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1. 发明申请

US20070066556A1 Antisense antiviral compound and method for treating picornavirus infection 失效
标题翻译：反义抗病毒化合物及治疗小RNA病毒感染的方法
公开(公告)号：US20070066556A1
公开(公告)日：2007-03-22
申请号：US11517757
申请日：2006-09-08
申请人： David Stein , Richard Bestwick , Patrick Iversen , Dwight Weller
发明人： David Stein , Richard Bestwick , Patrick Iversen , Dwight Weller
IPC分类号： A61K48/00 , C07F9/6533
CPC分类号： A61K38/00 , C12N15/1131 , C12N2310/11 , C12N2310/314 , C12N2310/3233 , C12N2770/32311 , C12N2770/32711
摘要： The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Picornaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Enterovirus and/or Rhinovirus infection in a mammal. The antisense antiviral compounds are substantially uncharged, morpholino oligonucleotides have a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with viral RNA sequences within a 32 nucleotide region of the viral 5′ untranslated region identified by SEQ ID NO:7.
摘要翻译：本发明提供反义抗病毒化合物及其在抑制小核糖核酸病毒科家族病毒生长和用于病毒感染治疗中的用途和生产方法。所述化合物特别可用于治疗哺乳动物中的肠病毒和/或鼻病毒感染。反义抗病毒化合物基本上不带电，吗啉代寡核苷酸具有12-40个亚基的序列，包括至少12个亚基，其具有与病毒5'非翻译的32个核苷酸区域内的病毒RNA序列相关的区域互补的靶向序列由SEQ ID NO：7鉴定的区域。

2. 发明申请

US20120073137A1 AIRCRAFT RIB-SPAR JOINT 有权
标题翻译：飞机RIB-SPAR接头
公开(公告)号：US20120073137A1
公开(公告)日：2012-03-29
申请号：US13238468
申请日：2011-09-21
申请人： Richard BESTWICK , Scott GRANT
发明人： Richard BESTWICK , Scott GRANT
IPC分类号： B21D53/92
CPC分类号： B64C3/187 , B64C3/185 , B64F5/10 , Y10T29/49622 , Y10T29/4978 , Y10T29/53978 , Y10T408/55
摘要： A method of forming a rib-spar joint during assembly of an aircraft wing, the method comprising: providing a spar with a fixedly attached rib post, the rib post having a first coordination feature; providing a rib having a web with a first tooling feature; providing a tooling component having a second tooling feature for cooperating with the first tooling feature, a second coordination feature for cooperating with the first coordination feature, and a plurality of drill bushings; fixedly attaching the tooling component to the rib web by aligning the first and second tooling features; aligning the rib with the spar by aligning the first and second coordination features; drilling fastener holes in the rib and the rib post off the drill bushings of the tooling component; removing the tooling component from the rib web; and fastening the rib to the rib post using the fastener holes to form a rib-spar joint. The method may be applied to form front and/or rear rib-spar joints.
摘要翻译：一种在飞行器机翼的组装期间形成肋 - 翼梁接头的方法，所述方法包括：提供具有固定附接的肋柱的翼梁，所述肋柱具有第一协调特征; 提供具有带有第一工具特征的网的肋; 提供具有用于与所述第一工具特征配合的第二工具特征的模具部件，用于与所述第一协调特征配合的第二协调特征以及多个钻套筒; 通过对准第一和第二工具特征将工具组件固定地连接到肋腹板上; 通过对准第一和第二协调特征来对准肋骨与翼梁; 在所述肋和所述肋中钻紧所述紧固件孔，从所述工具部件的所述钻套中脱出; 从所述肋网移除所述加工部件; 并且使用所述紧固件孔将所述肋条紧固到所述肋柱上以形成肋 - 翼梁接头。该方法可以应用于形成前肋和/或后肋骨接头。

3. 发明申请

US20070037764A1 Method and antisense composition for selective inhibition of HIV infection in hematopoietic cells 审中-公开
标题翻译：用于选择性抑制造血细胞中HIV感染的方法和反义组合物
公开(公告)号：US20070037764A1
公开(公告)日：2007-02-15
申请号：US11433257
申请日：2006-05-11
申请人： Dan Mourich , Patrick Iversen , Richard Bestwick , Dwight Weller
发明人： Dan Mourich , Patrick Iversen , Richard Bestwick , Dwight Weller
IPC分类号： A61K48/00 , C07F9/6533
CPC分类号： A61K31/675 , C07K2319/10 , C12N15/1132 , C12N2310/11 , C12N2810/6054
摘要： The invention provides antisense antiviral compounds and methods of their use in inhibition of growth of human immunodeficiency virus-1 (HOV-1), as in treatment of a viral infection. The antisense antiviral compounds have morpholino subunits linked by uncharged phosphorodiamidate linkages interspersed with cationic phosphorodiamidate linkages. An exemplary embodiment of the invention provides an antisense compound directed to the HIV Vif gene, causing the production of defective HIV- 1 virions in an infected individual.
摘要翻译：本发明提供了用于抑制人免疫缺陷病毒-1（HOV-1）生长的反义抗病毒化合物及其用于治疗病毒感染的方法。反义抗病毒化合物具有通过分散有阳离子磷酰二胺键的不带电的磷酰二胺键连接的吗啉亚基。本发明的一个示例性实施方案提供了针对HIV Vif基因的反义化合物，导致在感染个体中产生有缺陷的HIV-1病毒粒子。

4. 发明申请

US20070037763A1 Oligonucleotide compound and method for treating nidovirus infections 审中-公开
标题翻译：寡核苷酸化合物和治疗鼻病毒感染的方法
公开(公告)号：US20070037763A1
公开(公告)日：2007-02-15
申请号：US11432155
申请日：2006-05-10
申请人： David Stein , Richard Bestwick , Patrick Iversen , Benjamin Neuman , Michael Buchmeier , Dwight Weller
发明人： David Stein , Richard Bestwick , Patrick Iversen , Benjamin Neuman , Michael Buchmeier , Dwight Weller
IPC分类号： A61K48/00 , C07H21/02 , C07F9/6512
CPC分类号： C07H21/02 , C07K14/005 , C12N15/1131 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2770/20022
摘要： A method and oligonucleotide compound for inhibiting replication of a nidovirus in virus-infected animal cells are disclosed. The compound (i) has a nuclease-resistant backbone, (ii) is capable of uptake by the infected cells, (iii) contains between 8-25 nucleotide bases, and (iv) has a sequence capable of disrupting base pairing between the transcriptional regulatory sequences in the 5′ leader region of the positive-strand viral genome and negative-strand 3′ subgenomic region. In practicing the method, infected cells are exposed to the compound in an amount effective to inhibit viral replication.
摘要翻译：公开了用于抑制病毒感染的动物细胞中的Nidovirus复制的方法和寡核苷酸化合物。化合物（i）具有核酸酶抗性主链，（ii）能够被感染细胞摄取，（iii）含有8-25个核苷酸碱基之间，和（iv）具有能够破坏转录之间碱基配对的序列正链病毒基因组和负链3'亚基因组区域的5'前导区域中的调节序列。在实施该方法中，感染的细胞以有效抑制病毒复制的量暴露于化合物。

5. 发明授权

US08567066B2 Aircraft rib-spar joint 有权
标题翻译：飞机肋骨接头
公开(公告)号：US08567066B2
公开(公告)日：2013-10-29
申请号：US13238468
申请日：2011-09-21
申请人： Richard Bestwick , Scott Grant
发明人： Richard Bestwick , Scott Grant
IPC分类号： B21D53/88
CPC分类号： B64C3/187 , B64C3/185 , B64F5/10 , Y10T29/49622 , Y10T29/4978 , Y10T29/53978 , Y10T408/55
摘要： A method of forming a rib-spar joint during assembly of an aircraft wing, the method comprising: providing a spar with a fixedly attached rib post, the rib post having a first coordination feature; providing a rib having a web with a first tooling feature; providing a tooling component having a second tooling feature for cooperating with the first tooling feature, a second coordination feature for cooperating with the first coordination feature, and a plurality of drill bushings; fixedly attaching the tooling component to the rib web by aligning the first and second tooling features; aligning the rib with the spar by aligning the first and second coordination features; drilling fastener holes in the rib and the rib post off the drill bushings of the tooling component; removing the tooling component from the rib web; and fastening the rib to the rib post using the fastener holes to form a rib-spar joint. The method may be applied to form front and/or rear rib-spar joints.
摘要翻译：一种在飞行器机翼的组装期间形成肋 - 翼梁接头的方法，所述方法包括：提供具有固定附接的肋柱的翼梁，所述肋柱具有第一协调特征; 提供具有带有第一工具特征的网的肋; 提供具有用于与所述第一工具特征配合的第二工具特征的模具部件，用于与所述第一协调特征配合的第二协调特征以及多个钻套筒; 通过对准第一和第二工具特征将工具组件固定地连接到肋腹板上; 通过对准第一和第二协调特征来对准肋骨与翼梁; 在所述肋和所述肋中钻紧所述紧固件孔，从所述工具部件的所述钻套中脱出; 从所述肋网移除所述加工部件; 并且使用所述紧固件孔将所述肋条紧固到所述肋柱上以形成肋 - 翼梁接头。该方法可以应用于形成前肋和/或后肋骨接头。

6. 发明申请

US20050261249A1 Antisense composition and method for treating cancer 失效
标题翻译：反义成分和治疗癌症的方法
公开(公告)号：US20050261249A1
公开(公告)日：2005-11-24
申请号：US11077871
申请日：2005-03-10
申请人： Patrick Iversen , Hemant Roy , Richard Bestwick
发明人： Patrick Iversen , Hemant Roy , Richard Bestwick
IPC分类号： A61K48/00 , C12N15/113 , C12N15/85
CPC分类号： A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/0331 , C12N15/113 , C12N15/8509 , C12N2310/11 , C12N2310/3145 , C12N2310/3233
摘要： A method and composition for of treating cancer, and in particular, for arresting the progression of a solid or primary cancer to a more invasive, metastatic state, are disclosed. The composition includes a substantially uncharged antisense compound (i) having a nuclease-resistant backbone, (ii) capable of uptake by target cancer cells in the subject, (iii) containing between 10-40 nucleotide bases, and (iv) having a base sequence effective to hybridize to a region of processed or preprocessed human SNAIL RNA transcript. The compound, when administered to the subject, is effective to form within target cancer cells in the subject, a base-paired heteroduplex structure composed of human SNAIL RNA transcript and the oligonucleotide compound, where this structure is characterized by a Tm of dissociation of at least 45° C. The compound is administered in an amount sufficient to inhibit SNAIL expression in target cancer cells, thereby to inhibit the progression of the patient's cancer to a more invasive, metastatic state. Also disclosed are methods for preventing the transdifferentiation of peritoneal mesothelial cells and failure of ultrafiltration in a patient undergoing peritoneal dialysis, by including the compound in the patient dialysis fluid.
摘要翻译：公开了用于治疗癌症的方法和组合物，特别是用于将固体或原发癌的进展阻止到更具侵袭性的转移状态。组合物包括具有核酸酶抗性骨架的基本上不带电的反义化合物（i），（ii）能够被摄体中靶细胞摄取的能力，（iii）含有10-40个核苷酸碱基和（iv）具有碱基有效地与经处理或预处理的人SNAIL RNA转录物区域杂交的序列。该化合物当被施用于受试者时，在受试者的靶癌细胞内形成，由人SNAIL RNA转录物和寡核苷酸化合物组成的碱基配对的异源双链结构是有效的，其中该结构的特征在于解离的Tm 至少45℃。化合物以足以抑制靶癌细胞中SNAIL表达的量施用，从而抑制患者癌症进展到更具侵袭性的转移状态。还公开了通过将化合物包括在患者透析液中来防止腹膜间皮细胞的转分化和经历腹膜透析的患者中的超滤失败的方法。

7. 发明申请

US20050171044A1 Oligonucleotide compound and method for treating nidovirus infections 审中-公开
标题翻译：寡核苷酸化合物和治疗鼻病毒感染的方法
公开(公告)号：US20050171044A1
公开(公告)日：2005-08-04
申请号：US11022358
申请日：2004-12-22
申请人： David Stein , Richard Bestwick , Patrick Iversen , Benjamin Neuman , Michael Buchmeier
发明人： David Stein , Richard Bestwick , Patrick Iversen , Benjamin Neuman , Michael Buchmeier
IPC分类号： A61K48/00 , C07F9/6533 , C07H21/02 , C07K14/165 , C12N15/113
CPC分类号： C07H21/02 , C07K14/005 , C12N15/1131 , C12N2310/11 , C12N2310/3233 , C12N2310/3513 , C12N2770/20022
摘要： A method and oligonucleotide compound for inhibiting replication of a nidovirus in virus-infected animal cells are disclosed. The compound (i) has a nuclease-resistant backbone, (ii) is capable of uptake by the infected cells, (iii) contains between 8-25 nucleotide bases, and (iv) has a sequence capable of disrupting base pairing between the transcriptional regulatory sequences in the 5′ leader region of the positive-strand viral genome and negative-strand 3′ subgenomic region. In practicing the method, infected cells are exposed to the compound in an amount effective to inhibit viral replication.
摘要翻译：公开了用于抑制病毒感染的动物细胞中的Nidovirus复制的方法和寡核苷酸化合物。化合物（i）具有核酸酶抗性主链，（ii）能够被感染细胞摄取，（iii）含有8-25个核苷酸碱基之间，和（iv）具有能够破坏转录之间碱基配对的序列正链病毒基因组和负链3'亚基因组区域的5'前导区域中的调节序列。在实施该方法中，感染的细胞以有效抑制病毒复制的量暴露于化合物。

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