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1. 发明申请

US20120264122A1 METHODS AND COMPOSITIONS FOR NUCLEIC ACID AMPLIFICATION 有权
标题翻译：用于核酸扩增的方法和组合物
公开(公告)号：US20120264122A1
公开(公告)日：2012-10-18
申请号：US13460341
申请日：2012-04-30
申请人： Steven T. BRENTANO , Dmitry LYAKHOV , James D. CARLSON , Norman C. NELSON , Lyle J. ARNOLD, JR.
发明人： Steven T. BRENTANO , Dmitry LYAKHOV , James D. CARLSON , Norman C. NELSON , Lyle J. ARNOLD, JR.
IPC分类号： C12P19/34 , C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6881 , C12Q1/6834 , C12Q1/6844 , C12Q1/6865 , C12Q2525/155 , C12Q2525/186 , C12Q2525/197 , C12Q2531/143 , C12Q2565/543
摘要： Compositions that are used in nucleic acid amplification in vitro are disclosed, which include a target specific universal (TSU) promoter primer or promoter provider oligonucleotide that includes a target specific (TS) sequence that hybridizes specifically to a target sequence that is amplified and a universal (U) sequence that is introduced into the sequence that is amplified, by using a primer for the universal sequence. Methods of nucleic acid amplification in vitro are disclosed that use one or more TSU oligonucleotides to attached a U sequence to a target nucleic acid in a target capture step and then use a primer for a U sequence in subsequent amplification steps performed in substantially isothermal conditions to make amplification products that contain a U sequence that indicates the presence of the target nucleic acid in a sample.
摘要翻译：公开了用于体外核酸扩增的组合物，其包括目标特异性通用（TSU）启动子引物或启动子提供者寡核苷酸，其包括与扩增的靶序列特异性杂交的靶特异性（TS）序列和通用（U）序列，通过使用通用序列的引物引入扩增的序列。公开了体外核酸扩增方法，其中使用一种或多种TSU寡核苷酸将U序列连接到目标捕获步骤中的靶核酸，然后在基本上等温条件下进行的随后扩增步骤中使用U序列引物制备含有指示样品中靶核酸存在的U序列的扩增产物。

2. 发明授权

US06031091A Non-nucleotide linking reagents for nucleotide probes 失效
标题翻译：用于核苷酸探针的非核苷酸连接试剂
公开(公告)号：US06031091A
公开(公告)日：2000-02-29
申请号：US908535
申请日：1997-08-07
申请人： Lyle J. Arnold, Jr. , Mark A. Reynolds , Ram S. Bhatt
发明人： Lyle J. Arnold, Jr. , Mark A. Reynolds , Ram S. Bhatt
IPC分类号： C07F9/24 , C07H21/00 , C07F9/02
CPC分类号： C07H21/00 , C07F9/2408
摘要： A versatile reagent with a non-nucleotide monomeric unit having a ligand, and first and second coupling groups which are linked to the non-nucleotide monomeric unit. The ligand can be either a chemical moiety, such as a label or intercalator, or a linking arm which can be linked to such a moiety. Such reagent permits preparation of versatile nucleotide/non-nucleotide polymers, having any desired sequence of nucleotide and non-nucleotide monomeric units, each of the latter of which bear a desired ligand. These polymers can for example, be used as probes which can exhibit enhanced sensitivity and/or which are capable of detecting a genus of nucleotides each species of which has a common target nucleotide sequence of interest bridged by different sequences not of interest.
摘要翻译：具有具有配体的非核苷酸单体单元的多功能试剂和与非核苷酸单体单元连接的第一和第二偶联基团。配体可以是化学部分，例如标记或嵌入剂，或可以连接到这种部分的连接臂。这种试剂允许制备通用的核苷酸/非核苷酸聚合物，具有任何所需的核苷酸和非核苷酸单体单元序列，后者各自具有所需的配体。这些聚合物可以例如用作可以显示增强的灵敏度的探针和/或能够检测核苷酸属的核苷酸，其中每个物种具有由不感兴趣的不同序列桥接的共同目标核苷酸序列。

3. 发明授权

US6004745A Hybridization protection assay 失效
标题翻译：杂交保护试验
公开(公告)号：US6004745A
公开(公告)日：1999-12-21
申请号：US465435
申请日：1995-06-05
申请人： Lyle J. Arnold, Jr. , Norman C. Nelson
发明人： Lyle J. Arnold, Jr. , Norman C. Nelson
IPC分类号： C12Q1/68 , G01N33/53 , G01N33/532 , G01N33/533 , G01N33/542 , G01N33/58
CPC分类号： G01N33/58 , C12Q1/6816 , C12Q1/6823 , G01N33/5306 , G01N33/532 , G01N33/533 , G01N33/542
摘要： Improved homogenous diagnostic assay methods and labels for detecting an analyte in a medium when the analyte is a member of a specific binding pair. The methods and labels provide procedures for reducing background and increasing sensitivity. The binding partner of the analyte is labeled with a substance, the stability of which detectably changes whenever said analyte is bound as a member of the specific binding pair, In a closely related system, the analyte is labeled with a substance susceptible to differential degradation depending on whether or not the analyte is bound as a member of its specific binding pair. After incubation and selective degradation or chemical or biochemical alteration, the amount of analyte bound is detected by measuring either the stability change or the extent of degradation of the label. In a particular system, chemiluminescent acridinium ester labeled probes are used in a homogenous hybridization assay format for sensitively detecting the presence of complement any target polynucleotide sequences.
摘要翻译：当分析物是特异性结合对的成员时，改进的同源诊断测定方法和用于检测培养基中分析物的标记。方法和标签提供了降低背景和提高灵敏度的程序。分析物的结合配偶体用物质标记，每当所述分析物作为特异性结合对的成员结合时，其稳定性可检测地改变。在紧密相关的系统中，分析物用易受差异降解的物质标记关于分析物是否作为其特异性结合对的成员结合。孵育和选择性降解或化学或生物化学改变后，通过测量标签的稳定性变化或降解程度来检测分析物的结合量。在特定系统中，化学发光的吖啶酯标记的探针以均质杂交测定形式使用，以敏感地检测补体存在任何靶多核苷酸序列。

4. 发明授权

US5424413A Branched nucleic acid probes 失效
标题翻译：支链核酸探针
公开(公告)号：US5424413A
公开(公告)日：1995-06-13
申请号：US940652
申请日：1992-09-04
申请人： James J. Hogan , Lyle J. Arnold, Jr. , Norman C. Nelson , Robert Bezverkov
发明人： James J. Hogan , Lyle J. Arnold, Jr. , Norman C. Nelson , Robert Bezverkov
IPC分类号： C12N15/09 , C07H21/04 , C12N15/10 , C12Q1/68 , C12R1/36
CPC分类号： C12N15/1068 , C12Q1/6816 , C12Q1/6823 , Y10T436/143333
摘要： Nucleic acid hybridization probes having at least one nucleic acid strand which has at least two separate target specific regions that hybridize to a target nucleic acid sequence, and at least two distinct arm regions that do not hybridize with the target nucleic acid but possess complementary regions that are capable of hybridizing with one another. These regions are designed such that, under appropriate hybridization conditions, the complementary arm regions will not hybridize to one another in the absence of the target nucleic acid; but, in the presence of target nucleic acid the target-specific regions of the probe will anneal to the target nucleic acid, and the complementary arm regions will anneal to one another, thereby forming a branched nucleic acid structure.
摘要翻译：具有至少一个核酸链的核酸杂交探针，其具有与靶核酸序列杂交的至少两个分离的靶特异性区域，以及至少两个不与靶核酸杂交但具有互补区域的不同臂区域，能够彼此杂交。这些区域被设计成使得在适当的杂交条件下，互补臂区不会在不存在靶核酸的情况下彼此杂交; 但是在目标核酸的存在下，探针的靶特异性区域将与靶核酸退火，并且互补臂区域将彼此退火，由此形成支化核酸结构。

5. 发明授权

US08512955B2 Methods and compositions for nucleic acid amplification 有权
公开(公告)号：US08512955B2
公开(公告)日：2013-08-20
申请号：US12828676
申请日：2010-07-01
申请人： Steven T. Brentano , Dmitry Lyakhov , Norman C. Nelson , James D. Carlson , Michael M. Becker , Lyle J. Arnold, Jr.
发明人： Steven T. Brentano , Dmitry Lyakhov , Norman C. Nelson , James D. Carlson , Michael M. Becker , Lyle J. Arnold, Jr.
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/04
CPC分类号： C12Q1/6865 , C12Q1/6844 , C12Q1/6848 , C12Q1/6853 , C12Q2549/119 , C12Q2537/143 , C12Q2531/143
摘要： Compositions, reaction mixtures, and methods for performing an amplification reaction, including multiplex amplification reaction, wherein the method comprises using one or more amplification oligomer complexes comprising linked first and second amplification oligomer members. In one aspect, the amplification oligomer complex is hybridized to a target nucleic acid, the target nucleic acid with hybridized amplification oligomer complex is then captured, and other components are washed away. Target sequences of the target nucleic acids are pre-amplified to generate a first amplification product. The first amplification product is amplified in one or more secondary amplification reactions to generate second amplification products.

6. 发明申请

US20120178636A1 METHODS AND COMPOSITIONS FOR NUCLEIC ACID AMPLIFICATION 有权
标题翻译：用于核酸扩增的方法和组合物
公开(公告)号：US20120178636A1
公开(公告)日：2012-07-12
申请号：US13380018
申请日：2010-07-01
申请人： Steven T. Brentano , Dmitry Lyakhov , James D. Carlson , Michael M. Becker , Norman C. Nelson , Lyle J. Arnold, JR.
发明人： Steven T. Brentano , Dmitry Lyakhov , James D. Carlson , Michael M. Becker , Norman C. Nelson , Lyle J. Arnold, JR.
IPC分类号： C40B30/00
CPC分类号： C12Q1/6865 , C12Q1/6844 , C12Q1/6848 , C12Q1/6853 , C12Q2549/119 , C12Q2537/143 , C12Q2531/143
摘要： Compositions, reaction mixtures, and methods for performing an amplification reaction, including multiplex amplification reaction, wherein the method comprises using one or more amplification oligomer complexes comprising linked first and second amplification oligomer members. In one aspect, the amplification oligomer complex is hybridized to a target nucleic acid, the target nucleic acid with hybridized amplification oligomer complex is then captured, and other components are washed away. Target sequences of the target nucleic acids are pre-amplified to generate a first amplification product. The first amplification product is amplified in one or more secondary amplification reactions to generate second amplification products.
摘要翻译：用于进行扩增反应的组合物，反应混合物和方法，包括多重扩增反应，其中所述方法包括使用包含连接的第一和第二扩增寡聚体成员的一种或多种扩增寡聚体复合物。一方面，将扩增寡聚物复合物与靶核酸杂交，然后捕获具有杂交扩增寡聚物复合物的靶核酸，并洗涤其它组分。靶核酸的靶序列被预扩增以产生第一扩增产物。第一扩增产物在一个或多个二级扩增反应中扩增以产生第二扩增产物。

7. 发明授权

US5837856A Chirally enriched synthetic phosphonate oligomers 失效
标题翻译：手性富集合成膦酸酯低聚物
公开(公告)号：US5837856A
公开(公告)日：1998-11-17
申请号：US814053
申请日：1997-03-06
申请人： Lyle J. Arnold, Jr. , Mark A. Reynolds , Timothy A. Riley , David A. Schwartz
发明人： Lyle J. Arnold, Jr. , Mark A. Reynolds , Timothy A. Riley , David A. Schwartz
IPC分类号： C12N15/09 , A61K31/70 , A61K48/00 , C07H21/00 , C07H21/02 , C07H21/04 , C12N15/113 , C12Q1/68
CPC分类号： C12N15/1131 , C07H21/00
摘要： Oligomers having phosphonate internucleosidyl linkages which are enriched for phosphonate linkages of a preselected chirality which hybridize to an RNA target sequence and methods for their preparation are provided.
摘要翻译：提供了具有与RNA靶序列杂交的预选手性的富含膦酸酯键合的膦酸酯核苷间键的低聚物及其制备方法。

8. 发明授权

US5599667A Polycationic supports and nucleic acid purification separation and hybridization 失效
标题翻译：用于核酸纯化，分离和杂交的聚阳离子载体
公开(公告)号：US5599667A
公开(公告)日：1997-02-04
申请号：US311289
申请日：1994-09-23
申请人： Lyle J. Arnold, Jr. , Norman C. Nelson , Mark A. Reynolds , Alexander A. Waldrop, III
发明人： Lyle J. Arnold, Jr. , Norman C. Nelson , Mark A. Reynolds , Alexander A. Waldrop, III
IPC分类号： C07H1/06 , C07H21/00 , C12Q1/68 , C12N15/10
CPC分类号： C07H21/00 , C07H1/06 , C12Q1/6806 , C12Q1/6834 , C12Q1/689
摘要： Described herein is the use of polycationic solid supports in the purification of nucleic acids from solutions containing contaminants. The nucleic acids non-covalently bind to the support without significant binding of contaminants permitting their separation from the contaminants. The bound nucleic acids can be recovered from the support. Also described is the use of the supports as a means to separate polynucleotides and hybrids thereof with a nucleotide probe from unhybridized probe. Assays for target nucleotide sequences are described which employ this separation procedure.
摘要翻译：本文描述的是使用聚阳离子固体载体从含有污染物的溶液中纯化核酸。核酸与载体非共价结合，而不会使污染物与污染物分离而明显结合污染物。结合的核酸可以从载体中回收。还描述了使用载体作为用来自未杂交的探针的核苷酸探针分离多核苷酸和其杂交体的手段。描述了使用这种分离方法的靶核苷酸序列的测定。

9. 发明授权

US5451503A Method for use of branched nucleic acid probes 失效
标题翻译：分支核酸探针的使用方法
公开(公告)号：US5451503A
公开(公告)日：1995-09-19
申请号：US255553
申请日：1994-06-07
申请人： James J. Hogan , Lyle J. Arnold, Jr. , Norman C. Nelson , Robert Bezverkov
发明人： James J. Hogan , Lyle J. Arnold, Jr. , Norman C. Nelson , Robert Bezverkov
IPC分类号： C12N15/09 , C07H21/04 , C12N15/10 , C12Q1/68 , C12R1/36
CPC分类号： C12N15/1068 , C12Q1/6816 , C12Q1/6823 , Y10T436/143333
摘要： Nucleic acid hybridization probes having at least one nucleic acid strand which has at least two separate target specific regions that hybridize to a target nucleic acid sequence, and at least two distinct arm regions that do not hybridize with the target nucleic acid but possess complementary regions that are capable of hybridizing with one another. These regions are designed such that, under appropriate hybridization conditions, the complementary arm regions will not hybridize to one another in the absence of the target nucleic acid; but, in the presence of target nucleic acid the target-specific regions of the probe will anneal to the target nucleic acid, and the complementary arm regions will anneal to one another, thereby forming a branched nucleic acid structure.
摘要翻译：具有至少一个核酸链的核酸杂交探针，其具有与靶核酸序列杂交的至少两个分离的靶特异性区域，以及至少两个不与靶核酸杂交但具有互补区域的不同臂区域，能够彼此杂交。这些区域被设计成使得在适当的杂交条件下，互补臂区不会在不存在靶核酸的情况下彼此杂交; 但是在目标核酸的存在下，探针的靶特异性区域将与靶核酸退火，并且互补臂区域将彼此退火，由此形成支化核酸结构。

10. 发明授权

US5362866A Oligonucleotide polymeric support system with an oxidation cleavable link 失效
标题翻译：具有氧化可切割连接的寡核苷酸聚合物支持体系
公开(公告)号：US5362866A
公开(公告)日：1994-11-08
申请号：US852761
申请日：1992-03-17
申请人： Lyle J. Arnold, Jr.
发明人： Lyle J. Arnold, Jr.
IPC分类号： C07H21/00 , C12Q1/68
CPC分类号： C07H21/00 , Y02P20/55
摘要： A versatile polymeric support system for the synthesis of oligonucleotides is provided featuring a universal primer which allows chain elongation, in either the 3' or 5' direction, with any currently available DNA or RNA synthesis method, by a process which utilizes oxidatively cleaved primers to facilitate chain elongation and release. The support system is capable of withstanding mildly basic and acidic reaction conditions, while still permitting a convenient and quantitative release, either before or after removal of protecting groups from reactive groups, of synthesized oligonucleotides from a single polymeric support. Removal of the protecting groups before cleavage of the oligomer from the support permits the use of the immobilized oligomer as an affinity hybridization support for both isolating and detecting complementary polynucleic acids.
摘要翻译：提供了用于合成寡核苷酸的通用聚合物支持体系，其特征在于通用引物，其通过使用氧化性切割引物的方法，允许以任何目前可用的DNA或RNA合成方法在3'或5'方向上延伸3'或5' 促进链伸长和释放。支持体系能够承受轻度碱性和酸性的反应条件，同时在从单一聚合物载体除去合成的寡核苷酸的保护基团的反应性基团之前或之后仍然允许方便和定量的释放。在从载体裂解低聚物之前除去保护基允许使用固定的寡聚物作为分离和检测互补多核酸的亲和杂交支持物。

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