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公开(公告)号：US06706694B1
公开(公告)日：2004-03-16
申请号：US09588655
申请日：2000-06-06
申请人： Jon A. Wolff , David J. Duke , Philip L. Felgner
发明人： Jon A. Wolff , David J. Duke , Philip L. Felgner
IPC分类号： A61K4800
摘要： The present invention provides a method for delivering a pharmaceutical polypeptide to the interior of a cardiac cell of a vertebrate in vivo, comprising the step of introducing a preparation comprising a pharmaceutically acceptable injectable carrier and naked polynucleotide operatively coding for the polypeptide into the interstitial space of the heart, whereby the naked polynucleotide is taken up into the interior of the cell and has a pharmacological effect on the vertebrate. In a preferred embodiment wherein the polynucleotide encodes polypeptide immunologically foreign to the vertebrate, the delivery method preferably comprises delivering an immunosuppressive agent to the vertebrate to limit immune responses directed to the polypeptide.
摘要翻译： 本发明提供了一种用于在体内将药物多肽递送至脊椎动物心脏细胞内部的方法，其包括将包含药学上可接受的可注射载体的制剂和可操作地编码多肽的裸核苷酸引入到 心脏，其中裸多核苷酸被吸收到细胞内部并且对脊椎动物具有药理作用。 在其中多核苷酸编码对脊椎动物免疫外源的多肽的优选实施方案中，递送方法优选包括将免疫抑制剂递送至脊椎动物以限制针对多肽的免疫应答。
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2.发明授权Stimulating vascular growth by administration of DNA sequences encoding VEGF 失效通过施用编码VEGF的DNA序列刺激血管生长公开(公告)号：US06228844B1
公开(公告)日：2001-05-08
申请号：US08979686
申请日：1997-11-26
申请人： Jon A. Wolff , David J. Duke , Philip L. Felgner
发明人： Jon A. Wolff , David J. Duke , Philip L. Felgner
IPC分类号： A61K3800
摘要： The present invention provides a method for delivering a pharmaceutical polypeptide to the interior of a cardiac cell of a vertebrate in vivo, comprising the step of introducing a preparation comprising a pharmaceutically acceptable injectable carrier and naked polynucleotide operatively coding for the polypeptide into the interstitial space of the heart, whereby the naked polynucleotide is taken up into the interior of the cell and has a pharmacological effect on the vertebrate such as inducing vascular growth. In a preferred embodiment wherein the polynucleotide encodes polypeptide immunologically foreign to the vertebrate, the delivery method preferably comprises delivering an immunosuppressive agent to the vertebrate to limit immune responses directed to the polypeptide.
摘要翻译： 本发明提供了一种用于在体内将药物多肽递送至脊椎动物心脏细胞内部的方法，其包括将包含药学上可接受的可注射载体的制剂和可操作地编码多肽的裸核苷酸引入到 心脏，由此裸露的多核苷酸被吸收到细胞的内部并且对脊椎动物具有药理作用，例如诱导血管生长。 在其中多核苷酸编码对脊椎动物免疫外源的多肽的优选实施方案中，递送方法优选包括将免疫抑制剂递送至脊椎动物以限制针对多肽的免疫应答。
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3.发明授权
公开(公告)号：US5693622A
公开(公告)日：1997-12-02
申请号：US480039
申请日：1995-06-07
申请人： Jon A. Wolff , David J. Duke , Philip L. Felgner
发明人： Jon A. Wolff , David J. Duke , Philip L. Felgner
摘要： The present invention provides a method for delivering a pharmaceutical polypeptide to the interior of a cardiac cell of a vertebrate in vivo, comprising the step of introducing a preparation comprising a pharmaceutically acceptable injectable carrier and naked polynucleotide operatively coding for the polypeptide into the interstitial space of the heart, whereby the naked polynucleotide is taken up into the interior of the cell and has a pharmacological effect on the vertebrate. In a preferred embodiment wherein the polynucleotide encodes polypeptide immunologically foreign to the vertebrate, the delivery method preferably comprises delivering an immunosuppressive agent to the vertebrate to limit immune responses directed to the polypeptide.
摘要翻译： 本发明提供了一种用于在体内将药物多肽递送至脊椎动物心脏细胞内部的方法，其包括将包含药学上可接受的可注射载体的制剂和可操作地编码多肽的裸核苷酸引入到 心脏，其中裸多核苷酸被吸收到细胞内部并且对脊椎动物具有药理作用。 在其中多核苷酸编码对脊椎动物免疫外源的多肽的优选实施方案中，递送方法优选包括将免疫抑制剂递送至脊椎动物以限制针对多肽的免疫应答。
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公开(公告)号：US5580859A
公开(公告)日：1996-12-03
申请号：US215405
申请日：1994-03-18
IPC分类号： A61K9/127 , A61K48/00 , C07K14/16 , C07K14/61 , C12N9/02 , C12N9/10 , C12N9/12 , C12N9/78 , C12N15/87 , A01N43/04 , A61K31/70 , C12N15/00 , C12P21/06
CPC分类号： C07K14/005 , A61K48/00 , A61K9/1272 , C07K14/61 , C12N15/87 , C12N9/0069 , C12N9/1033 , C12N9/1247 , C12N9/78 , C12Y113/12007 , C12N2740/16122
摘要： Polynucleotide sequences, comprising DNA and RNA molecules can be directly administered, for example by injection, to tissues, such as muscle, and expressed as a protein, polypeptide or polypeptide. The polynucleotides can be contained within liposomes or the polynucleotides can free from association with transfection-facilitating proteins, viral particles, liposomal formulations, charged lipids and calcium phosphate precipitating agents.
摘要翻译： 包含DNA和RNA分子的多核苷酸序列可以例如通过注射直接施用于组织如肌肉，并以蛋白质，多肽或多肽表达。 多核苷酸可以包含在脂质体内，或多核苷酸可以与转染促进蛋白质，病毒颗粒，脂质体制剂，带电脂质和磷酸钙沉淀剂无关。
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5.发明授权Induction of a protective immune response in a mammal by injecting a DNA sequence 失效通过注射DNA序列诱导哺乳动物的保护性免疫应答
公开(公告)号：US5589466A
公开(公告)日：1996-12-31
申请号：US380131
申请日：1995-01-26
IPC分类号： A61K9/127 , A61K48/00 , C07K14/16 , C07K14/61 , C12N9/02 , C12N9/10 , C12N9/12 , C12N9/78 , C12N15/87 , C12N15/00
CPC分类号： C07K14/005 , A61K48/00 , A61K9/1272 , C07K14/61 , C12N15/87 , C12N9/0069 , C12N9/1033 , C12N9/1247 , C12N9/78 , C12Y113/12007 , C12N2740/16122
摘要： A method for delivering an isolated polynucleotide such as DNA or RNA, to the interior of a cell in a mammal comprising the injection of an isolated polynucleotide into a muscle of the mammal where the polynucleotide is taken up by the cells of the muscle and exerts a therapeutic effect on the mammal. The method can be used to deliver a therapeutic polypeptide to the cells of the mammal, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the mammal or to provide transitory gene therapy.
摘要翻译： 用于将分离的多核苷酸（例如DNA或RNA）递送到哺乳动物细胞内部的方法，包括将分离的多核苷酸注射到哺乳动物的肌肉中，其中所述多核苷酸被肌肉的细胞吸收，并施加 对哺乳动物的治疗作用。 该方法可用于向哺乳动物的细胞递送治疗性多肽，以在多核苷酸的体内翻译中提供免疫应答，递送反义多核苷酸，将受体递送至哺乳动物的细胞或提供短暂的基因治疗 。
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公开(公告)号：US08129509B2
公开(公告)日：2012-03-06
申请号：US10413942
申请日：2003-04-15
CPC分类号： G01N33/532 , C07H21/00
摘要： Compounds and methods are provided for a single-step covalent attachment of a label to a molecule comprising forming a covalently attachable labeling reagent for alkylating the molecule. Then, combining the covalently attachable labeling reagent with a mixture containing the molecule, under conditions wherein the labeling reagent has reactivity with the molecule thereby forming a covalent bond.
摘要翻译： 提供了化合物和方法用于将标记物与分子的单步共价连接，包括形成用于烷基化分子的共价连接的标记试剂。 然后，在标记试剂与分子具有反应性，从而形成共价键的条件下，将可共价连接的标记试剂与含有该分子的混合物结合。
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公开(公告)号：US08017109B2
公开(公告)日：2011-09-13
申请号：US12140703
申请日：2008-06-17
申请人： Darren H. Wakefield , David B. Rozema , Sean D. Monahan , Lori Higgs , Jon A. Wolff , James E. Hagstrom
发明人： Darren H. Wakefield , David B. Rozema , Sean D. Monahan , Lori Higgs , Jon A. Wolff , James E. Hagstrom
IPC分类号： A61K31/74
CPC分类号： C12N15/87 , A01K2217/058 , A01K2267/0362 , A61K47/58
摘要： The present invention is directed to membrane active polymers useful for cellular delivery of compounds. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.
摘要翻译： 本发明涉及可用于细胞递送化合物的膜活性聚合物。 描述了将靶向，抗调理作用，抗聚集和转染活性结合到小的生物相容性体内递送缀合物中的多偶联体系。 使用可逆修饰提供了生理反应活性调节。
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公开(公告)号：US07781415B2
公开(公告)日：2010-08-24
申请号：US10770588
申请日：2004-02-03
申请人： Hans Herweijer , Julia Hegge , Jon A. Wolff , David L. Lewis
发明人： Hans Herweijer , Julia Hegge , Jon A. Wolff , David L. Lewis
IPC分类号： A61K48/00
CPC分类号： A61K48/0083
摘要： A process for delivering a polynucleotide to a cardiac tissue cell in a mammal is described, comprising introducing a composition consisting of a polynucleotide into a blood vessel and increasing permeability of the blood vessel to the polynucleotide. The polynucleotide can be a small interfering RNA or microRNA and inhibit gene expression in the cell.
摘要翻译： 描述了将多核苷酸递送至哺乳动物心脏组织细胞的方法，包括将由多核苷酸组成的组合物引入血管并增加血管对多核苷酸的通透性。 多核苷酸可以是小干扰RNA或微小RNA并抑制细胞中的基因表达。
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9.发明授权Devices and processes for distribution of genetic material to mammalian limb 有权将遗传物质分配给哺乳动物肢体的装置和方法公开(公告)号：US07642248B2
公开(公告)日：2010-01-05
申请号：US11694140
申请日：2007-03-30
申请人： Vladimir G. Budker , Jon A. Wolff
发明人： Vladimir G. Budker , Jon A. Wolff
IPC分类号： A61K31/70
CPC分类号： A61K48/0075
摘要： A process is described for the delivery of a therapeutic polynucleotide to limb muscle tissue suffering from or potentially suffering from Muscular Dystrophy. The polynucleotide is inserted into a mammalian limb vessel such as an artery. Delivery efficiency and distribution is enhanced by combining injection of a solution containing the polynucleotide with the use of an externally applied cuff.
摘要翻译： 描述了将治疗性多核苷酸递送至患有或可能患有肌营养不良症的肢体肌肉组织的方法。 将多核苷酸插入哺乳动物肢体血管如动脉。 通过将含有多核苷酸的溶液的注入与使用外部应用的袖带组合来提高递送效率和分布。
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公开(公告)号：US07589059B2
公开(公告)日：2009-09-15
申请号：US10628792
申请日：2003-07-28
申请人： Jon A. Wolff , Vladimir G. Budker , Hans Herweijer , James E. Hagstrom , Sean D. Monahan , Julia Hegge , Vladimir Subbotin
发明人： Jon A. Wolff , Vladimir G. Budker , Hans Herweijer , James E. Hagstrom , Sean D. Monahan , Julia Hegge , Vladimir Subbotin
CPC分类号： A61K9/0019 , A61K38/00 , A61K48/0075 , C12N15/87 , C12N2799/022
摘要： Disclosed is a system for providing in vivo delivery of molecules or complexes to extravascular mammalian cells using an intravascular administration route. The molecules or complexes are inserted in an injection solution into a mammalian vasculature. Insertion of the injection solution at an appropriate rate transiently increases the volume of extravascular fluid in the tissue thereby facilitating delivery of the molecule to the cell.
摘要翻译： 公开了一种使用血管内施用途径向血管外哺乳动物细胞体内递送分子或复合物的系统。 将分子或复合物插入哺乳动物脉管系统的注射溶液中。 以适当的速率插入注射溶液瞬时增加组织中血管外流体的体积，从而便于将分子递送至细胞。
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