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1. 发明申请

WO02095071A3 MEANS AND METHODS FOR IDENTIFYING GENES AND PROTEINS INVOLVED IN THE PREVENTION AND/OR REPAIR OF A REPLICATION ERROR 审中-公开
标题翻译：用于鉴定涉及预防和/或修复复制错误的基因和蛋白的手段和方法
公开(公告)号：WO02095071A3
公开(公告)日：2003-04-17
申请号：PCT/NL0200322
申请日：2002-05-22
申请人： KONINK NL AKADEMIE VAN WETENSC , TIJSTERMAN MARCEL , PLASTERK RONALD H A
发明人： TIJSTERMAN MARCEL , PLASTERK RONALD H A
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6897 , C12Q1/6886 , C12Q2600/158
摘要： The DNA in a cell is prone to mutation. Since too many mutations are detrimental to the survival of a cell or an organism, special mechanism have developed to prevent and/or repair at least part of such mutations. Many of these mechanisms act before the mutation becomes fixed into the genome through replication of the DNA. Some of the genes involved in the prevention of mutations have been identified. However, prior to the invention there was no coherent and systematic way of doing so. The means and methods of the invention enable a person skilled in the art to determine whether a product of a gene is involved in the prevention of a mutation. Identified genes can be used to develop diagnostic tools or used as a target for drug development to manipulate cells on the basis of the presence or absence of function of this gene. Since DNA instability is one of the reasons for rapid tumor progression, it will be useful to provide cancer cells with additional product of such genes for instance through gene therapy.
摘要翻译：细胞中的DNA易于发生突变。由于过多的突变对细胞或生物体的存活是有害的，因此已经开发了预防和/或修复至少部分这种突变的特殊机制。许多这些机制在突变通过DNA复制固定到基因组中之前起作用。已经确定了参与预防突变的一些基因。然而，在发明之前，没有一致的和系统的方式来这样做。本发明的手段和方法使本领域技术人员能够确定基因产物是否参与预防突变。鉴定基因可用于开发诊断工具或用作药物开发的靶标，以基于该基因功能的存在或缺失来操纵细胞。由于DNA不稳定性是肿瘤快速进展的原因之一，因此例如通过基因治疗为癌细胞提供此类基因的额外产物将是有用的。

2. 发明申请

WO2009008720A2 SMALL RNA MOLECULES, PRECURSORS THEREOF, MEANS AND METHODS FOR DETECTING THEM, AND USES THEREOF IN TYPING SAMPLES 审中-公开
公开(公告)号：WO2009008720A2
公开(公告)日：2009-01-15
申请号：PCT/NL2008050459
申请日：2008-07-07
申请人： KONINK NL AKADEMIE VAN WETENSC , VERENIGING VOOR CHRISTELIJK HOGER ONDERWIJS WETENSCHAPPELIJK ONDERZOEK EN PATIENTENZORG , CUPPEN EDWIN PIETER JOHAN GERA , MEIJER GERRIT ALBERT , BEREZIKOV EUGENE , CALVO MARIA BEGONA DIOSDADO
发明人： CUPPEN EDWIN PIETER JOHAN GERARD , MEIJER GERRIT ALBERT , BEREZIKOV EUGENE , CALVO MARIA BEGONA DIOSDADO
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12N15/1072 , C12N15/113 , C12Q2600/112 , C12Q2600/118 , C12Q2600/172 , C12Q2600/178
摘要： The invention is related to small RNA molecules, precursors thereof and methods for detecting such molecules. The invention is in particular concerned with differentially expressed small RNA molecules and precursors thereof. Various collections of small RNA molecules, precursors thereof and collections of probe and primers that can be used to detect small RNA molecules, precursors thereof are provided. Further provided are diagnostic test based on this differential expression. Also provided are therapeutic applications using one or more of the members of the presented collections.

3. 发明申请

WO02095071A8 MEANS AND METHODS FOR IDENTIFYING GENES AND PROTEINS INVOLVED IN THE PREVENTION AND/OR REPAIR OF A REPLICATION ERROR 审中-公开
标题翻译：用于识别预防和/或修复复制错误参与的基因和蛋白质的手段和方法
公开(公告)号：WO02095071A8
公开(公告)日：2003-02-27
申请号：PCT/NL0200322
申请日：2002-05-22
申请人： KONINK NL AKADEMIE VAN WETENSC , TIJSTERMAN MARCEL , PLASTERK RONALD H A
发明人： TIJSTERMAN MARCEL , PLASTERK RONALD H A
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6897 , C12Q1/6886 , C12Q2600/158
摘要： The DNA in a cell is prone to mutation. Since too many mutations are detrimental to the survival of a cell or an organism, special mechanism have developed to prevent and/or repair at least part of such mutations. Many of these mechanisms act before the mutation becomes fixed into the genome through replication of the DNA. Some of the genes involved in the prevention of mutations have been identified. However, prior to the invention there was no coherent and systematic way of doing so. The means and methods of the invention enable a person skilled in the art to determine whether a product of a gene is involved in the prevention of a mutation. Identified genes can be used to develop diagnostic tools or used as a target for drug development to manipulate cells on the basis of the presence or absence of function of this gene. Since DNA instability is one of the reasons for rapid tumor progression, it will be useful to provide cancer cells with additional product of such genes for instance through gene therapy.
摘要翻译：细胞中的DNA容易发生突变。由于太多的突变对细胞或生物体的存活是有害的，所以开发了预防和/或修复至少部分这种突变的特殊机制。许多这些机制在突变通过DNA的复制固定入基因组之前起作用。已经鉴定了涉及预防突变的一些基因。然而，在发明之前，没有一致和有系统地这样做的方式。本发明的方法和方法使得本领域技术人员能够确定基因的产物是否参与预防突变。鉴定的基因可用于开发诊断工具或用作药物开发的目标，以在该基因的存在或不存在的基础上操纵细胞。由于DNA不稳定性是肿瘤进展迅速的原因之一，因此通过基因治疗为癌细胞提供此类基因的其他产物将是有用的。

4. 发明申请

WO2009022907A3 A METHOD FOR IDENTIFYING, EXPANDING, AND REMOVING ADULT STEM CELLS AND CANCER STEM CELLS 审中-公开
标题翻译：识别，扩增和移除成熟干细胞和癌细胞的方法
公开(公告)号：WO2009022907A3
公开(公告)日：2009-06-25
申请号：PCT/NL2008050543
申请日：2008-08-08
申请人： HUBRECHT INST , KONINK NL AKADEMIE VAN WETENSC , CLEVERS JOHANNES CAROLUS , BARKER NICHOLAS , HAEGEBARTH ANDREA , VAN DE WETERING MARCUS LAMBERT
发明人： CLEVERS JOHANNES CAROLUS , BARKER NICHOLAS , HAEGEBARTH ANDREA , VAN DE WETERING MARCUS LAMBERTUS
IPC分类号： A61K38/00 , C07K14/72 , C12N5/071 , C12N5/074
CPC分类号： A61K38/177 , A61K45/06 , C12N5/068 , G01N33/5011
摘要： The invention relates to the fieldsof biochemistry, pharmacyand oncology. The invention particularly relates to the use of novel stem cell markers for the isolation of stem cells. The invention further relates to the obtained stem cells and their use in for example research or treatment, for example, for the preparation of a medicament for the treatment of damaged or diseased tissue. In one of the embodiments, the invention provides a method for obtaining (or isolating) stem cells comprising optionally preparing a cell suspension from a tissue or organ sample, contacting said cell suspension with an Lgr 6or 5 binding compound, identify the cells bound to said binding compound, and optionally isolating the stem cells from said binding compound. The invention further relates to means suitable for cancer treatment and even more specific for the treatment of cancer by eradicating cancer stem cells.
摘要翻译：本发明涉及生物化学，药学和肿瘤学领域。本发明特别涉及新型干细胞标记物用于分离干细胞的用途。本发明还涉及获得的干细胞及其在例如研究或治疗中的用途，例如用于制备用于治疗损伤或患病组织的药物。在一个实施方案中，本发明提供了一种用于获得（或分离）干细胞的方法，包括任选地从组织或器官样品制备细胞悬浮液，使所述细胞悬浮液与Lgr 6或5结合化合物接触，鉴定与所述并且任选地从所述结合化合物中分离干细胞。本发明还涉及适用于癌症治疗的方法，甚至更具体地通过根除癌症干细胞来治疗癌症。

5. 发明申请

WO0140804A9 CLEARANCE OF ABERRANT PROTEIN IN CORRELATION WITH DISEASE 审中-公开
标题翻译： ABIDANT蛋白与疾病相关的清除
公开(公告)号：WO0140804A9
公开(公告)日：2002-09-12
申请号：PCT/NL0000887
申请日：2000-12-04
申请人： KONINK NL AKADEMIE VAN WETENSC , HOL ELISABETH MARIA , VAN LEEUWEN FREDERIK WILLEM
发明人： HOL ELISABETH MARIA , VAN LEEUWEN FREDERIK WILLEM
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N33/6893
摘要： The present invention provides means and methods for the detection of a disease or pathological condition associated with molecular misreading of coding sequences in the genome and/or associated with the secretion of aberrant protein, comprising providing a sample of a body fluid and/or tissue of a patient and determining a level of a proteins aberrant counterpart in said body fluid and/or tissue. Molecular misreading seems to be a general cause for the synthesis of nonsense transcripts. Previously, molecular misreading was deemed to occur in age related disease and was seen as one of the mechanisms causing age related disease. In the present invention we observed that molecular misreading also occurs in healthy individuals. Surprisingly, the levels of aberrant protein in the body fluids of healthy non demented individuals is higher than in individuals suffering from age related disease. Determining levels of aberrant proteins, such as a +1 protein, allows diagnosing Alzheimers disease in an early stage of this disease, when mild cognitive impairments are apparent in these patients, and allows detecting the effects of any treatment on the disease process.
摘要翻译：本发明提供用于检测与基因组中编码序列的分子误读和/或与异常蛋白质分泌相关的疾病或病理状况的方法和方法，包括提供体液和/或组织的样品确定所述体液和/或组织中蛋白异常对应物的水平。分子误读似乎是合成无义转录物的一般原因。以前，分子误读被认为是在年龄相关疾病中发生的，被认为是引起年龄相关疾病的机制之一。在本发明中，我们观察到分子误读也发生在健康个体中。令人惊讶的是，健康非痴呆个体的体液异常蛋白水平高于患有年龄相关疾病的个体。确定异常蛋白质（例如+1蛋白）的水平允许在该疾病的早期阶段诊断阿尔茨海默病，当这些患者中轻度认知障碍明显时，并允许检测任何治疗对疾病过程的影响。

6. 发明申请

WO2009008720A3 SMALL RNA MOLECULES, PRECURSORS THEREOF, MEANS AND METHODS FOR DETECTING THEM, AND USES THEREOF IN TYPING SAMPLES 审中-公开
标题翻译：小RNA分子，其前体，检测它们的方法和方法及其在类型样品中的用途
公开(公告)号：WO2009008720A3
公开(公告)日：2009-04-09
申请号：PCT/NL2008050459
申请日：2008-07-07
申请人： KONINK NL AKADEMIE VAN WETENSC , VERENIGING VOOR CHRISTELIJK HOGER ONDERWIJS WETENSCHAPPELIJK ONDERZOEK EN PATIENTENZORG , CUPPEN EDWIN PIETER JOHAN GERA , MEIJER GERRIT ALBERT , BEREZIKOV EUGENE , CALVO MARIA BEGONA DIOSDADO
发明人： CUPPEN EDWIN PIETER JOHAN GERARD , MEIJER GERRIT ALBERT , BEREZIKOV EUGENE , CALVO MARIA BEGONA DIOSDADO
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12N15/1072 , C12N15/113 , C12Q2600/112 , C12Q2600/118 , C12Q2600/172 , C12Q2600/178
摘要： The invention is related to small RNA molecules, precursors thereof and methods for detecting such molecules. The invention is in particular concerned with differentially expressed small RNA molecules and precursors thereof. Various collections of small RNA molecules, precursors thereof and collections of probe and primers that can be used to detect small RNA molecules, precursors thereof are provided. Further provided are diagnostic test based on this differential expression. Also provided are therapeutic applications using one or more of the members of the presented collections.
摘要翻译：本发明涉及小RNA分子，其前体和检测这种分子的方法。本发明特别涉及差异表达的小RNA分子及其前体。提供了可用于检测小RNA分子的各种小RNA分子，其前体和探针和引物的集合，其前体。进一步提供基于该差异表达的诊断测试。还提供了使用所呈现的集合的一个或多个成员的治疗应用。

7. 发明申请

WO2005010041A2 REGULATORY REGION FOR XENOPUS LEF-1 EXPRESSION AND ITS USE 审中-公开
标题翻译： XENOPUS LEF-1表达及其使用的法规地区
公开(公告)号：WO2005010041A2
公开(公告)日：2005-02-03
申请号：PCT/NL2004000515
申请日：2004-07-16
申请人： KONINK NL AKADEMIE VAN WETENSC , DESTREE OLIVIER HUBERT JOSEPH , SPIEKER NICOLE
发明人： DESTREE OLIVIER HUBERT JOSEPH , SPIEKER NICOLE
IPC分类号： C07K14/46
CPC分类号： C07K14/463
摘要： In the present invention a regulatory sequence directing Lef-1 expression in Xenopus was found and used to find compounds capable of altering the expression characteristics of Lef-1 both in vitro and in vivo. The sequence can be used to drive expression of a heterologous gene of interest and confer on that gene of interest an expression characteristic of Lef-1. The invention further provides the identification of a non-viral internal ribosomal entry site derived from the 5´untranslated region of Lef-1.
摘要翻译：在本发明中，发现了在非洲爪蟾中引导Lef-1表达的调控序列，并用于发现能够在体外和体内改变Lef-1表达特征的化合物。该序列可用于驱动感兴趣的异源基因的表达，并赋予该感兴趣的基因表达Lef-1的表达特征。本发明还提供了衍生自Lef-1的5'非翻译区的非病毒内部核糖体进入位点的鉴定。

8. 发明申请

WO2010016766A3 ANTIBODIES RECOGNIZING ENDOGENOUS HUMAN LGR5 AND/OR LGR6 审中-公开
标题翻译：抗体识别内源性人LGR5和/或LGR6
公开(公告)号：WO2010016766A3
公开(公告)日：2010-05-06
申请号：PCT/NL2009050486
申请日：2009-08-07
申请人： KONINK NL AKADEMIE VAN WETENSC , HUBRECHT LAB , CLEVERS JOHANNES CAROLUS , BARKER NICHOLAS , HAEGEBARTH ANDREA , VAN DE WETERING MARCUS LAMBERT
发明人： CLEVERS JOHANNES CAROLUS , BARKER NICHOLAS , HAEGEBARTH ANDREA , VAN DE WETERING MARCUS LAMBERTUS
IPC分类号： C07K14/72 , A61K38/00 , C12N5/071
CPC分类号： C07K16/28 , A61K2039/505 , C07K14/705 , C07K2317/56 , C07K2317/565 , C07K2319/30 , G01N33/574
摘要： The present invention provides novel antibodies that bind human Leucine-rich-repeat- containing G-protein-coupled Receptor 5 (Lgr5) and/or Lgr6. More specifically, the invention provides antibodies that recognize endogenous Lgr5 and/or Lgr6. The invention further provides methods for generating the antibodies and uses of the antibodies.
摘要翻译：本发明提供了结合含富含亮氨酸重链的G蛋白偶联受体5（Lgr5）和/或Lgr6的新型抗体。更具体地，本发明提供了识别内源性Lgr5和/或Lgr6的抗体。本发明还提供了产生抗体的方法和抗体的用途。

9. 发明申请

WO2007081204A3 NUCLEIC ACID MOLECULES AND COLLECTIONS THEREOF, THEIR APPLICATION AND MODIFICATION 审中-公开
标题翻译：核酸分子及其收集品及其应用与修改
公开(公告)号：WO2007081204A3
公开(公告)日：2008-03-27
申请号：PCT/NL2007000012
申请日：2007-01-10
申请人： KONINK NL AKADEMIE VAN WETENSC , PLASTERK RONALD HANS ANTON , BEREZIKOV EUGENE , CUPPEN EDWIN PIETER JOHAN GERA
发明人： PLASTERK RONALD HANS ANTON , BEREZIKOV EUGENE , CUPPEN EDWIN PIETER JOHAN GERA
IPC分类号： C12N15/113 , C12Q1/68
CPC分类号： C12N15/113 , C12N2310/141 , C12N2320/10 , C12Q1/6886 , C12Q2600/158 , C12Q2600/178
摘要： The invention provides a method for characterising a sample comprising nucleic acid derived from a cell. The method comprises determining whether a sample comprises at least a minimal sequence of at least one new microRNA (miRNA) according to the invention or a mammalian ortholog thereof and characterizing the sample on the basis of the presence or absence of the miRNA. The invention further provides nucleic acid molecules and collections thereof and their use in therapeutic and diagnostic applications. The invention furthermore provides a method for identifying a miRNA molecule or a precursor molecule thereof.
摘要翻译：本发明提供了表征包含衍生自细胞的核酸的样品的方法。该方法包括确定样品是否包含至少一种根据本发明的至少一种新的微小RNA（miRNA）或其哺乳动物直系同源物的最小序列，并且基于miRNA的存在或不存在来表征该样品。本发明还提供了核酸分子及其收集物及其在治疗和诊断应用中的用途。本发明还提供了鉴定miRNA分子或其前体分子的方法。

10. 发明申请

WO0140804A3 CLEARANCE OF ABERRANT PROTEIN IN CORRELATION WITH DISEASE 审中-公开
标题翻译： ABIDANT蛋白与疾病相关的清除
公开(公告)号：WO0140804A3
公开(公告)日：2001-12-06
申请号：PCT/NL0000887
申请日：2000-12-04
申请人： KONINK NL AKADEMIE VAN WETENSC , HOL ELISABETH MARIA , LEEUWEN FREDERIK WILLEM VAN
发明人： HOL ELISABETH MARIA , VAN LEEUWEN FREDERIK WILLEM
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N33/6893
摘要： The present invention provides means and methods for the detection of a disease or pathological condition associated with molecular misreading of coding sequences in the genome and/or associated with the secretion of aberrant protein, comprising providing a sample of a body fluid and/or tissue of a patient and determining a level of a proteins aberrant counterpart in said body fluid and/or tissue. Molecular misreading seems to be a general cause for the synthesis of nonsense transcripts. Previously, molecular misreading was deemed to occur in age related disease and was seen as one of the mechanisms causing age related disease. In the present invention we observed that molecular misreading also occurs in healthy individuals. Surprisingly, the levels of aberrant protein in the body fluids of healthy non demented individuals is higher than in individuals suffering from age related disease. Determining levels of aberrant proteins, such as a +1 protein, allows diagnosing Alzheimers disease in an early stage of this disease, when mild cognitive impairments are apparent in these patients, and allows detecting the effects of any treatment on the disease process.
摘要翻译：本发明提供用于检测与基因组中编码序列的分子误读和/或与异常蛋白质分泌相关的疾病或病理状况的方法和方法，包括提供体液和/或组织的样品确定所述体液和/或组织中蛋白异常对应物的水平。分子误读似乎是合成无义转录物的一般原因。以前，分子误读被认为是在年龄相关疾病中发生的，被认为是引起年龄相关疾病的机制之一。在本发明中，我们观察到分子误读也发生在健康个体中。令人惊讶的是，健康非痴呆个体的体液异常蛋白水平高于患有年龄相关疾病的个体。确定异常蛋白质（例如+1蛋白）的水平允许在该疾病的早期阶段诊断阿尔茨海默病，当这些患者中轻度认知障碍明显时，并允许检测任何治疗对疾病过程的影响。

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