
CPC分类号： G01N33/6848 , G01N33/6893 , G01N33/743 , G01N2333/47 , G01N2333/70567 , G01N2800/56 , G01N2800/7028
摘要： The current disclosure provides specific peptides, and derived ionization characteristics of the peptides from the estrogen receptor (ER) proteins that are particularly advantageous for quantifying the ER proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring / Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of an ER peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：目前的公开内容提供特定的肽，并且来自雌激素受体（ER）蛋白质的肽的特异性肽的衍生电离特征，其特别有利于通过选择反应监测/多重方法在福尔马林中固定的生物样品中直接定量ER蛋白质反应监测（SRM / MRM）质谱。如果它们以修饰或未修饰的形式存在，则可定量这些肽。 ER肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其他氨基酸残基的磷酸化。

50. 发明申请

WO2013044261A2 MRM/SRM ASSAY FOR DEATH RECEPTOR 5 PROTEIN 审中-公开
标题翻译： MRM / SRM测定死亡受体5蛋白
公开(公告)号：WO2013044261A2
公开(公告)日：2013-03-28
申请号：PCT/US2012/056961
申请日：2012-09-24
申请人： EXPRESSION PATHOLOGY, INC.
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno , LIAO, Wei-Liao
IPC分类号： G01N33/53
CPC分类号： G01N33/6848 , G01N33/6863 , G01N2333/70578 , G01N2800/56 , G01N2800/7028
摘要： Specific peptides, and derived ionization characteristics of those peptides from Death Receptor 5 (DR5) protein are provided that are particularly advantageous for quantifying the DR5 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring / Multiple Reaction Monitoring (SRM/MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from a biological sample using the Liquid Tissue™ reagents and protocol, and the DR5 protein are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described for one or more of the DR5 protein. These peptides can be quantitated if they reside in a modified or in an unmodified form. An example of a modified form of a DR5 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence
摘要翻译：提供了来自死亡受体5（DR5）蛋白质的那些肽的特异性肽和衍生电离特征，其特别有利的是通过选择反应监测/多反应监测方法直接在已经在福尔马林中固定在福尔马林中的生物样品中定量DR5蛋白（SRM / MRM）质谱。这些生物样品被化学保存和固定，其中生物样品选自用含甲醛的试剂/固定剂（包括福尔马林固定的组织/细胞，福尔马林固定/石蜡包埋的（FFPE）组织/细胞，FFPE组织块）和来自这些区块的细胞和已被福尔马林固定和石蜡包埋的组织培养细胞。使用Liquid Tissue TM试剂和方案从生物样品制备蛋白质样品，并且通过SRM / MRM质谱法的方法在液体组织样品中定量分析DR5蛋白质，通过在蛋白质样品中定量针对一种或多种DR5蛋白描述的至少一种或多种肽。如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 DR5肽的修饰形式的实例是肽序列内的酪氨酸，苏氨酸，丝氨酸和/或其它氨基酸残基的磷酸化

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