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1. 发明公开

EP0804603A1 USE OF A BACTERIAL COMPONENT TO ENHANCE TARGETED DELIVERY OF POLYNUCLEOTIDES TO CELLS 失效
标题翻译：有向BAKTERIELER组件POLYNUKLEOTIDENAUSLIEFERUNG到细胞来提高应用
公开(公告)号：EP0804603A1
公开(公告)日：1997-11-05
申请号：EP95925331.0
申请日：1995-06-27
申请人： TARGETECH, INC. , TARGETECH, INC.
发明人： WU, George, Y. , WU, Catherine, H. , ZHANG, Ying , SPITALNY, George, L. , CARMICHAEL, Ellen
IPC分类号： C12N15 , A61K47
CPC分类号： C12N15/87
摘要： An improved soluble molecular complex for targeting a polynucleotide to a specific cell is disclosed. The molecular complex comprises: (a) a polynucleotide; (b) a carrier made up of a polynucleotide binding agent and a cell-specific binding agent which binds to a surface molecule of the cell and is internalized into an endosome, and (c) a bacterial component or fragment thereof which lyses the endosome and causes the polynucleotide to be released into the cytoplasm of the cell. In a preferred embodiment of the invention the polynucleotide binding agent is polylysine, the cell-specific binding agent is an asialoglycoprotein, and the bacterial component is listeriolysin O. The disclosed soluble molecular complex and methods of use can be used therapeutically to deliver genes and antisense polynucleotides to specific cells in vivo.

2. 发明申请

WO1996000792A1 USE OF A BACTERIAL COMPONENT TO ENHANCE TARGETED DELIVERY OF POLYNUCLEOTIDES TO CELLS 审中-公开
标题翻译：使用细菌成分加强定向细胞转运多细胞
公开(公告)号：WO1996000792A1
公开(公告)日：1996-01-11
申请号：PCT/US1995008091
申请日：1995-06-27
申请人： UNIVERSITY OF CONNECTICUT , TARGETECH, INC.
发明人： UNIVERSITY OF CONNECTICUT , TARGETECH, INC. , WU, George, Y. , WU, Catherine, H. , ZHANG, Ying , SPITALNY, George, L. , CARMICHAEL, Ellen
IPC分类号： C12N15/87
CPC分类号： C12N15/87
摘要： An improved soluble molecular complex for targeting a polynucleotide to a specific cell is disclosed. The molecular complex comprises: (a) a polynucleotide; (b) a carrier made up of a polynucleotide binding agent and a cell-specific binding agent which binds to a surface molecule of the cell and is internalized into an endosome, and (c) a bacterial component or fragment thereof which lyses the endosome and causes the polynucleotide to be released into the cytoplasm of the cell. In a preferred embodiment of the invention the polynucleotide binding agent is polylysine, the cell-specific binding agent is an asialoglycoprotein, and the bacterial component is listeriolysin O. The disclosed soluble molecular complex and methods of use can be used therapeutically to deliver genes and antisense polynucleotides to specific cells in vivo.
摘要翻译：公开了将多核苷酸靶向特定细胞的改进的可溶性分子复合物。分子复合物包括：（a）多核苷酸; （b）由多核苷酸结合剂和细胞特异性结合剂构成的载体，其与细胞的表面分子结合并内化于内体，以及（c）裂解内体的细菌成分或片段，导致多核苷酸被释放到细胞的细胞质中。在本发明的一个优选实施方案中，多核苷酸结合剂是聚赖氨酸，细胞特异性结合剂是脱唾液酸糖蛋白，细菌组分是赖斯特赖菌素O.所公开的可溶性分子复合物和使用方法可用于治疗性递送基因和反义多核苷酸体内特异性细胞。

3. 发明公开

EP0584279A1 TARGETED DELIVERY OF GENES ENCODING IMMUNOGENIC PROTEINS 失效转让
标题翻译：展望基因免疫原性蛋白CODE供应。
公开(公告)号：EP0584279A1
公开(公告)日：1994-03-02
申请号：EP92913964.0
申请日：1992-05-14
申请人： THE UNIVERSITY OF CONNECTICUT , TARGETECH, INC.
发明人： WU, George, Y. , SPITALNY, George, L. , FINDEIS, Mark, A.
IPC分类号： A61K38 , A61K39 , A61K47 , A61K48 , C07K16 , C12N15 , C12P21
CPC分类号： C12N15/87 , A61K39/12 , A61K39/292 , A61K47/645 , A61K48/00 , A61K2039/53 , A61K2039/6093 , C07K16/00 , C07K16/082 , C12N2730/10134
摘要： Des complexe moléculaires peuvent être utilisés pour donner comme cible à un gène codant une protéine ou un polypeptide immunogène une cellule spécifique in vivo. Ledit gène est incorporé à une cellule cible et primé, puis le produit codé par le gène est sécrété et une réponse immunitaire à la protéine ou au polypeptide immunogène est obtenue. Le complexe moléculaire comprend un gène exprimable codant une protéine ou un polypeptide immunogène désiré(e) complexé(e) avec un porteur qui est un conjugué d'un agent de fixation spécifique à la cellule et d'un agent de fixation du gène. L'agent de fixation spécifique à la cellule est spécifique à la structure de la surface cellulaire qui induit l'internalisation de ligands par endocytose. Cet agent de fixation peut être par exemple le récepteur d'asialoglycoprotéine d'hépatocytes. L'agent de fixation du gène est un composé tel qu'un polycation qui complexe de façon stable le gène dans des conditions extracellulaires et libère le gène dans des conditions intracellulaires de façon qu'il puisse fonctionner à l'intérieur d'une cellule. Le complexe moléculaire est stable et soluble dans des liquides physiologiques et il peut être utilisé pour créer une réponse immunitaire à toute une variété d'immunogène dans un organisme, à des fins de vaccination ou pour la production d'anticorps.

4. 发明申请

WO1995018636A2 HEPATOCYTE-TARGETED DRUG CONJUGATES 审中-公开
标题翻译： HEPATOCYTE定向药物联合
公开(公告)号：WO1995018636A2
公开(公告)日：1995-07-13
申请号：PCT/US1995000448
申请日：1995-01-11
申请人： TARGETECH, INC.
发明人： TARGETECH, INC. , PLOURDE, Robert, Jr. , CARMICHAEL, Ellen , SPITALNY, George, L. , FINDEIS, Mark, A. , ERNST, Michael, F. , ROBINSON, Brett
IPC分类号： A61K47/48
CPC分类号： A61K47/62 , A61K47/61
摘要： The invention provides conjugates for targeting a therapeutic agent to a cell with asialoglycoprotein receptors. The conjugates comprise a therapeutic agent and ligand for the asialoglycoprotein receptor, wherein the therapeutic agent and the ligand are linked by a bridging agent. The bridging agent can be a crosslinker, a polyfunctional carrier molecule or a crosslinker and a polyfunctional carrier molecule. In a preferred embodiment, the therapeutic agent is a nucleoside analog or colchicine and the ligand is asialoorosomucoid, arabinogalactan or a Tris-(N-acetyl galactosamine aminohexyl glycoside) amide of tyrosyl(glutamyl)-glutamate. Preferred crosslinkers include aminoacyl derivatives, carboxyacyl derivatives, phosphate, peptides and reductively-labile crosslinkers. Preferred polyfunctional carrier molecules include polyamino acids and polysaccharides. The conjugates of the invention can be used to target a therapeutic agent to a cell, for example to inhibit viral DNA replication in a virally-infected hepatocyte.
摘要翻译：本发明提供用于将治疗剂靶向具有脱唾液酸糖蛋白受体的细胞的缀合物。缀合物包含用于脱唾液酸糖蛋白受体的治疗剂和配体，其中治疗剂和配体通过桥连剂连接。桥连剂可以是交联剂，多官能载体分子或交联剂和多官能载体分子。在一个优选的实施方案中，治疗剂是核苷类似物或秋水仙素，并且配体是阿糖胞苷类，阿拉伯半乳聚糖或酪氨酰（谷氨酰）谷氨酸的三 - （N-乙酰半乳糖胺氨基己基糖苷）酰胺。优选的交联剂包括氨基酰基衍生物，羧酰基衍生物，磷酸酯，肽和还原不稳定的交联剂。优选的多官能载体分子包括聚氨基酸和多糖。本发明的缀合物可用于将治疗剂靶向细胞，例如以抑制病毒感染的肝细胞中的病毒DNA复制。

5. 发明申请

WO1992020316A2 TARGETED DELIVERY OF GENES ENCODING IMMUNOGENIC PROTEINS 审中-公开
标题翻译：定点递送编码免疫原性蛋白的基因
公开(公告)号：WO1992020316A2
公开(公告)日：1992-11-26
申请号：PCT/US1992003875
申请日：1992-05-14
申请人： UNIVERSITY OF CONNECTICUT , TARGETECH, INC.
发明人： UNIVERSITY OF CONNECTICUT , TARGETECH, INC. , WU, George, Y. , SPITALNY, George, L. , FINDEIS, Mark, A.
IPC分类号： A61K0
CPC分类号： C12N15/87 , A61K39/12 , A61K39/292 , A61K47/645 , A61K48/00 , A61K2039/53 , A61K2039/6093 , C07K16/00 , C07K16/082 , C12N2730/10134
摘要： Molecular complexes can be used to target a gene encoding an immunogenic protein or polypeptide to a specific cell in vivo. The gene is incorporated into the target cell, expressed and the gene-encoded product is secreted and an immune response against the immunogenic protein or polypeptide is elicited. The molecular complex comprises an expressible gene encoding a desired immunogenic protein or polypeptide complexed with a carrier of a cell-specific binding agent and a gene-binding agent. The cell-specific binding agent is specific for a cellular surface structure which mediates internalization of ligands by endocytosis. An example is the asialoglycoprotein receptor of hepatocytes. The gene-binding agent is a compound such as a polycation which stably complexes the gene under extracellular conditions and releases the gene under intracellular conditions so that it can function within a cell. The molecular complex is stable and soluble in physiological fluids and can be used to elicit an immune response against a variety of immunogens in an organism for the purpose of vaccination or for the production of antibodies.
摘要翻译：分子复合物可用于将编码免疫原性蛋白或多肽的基因靶向体内特定细胞。该基因被并入目标细胞中，表达并且分泌基因编码的产物，并引发针对免疫原性蛋白质或多肽的免疫应答。分子复合物包含编码与细胞特异性结合剂和基因结合剂的载体复合的所需免疫原性蛋白质或多肽的可表达基因。细胞特异性结合剂对通过内吞作用介导配体内化的细胞表面结构是特异性的。一个例子是肝细胞的脱唾液酸糖蛋白受体。基因结合剂是诸如聚阳离子的化合物，其在细胞外条件下稳定地复合基因并在细胞内条件下释放基因，使得其可以在细胞内起作用。分子复合物是稳定的并且可溶于生理液体，并且可以用于在生物体内引发针对各种免疫原的免疫应答以用于疫苗接种或产生抗体。

6. 发明公开

EP0737077A1 HEPATOCYTE-TARGETED DRUG CONJUGATES 失效
标题翻译：肝细胞定向药物偶联物
公开(公告)号：EP0737077A1
公开(公告)日：1996-10-16
申请号：EP95908490.0
申请日：1995-01-11
申请人： TARGETECH, INC.
发明人： PLOURDE, Robert, Jr. , CARMICHAEL, Ellen , SPITALNY, George, L. , FINDEIS, Mark, A. , ERNST, Michael, F. , ROBINSON, Brett
IPC分类号： A61K47
CPC分类号： A61K47/62 , A61K47/61
摘要： The invention provides conjugates for targeting a therapeutic agent to a cell with asialoglycoprotein receptors. The conjugates comprise a therapeutic agent and ligand for the asialoglycoprotein receptor, wherein the therapeutic agent and the ligand are linked by a bridging agent. The bridging agent can be a crosslinker, a polyfunctional carrier molecule or a crosslinker and a polyfunctional carrier molecule. In a preferred embodiment, the therapeutic agent is a nucleoside analog or colchicine and the ligand is asialoorosomucoid, arabinogalactan or a Tris-(N-acetyl galactosamine aminohexyl glycoside) amide of tyrosyl(glutamyl)-glutamate. Preferred crosslinkers include aminoacyl derivatives, carboxyacyl derivatives, phosphate, peptides and reductively-labile crosslinkers. Preferred polyfunctional carrier molecules include polyamino acids and polysaccharides. The conjugates of the invention can be used to target a therapeutic agent to a cell, for example to inhibit viral DNA replication in a virally-infected hepatocyte.

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