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公开(公告)号：US10815482B2
公开(公告)日：2020-10-27
申请号：US16109638
申请日：2018-08-22
发明人： Meena , David Butler , Naoki Iwamoto , Nenad Svrzikapa , Gregory L. Verdine , Ivan Zlatev
IPC分类号： C12N15/113
摘要： The present invention relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer.
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公开(公告)号：US20200231620A1
公开(公告)日：2020-07-23
申请号：US16648146
申请日：2018-09-17
申请人： Keith Andrew BOWMAN , Chandra VARGEESE , David Charles Donnell BUTLER , Pachamuthu KANDASAMY , Mohammed Rowshon ALAM , Mamoru SHIMIZU , Stephany Michelle STANDLEY , Vincent ADUDA , Gopal Reddy BOMMINENI , Snehlata TRIPATHI , Ilia KORBOUKH , WAVE LIFE SCIENCES LTD.
发明人： Keith Andrew Bowman , Chandra Vargeese , David Charles Donnell Butler , Pachamuthu Kandasamy , Mohammed Rowshon Alam , Mamoru Shimizu , Stephany Michelle Standley , Vincent Aduda , Gopal Reddy Bommineni , Snehlata Tripathi , Ilia Korboukh
摘要： Among other things, the present disclosure provides technologies for oligonucleotide preparation, particularly chirally controlled oligonucleotide preparation, which technologies provide greatly improved crude purity and yield, and significantly reduce manufacturing costs.
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公开(公告)号：US20200157545A1
公开(公告)日：2020-05-21
申请号：US16618010
申请日：2018-06-01
申请人： Chandra VARGEESE , Naoki IWAMOTO , David Charles Donnell BUTLER , Subramanian MARAPPAN , Genliang LU , Jason Jingxin ZHANG , Vinod VATHIPADIEKAL , Maria David FRANK-KAMENETSKY , Luciano Henrique APPONI , WAVE LIFE SCIENCES LTD.
发明人： Chandra Vargeese , Naoki Iwamoto , David Charles Donnell Butler , Subramanian Marappan , Genliang Lu , Jason Jingxin Zhang , Vinod Vathipadiekal , Maria David Frank-Kamenetsky , Luciano Henrique Apponi , Young Jin Cho
IPC分类号： C12N15/113 , A61K31/712
摘要： Among other things, the present disclosure provides designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in RNA interference and/or RNase H-mediated knockdown.
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公开(公告)号：US20200080083A1
公开(公告)日：2020-03-12
申请号：US16551503
申请日：2019-08-26
发明人： Chandra Vargeese , Meena . , Nenad Svrzikapa , Susovan Mohapatra , Christopher J. Francis , Gregory L. Verdine , Anna Sokolovska
IPC分类号： C12N15/113 , A61P25/28 , C12N15/115
摘要： Among other things, the present disclosure relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer. In some embodiments, a chirally controlled oligonucleotide composition has any sequence of bases, and/or pattern or base modifications, sugar modifications, backbone modifications and/or stereochemistry, or combination of these elements, described herein.
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公开(公告)号：US20190209604A1
公开(公告)日：2019-07-11
申请号：US16305937
申请日：2017-06-02
发明人： Jason Jingxin Zhang , Naoki Iwamoto , Christopher J. Francis , Chandra Vargeese , David Charles Donnell Butler , Sethumadhavan Divakaramenon , Genliang Lu , Subramanian Marappan
IPC分类号： A61K31/7125 , C12N15/117 , A61P21/00
CPC分类号： A61K31/7125 , A61K31/7088 , A61P21/00 , C12N15/117 , C12N2310/17 , C12N2310/31 , C12N2310/315 , C12N2310/351 , C12N2310/3515
摘要： The present disclosure pertains to the recognition that immune responses mediated by CpG oligonucleotides can be affected by the stereochemistry of modified internucleotidic linkages such as phosphorothioates. In some embodiments, the present disclosure relates to chirally controlled CpG oligonucleotide compositions comprising CpG oligonucleotides comprising multiple modified internucleotidic linkages such as phosphorothioate linkages, wherein the oligonucleotides comprise one or more CpG region motifs having defined stereochemistry patterns of chiral internucleotidic linkages. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are capable of agonizing an immune response. In some embodiments, CpG oligonucleotides comprising one or more CpG region motifs are antagonistic. Methods for making and using chirally controlled CpG oligonucleotide compositions are also described. In some embodiments, no immune modulation is desired, and the present disclosure provides methods of identifying chirally controlled oligonucleotide compositions which have decreased immune modulation.
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公开(公告)号：US20190177357A1
公开(公告)日：2019-06-13
申请号：US16182302
申请日：2018-11-06
发明人： Mamoru Shimizu , Takeshi Wada
IPC分类号： C07H23/00 , C07H19/207 , C07H19/10 , C07H1/00 , C07F7/08 , C07D473/34 , C07B53/00 , C07D405/04 , C07D207/08 , C07H21/04 , C07H19/213 , C07H19/11 , C07D473/18
摘要： To provide a chiral reagent or a salt thereof.The chiral reagent has following chemical formula (I). In the formula (I), G1 and G2 are independently a hydrogen atom, a nitro group (—NO2), a halogen atom, a cyano group (—CN), a group of formula (II) or (III), or both G1 and G2 taken together to form a group of formula (IV).
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公开(公告)号：US10280192B2
公开(公告)日：2019-05-07
申请号：US15941494
申请日：2018-03-30
IPC分类号： A61K31/66 , A61K31/70 , C07H13/04 , C07H21/04 , C07C309/66 , C07D295/108
摘要： The present application, among other things, provides technologies, e.g., reagents, methods, etc. for preparing oligonucleotides comprising phosphorothiotriesters linkages. In some embodiments, provided methods comprise reacting an H-phosphonate of structure Ia or Ib with a silylating reagent to provide a silyloxyphosphonate, and reacting the silyloxyphosphonate with a thiosulfonate reagent of structure IIa or IIb to provide an oligonucleotide of structure IIIa or IIIb. In some embodiments, provided methods comprise reacting an H-phosphonate of structure Ic with a silylating reagent to provide a silyloxyphosphonate, reacting the silyloxyphosphonate with a bis(thiosulfonate) reagent of structure IVc to provide a phosphorothiotriester comprising a thiosulfonate group of structure Vc, and then reacting the phosphorothiotriester comprising a thiosulfonate group of structure Vc with a nucleophile of structure VIc to provide an oligonucleotide of structure IIIc. In some embodiments, the present application provides a thiosulfonate reagent of structure IIa:
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公开(公告)号：US20190106696A1
公开(公告)日：2019-04-11
申请号：US16109638
申请日：2018-08-22
发明人： Meena , David Butler , Naoki Iwamoto , Nenad Svrzikapa , Gregory L. Verdine , Ivan Zlatev
IPC分类号： C12N15/113
摘要： The present invention relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer.
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公开(公告)号：US20180222936A1
公开(公告)日：2018-08-09
申请号：US15941494
申请日：2018-03-30
IPC分类号： C07H21/04 , C07H13/04 , A61K31/66 , C07C309/66 , A61K31/70 , C07D295/108
CPC分类号： C07H21/04 , A61K31/66 , A61K31/70 , C07C309/66 , C07D295/108 , C07H13/04
摘要： Described herein are methods for the synthesis of derivatives of thiosulfonate reagents. Said reagents have utility for the synthesis of phosphorothiotriesters from H-phosphonates in a stereospecific fashion.
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公开(公告)号：US20240026358A1
公开(公告)日：2024-01-25
申请号：US18252029
申请日：2022-03-11
发明人： Prashant Monian , Chikdu Shakti Shivalila , Subramanian Marappan , Chandra Vargeese , Pachamuthu Kandasamy , Genliang Lu , Hui Yu , David Charles Donnell Butler , Luciano Henrique Apponi , Mamoru Shimizu , Stephany Michelle Standley , David John Boulay , Andrew Guzior Hoss , Jigar Desai , Jack David Godfrey , Hailin Yang , Naoki Iwamoto , Jayakanthan Kumarasamy , Anthony Lamattina , Tom Liantang Pu
IPC分类号： C12N15/113
CPC分类号： C12N15/113 , C12N2310/322 , C12N2310/321 , C12N2310/315 , C12N2320/34
摘要： Among other things, the present disclosure provides oligonucleotides and compositions thereof. In some embodiments, provided oligonucleotides and compositions are useful for adenosine modification. In some embodiments, the present disclosure provides methods for treating various conditions, disorders or diseases that can benefit from adenosine modification.
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