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1. 发明申请

WO0011214B1 MOLECULAR DIFFERENCES BETWEEN SPECIES OF THE M. TUBERCULOSIS COMPLEX 审中-公开
标题翻译： M.TUBERCULOSIS复合物种间的分子差异
公开(公告)号：WO0011214B1
公开(公告)日：2000-04-13
申请号：PCT/US9917939
申请日：1999-08-10
申请人： UNIV LELAND STANFORD JUNIOR , BEHR MARCEL , SMALL PETER , SCHOOLNIK GARY , WILSON MICHAEL A
发明人： BEHR MARCEL , SMALL PETER , SCHOOLNIK GARY , WILSON MICHAEL A
IPC分类号： C12N1/21 , C12Q1/68 , C12N15/11 , G01N33/53
CPC分类号： C12Q1/689 , C12Q2600/156
摘要： Specific genetic deletions are identified in mycobacteria isolates, including variations in the M. tuberculosis genome sequence between isolates, and numerous deletion present in BCG as compared to M. tb. These deletions are used as markers to distinguish between pathogenic and avirulent strains, and as a marker for particular M. tb isolates. Deletions specific to vaccine strains of BCG are useful in determining whether a positive tuberculin skin test is indicative of actual tuberculosis infection. The deleted sequences may be re-introduced into BCG to improve the efficacy of vaccination. Alternatively, the genetic sequence that corresponds to the deletion(s) is deleted from M. bovis or M. tuberculosis to attenuate the pathogenic bacteria.
摘要翻译：在分枝杆菌分离物中鉴定特异性遗传缺失，包括分离株之间的结核分枝杆菌基因组序列的变异，以及与M.bb相比在BCG中存在的许多缺失。这些缺失被用作区分病原菌和无毒菌株的标记物，并且作为特异性M.tb菌株的标记物。对BCG疫苗株特异性的缺失可用于确定阳性结核菌素皮肤试验是否表明实际的结核病感染。可将经删除的序列重新引入BCG以提高疫苗接种的效力。或者，对应于缺失的遗传序列从牛分枝杆菌或结核分枝杆菌中缺失，以减毒病原菌。

2. 发明申请

WO2004083448A2 MOLECULAR DIFFERENCES BETWEEN SPECIES OF THE M.TUBERCULOSIS COMPLEX 审中-公开
标题翻译： M.TUBERCULOSIS复合物种之间的分子差异
公开(公告)号：WO2004083448A2
公开(公告)日：2004-09-30
申请号：PCT/US2004007668
申请日：2004-03-11
申请人： UNIV LELAND STANFORD JUNIOR , STATENS SERUMINSTITUT , BEHR MARCEL , SMALL PETER , WILSON MICHAEL A , SCHOOLNIK GARY , AAGAARD CLAUS , ROSENKRANDS IDA , WELDINGH KARIN , ANDERSON PETER
发明人： BEHR MARCEL , SMALL PETER , WILSON MICHAEL A , SCHOOLNIK GARY , AAGAARD CLAUS , ROSENKRANDS IDA , WELDINGH KARIN , ANDERSON PETER
IPC分类号： C07K14/35 , C07K16/12 , C12Q20060101 , C12Q1/68 , C12Q
CPC分类号： C07K14/35 , C07K16/1289 , C12Q1/689
摘要： Specific genetic deletion are identified in mycobacteria isolates, including variations in the M. tuberculosis genome sequence between isolates, and numerous deletion present in BCG as compared to M. tbThe genetic markers can be used for diagnosis of M. tb. infection. One or more antigens provided from the genetic markers can be used in diagnostic assays, e.g. a serological assay.
摘要翻译：在分枝杆菌分离株中鉴定出特异性遗传缺失，包括分离株之间的结核分枝杆菌基因组序列的变异以及BCG中存在的许多缺失与M.tb相比。遗传标记可用于诊断M.bb。感染。从遗传标记提供的一种或多种抗原可用于诊断测定，例如血清学检测。

3. 发明申请

WO2006102767A1 TUBERCULOSIS VACCINE AND METHOD FOR MAKING SAME 审中-公开
标题翻译： TUBERCULOSIS VACCINE及其制备方法
公开(公告)号：WO2006102767A1
公开(公告)日：2006-10-05
申请号：PCT/CA2006/000503
申请日：2006-04-03
申请人： McGILL UNIVERSITY , BEHR, Marcel , MOSTOWY, Serge , CHARLET, Danielle , ALEXANDER, David
发明人： BEHR, Marcel , MOSTOWY, Serge , CHARLET, Danielle , ALEXANDER, David
IPC分类号： C12N15/31 , C40B40/06 , C12Q1/68 , C12P21/02 , C12P19/34 , C07H21/00 , A61K39/04 , C12N15/74 , C12N1/21 , C07K14/35
CPC分类号： A61K39/04 , A61K2039/523 , C07K14/35
摘要： The present invention relates to an improved tuberculosis (TB) vaccine and a method for making this vaccine. The present invention further includes a method for determining the potency of TB strains. Mycobacterium bovis Bacille Calmette-Guerin (BCG) strains are genetically and phenotypically heterogeneous. Expression of the antigenic proteins MPB70 and MPB83 is known to vary considerably across BCG strains; however, the reason for this phenotypic difference has remained unknown. Because the history of BCG strain dissemination has been recorded, it has been possible to precisely determine the chronology of specific genetic changes in BCG strains (Behr and Small, 1999). A number of these mutations affect putative regulatory genes (Behr et al., 1999; Brosch et al ., 2000; Spreadbury et al ., 2005), so it was hypothesized that a mutation in a regulatory gene was likely responsible for the variable production of MPB70 and MPB83. The production of MPB70 and MPB83 across a panel of BCG strains was therefore determined, in order to assign the chronology of this phenotypic change and thereby guide studies towards identifying the responsible mutation. Interestingly, the data implicate a start codon mutation in the M. tuberculosis sigma factor K (RvO445c or sigK) and point to a highly specific link between sigK and expression of MPB70 and MPB83.
摘要翻译：本发明涉及改良的结核病（TB）疫苗和制备该疫苗的方法。本发明还包括确定TB菌株效力的方法。牛分枝杆菌Baccal Calmette-Guerin（BCG）菌株具有遗传和表型异质性。已知抗原性蛋白质MPB70和MPB83的表达在BCG菌株中显着不同; 然而，这种表型差异的原因仍然未知。由于已经记录了BCG菌株传播的历史，所以可以准确地确定BCG菌株中特定遗传变化的年表（Behr and Small，1999）。许多这些突变影响推定的调控基因（Behr等，1999; Brosch等，2000; Spreadbury等，2005），因此假设调节基因中的突变可能导致可变生产的MPB70和MPB83。因此，确定了一组BCG菌株中的MPB70和MPB83的产生，以便分配该表型变化的年表，从而指导研究来鉴定负责的突变。有趣的是，该数据涉及结核分枝杆菌s因子K（RvO445c或sigK）中的起始密码子突变，并指出sigK与MPB70和MPB83的表达之间的高度特异性连锁。

4. 发明申请

WO2004083448A3 MOLECULAR DIFFERENCES BETWEEN SPECIES OF THE M.TUBERCULOSIS COMPLEX 审中-公开
公开(公告)号：WO2004083448A3
公开(公告)日：2004-09-30
申请号：PCT/US2004/007668
申请日：2004-03-11
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , STATENS SERUM INSTITUT , BEHR, Marcel , SMALL, Peter , WILSON, Michael, A. , SCHOOLNIK, Gary , AAGAARD, Claus , ROSENKRANDS, Ida , WELDINGH, Karin , ANDERSON, Peter
发明人： BEHR, Marcel , SMALL, Peter , WILSON, Michael, A. , SCHOOLNIK, Gary , AAGAARD, Claus , ROSENKRANDS, Ida , WELDINGH, Karin , ANDERSON, Peter
IPC分类号： C07K14/35
摘要： Specific genetic deletion are identified in mycobacteria isolates, including variations in the M. tuberculosis genome sequence between isolates, and numerous deletion present in BCG as compared to M. tb The genetic markers can be used for diagnosis of M. tb. infection. One or more antigens provided from the genetic markers can be used in diagnostic assays, e.g. a serological assay.

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