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1. 发明授权

US6166199A N-2 substituted purines 失效
标题翻译： N-2取代嘌呤
公开(公告)号：US6166199A
公开(公告)日：2000-12-26
申请号：US128834
申请日：1998-08-04
申请人： Phillip Dan Cook , Kanda S. Ramasamy , Muthiah Manoharan
发明人： Phillip Dan Cook , Kanda S. Ramasamy , Muthiah Manoharan
IPC分类号： C07D473/16 , A61K31/415 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7076 , A61K31/708 , A61K31/7088 , A61K38/00 , A61K47/48 , A61K48/00 , A61P31/12 , C07D473/18 , C07D487/04 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/167 , C07H19/173 , C07H19/20 , C07H21/00 , C07H21/02 , C07H21/04 , C07H23/00 , C07J43/00 , C12N9/02 , C12N15/113 , C12Q1/68 , C07H19/00
CPC分类号： C07H19/16 , A61K38/00 , A61K47/51 , A61K48/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/20 , C07H21/00 , C07H23/00 , C07J43/003 , C12N9/0069 , C12N15/113 , C12N15/1131 , C12N15/1132 , C12N15/1133 , C12N15/1135 , C12N15/1137 , C12N15/1138 , C12N2310/3125 , C12N2310/315 , C12N2310/318 , C12N2310/32 , C12N2310/321 , C12N2310/322 , C12N2310/33 , C12N2310/333 , C12N2310/336 , C12N2310/3521 , C12N2310/3523 , C12N2310/3527 , C12N2310/3531 , C12N2310/3533 , C12Q1/68 , C12Y113/11012
摘要： This invention presents novel purine-based compounds for inclusion into oligonucleotides. The compounds of the invention, when incorporated into oligonucleotides are especially useful as "antisense" agents--agents that are capable of specific hybridization with a nucleotide sequence of an RNA. Oligonucleotides are used for a variety of therapeutic and diagnostic purposes, such as treating diseases, regulating gene expression in experimental systems, assaying for RNA and for RNA products through the employment of antisense interactions with such RNA, diagnosing diseases, modulating the production of proteins, and cleaving RNA in site specific fashions. The compounds of the invention include novel heterocyclic bases, nucleosides, and nucleotides. When incorporated into oligonucleotides, the compounds of the invention can be useful for modulating the activity of RNA.
摘要翻译：本发明提供了用于纳入寡核苷酸的新型基于嘌呤的化合物。当掺入寡核苷酸时，本发明的化合物特别可用作能够与RNA的核苷酸序列特异性杂交的“反义”试剂。寡核苷酸用于各种治疗和诊断目的，例如通过使用与这种RNA的反义相互作用来治疗疾病，调节实验系统中的基因表达，测定RNA和RNA产物，诊断疾病，调节蛋白质的产生，并在现场具体时尚中切割RNA。本发明的化合物包括新的杂环碱基，核苷和核苷酸。当掺入寡核苷酸时，本发明的化合物可用于调节RNA的活性。

2. 发明授权

US06232463B1 Substituted purines and oligonucleotide cross-linking 失效
标题翻译：取代嘌呤和寡核苷酸交联
公开(公告)号：US06232463B1
公开(公告)日：2001-05-15
申请号：US09128508
申请日：1998-08-04
申请人： Phillip Dan Cook , Muthiah Manoharan , Kanda S. Ramasamy
发明人： Phillip Dan Cook , Muthiah Manoharan , Kanda S. Ramasamy
IPC分类号： C07H2102
CPC分类号： C07H19/16 , C07H19/20 , C07H21/00
摘要： This invention is directed to novel purine-based compounds for inclusion into oligonucleotides. The compounds of the invention, when incorporated into oligonucleotides are especially useful as “antisense” agents—agents that are capable of specific hybridization with a nucleotide sequence of an RNA. The compounds of the invention may also be used for cross-linking oligonucleotides. Oligonucleotides are used for a variety of therapeutic and diagnostic purposes, such as treating diseases, regulating gene expression in experimental systems, assaying for RNA and for RNA products through the employment of antisense interactions with such RNA, diagnosing diseases, modulating the production of proteins, and cleaving RNA in site specific fashions. The compounds of the invention include novel heterocyclic bases, nucleosides, and nucleotides. when incorporated into oligonucleotides, the compounds of the invention can be useful for modulating the activity of RNA.
摘要翻译：本发明涉及用于包含在寡核苷酸中的新型基于嘌呤的化合物。当掺入寡核苷酸时，本发明的化合物特别可用作能够与RNA的核苷酸序列特异性杂交的“反义”试剂。本发明的化合物也可用于交联寡核苷酸。寡核苷酸用于各种治疗和诊断目的，例如通过使用与这种RNA的反义相互作用来治疗疾病，调节实验系统中的基因表达，测定RNA和RNA产物，诊断疾病，调节蛋白质的产生，并在现场具体时尚中切割RNA。本发明化合物包括新的杂环碱基，核苷和核苷酸。当掺入寡核苷酸时，本发明的化合物可用于调节RNA的活性。

3. 发明授权

US5811534A Substituted purines and oligonucleotide cross-linking 失效
标题翻译：取代嘌呤和寡核苷酸交联
公开(公告)号：US5811534A
公开(公告)日：1998-09-22
申请号：US948151
申请日：1997-10-09
申请人： Phillip Dan Cook , Muthiah Manoharan , Kanda S. Ramasamy
发明人： Phillip Dan Cook , Muthiah Manoharan , Kanda S. Ramasamy
IPC分类号： A61K31/70 , A01N25/02 , A01N43/52 , A61K31/38 , A61K31/4178 , A61K31/7042 , A61K31/7052 , A61K31/7056 , A61K31/706 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/708 , A61K31/7088 , A61K38/00 , A61K48/00 , A61P31/04 , A61P31/12 , A61P43/00 , C07D409/12 , C07D473/04 , C07D473/16 , C07D473/40 , C07D487/04 , C07H19/00 , C07H19/04 , C07H19/052 , C07H19/056 , C07H19/06 , C07H19/10 , C07H19/12 , C07H19/14 , C07H19/16 , C07H19/167 , C07H19/173 , C07H19/19 , C07H19/20 , C07H19/23 , C07H21/00 , C07H21/02 , C07H21/04 , C07H23/00 , C07J43/00 , C07K14/16 , C12N9/02 , C12N15/09 , C12N15/113 , C12P21/00 , C12Q1/68 , C12Q1/70
CPC分类号： C07H19/16 , A61K48/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/20 , C07H21/00 , C07H23/00 , C07J43/003 , C07K14/005 , C12N15/113 , C12N15/1137 , C12N9/0069 , C12Q1/68 , C12Q1/6813 , C12Y113/11012 , A61K38/00 , C12N2310/3125 , C12N2310/315 , C12N2310/32 , C12N2310/321 , C12N2310/322 , C12N2310/33 , C12N2310/333 , C12N2310/336 , C12N2310/3511 , C12N2310/3521 , C12N2310/3523 , C12N2310/3527 , C12N2310/3531 , C12N2310/3533 , C12N2740/16322
摘要： This invention is directed to novel purine-based compounds for inclusion into oligonucleotides. The compounds of the invention, when incorporated into oligonucleotides are especially useful as "antisense" agents--agents that are capable of specific hybridization with a nucleotide sequence of an RNA. The compounds of the invention may also be used for cross-linking oligonucleotides. Oligonucleotides are used for a variety of therapeutic and diagnostic purposes, such as treating diseases, regulating gene expression in experimental systems, assaying for RNA and for RNA products through the employment of antisense interactions with such RNA, diagnosing diseases, modulating the production of proteins, and cleaving RNA in site specific fashions. The compounds of the invention include novel heterocyclic bases, nucleosides, and nucleotides. When incorporated into oligonucleotides, the compounds of the invention can be useful for modulating the activity of RNA.
摘要翻译：本发明涉及用于包含在寡核苷酸中的新型基于嘌呤的化合物。当掺入寡核苷酸时，本发明的化合物特别可用作能够与RNA的核苷酸序列特异性杂交的“反义”试剂。本发明的化合物也可用于交联寡核苷酸。寡核苷酸用于各种治疗和诊断目的，例如通过使用与这种RNA的反义相互作用来治疗疾病，调节实验系统中的基因表达，测定RNA和RNA产物，诊断疾病，调节蛋白质的产生，并在现场具体时尚中切割RNA。本发明的化合物包括新的杂环碱基，核苷和核苷酸。当掺入寡核苷酸时，本发明的化合物可用于调节RNA的活性。

4. 发明授权

US5808027A N-2 substituted purines in oligonucleotides 失效
标题翻译：寡核苷酸中的N-2取代嘌呤
公开(公告)号：US5808027A
公开(公告)日：1998-09-15
申请号：US762587
申请日：1996-12-10
申请人： Phillip Dan Cook , Kanda S. Ramasamy , Muthiah Manoharan
发明人： Phillip Dan Cook , Kanda S. Ramasamy , Muthiah Manoharan
IPC分类号： C07D473/16 , A61K31/415 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7076 , A61K31/708 , A61K31/7088 , A61K38/00 , A61K47/48 , A61K48/00 , A61P31/12 , C07D473/18 , C07D487/04 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/167 , C07H19/173 , C07H19/20 , C07H21/00 , C07H21/02 , C07H21/04 , C07H23/00 , C07J43/00 , C12N9/02 , C12N15/113 , C12Q1/68
CPC分类号： C07H19/16 , A61K47/48007 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/20 , C07H21/00 , C07H23/00 , C07J43/003 , C12N15/113 , C12N15/1131 , C12N15/1132 , C12N15/1133 , C12N15/1135 , C12N15/1137 , C12N15/1138 , C12N9/0069 , C12Q1/68 , C12Y113/11012 , A61K38/00 , A61K48/00 , C12N2310/3125 , C12N2310/315 , C12N2310/318 , C12N2310/32 , C12N2310/321 , C12N2310/322 , C12N2310/33 , C12N2310/333 , C12N2310/336 , C12N2310/3521 , C12N2310/3523 , C12N2310/3527 , C12N2310/3531 , C12N2310/3533
摘要： This invention presents novel purine-based compounds for inclusion into oligonucleotides. The compounds of the invention, when incorporated into oligonucleotides are especially useful as "antisense" agents--agents that are capable of specific hybridization with a nucleotide sequence of an RNA. Oligonucleotides are used for a variety of therapeutic and diagnostic purposes, such as treating diseases, regulating gene expression in experimental systems, assaying for RNA and for RNA products through the employment of antisense interactions with such RNA, diagnosing diseases, modulating the production of proteins, and cleaving RNA in site specific fashions. The compounds of the invention include novel heterocyclic bases, nucleosides, and nucleotides. When incorporated into oligonucleotides, the compounds of the invention can be useful for modulating the activity of RNA.
摘要翻译：本发明提供了用于包含在寡核苷酸中的新型基于嘌呤的化合物。当掺入寡核苷酸时，本发明的化合物特别可用作能够与RNA的核苷酸序列特异性杂交的“反义”试剂。寡核苷酸用于各种治疗和诊断目的，例如通过使用与这种RNA的反义相互作用来治疗疾病，调节实验系统中的基因表达，测定RNA和RNA产物，诊断疾病，调节蛋白质的产生，并在现场具体时尚中切割RNA。本发明的化合物包括新的杂环碱基，核苷和核苷酸。当掺入寡核苷酸时，本发明的化合物可用于调节RNA的活性。

5. 发明授权

US5681941A Substituted purines and oligonucleotide cross-linking 失效
标题翻译：取代嘌呤和寡核苷酸交联
公开(公告)号：US5681941A
公开(公告)日：1997-10-28
申请号：US189792
申请日：1994-02-01
申请人： Phillip Dan Cook , Muthiah Manoharan , Kanda S. Ramasamy
发明人： Phillip Dan Cook , Muthiah Manoharan , Kanda S. Ramasamy
IPC分类号： A61K31/70 , A01N25/02 , A01N43/52 , A61K31/38 , A61K31/4178 , A61K31/7042 , A61K31/7052 , A61K31/7056 , A61K31/706 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/708 , A61K31/7088 , A61K38/00 , A61K48/00 , A61P31/04 , A61P31/12 , A61P43/00 , C07D409/12 , C07D473/04 , C07D473/16 , C07D473/40 , C07D487/04 , C07H19/00 , C07H19/04 , C07H19/052 , C07H19/056 , C07H19/06 , C07H19/10 , C07H19/12 , C07H19/14 , C07H19/16 , C07H19/167 , C07H19/173 , C07H19/19 , C07H19/20 , C07H19/23 , C07H21/00 , C07H21/02 , C07H21/04 , C07H23/00 , C07J43/00 , C07K14/16 , C12N9/02 , C12N15/09 , C12N15/113 , C12P21/00 , C12Q1/68 , C12Q1/70
CPC分类号： C07H19/16 , A61K48/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/20 , C07H21/00 , C07H23/00 , C07J43/003 , C07K14/005 , C12N15/113 , C12N15/1137 , C12N9/0069 , C12Q1/68 , C12Q1/6813 , C12Y113/11012 , A61K38/00 , C12N2310/3125 , C12N2310/315 , C12N2310/32 , C12N2310/321 , C12N2310/322 , C12N2310/33 , C12N2310/333 , C12N2310/336 , C12N2310/3511 , C12N2310/3521 , C12N2310/3523 , C12N2310/3527 , C12N2310/3531 , C12N2310/3533 , C12N2740/16322
摘要： This invention is directed to novel purine-based compounds for inclusion into oligonucleotides. The compounds of the invention, when incorporated into oligonucleotides are especially useful as "antisense" agents--agents that are capable of specific hybridization with a nucleotide sequence of an RNA. The compounds of the invention may also be used for cross-linking oligonucleotides. Oligonucleotides are used for a variety of therapeutic and diagnostic purposes, such as treating diseases, regulating gene expression in experimental systems, assaying for RNA and for RNA products through the employment of antisense interactions with such RNA, diagnosing diseases, modulating the production of proteins, and cleaving RNA in site specific fashions. The compounds of the invention include novel heterocyclic bases, nucleosides, and nucleotides. When incorporated into oligonucleotides, the compounds of the invention can be useful for modulating the activity of RNA.
摘要翻译：本发明涉及用于包含在寡核苷酸中的新型基于嘌呤的化合物。当掺入寡核苷酸时，本发明的化合物特别可用作能够与RNA的核苷酸序列特异性杂交的“反义”试剂。本发明的化合物也可用于交联寡核苷酸。寡核苷酸用于各种治疗和诊断目的，例如通过使用与这种RNA的反义相互作用来治疗疾病，调节实验系统中的基因表达，测定RNA和RNA产物，诊断疾病，调节蛋白质的产生，并在现场具体时尚中切割RNA。本发明的化合物包括新的杂环碱基，核苷和核苷酸。当掺入寡核苷酸时，本发明的化合物可用于调节RNA的活性。

6. 发明授权

US06811975B2 Phosphorothioate oligonucleotides having modified internucleoside linkages 失效
标题翻译：具有修饰的核苷间键的硫代磷酸酯寡核苷酸
公开(公告)号：US06811975B2
公开(公告)日：2004-11-02
申请号：US09805630
申请日：2001-03-14
申请人： Phillip Dan Cook , Muthiah Manoharan
发明人： Phillip Dan Cook , Muthiah Manoharan
IPC分类号： C12Q168
CPC分类号： C07H21/00 , C07H19/04
摘要： Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids. In general, the compounds are phosphorothioate oligonucleotides wherein the 5′-terminal internucleoside linkage or the 5′- and 3′-terminal linkages are modified.
摘要翻译：模仿和/或调节野生型核酸活性的新型化合物。通常，化合物是硫代磷酸酯寡核苷酸，其中5'-末端核苷间键或5'-和3'-末端键被修饰。

7. 发明授权

US06747014B2 Compositions and methods for non-parenteral delivery of oligonucleotides 失效
标题翻译：用于非肠胃外递送寡核苷酸的组合物和方法
公开(公告)号：US06747014B2
公开(公告)日：2004-06-08
申请号：US10029598
申请日：2001-12-21
申请人： Ching-Leou Teng , Phillip Dan Cook , Lloyd Tillman , Gregory E. Hardee , David J. Ecker , Muthiah Manoharan
发明人： Ching-Leou Teng , Phillip Dan Cook , Lloyd Tillman , Gregory E. Hardee , David J. Ecker , Muthiah Manoharan
IPC分类号： A61K3170
CPC分类号： A61K48/0075 , A61K9/0014 , A61K9/0019 , A61K47/12 , A61K47/28 , A61K48/00 , C07H21/00 , Y10S514/946
摘要： The present invention relates to compositions and methods which enhance the local and systemic uptake and delivery of oligonucleotides and nucleic acids via non-parenteral routes of administration. Pharmaceutical compositions comprising oligonucleotides disclosed herein include, for systemic delivery, emulsion and microemulsion formulations for a variety of applications and oral dosage formulations. It has also surprisingly been discovered that oligonucleotides may be locally delivered to colonic sites by rectal enemas and suppositories in simple solutions, e.g., neat or in saline. Such pharmaceutical compositions of oligonucleotides may further include one or more penetration enhancers for the transport of oligonucleotides and other nucleic acids across mucosal membranes. The compositions and methods of the invention are utilized to effect the oral, buccal, rectal or vaginal administration of an antisense oligonucleotide to an animal in order to modulate the expression of a gene in the animal for investigative, therapeutic, palliative or prophylactic purposes.
摘要翻译：本发明涉及通过非肠胃外给药途径增强寡核苷酸和核酸的局部和全身摄取和递送的组合物和方法。包含本文公开的寡核苷酸的药物组合物包括用于全身递送的乳液和微乳液制剂用于各种应用和口服剂型。还令人惊讶地发现，可以用简单的溶液，例如纯的或盐水，通过直肠灌肠剂和栓剂将寡核苷酸局部递送至结肠部位。寡核苷酸的这种药物组合物可以进一步包括一种或多种用于将寡核苷酸和其它核酸转移穿过粘膜的渗透增强剂。本发明的组合物和方法用于对动物进行口服，口腔，直肠或阴道施用反义寡核苷酸，以调节动物中基因在调查，治疗，姑息或预防目的中的表达。

8. 发明授权

US06420549B1 Oligonucleotide analogs having modified dimers 失效
标题翻译：具有改性二聚体的寡核苷酸类似物
公开(公告)号：US06420549B1
公开(公告)日：2002-07-16
申请号：US09131102
申请日：1998-08-07
申请人： Phillip Dan Cook , Muthiah Manoharan , Balkrishen Bhat
发明人： Phillip Dan Cook , Muthiah Manoharan , Balkrishen Bhat
IPC分类号： C07H1900
CPC分类号： C12N15/1135 , C07H21/00 , C12N2310/315 , C12N2310/318 , C12N2310/321 , C12N2310/322 , C12N2310/341 , C12N2310/345 , C12N2310/346 , C12Q1/6876 , Y02P20/582 , C12N2310/3525
摘要： Modified dimers having a ribose sugar moiety in the 5′ nucleoside and a 2′ modified sugar in the 3′ nucleoside are provided. The modified dimers are useful in the preparation of oligonucleotide analogs having enhanced properties compared to native oligonucleotides, including increased nuclease resistance, enhanced binding affinity and improved protein binding.
摘要翻译：提供了在5'核苷中具有核糖部分和3'核苷中的2'修饰的糖的修饰二聚体。修饰的二聚体可用于制备与天然寡核苷酸相比具有增强的性质的寡核苷酸类似物，包括增加的核酸酶抗性，增强的结合亲和力和改善的蛋白质结合。

9. 发明授权

US06242589B1 Phosphorothioate oligonucleotides having modified internucleoside linkages 失效
标题翻译：具有修饰的核苷间键的硫代磷酸酯寡核苷酸
公开(公告)号：US06242589B1
公开(公告)日：2001-06-05
申请号：US09115027
申请日：1998-07-14
申请人： Phillip Dan Cook , Muthiah Manoharan
发明人： Phillip Dan Cook , Muthiah Manoharan
IPC分类号： C07H2104
CPC分类号： C07H21/00 , C07H19/04
摘要： Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids. In general, the compounds are phosphorothioate oligonucleotides wherein the 5′-terminal internucleoside linkage or the 5′- and 3′-terminal linkages are modified.
摘要翻译：模仿和/或调节野生型核酸活性的新型化合物。通常，化合物是硫代磷酸酯寡核苷酸，其中5'-末端核苷间键或5'-和3'-末端键被修饰。

10. 发明授权

US6043352A 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides 有权
标题翻译： 2'-O-二甲基氨基乙氧基乙基修饰的寡核苷酸
公开(公告)号：US6043352A
公开(公告)日：2000-03-28
申请号：US130566
申请日：1998-08-07
申请人： Muthiah Manoharan , Phillip Dan Cook
发明人： Muthiah Manoharan , Phillip Dan Cook
IPC分类号： C12N15/09 , A61K31/712 , A61P1/18 , A61P31/14 , C07H21/00 , C07H21/04 , C12N15/113
CPC分类号： C12N15/113 , C07H21/00 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341
摘要： 2'-O-Modified ribosyl nucleosides and modified oligonucleotides containing such nucleotides are disclosed. Oligonucleotides are disclosed that have increased binding affinity as shown by molecular modeling experiments. The 2'-O-modified nucleosides of the invention include ring structures that position the sugar moiety of the nucleosides preferentially in 3' endo geometries.
摘要翻译：公开了2'-O-修饰的核糖基核苷和含有这些核苷酸的修饰的寡核苷酸。公开了具有增强的结合亲和力的寡核苷酸，如分子建模实验所示。本发明的2'-O-修饰的核苷包括将核苷的糖部分优先置于3'内部几何形状的环结构。

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