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1. 发明公开

EP3230445A2 COMPOSITIONS AND METHODS FOR EDITING NUCLEIC ACIDS IN CELLS UTILIZING OLIGONUCLEOTIDES 有权
标题翻译：使用寡核苷酸编辑细胞中的核酸的组合物和方法
公开(公告)号：EP3230445A2
公开(公告)日：2017-10-18
申请号：EP15868062.9
申请日：2015-12-11
申请人： Woolf, Tod M. , Lebedev, Alexandre , Hogrefe, Richard I.
发明人： Woolf, Tod M. , Lebedev, Alexandre , Hogrefe, Richard I.
IPC分类号： C12N15/01 , C12N15/85
CPC分类号： C12N15/102 , A61K48/00 , C12N15/111 , C12N2310/11 , C12N2310/315 , C12N2310/333 , C12N2310/335 , C12N2310/344 , C12N2310/351 , C12N2320/34
摘要： The present invention includes compositions and methods for the treatment of a medical condition or disease utilizing editing oligonucleotides. The editing oligonucleotides contain a an oligonucleotide strand of about 10 to about 50 nucleotides on each side of the editing moiety which may contain a sugar or linker that positions the active editing moiety in the proper location for hybridization to the target nucleic acid. The editing oligonucleotides may also contain at least one nucleotide sequence change from the targeted sequence in the genome. The method includes modifying a genomic sequence within a cell utilizing an editing oligonucleotide without additional proteins or nucleic acids to assist in the editing process. The editing oligonucleotide may comprise backbone modifications that increase the nuclease stability of the oligonucleotide as compared to unmodified oligonucleotides or oligonucleotides having three phosphorothioates on each terminus.
摘要翻译：本发明包括利用编辑寡核苷酸治疗医学病症或疾病的组合物和方法。编辑寡核苷酸在编辑部分的每一侧含有约10至约50个核苷酸的寡核苷酸链，其可以含有将活性编辑部分定位在适合于与靶核酸杂交的位置的糖或接头。编辑寡核苷酸还可以含有来自基因组中靶向序列的至少一个核苷酸序列改变。该方法包括利用编辑寡核苷酸修饰细胞内的基因组序列，而无需额外的蛋白质或核酸以辅助编辑过程。与未修饰的寡核苷酸或每个末端具有三个硫代磷酸酯的寡核苷酸相比，编辑寡核苷酸可以包含增加寡核苷酸的核酸酶稳定性的骨架修饰。

2. 发明公开

EP4372091A2 COMPOSITIONS AND METHODS FOR EDITING NUCLEIC ACIDS IN CELLS UTILIZING OLIGONUCLEOTIDES 审中-实审
公开(公告)号：EP4372091A2
公开(公告)日：2024-05-22
申请号：EP24153079.9
申请日：2015-12-11
申请人： Woolf, Tod M. , Lebedev, Alexandre , Hogrefe, Richard I.
发明人： Woolf, Tod M. , Lebedev, Alexandre , Hogrefe, Richard I.
IPC分类号： C12N15/85
CPC分类号： A61K48/00 , C12N15/111 , C12N2310/1120130101 , C12N2310/31520130101 , C12N2310/33320130101 , C12N2310/33520130101 , C12N2310/34420130101 , C12N2310/35120130101 , C12N2320/3420130101 , C12N15/102 , A61P1/00 , A61P11/00 , A61P13/02 , A61P13/12 , A61P21/04 , A61P25/00 , A61P25/14 , A61P25/28 , A61P27/02 , A61P3/00 , A61P35/00 , A61P3/06 , A61P3/08 , A61P43/00 , A61P7/00 , A61P9/00
摘要： The present invention includes compositions and methods for the treatment of a medical condition or disease utilizing editing oligonucleotides. The editing oligonucleotides contain a an oligonucleotide strand of about 10 to about 50 nucleotides on each side of the editing moiety which may contain a sugar or linker that positions the active editing moiety in the proper location for hybridization to the target nucleic acid. The editing oligonucleotides may also contain at least one nucleotide sequence change from the targeted sequence in the genome. The method includes modifying a genomic sequence within a cell utilizing an editing oligonucleotide without additional proteins or nucleic acids to assist in the editing process. The editing oligonucleotide may comprise backbone modifications that increase the nuclease stability of the oligonucleotide as compared to unmodified oligonucleotides or oligonucleotides having three phosphorothioates on each terminus.

3. 发明公开

EP4372091A3 COMPOSITIONS AND METHODS FOR EDITING NUCLEIC ACIDS IN CELLS UTILIZING OLIGONUCLEOTIDES 审中-实审
公开(公告)号：EP4372091A3
公开(公告)日：2024-07-31
申请号：EP24153079.9
申请日：2015-12-11
申请人： Woolf, Tod M. , Lebedev, Alexandre , Hogrefe, Richard I.
发明人： Woolf, Tod M. , Lebedev, Alexandre , Hogrefe, Richard I.
IPC分类号： C12N15/01 , C12N15/85
CPC分类号： A61K48/00 , C12N15/111 , C12N2310/1120130101 , C12N2310/31520130101 , C12N2310/33320130101 , C12N2310/33520130101 , C12N2310/34420130101 , C12N2310/35120130101 , C12N2320/3420130101 , C12N15/102 , A61P1/00 , A61P11/00 , A61P13/02 , A61P13/12 , A61P21/04 , A61P25/00 , A61P25/14 , A61P25/28 , A61P27/02 , A61P3/00 , A61P35/00 , A61P3/06 , A61P3/08 , A61P43/00 , A61P7/00 , A61P9/00 , C12N2310/2020170501
摘要： The present invention includes compositions and methods for the treatment of a medical condition or disease utilizing editing oligonucleotides. The editing oligonucleotides contain a an oligonucleotide strand of about 10 to about 50 nucleotides on each side of the editing moiety which may contain a sugar or linker that positions the active editing moiety in the proper location for hybridization to the target nucleic acid. The editing oligonucleotides may also contain at least one nucleotide sequence change from the targeted sequence in the genome. The method includes modifying a genomic sequence within a cell utilizing an editing oligonucleotide without additional proteins or nucleic acids to assist in the editing process. The editing oligonucleotide may comprise backbone modifications that increase the nuclease stability of the oligonucleotide as compared to unmodified oligonucleotides or oligonucleotides having three phosphorothioates on each terminus.

4. 发明申请

WO2012094343A1 CHEMICALLY SUBSTITUTED THERMOSENSITIVE PROBES AND COFACTORS FOR HOT START LIGATION 审中-公开
标题翻译：化学取代的热敏探头和热源起始剂
公开(公告)号：WO2012094343A1
公开(公告)日：2012-07-12
申请号：PCT/US2012/020109
申请日：2012-01-03
申请人： TRILINK BIOTECHNOLOGIES , LEBEDEV, Alexandre , KOUKHAREVA, Inna
发明人： LEBEDEV, Alexandre , KOUKHAREVA, Inna
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6862 , C12Q1/682 , C12Q1/6827 , C12Q2527/125 , C12Q2527/127 , C12Q2525/161 , C12Q2537/125 , C12Q2537/143
摘要： Provided herein are methods for ligase mediated nucleic acid replication and amplification of oligo- and probes containing substituted ligase components, particularly substituted ligase cofactors, substituted oligo- and probe acceptors, substituted oligo- and probe donors, substituted adenylated oligo- and polynucleotide donor intermediates carrying thermolabile group or groups. The substituted ligase components are not active until Hot Start activation step converts them into unsubstituted or natural ligase components, which fully support ligase reaction. The described methods are readily applied to ligation-based assays, especially utilizing Ligase Chain Reaction (LCR), for detection of a nucleic acid sequence where the use of the substituted ligase components improves an overall efficiency of LCR, increase discrimination between matched and mismatched templates and reduces or eliminates appearance of false positive signal. Furthermore, the use of the substituted ligase components reduces or eliminates the false positive signal originated from the template independent and blunt-ended ligation.
摘要翻译：本文提供了连接酶介导的核酸复制和扩增含有取代的连接酶组分，特别是取代的连接酶辅因子，取代的寡核苷酸和探针受体，取代的寡核苷酸和探针供体的寡核苷酸和探针，取代的腺苷酸化寡核苷酸和多核苷酸供体中间体的方法不耐热组或组。取代的连接酶组分不活跃，直到热启动活化步骤将其转化为未完全支持连接酶反应的未取代或天然连接酶组分。所描述的方法容易地应用于基于连接的测定，特别是利用连接酶链反应（LCR）检测核酸序列，其中使用取代的连接酶组分改善LCR的总体效率，增加匹配和不匹配模板之间的鉴别并减少或消除假阳性信号的出现。此外，使用取代的连接酶组分减少或消除了源自模板独立和平端连接的假阳性信号。

5. 发明申请

WO2011005762A1 CHEMICALLY MODIFIED LIGASE COFACTORS, DONORS AND ACCEPTORS 审中-公开
标题翻译：化学改性助剂，助剂和接收剂
公开(公告)号：WO2011005762A1
公开(公告)日：2011-01-13
申请号：PCT/US2010/041069
申请日：2010-07-06
申请人： TRILINK BIOTECHNOLOGIES , PAUL, Natasha , SHUM, Jonathan , LEBEDEV, Alexandre , ZON, Gerald
发明人： PAUL, Natasha , SHUM, Jonathan , LEBEDEV, Alexandre , ZON, Gerald
IPC分类号： C12Q1/68 , C12N9/00
CPC分类号： C12Q1/6862 , C12Q1/6827 , C12Q1/6848 , C12Q2525/101 , C12Q2527/127 , C12Q2533/107 , C12Q2521/501
摘要： Provided herein are methods for ligation of polynucleotides containing modified ligation components, particularly modified ligase cofactors, modified acceptors and modified donors. The methods readily applied to ligation-based assays for detection of a nucleic acid sequence where the use of the modified cofactor improves discrimination between matched and mismatched templates. Furthermore, the use of the modified ligation components reduces or eliminates the ligation in the absence of nucleic acid template.
摘要翻译：本文提供了用于连接含有修饰的连接组分，特别是修饰的连接酶辅因子，修饰的受体和修饰的供体的多核苷酸的方法。该方法容易地应用于用于检测核酸序列的基于连接的测定，其中使用经修饰的辅因子改善了匹配和不匹配模板之间的区别。此外，修饰的连接组分的使用减少或消除了在没有核酸模板的情况下的连接。

6. 发明申请

WO2007139723A8 CHEMICALLYMODIFIED OLIGONUCLEOTIDE PRIMERS FOR NUCLEIC ACID AMPLIFICATION 审中-公开
标题翻译：用于核酸扩增的化学修饰的寡核苷酸引物
公开(公告)号：WO2007139723A8
公开(公告)日：2009-12-17
申请号：PCT/US2007011950
申请日：2007-05-17
申请人： TRILINK BIOTECHNOLOGIES , ZON GERALD , LEBEDEV ALEXANDRE
发明人： ZON GERALD , LEBEDEV ALEXANDRE
IPC分类号： C12P19/34
CPC分类号： C12Q1/6848 , C12Q2527/107 , C12Q2525/117
摘要： The present invention provides methods and compositions for nucleic acid amplification. These methods involve the use of oligonucleotide primers in temperature dependent nucleic acid amplification reactions. In certain aspects, the methods are accomplished by use of certain modified oligonucleotide primers which provide utility in nucleic acid amplification. In preferred embodiments, the oligonucleotide primers are modified with particular chemical groups such as esters.
摘要翻译：本发明提供了用于核酸扩增的方法和组合物。这些方法涉及在温度依赖性核酸扩增反应中使用寡核苷酸引物。在某些方面，所述方法通过使用在核酸扩增中提供效用的某些修饰的寡核苷酸引物来实现。在优选的实施方案中，寡核苷酸引物用特定的化学基团如酯改性。

7. 发明申请

WO2016094845A2 COMPOSITIONS AND METHODS FOR EDITING NUCLEIC ACIDS IN CELLS UTILIZING OLIGONUCLEOTIDES 审中-公开
标题翻译：用于使用寡核苷酸的细胞中编码核酸的组合物和方法
公开(公告)号：WO2016094845A2
公开(公告)日：2016-06-16
申请号：PCT/US2015/065348
申请日：2015-12-11
申请人： WOOLF, Tod M. , LEBEDEV, Alexandre , HOGREFE, Richard I.
发明人： WOOLF, Tod M. , LEBEDEV, Alexandre , HOGREFE, Richard I.
IPC分类号： A61K48/00 , C12N15/85
CPC分类号： C12N15/102 , A61K48/00 , C12N15/111 , C12N2310/11 , C12N2310/315 , C12N2310/333 , C12N2310/335 , C12N2310/344 , C12N2310/351 , C12N2320/34
摘要： The present invention includes compositions and methods for the treatment of a medical condition or disease utilizing editing oligonucleotides. The editing oligonucleotides contain a an oligonucleotide strand of about 10 to about 50 nucleotides on each side of the editing moiety which may contain a sugar or linker that positions the active editing moiety in the proper location for hybridization to the target nucleic acid. The editing oligonucleotides may also contain at least one nucleotide sequence change from the targeted sequence in the genome. The method includes modifying a genomic sequence within a cell utilizing an editing oligonucleotide without additional proteins or nucleic acids to assist in the editing process. The editing oligonucleotide may comprise backbone modifications that increase the nuclease stability of the oligonucleotide as compared to unmodified oligonucleotides or oligonucleotides having three phosphorothioates on each terminus.
摘要翻译：本发明包括利用编辑寡核苷酸治疗医学病症或疾病的组合物和方法。编辑寡核苷酸在编辑部分的每一侧含有约10至约50个核苷酸的寡核苷酸链，其可含有将活性编辑部分置于适当位置以与靶核酸杂交的糖或接头。编辑寡核苷酸还可以含有至少一个从基因组中靶向序列变化的核苷酸序列。该方法包括利用编辑寡核苷酸修饰细胞内的基因组序列而无需另外的蛋白质或核酸来辅助编辑过程。与未修饰的寡核苷酸或在每个末端具有三个硫代磷酸酯的寡核苷酸相比，编辑寡核苷酸可以包含增加寡核苷酸的核酸酶稳定性的骨架修饰。

8. 发明申请

WO2009151921A1 CHEMICALLY MODIFIED NUCLEOSIDE 5'-TRIPHOSPHATES FOR THERMALLY INITIATED AMPLIFICATION OF NUCLEIC ACID 审中-公开
标题翻译：化学改性核壳素5'-磷酸酯，用于热启动核酸扩增
公开(公告)号：WO2009151921A1
公开(公告)日：2009-12-17
申请号：PCT/US2009/044910
申请日：2009-05-21
申请人： TRILINK BIOTECHNOLOGIES , LEBEDEV, Alexandre V. , KOUKHAREVA, Inna
发明人： LEBEDEV, Alexandre V. , KOUKHAREVA, Inna
IPC分类号： C07H19/00
CPC分类号： C07H19/00 , C12Q1/686 , C12Q1/6862 , C12Q1/6869 , C12Q2525/101 , C12Q2525/186 , C12Q2545/101
摘要： Provided herein are methods and compositions for nucleic acid amplification. These methods involve the use of 3'-substituted nucleoside 5'-triphosphates or 3'-substituted terminated primers in nucleic acid amplification reactions. In certain aspects, the methods are accomplished by use of 3'-substituted NTPs and/or 3'-substituted terminated primers which provide utility in nucleic acid amplification. In preferred embodiments, the NTPs and/or primers are substituted at the 3'-position with particular heat labile chemical groups such as ethers, esters or carbonate esters.
摘要翻译：本文提供了用于核酸扩增的方法和组合物。这些方法涉及在核酸扩增反应中使用3'-取代核苷5'-三磷酸或3'-取代的封端引物。在某些方面，所述方法通过使用在核酸扩增中提供效用的3'-取代的NTP和/或3'-取代的封端引物来完成。在优选的实施方案中，NTP和/或引物在3'-位置被特定的热不稳定化学基团例如醚，酯或碳酸酯代替。

9. 发明申请

WO2007139723A1 CHEMICALLYMODIFIED OLIGONUCLEOTIDE PRIMERS FOR NUCLEIC ACID AMPLIFICATION 审中-公开
标题翻译：用于核酸扩增的化学修饰的寡核苷酸引物
公开(公告)号：WO2007139723A1
公开(公告)日：2007-12-06
申请号：PCT/US2007/011950
申请日：2007-05-17
申请人： TRILINK BIOTECHNOLOGIES , ZON, Gerald , LEBEDEV, Alexandre
发明人： ZON, Gerald , LEBEDEV, Alexandre
IPC分类号： C12P19/34
CPC分类号： C12Q1/6848 , C12Q2527/107 , C12Q2525/117
摘要： The present invention provides methods and compositions for nucleic acid amplification. These methods involve the use of oligonucleotide primers in temperature dependent nucleic acid amplification reactions. In certain aspects, the methods are accomplished by use of certain modified oligonucleotide primers which provide utility in nucleic acid amplification. In preferred embodiments, the oligonucleotide primers are modified with particular chemical groups such as esters.
摘要翻译：本发明提供用于核酸扩增的方法和组合物。这些方法涉及在温度依赖性核酸扩增反应中使用寡核苷酸引物。在某些方面，所述方法通过使用提供核酸扩增实用性的某些修饰的寡核苷酸引物来实现。在优选的实施方案中，寡核苷酸引物用特定的化学基团如酯改性。

10. 发明申请

WO2016094845A3 COMPOSITIONS AND METHODS FOR EDITING NUCLEIC ACIDS IN CELLS UTILIZING OLIGONUCLEOTIDES 审中-公开
标题翻译：使用寡核苷酸编辑细胞中的核酸的组合物和方法
公开(公告)号：WO2016094845A3
公开(公告)日：2017-06-15
申请号：PCT/US2015065348
申请日：2015-12-11
申请人： WOOLF TOD M , LEBEDEV ALEXANDRE , HOGREFE RICHARD I
发明人： WOOLF TOD M , LEBEDEV ALEXANDRE , HOGREFE RICHARD I
IPC分类号： C12N15/01 , C12N15/85
CPC分类号： C12N15/102 , A61K48/00 , C12N15/111 , C12N2310/11 , C12N2310/315 , C12N2310/333 , C12N2310/335 , C12N2310/344 , C12N2310/351 , C12N2320/34
摘要： The present invention includes compositions and methods for the treatment of a medical condition or disease utilizing editing oligonucleotides. The editing oligonucleotides contain a an oligonucleotide strand of about 10 to about 50 nucleotides on each side of the editing moiety which may contain a sugar or linker that positions the active editing moiety in the proper location for hybridization to the target nucleic acid. The editing oligonucleotides may also contain at least one nucleotide sequence change from the targeted sequence in the genome. The method includes modifying a genomic sequence within a cell utilizing an editing oligonucleotide without additional proteins or nucleic acids to assist in the editing process. The editing oligonucleotide may comprise backbone modifications that increase the nuclease stability of the oligonucleotide as compared to unmodified oligonucleotides or oligonucleotides having three phosphorothioates on each terminus.
摘要翻译：本发明包括利用编辑寡核苷酸治疗医学病症或疾病的组合物和方法。编辑寡核苷酸在编辑部分的每一侧含有约10至约50个核苷酸的寡核苷酸链，其可以含有将活性编辑部分定位在适合于与靶核酸杂交的位置的糖或接头。编辑寡核苷酸还可以含有来自基因组中靶向序列的至少一个核苷酸序列改变。该方法包括利用编辑寡核苷酸修饰细胞内的基因组序列，而无需额外的蛋白质或核酸以辅助编辑过程。与未修饰的寡核苷酸或每个末端具有三个硫代磷酸酯的寡核苷酸相比，编辑寡核苷酸可以包含增加寡核苷酸的核酸酶稳定性的骨架修饰。

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