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31. 发明授权

US5777092A Heteroatomic oligonucleoside linkages 失效
标题翻译：杂原子寡核苷键
公开(公告)号：US5777092A
公开(公告)日：1998-07-07
申请号：US795282
申请日：1997-02-04
申请人： Phillip Dan Cook , Yogesh Shantilal Sanghvi
发明人： Phillip Dan Cook , Yogesh Shantilal Sanghvi
IPC分类号： A61K47/48 , C07D405/04 , C07D405/14 , C07F7/18 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00 , C07H21/02 , C07H21/04 , A61K31/70
CPC分类号： A61K31/70 , A61K47/48192 , A61K47/48223 , C07D405/04 , C07D405/14 , C07F7/1856 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00
摘要： Oligonucleotide-mimicking macromolecules that have improved nuclease resistance are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligonucleotides with three or four atom linking groups provide unique oligonucleotide-mimicking macromolecules that are useful in regulating RNA expression and in therapeutics. Methods of synthesis and use also are disclosed.
摘要翻译：提供了具有改善的核酸酶抗性的寡核苷酸模拟大分子。用三个或四个原子连接基团替代天然寡核苷酸中发现的正常磷酸二酯糖苷键，提供了可用于调节RNA表达和治疗学的独特的寡核苷酸模拟大分子。也公开了合成和使用方法。

32. 发明授权

US5688941A Methods of making conjugated 4' desmethyl nucleoside analog compounds 失效
标题翻译：制备共轭4'脱甲基核苷类似物的方法
公开(公告)号：US5688941A
公开(公告)日：1997-11-18
申请号：US760848
申请日：1996-12-05
申请人： Phillip Dan Cook , Kelly Teng
发明人： Phillip Dan Cook , Kelly Teng
IPC分类号： A61K47/48 , C07D405/04 , C07D405/14 , C07F7/18 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00
CPC分类号： A61K31/70 , A61K47/48192 , A61K47/48215 , C07D405/04 , C07D405/14 , C07F7/1856 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H21/00
摘要： Tetrahydrofuranyl compounds are provided that are functionalized to include pendant conjugate groups, and which are useful in diagnostic assays and as research reagents. Novel intermediates for the synthesis of the compounds are also provided.
摘要翻译：提供四氢呋喃基化合物，其被官能化以包括侧挂缀合物基团，并且其可用于诊断测定和研究试剂。还提供了用于合成化合物的新型中间体。

33. 发明授权

US5670633A Sugar modified oligonucleotides that detect and modulate gene expression 无效
标题翻译：检测和调节基因表达的糖修饰寡核苷酸
公开(公告)号：US5670633A
公开(公告)日：1997-09-23
申请号：US835932
申请日：1992-03-05
申请人： Phillip Dan Cook , Andrew Mamoro Kawasaki
发明人： Phillip Dan Cook , Andrew Mamoro Kawasaki
IPC分类号： A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7056 , A61K31/706 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/708 , A61K31/7088 , A61K38/00 , A61K48/00 , A61P31/12 , A61P43/00 , C07H19/00 , C07H19/04 , C07H19/052 , C07H19/056 , C07H19/06 , C07H19/10 , C07H19/12 , C07H19/14 , C07H19/16 , 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 , A01N43/04 , C07H21/03
CPC分类号： A61K48/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , 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： Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least two of the 2'-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of HIV, herpes virus, papillomavirus and other infections is provided.
摘要翻译： PCT No.PCT / US91 / 05720 Sec。 371日期：1992年3月5日 102（e）1992年3月5日PCT PCT 1991年8月12日提交PCT公布。出版物WO92 / 03568 日期：1992年3月5日提供了用于治疗和诊断易于调节所选蛋白质生产的疾病的组成和方法。根据优选实施方案，提供寡核苷酸和寡核苷酸类似物，其与所选择的RNA或DNA序列特异性杂交，其中核苷单元的2'-脱氧呋喃糖基部分中的至少两个被修饰。提供了治疗艾滋病毒，疱疹病毒，乳头瘤病毒和其他感染。

34. 发明授权

US08481712B2 Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase 有权
公开(公告)号：US08481712B2
公开(公告)日：2013-07-09
申请号：US11701682
申请日：2007-02-02
申请人： Balkrishen Bhat , Anne B. Eldrup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
发明人： Balkrishen Bhat , Anne B. Eldrup , Thazha P. Prakash , Phillip Dan Cook , Robert L. LaFemina , Amy L. Simcoe , Carrie A. Rutkowski , Mario A. Valenciano
IPC分类号： C07H19/10 , C07H19/20
CPC分类号： C07H19/10 , A61K9/4858 , C07D471/04 , C07D473/34 , C07D487/04 , C07H17/02 , C07H19/06 , C07H19/16 , C07H19/207 , Y02P20/582
摘要： The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

35. 发明授权

US08377897B2 Compositions and methods for non-parenteral delivery of oligonucleotides 有权
公开(公告)号：US08377897B2
公开(公告)日：2013-02-19
申请号：US11237063
申请日：2005-09-28
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： A61K31/70 , C07H21/02 , C07H21/04
CPC分类号： A61K48/0008 , A61K9/0014 , A61K9/0031 , A61K9/107 , A61K9/1075 , A61K38/00 , A61K47/12 , A61K47/28 , A61K48/00 , A61K48/0025 , A61K48/0041 , C12N15/113 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3521 , C12N2310/3527 , C12N2310/3525
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.

36. 再颁专利

USRE39464E1 Oligonucleolotides having site specific chiral phosphorothioate internucleoside linkages 有权
标题翻译：寡核苷酸具有位点特异性手性硫代磷酸酯核苷间键
公开(公告)号：USRE39464E1
公开(公告)日：2007-01-09
申请号：US10925348
申请日：2004-08-24
申请人： Phillip Dan Cook , Muthiah Manoharan
发明人： Phillip Dan Cook , Muthiah Manoharan
IPC分类号： A61K31/70 , G01N33/53
CPC分类号： C07H21/00 , C07H19/04
摘要： Novel chiral compounds that mimic and/or modulate the activity of wild-type nucleic acids are disclosed. In general, the compounds are phosphorothioate oligonucleotides wherein the 5′, and the 3′-terminal internucleoside linkages are chirally Sp and internal internucleoside linkages are chirally Rp.
摘要翻译：公开了模拟和/或调节野生型核酸活性的新型手性化合物。通常，化合物是硫代磷酸酯寡核苷酸，其中5'和3'末端核苷间键是手性Sp，内部核苷间键是手性Rp。

37. 发明授权

US07125855B2 Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase 有权
公开(公告)号：US07125855B2
公开(公告)日：2006-10-24
申请号：US10688691
申请日：2003-10-17
申请人： Balkrishen Bhat , Neelima Bhat , Anne B. Eldrup , Thazha P. Prakash , Marija Prhavc , Quanlai Song , Phillip Dan Cook , Steven S. Carroll , Malcolm Maccoss , David B. Olsen
发明人： Balkrishen Bhat , Neelima Bhat , Anne B. Eldrup , Thazha P. Prakash , Marija Prhavc , Quanlai Song , Phillip Dan Cook , Steven S. Carroll , Malcolm Maccoss , David B. Olsen
IPC分类号： A61K31/70 , C07H19/14
CPC分类号： C07H19/16 , A61K9/4858 , A61K31/7056 , A61K31/7064 , A61K31/7076 , A61K38/21 , A61K45/06 , C07D473/00 , C07D487/04 , C07H19/00 , C07H19/06 , C07H19/10 , C07H19/12 , C07H19/14 , C07H19/20 , Y02P20/582 , A61K2300/00
摘要： The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

38. 发明授权

US07105499B2 Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase 有权
标题翻译：核苷衍生物作为RNA依赖性RNA病毒聚合酶的抑制剂
公开(公告)号：US07105499B2
公开(公告)日：2006-09-12
申请号：US10250873
申请日：2002-01-18
申请人： Steven S. Carroll , David B. Olsen , Malcolm MacCoss , Balkrishen Bhat , Phillip Dan Cook , Anne B. Eldrup , Thazha P. Prakash
发明人： Steven S. Carroll , David B. Olsen , Malcolm MacCoss , Balkrishen Bhat , Phillip Dan Cook , Anne B. Eldrup , Thazha P. Prakash
IPC分类号： A61K31/7052 , A61K31/7042 , A61K31/7068 , C07H19/04 , C07H19/06
CPC分类号： A61K45/06 , A61K9/4858 , A61K31/7056 , A61K31/7064 , A61K31/7068 , A61K31/7076 , A61K38/212 , A61K38/2292 , C07H19/10 , C07H19/14 , C07H19/20 , Y02P20/582 , A61K2300/00
摘要： The present invention provides nucleoside derivatives which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside derivatives alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside derivatives of the present invention.
摘要翻译：本发明提供作为RNA依赖性RNA病毒聚合酶抑制剂的核苷衍生物。这些化合物是RNA依赖性RNA病毒复制的抑制剂，可用于治疗RNA依赖性RNA病毒感染。它们特别可用作丙型肝炎病毒（HCV）NS5B聚合酶的抑制剂，作为HCV复制的抑制剂和/或用于治疗丙型肝炎感染。本发明还描述了单独或与其它对RNA依赖性RNA病毒感染，特别是HCV感染有活性的试剂组合的药物组合物。还公开了本发明的核苷衍生物抑制RNA依赖性RNA聚合酶，抑制RNA依赖性RNA病毒复制和/或治疗RNA依赖性RNA病毒感染的方法。

39. 发明授权

US06942966B1 Methods for processing chemical compounds having reactive functional groups 失效
标题翻译：处理具有反应性官能团的化合物的方法
公开(公告)号：US06942966B1
公开(公告)日：2005-09-13
申请号：US08709160
申请日：1996-09-06
申请人： Phillip Dan Cook
发明人： Phillip Dan Cook
IPC分类号： G01N33/15 , A61K31/33 , A61K31/395 , A61K31/435 , A61K31/53 , A61P29/00 , A61P31/04 , A61P43/00 , C07B61/00 , C07D255/02 , C07D273/00 , C07D471/08 , C07D471/18 , C07D498/08 , C07D515/08 , C07D521/00 , C12Q1/68
CPC分类号： C07D471/08 , B01J2219/0072 , C07D515/08
摘要： Novel macrocyclic compounds are constructed to include large cyclic structures that are interrupted by at least one ring system. Each interrupting ring system includes two bridgehead atoms. Bridgehead atoms are bonded to one or more bridges that interconnect one or more ring systems thereby forming a large cyclic structure. Located in each bridge are two or more nitrogenous moieties that are derivatized with chemical functional groups. The ring systems can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring. These can also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the macrocyclic compounds. In accordance with certain embodiments of the invention, libraries of such macrocyclic compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the library.
摘要翻译：构建新的大环化合物以包括被至少一个环系统中断的大环状结构。每个中断环系统包括两个桥头原子。桥头原子键合到一个或多个互连一个或多个环系统的桥，从而形成大的环状结构。位于每个桥中的是具有化学官能团衍生化的两个或多个含氮部分。环系统可以包括作为环原子的另外的含氮部分或连接到环上的侧基上。这些也可以用化学官能团衍生化。化学官能团的总体对大环化合物赋予某些构象和其他性质。根据本发明的某些实施方案，利用化学官能团和含氮部分的置换和组合来制备这种大环化合物的文库，从而构建文库的复杂性。

40. 发明授权

US06919439B2 Derivatized oligonucleotides having improved uptake and other properties 失效
标题翻译：具有改善摄取和其他性质的衍生寡核苷酸
公开(公告)号：US06919439B2
公开(公告)日：2005-07-19
申请号：US10154993
申请日：2002-05-23
申请人： Muthiah Manoharan , Phillip Dan Cook , Clarence Frank Bennett
发明人： Muthiah Manoharan , Phillip Dan Cook , Clarence Frank Bennett
IPC分类号： A01N43/04 , A61K38/00 , A61K48/00 , C07H19/04 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00 , C07H21/02 , C07H21/04 , C07H23/00 , C07J1/00 , C07J43/00 , C07J51/00 , C07K9/00 , C12N9/00 , C12N9/02 , C12N15/113 , C12Q1/68
CPC分类号： C07H19/04 , A61K38/00 , A61K47/542 , A61K47/551 , A61K47/64 , A61K48/00 , C07H19/06 , C07H19/10 , C07H19/16 , C07H19/20 , C07H21/00 , C07H23/00 , C07J43/003 , C07J51/00 , C12N9/0069 , C12N15/113 , C12N15/1137 , C12N2310/3125 , C12N2310/315 , 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： Linked nucleosides having at least one functionalized nucleosid that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2′-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining linked nucleosides are 2′-deoxy-2′-fluoro, 2′-O-methoxy, 2′-O-ethoxy, 2′-O-propoxy, 2′-O-aminoalkoxy or 2′-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3′ or the 5′ positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.
摘要翻译：具有至少一个具有取代基的官能化核苷的连接核苷，例如类固醇分子，报道分子，非芳族亲油性分子，报道酶，肽，蛋白质，水溶性维生素，脂溶性维生素，RNA 劈裂复合物，金属螯合剂，卟啉，烷基化剂，芘，混合光子核酸酶/嵌入剂或芳基叠氮化物光交联剂表现出增加的细胞摄取和其它性质。取代基可以通过连接基团连接在官能化核苷的2'-位上。如果至少一部分剩余连接的核苷是2'-脱氧-2'-氟，则2'-O-甲氧基，2'-O-乙氧基，2'-O-丙氧基，2'-O-氨基烷氧基或2 '-O-烯丙氧基核苷，取代基可以通过连接基团在核苷的3'或5'位置或核苷的杂环碱基上或连接核苷与核苷酸之间的核苷酸间连接相邻核苷。

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