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1. 发明授权

US06312893B1 Methods and compositions for determining the sequence of nucleic acid molecules 失效
标题翻译：用于确定核酸分子序列的方法和组合物
公开(公告)号：US06312893B1
公开(公告)日：2001-11-06
申请号：US08898180
申请日：1997-07-22
申请人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
发明人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
IPC分类号： C12Q168
CPC分类号： C07H21/00 , C07B2200/11 , C07D211/78 , C07H21/04 , C12Q1/6872 , C12Q1/6874 , C40B40/00 , Y10T436/24 , C12Q2565/629 , C12Q2563/167
摘要： Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.
摘要翻译：提供方法和化合物，包括其组合物，用于确定核酸分子的序列。该方法允许同时测定多个核酸序列。该化合物用作标签以产生与选定的靶核酸分子互补的标记的核酸片段。每个标签与特定核苷酸相关，并且在优选实施方案中可通过质谱法检测。在通过连续长度分离标记的片段之后，从标记的片段切割标签。在优选的实施方案中，通过质谱检测标签，并由此确定核酸分子的序列。方法的各个步骤可以以自动格式使用，例如通过并入系统。

2. 发明授权

US06444422B2 Computer method and system for correlating data 失效
标题翻译：用于数据相关的计算机方法和系统
公开(公告)号：US06444422B2
公开(公告)日：2002-09-03
申请号：US09120686
申请日：1998-07-21
申请人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
发明人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
IPC分类号： C12Q168
CPC分类号： G06F19/24 , C12Q1/6872 , G06F19/22 , Y10T436/24
摘要： A method and system for correlating characteristics (e.g., type of nucleotide) of biomolecules (e.g., DNA) to molecular tags with unique molecular weights that are associated with the biomolecule. In one embodiment. the molecular tags are applied to primers used when synthesizing the biomolecule. The system initially receives a mapping of each characteristic of the biomolecules to the corresponding molecular weight of the molecular tag. The system also receives an indication of the molecular weights detected when analyzing the biomolecules to which the molecular tags have been associated. For each molecular weight detected, the system determines based on the received mapping the characteristic corresponding to the detected molecular weight. The system then indicates that the analyzed biomolecule has the determined characteristic.
摘要翻译：将生物分子（例如DNA）的特征（例如，核苷酸的类型）与分子标签与生物分子相关联的独特分子量相关联的方法和系统。在一个实施例中。分子标签应用于合成生物分子时使用的引物。该系统首先接收生物分子的每个特征与分子标签的相应分子量的映射。当分析与分子标签相关联的生物分子时，该系统还接收检测到的分子量的指示。对于检测到的每个分子量，系统基于所接收的映射确定与检测到的分子量相对应的特征。然后系统表明分析的生物分子具有确定的特征。

3. 发明授权

US07164992B1 Method and system for polynucleotide synthesis 有权
标题翻译：多核苷酸合成方法和系统
公开(公告)号：US07164992B1
公开(公告)日：2007-01-16
申请号：US10104986
申请日：2002-03-22
申请人： John T. Mulligan , John C. Tabone , R. Gregg Brickner
发明人： John T. Mulligan , John C. Tabone , R. Gregg Brickner
IPC分类号： G06F19/00 , G11C17/00 , G05B15/00
CPC分类号： G06F19/702 , G06F19/10
摘要： Methods and systems for automated polynucleotide synthesis design are provided. Example embodiments provide an Automated Polynucleotide Synthesis Design System (“APSDS”), which automatically generates a synthesis design for a designated target sequence specification. In one embodiment, the APSDS comprises a synthesis design engine, user interface support, a synthesis rules data repository, and a synthesis data repository. The APSDS automatically generates a synthesis design by receiving a target sequence(s) specification, generating a potential synthesis design, evaluating the potential design against synthesis rules, and when the evaluation indicates that the potential design is not successful according to the synthesis rules, adjusting the design to generate a new potential synthesis design and repeating the process of evaluating and adjusting until a potential synthesis design is found that satisfies the synthesis rules or until no solution is found.
摘要翻译：提供了自动多核苷酸合成设计的方法和系统。实施例提供自动多核苷酸合成设计系统（“APSDS”），其自动产生用于指定的靶序列规范的合成设计。在一个实施例中，APSDS包括合成设计引擎，用户界面支持，综合规则数据存储库和综合数据存储库。 APSDS通过接收目标序列规范自动生成合成设计，产生潜在的合成设计，根据综合规则评估潜在设计，以及当评估根据合成规则表明潜在设计不成功时，调整设计产生新的潜在合成设计，并重复评估和调整的过程，直到找到满足合成规则或直到找不到解决方案的潜在合成设计为止。

4. 发明授权

US06815212B2 Methods and compositions for enhancing sensitivity in the analysis of biological-based assays 有权
标题翻译：用于增强基于生物学测定分析的灵敏度的方法和组合物
公开(公告)号：US06815212B2
公开(公告)日：2004-11-09
申请号：US10000467
申请日：2001-10-24
申请人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
发明人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
IPC分类号： G01N2400
CPC分类号： C12Q1/6872 , Y10T436/24 , C12Q2563/167
摘要： Methods are provided for detecting the binding of a first member to a second member of a ligand pair, comprising the steps of (a) combining a set of first tagged members with a biological sample which may contain one or more second members, under conditions, and for a time sufficient to permit binding of a first member to a second member, wherein said tag is correlative with a particular first member and detectable by non-fluorescent spectrometry, or potentiometry, (b) separating bound first and second members from unbound members, (c) cleaving the tag from the tagged first member, and (d) detecting the tag by non-fluorescent spectrometry, or potentiometry, and therefrom detecting the binding of the first member to the second member.

5. 发明授权

US6027890A Methods and compositions for enhancing sensitivity in the analysis of biological-based assays 失效
标题翻译：用于增强基于生物学测定分析的灵敏度的方法和组合物
公开(公告)号：US6027890A
公开(公告)日：2000-02-22
申请号：US898501
申请日：1997-07-22
申请人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
发明人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
IPC分类号： A01N43/04 , A61K38/00 , C07C69/74 , C12Q1/68 , G01N24/00 , G01N33/53 , G01N33/542
CPC分类号： C12Q1/6872 , Y10T436/24
摘要： Methods are provided for detecting the binding of a first member to a second member of a ligand pair, comprising the steps of (a) combining a set of first tagged members with a biological sample which may contain one or more second members, under conditions, and for a time sufficient to permit binding of a first member to a second member, wherein said tag is correlative with a particular first member and detectable by non-fluorescent spectrometry, or potentiometry, (b) separating bound first and second members from unbound members, (c) cleaving the tag from the tagged first member, and (d) detecting the tag by non-fluorescent spectrometry, or potentiometry, and therefrom detecting the binding of the first member to the second member.
摘要翻译：提供了用于检测第一成员与配体对的第二成员的结合的方法，其包括以下步骤：（a）在一些条件下，将一组第一标记成员与可包含一个或多个第二成员的生物样品组合，并且足以允许第一构件与第二构件结合的时间，其中所述标签与特定第一构件相关并且可通过非荧光光谱法或电位法检测，（b）将结合的第一和第二构件与未结合的成员分离，（c）从标记的第一构件切割标签，以及（d）通过非荧光光谱法或电位法检测标签，从而检测第一构件与第二构件的结合。

6. 发明授权

US06664112B2 Methods for improving the sequence fidelity of synthetic double-stranded oligonucleotides 有权
公开(公告)号：US06664112B2
公开(公告)日：2003-12-16
申请号：US09872761
申请日：2001-06-01
申请人： John T. Mulligan , John C. Tabone
发明人： John T. Mulligan , John C. Tabone
IPC分类号： G01N3300
CPC分类号： C07H21/00 , C07H1/06 , C12N15/101 , Y10T436/143333
摘要： Synthetic oligonucleotides, such as synthetic DNA, often contain sequence errors due to synthetic failures (e.g., side products and/or truncated products). Methods are provided herein for improving the sequence fidelity of synthetic double-stranded oligonucleotides by separative depletion of synthetic failures. Separation is effected by utilization of methodologies in a preparative mode under denaturing conditions. A preferred use of the methods relates to gene synthesis.

7. 发明授权

US06623928B2 Methods and compositions for determining the sequence of nucleic acid molecules 有权
公开(公告)号：US06623928B2
公开(公告)日：2003-09-23
申请号：US09855999
申请日：2001-05-14
申请人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
发明人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
IPC分类号： C12Q168
CPC分类号： C07H21/00 , C07B2200/11 , C07D211/78 , C07H21/04 , C12Q1/6872 , C12Q1/6874 , C40B40/00 , Y10T436/24 , C12Q2565/629 , C12Q2563/167
摘要： Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.

8. 发明授权

US06613508B1 Methods and compositions for analyzing nucleic acid molecules utilizing sizing techniques 失效
标题翻译：利用施胶技术分析核酸分子的方法和组合物
公开(公告)号：US06613508B1
公开(公告)日：2003-09-02
申请号：US08898564
申请日：1997-07-22
申请人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
发明人： Jeffrey Van Ness , John C. Tabone , J. Jeffry Howbert , John T. Mulligan
IPC分类号： C12Q168
CPC分类号： C07H21/00 , C07B2200/11 , C12Q1/6825 , C12Q1/6846 , C12Q1/6872 , C40B40/00 , C12Q2563/149 , C12Q2563/113 , C12Q2563/167 , C12Q2525/191
摘要： Tags and linkers specifically designed for a wide variety of nucleic acid reactions are disclosed, which are suitable for a wide variety of nucleic acid reactions wherein separation of nucleic acid molecules based upon size is required.
摘要翻译：公开了针对各种核酸反应专门设计的标签和接头，其适用于各种各样的核酸反应，其中需要基于尺寸分离核酸分子。

9. 发明授权

US08361396B2 Automated polymer-synthesis system 有权
标题翻译：自动聚合物合成系统
公开(公告)号：US08361396B2
公开(公告)日：2013-01-29
申请号：US12932334
申请日：2011-02-22
申请人： Hsing-Yeh Parker , John C. Tabone , John Mulligan
发明人： Hsing-Yeh Parker , John C. Tabone , John Mulligan
IPC分类号： B01J19/00 , G01N21/00
CPC分类号： B01J19/0046 , B01J2219/00286 , B01J2219/00315 , B01J2219/0036 , B01J2219/00414 , B01J2219/00423 , B01J2219/00722
摘要： Embodiments of the present invention are directed to automated-polymer-synthesis systems that include discrete reagent-solution-addition, wait-time, and reagent-solution-draining sub-systems which together significantly increase throughput and decrease sub-system idle time. The automated-polymer-synthesis systems that represent embodiments of the present invention additionally include switches at points in which carriers can be received from multiple input paths or output to multiple different output paths. The automated-polymer-synthesis systems that represent embodiments of the present invention generally include an input spur and output spur in addition to a main loop, allowing carriers containing only completed polymers to be removed and new carriers input, so that carriers traverse the automated-polymer-synthesis systems independently from one another.
摘要翻译：本发明的实施方案涉及自动聚合物合成系统，其包括离散的试剂 - 溶液添加，等待时间和试剂 - 溶液 - 排出子系统，这些子系统共同显着增加生产量并减少子系统空闲时间。代表本发明实施例的自动化 - 聚合物合成系统另外包括在多个输入路径上可以接收载波或输出到多个不同输出路径的点处的交换机。代表本发明实施例的自动化 - 聚合物 - 合成系统通常包括除了主回路之外的输入支线和输出支线，允许仅去除已完成的聚合物的载流子和新的载流子输入，使得载流子穿过自动化 - 聚合物合成系统彼此独立。

10. 发明授权

US5849482A Crosslinking oligonucleotides 失效
标题翻译：交联寡核苷酸
公开(公告)号：US5849482A
公开(公告)日：1998-12-15
申请号：US485611
申请日：1995-06-07
申请人： Rich B. Meyer, Jr. , Howard B. Gamper , Igor V. Kutyavin , Alexander A. Gall , Charles R. Petrie , John C. Tabone , Gerald D. Hurst
发明人： Rich B. Meyer, Jr. , Howard B. Gamper , Igor V. Kutyavin , Alexander A. Gall , Charles R. Petrie , John C. Tabone , Gerald D. Hurst
IPC分类号： A61K31/70 , A61K38/00 , A61K48/00 , A61P31/00 , A61P35/00 , C07H21/00 , C12N15/10 , C12N15/113 , C12Q1/68 , C07H21/04
CPC分类号： C12N15/113 , C07H21/00 , C12N15/102 , C12Q1/6839 , A61K38/00 , C12N2310/153 , C12N2310/311 , C12N2310/335 , C12N2310/3511
摘要： Oligonucleotides (ODNs) include a sequence that is complementary to a target sequence in single stranded RNA, or single or double stranded DNA, and an alkylating function which after hybridization alkylates the target sequence. ODNs adapted for alkylating single stranded RNA, such as messenger RNA, are complementary to the target sequence in the Watson Crick sense. ODNs adapted for alkylating double stranded DNA have at least two alkylating functions and are complementary to the target sequence in the Hoogsteen or reverse Hoogsteen sense. With these ODNs both strands of the target sequence are alkylated. A third class of ODNs have at least approximately 26 nucleotide units in a continous sequence which are complementary to the target sequence of double stranded DNA, and the alkylating function is covalently attached to a nucleotide unit in the continuous sequence. Alkylation or cross-linking with this class of ODNs occurs in the presence of a recombinase enzyme.
摘要翻译：寡核苷酸（ODN）包括与单链RNA或单链或双链DNA中的靶序列互补的序列，以及杂交后烷基化靶序列的烷基化功能。适用于烷基化单链RNA（如信使RNA）的ODN与Watson Crick意义上的靶序列互补。适于烷基化双链DNA的ODN具有至少两种烷基化功能，并且与Hoogsteen或反向Hoogsteen意义上的靶序列互补。使用这些ODN，靶序列的两条链被烷基化。第三类ODN在连续序列中具有至少约26个核苷酸单元，其与双链DNA的靶序列互补，并且烷基化功能以连续序列共价连接到核苷酸单元。与这类ODN的烷基化或交联发生在重组酶的存在下。

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