公开(公告)号：US20120165217A1

公开(公告)日：2012-06-28

申请号：US13391794

申请日：2010-04-03

申请人： Larry Gold ,  Edward N. Brody ,  Rachel M. Ostroff ,  Dominic Zichi ,  Alex A.E. Stewart ,  Michael Riel-Mehan ,  Mark Messenbaugh ,  Randee S. Schwartz ,  Jeffery Walker ,  Stephen Alaric Williams ,  Malti Nikrad

发明人： Larry Gold ,  Edward N. Brody ,  Rachel M. Ostroff ,  Dominic Zichi ,  Alex A.E. Stewart ,  Michael Riel-Mehan ,  Mark Messenbaugh ,  Randee S. Schwartz ,  Jeffery Walker ,  Stephen Alaric Williams ,  Malti Nikrad

IPC分类号： C40B30/04 ,  G06F19/00

CPC分类号： G01N33/57449 ,  G16B40/00

摘要： The present disclosure includes biomarkers, methods, devices, reagents, systems, and kits for the detection and diagnosis of cancer. In one aspect, the disclosure provides biomarkers that can be used alone or in various combinations to diagnose cancer. In another aspect, methods are provided for diagnosing cancer in an individual, where the methods include detecting, in a biological sample from an individual, at least one biomarker value corresponding to at least one biomarker selected from the group of biomarkers provided in Table 24, wherein the individual is classified as having cancer, or the likelihood of the individual having cancer is determined, based on the at least one biomarker value.

摘要翻译： 本公开包括用于癌症的检测和诊断的生物标志物，方法，装置，试剂，系统和试剂盒。 一方面，本公开提供可以单独使用或以各种组合使用以诊断癌症的生物标志物。 在另一方面，提供了用于诊断个体癌症的方法，其中所述方法包括在来自个体的生物样品中检测至少一种对应于选自表24中提供的生物标志物组的生物标志物的生物标记值， 其中所述个体基于所述至少一种生物标志物值被分类为具有癌症或确定个体患有癌症的可能性。

公开(公告)号：US20120115752A1

公开(公告)日：2012-05-10

申请号：US13382493

申请日：2010-07-09

申请人： Dominic Zichi ,  Sheri K. Wilcox ,  Chris Bock ,  Daniel J. Schneider ,  Bruce Eaton ,  Larry Gold ,  Thale C. Jarvis ,  Jeffrey D. Carter

发明人： Dominic Zichi ,  Sheri K. Wilcox ,  Chris Bock ,  Daniel J. Schneider ,  Bruce Eaton ,  Larry Gold ,  Thale C. Jarvis ,  Jeffrey D. Carter

IPC分类号： C40B30/04 ,  C12Q1/68 ,  C12Q1/70 ,  C07H21/00 ,  C12Q1/02 ,  B82Y15/00

CPC分类号： C12N15/1048 ,  C12N15/115 ,  C12N2310/16 ,  C12Q1/6811 ,  G01N33/5308 ,  C12Q2525/117 ,  C12Q2525/205 ,  C12Q2541/101

摘要： The present disclosure describes the identification and use of aptamers and photoaptamers having slower dissociation rate constants than those obtained using previously described methods. Specifically, the present disclosure describes methods for the identification and use of aptamers to one or more targets within a histological or cytological sample, which have slow rates of dissociation. The aptamers may be used to assess localization, relative density, and presence or absence of one or more targets in cytological and histological samples. Targets may be selected that are specific and diagnostic of a given disease state for which the sample was collected. The aptamers may also be used to introduce target specific signal moieties. In addition to target identification, the aptamers may be used to amplify signal generation through a variety of methods.

摘要翻译： 本公开描述了具有比使用先前描述的方法获得的那些更快的解离速率常数的适配体和光致抗体的鉴定和使用。 具体地，本公开描述了用于鉴定和使用适配体到组织学或细胞学样品中的一种或多种目标的方法，其具有缓慢的解离速率。 适配体可用于评估细胞学和组织学样品中的一种或多种靶标的定位，相对密度和存在或不存在。 可以选择对于样品收集的给定疾病状态的特异性和诊断性的靶标。 适体也可以用于引入目标特异性信号部分。 除目标识别之外，适体可用于通过各种方法放大信号产生。

公开(公告)号：US20120077695A1

公开(公告)日：2012-03-29

申请号：US13246388

申请日：2011-09-27

申请人： Rachel M. Ostroff ,  Alex A.E. Stewart ,  Stephen Alaric Williams ,  Edward N. Brody ,  Malti Nikrad ,  Michael Riel-Mehan

发明人： Rachel M. Ostroff ,  Alex A.E. Stewart ,  Stephen Alaric Williams ,  Edward N. Brody ,  Malti Nikrad ,  Michael Riel-Mehan

IPC分类号： C40B30/04 ,  C40B40/10

CPC分类号： C12Q1/6886 ,  C12Q2600/158 ,  G01N33/57407 ,  G01N2800/50

摘要： The present disclosure includes biomarkers, methods, devices, reagents, systems, and kits for the detection and diagnosis of cancer. In one aspect, methods are provided for diagnosing mesothelioma where the methods include detecting, in a biological sample, at least one biomarker value corresponding to at least one biomarker selected from the biomarkers provided in Table 1, wherein an individual is classified as having mesothelioma, or the likelihood of an individual having mesothelioma is determined, based on the at least one biomarker value. In another aspect, methods are provided for diagnosing cancer generally where the methods include detecting, in a biological sample at least one biomarker value corresponding to at least one biomarker selected from the biomarkers provided in Table 17, wherein an individual is classified as having cancer generally, or the likelihood of an individual having cancer is determined, based on the at least one biomarker value.

摘要翻译： 本公开包括用于癌症的检测和诊断的生物标志物，方法，装置，试剂，系统和试剂盒。 在一个方面，提供了用于诊断间皮瘤的方法，其中所述方法包括在生物样品中检测对应于选自表1中提供的生物标志物的至少一种生物标志物的至少一种生物标记值，其中个体被分类为具有间皮瘤， 或者基于所述至少一种生物标志物值确定个体具有间皮瘤的可能性。 在另一方面，提供了用于诊断癌症的方法，其中所述方法包括在生物样品中检测对应于选自表17中提供的生物标志物的至少一种生物标志物的至少一种生物标记值，其中个体被分类为具有癌症 或者确定个体患有癌症的可能性，基于至少一种生物标志物值。

公开(公告)号：US20100209935A1

公开(公告)日：2010-08-19

申请号：US12771895

申请日：2010-04-30

申请人： Larry Gold ,  Dominic Zichi

发明人： Larry Gold ,  Dominic Zichi

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6839 ,  C07B2200/11 ,  C12Q1/6834 ,  C12Q1/6837 ,  C40B40/00 ,  Y10S977/924 ,  C12Q2565/514 ,  C12Q2565/101 ,  C12Q2541/101 ,  C12Q2525/205

摘要： A nucleic acid ligand “biochip” is disclosed, consisting of a solid support to which one or more specific nucleic acid ligands is attached in a spatially defined manner. Each nucleic acid ligand binds specifically and avidly to a particular target molecule contained within a test mixture, such as a bodily fluid. The target molecules include, but are not limited to, proteins (cellular, viral, bacterial, etc.) hormones, sugars, metabolic byproducts, cofactor, and intermediates, drugs, and toxins. Contacting the test mixture with the biochip leads to the binding of a target molecule to its cognate nucleic acid ligand. The biochip may then be contacted with a reagent(s) that reacts covalently with proteins and not with nucleic acids. Each protein target in the test mixture may then detected by detecting the presence of the reagent at the appropriate address on the biochip.

摘要翻译： 公开了一种核酸配体“生物芯片”，其由以空间限定的方式连接一个或多个特定核酸配体的固体支持物组成。 每个核酸配体特异性地并且强烈地结合到测试混合物（例如体液）中所含的特定靶分子。 靶分子包括但不限于蛋白质（细胞，病毒，细菌等）激素，糖，代谢副产物，辅因子和中间体，药物和毒素。 将测试混合物与生物芯片接触导致靶分子与其同源核酸配体的结合。 然后生物芯片可以与与蛋白质共价反应的试剂与不与核酸反应的试剂接触。 然后可以通过检测生物芯片上适当地址处的试剂的存在来检测测试混合物中的每个蛋白质靶标。

公开(公告)号：US07709192B2

公开(公告)日：2010-05-04

申请号：US10375487

申请日：2003-02-27

申请人： Larry Gold ,  Dominic Zichi

发明人： Larry Gold ,  Dominic Zichi

IPC分类号： C12Q1/68 ,  G01N33/53

CPC分类号： C12Q1/6839 ,  C07B2200/11 ,  C12Q1/6834 ,  C12Q1/6837 ,  C40B40/00 ,  Y10S977/924 ,  C12Q2565/514 ,  C12Q2565/101 ,  C12Q2541/101 ,  C12Q2525/205

摘要： A nucleic acid ligand “biochip” is disclosed, consisting of a solid support to which one or more specific nucleic acid ligands is attached in a spatially defined manner. Each nucleic acid ligand binds specifically and avidly to a particular target molecule contained within a test mixture, such as a bodily fluid. The target molecules include, but are not limited to, proteins (cellular, viral, bacterial, etc.) hormones, sugars, metabolic byproducts, cofactor, and intermediates, drugs, and toxins. Contacting the test mixture with the biochip leads to the binding of a target molecule to its cognate nucleic acid ligand. The biochip may then be contacted with a reagent(s) that reacts covalently with proteins and not with nucleic acids. Each protein target in the test mixture may then detected by detecting the presence of the reagent at the appropriate address on the biochip.

摘要翻译： 公开了一种核酸配体“生物芯片”，其由以空间限定的方式连接一个或多个特定核酸配体的固体支持物组成。 每个核酸配体特异性地并且强烈地结合到测试混合物（例如体液）中所含的特定靶分子。 靶分子包括但不限于蛋白质（细胞，病毒，细菌等）激素，糖，代谢副产物，辅因子和中间体，药物和毒素。 将测试混合物与生物芯片接触导致靶分子与其同源核酸配体的结合。 然后生物芯片可以与与蛋白质共价反应的试剂与不与核酸反应的试剂接触。 然后可以通过检测生物芯片上适当地址处的试剂的存在来检测测试混合物中的每个蛋白质靶标。

公开(公告)号：US20100070191A1

公开(公告)日：2010-03-18

申请号：US12556480

申请日：2009-09-09

申请人： Larry Gold ,  Marty Stanton ,  Edward N. Brody ,  Rachel M. Ostroff ,  Dominic Zichi ,  Alex A.E. Stewart

发明人： Larry Gold ,  Marty Stanton ,  Edward N. Brody ,  Rachel M. Ostroff ,  Dominic Zichi ,  Alex A.E. Stewart

IPC分类号： G01N33/574 ,  C12Q1/02 ,  G06F19/00

CPC分类号： G01N33/57423

摘要： The present application includes biomarkers, methods, devices, reagents, systems, and kits for the detection and diagnosis of lung cancer. In one aspect, the application provides biomarkers that can be used alone or in various combinations to diagnose lung cancer or permit the differential diagnosis of pulmonary nodules as benign or malignant. In another aspect, methods are provided for diagnosing lung cancer in an individual, where the methods include detecting, in a biological sample from an individual, at least one biomarker value corresponding to at least one biomarker selected from the group of biomarkers provided in Table 1, Col. 2, wherein the individual is classified as having lung cancer, or the likelihood of the individual having lung cancer is determined, based on the at least one biomarker value.

摘要翻译： 本申请包括用于肺癌的检测和诊断的生物标志物，方法，装置，试剂，系统和试剂盒。 在一个方面，该应用提供可以单独使用或以各种组合使用以诊断肺癌或允许肺结节的鉴别诊断为良性或恶性的生物标志物。 在另一方面，提供了用于诊断个体中的肺癌的方法，其中所述方法包括在来自个体的生物样品中检测至少一种对应于选自表1中提供的生物标志物组的至少一种生物标志物的生物标记值 ，第2栏，其中基于所述至少一种生物标记值，将个体分类为具有肺癌或确定患有肺癌的个体的可能性。

公开(公告)号：US20090098549A1

公开(公告)日：2009-04-16

申请号：US12175388

申请日：2008-07-17

申请人： Daniel J. Schneider ,  Sheri K. Wilcox ,  Dominic Zichi ,  Dan Nieuwlandt ,  Jeff Carter ,  Larry Gold

发明人： Daniel J. Schneider ,  Sheri K. Wilcox ,  Dominic Zichi ,  Dan Nieuwlandt ,  Jeff Carter ,  Larry Gold

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6811 ,  C12N15/1048 ,  C12N15/111 ,  C12N15/115 ,  C12N2310/16 ,  C12N2320/13 ,  C12Q2541/101 ,  C12Q2525/205 ,  C12Q2525/117

摘要： The present disclosure describes improved SELEX methods for generating nucleic acid ligands that are capable of binding to target molecules and improved photoSELEX methods for generating photoreactive nucleic acid ligands that are capable of both binding and covalently crosslinking to target molecules. The disclosure further describes nucleic acid libraries having expanded physical and chemical properties and their use in SELEX and photoSELEX; methods for increasing the crosslinking efficiencies of photoaptamers; methods for producing photoaptamers having selective modifications that enhance functionality and minimize non-specific photoreactions; and methods for generating truncated nucleic acid ligands from nucleic acid ligands of longer length. The disclosure further describes aptamers and photoaptamers obtained by using any of the foregoing.

摘要翻译： 本公开描述了用于产生能够结合靶分子的核酸配体的改进的SELEX方法和用于产生能够与靶分子结合和共价交联的光反应性核酸配体的改进的photoSELEX方法。 本公开进一步描述了具有扩展的物理和化学性质及其在SELEX和photoSELEX中的用途的核酸文库; 提高光催化剂交联效率的方法; 制备具有增强功能并使非特异性光反应最小化的选择性修饰的光致抗体的方法; 以及用于从较长长度的核酸配体产生截短的核酸配体的方法。 本公开进一步描述了通过使用上述任何一种获得的适体和光致抗体。

公开(公告)号：US20040132067A1

公开(公告)日：2004-07-08

申请号：US10681822

申请日：2003-10-08

申请人： SOMALOGIC, INC.

发明人： Larry Gold ,  Michael Willis ,  Tad Koch ,  Steven Ringquist ,  Kirk Jensen ,  Brent Atkinson

IPC分类号： C12Q001/68 ,  C07H021/04 ,  C12P019/34

CPC分类号： G01N33/76 ,  B82Y5/00 ,  C07H19/06 ,  C07H19/10 ,  C07H21/00 ,  C07K14/001 ,  C12N9/1276 ,  C12N15/1048 ,  C12N2310/13 ,  C12N2310/322 ,  C12N2310/53 ,  C12Q1/37 ,  C12Q1/6804 ,  C12Q1/6811 ,  C12Q1/70 ,  C12Q1/703 ,  C40B40/00 ,  F02B2075/027 ,  G01N33/531 ,  G01N33/532 ,  G01N33/535 ,  G01N33/56988 ,  G01N33/68 ,  G01N2333/163 ,  G01N2333/8125 ,  G01N2333/96433 ,  G01N2333/966 ,  G01N2333/974 ,  C12Q2525/101

摘要： A method for identifying nucleic acid ligands to target molecules using the SELEX procedure wherein the candidate nucleic acids contain photoreactive groups and nucleic acid ligands identified thereby are claimed. The complexes of increased affinity nucleic acids and target molecules formed in the procedure are crosslinked by irradiation to facilitate separation from unbound nucleic acids. In other methods partitioning of high and low affinity nucleic acids is facilitated by primer extension steps as shown in the figure in which chain termination nucleotides, digestion resistant nucleotides or nucleotides that allow retention of the cDNA product on an affinity matrix are differentially incorporated into the cDNA products of either the high or low affinity nucleic acids and the cDNA products are treated accordingly to amplification, enzymatic or chemical digestion or by contact with an affinity matrix.

摘要翻译： 使用SELEX方法鉴定靶分子的核酸配体的方法，其中候选核酸含有由其鉴定的光反应性基团和核酸配体。 本方法中形成的增加的亲和核酸和靶分子的复合物通过照射进行交联，以促进与未结合核酸的分离。 在其他方法中，通过如图所示的引物延伸步骤促进了高亲和性核酸的分配，其中使得能够将亲和基质上的cDNA产物保留的链终止核苷酸，消化抗性核苷酸或核苷酸差异并入cDNA 相应地对高亲和性核酸和cDNA产物的产物进行扩增，酶促或化学消化或通过与亲和基质接触。

公开(公告)号：US20030087301A1

公开(公告)日：2003-05-08

申请号：US10331083

申请日：2002-12-27

申请人： SomaLogic, Inc.

发明人： Jonathan Drew Smith ,  Larry Gold

IPC分类号： C12Q001/68 ,  C07H021/04 ,  C12P019/34

CPC分类号： C12N15/1048

摘要： The invention provides method for producing nucleic acid ligands that generate a signal, or cause a decrease in the level of a signal, in the presence of a target molecule or an environmental stimulus. The methods of the instant invention are collectively termed Conditional SELEX. The nucleic acid ligands of the instant invention are useful in any application where it is desirable to measure the concentration of a target molecule or detect and quantitate an environmental stimulus.

摘要翻译： 本发明提供了在目标分子或环境刺激的存在下产生产生信号或引起信号水平降低的核酸配体的方法。 本发明的方法被统称为条件SELEX。 本发明的核酸配体可用于需要测量靶分子的浓度或检测和定量环境刺激的任何应用中。

公开(公告)号：US20020106652A1

公开(公告)日：2002-08-08

申请号：US09882246

申请日：2001-06-14

申请人： SomaLogic, Inc.

发明人： Larry Gold ,  Michael Willis ,  Tad Koch ,  Steven Ringquist ,  Kirk Jensen ,  Brent Atkinson

IPC分类号： C12Q001/68 ,  C07H021/04 ,  C12P019/34 ,  C08K003/00

CPC分类号： G01N33/76 ,  A61K47/547 ,  A61K47/549 ,  B82Y5/00 ,  C07H19/06 ,  C07H19/10 ,  C07H21/00 ,  C07K14/001 ,  C12N9/1276 ,  C12N15/1048 ,  C12N15/115 ,  C12N2310/13 ,  C12N2310/322 ,  C12N2310/53 ,  C12Q1/37 ,  C12Q1/6811 ,  C12Q1/703 ,  C40B40/00 ,  F02B2075/027 ,  G01N33/531 ,  G01N33/532 ,  G01N33/535 ,  G01N33/56988 ,  G01N33/68 ,  G01N2333/163 ,  G01N2333/575 ,  G01N2333/62 ,  G01N2333/8125 ,  G01N2333/96433 ,  G01N2333/96455 ,  G01N2333/966 ,  G01N2333/9726 ,  G01N2333/974 ,  G01N2333/976 ,  C12Q2541/101 ,  C12Q2523/313

摘要： A method for identifying nucleic acid ligands to target molecules using the SELEX procedure. Nucleic acid candidate sequences contain photoreactive groups. After exposure of the nucleic acid sequences to the target molecule, nucleic acid-target molecule complexes are formed between nucleic acids having increased affinity to the target molecule and the target molecule. The complexes are irradiated such that photocrosslinks form between the photoreactive groups of the bound nucleic acids and the target molecule. The photocrosslinked complexes are separated from unbound nucleic acids, and the nucleic acids amplified to yield a ligand-enriched mixture of nucleic acids. Described herein are methods for improved partitioning between high and low affinity nucleic acid ligands identified through the SELEX method, termed solution SELEX. The solution SELEX method achieves partitioning between high and low affinity nucleic acid-target complexes through a number of methods, including (1) primer extension inhibition which results in differentiable cDNA products. Primer extension inhibition is achieved with the use of nucleic acid polymerases, including DNA or RNA polymerases, reverse transcriptase, and Qnull-replicase; (2) exonuclease hydrolysis inhibition which results in only the highest affinity ligands amplifying during PCR. This is achieved with the use of any 3nullnull5null double-stranded exonuclease; (3) linear to circle formation to generate molecules amplifiable during PCR; or (4) PCR amplification of single-stranded nucleic acids. A central theme of the method of the present invention is that the nucleic acid candidate mixture is screened in solution and results in preferential amplification of the highest affinity RNA ligand or catalytic RNA.

摘要翻译： 使用SELEX方法鉴定靶向分子的核酸配体的方法。 核酸候选序列含有光反应性基团。 在将核酸序列暴露于靶分子后，在靶分子和靶分子之间具有增加的亲和力的核酸之间形成核酸 - 靶分子复合物。 照射复合物，使得结合的核酸的光反应性基团与目标分子之间形成光交联。 将光交联的复合物与未结合的核酸分离，并扩增核酸以产生富配体的核酸混合物。 本文描述了通过SELEX方法鉴定的称为溶液SELEX的高亲和力核酸配体和低亲和力核酸配体之间的分配改进方法。 解决方案SELEX方法通过多种方法实现高亲和力核酸 - 靶向复合物之间的分配，包括（1）导致差异化cDNA产物的引物延伸抑制。 引物延伸抑制通过使用核酸聚合酶，包括DNA或RNA聚合酶，逆转录酶和Qbeta复制酶来实现; （2）外切核酸酶水解抑制，其导致PCR期间最高亲和力配体扩增。 这是通过使用任何3' - > 5'双链外切核酸酶来实现的; （3）线性循环形成以产生PCR期间可扩增的分子; 或（4）单链核酸的PCR扩增。 本发明方法的中心主题是将核酸候选混合物在溶液中筛选并导致最高亲和力RNA配体或催化RNA的优先扩增。