公开(公告)号：US20070054279A1

公开(公告)日：2007-03-08

申请号：US11197753

申请日：2005-08-04

申请人： Muthiah Manoharan ,  Kallanthottathil Rajeev ,  Jie Xia

发明人： Muthiah Manoharan ,  Kallanthottathil Rajeev ,  Jie Xia

IPC分类号： C12Q1/68 ,  C07H21/02 ,  C07F9/6512 ,  C07F9/6533

CPC分类号： C07H21/00 ,  A61K31/7115 ,  C07F9/6561 ,  C07H21/02 ,  C12Q1/6883 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393 ,  Y02A50/395 ,  Y02A50/411 ,  Y02A50/463 ,  Y02A50/465 ,  Y02A50/467

摘要： One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.

摘要翻译： 本发明的一个方面涉及包含至少一个与改变的或非天然核碱基连接的配体的双链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吡咯基或硝基咪唑基。 在某些实施方案中，配体是类固醇或芳族化合物。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链中只有一条含有与改变的或非天然核碱基连接的配体。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链都独立地包含与改变的或非天然核碱基连接的配体。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一个与改变的或非天然核碱基连接的配体的单链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吡咯基或硝基咪唑基。 在某些实施方案中，配体是类固醇或芳族化合物。 在某些实施方案中，在核苷中天然存在的核糖部分被己糖，多环杂烷基环或环己烯基取代。 在某些实施方案中，寡核苷酸中的至少一个磷酸键被硫代磷酸酯键取代。

公开(公告)号：US20060035254A1

公开(公告)日：2006-02-16

申请号：US11186915

申请日：2005-07-21

申请人： Muthiah Manoharan ,  Jie Xia ,  Kallanthottathil Rajeev

发明人： Muthiah Manoharan ,  Jie Xia ,  Kallanthottathil Rajeev

IPC分类号： C12Q1/68 ,  C07H21/02 ,  C07F9/6512

CPC分类号： C07H21/00 ,  A61K31/7115 ,  C07F9/65515 ,  C07F9/65586 ,  C07F9/6561 ,  C07H21/02 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393 ,  Y02A50/395 ,  Y02A50/411 ,  Y02A50/463 ,  Y02A50/465 ,  Y02A50/467

摘要： One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.

公开(公告)号：US07893224B2

公开(公告)日：2011-02-22

申请号：US12533710

申请日：2009-07-31

申请人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Jie Xia

发明人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Jie Xia

IPC分类号： C07G3/00 ,  C07H21/04 ,  C12Q1/68

CPC分类号： C07H21/00 ,  A61K31/7115 ,  C07F9/6561 ,  C07H21/02 ,  C12Q1/6883 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393 ,  Y02A50/395 ,  Y02A50/411 ,  Y02A50/463 ,  Y02A50/465 ,  Y02A50/467

摘要： One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.

摘要翻译： 本发明的一个方面涉及包含至少一个与改变的或非天然核碱基连接的配体的双链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吡咯基或硝基咪唑基。 在某些实施方案中，配体是类固醇或芳族化合物。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链中只有一条含有与改变的或非天然核碱基连接的配体。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链都独立地包含与改变的或非天然核碱基连接的配体。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一个与改变的或非天然核碱基连接的配体的单链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吡咯基或硝基咪唑基。 在某些实施方案中，配体是类固醇或芳族化合物。 在某些实施方案中，在核苷中天然存在的核糖部分被己糖，多环杂烷基环或环己烯基取代。 在某些实施方案中，寡核苷酸中的至少一个磷酸键被硫代磷酸酯键取代。

公开(公告)号：US07772387B2

公开(公告)日：2010-08-10

申请号：US12495932

申请日：2009-07-01

申请人： Muthiah Manoharan ,  Jie Xia ,  Kallanthottathil G. Rajeev

发明人： Muthiah Manoharan ,  Jie Xia ,  Kallanthottathil G. Rajeev

IPC分类号： C07H21/02 ,  C07H21/04 ,  C12Q1/68

CPC分类号： C07H21/00 ,  A61K31/7115 ,  C07F9/65515 ,  C07F9/65586 ,  C07F9/6561 ,  C07H21/02 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393 ,  Y02A50/395 ,  Y02A50/411 ,  Y02A50/463 ,  Y02A50/465 ,  Y02A50/467

摘要： One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.

摘要翻译： 本发明的一个方面涉及包含至少一种非天然核碱基的双链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吲哚基，硝基吡咯基或硝基咪唑基。 在优选的实施方案中，非天然核碱基是二氟苯甲酰基。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链中只有一条含有非天然核碱基。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链都独立地含有非天然核碱基。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一种非天然核碱基的单链寡核苷酸。 在优选的实施方案中，非天然核碱基是二氟苯甲酰基。 在某些实施方案中，在核苷中天然存在的核糖部分被己糖，多环杂烷基环或环己烯基取代。 在某些实施方案中，寡核苷酸中的至少一个磷酸键被硫代磷酸酯键取代。

公开(公告)号：US07579451B2

公开(公告)日：2009-08-25

申请号：US11186915

申请日：2005-07-21

申请人： Muthiah Manoharan ,  Jie Xia ,  Kallanthottathil G. Rajeev

发明人： Muthiah Manoharan ,  Jie Xia ,  Kallanthottathil G. Rajeev

IPC分类号： C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C12Q1/68

CPC分类号： C07H21/00 ,  A61K31/7115 ,  C07F9/65515 ,  C07F9/65586 ,  C07F9/6561 ,  C07H21/02 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393 ,  Y02A50/395 ,  Y02A50/411 ,  Y02A50/463 ,  Y02A50/465 ,  Y02A50/467

摘要： One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.

摘要翻译： 本发明的一个方面涉及包含至少一种非天然核碱基的双链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吲哚基，硝基吡咯基或硝基咪唑基。 在优选的实施方案中，非天然核碱基是二氟苯甲酰基。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链中只有一条含有非天然核碱基。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链都独立地含有非天然核碱基。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一种非天然核碱基的单链寡核苷酸。 在优选的实施方案中，非天然核碱基是二氟苯甲酰基。 在某些实施方案中，在核苷中天然存在的核糖部分被己糖，多环杂烷基环或环己烯基取代。 在某些实施方案中，寡核苷酸中的至少一个磷酸键被硫代磷酸酯键取代。

公开(公告)号：US07632932B2

公开(公告)日：2009-12-15

申请号：US11197753

申请日：2005-08-04

申请人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Jie Xia

发明人： Muthiah Manoharan ,  Kallanthottathil G. Rajeev ,  Jie Xia

IPC分类号： C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  C12Q1/68

CPC分类号： C07H21/00 ,  A61K31/7115 ,  C07F9/6561 ,  C07H21/02 ,  C12Q1/6883 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393 ,  Y02A50/395 ,  Y02A50/411 ,  Y02A50/463 ,  Y02A50/465 ,  Y02A50/467

摘要： One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one ligand tethered to an altered or non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitropyrrolyl, or nitroimidazolyl. In certain embodiments, the ligand is a steroid or aromatic compound. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.

摘要翻译： 本发明的一个方面涉及包含至少一个与改变的或非天然核碱基连接的配体的双链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吡咯基或硝基咪唑基。 在某些实施方案中，配体是类固醇或芳族化合物。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链中只有一条含有与改变的或非天然核碱基连接的配体。 在某些实施方案中，包含双链寡核苷酸的两条寡核苷酸链都独立地包含与改变的或非天然核碱基连接的配体。 在某些实施方案中，寡核苷酸链包含至少一个修饰的糖部分。 本发明的另一方面涉及包含至少一个与改变的或非天然核碱基连接的配体的单链寡核苷酸。 在某些实施方案中，非天然核碱基是二氟苯甲酰基，硝基吡咯基或硝基咪唑基。 在某些实施方案中，配体是类固醇或芳族化合物。 在某些实施方案中，在核苷中天然存在的核糖部分被己糖，多环杂烷基环或环己烯基取代。 在某些实施方案中，寡核苷酸中的至少一个磷酸键被硫代磷酸酯键取代。

公开(公告)号：US07569686B1

公开(公告)日：2009-08-04

申请号：US11747042

申请日：2007-05-10

申请人： Balkrishen Bhat ,  Jie Xia ,  Punit P. Seth ,  Guillermo Vasquez ,  Michael T. Migawa ,  Charles Allerson ,  Thazha P. Prakash ,  Eric E. Swayze

发明人： Balkrishen Bhat ,  Jie Xia ,  Punit P. Seth ,  Guillermo Vasquez ,  Michael T. Migawa ,  Charles Allerson ,  Thazha P. Prakash ,  Eric E. Swayze

IPC分类号： C07H21/00

CPC分类号： C07H19/00

摘要： The present invention provides compounds and methods of using them for preparing bicyclic nucleosides. The bicyclic nucleosides are useful for preparing chemically modified oligomeric compounds. Oligomeric compounds comprising these bicyclic nucleosides have enhanced properties such as increased nuclease resistance.

摘要翻译： 本发明提供了使用它们制备双环核苷的化合物和方法。 双环核苷可用于制备化学修饰的低聚化合物。 包含这些双环核苷的低聚化合物具有增强的性质，例如增加的核酸酶抗性。

公开(公告)号：US06380031B1

公开(公告)日：2002-04-30

申请号：US09637090

申请日：2000-08-10

申请人： Freidoon Mehrad ,  Jie Xia ,  Sandra Zheng ,  Lancy Tsung

发明人： Freidoon Mehrad ,  Jie Xia ,  Sandra Zheng ,  Lancy Tsung

IPC分类号： H01L21336

CPC分类号： H01L27/11521 ,  H01L29/66825

摘要： A method to form an embedded FLASH integrated circuit with reduced processing steps is described. In the method a partial etch is performed on the control gate region of a polycrystalline silicon film (21). A multiple etch process is then used to simultaneously form the FLASH memory cell gate stack (54), the NMOS gate structure (94) and the PMOS gate structure (96).

摘要翻译： 描述了一种以缩短处理步骤形成嵌入式FLASH集成电路的方法。 在该方法中，对多晶硅膜（21）的控制栅极区域进行部分蚀刻。 然后使用多重蚀刻工艺同时形成闪存存储单元栅极堆叠（54），NMOS栅极结构（94）和PMOS栅极结构（96）。

公开(公告)号：US06451642B1

公开(公告)日：2002-09-17

申请号：US09599377

申请日：2000-06-22

申请人： Freidoon Mehrad ,  Jie Xia ,  Thomas M. Ambrose

发明人： Freidoon Mehrad ,  Jie Xia ,  Thomas M. Ambrose

IPC分类号： H01L218238

CPC分类号： H01L27/11526 ,  H01L21/31138 ,  H01L21/32137 ,  H01L27/105 ,  H01L27/11546

摘要： A method to implant NMOS polycrystalline silicon in embedded FLASH memory applications is described. In the method the polycrystalline silicon region (130) that will used to form the gate electrode of the NMOS transistor is doped simultaneously along with the source line in the FLASH memory array.

摘要翻译： 描述了在嵌入式FLASH存储器应用中注入NMOS多晶硅的方法。 在该方法中，将用于形成NMOS晶体管的栅极的多晶硅区域（130）与闪存存储器阵列中的源极线同时掺杂。

公开(公告)号：US06429093B1

公开(公告)日：2002-08-06

申请号：US09627258

申请日：2000-07-28

申请人： Jie Xia ,  Freidoon Mehrad ,  Mercer L. Brugler

发明人： Jie Xia ,  Freidoon Mehrad ,  Mercer L. Brugler

IPC分类号： H01L2176

CPC分类号： H01L27/11521 ,  H01L21/28518 ,  H01L21/3185 ,  H01L21/823481 ,  H01L27/115 ,  H01L29/66545

摘要： A method of forming a semiconductor component having a conductive line (24) and a silicide region (140) that crosses a trench (72). The method involves forming nitride sidewalls (127) to protect the stack during the silicidation process.

摘要翻译： 一种形成具有导电线（24）和穿过沟槽（72）的硅化物区域（140）的半导体部件的方法。 该方法包括在硅化过程中形成氮化物侧壁（127）以保护堆叠。