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1. 发明申请

WO2006076343A8 MYCOBACTERIA EXPRESSING HIV-1 AND MALARIA ANTIGENS 审中-公开
标题翻译： MYCBACTERIA表达HIV-1和疟疾抗原
公开(公告)号：WO2006076343A8
公开(公告)日：2006-10-26
申请号：PCT/US2006000790
申请日：2006-01-11
申请人： EINSTEIN COLL MED , BETH ISRAEL HOSPITAL , UNIV DUKE , JACOBS WILLIAM R JR , LETVIN NORMAN L , CAYABYAB MARK , HAYNES BARTON F , LIAO HUA-XIN , YU JAE-SUNG , HOVAV AVI-HAI
发明人： JACOBS WILLIAM R JR , LETVIN NORMAN L , CAYABYAB MARK , HAYNES BARTON F , LIAO HUA-XIN , YU JAE-SUNG , HOVAV AVI-HAI
IPC分类号： A61K49/00 , A01N63/00 , A01N65/00 , A61K39/00 , A61K39/04 , A61K39/12 , A61K48/00 , C12N1/00 , C12N1/12 , C12N1/20 , C12N7/00 , C12N7/01 , C12P1/00 , C12P21/04
CPC分类号： C07K14/445 , A61K39/015 , A61K2039/523 , C07K14/005 , C07K2319/02 , C07K2319/42 , C12N2740/16122 , 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：提供了表达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诱导针对HIV-1和疟疾病原体的免疫应答的疫苗。另外提供了在哺乳动物中诱导针对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诱导针对HIV-1的免疫应答的方法。该方法包括用任何上述分枝杆菌感染哺乳动物。

2. 发明申请

WO2006076519A3 MYCOBACTERIAL MUTANTS AFFECTING HOST APOPTOSIS 审中-公开
标题翻译：影响宿主病的MYCOBACTERIAL MUTANT
公开(公告)号：WO2006076519A3
公开(公告)日：2008-12-11
申请号：PCT/US2006001132
申请日：2006-01-12
申请人： EINSTEIN COLL MED , JACOBS WILLIAM R JR , PORCELLI STEVEN A , BRIKEN VOLKER , BRAUNSTEIN MIRIAM
发明人： JACOBS WILLIAM R JR , PORCELLI STEVEN A , BRIKEN VOLKER , BRAUNSTEIN MIRIAM
IPC分类号： A61K39/04 , A61K39/00 , A61K39/02 , A61K49/00 , C07H21/04 , C12P21/04
CPC分类号： C07K14/35 , A61K48/00 , A61K2039/522
摘要： Provided are recombinant mycobacteria having a mutation in annlaA 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：提供在annlaA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。

3. 发明申请

WO9517511A2 MYCOBACTERIA VIRULENCE FACTORS AND A METHOD FOR THEIR IDENTIFICATION 审中-公开
标题翻译： MYCOBACTERIA VIRULENCE因子及其鉴定方法
公开(公告)号：WO9517511A2
公开(公告)日：1995-06-29
申请号：PCT/US9414912
申请日：1994-12-23
申请人： AGRESEARCH NEW ZEALAND PASTORA , EINSTEIN COLL MED , JACOBS WILLIAM R JR , BLOOM BARRY R , COLLINS DESMOND MICHAEL , LISLE GEOFFREY W DE , PASCOPELLA LISA , KAWAKAMI RIKU PAMELA
发明人： JACOBS WILLIAM R JR , BLOOM BARRY R , COLLINS DESMOND MICHAEL , DE LISLE GEOFFREY W , PASCOPELLA LISA , KAWAKAMI RIKU PAMELA
IPC分类号： C12N15/09 , A61K39/00 , A61K39/04 , A61P31/04 , A61P31/06 , C07K14/35 , C12N1/21 , C12N5/10 , C12N15/00 , C12N15/31 , C12N15/63 , C12N15/74 , C12Q1/68 , C12R1/32 , G01N33/53
CPC分类号： C12N15/74 , A61K39/00 , C07K14/35 , C12Q1/68 , C12Q1/689
摘要： The present invention provides polynucleotides associated with virulence in mycobacteria, and particularly a fragment of DNA isolated from M. bovis that contains a region encoding a putative sigma factor. Also provided are methods for a DNA sequence or sequences associated with virulence determinants in mycobacteria, and particularly in M. tuberculosis and M. bovis. The invention also provides corresponding polynucleotides associated with avirulence in mycobacteria. In addition, the invention provides a method for producing strains with altered virulence or other properties which can themselves be used to identify and manipulate individual genes.
摘要翻译：本发明提供了与分枝杆菌中的毒力相关的多核苷酸，特别是分离自牛分枝杆菌的DNA片段，其含有编码推定的σ因子的区域。还提供了在分枝杆菌，特别是结核分枝杆菌和牛分枝杆菌中的DNA序列或与毒力决定簇相关的序列的方法。本发明还提供了与分枝杆菌中无毒性相关的相应多核苷酸。此外，本发明提供了一种用于产生具有改变的毒力或其他性质的菌株的方法，其本身可用于鉴定和操纵个体基因。

4. 发明申请

WO2009008912A2 MYCOBACTERIAL MUTANTS INDUCING IL-12 审中-公开
标题翻译：诱导IL-12的MYCOBACTERIAL突变体
公开(公告)号：WO2009008912A2
公开(公告)日：2009-01-15
申请号：PCT/US2008003204
申请日：2008-03-10
申请人： EINSTEIN COLL MED , JACOBS WILLIAM R JR , LAWRENCE KARI , DAO DEE , PORCELLI STEVEN A , CHAN JOHN , HSU TSUNGDA
发明人： JACOBS WILLIAM R JR , LAWRENCE KARI , DAO DEE , PORCELLI STEVEN A , CHAN JOHN , HSU TSUNGDA
IPC分类号： C12N1/21
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：只要在区域3ESAT-6样基因簇的至少一部分中缺失分枝杆菌。还提供了在roc-1基因中包含突变的分枝杆菌。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针对靶抗原的免疫的方法。

5. 发明专利

JP2000350578A EXPRESSION VEHICLE OF RECOMBINANT MYCOBACTERIUM AND USE THEREOF 失效
公开(公告)号：JP2000350578A
公开(公告)日：2000-12-19
申请号：JP2000072963
申请日：2000-03-15
申请人： WHITEHEAD BIOMEDICAL INST , EINSTEIN COLL MED , UNIV LELAND STANFORD JUNIOR
发明人： BLOOM BARRY R , DAVIS RONALD W , JACOBS WILLIAM R JR , YOUNG RICHARD A , HUSSON ROBERT N
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
摘要： PROBLEM TO BE SOLVED: To obtain a recombinant mycobacterium with slight adverse effects, excellent in immune responsiveness and useful for the production, etc., of a vaccine by expressing the objective DNA integrated with a plasmid. SOLUTION: This recombinant mycobacterium is capable of expressing the objective DNA integrated with a plasmid such as a mycobacterium-Escherichia coli hybrid plasmid capable of replicating and expressing the objective DNA in Escherichia coli and a mycobacterium. Furthermore, the recombinant mycobacterium BCG-Pasteur is a substrain P1173P2 transformed with a shuttle plasmid pYUP1100 deposited in the American Type Culture Collection with an accession No.67745 and the recombinant mycobacterium is obtained by transducing a plasmid containing the objective DNA and a DNA expressing the objective DNA into a mycobacterium.

6. 发明申请

WO0233118A3 ISOCITRATE LYASE ENZYME FROM MYCOBACTERIUM TUBERCULOSIS AND INHIBITORY AGENTS TO COMBAT PERSISTENT INFECTION 审中-公开
标题翻译：从MYCOBACTERIUM TUBCCOSOSIS和抑制剂中分离LYASE酶，以治疗持续感染
公开(公告)号：WO0233118A3
公开(公告)日：2003-05-30
申请号：PCT/US0124393
申请日：2001-08-03
申请人： TEXAS A & M UNIV SYS , UNIV CORNELL , UNIV ROCKEFELLER , EINSTEIN COLL MED
发明人： SACCHETTINI JAMES C , MCKINNEY JOHN D , RUSSELL DAVID G , JACOBS WILLIAM R JR , SHARMA VIVEK , SHARMA SUJATA , HENER ZU BENTRUP KERSTIN
IPC分类号： C12Q1/02 , C12Q1/04 , C12Q1/527 , G06F19/16 , G06F17/50 , C07K14/00 , C12N9/88 , C12Q1/18 , G06F19/00
CPC分类号： C12Q1/527 , C07K2299/00 , C12Q1/025 , C12Q1/045 , G01N2333/35 , G01N2333/40 , G06F19/16 , Y02A90/26
摘要： The invention provides methods and compositions for use in identifying inhibitors of biochemical pathways important for persistent infection, allowing the identification and/or design of improved therapeutics for treating persistent infection by pathogenic microbes. Particularly disclosed is the importance of the glyoxylate shut to the persistent phase of various infectious agents, including Mycobacteria, such as M.tuberculosis, and the identification of preferred targets for drug development, including the enzymes isocitrate lyase (ICL) and malate synthase. Crystals and three-dimensional structures of M.tuberculosis ICL, without ligand and in complex with two inhibitors are also disclosed, for exemplary use in the design of inhibitors and therapeutic agents.
摘要翻译：本发明提供用于鉴定对于持续感染重要的生物化学途径的抑制剂的方法和组合物，允许鉴定和/或设计改良的治疗剂以治疗病原微生物的持续感染。特别公开了乙醛酸封闭对包括分枝杆菌如结核分枝杆菌在内的各种感染因子的持续期的重要性，以及鉴定药物开发的优选靶标，包括酶异柠檬酸裂解酶（ICL）和苹果酸合酶。还公开了结核分枝杆菌ICL的结晶和三维结构，不含配体和与两种抑制剂的复合物，用于设计抑制剂和治疗剂的示例性用途。

7. 发明申请

WO0103730A9 UNMARKED DELETION MUTANTS OF MYCOBACTERIA AND METHODS OF USING SAME 审中-公开
标题翻译： MYCOBACTERIA的无标记删除突变体及其使用方法
公开(公告)号：WO0103730A9
公开(公告)日：2002-07-25
申请号：PCT/US0018453
申请日：2000-07-06
申请人： EINSTEIN COLL MED
发明人： JACOBS WILLIAM R JR , PAVELKA MARTIN S JR
IPC分类号： A61K39/00 , A61P31/04 , C12N1/21 , C12N9/02 , C12N15/74 , A61K39/02 , A61K39/04 , C12N1/20 , C12N15/09 , C12Q1/68 , G01N33/569
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, wherein 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：公开了包含至少一种含有未标记突变的分枝杆菌基因的重组慢生长分枝杆菌，其中“未标记突变”是引入分枝杆菌的突变核苷酸序列，其中所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。

8. 发明申请

WO0104267A9 ONE-STEP ALLELIC EXCHANGE IN MYCOBACTERIA WITH CONDITIONAL TRANSDUCING PHAGE 审中-公开
标题翻译：具有条件转移噬菌体的MYCOBACTERIA中的一步法律交换
公开(公告)号：WO0104267A9
公开(公告)日：2002-08-01
申请号：PCT/US0040311
申请日：2000-07-06
申请人： EINSTEIN COLL MED
发明人： JACOBS WILLIAM R JR , BARDAROV STOYAN S
IPC分类号： C12N1/21 , C12N15/74 , C12N15/00 , C12N15/63
CPC分类号： C12N15/74
摘要： The present invention provides a method for high frequency of allelic exchange in the slow-growing mycobacteria using in vitro generated specialized transducing mycobacteriophages, as well as the recombinant slow-growing mycobacteria generated using the disclosed method. A transducing mycobacteriophage of the present invention comprises a conditional mycobacteriophage containing an E . coli bacteriophage lambda cosmid inserted into a non-essential region of the mycobacteriophage, said cosmid containing a mutated DNA substrate which is homologous to a wildtype nucleic acid sequence of a slow-growing mycobacterium. When slow-growing mycobacteria infected with the conditional transducing phage are cultured under conditions wherein the conditional transducing phage does not replicate, the mutated DNA substrate is incorporated into the chromosomal DNA of the slow-growing mycobacteria by homologous recombination, thereby generating the recombinant slow-growing mycobacteria of the present invention. The disclosed method may be used to produce mycobacterial auxotrophs, including leucine and lysine auxotrophs.
摘要翻译：本发明提供了使用体外产生的专门转导分枝杆菌噬菌体的慢生长分枝杆菌以及使用所公开的方法产生的重组慢生长分枝杆菌进行高频等位基因交换的方法。本发明的转导性分枝杆菌噬菌体包含含有E的条件性分枝杆菌噬菌体。所述粘粒包含与缓慢生长的分枝杆菌的野生型核酸序列同源的突变的DNA底物，所述DNA底物与所述分枝杆菌的非必需区域插入。当条件转导噬菌体感染的慢生长分枝杆菌在条件转导噬菌体不复制的条件下培养时，通过同源重组将突变的DNA底物并入慢生长的分枝杆菌的染色体DNA中，从而产生重组慢 - 生长本发明的分枝杆菌。所公开的方法可用于产生分枝杆菌营养缺陷型营养缺陷型，包括亮氨酸和赖氨酸营养缺陷型。

9. 发明申请

WO9000594A3 RECOMBINANT MYCOBACTERIAL EXPRESSION VEHICLES AND USES THEREFOR 审中-公开
标题翻译：重组MYCOBACTERIAL表达车辆及其用途
公开(公告)号：WO9000594A3
公开(公告)日：1990-05-03
申请号：PCT/US8902962
申请日：1989-07-07
申请人： WHITEHEAD BIOMEDICAL INST , EINSTEIN COLL MED , UNIV LELAND STANFORD JUNIOR
发明人： BLOOM BARRY R , DAVIS RONALD W , JACOBS WILLIAM R JR , YOUNG RICHARD A , HUSSON ROBERT N
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 , C12N15/90 , C12Q1/68
CPC分类号： A61K39/04 , A61K39/00 , C07K14/005 , C07K14/35 , C12N15/74 , C12N15/87 , C12N2795/10022 , C12R1/32
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.

10. 发明公开

EP1846024A4 MYCOBACTERIAL MUTANTS AFFECTING HOST APOPTOSIS 失效转让
标题翻译：在主机上凋亡作用分枝杆菌突变体
公开(公告)号：EP1846024A4
公开(公告)日：2009-07-29
申请号：EP06733693
申请日：2006-01-12
申请人： EINSTEIN COLL MED
发明人： JACOBS WILLIAM R JR , PORCELLI STEVEN A , BRIKEN VOLKER , BRAUNSTEIN MIRIAM
IPC分类号： A61K39/04 , A61K39/00 , A61K39/02 , A61K49/00 , C07H21/04 , C12P21/04
CPC分类号： C07K14/35 , A61K48/00 , A61K2039/522

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