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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. 发明专利

AU683400B2 Use of a bacterial component to enhance targeted delivery of polynucleotides to cells 未知
公开(公告)号：AU683400B2
公开(公告)日：1997-11-06
申请号：AU2950295
申请日：1995-06-27
申请人： UNIV CONNECTICUT , TARGETECH INC
发明人： WU GEORGE Y , WU CATHERINE H , ZHANG YING , SPITALNY GEORGE L , CARMICHAEL ELLEN
IPC分类号： C12N15/09 , A61K47/48 , 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.

3. 发明专利

AU704562B2 Anti-hepatitis B poly- and oligonucleotides 未知
公开(公告)号：AU704562B2
公开(公告)日：1999-04-29
申请号：AU1680095
申请日：1995-01-11
申请人： TARGETECH INC A WHOLLY OWNED S
发明人： CARMICHAEL ELLEN
IPC分类号： G01N33/566 , A61K38/00 , A61K47/48 , A61K48/00 , A61P1/16 , A61P31/12 , C07H21/04 , C12N15/00 , C12N15/09 , C12N15/113 , C12R1/92 , G01N33/576 , C12N15/11 , A61K31/70

4. 发明专利

AU2155092A TARGETED DELIVERY OF GENES ENCODING IMMUNOGENIC PROTEINS 未知
公开(公告)号：AU2155092A
公开(公告)日：1992-12-30
申请号：AU2155092
申请日：1992-05-14
申请人： TARGETECH INC , UNIVERSITY OF CONNECTICUT THE
发明人： GEORGE Y WU , GEORGE L SPITALNY , MARK A FINDEIS
IPC分类号： A61K38/00 , A61K39/29 , A61K39/395 , A61K47/48 , A61K48/00 , C07K16/00 , C07K16/08 , C12N15/87 , C12P21/08
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.

5. 发明专利

CA2103064A1 TARGETED DELIVERY OF GENES ENCODING IMMUNOGENIC PROTEINS 未知
公开(公告)号：CA2103064A1
公开(公告)日：1992-11-15
申请号：CA2103064
申请日：1992-05-14
申请人： UNIV CONNECTICUT , TARGETECH INC
发明人： WU GEORGE Y , SPITALNY GEORGE L , FINDEIS MARK A
IPC分类号： A61K38/00 , A61K39/29 , A61K39/395 , A61K47/48 , A61K48/00 , C07K16/00 , C07K16/08 , C12N15/87 , C12P21/08 , A61K31/70 , A61K39/42
摘要： 2103064 9220316 PCTABS00017 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.

6. 发明专利

AU704562C Anti-hepatitis B poly- and oligonucleotides 未知
公开(公告)号：AU704562C
公开(公告)日：2007-08-23
申请号：AU1680095
申请日：1995-01-11
申请人： TARGETECH INC A WHOLLY OWNED S
发明人： CARMICHAEL ELLEN
IPC分类号： G01N33/566 , A61K38/00 , A61K47/48 , A61K48/00 , A61P1/16 , A61P31/12 , C07H21/04 , C12N15/00 , C12N15/09 , C12N15/113 , C12R1/92 , G01N33/576

7. 发明专利

AU686614B2 Targeted delivery of genes encoding antisense polyribonucleotides 未知
公开(公告)号：AU686614B2
公开(公告)日：1998-02-12
申请号：AU6497894
申请日：1994-04-04
申请人： UNIV CONNECTICUT , TARGETECH INC
发明人： CHIOU HENRY C , INNAIMO STEVEN F , WU GEORGE Y
IPC分类号： C12N15/09 , A61K31/70 , A61K47/48 , A61K48/00 , A61P31/00 , A61P31/04 , A61P31/12 , C07H21/04 , C12N9/00 , C12N15/113 , C12N15/87 , C12R1/92 , C12N15/11

8. 发明专利

AU6497894A Targeted delivery of genes encoding antisense polyribonucleotides 未知
公开(公告)号：AU6497894A
公开(公告)日：1994-10-24
申请号：AU6497894
申请日：1994-04-04
申请人： TARGETECH INC , UNIVERSITY OF CONNECTICUT THE
发明人： CHIOU HENRY C , INNAIMO STEVEN F , WU GEORGE Y
IPC分类号： C12N15/09 , A61K31/70 , A61K47/48 , A61K48/00 , A61P31/00 , A61P31/04 , A61P31/12 , C07H21/04 , C12N9/00 , C12N15/113 , C12N15/87 , C12R1/92 , C12N15/11
摘要： Molecular complexes for targeting a gene encoding an antisense polyribonucleotide to a specific cell in vivo obtaining production of the polyribonucleotide within the targeted cell, and effecting specific inhibition of the expression of cellular or noncellular genes are disclosed. An expressible gene encoding a desired antisense polyribonucleotide is complexed to a conjugate 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 in antisense gene therapy to selectively transfect cells in vivo or in vitro to provide for production of the antisense polyribonucleotide within the targeted cell, and inhibition of the expression of cellular or noncellular genes.

9. 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。

10. 发明申请

WO9518636A3 HEPATOCYTE-TARGETED DRUG CONJUGATES 审中-公开
标题翻译：肝细胞靶向药物偶联物
公开(公告)号：WO9518636A3
公开(公告)日：1995-08-10
申请号：PCT/US9500448
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： A61K47/48
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：本发明提供了用于将治疗剂靶向具有去唾液酸糖蛋白受体的细胞的缀合物。缀合物包含治疗剂和去唾液酸糖蛋白受体的配体，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，所述治疗剂是核苷类似物或秋水仙碱，并且所述配体是酪氨酰（谷氨酰） - 谷氨酸的asialoorosomucoid，阿拉伯半乳聚糖或Tris-（N-乙酰半乳糖胺氨基己糖苷）酰胺。优选的交联剂包括氨酰基衍生物，羧酰基衍生物，磷酸盐，肽和还原性不稳定交联剂。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，例如抑制病毒感染的肝细胞中的病毒DNA复制。

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