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1. 发明申请

WO2007106425A3 BIOMARKERS OF THE DYSPLASTIC STATE OF CELLS 审中-公开
标题翻译：细胞滋养状态的生物标志物
公开(公告)号：WO2007106425A3
公开(公告)日：2008-10-16
申请号：PCT/US2007006176
申请日：2007-03-12
申请人： UNIV NORTHEASTERN , CYTYC CORP , WU SHIAW-LIN , HANCOCK WILLIAM S , KARGER BARRY L , LINDER JAMES , HANLON DAVID W
发明人： WU SHIAW-LIN , HANCOCK WILLIAM S , KARGER BARRY L , LINDER JAMES , HANLON DAVID W
IPC分类号： C12Q1/68 , G01N33/53
CPC分类号： G01N33/57411
摘要： The invention relates to methods for detecting and identifying potential biomarkers of high-grade cervical dysplasia in an individual human subject. The invention also relates to newly discovered biomarkers, as set forth in Tables 1-4 herein, which are associated with the dysplastic state of cervical cells. It has been discovered that a differential level of expression of any of these markers or combination of these markers correlates with a dysplastic condition in a human subject, e.g., a patient.
摘要翻译：本发明涉及用于检测和鉴定个体人类受试者高级宫颈发育异常的潜在生物标志物的方法。本发明还涉及新发现的与本发明的表1-4所示的生物标志物，其与子宫颈细胞的发育不良状态相关。已经发现，这些标记物或这些标记物的组合的表达差异水平与人受试者例如患者中的发育异常状况相关。

2. 发明申请

WO2006026569A2 COMPREHENSIVE CHARACTERIZATION OF COMPLEX PROTEINS AT TRACE LEVELS 审中-公开
标题翻译：复杂蛋白质的综合表征
公开(公告)号：WO2006026569A2
公开(公告)日：2006-03-09
申请号：PCT/US2005030713
申请日：2005-08-29
申请人： UNIV NORTHEASTERN , WU SHIAW-LIN , HANCOCK WILLIAM S , KARGER BARRY L
发明人： WU SHIAW-LIN , HANCOCK WILLIAM S , KARGER BARRY L
IPC分类号： G01N33/50
CPC分类号： G01N33/6848 , G01N33/6842
摘要： An LC-MS platform, Extended Range Proteomic Analysis, which is able to achieve very high sequence coverage and comprehensive characterization of posttranslational modifications in complex proteins at the trace level (e.g., low pmole to fmole), is described. The platform according to the invention provides advantages of both the top-down and bottom-up proteomic approaches by combining, In a preferred embodiment of the method, (i) digestion of the protein with an enzyme, such as Lys-C, that cuts less frequently than trypsin, or limited digestion with, e.g., trypsin, leading to, on average, a higher molecular weight peptide size with greater than 90% of the protein's peptide backbone sequence contained in fragments that are between 500 and 25,000 Da; (ii) high-performance LC separation of these resulting fragments; (iii) a new data acquisition strategy using on-line coupling of specific separated fragments to analysis in, e.g., the LTQ-FTMS, a hybrid mass spectrometer that couples a linear ion trap with a Fourier transform ion cyclotron resonance (FTICR) cell, for peptide analysis, preferably of the fragments in the range of 3000 to 10,000 Da; and (iv) new data analysis methods for assigning large peptide structures and determining the site of attachment of posttranslational modifications as well as structural features from the accurate precursor mass together with MS
摘要翻译：描述了能够在痕量水平（例如低pmole至fmole）的复杂蛋白质中实现非常高的序列覆盖率和翻译后修饰的全面表征的LC-MS平台，扩展范围蛋白质组学分析。根据本发明的平台通过组合来提供自顶向下和自下而上的蛋白质组学方法的优点。在该方法的优选实施方案中，（i）将蛋白质与诸如Lys-C的酶消化，平均来说，胰蛋白酶的平均消化速度比胰蛋白酶低，或者限制在500到25,000Da之间的片段中含有大于蛋白质肽主链序列的90％的分子量肽; （ii）这些得到的片段的高效液相色谱分离; （iii）使用特定分离片段的在线耦合来分析例如LTQ-FTMS，将线性离子阱与傅立叶变换离子回旋共振（FTICR）单元耦合的混合质谱仪的新数据采集策略，用于肽分析，优选在3000至10,000Da范围内的片段; 和（iv）用于分配大肽结构并确定翻译后修饰的附着位点的新数据分析方法以及来自准确前体质量的结构特征以及MS

3. 发明申请

WO2007106425A2 PROTEOMIC METHODS FOR THE IDENTIFICATION AND USE OF PUTATIVE BIOMARKERS ASSOCIATED WITH THE DYSPLASTIC STATE IN CERVICAL CELLS OR OTHER CELL TYPES 审中-公开
标题翻译：用于鉴定和使用与细胞中的浮游状态或其他细胞类型相关的引诱生物标记物的预防方法
公开(公告)号：WO2007106425A2
公开(公告)日：2007-09-20
申请号：PCT/US2007/006176
申请日：2007-03-12
申请人： NORTHEASTERN UNIVERSITY , CYTYC CORPORATION , WU, Shiaw-Lin , HANCOCK, William, S. , KARGER, Barry, L. , LINDER, James , HANLON, David, W.
发明人： WU, Shiaw-Lin , HANCOCK, William, S. , KARGER, Barry, L. , LINDER, James , HANLON, David, W.
IPC分类号： C12Q1/68
CPC分类号： G01N33/57411
摘要： The invention relates to methods for detecting and identifying potential biomarkers of high-grade cervical dysplasia in an individual human subject. The invention also relates to newly discovered biomarkers, as set forth in Tables 1-4 herein, which are associated with the dysplastic state of cervical cells. It has been discovered that a differential level of expression of any of these markers or combination of these markers correlates with a dysplastic condition in a human subject, e.g. , a patient.
摘要翻译：本发明涉及用于检测和鉴定个体人类受试者高级宫颈发育异常的潜在生物标志物的方法。本发明还涉及新发现的与本发明的表1-4所示的生物标志物，其与子宫颈细胞的发育不良状态相关。已经发现，这些标记物或这些标记物的组合的差异水平的表达与人类受试者的发育不良状况相关，例如，，病人。

4. 发明申请

WO2013148323A1 METHODS OF ANALYZING AND PREPARING PROTEIN COMPOSITIONS 审中-公开
标题翻译：分析和制备蛋白质组合物的方法
公开(公告)号：WO2013148323A1
公开(公告)日：2013-10-03
申请号：PCT/US2013/032171
申请日：2013-03-15
申请人： SHIRE HUMAN GENETIC THERAPIES, INC. , LIN, Melanie , SALINAS, Paul , WU, Shiaw-lin
发明人： SHIRE HUMAN GENETIC THERAPIES, INC. , LIN, Melanie , SALINAS, Paul , WU, Shiaw-lin
IPC分类号： A61K38/46
CPC分类号： C12Q1/44 , G01N2560/00
摘要： Methods for analyzing protein samples of recombinant human arylsulfatase A(rhASA), having one or more disulfide linkages are described. In some instances, the samples are analyzed using enzyme digestion, e.g., multi-enzyme digestion and liquid chromatography-mass spectrometry (LC-MS). The proteins described herein can be glycosylated (e.g., fully or partially glycosylated) or non-glycosylated. The methods described herein can include one or more of enzymatic digestion, chromatography, and mass spectrometry, e.g., multi-enzyme digestion and/or liquid chromatography-mass spectrometry (LC-MS). In some embodiments, the mass spectrometry utilizes collision induced dissociation (CID) and/or electron transfer dissociation (ETD). For example, the mass spectrometry can utilize CID, ETD, and CID of the isolated charge-reduced ions (MS3), e.g., after ETD.
摘要翻译：描述了分析具有一个或多个二硫键的重组人芳基硫酸酯酶A（rhASA）的蛋白质样品的方法。在一些情况下，使用酶消化（例如多酶消化和液相色谱 - 质谱法（LC-MS））分析样品。本文所述的蛋白质可以被糖基化（例如完全或部分糖基化）或非糖基化。本文所述的方法可以包括酶消化，色谱法和质谱法中的一种或多种，例如多酶消化和/或液相色谱 - 质谱（LC-MS）。在一些实施方案中，质谱法利用碰撞诱导解离（CID）和/或电子转移离解（ETD）。例如，质谱可以利用分离的电荷还原离子（MS3）的CID，ETD和CID，例如在ETD之后。

5. 发明申请

WO2006026569A3 COMPREHENSIVE CHARACTERIZATION OF COMPLEX PROTEINS AT TRACE LEVELS 审中-公开
公开(公告)号：WO2006026569A3
公开(公告)日：2006-03-09
申请号：PCT/US2005/030713
申请日：2005-08-29
申请人： NORTHEASTERN UNIVERSITY , WU, Shiaw-Lin , HANCOCK, William, S. , KARGER, Barry, L.
发明人： WU, Shiaw-Lin , HANCOCK, William, S. , KARGER, Barry, L.
IPC分类号： G01N24/00 , G01N24/14
摘要： A combination of “bottom up” anf “top down” MS analysis of posstranslational modifications in complex proteins is described. The method comprises digestion of the protein with an enzyme that forms larger peptide fragments than trypsin (> 3000 D), performing HPLC with the fragments and applying a new data acquisition strategy using on-line coupling with e.g. LTQ-FTMS, a hybrid mass spectrometer that couples a linear ion trap with a Fourier transform ion cyclotron resonance (FTICR) cell. The method is applied to analysis of posstranslational modifications of protein isoforms.

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