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1. 发明授权

US5679533A Biotin-binding containment systems 失效
公开(公告)号：US5679533A
公开(公告)日：1997-10-21
申请号：US479390
申请日：1995-06-07
申请人： Przemyslaw Szafranski , Charlene M. Mello , Takeshi Sano , Kenneth A. Marx , Charles R. Cantor , David L. Kaplan , Cassandra L. Smith
发明人： Przemyslaw Szafranski , Charlene M. Mello , Takeshi Sano , Kenneth A. Marx , Charles R. Cantor , David L. Kaplan , Cassandra L. Smith
IPC分类号： C07K14/36 , C07K14/465 , C12N1/21 , C12N15/12 , C12N15/70 , G01N33/53
CPC分类号： C12N15/70 , C07K14/36 , C07K14/465
摘要： The present invention relates to genetic containment systems which express a biotin-binding component that can be used for selectively destroying recombinant cells such as genetically engineered microorganisms. These systems may comprise a streptavidin or an avidin gene whose expression is controlled by a regulatable promoter. The regulatory agent such as a transcriptional effector is expressed from another gene which may also be expressed and its expression controlled by the containment system. Expression of the agent can be designed to respond to physiological changes in the environment. The invention also relates to containment systems and methods for the selective detection or tracking of recombinant cells and to eukaryotic and prokaryotic cells which contain these genetic containment systems.

2. 发明授权

US5681745A Biotin-binding containment systems 失效
标题翻译：生物素结合遏制系统
公开(公告)号：US5681745A
公开(公告)日：1997-10-28
申请号：US432017
申请日：1995-05-01
申请人： Przemyslaw Szafranski , Charlene M. Mello , Takeshi Sano , Kenneth A. Marx , Charles R. Cantor , David L. Kaplan , Cassandra L. Smith
发明人： Przemyslaw Szafranski , Charlene M. Mello , Takeshi Sano , Kenneth A. Marx , Charles R. Cantor , David L. Kaplan , Cassandra L. Smith
IPC分类号： C07K14/36 , C07K14/465 , C12N1/21 , C12N15/12 , C12N15/70 , C12N5/10 , C12N1/13
CPC分类号： C12N15/70 , C07K14/36 , C07K14/465
摘要： The present invention relates to genetic containment systems which express a biotin-binding component that can be used for selectively destroying recombinant cells such as genetically engineered microorganisms. These systems may comprise a streptavidin or an avidin gene whose expression is controlled by a regulatable promoter. The regulatory agent such as a transcriptional effector is expressed from another gene which may also be expressed and its expression controlled by the containment system. Expression of the agent can be designed to respond to physiological changes in the environment. The invention also relates to containment systems and methods for the selective detection or tracking of recombinant cells and to eukaryotic and prokaryotic cells which contain these genetic containment systems.
摘要翻译：本发明涉及表达可用于选择性破坏重组细胞如遗传工程微生物的生物素结合成分的遗传容纳系统。这些系统可以包含链霉亲和素或抗生物素蛋白基因，其表达受可调节启动子控制。诸如转录效应子的调节剂由另外可能被表达的基因表达，其表达由遏制系统控制。试剂的表达可以设计成响应环境中的生理变化。本发明还涉及用于选择性检测或跟踪重组细胞和含有这些遗传包涵体系的真核和原核细胞的遏制系统和方法。

3. 发明授权

US06287844B1 Compositions and methods for controlling genetically engineered organisms 失效
标题翻译：用于控制转基因生物的组合物和方法
公开(公告)号：US06287844B1
公开(公告)日：2001-09-11
申请号：US09019966
申请日：1998-02-06
申请人： Przemyslaw Szafranski , Charlene Mello , Takeshi Sano , Cassandra L. Smith , David L. Kaplan , Charles R. Cantor
发明人： Przemyslaw Szafranski , Charlene Mello , Takeshi Sano , Cassandra L. Smith , David L. Kaplan , Charles R. Cantor
IPC分类号： C12N120
CPC分类号： C07K14/36 , C12N15/72 , C12N15/74
摘要： Compositions and methods for the control of genetically engineered organisms are described. A more effective cell suicide approach is contemplated based on the conditional expression of the lethal Streptomyces avidinii streptavidin gene. Toxicity of streptavidin is derived from its exceptionally high binding affinity for an essential prosthetic group, D-biotin. The general requirement for biotin through the living world makes streptavidin-based conditional lethal designs applicable to a broad range of containment strategies.
摘要翻译：描述了用于控制转基因生物的组合物和方法。基于致死性链霉菌链霉亲和素链霉亲和素基因的条件表达考虑了更有效的细胞自杀方法。链霉抗生物素蛋白的毒性源自其对必需的假基团D-生物素的极高的结合亲和力。生物素通过生活世界的一般要求使基于链霉亲和素的条件致命设计适用于广泛的遏制策略。

4. 发明授权

US6124129A Compositions and methods for controlling genetically engineered organisms 失效
标题翻译：用于控制转基因生物的组合物和方法
公开(公告)号：US6124129A
公开(公告)日：2000-09-26
申请号：US19966
申请日：1998-02-06
申请人： Przemyslaw Szafranski , Charlene Mello , Takeshi Sano , Cassandra L. Smith , David L. Kaplan , Charles R. Cantor
发明人： Przemyslaw Szafranski , Charlene Mello , Takeshi Sano , Cassandra L. Smith , David L. Kaplan , Charles R. Cantor
IPC分类号： C07K14/36 , C12N1/21 , C12N15/72 , C12N15/74 , C12N1/20
CPC分类号： C07K14/36 , C12N15/72 , C12N15/74
摘要： Compositions and methods for the control of genetically engineered organisms are described. A more effective cell suicide approach is contemplated based on the conditional expression of the lethal Streptomyces avidinii streptavidin gene. Toxicity of streptavidin is derived from its exceptionally high binding affinity for an essential prosthetic group, D-biotin. The general requirement for biotin through the living world makes streptavidin-based conditional lethal designs applicable to a broad range of containment strategies.
摘要翻译：描述了用于控制转基因生物的组合物和方法。基于致死性链霉菌链霉亲和素链霉亲和素基因的条件表达考虑了更有效的细胞自杀方法。链霉抗生物素蛋白的毒性源自其对必需的假基团D-生物素的极高的结合亲和力。生物素通过生活世界的一般要求使基于链霉亲和素的条件致命设计适用于广泛的遏制策略。

5. 发明授权

US5753439A Nucleic acid detection methods 失效
标题翻译：核酸检测方法
公开(公告)号：US5753439A
公开(公告)日：1998-05-19
申请号：US446102
申请日：1995-05-19
申请人： Cassandra L. Smith , Ron Yaar , Przemyslaw Szafranski , Charles R. Cantor
发明人： Cassandra L. Smith , Ron Yaar , Przemyslaw Szafranski , Charles R. Cantor
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34 , C12Q1/70
CPC分类号： C12Q1/6827 , C12Q1/6823
摘要： The invention relates to methods for rapidly determining the sequence and/or length a target sequence. The target sequence may be a series of known or unknown repeat sequences which are hybridized to an array of probes. The hybridized array is digested with a single-strand nuclease and free 3'-hydroxyl groups extended with a nucleic acid polymerase. Nuclease cleaved heteroduplexes can be easily distinguish from nuclease uncleaved heteroduplexes by differential labeling. Probes and target can be differentially labeled with detectable labels. Matched target can be detected by cleaving resulting loops from the hybridized target and creating free 3-hydroxyl groups. These groups are recognized and extended by polymerases added into the reaction system which also adds or releases one label into solution. Analysis of the resulting products using either solid phase or solution. These methods can be used to detect characteristic nucleic acid sequences, to determine target sequence and to screen for genetic defects and disorders. Assays can be conducted on solid surfaces allowing for multiple reactions to be conducted in parallel and, if desired, automated.
摘要翻译：本发明涉及用于快速确定靶序列的序列和/或长度的方法。靶序列可以是与探针阵列杂交的一系列已知或未知的重复序列。杂交阵列用单链核酸酶消化，游离的3'-羟基用核酸聚合酶延伸。核酸酶切割的异源双链体可以通过差异标记容易地与核酸酶未切割的异源双链体区分开。探针和靶可以用可检测的标记差异标记。可以通过从杂交靶标切割得到的环并产生游离的3-羟基来检测匹配的靶。这些基团被加入到反应体系中的聚合酶识别和扩增，该反应体系也将一个标记物添加或释放到溶液中。使用固相或溶液分析所得产物。这些方法可用于检测特征性核酸序列，确定靶序列并筛选遗传缺陷和病症。测定可以在固体表面进行，允许并行进行多个反应，如果需要，可以自动进行。

6. 发明授权

US07319003B2 Arrays of probes for positional sequencing by hybridization 失效
标题翻译：用于通过杂交进行位置测序的探针阵列
公开(公告)号：US07319003B2
公开(公告)日：2008-01-15
申请号：US09030571
申请日：1998-02-24
申请人： Charles R. Cantor , Marek Prezetakiewiczr , Cassandra L. Smith , Takeshi Sano
发明人： Charles R. Cantor , Marek Prezetakiewiczr , Cassandra L. Smith , Takeshi Sano
IPC分类号： C12Q1/68 , C12N1/36 , C07H21/04
CPC分类号： C12Q1/6874 , B01J19/0046 , B01J2219/00527 , B01J2219/00529 , B01J2219/0059 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00644 , B01J2219/00648 , B01J2219/00659 , B01J2219/00722 , C12Q1/6837 , C40B40/06 , C40B80/00 , C12Q2565/537 , C12Q2525/161 , C12Q2565/515 , C12Q2525/204 , C12Q2521/501
摘要： This invention is directed to methods and reagents useful for sequencing nucleic acid targets utilizing sequencing by hybridization technology comprising probes, arrays of probes and methods whereby sequence information is obtained rapidly and efficiently in discrete packages. That information can be used for the detection, identification, purification and complete or partial sequencing of a particular target nucleic acid. When coupled with a ligation step, these methods can be performed under a single set of hybridization conditions. The invention also relates to the replication of probe arrays and methods for making and replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Arrays created using PCR technology may comprise probes with 5′- and/or 3′-overhangs.
摘要翻译：本发明涉及可用于使用包括探针，探针阵列和方法的杂交技术测序的用于测序核酸靶的方法和试剂，从而在离散包装中快速有效地获得序列信息。该信息可以用于特定靶核酸的检测，鉴定，纯化和完全或部分测序。当与连接步骤相结合时，这些方法可以在单一杂交条件下进行。本发明还涉及探针阵列的复制和用于制备和复制探针阵列的方法，所述探针阵列可用于大规模制造用于筛选特定靶序列的生物样品的诊断辅助物。使用PCR技术产生的阵列可以包含具有5'和/或3'突出端的探针。

7. 发明授权

US5795714A Method for replicating an array of nucleic acid probes 失效
标题翻译：复制核酸探针阵列的方法
公开(公告)号：US5795714A
公开(公告)日：1998-08-18
申请号：US110691
申请日：1993-08-23
申请人： Charles R. Cantor , Marek Przetakiewicz , Cassandra L. Smith , Takeshi Sano
发明人： Charles R. Cantor , Marek Przetakiewicz , Cassandra L. Smith , Takeshi Sano
IPC分类号： G01N33/53 , B01J19/00 , C07H21/04 , C12M1/00 , C12N15/09 , C12Q1/68 , C40B40/06 , G01N37/00
CPC分类号： C12Q1/6874 , B01J19/0046 , C12Q1/6837 , C40B80/00 , B01J2219/00527 , B01J2219/00529 , B01J2219/0059 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00644 , B01J2219/00648 , B01J2219/00659 , B01J2219/00722 , C40B40/06
摘要： The invention relates to the replication of probe arrays and methods for replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Arrays created using PCR technology may comprise probes with 5'- and/or 3'-overhangs.
摘要翻译：本发明涉及用于复制探针阵列的探针阵列的复制和可用于大规模制造用于筛选特定靶序列的生物样品的诊断辅助物的方法。使用PCR技术产生的阵列可以包含具有5'和/或3'突出端的探针。

8. 发明申请

US20100255558A1 SUPRAMOLECULAR BIOCONJUGATES 审中-公开
公开(公告)号：US20100255558A1
公开(公告)日：2010-10-07
申请号：US12435665
申请日：2009-05-05
申请人： Christof M. Niemeyer , Charles R. Cantor , Takeshi Sano , Cassandra L. Smith
发明人： Christof M. Niemeyer , Charles R. Cantor , Takeshi Sano , Cassandra L. Smith
IPC分类号： C07K17/00 , C07K1/00 , C12N9/96
CPC分类号： B82Y5/00 , A61K47/54 , A61K47/55 , A61K47/557 , A61K47/6949 , A61K51/1268 , C03C17/30 , C03C17/3405 , C12Q1/6804 , C12Q1/682
摘要： The invention relates to supramolecular bioconjugates and to methods for assembling and utilizing supramolecular bioconjugates. Supramolecular bioconjugates comprise a plurality of first nucleic acids and a plurality of mediators wherein each mediator comprises a second nucleic acid complementary to a sequence within said plurality of first nucleic acids. To assemble a supramolecular bioconjugate, one or more sets of bioreactive agents are coupled to the plurality of mediators, forming a plurality of bioreactive complexes. The plurality of bioreactive complexes are hybridized to the plurality of first nucleic acids to form the supramolecular bioconjugate. Bioconjugates can be used to detect and isolate targets, to screen samples for targets such as antigens, to treat patients with multiple agents or to diagnose disorders in the form of a kit.
摘要翻译：本发明涉及超分子生物缀合物和组分和利用超分子生物缀合物的方法。超分子生物缀合物包含多个第一核酸和多个介体，其中每个介体包含与所述多个第一核酸内的序列互补的第二核酸。为了组装超分子生物缀合物，将一组或多组生物反应剂偶联至多个介体，形成多个生物反应性复合物。多个生物反应性复合物与多个第一核酸杂交以形成超分子生物缀合物。生物共轭物可用于检测和分离靶标，筛选靶标如抗原的样品，以治疗患有多种药物的患者或以试剂盒的形式诊断疾病。

9. 发明授权

US5665539A Immuno-polymerase chain reaction system for antigen detection 失效
标题翻译：抗原检测免疫聚合酶链反应体系
公开(公告)号：US5665539A
公开(公告)日：1997-09-09
申请号：US131301
申请日：1993-10-04
申请人： Takeshi Sano , Charles R. Cantor , Cassandra L. Smith
发明人： Takeshi Sano , Charles R. Cantor , Cassandra L. Smith
IPC分类号： A61K38/00 , A61K47/48 , C07K14/31 , C07K14/36 , C12Q1/68 , C12Q1/66
CPC分类号： C07K14/31 , B82Y5/00 , C07K14/36 , A61K38/00
摘要： A novel system and method for sensitive antigen detection. The system utilizes immuno-polymerase chain reaction in which a specific biotinylated nucleic acid molecule is used as the marker. The biotinylated marker is attached to antigen-antibody complex through a streptavidin-protein A chimeric protein that possesses tight and specific binding affinity both for biotin and immunoglobulin G. A segment of the attached biotinylated marker is amplified by polymerase chain reactions with appropriate primers and the polymerase chain reaction products are detected by agarose gel electrophoresis. The method can detect any antigen and has a greater sensitivity than any existing antigen detection system.
摘要翻译：一种用于敏感抗原检测的新型系统和方法。该系统利用免疫聚合酶链反应，其中使用特异性生物素化的核酸分子作为标记。生物素标记通过链霉抗生物素蛋白 - 蛋白A嵌合蛋白连接到抗原 - 抗体复合物上，该嵌合蛋白对于生物素和免疫球蛋白G都具有紧密和特异性的结合亲和力。通过与适当引物的聚合酶链反应扩增连接的生物素标记的片段，并且通过琼脂糖凝胶电泳检测聚合酶链反应产物。该方法可以检测任何抗原并且比任何现有的抗原检测系统具有更高的灵敏度。

10. 发明授权

US5561043A Self-assembling multimeric nucleic acid constructs 失效
公开(公告)号：US5561043A
公开(公告)日：1996-10-01
申请号：US189448
申请日：1994-01-31
申请人： Charles R. Cantor , Christof M. Niemeyer , Cassandra L. Smith , Takeshi Sano , Donald J. Hnatowich , Mary Rusckowski
发明人： Charles R. Cantor , Christof M. Niemeyer , Cassandra L. Smith , Takeshi Sano , Donald J. Hnatowich , Mary Rusckowski
IPC分类号： G01N33/566 , A61K38/00 , A61K38/16 , A61K38/21 , A61K38/22 , A61K38/27 , A61K38/43 , A61K39/00 , A61K39/395 , A61K45/00 , A61K47/48 , A61K49/00 , A61K51/00 , A61K51/12 , A61P31/04 , A61P31/12 , A61P35/00 , A61P35/02 , C03C17/30 , C03C17/34 , C07H21/04 , C12N15/09 , C12Q1/68 , C07H21/02
CPC分类号： B82Y5/00 , A61K47/481 , A61K47/48146 , A61K47/48961 , A61K51/1268 , C03C17/30 , C03C17/3405 , C12Q1/6804 , C12Q1/682 , Y10S977/80 , Y10S977/808 , Y10S977/898 , Y10S977/906 , Y10S977/92
摘要： The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products.

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