公开(公告)号：WO2011091438A1

公开(公告)日：2011-07-28

申请号：PCT/US2011/022463

申请日：2011-01-25

Applicant: GEORGE MASON INTELLECTUAL PROPERTIES, INC. ,  ESPINA, Virginia ,  LIOTTA, Lance, A. ,  MUELLER, Claudius

Inventor： ESPINA, Virginia ,  LIOTTA, Lance, A. ,  MUELLER, Claudius

IPC: A01N1/02 ,  G01N33/48

CPC classification number: G01N1/30 ,  A01N1/00

Abstract: The invention relates to a one-step chemical composition that preserves animal tissue, cells, and biomolecules, such as human tissue, human cells, and biomolecules therein. It improves the fidelity and morphologic structure of cells, organelles, and nuclear chromatin, and maintains and enhances the cellular antigenicity for immunohistochemistry and flow cytometry, while preserving proteins, post-translational modifications of proteins, and nucleic acids. In one embodiment, the composition comprises a) a non-aldehyde precipitating fixative at a concentration below 25% (volume/volume), b) a reversible/cleavable protein cross-linker that targets lipid-associated molecules, and c) a c reversible/cleavable protein cross-linker that targets water soluble molecules. In another embodiment, the composition further includes a kinase inhibitor, a phosphatase inhibitor, and a permeation enhancer. In still another embodiment, the compositions further include lactic acid at a concentration sufficient to maintain cellular nuclear volume at a level equivalent to aldehyde fixation of the same type of cell. In a further embodiment, the composition comprises: a) a precipitating fixative, b) a reversible/cleavable cross-linker, c) a permeation enhancer, d) a kinase inhibitor, e) a phosphatase inhibitor, and f) a carboxylic acid. In a still further embodiment, the invention comprises method for preserving a biological sample by contacting the sample with the composition of the invention under conditions effective for the preservation of the sample.

Abstract translation: 本发明涉及保留动物组织，细胞和生物分子的一步化学组合物，例如人组织，人细胞和生物分子。 它提高细胞，细胞器和核染色质的保真度和形态结构，并保持和增强免疫组织化学和流式细胞术的细胞抗原性，同时保留蛋白质，蛋白质的翻译后修饰和核酸。 在一个实施方案中，组合物包含a）浓度低于25％（体积/体积）的非醛沉淀固定剂，b）靶向脂质相关分子的可逆/可切割蛋白质交联剂，以及c）可逆可逆/ 可裂解的蛋白质交联剂，其靶向水溶性分子。 在另一个实施方案中，组合物还包含激酶抑制剂，磷酸酶抑制剂和渗透增强剂。 在另一个实施方案中，组合物还包括浓度足以将细胞核体积保持在与相同类型细胞的醛固定相当的水平的乳酸。 在另一个实施方案中，组合物包括：a）沉淀固定剂，b）可逆/可切割交联剂，c）渗透促进剂，d）激酶抑制剂，e）磷酸酶抑制剂，和f）羧酸。 在又一个实施方案中，本发明包括通过在有效保存样品的条件下使样品与本发明的组合物接触来保存生物样品的方法。

公开(公告)号：WO2011028960A1

公开(公告)日：2011-03-10

申请号：PCT/US2010/047751

申请日：2010-09-02

Applicant: LOMA LINDA UNIVERSITY MEDICAL CONDITIONS ,  GEORGE MASON INTELLECTUAL PROPERTIES, INC. ,  REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE ,  MUELLER, Claudius ,  LIOTTA, Lance ,  SCHRAG, Matthew ,  KIRSCH, Wolff, M. ,  VINTERS, Harry, V.

Inventor： MUELLER, Claudius ,  LIOTTA, Lance ,  SCHRAG, Matthew ,  KIRSCH, Wolff, M. ,  VINTERS, Harry, V.

IPC: G01N33/53

CPC classification number: G01N33/6896 ,  G01N2800/2821 ,  G01N2800/56 ,  G01N2800/60

Abstract: Methods and kits for identifying and/or monitoring neurological conditions in a patient using ratios of biomarkers are disclosed. The neurological conditions may include, for example, Alzheimer's disease or mild cognitive impairment. The particular biomarkers that may be useful in identifying and/or monitoring neurological conditions may include, for example, biliverdin reductase, biliverdin reductase, estrogen receptor alpha, superoxide dismutase, S100A7, hemeoxygenase 1, matrix metalloproteinase 9 and platelet derived growth factor receptor. In particular, ratios of these biomarkers are useful.

Abstract translation: 公开了使用生物标志物比例鉴定和/或监测患者神经系统状况的方法和试剂盒。 神经病症可包括例如阿尔茨海默病或轻度认知障碍。 可用于鉴定和/或监测神经病症的特定生物标志物可包括例如胆红素还原酶，胆红素还原酶，雌激素受体α，超氧化物歧化酶，S100A7，血液氧合酶1，基质金属蛋白酶9和血小板衍生生长因子受体。 特别地，这些生物标志物的比例是有用的。

公开(公告)号：WO2010019227A1

公开(公告)日：2010-02-18

申请号：PCT/US2009/004608

申请日：2009-08-12

Applicant: GEORGE MASON INTELLECTUAL PROPERTIES, INC. ,  ESPINA, Virginia ,  LIOTTA, Lance ,  PETRICOIN, Emanuel, F.

Inventor： ESPINA, Virginia ,  LIOTTA, Lance ,  PETRICOIN, Emanuel, F.

IPC: G01N33/48

CPC classification number: G01N33/56972 ,  G01N33/5011 ,  G01N2333/70596 ,  G01N2510/00 ,  G01N2800/52

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2008073187A3

公开(公告)日：2009-12-23

申请号：PCT/US2007022744

申请日：2007-10-26

Applicant: GEORGE MASON INTELLECTUAL PROP ,  LIOTTA LANCE A ,  PETRICOIN EMANUEL F ,  GEHO DAVID ,  ESPINA VIRGINIA A

Inventor： LIOTTA LANCE A ,  PETRICOIN EMANUEL F ,  GEHO DAVID ,  ESPINA VIRGINIA A

IPC: A01N1/00 ,  G01N1/30

CPC classification number: G01N1/30 ,  A01N1/00

Abstract: This invention relates, e.g., to a composition that, at room temperature, when contacted with a sample comprising phosphoproteins, can fix and stabilize cellular phosphoproteins, preserve cellular morphology, and allow the sample to be frozen to generate a cryostat frozen section suitable for molecular analysis. The composition comprises ( 1 ) a fixative that is effective to fix the phosphoproteins, and that has a sufficient water content to be soluble for a stabilizer and/or a permeability enhancing agent); (2) a stabilizer, comprising (a) a kinase inhibitor and (b) a phosphatase inhibitor and, optionally, (c) a protease (e.g., proteinase) inhibitor; and (3) a permeability enhancing agent (e.g. PEG). Methods are described for preserving phosphoproteins, using such a composition. Also described are endogenous surrogate markers for monitoring protein degradation, including the loss of posttranslational modifications (such as phosphorylation), e.g. the following removal of a cell or tissue from a subject; and exogenous molecular sentinels (e.g. phosphoproteins attached to magnetic nanoparticles) that allow one to evaluate the processing history of a cellular or tissue population sample.

Abstract translation: 本发明涉及例如在室温下与包含磷蛋白的样品接触时可以固定和稳定细胞磷酸蛋白的组合物，保留细胞形态，并允许样品冷冻以产生适于分子的低温恒温器冷冻部分 分析。 组合物包含（1）固定磷酸蛋白有效的固定剂，并且其具有足够的水含量可溶于稳定剂和/或渗透性增强剂）; （2）稳定剂，其包含（a）激酶抑制剂和（b）磷酸酶抑制剂和任选的（c）蛋白酶（例如蛋白酶）抑制剂; 和（3）渗透性增强剂（例如PEG）。 描述了使用这种组合物来保存磷蛋白的方法。 还描述了用于监测蛋白质降解的内源替代标记，包括翻译后修饰（例如磷酸化）的丧失，例如， 以下从受试者中除去细胞或组织; 和外源性分子前哨蛋白（例如连接到磁性纳米颗粒的磷酸蛋白），其允许评价细胞或组织群体样品的加工历史。

公开(公告)号：WO2009014761A3

公开(公告)日：2009-05-14

申请号：PCT/US2008009105

申请日：2008-07-28

Applicant: GEORGE MASON INTELLECTUAL PROP ,  PETRICOIN EMANUEL F III ,  LIOTTA LANCE A ,  WULFKUHLE JULIA D

Inventor： PETRICOIN EMANUEL F III ,  LIOTTA LANCE A ,  WULFKUHLE JULIA D

IPC: G01N33/50

CPC classification number: G01N33/57415 ,  G01N2800/52

Abstract: This invention relates, e.g., to a method for predicting the response of a subject having, or at risk of developing, breast cancer to Tamoxifen therapy. The method comprises measuring the amount of phosphorylation at residues S70 of Bcl-2, Y992 of EGFR, and/or Y527 of Src in a suitable sample from the subject, wherein a statistically significantly elevated level of phosphorylation at one or more of the three residues compared to a baseline value indicates that the subject is likely to be responsive to Tamoxifen therapy.

Abstract translation: 本发明涉及例如用于预测患有乳腺癌或有患乳腺癌风险的受试者对他莫昔芬疗法的反应的方法。 该方法包括测量来自受试者的合适样品中Bcl-2的残基S70，EGFR的残基S90，和/或Src的Y527的磷酸化的量，其中三个残基中的一个或多个的统计学显着升高的磷酸化水平 与基线值相比表明受试者可能对他莫昔芬治疗有反应。

公开(公告)号：WO2008115707A3

公开(公告)日：2009-04-16

申请号：PCT/US2008056038

申请日：2008-03-06

Applicant: GEORGE MASON INTELLECTUAL PROP ,  POPOV SERGUEI G ,  POPOVA TAISSIA ,  ESPINA VIRGINIA ,  BAILEY CHARLES ,  LIOTTA LANCE A ,  PETRICOIN EMANUEL

Inventor： POPOV SERGUEI G ,  POPOVA TAISSIA ,  ESPINA VIRGINIA ,  BAILEY CHARLES ,  LIOTTA LANCE A ,  PETRICOIN EMANUEL

IPC: A61K31/496 ,  A61K45/06 ,  A61P31/04

CPC classification number: A61K45/06 ,  A61K31/496 ,  A61K2300/00

Abstract: The invention provides methods and materials for identifying agents for preventing and/or treating anthrax and similar diseases. Embodiments provide strains and model systems for studying non-lethal and lethal exposure to anthrax and similar disease vectors. Embodiments provide materials and methods for using the strains and model systems for differential profiling, such as proteomic profiling, such as differentiation phosphorylation profiling, to target identification and therapeutics discovery and development. Embodiments provide pharmaceutically acceptable compositions, and methods for using them to prevent and/or treat anthrax and similar diseases comprising an agent that decreases the activity of caspase 1/4, such as YVAD, and/or an agent that increases the phosphorylation of AKT, such as IB-MECA or Cl-IB-MECA, together with, in particular embodiments, an antibiotic, such as ciprofloxacin. Kits comprising the same are provided as well, among other things.

Abstract translation: 本发明提供用于鉴定用于预防和/或治疗炭疽和类似疾病的药剂的方法和材料。 实施例提供用于研究非致死和致死性暴露于炭疽和类似疾病载体的菌株和模型系统。 实施例提供了使用菌株和模型系统进行差异谱分析的材料和方法，例如蛋白质组学分析，例如分化磷酸化分析，靶向鉴定和治疗发现和发展。 实施方案提供了药学上可接受的组合物，以及使用它们来预防和/或治疗炭疽和类似疾病的方法，所述疾病包括降低半胱天冬酶1/4的活性的试剂，例如YVAD，和/或增加AKT磷酸化的试剂， 例如IB-MECA或Cl-IB-MECA，以及在具体实施方案中，抗生素，如环丙沙星。 还提供了包括其的套件，以及其他。

公开(公告)号：WO2008115653A2

公开(公告)日：2008-09-25

申请号：PCT/US2008/054568

申请日：2008-02-21

Applicant: CENTER FOR APPLIED PROTEOMICS AND MOLECULAR MEDICINE ,  LUCHINI, Alessandra ,  LIOTTA, Lance ,  PETRICOIN, Emanuel ,  GEHO, David

Inventor： LUCHINI, Alessandra ,  LIOTTA, Lance ,  PETRICOIN, Emanuel ,  GEHO, David

IPC: C12Q1/68

CPC classification number: B01J20/26 ,  B01D15/34 ,  B01J20/265 ,  B01J20/28078 ,  B01J20/28095 ,  B01J2220/54 ,  C12Q1/6816 ,  G01N33/54313 ,  G01N33/54353 ,  G01N33/5436 ,  Y10S435/81 ,  Y10S436/808 ,  Y10T436/255 ,  C12Q2565/518

Abstract: Capture particles for harvesting analytes from solution and methods for using them are described. The capture particles are made up of a polymeric matrix having pore size that allows for the analytes to enter the capture particles. The pore size of the capture particles may be changeable upon application of a stimulus to the particles, allowing the pore size of the particles to be changed so that analytes of interest remain sequestered inside the particles. The polymeric matrix of the capture particles may be made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle. The capture particles may be used to isolate and identify analytes present in a mixture. They may also be used to protect analytes which are typically subject to degradation upon harvesting and to concentrate low an analyte in low abundance in a fluid.

Abstract translation: 描述从溶液中收集分析物的捕获颗粒和使用它们的方法。 捕获颗粒由具有允许分析物进入捕获颗粒的孔径的聚合物基质构成。 当对颗粒施加刺激时，捕获颗粒的孔径可以变化，允许改变颗粒的孔径，使得目标分析物保留在颗粒内。 捕获颗粒的聚合物基质可以由具有结构单体和亲和单体的共聚物材料制成，亲和单体具有将分析物吸引到捕获颗粒的性质。 捕获颗粒可用于分离和鉴定混合物中存在的分析物。 它们也可用于保护在收获时通常会降解的分析物，并将低分析物浓缩在液体中的丰度低。

公开(公告)号：WO2008063369A2

公开(公告)日：2008-05-29

申请号：PCT/US2007/023026

申请日：2007-11-01

Applicant: GEORGE MASON INTELLECTUAL PROPERTIES, INC. ,  LOMA LINDA UNIVERSITY ,  LIOTTA, Lance ,  ZHOU, Wediong ,  KIRSCH, Wolff ,  ESPINA, Virginia ,  PETRICOIN, Emanuel ,  ROSS, Mark ,  MUELLER, Claudius ,  MAGAKI, Shino

Inventor： LIOTTA, Lance ,  ZHOU, Wediong ,  KIRSCH, Wolff ,  ESPINA, Virginia ,  PETRICOIN, Emanuel ,  ROSS, Mark ,  MUELLER, Claudius ,  MAGAKI, Shino

IPC: G01N33/53

CPC classification number: G01N33/6896 ,  G01N2800/2821 ,  G01N2800/2871

Abstract: Low molecular weight (LMW) peptides have been discovered that are indicative of neurological conditions, such as Alzheimer's Disease (AD), cognitive impairment and brain microhemmorhages. Evaluating patient samples for the presence of such LMW peptides is an effective means of detecting neurological conditions and monitoring the progression of the disease. The LMW peptides are particularly useful in detecting neurological conditions during the early stages without invasive procedures.

Abstract translation: 已经发现低分子量（LMW）肽指示神经病症，例如阿尔茨海默病（AD），认知障碍和脑微血管增生。 评估患者样品中是否存在这种LMW肽是检测神经疾病和监测疾病进展的有效手段。 LMW肽特别适用于在没有侵入性操作的早期阶段检测神经疾病。

公开(公告)号：WO2007106432A3

公开(公告)日：2007-09-20

申请号：PCT/US2007/006199

申请日：2007-03-12

Applicant: GEORGE MASON INTELLECTUAL PROPERTIES, INC. ,  ESPINA, Virginia ,  LIOTTA, Lance ,  PETRICOIN, Emanuel ,  ARAUJO, Robyn, Patrice, Deakin ,  GUARNIERE, Amy, Jayne, VanMeter ,  CALVERT, Valerie

Inventor： ESPINA, Virginia ,  LIOTTA, Lance ,  PETRICOIN, Emanuel ,  ARAUJO, Robyn, Patrice, Deakin ,  GUARNIERE, Amy, Jayne, VanMeter ,  CALVERT, Valerie

IPC: C12Q1/48 ,  A61K45/00 ,  G01N33/574

Abstract: This invention relates, e.g., to a method for predicting the response of a subject having a disease or condition mediated by EGFR (e.g., a cancer of epithelial origin, such as NSCLC) to an EGFR kinase inhibitor (e.g., Iressa® (gefitinib) and/or Tarceva® (erlotinib)). The method comprises measuring the amount of phosphorylation at residues Y1068 and T1148 in EGFR in a sample from the subject, wherein a significantly elevated level of phosphorylation at the two residues compared to a baseline value indicates that the subject is likely to be responsive to an agent that inhibits the kinase activity of EGFR. Other sites of phosphorylation that can be employed are also disclosed, including other residues in EGFR, as well as sites in other proteins of the EGFR signaling cascade.

公开(公告)号：WO2002077176A3

公开(公告)日：2002-10-03

申请号：PCT/US2002/008847

申请日：2002-03-22

Applicant: THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  MT. SINAI SCHOOL OF MEDICINE ,  PETRICOIN, Emanuel, Frank, III ,  LIOTTA, Lance, A. ,  EMMERT-BUCK, Michael, R. ,  ZHAO, Yingming

Inventor： PETRICOIN, Emanuel, Frank, III ,  LIOTTA, Lance, A. ,  EMMERT-BUCK, Michael, R. ,  ZHAO, Yingming

IPC: G01N33/53

Abstract: Provided herein are specific examples of tumor or tumor-stage linked protein fingerprints and specific proteins identified from these fingerprints as being aberrantly expressed in specific diseased cell types. Methods of using these fingerprints, sub-sets thereof, and individual proteins in the diagnosis, prognosis, treatment, treatment selection, and drug development for disease are also provided.