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11.发明授权Recombinant M. tuberculosis auxotrophic for leucine and vaccines using same 失效用于亮氨酸的重组结核分枝杆菌营养缺陷型和使用其的疫苗公开(公告)号：US06562348B2
公开(公告)日：2003-05-13
申请号：US09349739
申请日：1999-07-08
IPC分类号： A61K3902
CPC分类号： C12R1/32 , A61K2039/52 , C12N15/52
摘要： The present invention provides a recombinant M. tuberculosis mycobacterium that is auxotrophic for leucine. The present invention also provides a vaccine comprising a recombinant M. tuberculosis mycobacterium that is auxotrophic for leucine, as well as a method for treating or preventing tuberculosis in a subject comprising administering to the subject a recombinant M. tuberculosis mycobacterium that is auxotrophic for leucine in an amount effective to treat or prevent tuberculosis in the subject.
摘要翻译： 本发明提供了对于亮氨酸是营养缺陷型的重组结核分枝杆菌分枝杆菌。 本发明还提供一种疫苗，其包含对亮氨酸有营养缺陷型的重组结核分枝杆菌分枝杆菌，以及用于治疗或预防受试者中的结核病的方法，其包括对所述受试者施用对于亮氨酸营养缺陷型的重组结核分枝杆菌分枝杆菌 有效治疗或预防受试者结核病的数量。
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公开(公告)号：US06268201B1
公开(公告)日：2001-07-31
申请号：US09177349
申请日：1998-10-23
IPC分类号： C12N112
CPC分类号： C07K14/35 , A61K2039/53 , C12N15/74 , Y02A50/412 , Y02A50/466 , Y10S435/863 , Y10S435/864 , Y10S435/865 , Y10S435/866
摘要： This invention relates to the identification, cloning, sequencing and characterization of the iniB, iniA and iniC genes of mycobacteria which are induced by a broad class of antibiotics that act by inhibiting cell wall biosynthesis, including the first line antituberculosis agents, isoniazid and ethambutol. The present invention provides purified and isolated iniB, iniA, iniC and iniB promoter nucleic acids which may comprise the iniBAC operon, as well as mutated forms of these nucleic acids. The present invention also provides one or more single-stranded nucleic acid probes which specifically hybridize to the iniB, iniA, iniC and iniB promoter nucleic acids, and mixtures thereof, which may be formulated in kits, and used in the diagnosis of drug-resistant mycobacterial strain. The present invention also provides methods for the screening and identification of drugs effective against Mycobacterium tuberculosis using induction of the iniB promoter.
摘要翻译： 本发明涉及由通过抑制细胞壁生物合成起作用的广泛类型的抗生素诱导的分枝杆菌iniB，iniA和iniC基因的鉴定，克隆，测序和表征，包括第一线抗结核剂，异烟肼和乙胺丁醇。 本发明提供纯化和分离的iniB，iniA，iniC和iniB启动子核酸，其可以包含iniBAC操纵子，以及这些核酸的突变形式。 本发明还提供了一种或多种与iniB，iniA，iniC和iniB启动子核酸及其混合物特异性杂交的单链核酸探针，其可以配制在试剂盒中，并用于诊断耐药性 分枝杆菌菌株。 本发明还提供了利用iniB启动子的诱导来筛选和鉴定对结核分枝杆菌有效的药物的方法。
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公开(公告)号：US06733761B2
公开(公告)日：2004-05-11
申请号：US10029715
申请日：2001-12-20
IPC分类号： A61K3904
CPC分类号： C12N9/88
摘要： The present invention provides a purified and isolated nucleic acid encoding mycobacterial isocitrate lyase, as well as mutated forms of the nucleic acid. Further provided are purified and isolated isocitrate lyase proteins and mutated isocitrate lyase proteins. Additionally, the present invention provides vectors which comprises nucleic acid sequences encoding mycobacterial isocitrate lyase and mutated forms of this nucleic acid, as well as host cells containing these vectors. Also provided is a mycobacterium containing one or more mutations in its isocitrate lyase gene. Further provided by the present invention are agents that inhibit the activity or expression of a mycobacterial lyase protein, a method of identifying these, and a method of producing them. Finally, the present invention also provides a method of identifying genes required for persistence of mycobacteria.
摘要翻译： 本发明提供了编码分枝杆菌异柠檬酸裂解酶的纯化和分离的核酸，以及核酸的突变形式。 还提供纯化和分离的异柠檬酸裂合酶蛋白和突变的异柠檬酸裂合酶蛋白。 另外，本发明提供了包含编码分枝杆菌异柠檬酸裂合酶和突变形式的核酸的核酸序列以及含有这些载体的宿主细胞的载体。 还提供了在其异柠檬酸裂合酶基因中含有一个或多个突变的分枝杆菌。 本发明进一步提供的是抑制分枝杆菌裂解酶蛋白的活性或表达的试剂，鉴定这些的方法及其制备方法。 最后，本发明还提供了鉴定分枝杆菌持久性所需的基因的方法。
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公开(公告)号：US07998471B2
公开(公告)日：2011-08-16
申请号：US11794373
申请日：2006-01-11
申请人： William R. Jacobs, Jr. , Norman L. Letvin , Mark Cayabyab , Barton F. Haynes , Hua-Xin Liao , Jae-Sung Yu , Avi-Hai Hovav
发明人： William R. Jacobs, Jr. , Norman L. Letvin , Mark Cayabyab , Barton F. Haynes , Hua-Xin Liao , Jae-Sung Yu , Avi-Hai Hovav
CPC分类号： C07K14/445 , A61K39/015 , A61K2039/523 , C07K14/005 , C07K2319/02 , C07K2319/42 , C12N2740/16122 , Y02A50/412 , A61K2300/00
摘要： Provided are recombinant mycobacteria expressing an HIV-1 antigen and a malarial antigen. Also provided are Mycobacterium smegmatis expressing an HIV-1 antigen. Further provided are vaccines capable of inducing an immune response in a mammal against HIV-1 and the malarial pathogen. Additionally provided are methods of inducing an immune response in a mammal against HIV-1 and a malarial pathogen. Also provided are methods of inducing an immune response in a mammal against HIV-1. The methods comprise infecting the mammal with any of the above-described mycobacteria.
摘要翻译： 提供表达HIV-1抗原和疟疾抗原的重组分枝杆菌。 还提供了表达HIV-1抗原的耻垢分枝杆菌。 还提供了能够在哺乳动物中针对HIV-1和疟疾病原体诱导免疫应答的疫苗。 另外提供了诱导哺乳动物针对HIV-1和疟疾病原体的免疫应答的方法。 还提供了在哺乳动物中针对HIV-1诱导免疫应答的方法。 所述方法包括用任何上述分枝杆菌感染哺乳动物。
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公开(公告)号：US06290966B1
公开(公告)日：2001-09-18
申请号：US09350326
申请日：1999-07-09
IPC分类号： A61K3902
CPC分类号： C12R1/32 , A61K2039/52 , C07K14/35
摘要： Disclosed are novel recombinant mutant strains of mycobacteria that are deficient for the synthesis or transport of dimycoserosalphthiocerol (“DIM”). The present invention also provides a method of producing a recombinant mutant mycobacterium that is deficient for the synthesis or transport of DIM, comprising mutating a nucleic acid responsible for the synthesis or transport of dimycoserosalphthiocerol, including a nucleic acid comprising the promoter for the pps operon, fadD28 or mmpL7. The present invention also provides a vaccine comprising a DIM mutant mycobacterium of the present invention, as well as a method for the treatment or prevention of tuberculosis in a subject using the vaccine.
摘要翻译： 公开了分子细菌的新型重组突变菌株，其用于合成或转运二环神经节硫辛（“DIM”）。 本发明还提供了一种制备DIM的合成或转运缺陷的重组突变型分枝杆菌的方法，包括突变负责合成或转运二环神经节硫蛋白的核酸，包括包含用于pps操纵子的启动子的核酸， fadD28或mmpL7。 本发明还提供了包含本发明的DIM突变型分枝杆菌的疫苗，以及使用疫苗治疗或预防受试者的结核病的方法。
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公开(公告)号：US08591918B2
公开(公告)日：2013-11-26
申请号：US12450193
申请日：2008-03-10
申请人： William R. Jacobs, Jr. , Kari Sweeney , Dee Dao , Steven A. Porcelli , John Chan , Tsungda Hsu
发明人： William R. Jacobs, Jr. , Kari Sweeney , Dee Dao , Steven A. Porcelli , John Chan , Tsungda Hsu
CPC分类号： C07K14/35
摘要： Provided are mycobacteria deleted in at least a portion of a region 3 ESAT-6-like gene cluster. Also provided are mycobacteria comprising a mutation in an roc-1 gene. Additionally, vaccines comprising these mycobacteria are provided. Further provided are methods of making a recombinant mycobacterium, methods of inducing an immune response in a mammal, methods of inhibiting IL-12 production in a mammal, and methods of stimulating IL-12 production in a mammal. Vaccine adjuvants are also provided, as are methods of inducing immunity to a target antigen in a mammal.
摘要翻译： 提供在区域3 ESAT-6样基因簇的至少一部分中缺失分枝杆菌。 还提供了包含roc-1基因突变的分枝杆菌。 另外，提供了包含这些分枝杆菌的疫苗。 进一步提供了制备重组分枝杆菌的方法，在哺乳动物中诱导免疫应答的方法，抑制哺乳动物中IL-12产生的抑制方法，以及刺激哺乳动物中IL-12产生的方法。 还提供疫苗佐剂，以及在哺乳动物中诱导免疫目标抗原的方法。
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公开(公告)号：US08394388B2
公开(公告)日：2013-03-12
申请号：US11794506
申请日：2006-01-12
CPC分类号： C07K14/35 , A61K48/00 , A61K2039/522
摘要： Provided are recombinant mycobacteria having a mutation in an nlaA gene or in a nuoG gene. Also provided are isolated and purified nlaA proteins and nuoG proteins from a mycobacterium. Additionally provided are isolated and purified nucleic acids comprising a recombinant nlaA gene or a recombinant nuoG gene. Further provided are methods of inducing an immune response in a mammal and methods of making a recombinant mycobacterium using the nlaA gene or the nuoG gene.
摘要翻译： 提供了在nlaA基因或nuoG基因中具有突变的重组分枝杆菌。 还提供了分离和纯化的来自分枝杆菌的nlaA蛋白和nuoG蛋白。 另外提供了分离和纯化的包含重组nlaA基因或重组nuoG基因的核酸。 还提供了在哺乳动物中诱导免疫应答的方法和使用nlaA基因或nuoG基因制备重组分枝杆菌的方法。
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公开(公告)号：US06566121B1
公开(公告)日：2003-05-20
申请号：US08850977
申请日：1997-05-05
IPC分类号： C12N112
CPC分类号： A61K39/04 , A61K39/00 , C07K14/35 , C12N15/74 , Y10S435/863 , Y10S435/864 , Y10S435/865 , Y10S435/866
摘要： A mutated mycobacterium selected from the class consisting of mutated M.bovis-BCG, mutated M.tuberculosis, and mutated M. leprae. The mutation of M.bovis-BCG, M.tuberculosis, or M. leprae is preferably effected through an insertional mutation of a mycobacterial gene. The insertional mutagenesis may be effected, for example, through illegitimate recombination or by a mycobacterial transposon. Such mutated mycobacteria may then be transformed with an expression vector(s) containing a complement gene to the gene which is mutated, and preferably also including a heterologous gene.
摘要翻译： 选自突变的M.bovis-BCG，突变的结核分枝杆菌和突变的麻疯病的类别的突变的分枝杆菌。 M.bovis-BCG，结核分枝杆菌或麻疯病毒的突变优选通过分枝杆菌基因的插入突变来实现。 插入诱变可以例如通过非法重组或通过分枝杆菌转座子进行。 然后可以将这种突变的分枝杆菌用含有突变基因的补体基因的表达载体转化，并且优选还包括异源基因。
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公开(公告)号：US06423545B1
公开(公告)日：2002-07-23
申请号：US09350047
申请日：1999-07-08
IPC分类号： C12N1500
CPC分类号： C12N9/0004 , A61K39/00 , C12N15/74 , C12R1/32
摘要： Disclosed is a recombinant slow-growing mycobacterium comprising at least one mycobacterial gene containing an unmarked mutation, where an “unmarked mutation” is a mutated nucleotide sequence introduced into a mycobacterium where the introduced mutated nucleotide sequence does not contain a selectable marker, such as a gene conferring antibiotic resistance to the recombinant mycobacterium incorporating the mutated nucleotide sequence. Also disclosed is a method for preparing a recombinant slow-growing mycobacterium comprising at least one mycobacterial gene containing an unmarked mutation, as well as a vaccine comprising a recombinant slow-growing mycobacterium having at least one mycobacterial gene containing an unmarked mutation dispersed in a physiologically acceptable carrier. Further disclosed is a method of treating or preventing tuberculosis in a subject comprising administering the vaccine of the present invention in an amount effective to treat or prevent tuberculosis in the subject.
摘要翻译： 公开了一种重组慢生长分枝杆菌，其包含至少一种含有未标记突变的分枝杆菌基因，其中“未标记突变”是引入分枝杆菌的突变核苷酸序列，其中引入的突变核苷酸序列不含可选择标记，例如 基因对赋予突变核苷酸序列的重组分枝杆菌赋予抗生素抗性。 还公开了一种制备重组慢生长分枝杆菌的方法，其包含至少一种含有未标记突变的分枝杆菌基因，以及包含重组慢生长分枝杆菌的疫苗，其具有至少一种分散在生理学上的未标记突变的分枝杆菌基因 可接受的载体 进一步公开的是治疗或预防受试者结核病的方法，包括以有效治疗或预防受试者结核病的量施用本发明的疫苗。
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公开(公告)号：US06221364B1
公开(公告)日：2001-04-24
申请号：US08747177
申请日：1996-11-12
IPC分类号： A61K3904
CPC分类号： A61K39/04 , C12N15/74 , Y02A50/41 , Y02A50/412 , Y02A50/423
摘要： The present invention refers in general to novel recombinant mycobacteria that are auxotrophic for diaminopimelate. In particular, this invention relates to novel auxotrophic recombinant mycobacteria, to methods of making the mycobacteria, and to uses of the mycobacteria to deliver vaccines. This invention also provides for uses of the mycobacteria in drug screening processes.
摘要翻译： 本发明一般涉及用于二氨基庚二酸的营养缺陷型的新型重组分枝杆菌。 特别地，本发明涉及新的营养缺陷性重组分枝杆菌，制备分枝杆菌的方法以及分枝杆菌递送疫苗的用途。 本发明还提供分枝杆菌在药物筛选过程中的用途。
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