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。

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.

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。

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。

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。

公开(公告)号：US06900297B1

公开(公告)日：2005-05-31

申请号：US08464953

申请日：1995-06-05

申请人： Phillip Dan Cook ,  Muthiah Manoharan ,  Charles J. Guinosso

发明人： Phillip Dan Cook ,  Muthiah Manoharan ,  Charles J. Guinosso

IPC分类号： A01N43/04 ,  A61K38/00 ,  A61K47/48 ,  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： C12N15/113 ,  A61K38/00 ,  A61K47/51 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C07J51/00 ,  C12N9/0069 ,  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： Nucleotides and oligonucleosides functionalized to include alkylamino functionality, and derivatives thereof. In certain embodiments, the compounds of the invention further include steroids, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleotides through the alkylamino group.

摘要翻译： 功能化为包括烷基氨基官能团的核苷酸和寡核苷酸及其衍生物。 在某些实施方案中，本发明的化合物还包括通过烷基氨基连接到核苷酸上的类固醇，报告分子，报道酶，亲脂性分子，肽或蛋白质。

公开(公告)号：US06610663B2

公开(公告)日：2003-08-26

申请号：US09974326

申请日：2001-10-10

申请人： Phillip Dan Cook ,  Thomas Bruice ,  Charles John Guinosso ,  Andrew Mamoru Kawasaki ,  Richard Griffey

发明人： Phillip Dan Cook ,  Thomas Bruice ,  Charles John Guinosso ,  Andrew Mamoru Kawasaki ,  Richard Griffey

IPC分类号： A61K4800

CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C07H19/04 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  C07H23/00 ,  C07J43/003 ,  C07K14/005 ,  C12N9/0069 ,  C12N15/1137 ,  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 ,  C12Q1/68 ,  C12Q1/6813 ,  C12Y113/11012

摘要： Compositions and methods for modulating the activity of RNA are disclosed. In accordance with preferred embodiments, antisense compositions are prepared comprising targeting and reactive portions. The reactive portions preferably comprise one or two imidazole functionalities conjugated to the targeting oligonucleotide via linkers with or without intervening intercalating moieties. Therapeutics, diagnostics and research methods also are disclosed, as are synthetic nucleosides and nucleoside fragments that can be elaborated into oligonucleotides.

公开(公告)号：US06359124B1

公开(公告)日：2002-03-19

申请号：US09248386

申请日：1999-02-12

申请人： David J. Ecker ,  Phillip Dan Cook ,  Brett P. Monia ,  Susan M. Freier ,  Yogesh S. Sanghvi

发明人： David J. Ecker ,  Phillip Dan Cook ,  Brett P. Monia ,  Susan M. Freier ,  Yogesh S. Sanghvi

IPC分类号： C07H2102

CPC分类号： C12N15/1135 ,  C07H21/00 ,  C12N2310/315 ,  C12N2310/318 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/341 ,  C12N2310/345 ,  C12N2310/346 ,  C12Q1/6876 ,  C12Q2600/158 ,  C12N2310/3525

摘要： Compositions and methods are provided for the modulation of expression of the human ras gene in both the normal and activated forms. Oligonucleotides are provided that have methylene(methylimino) linkages alternating with phosphorothioate or phosphodiester linkages. Further oligonucleotides are provide that have a first region having a methylene(methylimino) linkage alternating with a phosphorothioate or phosphodiester linkage and a second region having phosphorothioate linkages. Such oligonucleotides can be used for diagnostics as well as for research purposes including methods for diagnosis, detection and treatment of conditions arising from the activation of the H-ras gene.

摘要翻译： 提供组合物和方法用于调节正常和活化形式的人ras基因的表达。 提供了具有与硫代磷酸酯或磷酸二酯键交替的亚甲基（甲基亚氨基）键的寡核苷酸。 提供另外的寡核苷酸，其具有与硫代磷酸酯或磷酸二酯键交替的亚甲基（甲基亚氨基）键的第一区域和具有硫代磷酸酯键的第二区域。 这样的寡核苷酸可用于诊断以及研究目的，包括用于诊断，检测和治疗由H-ras基因激活产生的病症的方法。

公开(公告)号：US06329523B1

公开(公告)日：2001-12-11

申请号：US09230773

申请日：1999-03-10

申请人： Phillip Dan Cook ,  Haoyun An

发明人： Phillip Dan Cook ,  Haoyun An

IPC分类号： C07D24142

CPC分类号： C07D213/20 ,  C12Q1/18 ,  C40B40/00 ,  G01N33/573 ,  G01N33/68 ,  G01N33/6872

摘要： Novel compounds having the formula: wherein the constituent variables are defined herein. The compounds are constructed to include a central aromatic, aliphatic, or heterocyclic ring system. Attached to the central ring system are two linear groups having nitrogenous moieties that are derivatized with chemical functional groups. The ring system can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring, that may also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the these compounds. In accordance with certain embodiments of the invention, libraries of such compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the libraries.

摘要翻译： 具有下式的新型化合物：其中组分变量在本文中定义。 该化合物构建成包括中心芳族，脂族或杂环环系。 连接到中心环系统是具有用化学官能团衍生的含氮部分的两个线性基团。 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的侧基，其也可以被化学官能团衍生化。 化学官能团的整体赋予这些化合物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些化合物的文库，以构建文库的复杂性。

公开(公告)号：US06322987B1

公开(公告)日：2001-11-27

申请号：US09688394

申请日：2000-10-16

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 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07J1/00

摘要： Nucleosides and oligonucleosides functionalized to include carbamate functionality, and derivatives thereof. In certain embodiments, the compounds of the invention further include steroids, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleosides through the carbamate group.

摘要翻译： 功能化为包括氨基甲酸酯官能团的核苷和寡核苷酸及其衍生物。 在某些实施方案中，本发明的化合物还包括通过氨基甲酸酯基团连接到核苷上的类固醇，报道分子，报道酶，亲脂性分子，肽或蛋白质。