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。

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。

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。