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。

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。

公开(公告)号：US5939401A

公开(公告)日：1999-08-17

申请号：US680354

申请日：1996-07-15

申请人： John Marshall ,  David J. Harris ,  Edward R. Lee ,  Craig S. Siegel ,  Simon J. Eastman ,  Chau-Dung Chang ,  Ronald K. Scheule ,  Seng H. Cheng

发明人： John Marshall ,  David J. Harris ,  Edward R. Lee ,  Craig S. Siegel ,  Simon J. Eastman ,  Chau-Dung Chang ,  Ronald K. Scheule ,  Seng H. Cheng

IPC分类号： A61K47/48 ,  A61K9/127 ,  A61K31/70 ,  A61K47/28 ,  A61K48/00 ,  C07J41/00 ,  C07J43/00 ,  C12N15/87 ,  C12N15/88 ,  A61K38/00 ,  C07J9/00

CPC分类号： A61K9/1272 ,  A61K47/48038 ,  A61K47/48046 ,  A61K47/48123 ,  C07J41/0005 ,  C07J41/0055 ,  C07J41/0061 ,  C07J43/003 ,  C12N15/88 ,  A61K48/00

摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. By this invention, such cationic amphiphile is used in a state in which it is capable of accepting additional protons, i.e., it is not fully protonated. For purposes of this invention, cationic amphiphiles may be considered to encompass four general categories: (A) T-shaped/steroid-based amphiphiles; (B) T-shaped/non steroid-based amphiphiles; (C) non T-shaped/steroid based amphiphiles and (D) non T-shaped/non steroid-based amphiphiles.

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。 通过本发明，这种阳离子两亲物以其能够接受另外的质子即不完全质子化的状态使用。 为了本发明的目的，阳离子两亲物可以被认为包括四个一般类别：（A）T型/类固醇基两亲物; （B）T型/非类固醇基两亲物; （C）非T型/类固醇基两亲物和（D）非T型/非类固醇基两亲物。

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。