公开(公告)号：US06416785B1

公开(公告)日：2002-07-09

申请号：US09644952

申请日：2000-08-23

申请人： Dieter Riesenberg ,  Volker Schroeckh ,  Burkhard Gitter ,  Wolfgang Neuberger

发明人： Dieter Riesenberg ,  Volker Schroeckh ,  Burkhard Gitter ,  Wolfgang Neuberger

IPC分类号： A61K9127

CPC分类号： A61K31/00

摘要： A new approach for targeting chemotherapeutics to focal bacterial infections is provided. Such focal infections are characterized by high densities of different bacteria and thus high concentrations of their extracellular signal molecules sensing the cell density. In gram-negative bacteria, one of such signal molecules is acyl-homoserine lactone (acyl-HSL, member of the autoinducer family AI-1), wherein species-specificity is achieved by acyl-residues, and HSLs are common for all gram-negative bacteria. In gram-positive bacteria, oligopeptides secreted by the bacteria communicate the cell density. In addition, there are cell density signal molecules (members of the autoinducer family AI-2) which communicate between gram-positive and gram-negative bacteria. The general scheme of the present invention is molecular modules that comprise both a targeting component and a chemotherapeutical component which serves for photodynamic antimicrobial chemotherapy (PACT). One preferred embodiment of the present invention is to target photosensitizers to the extracellular signal molecules instead of on the bacteria themselves. Targeting of the photosensitizers is mediated via molecules with efficient binding to the HSL-moiety of the acyl-HSL, so that a broad spectrum of gram-negative bacteria can be knocked out. Photosensitizers used in the present invention can be packed into special liposomes with lipid chelators or multiple coupled to dendrimers, so that they are especially effective for PACT. In addition, selected molecules with high affinity to a common moiety of such signal molecules, like HSL, may be used as molecular probes for the search of yet undiscovered cell density dependent signals.

摘要翻译： 提供了一种将化学治疗剂靶向局灶性细菌感染的新方法。 这种局部感染的特征在于不同细菌的高密度，因此其细胞外信号分子的高浓度感测细胞密度。 在革兰氏阴性细菌中，这种信号分子之一是酰基高丝氨酸内酯（酰基-HSL，自身诱导者家族AI-1的成员），其中通过酰基残基实现物种特异性，并且HSL对于所有革兰氏阴性细菌是常见的， 阴性细菌。 在革兰氏阳性细菌中，由细菌分泌的寡肽传播细胞密度。 此外，存在细胞密度信号分子（自体诱导者家族成员AI-2），其在革兰氏阳性和革兰氏阴性细菌之间进行通信。 本发明的一般方案是包含用于光动力学抗微生物化疗（PACT）的靶向组分和化学治疗组分的分子模块。 本发明的一个优选实施方案是将光敏剂靶向细胞外信号分子而不是细菌本身。 光敏剂的靶向通过与酰基HSL的HSL-部分有效结合的分子介导，从而可以敲除广谱的革兰氏阴性细菌。 本发明中使用的光敏剂可以用脂质螯合剂或多个偶联至树状聚合物的特殊脂质体包装，使得它们对于PACT特别有效。 此外，对这种信号分子（如HSL）的共同部分具有高亲和力的选择的分子可以用作搜索尚未发现的细胞密度相关信号的分子探针。

公开(公告)号：US06410270B1

公开(公告)日：2002-06-25

申请号：US09077549

申请日：1998-11-16

申请人： Wolfgang Strittmatter ,  Siegfried Matzku ,  Dieter Riesenberg ,  Uwe Horn ,  Uwe Knüpeer ,  Marian Kujau ,  Rolf Wenderoth ,  Andreas Plückthun ,  Anke Krebber

发明人： Wolfgang Strittmatter ,  Siegfried Matzku ,  Dieter Riesenberg ,  Uwe Horn ,  Uwe Knüpeer ,  Marian Kujau ,  Rolf Wenderoth ,  Andreas Plückthun ,  Anke Krebber

IPC分类号： C12N1500

CPC分类号： C07K16/2863 ,  C12N15/72 ,  C12P21/02

摘要： The invention relates to a fed-batch fermentation process which uses special E. coli host/vector systems for the purpose of efficiently forming recombinant proteins, in particular recombinant antibody molecules, preferably antibody fragments such as miniantibodies. Under the given conditions, the E. coli cells are able to grow at a maximum specific growth rate up to very high cell densities. After the recombinant product formation has been switched on, it is only the formed product which restricts growth; there is no growth restriction due to substrates or metabolic by-products. High space-time yields of recombinant proteins can be achieved in this manner.

摘要翻译： 本发明涉及一种补料分批发酵方法，其使用特殊的大肠杆菌宿主/载体系统，以有效形成重组蛋白，特别是重组抗体分子，优选抗体片段，例如微型抗体。 在给定的条件下，大肠杆菌细胞能够以最大比生长速率生长直到非常高的细胞密度。 在重组产物形成开始后，只有限制生长的形成产物; 由于底物或代谢副产物没有生长限制。 可以以这种方式实现重时蛋白质的高空时产量。