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51. 发明授权

US06271002B1 RNA amplification method 有权
标题翻译： RNA扩增法
公开(公告)号：US06271002B1
公开(公告)日：2001-08-07
申请号：US09411074
申请日：1999-10-04
申请人： Peter S. Linsley , Janell M. Schelter
发明人： Peter S. Linsley , Janell M. Schelter
IPC分类号： C12P1934
CPC分类号： C12N15/1096
摘要： The present invention relates to methods and kits for amplification of mRNA using a primer in PCR that contains an RNA polymerase promoter. The invention provides methods for amplification and detection of RNA derived from a population of cells, preferably eukaryotic cells and most preferably mammalian cells, which methods preserve fidelity with respect to sequence and transcript representation, and additionally enable amplification of extremely small amounts of mRNA, such as might be obtained from 106 mammalian cells. In typical embodiments of the invention, an RNA polymerase promoter (RNAP) is incorporated into ds cDNA by priming cDNA amplification by polymerase chain reaction (PCR) with an RNAP-containing primer. Following less than 20 cycles of PCR, the resultant RNAP-containing ds cDNA is transcribed into RNA using an RNA polymerase capable of binding to the RNAP introduced during cDNA synthesis. This combination of PCR and in vitro transcription (IVT) enables the generation of a relatively large amount of RNA from a small starting number of cells without loss of fidelity. RNAs generated using this method may be labeled and employed to profile gene expression in different populations of cells, e.g., by use of a polynucleotide microarray.
摘要翻译：本发明涉及使用含有RNA聚合酶启动子的PCR中的引物扩增mRNA的方法和试剂盒。本发明提供了用于扩增和检测衍生自细胞群（优选真核细胞，最优选哺乳动物细胞）的RNA的方法，所述方法保持关于序列和转录物表达的保真度，并且还能够扩增极少量的mRNA，例如可以从106个哺乳动物细胞获得。在本发明的典型实施方案中，通过用含有RNAP的引物通过聚合酶链反应（PCR）引发cDNA扩增，将RNA聚合酶启动子（RNAP）引入ds cDNA。在不到20个PCR循环后，使用能够结合cDNA合成引入的RNAP的RNA聚合酶将得到的含RNAP的ds cDNA转录成RNA。 PCR和体外转录（IVT）的这种组合使得能够从小的起始数量的细胞产生相对大量的RNA而不失去保真度。使用该方法产生的RNA可以被标记并用于分析不同细胞群体中的基因表达，例如通过使用多核苷酸微阵列。

52. 发明申请

US20110301048A1 DIAGNOSIS AND PROGNOSIS OF BREAST CANCER PATIENTS 审中-公开
标题翻译：乳腺癌患者的诊断和预防
公开(公告)号：US20110301048A1
公开(公告)日：2011-12-08
申请号：US12953314
申请日：2010-11-23
申请人： HongYue Dai , Yudong He , Peter S. Linsley , Mao Mao , Christopher J. Roberts , Laura Johanna Van't Veer , Marc J. Van de Vijver , Rene Bernards , A.A. M. Hart
发明人： HongYue Dai , Yudong He , Peter S. Linsley , Mao Mao , Christopher J. Roberts , Laura Johanna Van't Veer , Marc J. Van de Vijver , Rene Bernards , A.A. M. Hart
IPC分类号： C40B30/02 , C40B40/06 , C40B30/04
CPC分类号： C12Q1/6886 , C12Q2600/158 , G01N33/57415 , G06F19/00 , G16B25/00 , G16B40/00 , Y02A90/22 , Y02A90/26
摘要： The present invention relates to genetic markers whose expression is correlated with breast cancer. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate clinical conditions associated with breast cancer, such as the presence or absence of the estrogen receptor ESR1, and BRCA1 and sporadic tumors, and to provide information on the likelihood of tumor distant metastases within five years of initial diagnosis. The invention relates to methods of using these markers to distinguish these conditions. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the statistical methods disclosed herein.
摘要翻译：本发明涉及其表达与乳腺癌相关的遗传标记。具体地，本发明提供了一组标志物，其表达模式可用于区分与乳腺癌相关的临床病症，例如雌激素受体ESR1和BRCA1和散发性肿瘤的存在或不存在，并提供关于肿瘤可能性的信息初步诊断五年内远处转移。本发明涉及使用这些标记来区分这些条件的方法。本发明还涉及包含即用型微阵列的试剂盒和用于使用本文公开的统计学方法进行数据分析的计算机软件。

53. 发明申请

US20110250591A1 METHOD OF DESIGNING siRNAS FOR GENE SILENCING 有权
标题翻译：设计用于基因沉默的siRNA的方法
公开(公告)号：US20110250591A1
公开(公告)日：2011-10-13
申请号：US13100836
申请日：2011-05-04
申请人： Aimee L. Jackson , Steven R. Bartz , Julja Burchard , Peter S. Linsley , Wei Ge , Guy L. Cavet
发明人： Aimee L. Jackson , Steven R. Bartz , Julja Burchard , Peter S. Linsley , Wei Ge , Guy L. Cavet
IPC分类号： C12Q1/68
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/11 , C12N2330/31 , G06F19/18 , G06F19/22
摘要： The present invention provides a method for identifying siRNA target motifs in a transcript using a position-specific score matrix approach. The invention also provides a method for identifying off-target genes of an siRNA using a position-specific score matrix approach. The invention further provides a method for designing siRNAs with higher silencing efficacy and specificity. The invention also provides a library of siRNAs comprising siRNAs with high silencing efficacy and specificity.
摘要翻译：本发明提供使用位置特异性评分矩阵法来鉴定转录物中的siRNA靶基序的方法。本发明还提供了一种使用位置特异性评分矩阵方法鉴定siRNA的靶外基因的方法。本发明还提供了设计具有较高沉默功效和特异性的siRNA的方法。本发明还提供了包含具有高沉默功效和特异性的siRNA的siRNA文库。

54. 发明申请

US20100183612A1 METHODS OF TREATMENT USING CTLA4 MUTANT MOLECULES 审中-公开
标题翻译：使用CTLA4突变体分子进行治疗的方法
公开(公告)号：US20100183612A1
公开(公告)日：2010-07-22
申请号：US12694327
申请日：2010-01-27
申请人： Robert J. Peach , Joseph R. Naemura , Peter S. Linsley , Jurgen Bajorath
发明人： Robert J. Peach , Joseph R. Naemura , Peter S. Linsley , Jurgen Bajorath
IPC分类号： A61K39/395 , A61K39/00 , A61P37/06 , A61P35/02 , A61P35/00 , A61P3/10 , A61P17/06
CPC分类号： C07K14/7051 , A61K38/00 , A61K38/1774 , A61K39/39 , A61K39/3955 , A61K2039/505 , C07H21/04 , C07K14/70521 , C07K2319/30 , C12N5/0636 , C12N2501/51
摘要： The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.
摘要翻译：本发明提供与野生型CTLA4或非突变型CTLA4Ig相比，其结合比CD80和/或CD86抗原更高亲合力的可溶性CTLA4突变体分子。可溶性CTLA4分子具有包含CTLA4细胞外结构域的第一个氨基酸序列，其中S25-R33区域和M97-G107区域内的某些氨基酸残基被突变。本发明的突变分子还可以包括增加突变分子的溶解度的第二个氨基酸序列。

55. 发明授权

US07700556B2 Methods of treatment using CTLA4 mutant molecules 有权
标题翻译：使用CTLA4突变体分子的治疗方法
公开(公告)号：US07700556B2
公开(公告)日：2010-04-20
申请号：US11725762
申请日：2007-03-20
申请人： Robert James Peach , Joseph Naemura , Peter S. Linsley , Jurgen Bajorath
发明人： Robert James Peach , Joseph Naemura , Peter S. Linsley , Jurgen Bajorath
IPC分类号： A61K38/16
CPC分类号： C07K14/7051 , A61K38/00 , A61K38/1774 , A61K39/39 , A61K39/3955 , A61K2039/505 , C07H21/04 , C07K14/70521 , C07K2319/30 , C12N5/0636 , C12N2501/51
摘要： The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.
摘要翻译：本发明提供与野生型CTLA4或非突变型CTLA4Ig相比，其结合比CD80和/或CD86抗原更高亲合力的可溶性CTLA4突变体分子。可溶性CTLA4分子具有包含CTLA4细胞外结构域的第一个氨基酸序列，其中S25-R33区域和M97-G107区域内的某些氨基酸残基被突变。本发明的突变分子还可以包括增加突变分子的溶解度的第二个氨基酸序列。

56. 发明授权

US07595387B2 Modified polynucleotides for reducing off-target effects in RNA interference 有权
标题翻译：用于减少RNA干扰中的脱靶效应的修饰多核苷酸
公开(公告)号：US07595387B2
公开(公告)日：2009-09-29
申请号：US11019831
申请日：2004-12-22
申请人： Devin Leake , Angela Reynolds , Anastasia Khvorova , William Marshall , Peter S. Linsley
发明人： Devin Leake , Angela Reynolds , Anastasia Khvorova , William Marshall , Peter S. Linsley
IPC分类号： C07H21/04
CPC分类号： C12N15/111 , C12N15/1137 , C12N15/1138 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2320/11 , C12N2330/30 , C12Y207/11024 , C12Y301/03001 , C12N2310/3521
摘要： Methods and compositions for performing RNA interference with decreased off-target effects are provided The methods and compositions permit effective and efficient applications of RNA interference to applications such as diagnostics and therapeutics through the use of modifications to the siRNA. Uniquely modified siRNAs have been developed that reduce off-target effects incurred in gene-silencing. The modifications comprise 2′-O-alkyl or mismatch modification(s) at specific positions on the sense and/or antisense strands.
摘要翻译：提供了用于进行具有降低的脱靶效应的RNA干扰的方法和组合物。该方法和组合物允许通过使用对siRNA的修饰来有效和有效地将RNA干扰应用于诸如诊断和治疗的应用。已经开发了独特修饰的siRNA，其减少在基因沉默中引起的脱靶效应。修饰包括在有义和/或反义链上的特定位置上的2'-O-烷基或错配修饰。

57. 发明申请

US20090136957A1 Methods and compositions for regulating cell cycle progression via the miR-106B family 审中-公开
标题翻译：通过miR-106B家族调节细胞周期进程的方法和组合物
公开(公告)号：US20090136957A1
公开(公告)日：2009-05-28
申请号：US12283903
申请日：2008-09-15
申请人： Irena Ivanovska , Michael O. Carleton , Aimee L. Jackson , Michele A. Cleary , Peter S. Linsley
发明人： Irena Ivanovska , Michael O. Carleton , Aimee L. Jackson , Michele A. Cleary , Peter S. Linsley
IPC分类号： C12Q1/68 , C12N5/06
CPC分类号： C12N15/113 , C12N2310/113 , C12N2310/321 , C12N2310/3231 , C12N2310/3521
摘要： In one aspect, a method is provided of inhibiting proliferation of a mammalian cell comprising introducing into said cell an effective amount of at least one microRNA-specific inhibitor of at least one miR-106b family member. In another aspect a method is provided for accelerating proliferation of a mammalian cell comprising introducing into said cell an effective amount of at least one miR-106b family member.
摘要翻译：在一个方面，提供了抑制哺乳动物细胞增殖的方法，包括向所述细胞中引入有效量的至少一种miR-106b家族成员的至少一种微小RNA特异性抑制剂。在另一方面，提供了一种用于促进哺乳动物细胞增殖的方法，包括将有效量的至少一种miR-106b家族成员引入所述细胞。

58. 发明授权

US07439230B2 Methods of treatment using CTLA4 mutant molecules 有权
标题翻译：使用CTLA4突变体分子的治疗方法
公开(公告)号：US07439230B2
公开(公告)日：2008-10-21
申请号：US10980742
申请日：2004-11-03
申请人： Robert J. Peach , Joseph R. Naemura , Peter S. Linsley , Jurgen Bajorath
发明人： Robert J. Peach , Joseph R. Naemura , Peter S. Linsley , Jurgen Bajorath
IPC分类号： A61K38/16 , A61K39/395 , C07K14/00 , C07K14/725 , C07K16/46
CPC分类号： C07K14/7051 , A61K38/00 , A61K38/1774 , A61K39/39 , A61K39/3955 , A61K2039/505 , C07H21/04 , C07K14/70521 , C07K2319/30 , C12N5/0636 , C12N2501/51
摘要： The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.
摘要翻译：本发明提供与野生型CTLA4或非突变型CTLA4Ig相比，其结合比CD80和/或CD86抗原更高亲合力的可溶性CTLA4突变体分子。可溶性CTLA4分子具有包含CTLA4细胞外结构域的第一个氨基酸序列，其中S25-R33区域和M97-G107区域内的某些氨基酸残基被突变。本发明的突变分子还可以包括增加突变分子的溶解度的第二个氨基酸序列。

59. 发明授权

US07041634B2 Method of inhibiting immune system destruction of transplanted viable cells 失效
标题翻译：抑制移植活细胞免疫系统破坏的方法
公开(公告)号：US07041634B2
公开(公告)日：2006-05-09
申请号：US09049865
申请日：1998-03-27
申请人： Collin J. Weber , Mary K. Hagler , Peter S. Linsley , Judith A. Kapp , Susan A. Safley
发明人： Collin J. Weber , Mary K. Hagler , Peter S. Linsley , Judith A. Kapp , Susan A. Safley
IPC分类号： A61K38/00
CPC分类号： A61K9/5073 , A61K35/39 , A61K38/00 , A61K48/00 , C07K14/70521 , C07K2319/30 , C12N5/0676 , C12N5/0677 , Y10S424/812 , A61K2300/00
摘要： This invention provides a method of inhibiting viable cells transplanted into a subject from being destroyed by the subject's immune system which comprises: a) containing the viable cells, or tissue comprising the viable cells, prior to transplantation within a device comprising a semipermeable membrane; and b) treating the subject with a substance which inhibits an immune-system costimulation event in an amount effective to inhibit the subject's immune system from responding to said contained cells or tissue. In one embodiment, the substance which inhibits an immune-system costimulation event is CTLA4. Also provided by this invention is a method of treating diabetes in a subject which comprises: a) containing viable insulin-producing cells, or tissue comprising such cells, within a device comprising a semipermeable membrane; b) transplanting an effective amount of such contained viable insulin-producing cells into the subject; and c) treating the subject with an effective amount of a substance which inhibits an immune-system costimulation event.
摘要翻译：本发明提供一种抑制移植到受试者中的活细胞被受试者的免疫系统破坏的方法，该方法包括：a）在包含半透膜的装置内移植前含有活细胞或包含活细胞的组织; 和b）用抑制免疫系统共刺激事件的物质以有效抑制受试者的免疫系统对所述包含的细胞或组织的反应的物质治疗受试者。在一个实施方案中，抑制免疫系统共刺激事件的物质是CTLA4。本发明还提供了一种治疗受试者的糖尿病的方法，其包括：a）在包含半透膜的装置内含有存活的产生胰岛素的细胞或包含此类细胞的组织; b）将有效量的这种含有活体胰岛素的细胞移植到受试者中; 和c）用有效量的抑制免疫系统共刺激事件的物质治疗受试者。

60. 发明授权

US5618715A Oncostatin M and novel compositions having anti-neoplastic activity 失效
标题翻译：制瘤素M和具有抗肿瘤活性的新型组合物
公开(公告)号：US5618715A
公开(公告)日：1997-04-08
申请号：US75199
申请日：1993-06-10
申请人： Mohammed Shoyab , Joyce M. Zarling , Hans Marquardt , Marcia B. Hanson , Najma Malik , Peter S. Linsley , Timothy M. Rose , Anthony F. Purchio
发明人： Mohammed Shoyab , Joyce M. Zarling , Hans Marquardt , Marcia B. Hanson , Najma Malik , Peter S. Linsley , Timothy M. Rose , Anthony F. Purchio
IPC分类号： A61K38/00 , C07K14/07 , C07K14/475 , C07K14/495 , C07K14/52 , C07K16/22 , C07K16/24 , C12N15/62 , C12N15/73 , C12N5/00 , C07H17/00 , C12N15/00 , C12P21/06
CPC分类号： C07K14/005 , A61K38/191 , A61K38/204 , C07K14/475 , C07K14/495 , C07K14/52 , C07K14/522 , C07K16/22 , C07K16/24 , C12N15/625 , C12N15/73 , C07K2319/00 , C07K2319/02 , C07K2319/50 , C07K2319/75 , C12N2710/24122
摘要： Novel compositions comprising Oncostatin M and congeners thereof, as well as methods for their preparation and methods for their use are provided. The compositions may be prepared by isolation from natural sources, or by recombinant means in either prokaryotic or eukaryotic host cells. In addition, the DNA and polypeptide sequences for Oncostatin M are disclosed. The compositions find use in modulating growth of cells, in particular inhibition of tumor cell proliferation, and stimulation of normal cell growth, especially cells involved in hematopoiesis. Cell growth inhibition compositions may additionally include an adjunctive agent comprising at least one of a transforming growth factor, tumor necrosis factor, or an interferon. Receptors having high affinity for Oncostatin M may additionally be used to screen polypeptides for Oncostatin M-like activity. Methods for use of antibodies to the compositions and probes specific for Oncostatin M mRNA as a means for detecting tumor cells are also provided.
摘要翻译：提供了包含制瘤素M及其同源物的新型组合物，以及其制备方法及其使用方法。组合物可以通过从天然来源或通过重组方法在原核或真核宿主细胞中分离来制备。此外，公开了制瘤素M的DNA和多肽序列。该组合物可用于调节细胞的生长，特别是抑制肿瘤细胞增殖，刺激正常的细胞生长，特别是涉及造血的细胞。细胞生长抑制组合物可另外包括包含转化生长因子，肿瘤坏死因子或干扰素中的至少一种的辅助剂。对制瘤素M具有高亲和力的受体可以另外用于筛选多肽用于制瘤素M样活性。还提供了使用针对制瘤素M mRNA特异性的组合物和探针的抗体作为肿瘤细胞检测手段的方法。

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