公开(公告)号：US20170052197A1

公开(公告)日：2017-02-23

申请号：US15307777

申请日：2015-04-30

申请人： EXPRESSION PATHOLOGY, INC.

发明人： David B. KRIZMAN ,  Todd HEMBROUGH ,  Sheeno THYPARAMBIL ,  Eunkyung AN

IPC分类号： G01N33/68

CPC分类号： G01N33/6848 ,  G01N33/743 ,  G01N2333/723 ,  G01N2800/56 ,  G01N2800/7028

摘要： Methods are provided for quantifying the Androgen receptor protein (AR) protein directly in biological samples that have been fixed in formalin, using Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. The biological samples are chemically preserved and fixed and can be, for example, tissues 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. A protein sample is prepared from said biological sample using, for example, the Liquid Tissue protocol and the AR 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.

摘要翻译： 提供了使用选择反应监测（SRM）/多重反应监测（MRM）质谱法在已经在福尔马林中固定的生物样品中直接定量雄激素受体蛋白（AR）蛋白的方法。 生物样品被化学保存和固定，并且可以是例如用含甲醛的试剂/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。 使用例如液体组织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AR蛋白质，通过在蛋白质样品中定量至少一种或多种 描述的肽。

公开(公告)号：US20170052196A1

公开(公告)日：2017-02-23

申请号：US15307753

申请日：2015-04-30

申请人： EXPRESSION PATHOLOGY, INC.

发明人： David KRIZMAN ,  Todd HEMBROUGH ,  Adele BLACKLER ,  Wei-Li LIAO

IPC分类号： G01N33/68

CPC分类号： G01N33/6848 ,  G01N33/57492 ,  G01N33/68 ,  G01N2333/912 ,  G01N2333/91205 ,  G01N2800/56 ,  G01N2800/7028

摘要： Peptides from the tyrosine-protein kinase receptor UFO protein (AXL) are provided 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)/Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and include formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks. A protein digest is prepared from the biological sample 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.

摘要翻译： 提供来自酪氨酸 - 蛋白激酶受体UFO蛋白（AXL）的肽，其特别有利的是通过选择反应监测（SRM）/多重反应监测（MRM）的方法在已经在福尔马林中固定的生物样品中直接定量AXL蛋白 ） 质谱。 这些生物样品被化学保存和固定，并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。 从生物样品制备蛋白质消化物，并通过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所述的肽。

公开(公告)号：US20170030923A1

公开(公告)日：2017-02-02

申请号：US15225824

申请日：2016-08-01

申请人： Expression Pathology, Inc.

发明人： Todd HEMBROUGH ,  Fabiola CECCHI ,  Eunkyung AN ,  Manish MONGA

IPC分类号： G01N33/68 ,  A61K33/24 ,  A61K31/519

CPC分类号： G01N33/6848 ,  A61K31/519 ,  A61K33/24 ,  G01N2333/705 ,  G01N2333/9015 ,  A61K2300/00

摘要： Improved methods are provided for treating cancer patients, particularly patients suffering from lung cancer. Methods are provided for identifying whether a lung tumor will be responsive to treatment with a therapeutic regimen that includes pemetrexed and optionally includes cisplatin. A specific FR-α fragment peptide and a specific GART fragment peptide are precisely detected and quantitated by SRM-mass spectrometry directly in lung tumor cells collected from lung tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with the c therapeutic regimen.

摘要翻译： 提供改进的方法来治疗癌症患者，特别是患有肺癌的患者。 提供了用于鉴定肺肿瘤是否对包括培美曲塞的治疗方案进行治疗有反应并且任选地包括顺铂的方法。 通过SRM质谱法直接在从癌症患者获得的肺肿瘤组织收集的肺肿瘤细胞中精确检测和定量特异性FR-α片段肽和特异性GART片段肽，并与参考水平进行比较，以确定是否 肺癌患者将以c治疗方案积极应对治疗。

公开(公告)号：US20160313343A1

公开(公告)日：2016-10-27

申请号：US15203704

申请日：2016-07-06

申请人： Expression Pathology, Inc.

发明人： David B. KRIZMAN ,  Todd HEMBROUGH ,  Sheeno THYPARAMBIL ,  Wei-Li LIAO ,  Eunkyung An

IPC分类号： G01N33/68 ,  C07K16/28

CPC分类号： G01N33/6848 ,  A61K2039/507 ,  C07K16/2827 ,  G01N33/57423 ,  G01N2333/70596

摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the PD-L1 protein that are particularly advantageous for quantifying the PD-L1 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. PD-L1 peptides having modified or unmodified residues can be quantitated. An example of a modification of a PD-L1 fragment peptide is a phosphorylated 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PD-L1蛋白质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PD-L1蛋白 （SRM）质谱法，还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/或石蜡包埋的组织培养细胞。 可以定量具有修饰或未修饰残基的PD-L1肽。 PD-L1片段肽的修饰的实例是肽序列内的磷酸化酪氨酸，苏氨酸，丝氨酸和/或其它氨基酸残基。

公开(公告)号：US20150072895A1

公开(公告)日：2015-03-12

申请号：US14543610

申请日：2014-11-17

申请人： EXPRESSION PATHOLOGY, INC.

发明人： David B. KRIZMAN ,  Wei-Li LIAO ,  Sheeno THYPARAMBIL ,  Todd HEMBROUGH

IPC分类号： G01N33/574 ,  G01N33/68

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 KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins that are particularly advantageous for quantifying the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 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. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the KRT5, KRT7, NapsinA, TTF1, TP63, and/or MUC1 proteins 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. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a KRT5, KRT7, NapsinA, TTF1, TP63, and MUC1 fragment 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来自KRT5，KRT7，NapsinA，TTF1，TP63和/或MUC1蛋白的特定肽和衍生的电离特征，其特别有利于定量KRT5，KRT7，NapsinA，TTF1，TP63， 和/或MUC1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Liquid Tissue TM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质量的方法在Liquid Tissue TM样品中定量KRT5，KRT7，NapsinA，TTF1，TP63和/或MUC1蛋白质 通过在蛋白质样品中定量至少一种或多种所述的肽来进行光谱测定。 如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 KRT5，KRT7，NapsinA，TTF1，TP63和MUC1片段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。

公开(公告)号：US20140206775A1

公开(公告)日：2014-07-24

申请号：US14222387

申请日：2014-03-21

申请人： Expression Pathology, Inc.

发明人： David B. KRIZMAN ,  Todd HEMBROUGH ,  Sheeno THYPARAMBIL ,  Wei-Li LIAO

IPC分类号： C12Q1/48 ,  G01N33/573

CPC分类号： G01N33/57484 ,  C12Q1/48 ,  G01N33/573 ,  G01N33/6848 ,  G01N2333/91051 ,  G01N2333/91057

摘要： Specific peptides, and derived ionization characteristics of the peptides, from the Fatty acid synthase (FASN) protein are provided that are particularly advantageous for quantifying the FASN 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 and are 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 FASN 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 FASN peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.

摘要翻译： 提供了来自脂肪酸合成酶（FASN）蛋白质的肽的特异性肽和衍生的电离特征，其特别有利于通过选择反应监测（SRM）的方法在福尔马林中固定的生物样品中直接定量FASN蛋白 ）质谱，或什么也可以称为多反应监测（MRM）质谱。 这些生物样品被化学保存和固定，并且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组织块和来自那些的FFPE组织块和细胞）处理的组织和细胞 块和组织培养细胞，其已被福尔马林固定和石蜡包埋。 使用Liquid Tissue TM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Liquid Tissue TM样品中定量FASN蛋白质，通过在蛋白质样品中定量至少一种或多种 描述的肽。 如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 FASN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。

公开(公告)号：US20140199717A1

公开(公告)日：2014-07-17

申请号：US14223524

申请日：2014-03-24

申请人： Expression Pathology, Inc.

发明人： David B. KRIZMAN ,  Todd HEMBROUGH ,  Sheeno THYPARAMBIL ,  Wei-Li LIAO

IPC分类号： G01N33/68

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), progesterone receptor (PR), and/or antigen Ki67 (Ki67) proteins that are particularly advantageous for quantifying the ER, PR, and/or Ki67 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. 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 ER, PR, and/or Ki67 proteins 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 ER, PR, and/or Ki67 proteins. 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, PR, and/or Ki67 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异性肽，以及来自雌激素受体（ER），孕酮受体（PR）和/或抗原Ki67（Ki67）蛋白质的肽的衍生电离特征，其特别有利于定量ER，PR和/ 或通过选择反应监测/多反应监测（SRM / 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存在Ki67蛋白。 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，并通过SRM / MRM质谱法的方法在液体组织样品中定量分析ER，PR和/或Ki67蛋白质， 蛋白质样品至少一种或多种针对一种或多种ER，PR和/或Ki67蛋白质描述的肽。 如果它们以修饰或未修饰的形式存在，则可以定量这些肽。 ER，PR和/或Ki67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。

公开(公告)号：US20200271654A1

公开(公告)日：2020-08-27

申请号：US16480530

申请日：2018-02-06

申请人： Expression Pathology, Inc.

发明人： Todd HEMBROUGH ,  Sarit SCHWARTZ ,  Fabiola CECCHI

IPC分类号： G01N33/574 ,  A61K31/495 ,  G01N33/68

摘要： Methods are provided for identifying whether a tumor, and especially a colon tumor, will be responsive to treatment with the therapeutic agent temozolomide. A specific MGMT fragment peptide is precisely detected and quantitated by SRM-mass spectrometry directly in colon cancer cells collected from colon tumor tissue obtained from a cancer patient. Comparison to reference levels determines if the cancer patient will respond positively or negatively to treatment with the chemotherapeutic agent temozolomide.

公开(公告)号：US20190293652A1

公开(公告)日：2019-09-26

申请号：US16071815

申请日：2017-01-20

申请人： EXPRESSION PATHOLOGY, INC.

发明人： Fabiola CECCHI ,  Adele BLACKLER ,  Wei-Li LIAO ,  Todd HEMBROUGH ,  Daniel CATENACCI

IPC分类号： G01N33/574 ,  C07K16/28

摘要： Methods are provided for identifying whether a tumor will be responsive to treatment with an anti-EGFR agent. Specific protein fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in tumor cells collected from tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with an anti-EGFR agent such as, for example, pamitumumab and/or erbitux.

公开(公告)号：US20190285647A1

公开(公告)日：2019-09-19

申请号：US16463706

申请日：2017-12-04

申请人： Expression Pathology, Inc.

发明人： Todd HEMBROUGH ,  Fabiola CECCHI ,  Sarit SCHWARTZ ,  Kerry SCOTT

IPC分类号： G01N33/68 ,  G01N33/574 ,  G01N33/74 ,  H01J49/00

摘要： Methods are provided for quantifying CD56 and CHGA proteins directly in formalin-fixed biological samples by Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. The biological samples may include formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, and FFPE tissue blocks and cells from those blocks. A protein sample may be prepared from said biological sample using the Liquid Tissue reagents and protocol and a designated 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 peptide fragment derived from each of the proteins.