公开(公告)号：US06833135B1

公开(公告)日：2004-12-21

申请号：US09269717

申请日：1999-06-03

申请人： Jose A. Frazao Moniz Pereira ,  Alcino Freitas Vieira ,  Elsa M. Ribeiro Dos Santos-Anes ,  Miguel A. Da Costa Garcia ,  Paulo J. Da Silva Alves

发明人： Jose A. Frazao Moniz Pereira ,  Alcino Freitas Vieira ,  Elsa M. Ribeiro Dos Santos-Anes ,  Miguel A. Da Costa Garcia ,  Paulo J. Da Silva Alves

IPC分类号： A61K3904

CPC分类号： C12N9/22 ,  A61K39/00 ,  C12N15/74 ,  C12N15/90 ,  C12N2310/111 ,  C12N2799/021 ,  Y10S435/866

摘要： The present invention discloses a DNA fragment that can direct the insertion of heterologous DNA into a specific site (tRNAAla gene) of Mycobacterium spp. genome. This DNA fragment includes the attachment site region (attP) and the integrase gene of the mycobacteriophage Ms6. Heterologous DNA linked to this DNA fragment can be carried into the mycobacterial genome through a site-specific integration mechanism. A new DNA integration process is disclosed that consists in providing the integrase gene on a suicide vector, that transiently produces the integrase required for the insertion of the gene or genes linked to the Ms6 attP region contained in a separated plasmid vector. This process allows the construction of highly stable recombinant mycobacteria which may be used as vaccines and/or therapeutic vehicles.

摘要翻译： 本发明公开了可将异源DNA插入分枝杆菌的特定位点（tRNA 基因）的DNA片段。 基因组 该DNA片段包括附着位点区域（attP）和分枝杆菌噬菌体Ms6的整合酶基因。 与该DNA片段连接的异源DNA可以通过位点特异性整合机制携带到分枝杆菌基因组中。 公开了一种新的DNA整合方法，其包括在自杀载体上提供整合酶基因，其瞬时产生插入分离的质粒载体中包含的Ms6 attP区的基因或基因所需的整合酶。 该方法允许构建可用作疫苗和/或治疗载体的高度稳定的重组分枝杆菌。

公开(公告)号：US06238676B1

公开(公告)日：2001-05-29

申请号：US08501600

申请日：1995-07-12

申请人： Steven A. Porcelli ,  Michael B. Brenner ,  Evan M. Beckman ,  Stephen T. Furlong

发明人： Steven A. Porcelli ,  Michael B. Brenner ,  Evan M. Beckman ,  Stephen T. Furlong

IPC分类号： A61K3904

CPC分类号： A61K39/04 ,  A61K39/00 ,  C07K14/70539 ,  C07K16/2803 ,  C12P19/04

摘要： Provided are CD-1 presented antigens, compositions, cells, inhibitors and methods relating to the use of hydrophobic antigen presentation by CD1 molecules, including: methods for detecting the presence of a CD1-presented hydrophobic antigen in a sample; methods for isolating such CD1-presented antigens and the isolated antigens; vaccines containing CD1-presented antigens and vaccination methods; methods of blocking CD1 antigen presentation; methods of identifying and/or isolating CD1 blocking agents and the isolated CD1 blocking agents; methods of inducing CD1 expression; and T-cells for use in the methods disclosed.

摘要翻译： CD-1提供的抗原，组合物，细胞，抑制剂和与使用CD1分子疏水抗原呈递有关的方法，包括：用于检测样品中CD1呈递的疏水性抗原的存在的方法;用于分离此类CD1的方法 表达的抗原和分离的抗原;含有CD1呈递的抗原和疫苗接种方法的疫苗;阻断CD1抗原呈递的方法;鉴定和/或分离CD1阻断剂和分离的CD1阻断剂的方法;诱导CD1表达的方法; 和T细胞用于所公开的方法。

公开(公告)号：US06224881B1

公开(公告)日：2001-05-01

申请号：US08689411

申请日：1996-08-07

申请人： Lee W. Riley ,  Pele Chong

发明人： Lee W. Riley ,  Pele Chong

IPC分类号： A61K3904

CPC分类号： C07K14/35 ,  A61K38/00 ,  A61K39/00 ,  A61K48/00

摘要： The present invention relates to a DNA molecule conferring on Mycobacterium tuberculosis an ability to enter mammalian cells and to survive within macrophages. Peptides, proteins, or polypeptides (e.g. the Mycobacterium cell entry protein or Mcep) encoded by this gene fragment are useful in vaccines to prevent infection by Mycobacterium tuberculosis, while the antibodies raised against these peptides, proteins, or polypeptides can be employed in passively immunizing those already infected by the organism. These proteins, peptides, polypeptides, and antibodies may be utilized in diagnostic assays to detect Mycobacterium tuberculosis in tissue or bodily fluids. The peptides, proteins, or polypeptides of the present invention can be associated with various other therapeutic materials, for administration to mammals, particularly humans, to achieve uptake of those materials by such cells. Synthetically constructed peptides based on the disclosed amino acid sequences exhibit the same mammalian cell uptake activity observed with Mcep.

摘要翻译： 本发明涉及赋予结核分枝杆菌进入哺乳动物细胞并在巨噬细胞内存活的能力的DNA分子。 由该基因片段编码的肽，蛋白质或多肽（例如分枝杆菌细胞进入蛋白或Mcep）可用于预防结核分枝杆菌感染的疫苗中，而针对这些肽，蛋白质或多肽产生的抗体可用于被动免疫 那些已被感染的生物体。 这些蛋白质，肽，多肽和抗体可用于诊断测定以检测组织或体液中的结核分枝杆菌。 本发明的肽，蛋白质或多肽可以与各种其它治疗材料相关联，用于给予哺乳动物，特别是人以实现这些细胞对这些材料的摄取。 基于所公开的氨基酸序列的合成构建的肽表现出与Mcep观察到的相同的哺乳动物细胞摄取活性。

公开(公告)号：US06733761B2

公开(公告)日：2004-05-11

申请号：US10029715

申请日：2001-12-20

申请人： John D. McKinney ,  William R. Jacobs, Jr.

发明人： John D. McKinney ,  William R. Jacobs, Jr.

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。

公开(公告)号：US06596281B1

公开(公告)日：2003-07-22

申请号：US09491795

申请日：2000-01-26

申请人： Maria L. Gennaro ,  Konstantin P. Lyashchenko ,  Claudia M. A. Manca

发明人： Maria L. Gennaro ,  Konstantin P. Lyashchenko ,  Claudia M. A. Manca

IPC分类号： A61K3904

CPC分类号： C07K14/35 ,  A61K2039/53 ,  Y02A50/41 ,  Y02A50/412

摘要： Two genes for proteins of M. tuberculosis have been sequenced. The DNAs and their encoded polypeptides can be used for immunoassays and vaccines. Cocktails of at least three purified recombinant antigens, and cocktails of at least three DNAs encoding them can be used for improved assays and vaccines for bacterial pathogens and parasites.

摘要翻译： 对结核分枝杆菌蛋白质的两个基因进行了测序。 DNA和其编码的多肽可用于免疫测定和疫苗。至少三种纯化的重组抗原的尾部和至少三种编码它们的DNA的鸡尾酒可用于改进细菌病原体和寄生虫的测定和疫苗。

公开(公告)号：US06569436B1

公开(公告)日：2003-05-27

申请号：US09166174

申请日：1998-10-05

申请人： Graham Stephen Le Gros ,  Charles Richard William Beasley ,  John William Holloway ,  Klaus Erb

发明人： Graham Stephen Le Gros ,  Charles Richard William Beasley ,  John William Holloway ,  Klaus Erb

IPC分类号： A61K3904

CPC分类号： A61K39/04 ,  A61K2039/52 ,  A61K2039/521 ,  A61K2039/544 ,  A61K2039/57

摘要： This invention is directed to methods of preventing or reducing the severity of asthma or the risk of development of same in an individual. The method relies on administration to the airways of the individual of an immunologically effective dose of a mycobacterium based vaccine. The mycobacteria are effective in inducing a Thl type immune response in the individual.

摘要翻译： 本发明涉及预防或减轻哮喘严重程度或个体发展风险的方法。 该方法依赖于免疫有效剂量的基于分枝杆菌的疫苗对个体的气道施用。 分枝杆菌在个体中诱导Th1型免疫应答是有效的。

公开(公告)号：US06503514B1

公开(公告)日：2003-01-07

申请号：US09612481

申请日：2000-07-07

申请人： Bruno Flesselles ,  Michel H. Klein

发明人： Bruno Flesselles ,  Michel H. Klein

IPC分类号： A61K3904

CPC分类号： C12R1/32 ,  A61K39/00 ,  C07K14/35 ,  Y10S530/80 ,  Y10S530/82 ,  Y10S530/825

摘要： Attenuated strains of Mycobacterium, particularly species of the tuberculosis complex, have the mycobacterial cell entry (mce) gene functionally disabled. The gene may be disabled by an insertion into the gene which disrupts the mycobacterial cell entry function thereof of a selectable marker which is used for screen for homologous recombinants in which a double cross-over event has been effected. The attenuated strains may be used in the immunization of hosts against Mycobacterium disease.

摘要翻译： 分枝杆菌的减毒菌株，特别是结核病复合物的种类，使分枝杆菌细胞进入（mce）基因功能失活。 该基因可以通过插入基因中而被阻断，该基因破坏了其中已经实现双交叉事件的同源重组体筛选的选择性标记的分枝杆菌细胞进入功能。 减毒菌株可用于宿主免疫分枝杆菌病。

公开(公告)号：US06723327B1

公开(公告)日：2004-04-20

申请号：US09710425

申请日：2000-11-08

申请人： James D. Watson ,  Paul L. J. Tan ,  Ross Prestidge ,  Nevin Abernethy

发明人： James D. Watson ,  Paul L. J. Tan ,  Ross Prestidge ,  Nevin Abernethy

IPC分类号： A61K3904

CPC分类号： A61K35/74 ,  A61K39/04

摘要： Methods for the prevention and treatment of disorders, including disorders of the skin and respiratory system, such as infection with mycobacteria such as M. tuberculosis or M. avium, sarcoidosis, asthma, allergic rhinitis, allergic dermatitis and lung cancers are provided, such methods comprising administering a composition comprising at least one derivative of delipidated and deglycolipidated M. vaccae cells.

摘要翻译： 提供了预防和治疗疾病（包括皮肤和呼吸系统疾病）的方法，例如分枝杆菌感染如结核分枝杆菌或鸟分枝杆菌，结节病，哮喘，过敏性鼻炎，过敏性皮炎和肺癌。 包括施用包含至少一种脱脂和去糖脂化的疫苗接种细胞的衍生物的组合物。

公开(公告)号：US06596282B1

公开(公告)日：2003-07-22

申请号：US09913523

申请日：2001-09-13

申请人： John L. Stanford ,  Graham A. W. Rook ,  Cynthia A. Stanford

发明人： John L. Stanford ,  Graham A. W. Rook ,  Cynthia A. Stanford

IPC分类号： A61K3904

CPC分类号： A61K39/04 ,  A61K35/74 ,  A61K2039/55594

摘要： The present invention provides the use of an M. vaccae preparation for the manufacture of a medicament for use in the treatment of a chronic viral infection, excluding an HIV infection. Chronic viral infections include HPV infection, such as HPV infection associated with cervical dysplasia, herpes virus infection, subacute sclerosing pan-encephalitis and hepatitis virus infection.

摘要翻译： 本发明提供了M.疫苗制剂用于制备用于治疗慢性病毒感染（不包括HIV感染）的药物的用途。 慢性病毒感染包括HPV感染，如与宫颈发育不良相关的HPV感染，疱疹病毒感染，亚急性硬化性泛脑炎和肝炎病毒感染。

公开(公告)号：US06572865B1

公开(公告)日：2003-06-03

申请号：US09477135

申请日：2000-01-03

申请人： Francis E. Nano

发明人： Francis E. Nano

IPC分类号： A61K3904

CPC分类号： G01N33/5695 ,  A61K39/00 ,  C07K14/35 ,  G01N2333/35

摘要： Nucleotide sequences isolated from Mycobacterium tuberculosis are disclosed. These sequences encode immunostimulatory peptides. Also disclosed are vaccine preparations formulated using these peptides.