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1. 发明授权

US6071890A Organ-specific targeting of cationic amphiphile/DNA complexes for gene therapy 失效
标题翻译：用于基因治疗的阳离子两亲物/ DNA复合物的器官特异性靶向
公开(公告)号：US6071890A
公开(公告)日：2000-06-06
申请号：US545473
申请日：1995-10-19
申请人： Ronald K. Scheule , Rebecca G. Bagley , Simon J. Eastman , Seng H. Cheng , John Marshall , Nelson S. Yew , David J. Harris , Edward R. Lee , Craig S. Siegel
发明人： Ronald K. Scheule , Rebecca G. Bagley , Simon J. Eastman , Seng H. Cheng , John Marshall , Nelson S. Yew , David J. Harris , Edward R. Lee , Craig S. Siegel
IPC分类号： C12N15/09 , A61K9/127 , A61K47/28 , A61K47/48 , A61K48/00 , A61P29/00 , A61P43/00 , C07C211/13 , C07C217/28 , C07C237/06 , C07C271/20 , C07C271/34 , C07C275/14 , C07C279/12 , C07C323/25 , C07C327/42 , C07C333/04 , C07J41/00 , C07J43/00 , C12N15/88 , A01N43/04
CPC分类号： A61K47/48023 , A61K47/48038 , A61K47/48046 , A61K47/48123 , A61K48/00 , A61K9/1272 , C07J41/0005 , C07J41/0055 , C07J41/0061 , C07J43/003 , C12N15/88
摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.
摘要翻译：提供了新的阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。两亲物含有衍生自类固醇的单亲或二烷基胺或烷基或酰基的亲脂基团; 和在生理pH下可质子化的阳离子基团，衍生自胺，烷基胺或多烷基胺。还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。还公开了新型和高效的质粒构建体，包括在为炎症复杂的临床病症提供基因治疗方面特别有效的质粒构建体。另外，描述了通过静脉内施用治疗组合物靶向用于基因治疗的器官。

2. 发明授权

US5935936A Compositions comprising cationic amphiphiles and co-lipids for intracellular delivery of therapeutic molecules 失效
标题翻译：包含阳离子两亲物和用于细胞内递送治疗性分子的共 - 脂质的组合物
公开(公告)号：US5935936A
公开(公告)日：1999-08-10
申请号：US657238
申请日：1996-06-03
申请人： Allen J. Fasbender , Michael J. Welsh , Craig S. Siegel , Edward R. Lee , Chau-Dung Chang , John Marshall , Seng H. Cheng , David J. Harris , Simon J. Eastman , Shirley C. Hubbard , Mathieu B. Lane , Eric A. Rowe , Ronald K. Scheule , Nelson S. Yew
发明人： Allen J. Fasbender , Michael J. Welsh , Craig S. Siegel , Edward R. Lee , Chau-Dung Chang , John Marshall , Seng H. Cheng , David J. Harris , Simon J. Eastman , Shirley C. Hubbard , Mathieu B. Lane , Eric A. Rowe , Ronald K. Scheule , Nelson S. Yew
IPC分类号： A61K47/28 , A61K9/127 , A61K31/70 , A61K31/7088 , A61K48/00 , C07K14/47 , C12N15/88 , A01N43/04
CPC分类号： C12N15/88 , A61K9/1272 , C07K14/4712
摘要： Novel compositions are provided. Typically, the compositions comprise one or more neutral co-lipids and also a cationic amphiphile. Therapeutic compositions are prepared according to the practice of the invention by contacting a therapeutically active molecule with a dispersion of neutral co-lipid(s) and amphiphile(s).
摘要翻译：提供了新的组合物。通常，组合物包含一种或多种中性助脂和阳离子两亲物。通过使治疗活性分子与中性助脂质和两亲物的分散体接触，根据本发明的实践制备治疗组合物。

3. 发明申请

US20080035219A1 GAS DELIVERY SYSTEM 审中-公开
标题翻译：气体输送系统
公开(公告)号：US20080035219A1
公开(公告)日：2008-02-14
申请号：US11838357
申请日：2007-08-14
申请人： Edward R. Lee , Robert C. Jones , Jeromey Treg Yowell , Randy Scott Wheaton
发明人： Edward R. Lee , Robert C. Jones , Jeromey Treg Yowell , Randy Scott Wheaton
IPC分类号： F17D1/04 , B62D63/04 , B67D5/36
CPC分类号： B60P3/36 , F16L41/03 , F17C2265/066 , Y10T137/87249
摘要： A gas delivery system for a recreational vehicle comprising an inlet hose configured to be connected to a source of gas, a manifold connected to the inlet hose, a plurality of supply hoses connected to the manifold, and a plurality of appliances configured to be positioned within the recreational vehicle, with each one of the appliances being connected to one of the supply hoses. Gas can be supplied to each of the appliances via the inlet hose, the manifold and one of the supply hoses.
摘要翻译：一种用于娱乐车辆的气体输送系统，包括被配置为连接到气源的入口软管，连接到入口软管的歧管，连接到歧管的多个供应软管，以及被配置为位于内部娱乐车辆，其中每个设备连接到一个供应软管。可以通过入口软管，歧管和供应软管之一向每个设备提供气体。

4. 发明授权

US5948767A Cationic amphiphile/DNA complexes 失效
标题翻译：阳离子两亲物/ DNA复合物
公开(公告)号：US5948767A
公开(公告)日：1999-09-07
申请号：US679514
申请日：1996-07-12
申请人： Ronald K. Scheule , Rebecca G. Bagley , Simon J. Eastman , Seng H. Cheng , John Marshall , Nelson S. Yew , David J. Harris , Edward R. Lee , Craig S. Siegel , Chau-Dung Chang , S. Catherine Hubbard
发明人： Ronald K. Scheule , Rebecca G. Bagley , Simon J. Eastman , Seng H. Cheng , John Marshall , Nelson S. Yew , David J. Harris , Edward R. Lee , Craig S. Siegel , Chau-Dung Chang , S. Catherine Hubbard
IPC分类号： A61K47/18 , A61K9/127 , A61K31/7105 , A61K31/711 , A61K38/00 , A61K38/22 , A61K47/28 , A61K47/48 , A61K48/00 , A61P7/00 , A61P9/00 , A61P11/00 , A61P21/00 , A61P25/00 , A61P35/00 , C07J41/00 , C07J43/00 , C12N15/88
CPC分类号： A61K9/1272 , A61K47/48023 , A61K47/48038 , A61K47/48046 , A61K47/48123 , A61K48/00 , C07J41/0005 , C07J41/0055 , C07J41/0061 , C07J43/003 , C12N15/88
摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile.Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.
摘要翻译：提供了新的阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。两亲物含有衍生自类固醇的单亲或二烷基胺或烷基或酰基的亲脂基团; 和在生理pH下可质子化的阳离子基团，衍生自胺，烷基胺或多烷基胺。还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。还公开了新型和高效的质粒构建体，包括在为炎症复杂的临床病症提供基因治疗方面特别有效的质粒构建体。另外，描述了通过静脉内施用治疗组合物靶向用于基因治疗的器官。

5. 发明授权

US5783565A Cationic amphiphiles containing spermine or spermidine cationic group for intracellular delivery of therapeutic molecules 失效
标题翻译：含有精胺或亚精胺阳离子基团的阳离子两亲物用于细胞内递送治疗分子
公开(公告)号：US5783565A
公开(公告)日：1998-07-21
申请号：US595375
申请日：1996-02-01
申请人： Edward R. Lee , David J. Harris , Craig S. Siegel , Seng H. Cheng , Simon J. Eastman , John Marshall , Ronald K. Scheule
发明人： Edward R. Lee , David J. Harris , Craig S. Siegel , Seng H. Cheng , Simon J. Eastman , John Marshall , Ronald K. Scheule
IPC分类号： A61K9/127 , A61K47/48 , A61K48/00 , C07J41/00 , C07J43/00 , C12N15/88 , B01F17/16 , C12N15/00
CPC分类号： B82Y5/00 , A61K47/48023 , A61K47/48038 , A61K47/48046 , A61K47/48123 , A61K48/00 , A61K9/1272 , C07J41/0005 , C07J41/0055 , C07J41/0061 , C07J43/003 , C12N15/88 , Y10S516/07
摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.
摘要翻译：提供了新的阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。两亲物含有衍生自类固醇的单亲或二烷基胺或烷基或酰基的亲脂基团; 和在生理pH下可质子化的阳离子基团，衍生自胺，烷基胺或多烷基胺。还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。还公开了新型和高效的质粒构建体，包括在为炎症复杂的临床病症提供基因治疗方面特别有效的质粒构建体。另外，描述了通过静脉内施用治疗组合物靶向用于基因治疗的器官。

6. 发明授权

US06383814B1 Cationic amphiphiles for intracellular delivery of therapeutic molecules 有权
标题翻译：阳离子两亲物用于细胞内递送治疗分子
公开(公告)号：US06383814B1
公开(公告)日：2002-05-07
申请号：US09228232
申请日：1999-01-11
申请人： Edward R. Lee , David J. Harris , Craig S. Siegel , Mathieu B. Lane , Shirley C. Hubbard , Seng H. Cheng , Simon J. Eastman , John Marshall , Ronald K Scheule , Nelson S. Yew
发明人： Edward R. Lee , David J. Harris , Craig S. Siegel , Mathieu B. Lane , Shirley C. Hubbard , Seng H. Cheng , Simon J. Eastman , John Marshall , Ronald K Scheule , Nelson S. Yew
IPC分类号： C12N1588
CPC分类号： C12N15/88 , A61K9/1272 , A61K47/542 , A61K47/543 , A61K47/554 , A61K48/00 , C07J41/0005 , C07J41/0055 , C07J41/0061 , C07J43/003
摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.
摘要翻译：提供了新的阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。两亲物含有衍生自类固醇的单亲或二烷基胺或烷基或酰基的亲脂基团; 和在生理pH下可质子化的阳离子基团，衍生自胺，烷基胺或多烷基胺。还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。关于用于基因治疗的治疗组合物，DNA通常以用于与阳离子两亲物络合的质粒的形式提供。还公开了新的和高效的质粒构建体，包括在为临床条件提供基因治疗方面特别有效的炎症复杂。此外，描述了通过静脉内施用治疗组合物靶向用于基因治疗的器官。

7. 发明授权

US06331524B1 Organ-specific targeting of cationic amphiphile / DNA complexes for gene therapy 失效
标题翻译：用于基因治疗的阳离子两亲物/ DNA复合物的器官特异性靶向
公开(公告)号：US06331524B1
公开(公告)日：2001-12-18
申请号：US08835213
申请日：1997-04-07
申请人： Ronald K. Scheule , Rebecca G. Bagley , Simon J. Eastman , Seng H. Cheng , John Marshall , David J. Harris , Edward R. Lee , Craig S. Siegel , Chau-Dung Chang , S. Catherine Hubbard , Duane E. Johnson , Daniel C. Maneval , H. Michael Shepard , Richard J. Gregory
发明人： Ronald K. Scheule , Rebecca G. Bagley , Simon J. Eastman , Seng H. Cheng , John Marshall , David J. Harris , Edward R. Lee , Craig S. Siegel , Chau-Dung Chang , S. Catherine Hubbard , Duane E. Johnson , Daniel C. Maneval , H. Michael Shepard , Richard J. Gregory
IPC分类号： A61K4800
CPC分类号： C07J41/0055 , A61K9/1272 , A61K47/54 , A61K47/542 , A61K47/543 , A61K47/554 , A61K48/00 , C07J41/0005 , C07J41/0061 , C07J43/003 , C12N15/88
摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.
摘要翻译：提供了新的阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。两亲物含有衍生自类固醇的单亲或二烷基胺或烷基或酰基的亲脂基团; 和在生理pH下可质子化的阳离子基团，衍生自胺，烷基胺或多烷基胺。还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。还公开了新型和高效的质粒构建体，包括在为炎症复杂的临床病症提供基因治疗方面特别有效的质粒构建体。另外，描述了通过静脉内施用治疗组合物靶向用于基因治疗的器官。

8. 发明授权

US06323191B1 Small molecule chloride transport 失效
标题翻译：小分子氯化物运输
公开(公告)号：US06323191B1
公开(公告)日：2001-11-27
申请号：US09334936
申请日：1999-06-17
申请人： David J. Harris , Edward R. Lee , Canwen Jiang , Seng H. Cheng , Mathieu Lane
发明人： David J. Harris , Edward R. Lee , Canwen Jiang , Seng H. Cheng , Mathieu Lane
IPC分类号： A01N4500
CPC分类号： A61K47/28 , A61K31/00 , A61K31/56 , A61K31/573 , A61K31/6615 , Y10S514/851
摘要： Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride (Cl−) channel regulated by phosphorylation and intracellular nucleotides. CFTR is the major Cl− transport pathway in airway epithelial cells. The abnormal transepithelial Cl− transport and subsequent defective fluid transport caused by CF is a result of the genetic mutations of the gene coding for the CFTR protein. The present invention is directed to the novel use of ionophores as artificial Cl− transport pathways into CF epithelia to treat the defective Cl− and fluid transport lonophores and in particular, small molecule ionophores, represent a potential novel means of treating CF. The invention also includes using an ionophore to generate chloride secretion on intact monolayers of airway epithelia cells and other epithelia cells by administering an ionophore to a mammal.
摘要翻译：囊性纤维化跨膜电导调节因子（CFTR）是通过磷酸化和细胞内核苷酸调节的氯化物（Cl-）通道。 CFTR是气道上皮细胞中主要的Cl-转运途径。由CF引起的异常跨上皮性Cl-转运和随后的有缺陷的流体转运是编码CFTR蛋白的基因的遗传突变的结果。本发明涉及离子载体作为人造Cl-转运途径进入CF上皮以治疗有缺陷的Cl-和液体转运离子的新颖应用，特别是小分子离子载体，代表了治疗CF的潜在的新方法。本发明还包括使用离子载体通过向哺乳动物施用离子载体来在气道上皮细胞和其它上皮细胞的完整单层上产生氯化物分泌。

9. 外观设计

USD362298S Gas regulator 失效
公开(公告)号：USD362298S
公开(公告)日：1995-09-12
申请号：US27484
申请日：1994-08-22
申请人： Edward R. Lee
设计人： Edward R. Lee

10. 外观设计

USD362297S Gas regulator 失效
公开(公告)号：USD362297S
公开(公告)日：1995-09-12
申请号：US27460
申请日：1994-08-22
申请人： Edward R. Lee
设计人： Edward R. Lee

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