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1. 发明申请

US20110189173A1 PHOSPHORYLATED C-ErbB2 AS A SUPERIOR PREDICTIVE THERANOSTIC MARKER FOR THE DIAGNOSIS AND TREATMENT OF CANCER 有权
标题翻译：磷酸化C-ErbB2作为诊断和治疗癌症的高级预测性治疗标记
公开(公告)号：US20110189173A1
公开(公告)日：2011-08-04
申请号：US13003206
申请日：2009-07-08
申请人： Emanuel F. Petricoin, III , Lance A. Liotta , Virginia Espina , Julia D. Wulfkuhle
发明人： Emanuel F. Petricoin, III , Lance A. Liotta , Virginia Espina , Julia D. Wulfkuhle
IPC分类号： A61K39/395 , C40B30/00 , G01N33/574 , A61K31/517 , C12Q1/48 , A61P35/00
CPC分类号： G01N33/57492 , A61K31/517 , A61K39/39558 , A61K2039/505 , C12Q1/6841 , C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , G01N1/30 , G01N33/54366 , G01N33/574 , G01N33/57415 , G01N2033/57403 , G01N2333/71 , G01N2800/52
摘要： The present invention provides reliable methods to identify subsets of subjects with a cancer of epithelial origin characterized by a high level of phosphorylated c-erbB2 which does not correlate with the over-expression of total c-erbB2 as measured by IHC or FISH, for selection and inclusion for c-erbB2-direct treatment and therapy. Furthermore, the present invention provides a reliable method to determine whether a subject with a cancer of epithelial origin who has been determined to be c-erbB2 positive by IHC and by FISH should be excluded from c-erbB2-direct treatment because of a non-significant level of phosphorylated c-erbB2 in epithelial tumor tissue.
摘要翻译：本发明提供了可靠的方法来鉴定具有上皮起源癌症的受试者的亚群，其特征在于高水平的磷酸化c-erbB2，其与通过IHC或FISH测量的总c-erbB2的过表达不相关，用于选择并包括c-erbB2直接治疗和治疗。此外，本发明提供了一种可靠的方法，用于确定由IHC和FISH确定为c-erbB2阳性的具有上皮起源癌症的受试者是否应从c-erbB2直接治疗中排除，磷酸化c-erbB2在上皮肿瘤组织中的显着水平。

2. 发明授权

US09086414B2 Phosphorylated C-ErbB2 as a superior predictive theranostic marker for the diagnosis and treatment of cancer 有权
标题翻译：磷酸化的C-ErbB2作为癌症诊断和治疗的优越预测因素
公开(公告)号：US09086414B2
公开(公告)日：2015-07-21
申请号：US13003206
申请日：2009-07-08
申请人： Emanuel F. Petricoin, III , Lance A. Liotta , Virginia Espina , Julia D. Wulfkuhle
发明人： Emanuel F. Petricoin, III , Lance A. Liotta , Virginia Espina , Julia D. Wulfkuhle
IPC分类号： A61K39/395 , A01N43/48 , G01N33/53 , G01N33/543 , G01N33/574 , C12Q1/68 , A61K31/517 , G01N1/30 , A61K39/00
CPC分类号： G01N33/57492 , A61K31/517 , A61K39/39558 , A61K2039/505 , C12Q1/6841 , C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , G01N1/30 , G01N33/54366 , G01N33/574 , G01N33/57415 , G01N2033/57403 , G01N2333/71 , G01N2800/52
摘要： The present invention provides reliable methods to identify subsets of subjects with a cancer of epithelial origin characterized by a high level of phosphorylated c-erbB2 which does not correlate with the over-expression of total c-erbB2 as measured by IHC or FISH, for selection and inclusion for c-erbB2-direct treatment and therapy. Furthermore, the present invention provides a reliable method to determine whether a subject with a cancer of epithelial origin who has been determined to be c-erbB2 positive by IHC and by FISH should be excluded from c-erbB2-direct treatment because of a non-significant level of phosphorylated c-erbB2 in epithelial tumor tissue.
摘要翻译：本发明提供了可靠的方法来鉴定具有上皮起源癌症的受试者的亚群，其特征在于高水平的磷酸化c-erbB2，其与通过IHC或FISH测量的总c-erbB2的过表达不相关，用于选择并包括c-erbB2直接治疗和治疗。此外，本发明提供了一种可靠的方法，用于确定由IHC和FISH确定为c-erbB2阳性的具有上皮起源癌症的受试者是否应从c-erbB2直接治疗中排除，磷酸化c-erbB2在上皮肿瘤组织中的显着水平。

3. 发明申请

US20110207627A1 EX VIVO THERAPEUTICS SCREENING OF LIVING BONE MARROW CELLS FOR MULTIPLE MYELOMA 审中-公开
标题翻译：用于多发性骨髓瘤的生物骨髓细胞的筛查治疗
公开(公告)号：US20110207627A1
公开(公告)日：2011-08-25
申请号：US13057978
申请日：2009-08-12
申请人： Lance A. Liotta , Emanuel F. Petricoin, III , Virginia Espina
发明人： Lance A. Liotta , Emanuel F. Petricoin, III , Virginia Espina
IPC分类号： C12Q1/02 , G01N33/566 , C40B30/04 , C12Q1/37 , C12Q1/48 , H01J49/26
CPC分类号： G01N33/56972 , G01N33/5011 , G01N2333/70596 , G01N2510/00 , G01N2800/52
摘要： Methods of selecting a treatment for a patient with multiple myeloma are provided. Prior to commencing a treatment regime, bone marrow aspirates are isolated from a patient and incubated with one or more candidate therapeutics. The methods identify the therapy or combination of therapies most likely to yield the best results for a particular individual. In addition to improving clinical outcome, such theranostic evaluations dramatically reduce health care costs, by avoiding ineffective therapies. Screening assays for identifying treatments for multiple myeloma also are provided.
摘要翻译：提供了选择多发性骨髓瘤患者的治疗方法。在开始治疗方案之前，从患者中分离骨髓抽吸物并与一种或多种候选治疗剂一起温育。该方法确定最有可能为特定个体产生最佳结果的治疗或疗法组合。除了改善临床结果之外，这种诊断性评估通过避免无效疗法，大大降低了医疗保健成本。还提供了用于鉴定多发性骨髓瘤治疗的筛选试验。

4. 发明授权

US08628931B2 mTOR pathway theranostic 有权
标题翻译： mTOR通路
公开(公告)号：US08628931B2
公开(公告)日：2014-01-14
申请号：US12083866
申请日：2006-10-18
申请人： Lance A. Liotta , Emanuel F. Petricoin, III , Virginia Espina
发明人： Lance A. Liotta , Emanuel F. Petricoin, III , Virginia Espina
IPC分类号： G01N33/53 , G01N33/50 , G01N33/52
CPC分类号： G01N33/6842 , G01N2800/52
摘要： This invention relates, e.g., to a method for predicting a subject's response to a chemotherapeutic agent and/or the subject's prognosis, comprising measuring the phosphorylation state of at least one member of the mTOR pathway, and/or of at least one member of an interconnected polypeptide pathway (e.g. a member of the Akt pathway or a member of the IRS pathway), compared to a baseline value, in a cancer tissue or cancer cell sample from the subject, wherein an elevated level of the phosphorylation state compared to the baseline value indicates that the subject is a non-responder to the chemotherapeutic agent and/or has a poor prognosis. Also described is a method for treating a cancer in a subject in need thereof, wherein the subject exhibits an elevated level of the phosphorylation state, comprising administering one or more inhibitors of the mTOR and/or an interconnected pathway.
摘要翻译：本发明涉及例如用于预测受试者对化学治疗剂和/或受试者预后的反应的方法，包括测量mTOR途径的至少一个成员的磷酸化状态和/或至少一种成员相互作用的多肽途径（例如Akt途径的成员或IRS途径的成员）与来自受试者的癌症组织或癌细胞样品中的基线值相比，其中与基线相比提高了磷酸化水平值表明受试者是化疗药物的无反应者和/或预后不良。还描述了在有需要的受试者中治疗癌症的方法，其中所述受试者表现出升高的磷酸化状态水平，包括施用一种或多种mTOR抑制剂和/或互连途径。

5. 发明授权

US06925389B2 Process for discriminating between biological states based on hidden patterns from biological data 有权
标题翻译：基于生物数据隐藏模式区分生物状态的过程
公开(公告)号：US06925389B2
公开(公告)日：2005-08-02
申请号：US09906661
申请日：2001-07-18
申请人： Ben A. Hitt , Emanuel F. Petricoin, III , Peter J. Levine , Lance A. Liotta
发明人： Ben A. Hitt , Emanuel F. Petricoin, III , Peter J. Levine , Lance A. Liotta
IPC分类号： G01N27/62 , G01N33/48 , G06F19/00 , G01N33/50 , G06F7/00 , G06G7/48
CPC分类号： G06F19/24 , G06F19/00 , G06F19/20 , G16H10/40 , G16H50/70 , Y10S707/99933 , Y10S707/99943
摘要： The invention describes a process for determining a biological state through the discovery and analysis of hidden or non-obvious, discriminatory biological data patterns. The biological data can be from health data, clinical data, or from a biological sample, (e.g., a biological sample from a human, e.g., serum, blood, saliva, plasma, nipple aspirants, synovial fluids, cerebrospinal fluids, sweat, urine, fecal matter, tears, bronchial lavage, swabbings, needle aspirantas, semen, vaginal fluids, pre-ejaculate.), etc. which is analyzed to determine the biological state of the donor. The biological state can be a pathologic diagnosis, toxicity state, efficacy of a drug, prognosis of a disease, etc. Specifically, the invention concerns processes that discover hidden discriminatory biological data patterns (e.g., patterns of protein expression in a serum sample that classify the biological state of an organ) that describe biological states.
摘要翻译：本发明描述了通过发现和分析隐藏或非明显的歧视性生物数据模式来确定生物学状态的过程。生物数据可以来自健康数据，临床数据或来自生物样品（例如，来自人的生物样品，例如血清，血液，唾液，血浆，乳头吸入剂，滑液，脑脊液，汗液，尿液，粪便，眼泪，支气管灌洗液，拭子，针头精液，精液，阴道液，射精前剂量）等进行分析，以确定供体的生物学状态。生物学状态可以是病理诊断，毒性状态，药物功效，疾病预后等。具体地，本发明涉及发现隐藏的歧视性生物数据模式的过程（例如，血清样品中的蛋白质表达模式，其分类描述生物状态的器官的生物学状态）。

6. 发明申请

US20100203549A1 CALIBRATED RPMA ASSAY 审中-公开
标题翻译：校准RPMA测定
公开(公告)号：US20100203549A1
公开(公告)日：2010-08-12
申请号：US12676257
申请日：2008-09-05
申请人： Emanuel F. Petricoin, III , Lance A. Liotta
发明人： Emanuel F. Petricoin, III , Lance A. Liotta
IPC分类号： G01N33/53 , C08B5/02
CPC分类号： G01N33/96 , G01N33/5005
摘要： This invention relates, e.g., to a set of calibrants for determining the amount in a sample of an analyte (e.g., a protein, such as a protein that has been post-translationally modified), comprising a plurality of calibrants, which contain a range of amounts (e.g., defined amounts and/or serial dilutions) of the analyte, spanning the expected amount of the analyte in the sample. In each of the calibrants, a defined amount of the analyte is present in the same suitable, biological diluent (e.g., a cell or tissue lysate, or a bodily fluid). In one embodiment of the invention, the diluent reflects the same or a similar biological milieu (proteins, lipids, serum proteins, serum matrix proteins, etc.) as that in the sample in which the analyte to be measured is present. In embodiments of the invention, a single calibrant (e.g., a cell lysate) may comprise as many as hundreds of analytes, and can be used for the quantification of those hundreds of analytes in a sample. Methods are described for performing an assay (e.g. RPMA analysis), in which the calibrants of a set of calibrants of the invention are immobilized on each of the surfaces to which samples to be analyzed are immobilized, thereby providing an internal calibration curve for quantifying an RPMA assay.
摘要翻译：本发明涉及例如用于确定分析物样品中的量（例如蛋白质，例如经翻译后修饰的蛋白质）的一组校准剂，其包含多个校准物，其包含范围的分析物的量（例如，定义的量和/或连续稀释度），跨越样品中分析物的预期量。在每个校准中，一定量的分析物存在于相同的合适的生物稀释剂（例如，细胞或组织裂解液或体液）中。在本发明的一个实施方案中，稀释剂反映与待测分析物存在的样品中相同或相似的生物环境（蛋白质，脂质，血清蛋白，血清基质蛋白等）。在本发明的实施方案中，单个校准物（例如，细胞裂解物）可以包含多达数百种分析物，并且可以用于量化样品中数百种分析物。描述了用于进行测定（例如RPMA分析）的方法，其中将本发明的一组校准物的校准物固定在固定有待分析样品的每个表面上，从而提供内部校准曲线，用于量化 RPMA测定。

7. 发明申请

US20110200597A1 SIGNAL PATHWAY ALTERATIONS AND DRUG TARGET ELEVATIONS IN PRIMARY METACHRONOUS METASTATIC COLORECTAL CANCER COMPARED TO NON-METASTATIC DISEASE 审中-公开
标题翻译：与非分子性疾病相比，主要METACHRUSOUS METASTATIC COLORECTAL CANCER中的信号途径改变和药物目标高度
公开(公告)号：US20110200597A1
公开(公告)日：2011-08-18
申请号：US13057409
申请日：2009-08-05
申请人： Emanuel F. Petricoin, III , Lance A. Liotta , Mariaelena Pierobon , Alessandra Sllvestri
发明人： Emanuel F. Petricoin, III , Lance A. Liotta , Mariaelena Pierobon , Alessandra Sllvestri
IPC分类号： A61K39/395 , C12Q1/48 , C12Q1/37 , C40B30/04 , C12Q1/02 , G01N33/53 , G01N33/573 , A61K31/415 , A61K31/365 , A61K31/439 , A61K31/517 , A61K31/5377 , A61K31/506 , A61K31/404 , A61K31/4164 , A61P35/00 , A61P35/04 , G06F19/00
CPC分类号： G01N33/57419 , G01N2800/60
摘要： The present invention relates to the identification and diagnostic use of biomarkers in primary colorectal cancer tumors whose activation level are predictive of the likelihood of the onset of metastatic disease. These biomarkers may be used to determine the suitability of a patient for aggressive and/or targeted treatments. Kits and compositions of the invention are also provided.
摘要翻译：本发明涉及生物标志物在原发性结肠直肠癌肿瘤中的鉴定和诊断用途，其活化水平预示出转移性疾病发病的可能性。这些生物标志物可用于确定患者对侵袭性和/或靶向治疗的适合性。还提供了本发明的试剂盒和组合物。

8. 发明申请

US20100074895A1 METHOD FOR DETECTING AND CONTROLLING CANCER 有权
标题翻译：检测和控制癌症的方法
公开(公告)号：US20100074895A1
公开(公告)日：2010-03-25
申请号：US12513040
申请日：2007-10-31
申请人： Emanuel F. Petricoin, III , Mariaelena Pierobon , Valerie Calvert , Lance A. Liotta
发明人： Emanuel F. Petricoin, III , Mariaelena Pierobon , Valerie Calvert , Lance A. Liotta
IPC分类号： A61K39/395 , G01N33/48 , A61K31/497 , A61K31/517
CPC分类号： G01N33/57419 , A61K31/506 , A61K39/39558 , C07K16/22 , G01N33/57438 , G01N2800/52
摘要： Methods are provided for treating cancer metastasis by administering a therapeutic composition targeting a kinase substrate cascade.
摘要翻译：提供了通过施用靶向激酶底物级联的治疗组合来治疗癌症转移的方法。

9. 发明授权

US09335328B2 Method and apparatus for signal transduction pathway profiling 有权
标题翻译：用于信号转导途径分析的方法和装置
公开(公告)号：US09335328B2
公开(公告)日：2016-05-10
申请号：US10182354
申请日：2001-02-02
申请人： Lance A. Liotta , Emanuel F. Petricoin, III , Katherine L. Paweletz , Alan R. Day
发明人： Lance A. Liotta , Emanuel F. Petricoin, III , Katherine L. Paweletz , Alan R. Day
IPC分类号： G01N33/558 , G01N33/68
CPC分类号： G01N33/6842 , G01N33/5014 , G01N33/502 , G01N33/6803 , G01N33/6845
摘要： An assay device for determining the presence of analytes in a cell lysate comprises a porous support member and a plurality of binding reagents arranged and immobilized at multiple reaction sites on the support member. The binding reagents are selected and arranged to assess the status of a selected cellular signal transduction pathway/protein-protein interactive network. In a further aspect, a method for assessing the status of a signal transduction pathway comprises generating a lysate of cells, the lysate retaining one or more pathway molecules present in one or more states and the pathway molecules reflecting signal transduction events taking place in the cells. The method further includes applying the lysate to an immobilized series of binding reagents which can discriminate the pathway molecules and their states. Binding events between the pathway molecules and the binding reagents are identified and the state of the selected signal pathway is determined.
摘要翻译：用于确定细胞裂解物中分析物的存在的测定装置包括多孔支撑构件和多个结合试剂，其布置并固定在支撑构件上的多个反应位点处。选择和排列结合试剂以评估所选择的细胞信号转导途径/蛋白质 - 蛋白质相互作用网络的状态。在另一方面，用于评估信号转导途径的状态的方法包括产生细胞的裂解物，保留一个或多个状态中存在的一种或多种途径分子的裂解物和反映发生在细胞中的信号转导事件的途径分子。该方法还包括将裂解物应用于可以区分途径分子及其状态的固定化的一系列结合试剂。鉴定途径分子和结合试剂之间的结合事件，并确定所选信号通路的状态。

10. 发明申请

US20100003247A1 ASSAY FOR METASTATIC COLORECTAL CANCER 审中-公开
标题翻译：分析性分析癌症
公开(公告)号：US20100003247A1
公开(公告)日：2010-01-07
申请号：US12446910
申请日：2007-10-29
申请人： Emanuel F. Petricoin, III , Lance A. Liotta , Mariaelena Pierobon , Valerie Calvert
发明人： Emanuel F. Petricoin, III , Lance A. Liotta , Mariaelena Pierobon , Valerie Calvert
IPC分类号： A61K39/395 , C12Q1/02 , A61K31/4545 , A61K31/496 , A61K31/404 , A61K31/517 , A61K31/34 , A61K31/415 , A61P35/00
CPC分类号： G01N33/57419 , C12Q1/485 , G01N2333/90245
摘要： This invention relates, e.g., to a method for predicting the prognosis, the likelihood of metastasis in, or the desirability of administering an aggressive therapy to, a subject with colorectal cancer, comprising determining, in a sample from the subject, the level of phosphorylation compared to a positive and/or negative reference standard, of one or more of: (a) AKT (S473); (b) BAD (S112); (c) cABL (T735); (d) ERK (T42/44); (e) MARCKS (S152-156); (0 p38MAPK (T180-182): (g) STAT 1 (Y701 ); (h) PTEN (S380); (i) EGFR (Y992); (j) PAK 1/2 (S 1 19/204); or (k) PKC zeta/lambda (T410-403); or the total amount of (1) COX-2 protein; wherein if the level of phosphorylation of one or more of a-i or the total amount of COX-2 protein (1) is elevated compared to the negative reference standard, and/or if the level of phosphorylation of j or k is decreased compared to the positive reference standard, the subject has poor prognosis, is likely to undergo metastasis, and/or is a good candidate for aggressive therapy. Also described are methods for treating subjects likely to develop metastatic colorectal carcinoma, and pharmaceutical compositions and kits for implementing methods of the invention.
摘要翻译：本发明涉及例如用于预测具有结肠直肠癌的受试者的预后，转移的可能性或对其进行侵袭性治疗的可行性的方法，其包括在受试者的样品中测定磷酸化水平与正和/或负参考标准相比，以下一个或多个：（a）AKT（S473）; （b）BAD（S112）; （c）cABL（T735）; （d）ERK（T42 / 44）; （e）MARCKS（S152-156）; （0 p38MAPK（T180-182）：（g）STAT1（Y701）;（h）PTEN（S380）;（i）EGFR（Y992）;（j）PAK 1/2（S 19/204）;或（k）PKCζ/λ（T410-403）;或（1）COX-2蛋白的总量;其中如果ai中的一种或多种或COX-2蛋白（1）的总量的磷酸化水平，与阴性参考标准相比升高，和/或如果j或k的磷酸化水平与阳性参照标准相比降低，则受试者的预后不良，可能经历转移，和/或是还描述了治疗可能产生转移性结直肠癌的受试者的方法，以及用于实施本发明方法的药物组合物和试剂盒。

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