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1. 发明申请

WO2018145076A1 QUANTIFYING MGMT PROTEIN FOR OPTIMAL CANCER THERAPY 审中-公开
公开(公告)号：WO2018145076A1
公开(公告)日：2018-08-09
申请号：PCT/US2018/017028
申请日：2018-02-06
申请人： EXPRESSION PATHOLOGY, INC.
发明人： HEMBROUGH, Todd , SCHWARTZ, Sarit , CECCHI, Fabiola
IPC分类号： A61B5/11 , A61K31/70 , A61K33/24 , C12Q1/48 , C12Q1/37 , G01N33/483
CPC分类号： G01N33/57446 , A61K31/495 , G01N33/6848 , G01N2333/91017
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.

2. 发明申请

WO2017184905A1 METHOD FOR IMPROVED HEPATOCELLULAR CANCER DIAGNOSIS 审中-公开
标题翻译：改进的肝细胞癌诊断方法
公开(公告)号：WO2017184905A1
公开(公告)日：2017-10-26
申请号：PCT/US2017/028698
申请日：2017-04-20
申请人： EXPRESSION PATHOLOGY, INC. , LIAO, Wei-Li , THYPARAMBIL, Sheeno
发明人： RABIZADEH, Shahrooz , HEMBROUGH, Todd , CECCHI, Fabiola , YAU, Christina , KRIZMAN, David
IPC分类号： C12Q1/37 , G01N30/72 , G01N33/48 , G01N33/50 , G01N33/68
CPC分类号： G01N33/57438 , G01N33/6848 , G01N2333/70596 , G01N2333/71 , G01N2333/90203 , G01N2333/90666 , G01N2560/00 , G01N2800/56
摘要： Methods are provided for determining the diagnosis of whether a liver mass is a benign hepatocellular adenoma or a pre-malignant hepatocellular dysplastic nodule and/or a malignant hepatocellular carcinoma. Specific protein fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in liver mass cells collected from liver mass tissue that was obtained from a patient suffering from the liver mass and compared to reference levels in order to determine if the liver mass is a benign growth or a pre-cancer and/or cancer.
摘要翻译：提供了用于确定肝脏肿块是良性肝细胞腺瘤或恶变前恶化的肝细胞发育不良结节和/或恶性肝细胞癌的诊断的方法。通过SRM质谱法直接在从肝脏肿块组织获得的肝脏肿块细胞中精确检测和定量特异性蛋白质片段肽，所述肝脏肿瘤组织是从患有肝脏肿块的患者获得的并且与参考水平进行比较以确定肝脏肿块是否为良性生长或癌症前期和/或癌症。

3. 发明申请

WO2016191368A1 SRM/MRM ASSAY FOR THE CYCLIN-DEPENDENT KINASE INHIBITOR 2A (P16) PROTEIN 审中-公开
标题翻译：循环依赖性激酶抑制剂2A（P16）蛋白的SRM / MRM测定
公开(公告)号：WO2016191368A1
公开(公告)日：2016-12-01
申请号：PCT/US2016/033776
申请日：2016-05-23
申请人： EXPRESSION PATHOLOGY, INC.
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , AN, Eunkyung
IPC分类号： B01D59/44 , C12Q1/37 , G01N30/06 , G01N24/00 , G01N33/559
CPC分类号： G01N33/4833 , G01N33/57484 , G01N33/6848 , G01N2333/47 , G01N2333/4704
摘要： Methods are provided for quantifying the cyclin-dependent kinase inhibitor 2A protein (p16) p16 protein directly in biological samples that have been fixed in formalin by SRM/MRM mass spectrometry. A protein sample is prepared from the biological sample using, for example, the Liquid Tissue reagents and protocol and the p16 protein is quantitated in the resulting sample by quantitating in the protein sample at least one fragment peptide from p16. Peptides can be quantitated in modified or unmodified form. An example of a modified form of a p16 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
摘要翻译：提供了用于通过SRM / MRM质谱法在福尔马林中固定的生物样品中直接定量细胞周期蛋白依赖性激酶抑制剂2A蛋白（p16）p16蛋白的方法。使用例如液体组织试剂和方案从生物样品制备蛋白质样品，并通过在蛋白质样品中定量来自p16的至少一个片段肽来定量所得样品中的p16蛋白质。肽可以以修饰或未修饰的形式进行定量。 p16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。

4. 发明申请

WO2012097276A2 BCL-2-LIKE PROTEIN 11 SRM/MRM ASSAY 审中-公开
标题翻译： BCL-2样蛋白11 SRM / MRM测定
公开(公告)号：WO2012097276A2
公开(公告)日：2012-07-19
申请号：PCT/US2012/021283
申请日：2012-01-13
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno , LIAO, Wei-li
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno , LIAO, Wei-li
IPC分类号： C12Q1/37
CPC分类号： G01N33/6893 , C07K14/4747 , C07K16/2863 , C07K16/32 , C07K2317/76 , C12Q1/485 , C12Q1/6886 , C12Q2600/158 , G01N33/5088 , G01N33/574 , G01N33/6848 , G01N2333/4703 , G01N2800/44 , G01N2800/52 , G01N2800/56
摘要： Specific peptides, and derived ionization characteristics of those peptides, from the Bcl-2-like protein 11 (BIM) are provided that are particularly advantageous for quantifying the BIM 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). Such biological samples are chemically preserved and fixed where 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 the biological sample using the Liquid Tissue™ reagents and protocol, and the BIM 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 a BIM 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Bcl-2样蛋白11（BIM）的那些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的方法在福尔马林中固定的生物样品中直接定量BIM蛋白监测（SRM）质谱，或什么也可以称为多反应监测（MRM）。在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 TissueTM试剂和方案从生物样品制备蛋白质样品，并且通过SRM / MRM质谱法通过在蛋白质样品中定量至少一种或多种的蛋白质样品，在Liquid TissueTM样品中定量BIM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。 BIM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。

5. 发明申请

WO2012092531A1 HER3 PROTEIN SRM/MRM ASSAY 审中-公开
标题翻译： HER3蛋白SRM / MRM测定
公开(公告)号：WO2012092531A1
公开(公告)日：2012-07-05
申请号：PCT/US2011/067998
申请日：2011-12-29
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
发明人： KRIZMAN, David, B. , HEMBROUGH, Todd , THYPARAMBIL, Sheeno
IPC分类号： C07K16/18
CPC分类号： G01N33/6848 , G01N33/574 , G01N33/6893 , G01N33/74 , G01N2333/485 , G01N2333/71 , G01N2333/912 , G01N2333/9121
摘要： The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Receptor Tyrosine-Protein Kinase erbB-3, or Her3. that are particularly advantageous for quantifying the Her3 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.
摘要翻译：目前的公开内容提供了来自受体酪氨酸 - 蛋白激酶erbB-3或Her3的肽的特定肽和衍生的电离特征。这特别有利于通过选择反应监测（SRM）质谱法或还可以称作多重反应监测（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Her3蛋白。这样的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组织块和细胞）处理的组织和细胞从那些块和已经被福尔马林固定和石蜡包埋的组织培养细胞。

6. 发明申请

WO2012016182A1 C-SRC SELECTED REACTION MONITORING ASSAY 审中-公开
标题翻译： C-SRC选择的反应监测测定
公开(公告)号：WO2012016182A1
公开(公告)日：2012-02-02
申请号：PCT/US2011/045960
申请日：2011-07-29
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B.
发明人： KRIZMAN, David, B.
IPC分类号： G01N33/483 , G01N30/72
CPC分类号： C12Q1/485 , G01N33/6848 , G01N2333/91205
摘要： Objective quantitation of the c-Src protein directly in cancer patient tissue can aid in determining die aggressiveness of an individual patient's tumor as well as help make more informed decisions about choice of therapy. However, fee c-Src protein is currently analyzed directly in formalin fixed patient tissue only by immunohistoehemistry methodology which is at best subjectively semi-quantitative. This invention describes an objective quantitative assay for the c-Sre protein using mass spectrometry as the analytical methodology, Specific peptides, experimentally discovered characteristics about the peptides, and experimentally established assay conditions based on those peptide characteristics are provided for use in a mass speetronieiry-based Selected Reaction Monitoring (SRM) assay in order to measure relative- or absolute quantitative levels of c-Src directly in a protein preparation obtained from a formalin fixed cancer patient tissue sample.
摘要翻译： c-Src蛋白直接在癌症患者组织中的客观定量可以帮助确定个体患者肿瘤的侵袭性，并帮助对治疗选择作出更明智的决定。然而，费用c-Src蛋白质目前仅在福尔马林固定患者组织中通过免疫组织化学方法进行直接分析，该方法最多在主观上半定量。本发明描述了使用质谱法作为分析方法的c-Sre蛋白质的客观定量测定法，特异性肽，关于肽的实验发现的特征以及基于这些肽特征的实验建立的测定条件被提供用于大规模特异性 - 基于选择反应监测（SRM）测定，以便直接在从福尔马林固定的癌症患者组织样品获得的蛋白质制剂中测量c-Src的相对或绝对定量水平。

7. 发明申请

WO2009126969A3 BIOMARKERS FOR ENDOMETRIAL DISEASE 审中-公开
标题翻译：生物标志物内分泌疾病
公开(公告)号：WO2009126969A3
公开(公告)日：2010-03-25
申请号：PCT/US2009040399
申请日：2009-04-13
申请人： EXPRESSION PATHOLOGY INC , KRIZMAN DAVID B , GUIEL THOMAS G
发明人： KRIZMAN DAVID B , GUIEL THOMAS G
IPC分类号： G01N33/574
CPC分类号： G01N33/57442
摘要： This patent application discloses and describes a list of proteins that are found to be differentially expressed between normal endometrial epithelial cells and early stage cancerous endometrial epithelial cells. These proteins can be used either individually or in specific combinations in diagnostic and prognostic protein assays on various biological samples from endometrial cancer patients, or individuals suspected on having endometrial cancer. In addition, these proteins are also differentially expressed between normal endometrial epithelial cells and epithelial cells of other types of endometrial disease, and thus such diseases can be diagnosed using assays based on these proteins. The full length intact proteins can be assayed or peptides derived from these proteins can be assayed as reporters for these proteins. These proteins can also be identified as "companion diagnostic" proteins, wherein they are not only differentially expressed for use as diagnostic and prognostic indicators of endometrial cancer and other endometrial diseases, but the same proteins are also targets for therapeutic intervention of endometrial cancer and other endometrial diseases.
摘要翻译：该专利申请公开并描述了发现在正常子宫内膜上皮细胞和早期癌性子宫内膜上皮细胞之间差异表达的蛋白质列表。这些蛋白质可以在来自子宫内膜癌患者或怀疑患有子宫内膜癌的个体的各种生物样品的诊断和预后蛋白测定中单独使用或以特定组合使用。此外，这些蛋白质也在正常子宫内膜上皮细胞和其他类型的子宫内膜疾病的上皮细胞之间差异表达，因此可以使用基于这些蛋白质的测定来诊断这些疾病。可以测定全长完整蛋白质，或者可以将这些蛋白质衍生的肽作为这些蛋白质的报告物进行测定。这些蛋白质也可以被鉴定为“伴侣诊断”蛋白质，其中它们不仅差异表达以用作子宫内膜癌和其他子宫内膜疾病的诊断和预后指标，而且相同的蛋白质也是子宫内膜癌和其他的治疗性干预的靶标子宫内膜疾病

8. 发明申请

WO2006127860A2 MULTIPLEX METHOD FOR INCREASED PROTEOMIC COVERAGE FROM HISTOPATHOLOGICALLY PROCESSED BIOLOGICAL SAMPLES USING LIQUID TISSUE PREPARATIONS 审中-公开
标题翻译：使用液体组织制剂从组织病理学处理的生物样品中增加保护性覆盖物的多重方法
公开(公告)号：WO2006127860A2
公开(公告)日：2006-11-30
申请号：PCT/US2006/020166
申请日：2006-05-25
申请人： EXPRESSION PATHOLOGY, INC. , KRIZMAN, David, B. , GUIEL, Thomas, G. , DARFLER, Marlene, M.
发明人： KRIZMAN, David, B. , GUIEL, Thomas, G. , DARFLER, Marlene, M.
IPC分类号： G01N33/574 , G01N33/53
CPC分类号： G01N33/6803 , G01N1/30 , G01N33/6848
摘要： The invention provides methods for multiplex analysis of biological samples of formalin-fixed tissue samples. The invention provides for a method to achieve a multiplexed, multi-staged plurality of Liquid Tissue preparations simultaneously from a single histopathologically processed biological sample, where the protocol for each Liquid Tissue preparation imparts a distinctive set of biochemical effects on biomolecules procured from histopathologically processed biological samples and which when each of the preparations is analyzed can render additive and complementary data about the same histopathologically processed biological sample.
摘要翻译：本发明提供了福尔马林固定组织样品的生物样品的多重分析方法。本发明提供了一种从单一组织病理学处理的生物样品同时获得多重多级液体组织制剂的方法，其中每种液体组织制剂的方案对从组织病理学处理的生物学样品中获得的生物分子赋予特殊的生物化学效应样品以及当分析每种制剂时可以提供关于相同组织病理学处理的生物样品的添加剂和补充数据。

9. 发明申请

WO2018223112A1 PREDICTING GASTRIC CANCER TREATMENT OUTCOME 审中-公开
公开(公告)号：WO2018223112A1
公开(公告)日：2018-12-06
申请号：PCT/US2018/035788
申请日：2018-06-04
申请人： EXPRESSION PATHOLOGY, INC.
发明人： HEMBROUGH, Todd , CECCHI, Fabiola , SCHWARTZ, Sarit , YAU, Christina
IPC分类号： A61K45/00 , A61P35/00 , C07K14/47
摘要： Methods are provided for identifying whether a cancer patient, and especially a gastric cancer patient, will be responsive to treatment with a sequential therapeutic strategy comprising a first administration of the FOLFIRI regimen (irinotecan/5-fluoruracil/folinic acid) followed by a separate sequential administration of the combination of the chemotherapy agents docetaxel and cisplatin (FOLFIRI + docetaxel/cisplatin). Specified TUBB3 and TYMP fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in tumor cells, and especially gastric cancer tumor cells, that are collected from tumor tissue obtained from a cancer patient and compared to reference levels in order to determine if the cancer patients will positively respond to treatment with the sequential combination treatment of FOLFIRI + docetaxel/cisplatin.

10. 发明申请

WO2018102827A1 IMPROVED METHODS OF TREATING LUNG CANCER BY PREDICTING RESPONDERS TO CISPLATIN-PEMETREXED COMBINATION THERAPY 审中-公开
公开(公告)号：WO2018102827A1
公开(公告)日：2018-06-07
申请号：PCT/US2017/064562
申请日：2017-12-04
申请人： EXPRESSION PATHOLOGY, INC.
发明人： HEMBROUGH, Todd , CECCHI, Fabiola , SORIA, Jean-Charles
IPC分类号： G01N33/574 , G01N33/68
摘要： Methods are provided for identifying whether a lung tumor will be responsive to treatment with the combination of the therapeutic agents cisplatin and pemetrexed. Specified ERCC1, TS, p16, and FRα fragment peptides 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 combination of cisplatin and pemetrexed therapeutic agents.

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