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1. 发明授权

US07807181B2 Neisseria mutants, lipooligosaccharides and immunogenic compositions 有权
标题翻译：奈瑟氏球菌突变体，脂寡糖和免疫原性组合物
公开(公告)号：US07807181B2
公开(公告)日：2010-10-05
申请号：US10508309
申请日：2003-03-20
申请人： David S. Stephens , Yih-Ling Tzeng , Susu Zughaier , Shanta Zimmer
发明人： David S. Stephens , Yih-Ling Tzeng , Susu Zughaier , Shanta Zimmer
IPC分类号： A61K39/02 , A61K39/095 , A61K39/38 , A01N43/04 , C07H1/00
CPC分类号： C12N15/52 , A61K39/095 , A61K2039/522 , A61K2039/523 , A61K2039/53 , C07K14/22 , C07K2319/23
摘要： Provided herein are mutant strains of Neisseria meningitidis which produce Kdo-free lipid A as well as the Kdo-free lipid A molecules and immunogenic compositions containing such Kdo-free lipid A molecules from a Neisseria strain containing a genetically stable mutation which inactivates a gene selected from the group consisting of genes encoding arabinose-5-phosphate isomerase, CMP-Kdo synthetase and CMP-Kdo transferase. N. meningitidis NMB206 is a specifically exemplified strain which harbors a stable insertion mutation in the gene (kpsF) encoding A5P isomerase; strain NMB-249 is a specifically exemplified strain with a stable insertion mutation in the gene (kdtA) encoding CMP-Kdo synthetase, and strain NMB259 is specifically exemplified strain with a stable insertion mutation in the gene (kdsB) encoding CMP-Kdo transferase. Also provided by the present invention are methods for the production of Lipid A flee of 3-keto-3-deoxyoctanoic acid using these genetically stable N. meningitidis mutants. Also describes is pYT250, a plasmid functional in neisseriae and in enterics such as Escherichia coli.
摘要翻译：本文提供脑膜炎奈瑟球菌的突变菌株，其产生不含Kdo的脂质A以及不含Kdo的脂质A分子和含有来自包含基因稳定突变的不含Kdo的脂质A分子的免疫脂质A分子的灭活组合，所述遗传稳定突变使选择的基因失活来自编码阿拉伯糖-5-磷酸异构酶，CMP-Kdo合成酶和CMP-Kdo转移酶的基因组。脑膜炎奈瑟球菌NMB206是在编码A5P异构酶的基因（kpsF）中具有稳定插入突变的特异性例证菌株; 菌株NMB-249是编码CMP-Kdo合成酶的基因（kdtA）中具有稳定插入突变的特异性例证菌株，并且菌株NMB259具体示例是在编码CMP-Kdo转移酶的基因（kdsB）中具有稳定插入突变的菌株。本发明还提供了使用这些遗传稳定的脑膜炎奈瑟球菌突变体生产3-酮-3-脱氧辛酸脂质A的方法。还描述了pYT250，一种在奈瑟氏菌中和在诸如大肠杆菌等肠道中功能的质粒。

2. 发明申请

US20120053199A1 NOSCAPINE AND ANALOGS AND METHODS RELATED THERETO 有权
标题翻译：非特异性和类似物及其相关方法
公开(公告)号：US20120053199A1
公开(公告)日：2012-03-01
申请号：US13216458
申请日：2011-08-24
申请人： Susu Zughaier , Ritu Aneja , David S. Stephens
发明人： Susu Zughaier , Ritu Aneja , David S. Stephens
IPC分类号： A61K31/4355 , A61P37/00 , A61P25/28 , A61P19/02 , A61P11/06 , A61P9/10 , A61P1/00 , A61P17/00 , A61P31/14 , A61P19/04 , A61P25/16 , A61P11/00 , A61P11/08 , A61P37/06 , A61P1/16 , A61P29/00
CPC分类号： A61K31/4355
摘要： The invention relates to the innate immune pathway and anti-inflammatory molecules with therapeutic properties. In some embodiments, the invention relates to compounds and pharmaceutical compositions and methods of using the compounds and compositions to treat inflammatory diseases including inflammation associated with auto-immune diseases.
摘要翻译：本发明涉及具有治疗性质的先天免疫途径和抗炎分子。在一些实施方案中，本发明涉及使用化合物和组合物治疗炎性疾病（包括与自身免疫性疾病相关的炎症）的化合物和药物组合物和方法。

3. 发明授权

US08841317B2 Noscapine and analogs and methods related thereto 有权
标题翻译：诺斯卡品及其相关的类似物和方法
公开(公告)号：US08841317B2
公开(公告)日：2014-09-23
申请号：US13216458
申请日：2011-08-24
申请人： Susu Zughaier , Ritu Aneja , David S. Stephens
发明人： Susu Zughaier , Ritu Aneja , David S. Stephens
IPC分类号： A61K31/44 , A61K31/4355
CPC分类号： A61K31/4355
摘要： The invention relates to the innate immune pathway and anti-inflammatory molecules with therapeutic properties. In some embodiments, the invention relates to compounds and pharmaceutical compositions and methods of using the compounds and compositions to treat inflammatory diseases including inflammation associated with auto-immune diseases.
摘要翻译：本发明涉及具有治疗性质的先天免疫途径和抗炎分子。在一些实施方案中，本发明涉及使用化合物和组合物治疗炎性疾病（包括与自身免疫性疾病相关的炎症）的化合物和药物组合物和方法。

4. 发明申请

US20090208533A1 NEISSERIA MENINGITIDIS SEROGROUP A CAPSULAR POLYSACCHARIDE ACETYLTRANSFERASE, METHODS AND COMPOSITIONS 失效
标题翻译： IA IS IS IS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS TIONS
公开(公告)号：US20090208533A1
公开(公告)日：2009-08-20
申请号：US11943326
申请日：2007-11-20
申请人： David S. Stephens , Seshu K. Gudlavalleti , Yih-Ling Tzeng , Anup K. Datta , Russell W. Carlson
发明人： David S. Stephens , Seshu K. Gudlavalleti , Yih-Ling Tzeng , Anup K. Datta , Russell W. Carlson
IPC分类号： A61K39/095 , C12N9/10 , C12P19/04 , A61P31/04
CPC分类号： A61K39/095 , A61K39/00 , C12N9/1029 , C12P19/44
摘要： Provided are methods for recombinant production of an O-acetyltransferase and methods for acetylating capsular polysaccharides, especially those of a Serogroup A Neisseria meningitidis using the recombinant O-acetyltransferase, and immunogenic compositions comprising the acetylated capsular polysaccharide.
摘要翻译：提供了用于重组生产O-乙酰转移酶的方法和使用重组O-乙酰转移酶乙酰化荚膜多糖的方法，特别是使用血清组织A脑膜炎奈瑟氏球菌的方法，以及包含乙酰化荚膜多糖的免疫原性组合物。

5. 发明授权

US07883876B2 Neisseria meningitidis serogroup A capsular polysaccharide acetyltransferase, methods and compositions 失效
标题翻译：脑膜炎奈瑟菌血清群A荚膜多糖乙酰转移酶，方法和组成
公开(公告)号：US07883876B2
公开(公告)日：2011-02-08
申请号：US11943326
申请日：2007-11-20
申请人： David S. Stephens , Seshu K. Gudlavalleti , Yih-Ling Tzeng , Anup K. Datta , Russell W. Carlson
发明人： David S. Stephens , Seshu K. Gudlavalleti , Yih-Ling Tzeng , Anup K. Datta , Russell W. Carlson
IPC分类号： C12P19/04 , A61K39/095
CPC分类号： A61K39/095 , A61K39/00 , C12N9/1029 , C12P19/44
摘要： Provided are methods for recombinant production of an O-acetyltransferase and methods for acetylating capsular polysaccharides, especially those of a Serogroup A Neisseria meningitidis using the recombinant O-acetyltransferase, and immunogenic compositions comprising the acetylated capsular polysaccharide.
摘要翻译：提供了用于重组生产O-乙酰转移酶的方法和使用重组O-乙酰转移酶乙酰化荚膜多糖的方法，特别是使用血清组织A脑膜炎奈瑟氏球菌的方法，以及包含乙酰化荚膜多糖的免疫原性组合物。

6. 发明授权

US07348161B2 Macrolide efflux genetic assembly 有权
标题翻译：大环内酯外排基因组装
公开(公告)号：US07348161B2
公开(公告)日：2008-03-25
申请号：US10472801
申请日：2002-03-15
申请人： Kathryn Gay , David S. Stephens
发明人： Kathryn Gay , David S. Stephens
IPC分类号： C12Q1/37 , C12Q1/14 , C07K14/325 , C12N1/20
CPC分类号： C07K14/3156
摘要： Macrolide resistance associated with macrolide efflux (mef) in Streptococcus pneumoniae has been defined with respect to the genetic structure and dissemination of a novel mefE-containing chromosomal insertion element. The mefE gene is found on the 5′-end of a 5.5 kb or 5.4 kb insertion designated mega (macrolide efflux genetic assembly) found in at least four distinct sites of the pneumococcal genome. The element is transformable and confers macrolide resistance to susceptible S. pneumoniae. The first two open reading frames (ORFs) of the element form an operon composed of mefE and a predicted ATP-binding cassette homologous to msrA. Convergent to this efflux operon are three ORFs with homology to stress response genes of Tn5252. Mega is related to mefA-containing element Tn1207.1. Macrolide resistance due to mega has been rapidly increased by clonal expansion of bacteria containing it and horizontally by transformation of previously sensitive bacteria.
摘要翻译：关于肺炎链球菌中的大环内酯类外排（mef）的大环内酯抗药性已经被定义在遗传结构和新颖的含有mefE的染色体插入元件的传播方面。 mefE基因位于5.5 kb或5.4 kb插入的5'末端，命名为大量（大环内酯类，“U STYLE =”SINGLE“ U STYLE =“SINGLE”>装置）发现在肺炎球菌基因组的至少四个不同的位点。该元件是可转化的，并赋予大肠杆菌对易感肺炎链球菌的抗性。元素的前两个开放阅读框（ORFs）形成由mefE组成的操纵子和与msrA同源的预测的ATP结合盒。与这种流出操纵子的融合是与Tn5252的应激反应基因同源的三个ORF。 Mega与含有mefA的元件Tn1207.1相关。由于大量的大环内酯类药物的抗性已经通过含有它的细菌的克隆扩增并且通过先前敏感的细菌的转化水平而迅速增加。

7. 发明授权

US06403306B1 Serogroup-specific nucleotide sequences in the molecular typing of bacterial isolates and the preparation of vaccines thereto 失效
标题翻译：细菌分离物的分子分型中的血清型特异性核苷酸序列及其疫苗的制备
公开(公告)号：US06403306B1
公开(公告)日：2002-06-11
申请号：US08936107
申请日：1997-09-23
申请人： David S. Stephens , John S. Swartley
发明人： David S. Stephens , John S. Swartley
IPC分类号： C12Q168
CPC分类号： C07K14/22 , A61K38/00 , A61K39/00 , C12N9/1048 , C12N9/88 , C12N9/90 , C12N15/52 , Y10S435/975
摘要： The present invention is based on the discovery of meningococcal isolates having genetic markers of a particular serogroup but expressing a capsular polysaccharide of a different serogroup. These isolates and prototype serogroup A, B, C, Y and W-135 strains were used to define the capsular biosynthetic operon of the major meningococcal serogroups and to show that capsule switching occurs as a result of allelic exchange of, for example, the polysialyl-transferase gene. Findings of capsule switching in vivo indicate that closely related virulent meningococcal clones may not be recognized by traditional serogroup-based surveillance and can escape vaccine-induced or natural protective immunity by capsule switching. The invention provides recombinant meningococcal strains, recombinant DNA constructs and immunological preparations useful as diagnostic probes for detection and diagnosis of meningococcal diseases, screening for specific meningococcal serogroups and broad based immunizations with multivalent capsular polysaccharide conjugate vaccines.
摘要翻译：本发明基于具有特定血清组的遗传标记但表达不同血清群的荚膜多糖的脑膜炎球菌分离物的发现。这些分离株和原型血清群A，B，C，Y和W-135菌株用于定义主要脑膜炎球菌血清群的荚膜生物合成操纵子，并显示由于等位基因交换而发生的胶囊切换，例如唾液酸转移酶基因。胶体切换体内的结果表明，密切相关的毒性脑膜炎球菌克隆可能不被传统的基于血清群的监测所识别，并且可以通过胶囊切换逃避疫苗诱导的或天然的保护性免疫。本发明提供重组脑膜炎球菌菌株，重组DNA构建体和免疫学制剂，其可用作脑膜炎球菌疾病的检测和诊断，筛选特定脑膜炎球菌血清群和用多价荚膜多糖缀合疫苗进行广泛基础免疫的诊断探针。

8. 发明授权

US5976536A Neisseria mutants, lipooligosaccharides and immunogenic compositions 失效
标题翻译：奈瑟氏球菌突变体，脂寡糖和免疫原性组合物
公开(公告)号：US5976536A
公开(公告)日：1999-11-02
申请号：US512955
申请日：1995-08-09
申请人： David S. Stephens , Charlene Marree Kahler
发明人： David S. Stephens , Charlene Marree Kahler
IPC分类号： A61K39/095 , A61P31/04 , A61K39/00 , A01N63/00 , A61K39/02
CPC分类号： C12R1/36 , A61K39/095
摘要： Provided herein are mutant strains of Neisseria meningitidis which produce lipooligosaccharide (LOS) differing from the wild-type LOS in structure as well as the mutant LOS molecules and immunogenic compositions containing truncated LOS molecules from a Neisseria strain containing a genetically stable in a gene selected from the group consisting of genes encoding .alpha.-1,2-N-acetylglucosamine transferase and a gene homology to an Escherichia coli gene encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase. N. meningitidis NMB-559 harbors an insertion mutation in the gene encoding .alpha.-1, 2-N-acetylglucosamine transferase, and N. meningitidis NMB-469 harbors an insertion mutation in an nlaB gene, the protein product of which has significant amino acid sequence homology to the E. coli gene encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase.
摘要翻译：本文提供了产生不同于结构中的野生型LOS的脂多糖（LOS）和突变型LOS分子的脑膜炎奈瑟氏球菌的突变菌株和含有在选自以下的基因中的基因稳定的奈瑟氏球菌菌株的截短的LOS分子的免疫原性组合物由编码α-1,2-N-乙酰葡糖胺转移酶的基因和与编码1-酰基-sn-甘油-3-磷酸酰基转移酶的大肠杆菌基因同源的基因组。脑膜炎奈米斯NMB-559在编码α-1,2-N-乙酰氨基葡萄糖转移酶的基因中插入突变，脑膜炎奈瑟氏球菌NMB-469在+ E，非nla + EE B基因中插入突变，蛋白其产物与编码1-酰基-sn-甘油-3-磷酸酰基转移酶的大肠杆菌基因具有显着的氨基酸序列同源性。

9. 发明授权

US06472518B1 Invasion associated genes from Neisseria meningitidis serogroup B 失效
标题翻译：来自脑膜炎奈瑟氏球菌血清群B的入侵相关基因
公开(公告)号：US06472518B1
公开(公告)日：2002-10-29
申请号：US09284926
申请日：1999-08-17
申请人： Efrain M. Ribot , David S. Stephens , Nigel Raymond , Frederick D. Quinn
发明人： Efrain M. Ribot , David S. Stephens , Nigel Raymond , Frederick D. Quinn
IPC分类号： C07H2104
CPC分类号： C07K14/22 , A61K38/00
摘要： Genes isolated from Neisseria memingitidis, as well as isolated nucleic acids, probes, expression cassettes, polypeptides, antibodies, immunogenic compositions, antisense nucleic acids, amplification mixtures, and new invasion deficient swains of Neisseria meningitidis are provided Methods of detecting Neisseria meningitidis and Neisseria meningitidis nucleic acids, and methods of inhibiting the invasion of mammalian cells by Neisseria meningitidis are also provided.
摘要翻译：提供从奈瑟氏球菌分离的基因，以及分离的核酸，探针，表达盒，多肽，抗体，免疫原性组合物，反义核酸，扩增混合物和脑膜炎奈瑟球菌新入侵缺陷病毒的检测方法脑膜炎奈瑟氏球菌和脑膜炎奈瑟氏球菌检测方法还提供了脑膜炎奈瑟球菌抑制哺乳动物细胞侵袭的核酸和方法。

10. 发明申请

US20090035827A1 O-acetyltransferase from Neisseria Meningitidis, Compositions and Methods 审中-公开
标题翻译：脑膜炎奈瑟氏球菌，组合物和方法的O-乙酰转移酶
公开(公告)号：US20090035827A1
公开(公告)日：2009-02-05
申请号：US11843933
申请日：2007-08-23
申请人： David S. Stephens , Charlene Kahler
发明人： David S. Stephens , Charlene Kahler
IPC分类号： C12P19/04 , C12N1/21 , C12N9/10 , C12N15/54
CPC分类号： C12N9/1029 , A61K31/702 , A61K38/00 , C12P19/04
摘要： Provided are recombinant DNA molecules that do not occur in nature encoding a Lot3 O-acetyltransferase, vectors that direct expression of a Lot O-acetyltransferase, recombinant host cells which express a Lot3 O-acetyltransferase, methods for recombinant production of a Lot3 O-acetyltransferase, methods for acetylating lipooligosaccharides, especially those of a Neisseria meningitidis using a recombinant Lot O-acetyltransferase, and immunogenic compositions comprising the acetylated lipooligosaccharide.
摘要翻译：提供了在编码Lot3 O-乙酰转移酶的自然界中不发生的重组DNA分子，指示表达Lot O-乙酰转移酶的载体，表达Lot3 O-乙酰转移酶的重组宿主细胞，用于重组产生Lot3 O-乙酰转移酶的方法，使用重组Lot O-乙酰转移酶乙酰化脂寡糖，特别是脑膜炎奈瑟氏球菌的方法和包含乙酰化脂寡糖的免疫原性组合物的方法。

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