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1. 发明申请

US20090208461A1 RECOMBINANT BACTERIA WITH E.COLI HEMOLYSIN SECRETION SYSTEM AND INCREASED EXPRESSION AND/OR SECRETION OF HLYA, PROCESS OF MANUFACTURING AND USES THEREOF 审中-公开
标题翻译：具有E.COLI HEMOLYSIN分泌系统的重组细菌和增加的HLYA的表达和/或分泌，其制造过程及其用途
公开(公告)号：US20090208461A1
公开(公告)日：2009-08-20
申请号：US12365944
申请日：2009-02-05
申请人： Christian HOTZ , Ivaylo Gentschev , Ulf Rapp , Werner Goebel , Joachim Fensterle
发明人： Christian HOTZ , Ivaylo Gentschev , Ulf Rapp , Werner Goebel , Joachim Fensterle
IPC分类号： A61K35/74 , C12N1/21 , C12N15/87
CPC分类号： C07K14/245 , C07K14/255 , C07K2319/036 , C12N1/20
摘要： The invention relates to a recombinant bacterium with E. coli hemolysin secretion system and increased expression and/or increased secretion of full length or partial HlyA.
摘要翻译：本发明涉及具有大肠杆菌溶血素分泌系统并增加全长或部分HlyA的表达和/或增加的分泌的重组细菌。

2. 发明申请

US20060105423A1 Microorganisms as carriers of nucleotide sequences coding for cell antigens used for the treatment of tumors 审中-公开
标题翻译：微生物作为编码用于治疗肿瘤的细胞抗原的核苷酸序列的载体
公开(公告)号：US20060105423A1
公开(公告)日：2006-05-18
申请号：US10506096
申请日：2003-02-13
申请人： Ulf Rapp , Werner Goebel , Ivaylo Gentschev , Joachim Fensterle
发明人： Ulf Rapp , Werner Goebel , Ivaylo Gentschev , Joachim Fensterle
IPC分类号： C07K14/195 , C07K14/245 , C07H21/04 , C12P21/06 , C12N15/74 , C12N1/21
CPC分类号： C12N9/1205 , A61K39/00 , A61K39/0011 , A61K2039/523 , A61K2039/53 , C07K14/255 , C07K14/4748 , C07K2319/02 , C12R1/42
摘要： The invention relates to a microorganism with a nucleotide sequence coding for a cell antigen in which the following components are inserted and are expressible: I) a nucleotide sequence coding for at least one epitope of an antigen of a tumor cell and/or a nucleotide sequence for at least one epitope of an antigen that is specific for a tissue cell from which the tumor originates; II) an optional nucleotide sequence coding for a protein that stimulates cells of the immune system; IIIA) a nucleotide sequence for a transport system which makes it possible to express the expression product of components I) and, optionally, II) on the outer surface of the bacterium and/or secrete the expression product of component I) and, optionally, of component II); and/or IIIB) a nucleotide sequence for a protein used for lysing the microorganisms in the cytosol of mammalian cells and for intracellularly releasing plasmids which are contained in the lysed microorganisms; and IV) an activation sequence for expressing one or several of components I) to IIIB), said activation sequence being selected among the group consisting of an activation sequence which is capable of being activated in the microorganism, is tissue-cell-specific but not cell-specific. Each of components I) to IV) can be identically or differently arranged in an individual or multiple manner. Also disclosed are uses of such a microorganism for the production of a medicament.
摘要翻译：本发明涉及具有编码细胞抗原的核苷酸序列的微生物，其中插入以下组分并且是可表达的：I）编码肿瘤细胞抗原和/或核苷酸序列的至少一个表位的核苷酸序列对于来自肿瘤的组织细胞特异性的抗原的至少一个表位; II）编码刺激免疫系统细胞的蛋白质的任选的核苷酸序列; IIIA）用于运输系统的核苷酸序列，其使得可以在细菌的外表面上表达组分I）和任选的II）的表达产物和/或分泌组分I）的表达产物，并且任选地，的组分II）; 和/或IIIB）用于裂解哺乳动物细胞的细胞质中的微生物和细胞内释放裂解微生物中所含质粒的蛋白质的核苷酸序列; 和IV）用于表达组分I）至IIIB）中的一种或几种的活化序列，所述活化序列选自能够在微生物中活化的活化序列是组织细胞特异性但不是组织细胞特异性细胞特异性组件I）至IV中的每一个）可以以单独或多种方式相同或不同地布置。还公开了这种微生物用于制备药物的用途。

3. 发明申请

US20050244374A1 Enveloped miroorganism 审中-公开
标题翻译：包容的微生物
公开(公告)号：US20050244374A1
公开(公告)日：2005-11-03
申请号：US10504944
申请日：2003-02-13
申请人： Werner Goebel , Ulf Rapp , Hans-Harald Sedlacek , Joachim Fensterle , Ivaylo Gentschev
发明人： Werner Goebel , Ulf Rapp , Hans-Harald Sedlacek , Joachim Fensterle , Ivaylo Gentschev
IPC分类号： C12N15/09 , A61K35/74 , A61K35/76 , A61K39/00 , A61K48/00 , A61P29/00 , A61P35/00 , A61P35/02 , A61P37/02 , A61P37/06 , C07K14/705 , C07K14/765 , C12N1/00 , C12N1/21 , C12N7/04 , C12N9/24 , C12N15/63 , C12N15/74
CPC分类号： C12Y302/01031 , A61K48/00 , A61K48/0008 , C07K14/70575 , C07K14/765 , C07K2319/02 , C12N9/16 , C12N9/2402 , C12N9/2434 , C12N15/74 , C12Y301/16001
摘要： The invention relates to an enveloped microorganism in whose genome the following components are inserted and can be expressed: I) a nucleotide sequence that encodes a directly or indirectly, antiproliferatively or cytotoxically active expression product or a plurality of said expression products, II) a nucleotide sequence that encodes or is constitutively active for a blood plasma protein under the control of a activation sequence that can be activated in the microorganism, III) optionally, a nucleotide sequence that encodes or is constitutively active for a cell-specific ligand under the control of an activation sequence that can be activated in the microorganism, IV) a nucleotide sequence for a transport system that induces expression of the expression products of components I) and II) and optionally III) on the outer surface of the microorganism or that induces secretion of the expression products of component I) and expression of component II) and optionally component III) and that is preferably constitutively active, V) optionally a nucleotide sequence for a protein used for lysis of the microorganism in the cytosol of mammalian cells and for the intracellular release of plasmids with at least one or more components I) and VI) contained in the lysed microorganism, and VI) an activation sequence that can be activated in the microorganism, and/or that is tissue-specific, tumor cell-specific, function-specific or not cell-specific, for expressing component I). The inventive microorganism is further characterized in that any of components I) to VI) can be present either single or several times, and can be either identical or different.
摘要翻译：本发明涉及其包含的微生物，其基因组中插入以下组分并可以表达：I）编码直接或间接抗增殖或细胞活性的表达产物或多种所述表达产物的核苷酸序列，II）核苷酸在可在微生物中活化的活化序列的控制下编码或组成型的血浆蛋白质的序列，III）任选地，编码或组成型活性的细胞特异性配体的控制下的核苷酸序列可以在微生物中活化的活化序列，IV）诱导表达产物的转运体系的核苷酸序列，其诱导组分I）和II）和任选地III）的表达产物在微生物的外表面上，或诱导分泌组分I）和组分II）和任选的组分III）和tha的表达产物 t优选是组成型活性的，V）任选的用于在哺乳动物细胞的细胞溶质中裂解微生物的蛋白质的核苷酸序列，以及用裂解的细胞内含有至少一种或多种组分I）和VI）的质粒的细胞内释放的核苷酸序列微生物和VI）可以在微生物中活化的活化序列和/或组织特异性，肿瘤细胞特异性，功能特异性或非细胞特异性的表达组分I）的活化序列。本发明的微生物的特征还在于组分I）至VI）中的任何一种可以单独或多次存在，并且可以是相同的或不同的。

4. 发明申请

US20060240038A1 Cells used as carriers for bacteria 审中-公开
标题翻译：细胞用作细菌的载体
公开(公告)号：US20060240038A1
公开(公告)日：2006-10-26
申请号：US10559663
申请日：2004-06-07
申请人： Joachim Fensterle , Werner Goebel , Ulf Rapp , Jochen Stritzker , Andreas Schmidt , Ivatlo Gentschev , Tamara Potapenko
发明人： Joachim Fensterle , Werner Goebel , Ulf Rapp , Jochen Stritzker , Andreas Schmidt , Ivatlo Gentschev , Tamara Potapenko
IPC分类号： A61K39/12
CPC分类号： A61K35/17 , A61K35/12 , A61K35/13 , A61K35/15 , A61K35/74 , A61K2035/11 , A61K2039/5152 , A61K2039/5154 , A61K2039/521 , A61K2039/522 , A61K2039/523 , Y02A50/478 , Y02A50/484
摘要： The invention relates to the use of a cell, which is charged with a micro-organism that contains foreign DNA, in particular a bacterial micro-organism, to produce a pharmaceutical composition. Preferably, the foreign DNA codes for a defined active agent and the pharmaceutical composition is designed for use in the prophylaxis or treatment of a disease that can be treated with said active agent.
摘要翻译：本发明涉及细胞的使用，其中装有含有外来DNA的微生物，特别是细菌微生物，以产生药物组合物。优选地，将限定的活性剂和药物组合物的外源DNA编码设计用于预防或治疗可用所述活性剂治疗的疾病。

5. 发明申请

US20120171159A1 NON-PATHOGENIC AND/OR ATTENUATED BACTERIA CAPABLE OF INDUCING APOPTOSIS IN MACROPHAGES, PROCESS OF MANUFACTURING AND USES THEREOF 失效
标题翻译：非致病性和/或破坏性细菌可诱发巨噬细胞病变，制造过程及其用途
公开(公告)号：US20120171159A1
公开(公告)日：2012-07-05
申请号：US13364437
申请日：2012-02-02
申请人： Joachim Fensterle , Katharina Galmbacher , Ulf Rapp , Werner Goebel , Christian Hotz
发明人： Joachim Fensterle , Katharina Galmbacher , Ulf Rapp , Werner Goebel , Christian Hotz
IPC分类号： A61K35/74 , A61P35/02 , A61P31/00 , A61P3/10 , A61P31/04 , A61P31/16 , A61P29/00 , A61P37/00 , A61P35/00 , A61P31/12
CPC分类号： C12N1/20 , A61K35/74 , C12R1/42 , Y02A50/471 , Y02A50/473 , Y02A50/475 , Y02A50/483
摘要： The invention relates to an non-pathogenic and/or attenuated bacterium which is capable of inducing apoptosis in macrophages.
摘要翻译：本发明涉及能诱导巨噬细胞凋亡的非致病和/或减毒细菌。

6. 发明授权

US08679473B2 Non-pathogenic and/or attenuated bacteria capable of inducing apoptosis in macrophages, process of manufacturing and uses thereof 失效
标题翻译：能够诱导巨噬细胞凋亡的非致病性和/或减毒细菌，制造方法及其用途
公开(公告)号：US08679473B2
公开(公告)日：2014-03-25
申请号：US13364437
申请日：2012-02-02
申请人： Joachim Fensterle , Katharina Galmbacher , Ulf Rapp , Werner Goebel , Christian Hotz
发明人： Joachim Fensterle , Katharina Galmbacher , Ulf Rapp , Werner Goebel , Christian Hotz
IPC分类号： A01N63/00 , A01N65/00
CPC分类号： C12N1/20 , A61K35/74 , C12R1/42 , Y02A50/471 , Y02A50/473 , Y02A50/475 , Y02A50/483
摘要： The invention relates to an non-pathogenic and/or attenuated bacterium which is capable of inducing apoptosis in macrophages.
摘要翻译：本发明涉及能诱导巨噬细胞凋亡的非致病和/或减毒细菌。

7. 发明申请

US20110287037A1 MICROORGANISMS AS CARRIERS OF NUCLEOTIDE SEQUENCES CODING FOR ANTIGENS AND PROTEIN TOXINS, PROCESS OF MANUFACTURING AND USES THEREOF 有权
标题翻译：微生物作为核苷酸序列编码抗原和蛋白质毒素的方法，其制造方法及其用途
公开(公告)号：US20110287037A1
公开(公告)日：2011-11-24
申请号：US11939254
申请日：2007-11-13
申请人： Ivaylo Nikolov Gentschev , Joachim Fensterle , Ulf R. Rapp , Werner Goebel
发明人： Ivaylo Nikolov Gentschev , Joachim Fensterle , Ulf R. Rapp , Werner Goebel
IPC分类号： A61K35/66 , A61K39/12 , A61K39/02 , A61K39/145 , A61P37/00 , A61P35/00 , A61P35/02 , A61P31/00 , A61P31/12 , A61P31/04 , A61P29/00 , A61P31/16 , C12N1/21 , C12N15/63 , A61K39/00
CPC分类号： C12N15/62 , A61K39/00 , A61K2039/5156 , A61K2039/523 , A61K2039/6037 , C07K2319/02 , C07K2319/035 , C07K2319/036 , C07K2319/55 , C12N15/625 , Y02A50/472 , Y02A50/476 , Y02A50/484
摘要： The invention relates to a microorganism as a carrier of nucleotide sequences coding for antigens and protein toxins comprising the following components: (I) at least one nucleotide sequence coding for at least one complete or partial antigen of at least one wild-type or mutated protein; and (II) at least one nucleotide sequence coding for at least one protein toxin and/or at least one protein toxin subunit; and (III) a) at least one nucleotide sequence coding for at least one transport system which enables the expression of the expression products of component (I) and component (II) on the outer surface of the microorganism and/or enables the secretion of the expression products of component (I) and component (II); and/or coding for at least one signal sequence which enables the secretion of the expression products of component (I) and component (II); and/or (III) b) optionally, at least one nucleotide sequence coding for at least one protein for lysing the microorganism in the cytosol of mammalian cells and for intracellularly releasing plasmids or expression vectors, which are contained in the lysed microorganism; and (IV) at least one nucleotide sequence for at least one activation sequence for the expression of one or more of components (I) to (III), wherein said activation sequence can be activated in the microorganism and/or is tissue cell-specific, tumor cell-specific, macrophage-specific, dendrite-specific, lymphocyte-specific, function-specific or non-cell-specific”; wherein any of components (I) to (IV) can be present either once or several times and either identical or different. Also disclosed are a process of manufacturing thereof, corresponding plasmids or expression vectors and uses of the microorganism as a medicament.
摘要翻译：本发明涉及作为编码抗原和蛋白质毒素的核苷酸序列的载体的微生物，其包含以下组分：（I）编码至少一种野生型或突变型蛋白质的至少一种完整或部分抗原的至少一种核苷酸序列 ; 和（II）编码至少一种蛋白质毒素和/或至少一种蛋白质毒素亚基的至少一个核苷酸序列; 和（III）a）至少一个编码至少一种能够在组织（I）和组分（II）的表达产物在微生物外表面上表达的转运系统的核苷酸序列和/或使得能够分泌组分（I）和组分（II）的表达产物; 和/或编码能够分泌组分（I）和组分（II）的表达产物的至少一种信号序列; 和/或（III）b）任选地至少一种编码至少一种蛋白质的核酸序列，用于裂解哺乳动物细胞的细胞质中的微生物和细胞内释放质粒或表达载体，所述质粒或表达载体包含在裂解的微生物中; 至少一个用于表达一种或多种组分（I）至（III）的活化序列的至少一个核苷酸序列，其中所述活化序列可以在微生物中活化和/或是组织细胞特异性，肿瘤细胞特异性，巨噬细胞特异性，枝晶特异性，淋巴细胞特异性，功能特异性或非细胞特异性“; 其中组分（I）至（IV）中的任何一种可以存在一次或几次，并且相同或不同。还公开了其制备方法，相应的质粒或表达载体以及微生物作为药物的用途。

8. 发明授权

US08669091B2 Microorganisms as carriers of nucleotide sequences coding for antigens and protein toxins, process of manufacturing and uses thereof 有权
标题翻译：微生物作为编码抗原和蛋白质毒素的核苷酸序列的载体，其制备方法及其用途
公开(公告)号：US08669091B2
公开(公告)日：2014-03-11
申请号：US11939254
申请日：2007-11-13
申请人： Ivaylo Nikolov Gentschev , Joachim Fensterle , Ulf R. Rapp , Werner Goebel
发明人： Ivaylo Nikolov Gentschev , Joachim Fensterle , Ulf R. Rapp , Werner Goebel
IPC分类号： A01N63/00 , A61K48/00 , C12N1/20
CPC分类号： C12N15/62 , A61K39/00 , A61K2039/5156 , A61K2039/523 , A61K2039/6037 , C07K2319/02 , C07K2319/035 , C07K2319/036 , C07K2319/55 , C12N15/625 , Y02A50/472 , Y02A50/476 , Y02A50/484
摘要： A Escherichia, Salmonella, Yersinia, Vibrio, Listeria, Shigella, or Pseudomonas bacterium that has the following components: (I) a polynucleotide encoding a heterologous antigenic determinant that induces a CTL response against a tumor cell; (II) a polynucleotide encoding a heterologous protein toxin or toxin subunit; and (III) (a) a polynucleotide encoding a transport system that expresses the products of (I) and (II) on the outer surface of the bacterium or that secretes products of (I) and (II) from the bacterium; and (IV) a polynucleotide that activates the expression of one or more of (I). (II), and/Or (III) in the bacterium wherein polynucleotides (I), (II), (III) and (IV) are different from each other and polynucleotides (I), (II) and (III) encode proteins that are different from each other.
摘要翻译：具有以下组分的大肠杆菌，沙门氏菌，耶尔森氏菌，弧菌属，利斯特氏菌属，志贺氏菌属或假单胞菌属细菌：（I）编码诱导针对肿瘤细胞的CTL应答的异源抗原决定簇的多核苷酸; （II）编码异源蛋白毒素或毒素亚基的多核苷酸; 和（III）（a）编码在细菌外表面上表达（I）和（II）的产物的运输系统的多核苷酸，或从细菌中分泌（I）和（II）的产物; 和（IV）激活（I）中的一种或多种的表达的多核苷酸。（I），（II），（III）和（IV）彼此不同的细菌中的多核苷酸（II）和/或（III），并且多核苷酸（I），（II）和（III）这是不同的。

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