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71. 发明授权

US07504111B2 Gonococcal proteins and nucleic acids 有权
标题翻译：淋球菌蛋白质和核酸
公开(公告)号：US07504111B2
公开(公告)日：2009-03-17
申请号：US10467657
申请日：2002-02-12
申请人： Maria Rita Fontana , Mariagrazia Pizza , Vega Masiganani , Elisabetta Monaci
发明人： Maria Rita Fontana , Mariagrazia Pizza , Vega Masiganani , Elisabetta Monaci
IPC分类号： A61K39/095 , A61K39/00 , C12P21/04 , C07H21/04 , C07K14/00
CPC分类号： C07K14/22 , A61K38/00
摘要： The invention provides proteins from gonococcus (Neisseria gonorrhoeae), including amino acid sequences, the corresponding nucleotide sequences, expression data, and serological data. The proteins are useful antigens for vaccines, immunogenic compositions, and/or diagnostics. They are also useful for distinguishing between gonococcus and meningococcus and, in particular, between gonococcus and serogroup B meningococcus.
摘要翻译：本发明提供来自淋球菌（Neisseria gonorrhoeae）的蛋白质，包括氨基酸序列，相应的核苷酸序列，表达数据和血清学数据。蛋白质是疫苗，免疫原性组合物和/或诊断的有用的抗原。它们也可用于区分淋球菌和脑膜炎球菌，特别是在淋球菌和血清群B脑膜炎球菌之间。

72. 发明授权

US07410646B1 Immunologically active polypeptides with altered toxicity useful for the preparation of an antipertussis vaccine 失效
标题翻译：具有改变的毒性的免疫活性多肽可用于制备抗百日咳疫苗
公开(公告)号：US07410646B1
公开(公告)日：2008-08-12
申请号：US08261692
申请日：1994-06-17
申请人： Mariagrazia Pizza , Antonella Bartoloni , Rino Rappuoli
发明人： Mariagrazia Pizza , Antonella Bartoloni , Rino Rappuoli
IPC分类号： A61K39/10 , C07K14/235
CPC分类号： C07K14/235 , A61K39/00
摘要： Immunologically active polypeptides with no or reduced toxicity useful for the preparation of an antipertussis vaccine. Method for the preparation of said polypeptides which comprises, cultivating a microorganism transformed with a hybrid plasmid including the gene/s which codes for at least one of said polypeptides in a suitable medium and recovering the desired polypeptide from the cells or from the culture medium.
摘要翻译：无毒性或降低毒性的免疫活性多肽可用于制备抗百日咳疫苗。用于制备所述多肽的方法，其包括用合适培养基培养用包含编码所述多肽的至少一种的基因的杂交质粒转化的微生物，并从所述细胞或培养基中回收所需的多肽。

73. 发明申请

US20060166344A1 Bacterial outer memberane vesicles 审中-公开
标题翻译：细菌外囊泡
公开(公告)号：US20060166344A1
公开(公告)日：2006-07-27
申请号：US10526113
申请日：2003-09-01
申请人： Mariagrazia Pizza , Davide Serruto , Rino Rappuoli
发明人： Mariagrazia Pizza , Davide Serruto , Rino Rappuoli
IPC分类号： C12N9/00
CPC分类号： A61K39/095 , A61K2039/55555 , C07K14/22 , C12N1/06 , C12N1/20 , C12N13/00
摘要： Existing methods of meningococcal OMV preparation involve the use of detergent during disruption of the bacterial membrane. According to the invention, membrane disruption is performed substantially in the absence of detergent. The resulting OMVs which retain important bacterial immunogenic components, particularly (i) the protective NspA surface protein, (ii) protein NMB2132 and (iii) protein NMB 1870. A Typical process involves the following steps: (a) treating bacterial cells in the substantial absence of detergent; (b) centrifuging the composition from step (a) to separate the outer membrane vesicles from treated cells and cell debris, and collecting the supernatant; (c) performing a high speed centrifugation of the supernatant from step (b) and collecting the outer membrane vesicles in a pellet; (d) re-dispersing the pellet from step (c) in a buffer; (e) performing a second high speed centrifugation in accordance with step (c), collecting the outer membrane vesicles in a pellet; (f) re-dispersing the pellet from step (e) in an aqueous medium.
摘要翻译：脑膜炎球菌OMV制剂的现有方法涉及在细菌膜破坏期间使用洗涤剂。根据本发明，膜破坏基本上在没有洗涤剂的情况下进行。所产生的OMV保留了重要的细菌免疫原性成分，特别是（i）保护性NspA表面蛋白，（ii）蛋白NMB2132和（iii）蛋白NMB1870。典型的方法包括以下步骤：（a）不含洗涤剂; （b）将来自步骤（a）的组合物离心以将外膜囊泡与经处理的细胞和细胞碎片分离，并收集上清液; （c）对来自步骤（b）的上清液进行高速离心并将颗粒中的外膜囊泡收集; （d）将来自步骤（c）的沉淀物重新分散在缓冲液中; （e）根据步骤（c）进行第二高速离心，将外膜囊泡收集在颗粒中; （f）将来自步骤（e）的沉淀物重新分散在水性介质中。

74. 发明申请

US20060008476A1 Adjuvanted antigenic meningococcal compositions 审中-公开
标题翻译：佐剂抗原性脑膜炎球菌组合物
公开(公告)号：US20060008476A1
公开(公告)日：2006-01-12
申请号：US10497709
申请日：2002-12-04
申请人： Mariagrazia Pizza , Marzia Guiliani
发明人： Mariagrazia Pizza , Marzia Guiliani
IPC分类号： A61K39/095
CPC分类号： A61K39/095 , A61K2039/55544 , Y02A50/466
摘要： A composition comprising a Neisserial antigen and a detoxified ADP-ribosylating toxin. These compositions have been found to be useful for mucosal immunisation, particularly nasal immunisation against Neisseria meningitidis.
摘要翻译：包含奈索氏菌抗原和解毒的ADP-核糖基化毒素的组合物。已经发现这些组合物可用于粘膜免疫，特别是针对脑膜炎奈瑟氏球菌的鼻部免疫。

75. 发明申请

US20050244436A1 Combination Neisserial compositions 审中-公开
标题翻译：组合Neisserial组合物
公开(公告)号：US20050244436A1
公开(公告)日：2005-11-03
申请号：US10984376
申请日：2004-11-09
申请人： Marzia Giuliani , Mariagrazia Pizza , Rino Rappuoli
发明人： Marzia Giuliani , Mariagrazia Pizza , Rino Rappuoli
IPC分类号： C12N15/09 , A61K38/16 , A61K39/00 , A61K39/095 , A61P31/04 , C07K14/22 , C12N15/31 , C12N1/20
摘要： Compositions comprising a first biological molecule from a Neisseria bacterium and a second biological molecule from a Neisseria bacterium. The term “biological molecule” includes proteins and nucleic acids. Preferred Neisseria species are N.meningitidis and N.gonorrhoeae.
摘要翻译：组合物包含来自奈瑟氏球菌细菌的第一生物分子和来自奈顿球菌细菌的第二生物分子。术语“生物分子”包括蛋白质和核酸。优选的奈瑟氏菌属是脑膜炎奈瑟氏球菌和淋病奈瑟氏球菌。

76. 发明申请

US20050136076A1 Immunogenic detoxified mutants of cholera toxin 失效
标题翻译：霍乱毒素的免疫原性解毒突变体
公开(公告)号：US20050136076A1
公开(公告)日：2005-06-23
申请号：US10986582
申请日：2004-11-12
申请人： Mariagrazia Pizza , Maria Fontana , Valentina Giannelli , Rino Rappuoli
发明人： Mariagrazia Pizza , Maria Fontana , Valentina Giannelli , Rino Rappuoli
IPC分类号： A61K38/00 , A61K39/00 , C07K14/245 , C07K14/28 , C12N1/21 , C12N15/31 , A61K39/02 , C07H21/04 , C12N15/74
CPC分类号： C07K14/28 , A61K38/00 , A61K39/00 , C07K14/245 , C07K2319/00 , C12N2799/026 , Y02A50/472
摘要： An immunogenic detoxified protein comprising the amino acid sequence of subunit A of a cholera toxin (CT-A) or a fragment thereof or the amino acid sequence of subunit A of an Escherichia coli heat labile toxin (LT-A) or a fragment thereof wherein the amino acids at, or in positions corresponding to Ser-63 and Arg-192 are replaced with another amino acid. The immunogenic detoxified protein is useful as vaccine for Vibrio cholerae or an enterotoxigenic strain of Escherichia coli and is produced by recombinant DNA means by site-directed mutagenesis.
摘要翻译：包含霍乱毒素（CT-A）或其片段的亚基A的氨基酸序列或大肠杆菌热不稳定毒素（LT-A）或其片段的亚基A的氨基酸序列的免疫原性解毒蛋白，其中对应于Ser-63和Arg-192的位置或位置的氨基酸被另外的氨基酸替代。免疫原性解毒蛋白质可用作霍乱弧菌或大肠杆菌肠毒素菌株的疫苗，并通过重组DNA方法通过定点诱变产生。

77. 发明授权

US09579372B2 Meningococcal fHBP polypeptides 有权
标题翻译：脑膜炎球菌fHBP多肽
公开(公告)号：US09579372B2
公开(公告)日：2017-02-28
申请号：US12918729
申请日：2009-02-20
申请人： Mariagrazia Pizza , Maria Scarselli , Marzia Monica Giuliani , Maria Arico , Rino Rappuoli
发明人： Mariagrazia Pizza , Maria Scarselli , Marzia Monica Giuliani , Maria Arico , Rino Rappuoli
IPC分类号： A61K39/095 , A61K39/02 , A61K39/38 , A61K38/00 , C07K1/00 , C07H21/04 , C12N15/00 , C07K14/22 , A61K39/00
CPC分类号： A61K39/095 , A61K39/00 , C07K14/22
摘要： fHBP is a protein in Neisseria meningitidis. Three families of fHBP are known. To increase the ability of a fHBP protein to elicit antibodies that are cross-reactive between the families, fHBP is selected or engineered to have a sequence which can elicit broad-spectrum bactericidal anti-meningococcal antibodies after administration to a host animal.
摘要翻译： fHBP是脑膜炎奈瑟菌中的蛋白质。已知三个fHBP家族。为了增加fHBP蛋白引起家族之间交叉反应的抗体的能力，选择或改造fHBP以具有在给予宿主动物后可引发广谱杀菌抗脑膜炎球菌抗体的序列。

78. 发明授权

US09206399B2 Immunogenic bacterial vesicles with outer membrane proteins 有权
标题翻译：具有外膜蛋白的免疫原性细胞囊泡
公开(公告)号：US09206399B2
公开(公告)日：2015-12-08
申请号：US11666786
申请日：2005-10-28
申请人： Jeannette Adu-Bobie , Mariagrazia Pizza , Nathalie Norais , Germano Ferrari , Guido Grandi
发明人： Jeannette Adu-Bobie , Mariagrazia Pizza , Nathalie Norais , Germano Ferrari , Guido Grandi
IPC分类号： A61K39/095 , C12N9/10 , A61K39/108
CPC分类号： C07K14/245 , A61K39/00 , A61K39/0258 , A61K39/095 , C07K14/22 , C12N9/1051 , Y02A50/474
摘要： Knockout of the meningococcal mltA homolog gives bacteria that spontaneously release vesicles that are rich in immunogenic outer membrane proteins and that can elicit cross-protective antibody responses with higher bactericidal titres than OMVs prepared by normal production processes. Thus the invention provides a bacterium having a knockout mutation of its mltA gene. The invention also provides a bacterium, wherein the bacterium: (i) has a cell wall that includes peptidoglycan; and (ii) does not express a protein having the lytic transglycosylase activity of MltA protein. The invention also provides compositions comprising vesicles that, during culture of bacteria of the invention, are released into the culture medium.
摘要翻译：脑膜炎球菌mltA同系物的敲除使细菌自发释放富含免疫原性外膜蛋白的囊泡，并且能够以比正常生产过程制备的OMV更高的杀菌滴度引发交叉保护性抗体应答。因此，本发明提供了具有其mltA基因的敲除突变的细菌。本发明还提供了一种细菌，其中所述细菌：（i）具有包含肽聚糖的细胞壁; 和（ii）不表达具有MltA蛋白的裂解转糖苷酶活性的蛋白质。本发明还提供包含囊泡的组合物，其在本发明的细菌培养期间释放到培养基中。

79. 发明申请

US20150118261A1 ESCHERICHIA COLI VACCINE COMBINATION 有权
标题翻译： ESCHERICHIA COLI VACCINE组合
公开(公告)号：US20150118261A1
公开(公告)日：2015-04-30
申请号：US14344892
申请日：2012-09-14
申请人： Laura Serino , Mariagrazia Pizza
发明人： Laura Serino , Mariagrazia Pizza
IPC分类号： A61K39/108 , C07K14/245
CPC分类号： A61K39/0258 , A61K2039/54 , A61K2039/541 , A61K2039/542 , A61K2039/543 , A61K2039/552 , A61K2039/55516 , A61K2039/55544 , A61K2039/70 , C07K14/245 , Y02A50/474
摘要： The invention provides an immunogenic composition comprising a combination of (i) bacterial Ig-like domain protein fragment (orf405B) having the amino acid sequence set forth in SEQ ID NO:2 or a protein having at least 80% similarity thereto, and (ii) putative Lipoprotein (orf3526) having the amino acid sequence set forth in SEQ ID NO:8 or a protein having at least 80% similarity thereto.
摘要翻译：本发明提供了包含以下组合的免疫原性组合物：（i）具有SEQ ID NO：2所示氨基酸序列的细菌Ig样结构域蛋白片段（orf405B）或与其具有至少80％相似性的蛋白质，和）推定的具有SEQ ID NO：8所示氨基酸序列的脂蛋白（orf3526）或与其具有至少80％相似性的蛋白质。

80. 发明授权

US08808711B2 Meningococcal outer membrane vesicles 有权
标题翻译：脑膜炎球菌外膜囊泡
公开(公告)号：US08808711B2
公开(公告)日：2014-08-19
申请号：US11661996
申请日：2005-09-05
申请人： Philipp Oster , Mariagrazia Pizza , Rino Rappouli
发明人： Philipp Oster , Mariagrazia Pizza , Rino Rappouli
IPC分类号： A61K39/095
CPC分类号： A61K39/095 , A61K2039/545 , A61K2039/55555
摘要： OMVs targeted against specific epidemic strains can be highly effective in controlling localized outbreaks of disease. In combination with large-scale and reproducible manufacturing techniques, a vaccine can be rapidly produced after an outbreak. The invention provides a method for preparing a meningococcal outer membrane vesicle (OMV) vaccine, comprising the steps of: (i) identifying the serosubtype of a meningococcal strain associated with an outbreak of meningococcal meningitis; (ii) preparing OMVs from a meningococcal strain having the serosubtype identified in step (i) for use in vaccine manufacture. The method may comprise one or both of the further steps of (iii) formulating said OMVs as a vaccine; and (iv) distributing said vaccine in a geographical area affected by or likely to be affected by said outbreak. The meningococcal strain will typically be in serogroup B, but may be instead by in serogroup A, C, W135, Y, etc.
摘要翻译：针对特定流行株的OMV可以有效控制局部的疾病暴发。结合大规模和可重现的制造技术，疫苗可以在爆发后迅速生产。本发明提供了一种制备脑膜炎球菌外膜囊泡（OMV）疫苗的方法，包括以下步骤：（i）鉴定与脑膜炎球菌脑膜炎爆发相关的脑膜炎球菌菌株的血清型; （ii）从具有步骤（i）中鉴定的血清型的脑膜炎球菌菌株制备用于疫苗制造的OMV。该方法可以包括以下一个或两个步骤：（iii）将所述OMV配制为疫苗; 和（iv）在受该疫情影响或受其影响的地理区域内分发疫苗。脑膜炎球菌病毒株通常在血清组B中，但可以代之以血清群A，C，W135，Y等。

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