公开(公告)号：US5372809A

公开(公告)日：1994-12-13

申请号：US830313

申请日：1992-01-31

申请人： Lance A. Liotta ,  William Stetler-Stevenson ,  Henry Krutzsch

发明人： Lance A. Liotta ,  William Stetler-Stevenson ,  Henry Krutzsch

IPC分类号： G01N33/53 ,  A61K9/08 ,  A61K38/55 ,  A61P19/02 ,  A61P35/00 ,  A61P43/00 ,  C07H21/04 ,  C07K7/06 ,  C07K7/08 ,  C07K14/00 ,  C07K14/81 ,  C07K16/00 ,  C07K16/38 ,  C07K17/00 ,  C12N5/10 ,  C12N9/99 ,  C12N15/09 ,  G01N33/573 ,  A61K37/547 ,  C07K17/02

CPC分类号： C07K14/8146 ,  G01N33/573 ,  Y10S530/806 ,  Y10S530/81

摘要： A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence RKPRC or analogs thereof. The cysteine residue is required for activity. Affinity purified antibodies directed against specific peptides can be used to a) detect any general metalloproteinase enzyme with the sequence in part VAAHE or PRCGNPD, and distinguish it from other known members of the metalloproteinase family, b) block functional domains resulting in the inhibition of enzyme activity, and c) distinguish latent from activated forms of the enzyme.

摘要翻译： 存在切割细胞外基质分子的金属蛋白酶家族。 这些金属蛋白酶以潜伏活性形式分泌并需要活化以特异性切割优选的底物。 已经基于IV型原胶原酶的完整序列分析制备了一系列肽。 合成肽抑制剂，其对应于半胱氨酸重复区域和组氨酸区域; 这些肽的作用机理涉及抑制酶与底物的结合。 合成肽抑制剂，其对应于在活化期间切除的肽，并构成新型的金属蛋白酶抑制剂。 这些抑制剂是含有核心氨基酸序列RKPRC或其类似物的一系列肽的成员。 活性需要半胱氨酸残基。 针对特异性肽的亲和纯化抗体可用于a）用部分VAAHE或PRCGNPD中的序列检测任何一般金属蛋白酶，并将其与其他已知的金属蛋白酶家族成员区分开，b）阻断功能结构域，导致酶的抑制 活性，和c）区分潜在和酶的活化形式。

公开(公告)号：US5270447A

公开(公告)日：1993-12-14

申请号：US317407

申请日：1989-03-01

申请人： Lance A. Liotta ,  William Stetler-Stevenson ,  Henry Krutzsch

发明人： Lance A. Liotta ,  William Stetler-Stevenson ,  Henry Krutzsch

IPC分类号： C07K14/81 ,  G01N33/573 ,  A61K37/02 ,  C12N11/08

CPC分类号： C07K14/8146 ,  G01N33/573

摘要： A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV Procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence PRCG. The cysteine residue is required for activity. Affinity purified antibodies directed against specific peptides can be used to a) detect any general metalloproteinase enzyme with the sequence in part VAAHE or PRCGNPD, and distinguish it from other known members of the metalloproteinase family, b) block functional domains resulting in the inhibition of enzyme activity, and c) distinguish latent from activated forms of the enzyme.

摘要翻译： 存在切割细胞外基质分子的金属蛋白酶家族。 这些金属蛋白酶以潜伏活性形式分泌并需要活化以特异性切割优选的底物。 基于IV型原胶原酶的完整序列分析，已经制备了一系列肽。 合成肽抑制剂，其对应于半胱氨酸重复区域和组氨酸区域; 这些肽的作用机理涉及抑制酶与底物的结合。 合成肽抑制剂，其对应于在活化期间切除的肽，并构成新型的金属蛋白酶抑制剂。 这些抑制剂是含有核心氨基酸序列PRCG的一系列肽的成员。 活性需要半胱氨酸残基。 针对特异性肽的亲和纯化抗体可用于a）用部分VAAHE或PRCGNPD中的序列检测任何一般金属蛋白酶，并将其与其他已知的金属蛋白酶家族成员区分开，b）阻断功能结构域，导致酶的抑制 活性，和c）区分潜在和酶的活化形式。

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。

公开(公告)号：US08765386B2

公开(公告)日：2014-07-01

申请号：US13372627

申请日：2012-02-14

申请人： Jonathan Zmuda ,  Lance A. Liotta ,  Gordon Whiteley

发明人： Jonathan Zmuda ,  Lance A. Liotta ,  Gordon Whiteley

IPC分类号： G01N33/576 ,  A61K39/29

CPC分类号： G01N33/558 ,  G01N33/563 ,  G01N33/5767 ,  G01N2469/20

摘要： A method and device to detect Hepatitis C (HCV) antibodies in oral fluid is provided. This method introduces a non-antibody detection molecule that labels all classes of patient antibodies in oral fluid, followed by the specific concentration of labeled anti-HCV antibodies by selective capture in a trapping zone consisting of peptide antigens derived from the HCV genome. Signal generated by the labeled antibodies present in the trapping zone is proportional to the number of anti-HCV antibodies bound to the antigens present in the trapping zone. Presence of signal derived from the capture of antibody/detection molecule complexes in the trapping zone is indicative of past exposure to HCV.

摘要翻译： 提供了一种在口腔液中检测丙型肝炎（HCV）抗体的方法和装置。 该方法引入了在口腔液中标记所有类别的患者抗体的非抗体检测分子，随后通过在由HCV基因组衍生的肽抗原构成的捕获区中选择性捕获来标记抗HCV抗体的特异性浓度。 由捕获区中存在的标记抗体产生的信号与与捕获区中存在的抗原结合的抗HCV抗体的数量成比例。 来自俘获区域中抗体/检测分子复合物捕获的信号的存在表明过去暴露于HCV。

公开(公告)号：US20130137094A1

公开(公告)日：2013-05-30

申请号：US13575001

申请日：2011-01-25

申请人： Virginia A. Espina ,  Lance A. Liotta ,  Claudius Mueller

发明人： Virginia A. Espina ,  Lance A. Liotta ,  Claudius Mueller

IPC分类号： G01N1/30

CPC分类号： G01N1/30 ,  A01N1/00

摘要： 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.

摘要翻译： 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：US20120276521A1

公开(公告)日：2012-11-01

申请号：US13372627

申请日：2012-02-14

申请人： Jonathan Zmuda ,  Lance A. Liotta ,  Gordon Whiteley

发明人： Jonathan Zmuda ,  Lance A. Liotta ,  Gordon Whiteley

IPC分类号： C12Q1/70

CPC分类号： G01N33/558 ,  G01N33/563 ,  G01N33/5767 ,  G01N2469/20

摘要： A method and device to detect Hepatitis C (HCV) antibodies in oral fluid is provided. This method introduces a non-antibody detection molecule that labels all classes of patient antibodies in oral fluid, followed by the specific concentration of labeled anti-HCV antibodies by selective capture in a trapping zone consisting of peptide antigens derived from the HCV genome. Signal generated by the labeled antibodies present in the trapping zone is proportional to the number of anti-HCV antibodies bound to the antigens present in the trapping zone. Presence of signal derived from the capture of antibody/detection molecule complexes in the trapping zone is indicative of past exposure to HCV.

摘要翻译： 提供了一种在口腔液中检测丙型肝炎（HCV）抗体的方法和装置。 该方法引入了在口腔液中标记所有类别的患者抗体的非抗体检测分子，随后通过在由HCV基因组衍生的肽抗原构成的捕获区中选择性捕获来标记抗HCV抗体的特异性浓度。 由捕获区中存在的标记抗体产生的信号与与捕获区中存在的抗原结合的抗HCV抗体的数量成比例。 来自俘获区域中抗体/检测分子复合物捕获的信号的存在表明过去暴露于HCV。

公开(公告)号：US08124348B2

公开(公告)日：2012-02-28

申请号：US10912405

申请日：2004-08-05

申请人： Jonathan Zmuda ,  Lance A. Liotta ,  Gordon Whiteley

发明人： Jonathan Zmuda ,  Lance A. Liotta ,  Gordon Whiteley

IPC分类号： G01N33/576 ,  A61K39/29

CPC分类号： G01N33/558 ,  G01N33/563 ,  G01N33/5767 ,  G01N2469/20

摘要： A method and device to detect Hepatitis C (HCV) antibodies in oral fluid is provided. This method introduces a non-antibody detection molecule that labels all classes of patient antibodies in oral fluid, followed by the specific concentration of labeled anti-HCV antibodies by selective capture in a trapping zone consisting of peptide antigens derived from the HCV genome. Signal generated by the labeled antibodies present in the trapping zone is proportional to the number of anti-HCV antibodies bound to the antigens present in the trapping zone. Presence of signal derived from the capture of antibody/detection molecule complexes in the trapping zone is indicative of past exposure to HCV.

摘要翻译： 提供了一种在口腔液中检测丙型肝炎（HCV）抗体的方法和装置。 该方法引入了在口腔液中标记所有类别的患者抗体的非抗体检测分子，随后通过在由HCV基因组衍生的肽抗原构成的捕获区中选择性捕获来标记抗HCV抗体的特异性浓度。 由捕获区中存在的标记抗体产生的信号与与捕获区中存在的抗原结合的抗HCV抗体的数量成比例。 来自俘获区域中抗体/检测分子复合物捕获的信号的存在表明过去暴露于HCV。

公开(公告)号：US20110236999A1

公开(公告)日：2011-09-29

申请号：US13061507

申请日：2009-08-26

申请人： Lance A. Liotta ,  Alessandra Luchini ,  Emaneul F. Petricoin ,  Virginia Espina

发明人： Lance A. Liotta ,  Alessandra Luchini ,  Emaneul F. Petricoin ,  Virginia Espina

IPC分类号： G01N33/543 ,  B82Y15/00

CPC分类号： G01N33/521 ,  G01N33/54333 ,  G01N33/54346

摘要： An immunoassay device incorporating porous polymeric capture nanoparticles within either the sample collection vessel or pre-impregnated into a porous substratum within fluid flow path of the analytical device is presented. This incorporation of capture particles within the immunoassay device improves sensitivity while removing the requirement for pre-processing of samples prior to loading the immunoassay device. A preferred embodiment is coreshell bait containing capture nanoparticles which perform three functions in one step, in solution: a) molecular size sieving, b) target analyte sequestration and concentration, and c) protection from degradation. 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. This device is useful for point of care diagnostic assays for biomedical applications and as field deployable assays for environmental, pathogen and chemical or biological threat identification.

摘要翻译： 提供了在分析装置的流体流动路径内将多孔聚合物捕获纳米颗粒结合到样品采集容器中或预浸渍到多孔基质内的免疫测定装置。 这种在免疫测定装置内的捕获颗粒的并入提高了灵敏度，同时在加载免疫测定装置之前消除了样品预处理的要求。 优选的实施方案是含有捕获纳米颗粒的芯壳诱饵，其在一个步骤中在溶液中进行三个功能：a）分子筛分，b）目标分析物螯合和浓缩，以及c）防止降解。 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制成，亲和单体具有将分析物吸引到捕获颗粒的性质。 该设备可用于生物医学应用的护理点诊断分析以及环境，病原体和化学或生物威胁鉴定的现场部署测定。

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。

公开(公告)号：US06793172B2

公开(公告)日：2004-09-21

申请号：US10296137

申请日：2003-06-30

申请人： Lance A. Liotta

发明人： Lance A. Liotta

IPC分类号： B64C300

CPC分类号： B64C39/066 ,  A63H27/00 ,  B64C39/028 ,  B64C2201/105 ,  B64C2201/107

摘要： An aircraft which is designed for remote controlled slow flight, indoor or in a small outdoor yard or field. The aerial lifting body is defined by a series of lightweight planar or thin airfoil surfaces (A1, A2, A3, A4) arranged in a radially symmetrical configuration. Suspended within the cavity (O) formed by the thin airfoil surfaces (A1, A2, A3, A4) is a thrust generating propeller system (C) that is angled upwardly and that can be regulated remotely so as to change the angle of the thrust vector within the cavity (O) for steering. Lifting, stability, turning, and general control of the direction of motion in flight is accomplished without any formal wings, rudder, tail, or control surfaces.

摘要翻译： 一种专为遥控慢速飞行，室内或室外小型场地设计的飞机。 升降体由一系列以径向对称构造布置的轻型平面或薄型翼型表面（A1，A2，A3，A4）限定。 悬挂在由薄翼面（A1，A2，A3，A4）形成的空腔（O）内的是推力发生螺旋桨系统（C），其向上倾斜并且可以远程调节，以便改变推力角 在腔（O）内的向量用于转向。 飞行中的运动方向的提升，稳定性，转向和一般控制是在没有任何正式的机翼，方向舵，尾翼或控制面的情况下完成的。