公开(公告)号：US20120052083A1

公开(公告)日：2012-03-01

申请号：US13190818

申请日：2011-07-26

申请人： Peter Sebo ,  Claude Leclerc ,  Adriana Osickova ,  Catherine Fayolle ,  Jiri Masin ,  Jan Krusek ,  Radim Osicka ,  Marek Basler

发明人： Peter Sebo ,  Claude Leclerc ,  Adriana Osickova ,  Catherine Fayolle ,  Jiri Masin ,  Jan Krusek ,  Radim Osicka ,  Marek Basler

IPC分类号： A61K39/385 ,  C12N9/96 ,  A61K38/51 ,  A61P35/00 ,  A61P31/12 ,  A61P31/18 ,  A61P31/04 ,  A61P31/10 ,  A61K39/10 ,  A61P33/00 ,  A61P37/04 ,  A61P31/16 ,  C12N9/88 ,  A61P31/14

CPC分类号： C12N9/88 ,  A61K38/00

摘要： The invention relates to mutant CyaA/E570Q+K860 polypeptides suitable for use as proteinaceous vectors for delivering one or more molecules of interest into a cell, in particular into a cell expressing the COM receptor. The invention further relates to polypeptide derivatives suitable for eliciting an immune response in a host.The invention is more particularly directed to polypeptides derived from an adenylate cyclase protein (CyaA) either under the form of a toxin or of a toxoid, which are mutant polypeptides. Said mutant polypeptides are capable of retaining the binding activity of native CyaA to a target cell and preferably of also retaining the translocating activity of native CyaA through its N-terminal domain into target cells and furthermore have a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.

摘要翻译： 本发明涉及适合用作蛋白质载体的突变型CyaA / E570Q + K860多肽，用于将一种或多种感兴趣的分子递送至细胞，特别是表达COM受体的细胞中。 本发明还涉及适于在宿主中引发免疫应答的多肽衍生物。 本发明更具体涉及衍生自作为突变体多肽的毒素或类毒素形式的腺苷酸环化酶蛋白（CyaA）的多肽。 所述突变体多肽能够将天然CyaA的结合活性保留到靶细胞，并且优选还将天然CyaA的易位活性通过其N-末端结构域保留到靶细胞中，并且还具有减少或抑制的造孔活性 与天然CyaA毒素相比。

公开(公告)号：US20120071393A1

公开(公告)日：2012-03-22

申请号：US13257569

申请日：2010-03-23

申请人： Peter Sebo ,  Adriana Osickova ,  Jiri Masin ,  Catherine Fayolle ,  Jan Krusek ,  Merek Basler ,  Claude Leclerc ,  Radim Osicka

发明人： Peter Sebo ,  Adriana Osickova ,  Jiri Masin ,  Catherine Fayolle ,  Jan Krusek ,  Merek Basler ,  Claude Leclerc ,  Radim Osicka

IPC分类号： A61K38/00 ,  A61P31/12 ,  A61P31/14 ,  C07K14/235 ,  A61P35/00

CPC分类号： C12N9/88 ,  C12Y406/01001

摘要： The invention relates to mutant CyaA/E570Q+K860 polypeptides suitable for use as proteinaceous vectors for delivering one or more molecules of interest into a cell, in particular into a cell expressing the CD11b receptor. The invention further relates to polypeptide derivatives suitable for eliciting an immune response in a host.The invention is more particularly directed to polypeptides derived from an adenylate cyclase protein (CyaA) either under the form of a toxin or of a toxoid, which are mutant polypeptides. Said mutant polypeptides are capable of retaining the binding activity of native CyaA to a target cell and preferably of also retaining the translocating activity of native CyaA through its N-terminal domain into target cells and furthermore have a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.

摘要翻译： 本发明涉及适用于蛋白质载体的突变型CyaA / E570Q + K860多肽，用于将一种或多种感兴趣的分子递送至细胞，特别是表达CD11b受体的细胞中。 本发明还涉及适于在宿主中引发免疫应答的多肽衍生物。 本发明更具体涉及衍生自作为突变体多肽的毒素或类毒素形式的腺苷酸环化酶蛋白（CyaA）的多肽。 所述突变体多肽能够将天然CyaA的结合活性保留到靶细胞，并且优选还将天然CyaA的易位活性通过其N-末端结构域保留到靶细胞中，并且还具有减少或抑制的造孔活性 与天然CyaA毒素相比。

公开(公告)号：US08017132B2

公开(公告)日：2011-09-13

申请号：US12409324

申请日：2009-03-23

申请人： Peter Sebo ,  Claude Leclerc ,  Adriana Osickova ,  Catherine Fayolle ,  Jiri Masin ,  Jan Krusek ,  Radim Osicka ,  Marek Basler

发明人： Peter Sebo ,  Claude Leclerc ,  Adriana Osickova ,  Catherine Fayolle ,  Jiri Masin ,  Jan Krusek ,  Radim Osicka ,  Marek Basler

IPC分类号： A61K39/10

CPC分类号： C12N9/88 ,  A61K38/00

摘要： The invention relates to mutant CyaA/E570Q+K860 polypeptides suitable for use as proteinaceous vectors for delivering one or more molecules of interest into a cell, in particular into a cell expressing the CD11b receptor. The invention further relates to polypeptide derivatives suitable for eliciting an immune response in a host.The invention is more particularly directed to polypeptides derived from an adenylate cyclase protein (CyaA) either under the form of a toxin or of a toxoid, which are mutant polypeptides. Said mutant polypeptides are capable of retaining the binding activity of native CyaA to a target cell and preferably of also retaining the translocating activity of native CyaA through its N-terminal domain into target cells and furthermore have a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.

摘要翻译： 本发明涉及适用于蛋白质载体的突变型CyaA / E570Q + K860多肽，用于将一种或多种感兴趣的分子递送至细胞，特别是表达CD11b受体的细胞中。 本发明还涉及适于在宿主中引发免疫应答的多肽衍生物。 本发明更具体涉及衍生自作为突变体多肽的毒素或类毒素形式的腺苷酸环化酶蛋白（CyaA）的多肽。 所述突变体多肽能够将天然CyaA的结合活性保留到靶细胞，并且优选还将天然CyaA的易位活性通过其N-末端结构域保留到靶细胞中，并且还具有减少或抑制的造孔活性 与天然CyaA毒素相比。

公开(公告)号：US09222143B2

公开(公告)日：2015-12-29

申请号：US13257569

申请日：2010-03-23

申请人： Peter Sebo ,  Adriana Osickova ,  Jiri Masin ,  Catherine Fayolle ,  Jan Krusek ,  Marek Basler ,  Claude Leclerc ,  Radim Osicka

发明人： Peter Sebo ,  Adriana Osickova ,  Jiri Masin ,  Catherine Fayolle ,  Jan Krusek ,  Marek Basler ,  Claude Leclerc ,  Radim Osicka

IPC分类号： C12N9/88

CPC分类号： C12N9/88 ,  C12Y406/01001

摘要： A polypeptide comprises a mutated Bordetella pertussis CyaA (SEQ ID NO:1), Bordetella parapertussis CyaA (SEQ ID NO:7), Bordetella hinzii CyaA (SEQ ID NO:8), or Bordetella bronchiseptica CyaA (SEQ ID NO:9), or a fragment thereof lacking all or part of the N-terminal catalytic domain of the CyaA, or a polypeptide having at least 95% sequence identity with SEQ ID NOS: 1, 7, 8, or 9. The glutamic acid residue at position 570 of SEQ ID NO: 1, 7, 8 or at position 569 of SEQ ID NO:9 has been substituted by a conservative amino acid residue. The lysine residue at position 860 of SEQ ID NO: 1, 7, 8 or at position 859 of SEQ ID NO:9 has been substituted by a conservative amino acid residue. The polypeptide retains the binding activity of native CyaA to CD11b expressing cell, and has a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.

摘要翻译： 多肽包括突变型百日咳杆菌CyaA（SEQ ID NO：1），百日咳杆菌CyaA（SEQ ID NO：7），Bordetella hinzii CyaA（SEQ ID NO：8）或支气管炎博德特氏菌CyaA（SEQ ID NO：9）， 或其缺少CyaA的全部或部分N末端催化结构域的片段，或与SEQ ID NO：1,7,8或9具有至少95％序列同一性的多肽。570位的谷氨酸残基 的SEQ ID NO：1,7,8或SEQ ID NO：9的位置569已被保守的氨基酸残基取代。 SEQ ID NO：1,7,8或SEQ ID NO：9的859位的860位的赖氨酸残基被保守的氨基酸残基取代。 多肽保留天然CyaA与表达CD11b的细胞的结合活性，并且与天然CyaA毒素相比具有减少或抑制的成孔活性。

公开(公告)号：US20100239550A1

公开(公告)日：2010-09-23

申请号：US12409324

申请日：2009-03-23

申请人： Peter Sebo ,  Claude Leclerc ,  Adriana Osickova ,  Catherine Fayolle ,  Jiri Masin ,  Jan Krusek ,  Radim Osicka ,  Marek Basler

发明人： Peter Sebo ,  Claude Leclerc ,  Adriana Osickova ,  Catherine Fayolle ,  Jiri Masin ,  Jan Krusek ,  Radim Osicka ,  Marek Basler

IPC分类号： A61K38/43 ,  C12N9/00

CPC分类号： C12N9/88 ,  A61K38/00

摘要： The invention relates to mutant CyaA/E570Q+K860 polypeptides suitable for use as proteinaceous vectors for delivering one or more molecules of interest into a cell, in particular into a cell expressing the CD11b receptor. The invention further relates to polypeptide derivatives suitable for eliciting an immune response in a host.The invention is more particularly directed to polypeptides derived from an adenylate cyclase protein (CyaA) either under the form of a toxin or of a toxoid, which are mutant polypeptides. Said mutant polypeptides are capable of retaining the binding activity of native CyaA to a target cell and preferably of also retaining the translocating activity of native CyaA through its N-terminal domain into target cells and furthermore have a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.

摘要翻译： 本发明涉及适用于蛋白质载体的突变型CyaA / E570Q + K860多肽，用于将一种或多种感兴趣的分子递送至细胞，特别是表达CD11b受体的细胞中。 本发明还涉及适于在宿主中引发免疫应答的多肽衍生物。 本发明更具体涉及衍生自作为突变体多肽的毒素或类毒素形式的腺苷酸环化酶蛋白（CyaA）的多肽。 所述突变体多肽能够将天然CyaA的结合活性保留到靶细胞，并且优选还将天然CyaA的易位活性通过其N-末端结构域保留到靶细胞中，并且还具有减少或抑制的造孔活性 与天然CyaA毒素相比。