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131. 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。

132. 发明授权

US06492111B1 In situ binary synthesis of biologically effective molecules 失效
标题翻译：生物有效分子的原位二元合成
公开(公告)号：US06492111B1
公开(公告)日：2002-12-10
申请号：US09200107
申请日：1998-11-25
申请人： David J. Ecker
发明人： David J. Ecker
IPC分类号： C12Q168
CPC分类号： C12N15/113 , A61K38/00 , C12N2310/351 , C12Q1/6841 , Y02A50/469 , C12Q2565/101
摘要： A plurality of oligonucleotides are caused to bind specifically to target nucleic acid which is predictive of a disease state or a biological condition within cells containing the target nucleic acid. The respective oligonucleotides, which may be functionilized or may be present in the form of oligonucleotide analogs, carry with them a plurality of synthons. Such synthons, which may be identiphores, toxiphores, or other precursors to biologically effective molecules, interact when specific binding of the respective oligonucleotides occurs at sites adjacent to each other on the target nucleic acid. The resulting interaction gives rise to the synthesis, generation or release of highly active biological molecules in situ in the cell in which the specific binding takes place. This permits the use of extraordinarily toxic molecules for use in killing cells containing the target nucleic acids. Imaging and other uses are also provided by the present invention.
摘要翻译：导致多个寡核苷酸特异性结合预测含有靶核酸的细胞内的疾病状态或生物学条件的靶核酸。可以被功能化或可以寡核苷酸类似物形式存在的各个寡核苷酸携带多个合成子。当相应寡核苷酸的特异性结合发生在靶核酸上彼此相邻的位点时，这种可能是识别的氨基酸，毒素或生物有效分子的其它前体相互作用。所产生的相互作用导致在发生特异性结合的细胞中原位生成高度活性的生物分子的合成，产生或释放。这允许使用非常有毒的分子用于杀死含有靶核酸的细胞。成像和其他用途也由本发明提供。

133. 发明授权

US06277334B1 Chemical synthesis apparatus employing a droplet generator 有权
公开(公告)号：US06277334B1
公开(公告)日：2001-08-21
申请号：US09313403
申请日：1999-05-18
申请人： David J. Ecker , Oscar Acevedo , Normand Hebert , Peter W. Davis , Jacqueline R. Wyatt , John S. Kiely
发明人： David J. Ecker , Oscar Acevedo , Normand Hebert , Peter W. Davis , Jacqueline R. Wyatt , John S. Kiely
IPC分类号： B01L300
CPC分类号： B01L3/0268 , B01J19/0046 , B01J2219/00315 , B01J2219/00333 , B01J2219/00351 , B01J2219/00378 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00729 , C07B2200/11 , C07H21/00 , C07K1/047 , C12P19/34 , C40B40/06 , C40B40/10 , C40B60/14
摘要： Chemical reaction apparatus, materials and methods are provided for the automatable, efficient synthesis of chemical species and libraries. In accordance with preferred embodiments, chemical droplet generation and direction techniques are employed to prepare oligomers and libraries of chemical species. Reaction assemblies adapted for efficient synthetic employment and for improved collection are also disclosed.

134. 发明授权

US5925732A Chemical reaction apparatus for performing multiple reaction on a surface and collecting the product 失效
标题翻译：用于在表面上进行多次反应并收集产品的化学反应装置
公开(公告)号：US5925732A
公开(公告)日：1999-07-20
申请号：US778876
申请日：1997-01-02
申请人： David J. Ecker , Oscar Acevedo , Normand Hebert , Peter W. Davis , Jacqueline R. Wyatt , John S. Kiely
发明人： David J. Ecker , Oscar Acevedo , Normand Hebert , Peter W. Davis , Jacqueline R. Wyatt , John S. Kiely
IPC分类号： B01J19/00 , B01L3/02 , C07B61/00 , C07H21/00 , C07K1/04 , C12P19/34 , C40B40/06 , C40B40/10 , C40B60/14 , G01N33/53 , C12Q1/68
CPC分类号： B01L3/0268 , B01J19/0046 , C07H21/00 , C07K1/047 , C12P19/34 , B01J2219/00315 , B01J2219/00333 , B01J2219/00351 , B01J2219/00378 , B01J2219/00527 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/0072 , B01J2219/00722 , B01J2219/00725 , B01J2219/00729 , C07B2200/11 , C40B40/06 , C40B40/10 , C40B60/14
摘要： Chemical reaction apparatus, materials and methods are provided for the automatable, efficient synthesis of chemical species and libraries. In accordance with preferred embodiments, chemical droplet generation and direction techniques are employed to prepare oligomers and libraries of chemical species. Reaction assemblies adapted for efficient synthetic employment and for improved collection are also disclosed.
摘要翻译：提供化学反应装置，材料和方法用于化学物质和文库的可自动化，有效的合成。根据优选实施方案，采用化学液滴产生和方向技术来制备化学物质的低聚物和文库。还公开了适于高效合成使用和改进收集的反应组件。

135. 发明授权

US5691461A Oligonucleotides inhibiting candida germ tube formation 失效
标题翻译：抑制念珠菌胚管形成的寡核苷酸
公开(公告)号：US5691461A
公开(公告)日：1997-11-25
申请号：US229145
申请日：1994-04-18
申请人： David J. Ecker , Glenn D. Hoke
发明人： David J. Ecker , Glenn D. Hoke
IPC分类号： A61K38/00 , C07K14/40 , C12N15/113 , C07H21/04
CPC分类号： C12N15/113 , C07K14/40 , A61K38/00 , C12N2310/315
摘要： Compositions and methods are provided for the treatment and diagnosis of Candida infections. In accordance with preferred embodiments, oligonucleotides are provided which are specifically hybridizable with at least a portion of a Candida mRNA. Preferred targets are the mRNAs which encode .beta.-tubulin, aspartate protease, actin and chitin synthetase, as well as the mRNA's which encode the ribosomal L25 protein, translation elongation factors 1 and 2 (TEF1 and TEF2), the b subunit of ATPase, and cytochrome P450 lanosterol 14.alpha.-demethylase (L1A1). The oligonucleotides comprise nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5'-untranslated sequences, 3' untranslated sequences, 5' cap, and intron/exon junction of the mRNAs. Methods of treating animals suffering from Candida infection are disclosed.
摘要翻译：提供组合物和方法用于治疗和诊断念珠菌感染。根据优选实施方案，提供了与至少一部分念珠菌mRNA特异性杂交的寡核苷酸。优选的靶标是编码β-微管蛋白，天冬氨酸蛋白酶，肌动蛋白和几丁质合成酶的mRNA，以及编码核糖体L25蛋白的mRNA，翻译延伸因子1和2（TEF1和TEF2），ATP酶的b亚基和细胞色素P450羊毛甾醇14α-甲基化酶（L1A1）。寡核苷酸包含足以实现所述特异性杂交的同一性和数目的核苷酸单元。在其它优选的实施方案中，寡核苷酸与mRNA的转录起始位点，翻译起始位点，5'-非翻译序列，3'非翻译序列，5'帽和内含子/外显子连接物特异性杂交。公开了治疗念珠菌感染动物的方法。

136. 发明授权

US5580767A Inhibition of influenza viruses by antisense oligonucleotides 失效
标题翻译：通过反义寡核苷酸抑制流感病毒
公开(公告)号：US5580767A
公开(公告)日：1996-12-03
申请号：US955718
申请日：1992-09-22
申请人： Lex M. Cowsert , David J. Ecker
发明人： Lex M. Cowsert , David J. Ecker
IPC分类号： A61K31/70 , A61K38/00 , A61K48/00 , A61P31/12 , A61P31/16 , C07H21/00 , C07K14/11 , C12N15/09 , C12N15/113 , C12N15/00 , C07H21/04
CPC分类号： C12N15/1131 , C07K14/005 , A61K38/00 , C12N2310/13 , C12N2310/315 , C12N2310/321 , C12N2310/322 , C12N2310/3521 , C12N2310/3527 , C12N2310/3533 , C12N2760/16122
摘要： Compositions and methods are provided for the treatment and diagnosis of influenza virus infections. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with viral RNAs. The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5'-untranslated sequences, 3'-untranslated sequences, and intron/exon junction of influenza virus mRNAs. In additional preferred embodiments, the oligonucleotides are specifically hybridizable with RNA sequences involved in splicing of the viral RNA, or in viral packaging. Methods of treating animals suffering from influenza virus infection are disclosed.
摘要翻译： PCT No.PCT / US91 / 05742 Sec。 371日期：1992年9月22日 102（e）日期1992年9月22日PCT 1991年8月13日PCT PCT。第WO92 / 03454号公报日期：1992年3月5日提供了治疗和诊断流感病毒感染的方法和方法。根据优选的实施方案，提供了与病毒RNA特异性杂交的寡核苷酸和寡核苷酸类似物。所述寡核苷酸包含足以实现所述特异性杂交的同一性和数目的核苷酸单元。在其它优选实施方案中，寡核苷酸可与转录起始位点，翻译起始位点，5'-非翻译序列，3'非翻译序列以及流感病毒mRNA的内含子/外显子连接物特异性杂交。在另外的优选实施方案中，寡核苷酸与参与病毒RNA剪接的RNA序列或病毒包装特异性杂交。公开了治疗流感病毒感染动物的方法。

137. 发明授权

US5523389A Inhibitors of human immunodeficiency virus 失效
标题翻译：人体免疫缺陷病毒的抑制剂
公开(公告)号：US5523389A
公开(公告)日：1996-06-04
申请号：US128011
申请日：1993-09-28
申请人： David J. Ecker , Jacqueline R. Wyatt , Jean L. Imbach
发明人： David J. Ecker , Jacqueline R. Wyatt , Jean L. Imbach
IPC分类号： C12N15/09 , A01N63/00 , A61K31/70 , A61K38/00 , A61P31/12 , A61P31/16 , A61P35/00 , C07H21/00 , C07H21/04 , C12N15/113 , C12N15/115 , C12N15/117 , C12P19/34 , C12Q1/68 , C12Q1/70 , C12N15/11
CPC分类号： A61K31/70 , C07H21/00 , C12N15/1133 , C12N15/1137 , C12N15/115 , C12N15/117 , C12Q1/701 , C12Y207/07049 , C12Y301/01004 , A61K38/00 , C12N2310/151 , C12N2310/18 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346
摘要： The phosphorothioate oligonucleotide T.sub.2 G4T2 was identified as an inhibitor of HIV infection in vitro by combinatorial screening of a library of phosphorothioate oligonucleotides that contained all possible 8-nucleotide sequences. The oligonucleotide forms a parallel-stranded tetrameric guanosinequartet (G-quartet) structure. Tetramer formation and the phosphorothioate backbone are essential for antiviral activity. The G-quartet structure binds to the HIV envelope protein gp120 at the V3 loop and inhibits both cell-to-cell and virus-to-cell infection.
摘要翻译：通过组合筛选含有所有可能的8个核苷酸序列的硫代磷酸酯寡核苷酸文库，将硫代磷酸酯寡核苷酸T2G4T2鉴定为体外HIV感染抑制剂。寡核苷酸形成平行链四聚鸟苷酸（G-四重奏）结构。四聚体形成和硫代磷酸酯骨架对抗病毒活性至关重要。 G四重结构在V3环结合HIV包膜蛋白gp120并且抑制细胞对细胞和病毒对细胞的感染。

138. 发明授权

US08153602B1 Composition and methods for the pulmonary delivery of nucleic acids 有权
标题翻译：用于肺部递送核酸的组合物和方法
公开(公告)号：US08153602B1
公开(公告)日：2012-04-10
申请号：US09315292
申请日：1999-05-20
申请人： Clarence Frank Bennett , David J. Ecker , Phillip Dan Cook
发明人： Clarence Frank Bennett , David J. Ecker , Phillip Dan Cook
IPC分类号： A61K48/00 , C07H21/04 , C07H21/02
CPC分类号： A61K48/0075
摘要： The present invention relates to compositions and methods for the pulmonary delivery of nucleic acids, particularly oligonucleotides. In one preferred embodiment, the compositions and methods of the invention are utilized to effect the pulmonary delivery of an antisense oligonucleotide to an animal in order to modulate the expression of a gene in the animal for investigative, therapeutic or prophylactic purposes.
摘要翻译：本发明涉及用于肺部递送核酸，特别是寡核苷酸的组合物和方法。在一个优选的实施方案中，本发明的组合物和方法用于将动物的反义寡核苷酸肺部递送至动物，以调节动物中基因的表达用于调查，治疗或预防目的。

139. 发明申请

US20110213014A1 COMPOSITIONS AND METHODS FOR TOPICAL DELIVERY OF OLIGONUCLEOTIDES 审中-公开
标题翻译：用于局部输送寡核苷酸的组合物和方法
公开(公告)号：US20110213014A1
公开(公告)日：2011-09-01
申请号：US13107131
申请日：2011-05-13
申请人： Rahul C. Mehta , Gregory E. Hardee , Phillip Dan Cook , David J. Ecker , Yali Jennifer Tsai , Michael V. Templin
发明人： Rahul C. Mehta , Gregory E. Hardee , Phillip Dan Cook , David J. Ecker , Yali Jennifer Tsai , Michael V. Templin
IPC分类号： A61K31/7088 , A61P31/00 , A61P35/00 , A61P37/00
CPC分类号： A61K48/0008 , A61K48/0025 , A61K48/0041 , A61K48/0075
摘要： The present invention relates to compositions and methods which enhance the delivery of oligonucleotides and other nucleosidic moieties via topical routes of administration. Preferred compositions include liposomes or penetration enhancers for the delivery of such moieties to dermal and/or epidermal tissue in an animal for investigative, therapeutic or prophylactic purposes.
摘要翻译：本发明涉及通过局部施用途径增强寡核苷酸和其它核苷部分的递送的组合物和方法。优选的组合物包括用于将这些部分递送到动物中用于调查，治疗或预防目的的皮肤和/或表皮组织的脂质体或渗透增强剂。

140. 发明授权

US07964579B2 Compositions and methods for topical delivery of oligonucleotides 失效
标题翻译：用于局部递送寡核苷酸的组合物和方法
公开(公告)号：US07964579B2
公开(公告)日：2011-06-21
申请号：US12545778
申请日：2009-08-21
申请人： Rahul C. Mehta , Gregory E. Hardee , Phillip Dan Cook , David J. Ecker , Yali Jennifer Tsai , Michael V. Templin
发明人： Rahul C. Mehta , Gregory E. Hardee , Phillip Dan Cook , David J. Ecker , Yali Jennifer Tsai , Michael V. Templin
IPC分类号： C07H21/02 , C07H21/04 , A61K31/70 , C12Q1/68
CPC分类号： A61K48/0008 , A61K48/0025 , A61K48/0041 , A61K48/0075
摘要： The present invention relates to compositions and methods which enhance the delivery of oligonucleotides and other nucleosidic moieties via topical routes of administration. Preferred compositions include liposomes or penetration enhancers for the delivery of such moieties to dermal and/or epidermal tissue in an animal for investigative, therapeutic or prophylactic purposes.
摘要翻译：本发明涉及通过局部施用途径增强寡核苷酸和其它核苷部分的递送的组合物和方法。优选的组合物包括用于将这些部分递送到动物中用于调查，治疗或预防目的的皮肤和/或表皮组织的脂质体或渗透增强剂。

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