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1. 发明授权

US06697669B2 Skin and muscle-targeted gene therapy by pulsed electrical field 有权
公开(公告)号：US06697669B2
公开(公告)日：2004-02-24
申请号：US09352809
申请日：1999-07-13
申请人： Nagendu B. Dev , Gunter A. Hofmann , Edward Nolan , Dietmar P. Rabussay , Arnt Tonnessen , Georg Widera , Lei Zhang
发明人： Nagendu B. Dev , Gunter A. Hofmann , Edward Nolan , Dietmar P. Rabussay , Arnt Tonnessen , Georg Widera , Lei Zhang
IPC分类号： A61N130
CPC分类号： A61N1/327 , A61N1/0424 , A61N1/0452 , A61N1/306 , A61N1/325
摘要： The present invention describes an in vivo method, using pulsed electric field to deliver therapeutic agents into cells of the skin and muscle for local and systemic treatments. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.

2. 发明授权

US07171264B1 Intradermal delivery of active agents by needle-free injection and electroporation 有权
标题翻译：通过无针注射和电穿孔活性剂的皮内递送
公开(公告)号：US07171264B1
公开(公告)日：2007-01-30
申请号：US10339708
申请日：2003-01-08
申请人： Gunter A. Hofmann , Dietmar P. Rabussay , Lei Zhang
发明人： Gunter A. Hofmann , Dietmar P. Rabussay , Lei Zhang
IPC分类号： A61N1/30
CPC分类号： A61N1/0424 , A61N1/0428 , A61N1/325
摘要： Methods are proved for introducing a biologically active agent into cells of a subject by introducing the agent in a form suitable for electrotransport into a region of tissue of the subject using one or more needle-free injectors, and applying a pulsed electric field to the region of tissue, thereby causing electroporation of the region of tissue. The combination of needle-free injection and electroporation is sufficient to introduce the agent into cells in skin, muscle or mucosa. For example, the region of tissue can be contacted with two oppositely charged injectors, one acting as the donor electrode and one acting as the counter electrode, or a single injector and one or more electrodes can be used. In addition, needle-free injection may be used in combination with suitable non-invasive electrode configurations. The active agents delivered into cells using the invention method can be small molecules, polynucleotides, polypeptides, and the like.
摘要翻译：证明通过使用一种或多种无针注射器将适合于电转移到受试者组织区域的形式引入生物活性剂来引入生物活性剂的方法，以及向该区域施加脉冲电场的组织，从而引起组织区域的电穿孔。无针注射和电穿孔的组合足以将药剂引入皮肤，肌肉或粘膜中的细胞中。例如，组织区域可以与两个相反电荷的注射器接触，一个充当施主电极，另一个充当对电极，或者可以使用单个注射器和一个或多个电极。此外，无针注射可以与合适的非侵入性电极结构组合使用。使用本发明方法递送到细胞中的活性剂可以是小分子，多核苷酸，多肽等。

3. 发明授权

US06654636B1 Skin and muscle-targeted gene therapy by pulsed electrical field 有权
标题翻译：通过脉冲电场进行皮肤和肌肉靶向基因治疗
公开(公告)号：US06654636B1
公开(公告)日：2003-11-25
申请号：US09625825
申请日：2000-07-26
申请人： Nagendu B. Dev , Gunter A. Hofmann , Edward Nolan , Dietmar P. Rabussay , Arnt Tonnessen , Georg Widera , Lei Zhang
发明人： Nagendu B. Dev , Gunter A. Hofmann , Edward Nolan , Dietmar P. Rabussay , Arnt Tonnessen , Georg Widera , Lei Zhang
IPC分类号： A61N130
CPC分类号： A61N1/327 , A61N1/0424 , A61N1/0452 , A61N1/306 , A61N1/325
摘要： The present invention describes an in vivo method, using pulsed electric field to deliver therapeutic agents into cells of the skin and muscle for local and systemic treatments. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.
摘要翻译：本发明描述了体内方法，使用脉冲电场将治疗剂递送到皮肤和肌肉的细胞中用于局部和全身治疗。特别地，治疗剂包括裸体或配制的核酸，多肽和化学治疗剂。

4. 发明授权

US06520950B1 Method of electroporation-enhanced delivery of active agents 有权
标题翻译：电穿孔增强活性剂递送方法
公开(公告)号：US06520950B1
公开(公告)日：2003-02-18
申请号：US09567404
申请日：2000-05-08
申请人： Gunter A. Hofmann , Dietmar P. Rabussay , Lei Zhang
发明人： Gunter A. Hofmann , Dietmar P. Rabussay , Lei Zhang
IPC分类号： A61M2500
CPC分类号： A61N1/327 , A61N1/0412 , A61N1/0424 , A61N1/0428 , A61N1/0476 , A61N1/30 , A61N1/306 , A61N1/325 , Y10S977/906
摘要： Methods are provided for introducing a biologically active agent into cells of a subject by injecting the agent with a needle-free injector and applying a pulsed electric field to the region of tissue to cause electrotransport of the agent into cells of the tissue. Preferably the agent is either ionized to some degree or contained in an ionized medium for electrotransport. The needle-free injector can serve as an electrode by which the pulsed electric field is applied to the region of tissue. The active agents delivered into cells by this method include small molecules, polynucleotides, polypeptides, and the like. Polynucleotides introduced into cells using this method can be used to accomplish gene therapy or to modulate expression of an endogenous gene.
摘要翻译：提供了通过用无针注射器注入药剂并将组织上的脉冲电场施加到组织区域以引起药物转移到组织细胞中而将生物活性剂引入受试者细胞的方法。优选地，试剂在一定程度上被电离或包含在用于电转运的电离介质中。无针注射器可用作电极，通过该电极将脉冲电场施加到组织区域。通过该方法递送到细胞中的活性剂包括小分子，多核苷酸，多肽等。使用该方法引入细胞的多核苷酸可用于完成基因治疗或调节内源基因的表达。

5. 发明授权

US07922709B2 Enhanced delivery of naked DNA to skin by non-invasive in vivo electroporation 有权
标题翻译：通过非侵入性体内电穿孔增强裸DNA的表达
公开(公告)号：US07922709B2
公开(公告)日：2011-04-12
申请号：US11291459
申请日：2005-11-30
申请人： Lei Zhang , Dietmar P. Rabussay
发明人： Lei Zhang , Dietmar P. Rabussay
IPC分类号： A61N1/30
CPC分类号： A61N1/327 , A61N1/306
摘要： In vivo methods are provided for using an electric field to delivery therapeutic or immunizing treatment to a subject by applying non-invasive, user-friendly electrodes to the surface of the skin. Thus, therapeutic or immunizing agents can be delivered into cells of skin for local and systemic treatments or for immunization with optimal gene expression and minimal tissue damage. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.
摘要翻译：提供体内方法，通过将非侵入性的，用户友好的电极施加到皮肤表面，使用电场来传递对受试者的治疗或免疫治疗。因此，治疗或免疫剂可以递送到皮肤细胞中用于局部和全身治疗或用最佳基因表达和最小组织损伤进行免疫。特别地，治疗剂包括裸体或配制的核酸，多肽和化学治疗剂。

6. 发明授权

US07570992B2 Electrical field therapy with reduced histopathological change in muscle 有权
标题翻译：电场治疗减少肌肉组织病理学变化
公开(公告)号：US07570992B2
公开(公告)日：2009-08-04
申请号：US10756946
申请日：2004-01-13
申请人： Edward Nolan , Dietmar P. Rabussay , Georg Widera , Lei Zhang
发明人： Edward Nolan , Dietmar P. Rabussay , Georg Widera , Lei Zhang
IPC分类号： A61N1/30 , A61M31/00
CPC分类号： A61N1/325 , A61N1/306
摘要： In vivo methods are provided for using an electric field to delivery therapeutic treatment to a subject while reducing inducement of histopathological change in the target muscle tissue, such as is associated with induction or amplification of an immune response caused by the pulsed electric field. Therapeutic agents can be delivered nto cells of muscle for local and systemic treatments with optimal gene expression and minimal tissue damage. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.
摘要翻译：提供体内方法，用于使电场向受试者递送治疗性治疗，同时减少诱导靶肌肉组织中的组织病理学变化，例如与由脉冲电场引起的免疫应答的诱导或扩增相关。治疗剂可以递送到肌肉细胞，用于局部和全身治疗，具有最佳的基因表达和最小的组织损伤。特别地，治疗剂包括裸体或配制的核酸，多肽和化学治疗剂。

7. 发明授权

US06972013B1 Enhanced delivery of naked DNA to skin by non-invasive in vivo electroporation 有权
标题翻译：通过非侵入性体内电穿孔增强裸DNA的表达
公开(公告)号：US06972013B1
公开(公告)日：2005-12-06
申请号：US10233007
申请日：2002-08-30
申请人： Lei Zhang , Dietmar P. Rabussay
发明人： Lei Zhang , Dietmar P. Rabussay
IPC分类号： A61N1/30 , A61N1/32
CPC分类号： A61N1/327 , A61N1/306
摘要： In vivo methods are provided for using an electric field to delivery therapeutic or immunizing treatment to a subject by applying non-invasive, user-friendly electrodes to the surface of the skin. Thus, therapeutic or immunizing agents can be delivered into cells of skin for local and systemic treatments or for immunization with optimal gene expression and minimal tissue damage. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.
摘要翻译：提供体内方法，通过将非侵入性的，用户友好的电极施加到皮肤表面，使用电场来传递对受试者的治疗或免疫治疗。因此，治疗或免疫剂可以递送到皮肤细胞中用于局部和全身治疗或用最佳基因表达和最小组织损伤进行免疫。特别地，治疗剂包括裸体或配制的核酸，多肽和化学治疗剂。

8. 发明授权

US06678556B1 Electrical field therapy with reduced histopathological change in muscle 有权
标题翻译：电场治疗减少肌肉组织病理学变化
公开(公告)号：US06678556B1
公开(公告)日：2004-01-13
申请号：US10165657
申请日：2002-06-07
申请人： Edward Nolan , Dietmar P. Rabussay , Georg Widera , Lei Zhang
发明人： Edward Nolan , Dietmar P. Rabussay , Georg Widera , Lei Zhang
IPC分类号： A61N130
CPC分类号： A61N1/325 , A61N1/306
摘要： In vivo methods are provided for using an electric field to delivery therapeutic treatment to a subject while reducing inducement of histopathological change in the target muscle tissue, such as is associated with induction or amplification of an immune response caused by the pulsed electric field. Therapeutic agents can be delivered nto cells of muscle for local and systemic treatments with optimal gene expression and minimal tissue damage. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.
摘要翻译：提供体内方法，用于使电场向受试者递送治疗性治疗，同时减少诱导靶肌肉组织中的组织病理学变化，例如与由脉冲电场引起的免疫应答的诱导或扩增相关。治疗剂可以递送到肌肉细胞，用于局部和全身治疗，具有最佳的基因表达和最小的组织损伤。特别地，治疗剂包括裸体或配制的核酸，多肽和化学治疗剂。

9. 发明授权

US07395110B2 Electrode apparatus and method for the delivery of drugs and genes into tissue 失效
标题翻译：用于将药物和基因递送到组织中的电极装置和方法
公开(公告)号：US07395110B2
公开(公告)日：2008-07-01
申请号：US10783164
申请日：2004-02-20
申请人： Günter A. Hofmann , Dietmar P. Rabussay , Zei Zhang
发明人： Günter A. Hofmann , Dietmar P. Rabussay , Zei Zhang
IPC分类号： A61N1/30
CPC分类号： A61N1/0424 , A61N1/042 , A61N1/0436 , A61N1/044 , A61N1/30 , A61N1/325
摘要： An electrode assembly for an apparatus for trans-surface molecular includes a non-conductive carrier having a proximal surface, a distal surface, and a plurality of through holes from the proximal surface to the distal surface, a plurality of first electrodes disposed on the proximal surface, a first conductor disposed on at least a first portion of the distal surface and extending through at least a first portion of the plurality of through holes and connected to the first electrodes on the proximal surface, a plurality of second electrodes disposed on the proximal surface, and a second conductor disposed on at least a second portion of the distal surface and extending through at least a second portion of the plurality of through holes and connected to the second electrodes on the proximal surface, wherein the first electrodes and the second electrodes are configured and disposed in closely spaced relation on the proximal surface for engaging the tissue surface and applying an electric field.
摘要翻译：用于反式表面分子的装置的电极组件包括具有近端表面，远端表面和从近端表面到远端表面的多个通孔的非导电载体，多个第一电极，其设置在近端表面，设置在所述远端表面的至少第一部分上并延伸穿过所述多个通孔的至少第一部分并且连接到所述近端表面上的所述第一电极的第一导体，设置在所述近端的多个第二电极表面和第二导体，其设置在远端表面的至少第二部分上并且延伸穿过多个通孔的至少第二部分并且连接到近端表面上的第二电极，其中第一电极和第二电极在近侧表面上以紧密间隔的关系配置和设置，用于接合组织表面并施加电极 c字段。

10. 发明申请

US20080215032A1 Minimizing Metal Toxicity During Electroporation Enhanced Delivery of Polynucleotides 审中-公开
标题翻译：电穿孔期间金属毒性最小化增强多核苷酸的递送
公开(公告)号：US20080215032A1
公开(公告)日：2008-09-04
申请号：US10516757
申请日：2003-03-25
申请人： Dietmar P. Rabussay
发明人： Dietmar P. Rabussay
IPC分类号： A61N1/30 , A61M31/00 , A61N1/32 , A61N1/05 , A61K31/7088
CPC分类号： C12N15/87 , A61K48/0083
摘要： Methods are provided for introducing a polynucleotide into healthy tissue and generating a pulsed electric field in the tissue via invasive electrodes, resulting in enhanced delivery of the polynucleotide into cells of the tissue, while minimizing local side effects to the electroporated tissue and systemic side effects to the electroporated organism due to metal contaminants released from said electrodes. In one embodiment, the invention methods Use electrodes of gold, gold alloys, or other metal that minimize the introduction of toxic amounts of the metal into electroporated tissue. In other embodiments, the invention methods are utilized for the gene therapy by administering DNA to cells of suitable target tissue, and for the induction of an immune response by administration of a DNA vaccine.
摘要翻译：提供了用于将多核苷酸引入健康组织中并通过侵入电极在组织中产生脉冲电场的方法，导致多核苷酸进入组织细胞的增强递送，同时最小化对电穿孔组织的局部副作用和全身副作用由于从所述电极释放的金属污染物导致的电穿孔生物体。在一个实施方案中，本发明方法使用金，金合金或其它金属的电极，其将毒性量的金属引入电穿孔组织中最小化。在其它实施方案中，本发明方法用于通过向合适的靶组织的细胞施用DNA以及通过施用DNA疫苗来诱导免疫应答来进行基因治疗。

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