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公开(公告)号：US06300061B1
公开(公告)日：2001-10-09
申请号：US08705557
申请日：1996-08-29
IPC分类号： C12Q168
CPC分类号： C07K14/005 , C07K14/35 , C12N7/00 , C12N15/74 , C12N2795/10322 , C12Q1/18 , C12Q1/6897 , G01N33/5695
摘要： This invention relates to mycobacterial species-specific reporter mycobacteriophages (reporter mycobacteriophages), methods of producing said reporter mycobacteriophages and the use of said reporter mycobacteriophages for the rapid diagnosis of mycobacterial infection and the assessment of drug susceptibilities of mycobacterial strains in clinical samples. In particular, this invention is directed to the production and use of luciferase reporter mycobacteriophages to diagnose tuberculosis. The mycobacterial species-specific reporter mycobacteriophages comprise mycobacterial species-specific mycobacteriophages which contain reporter genes and transcriptional promoters therein. When the reporter mycobacteriophages are incubated with clinical samples which may contain the mycobacteria of interest, the gene product of the reporter genes will be expressed if the sample contains the mycobacteria of interest, thereby diagnosing mycobacterial infection.
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公开(公告)号：US6139843A
公开(公告)日：2000-10-31
申请号：US946525
申请日：1997-10-07
申请人： Arye Rubinstein , Barry R. Bloom , Yair Devash , Stanley J. Cryz
发明人： Arye Rubinstein , Barry R. Bloom , Yair Devash , Stanley J. Cryz
IPC分类号： A61K39/21 , A61P31/18 , C07K14/16 , C07K14/21 , C07K14/33 , C07K14/35 , C07K16/10 , A61K39/00 , A61K39/38 , A61K39/385
CPC分类号： C07K14/005 , A61K39/12 , A61K39/21 , C07K14/21 , C07K14/33 , C07K14/35 , C07K16/1063 , C07K16/1072 , A61K2039/54 , A61K2039/545 , A61K2039/57 , A61K2039/6037 , A61K2039/6068 , A61K2039/6081 , A61K2039/70 , C12N2740/16122 , C12N2740/16134 , C12N2740/16322 , C12N2740/16334
摘要： The present invention provides for peptide conjugate compositions, methods of using the peptide conjugate compositions, and pharmaceutical compositions comprising the peptide conjugate compositions. The peptide conjugate compositions comprise peptides with amino acid sequences similar to the gp120 principal neutralizing domain (PND) of HIV, gp41, and Nef (p27) of HIV and carriers which enhance immunogenicity. The peptide conjugate compositions of the present invention may comprise a multivalent cocktail of several different peptide conjugates. Also provided by present invention is a method for reducing the level of HIV titers in a mammal by administering to the mammal a peptide composition of the present invention in an amount effective to reduce the level of HIV titers. The peptide conjugate compositions of the present invention induce prolonged antibody response in serum, a high level of antibody in the mucosa, and the production of cytotoxic lymphocytes. The peptide conjugate compositions of the present invention also elicit neutralizing antibodies and decrease viral loads in a subject.
摘要翻译： 本发明提供了肽缀合物组合物，使用肽缀合物组合物的方法和包含肽缀合物组合物的药物组合物。 肽缀合物组合物包含具有类似于HIV的gp120主要中和结构域（PND），HIV，gp41和Nef（p27）以及增强免疫原性的载体的氨基酸序列的肽。 本发明的肽缀合物组合物可以包含若干不同肽缀合物的多价混合物。 本发明还提供了通过向哺乳动物施用有效降低HIV滴度水平的量的本发明的肽组合物来降低哺乳动物的HIV滴度水平的方法。 本发明的肽缀合物组合物诱导血清中延长的抗体应答，粘膜中的高水平抗体和细胞毒性淋巴细胞的产生。 本发明的肽缀合物组合物还引发中和抗体并降低受试者的病毒载量。
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公开(公告)号：US5854055A
公开(公告)日：1998-12-29
申请号：US463942
申请日：1995-06-05
申请人： Barry R. Bloom , William R. Jacobs, Jr. , Ronald W. Davis , Richard A. Young , Robert N. Husson
发明人： Barry R. Bloom , William R. Jacobs, Jr. , Ronald W. Davis , Richard A. Young , Robert N. Husson
IPC分类号： G01N33/53 , A61K39/00 , A61K39/04 , A61K39/39 , A61P31/04 , A61P31/06 , A61P31/08 , A61P31/12 , A61P31/16 , A61P31/18 , A61P31/22 , A61P37/04 , A61P39/02 , C07K14/01 , C07K14/35 , C12N1/21 , C12N15/09 , C12N15/74 , C12N15/87 , C12P21/02 , C12R1/19 , C12R1/32 , C12R1/325 , C12R1/33 , C12R1/34 , G01N33/50 , C12N15/64 , C12N15/66
CPC分类号： A61K39/04 , C07K14/005 , C07K14/35 , C12N15/74 , C12N15/87 , C12R1/32 , A61K39/00 , C12N2795/10022
摘要： Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E. coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance). The present invention also relates to two types of recombinant vectors useful in introducing DNA of interest into mycobacteria, where it is expressed. One type of vector is a recombinant plasmid capable of replicating as a plasmid in E. coli and of lysogenizing a mycobacterial host. The other type of vector is a recombinant plasmid which can be introduced into mycobacteria, where it is stably maintained extrachromosomally.
摘要翻译： 能够表达目的的DNA的重组分枝杆菌疫苗载体，其编码针对至少一种需要免疫应答的至少一种病原体的至少一种蛋白质抗原并且可以并入分枝杆菌中或稳定整合到分枝杆菌基因组中。 疫苗载体用于哺乳动物宿主用于免疫的目的。 还公开了在大肠杆菌中但不在分枝杆菌中复制的重组载体。 重组载体包括1）与用重组质粒转化的分枝杆菌基因组中与同源序列重组所必需的分枝杆菌基因或其部分; 2）编码在用重组质粒转化的分枝杆菌中表达所需的多肽或蛋白质的基因的全部或部分; 3）在大肠杆菌中复制和选择所需的DNA序列; 和4）在分枝杆菌中选择所需的DNA序列（例如耐药性）。 本发明还涉及可用于将感兴趣的DNA引入分枝杆菌的两种类型的重组载体，其中它被表达。 一种载体是能够在大肠杆菌中作为质粒复制并使分解细菌宿主溶解的重组质粒。 另一种载体是可以引入分枝杆菌的重组质粒，其在染色体外稳定地保持。
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公开(公告)号：US5656424A
公开(公告)日：1997-08-12
申请号：US388916
申请日：1995-02-15
申请人： Stewart Jurgensen , Michael C. Little , Paul T. Hamilton , Paul Riska , John Chan , Barry R. Bloom
发明人： Stewart Jurgensen , Michael C. Little , Paul T. Hamilton , Paul Riska , John Chan , Barry R. Bloom
CPC分类号： C12Q1/66 , C12Q1/6897
摘要： Methods for using reporter mycobacteriophage (RM) and p-nitro-.alpha.-acetylamino-.beta.-hydroxy-propiophenone (NAP) to identify TB complex mycobacteria and distinguish these species from MOTT. RM-infected MOTT show little or no reduction in signal when treated with NAP. In contrast, TB complex mycobacteria infected with RM are distinguishable from RM-infected MOTT by a reduction in signal with NAP treatment.
摘要翻译： 使用报道分枝杆菌噬菌体（RM）和对硝基-α-乙酰氨基-β-羟基 - 苯丙酮（NAP）的方法来鉴定TB复合分枝杆菌并将这些物种与MOTT区分开来。 在用NAP治疗的情况下，RM感染的MOTT显示很少或没有减少信号。 相比之下，感染RM的TB复合分枝杆菌通过NAP治疗的信号减少与RM感染的MOTT区分开。
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公开(公告)号：US06821769B2
公开(公告)日：2004-11-23
申请号：US09918951
申请日：2001-07-31
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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6.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：US06447778B1
公开(公告)日：2002-09-10
申请号：US09599286
申请日：2000-06-22
申请人： Arye Rubinstein , Barry R. Bloom , Yair Devash , Stanley J. Cryz
发明人： Arye Rubinstein , Barry R. Bloom , Yair Devash , Stanley J. Cryz
IPC分类号： A61K3804
CPC分类号： C07K14/005 , A61K39/12 , A61K39/21 , A61K2039/54 , A61K2039/545 , A61K2039/57 , A61K2039/6037 , A61K2039/6068 , A61K2039/6081 , A61K2039/70 , C07K14/21 , C07K14/33 , C07K14/35 , C07K16/1063 , C07K16/1072 , C12N2740/16122 , C12N2740/16134 , C12N2740/16322 , C12N2740/16334
摘要： The present invention provides for peptide conjugate compositions, methods of using the peptide conjugate compositions, and pharmaceutical compositions comprising the peptide conjugate compositions. The peptide conjugate compositions comprise peptides with amino acid sequences similar to the gp120 principal neutralizing domain (PND) of HIV, gp41, and Nef (p27) of HIV and carriers which enhance immunogenicity. The peptide conjugate compositions of the present invention may comprise a multivalent cocktail of several different peptide conjugates. Also provided by present invention is a method for reducing the level of HIV titers in a mammal by administering to the mammal a peptide composition of the present invention in an amount effective to reduce the level of HIV titers. The peptide conjugate compositions of the present invention induce prolonged antibody response in serum, a high level of antibody in the mucosa, and the production of cytotoxic lymphocytes. The peptide conjugate compositions of the present invention also elicit neutralizing antibodies and decrease viral loads in a subject.
摘要翻译： 本发明提供了肽缀合物组合物，使用肽缀合物组合物的方法和包含肽缀合物组合物的药物组合物。 肽缀合物组合物包含具有类似于HIV的gp120主要中和结构域（PND），HIV，gp41和Nef（p27）以及增强免疫原性的载体的氨基酸序列的肽。 本发明的肽缀合物组合物可以包含若干不同肽缀合物的多价混合物。 本发明还提供了通过向哺乳动物施用有效降低HIV滴度水平的量的本发明的肽组合物来降低哺乳动物的HIV滴度水平的方法。 本发明的肽缀合物组合物诱导血清中延长的抗体应答，粘膜中的高水平抗体和细胞毒性淋巴细胞的产生。 本发明的肽缀合物组合物还引发中和抗体并降低受试者的病毒载量。
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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：US06270776B1
公开(公告)日：2001-08-07
申请号：US08454075
申请日：1995-05-30
申请人： Barry R. Bloom , Ronald W. Davis , William R. Jacobs, Jr. , Richard A. Young , Robert N. Husson
发明人： Barry R. Bloom , Ronald W. Davis , William R. Jacobs, Jr. , Richard A. Young , Robert N. Husson
IPC分类号： A61K3500
CPC分类号： A61K39/04 , A61K39/00 , C07K14/005 , C07K14/35 , C12N15/74 , C12N15/87 , C12N2795/10022 , C12R1/32 , Y02A50/412 , Y02A50/476
摘要： Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E. coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance). The present invention also relates to two types of recombinant vectors useful in introducing DNA of interest into mycobacteria, where it is expressed. One type of vector is a recombinant phasmid capable of replicating as a plasmid in E. coli and of lysogenizing a mycobacterial host. The other type of vector is a recombinant plasmid which can be introduced into mycobacteria, where it is stably maintained extrachromosomally.
摘要翻译： 能够表达目的的DNA的重组分枝杆菌疫苗载体，其编码针对至少一种需要免疫应答的至少一种病原体的至少一种蛋白质抗原并且可以并入分枝杆菌中或稳定整合到分枝杆菌基因组中。 疫苗载体用于哺乳动物宿主用于免疫的目的。 还公开了在大肠杆菌中但不在分枝杆菌中复制的重组载体。 重组载体包括1）与用重组质粒转化的分枝杆菌基因组中与同源序列重组所必需的分枝杆菌基因或其部分; 2）编码在用重组质粒转化的分枝杆菌中表达所需的多肽或蛋白质的基因的全部或部分; 3）在大肠杆菌中复制和选择所需的DNA序列; 和4）在分枝杆菌中选择所需的DNA序列（例如耐药性）。 本发明还涉及可用于将感兴趣的DNA引入分枝杆菌的两种类型的重组载体，其中它被表达。 一种载体是能够在大肠杆菌中作为质粒复制并使分枝杆菌宿主溶解的重组噬菌粒。 另一种载体是可以引入分枝杆菌的重组质粒，其在染色体外稳定地保持。
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公开(公告)号：US06225066B1
公开(公告)日：2001-05-01
申请号：US09426436
申请日：1999-10-25
IPC分类号： C12Q168
CPC分类号： C07K14/005 , C07K14/35 , C12N7/00 , C12N15/74 , C12N2795/10322 , C12Q1/18 , C12Q1/6897 , G01N33/5695
摘要： This invention relates to mycobacterial species-specific reporter mycobacteriophages (reporter mycobacteriophages), methods of producing said reporter mycobacteriophages and the use of said reporter mycobacteriophages for the rapid diagnosis of mycobacterial infection and the assessment of drug susceptibilities of mycobacterial strains in clinical samples. In particular, this invention is directed to the production and use of luciferase reporter mycobacteriophages to diagnose tuberculosis. The mycobacterial species-specific reporter mycobacteriophages comprise mycobacterial species-specific mycobacteriophages which contain reporter genes and transcriptional promoters therein. When the reporter mycobacteriophages are incubated with clinical samples which may contain the mycobacteria of interest, the gene product of the reporter genes will be expressed if the sample contains the mycobacteria of interest, thereby diagnosing mycobacterial infection.
摘要翻译： 本发明涉及分枝杆菌物种特异性报道分枝杆菌噬菌体（报道分枝杆菌噬菌体），产生所述报道分枝杆菌噬菌体的方法和所述报道分枝杆菌噬菌体用于快速诊断分枝杆菌感染和评估临床样品中分枝杆菌菌株药物敏感性的用途。 特别地，本发明涉及荧光素酶报道分枝杆菌噬菌体的生产和使用以诊断结核病。 分枝杆菌种特异性报道分枝杆菌噬菌体包含含有报道基因和转录促进剂的分枝杆菌种特异性分枝杆菌噬菌体。 当报道分枝杆菌噬菌体与可能含有感兴趣分枝杆菌的临床样品一起孵育时，如果样品含有感兴趣的分枝杆菌，报告基因的基因产物将被表达，从而诊断分枝杆菌感染。
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