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。

公开(公告)号：US06372478B1

公开(公告)日：2002-04-16

申请号：US09314207

申请日：1999-05-19

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： C12N120

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。

公开(公告)号：US5968733A

公开(公告)日：1999-10-19

申请号：US14560

申请日：1998-01-28

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： 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 ,  C12Q1/70 ,  C07H21/04

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 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。

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。

公开(公告)号：US5504005A

公开(公告)日：1996-04-02

申请号：US361944

申请日：1989-06-05

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： 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 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。

公开(公告)号：US4906742A

公开(公告)日：1990-03-06

申请号：US892095

申请日：1986-07-31

申请人： Richard A. Young ,  Barry R. Bloom ,  Ronald W. Davis

发明人： Richard A. Young ,  Barry R. Bloom ,  Ronald W. Davis

IPC分类号： A61K39/00 ,  C07K14/35

CPC分类号： C07K14/35 ,  A61K39/00

摘要： Genes encoding five immunodeterminant protein antigens of the leprosy parasite Mycobacterium leprae have been isolated. The gene encoding the M. leprae 65kD antigen was sequenced and a lambda gt11 gene sublibrary was constructed with fragments of the gene. Recombinant DNA clones producing specific antigenic determinants were isolated using monoclonal antibodies and the sequences of their insert DNAs were determined with a rapid primer extension method. Amino acid sequences for six different epitopes of the M. leprae protein were elucidated. A peptide containing sequences for one of these epitopes, which is unique to M. leprae, was synthesized and shown to bind the appropriate monoclonal antibody; The approach described here can be used to elucidate rapidly protein epitopes that are recognized by antibodies or T cells. In addition, the well-characterized M. leprae antigens can be used in prevention, diagnosis and treatment of leprosy.

摘要翻译： 已经分离了编码麻风病寄生虫分枝杆菌分枝杆菌的五种免疫决定簇蛋白质抗原的基因。 对编码麻风病65kD抗原的基因进行测序，并用该基因的片段构建λgt11基因亚型图谱。 使用单克隆抗体分离产生特异性抗原决定簇的重组DNA克隆，并用快速引物延伸法测定其插入DNA序列。 阐明了六种不同表型的麻风树皮蛋白的氨基酸序列。 合成了一种含有这些表位之一的序列的肽，其是麻疯皮病特有的，并显示结合合适的单克隆抗体; 这里描述的方法可用于阐明由抗体或T细胞识别的蛋白质表位。 此外，良好表征的麻疯病抗原可用于预防，诊断和治疗麻风病。

公开(公告)号：US4788135A

公开(公告)日：1988-11-29

申请号：US786883

申请日：1985-10-10

申请人： Ronald W. Davis ,  Richard A. Young

发明人： Ronald W. Davis ,  Richard A. Young

IPC分类号： C12N15/10 ,  C12N15/62 ,  C12N15/70 ,  C12Q1/68 ,  G01N33/68 ,  C12N1/00 ,  C12N15/00

CPC分类号： C12N15/1086 ,  C12N15/62 ,  C12N15/70 ,  C12Q1/68 ,  G01N33/6854

摘要： Systems are provided for the dual purpose of cloning genes using antibodies as probes and isolating unknown proteins encoded by cloned DNA. The method employs a vector derived from phage which is used in combination with a high frequency lysogenic host. The vector is further characterized by having an inducible promoter regulating expression of a gene into which the foreign DNA may be introduced to produce a fused protein, and controlled induction of the prophage with rapid increase in copy number and high level transcription of foreign DNA. The technique is exemplified with a specific lambda phage construct in conjunction with the .beta.-galactosidase structural gene lacZ.

摘要翻译： 提供系统用于克隆使用抗体作为探针并分离由克隆DNA编码的未知蛋白的基因的双重目的。 该方法采用与高频溶素宿主组合使用的来自噬菌体的载体。 载体的特征还在于具有调节外源DNA可能被引入以产生融合蛋白的基因的表达的诱导型启动子，并且能够迅速增加外源DNA的拷贝数和高水平转录来控制原噬菌体的诱导。 该技术用与β-半乳糖苷酶结构基因lacZ结合的特异性λ噬菌体构建体来举例说明。

公开(公告)号：US20090221428A1

公开(公告)日：2009-09-03

申请号：US12065076

申请日：2006-09-07

申请人： Richard A. Young ,  Tong Ihn Lee ,  Matthew Guenther ,  Laurie A. Boyer

发明人： Richard A. Young ,  Tong Ihn Lee ,  Matthew Guenther ,  Laurie A. Boyer

IPC分类号： C40B20/04 ,  C12Q1/68 ,  C07H1/00 ,  C40B50/14

CPC分类号： C12Q1/6809 ,  C12Q1/6837 ,  C12Q2565/501 ,  C12Q2523/101 ,  C12Q2522/101

摘要： The invention relates to improved methods of identifying the genomic regions to which a protein of interest binds, and in particular, to methods that apply to stem cells such as but not limited to; embryonic stem cells and adult stem cells. The invention also provides methods of identifying agents which modulate differentiation of stem cells. The invention also provides methods of defining the differentiation potential of a cell and of designing array oligonucleotides.

摘要翻译： 本发明涉及鉴定目标蛋白质结合的基因组区域的改进方法，特别涉及适用于干细胞的方法，例如但不限于： 胚胎干细胞和成体干细胞。 本发明还提供鉴定调节干细胞分化的药剂的方法。 本发明还提供了定义细胞的分化潜能和设计阵列寡核苷酸的方法。

公开(公告)号：US06653071B1

公开(公告)日：2003-11-25

申请号：US09326137

申请日：1999-06-04

申请人： Frank C. P. Holstege ,  Richard A. Young

发明人： Frank C. P. Holstege ,  Richard A. Young

IPC分类号： C12Q168

CPC分类号： G01N33/5023 ,  C07K14/4702 ,  G01N33/5008 ,  G01N33/5041

摘要： A method of identifying cellular regulatory circuits which employ at least one component of a subcomplex of regulatory proteins within the RNA II polymerase holoenzyme which behaves as a signal processor for gene-specific regulators (at least one component of a eukaryotic transcription initiation apparatus) and of determining the set of components of the apparatus which are responsible for regulation of each gene and the set of genes which are coordinately controlled by each transcription factor.

摘要翻译： 鉴定在RNAII聚合酶全酶中使用调节蛋白亚复合物的至少一种组分的细胞调节电路的方法，其作为基因特异性调节剂（真核转录起始装置的至少一种成分）的信号处理器和 确定负责每个基因的调节的装置的组成和由每个转录因子协调控制的一组基因。

公开(公告)号：US06482614B1

公开(公告)日：2002-11-19

申请号：US09468041

申请日：1999-12-21

申请人： Richard A. Young

发明人： Richard A. Young

IPC分类号： C12P2104

CPC分类号： A61K39/21 ,  A61K39/00 ,  A61K39/0008 ,  A61K39/04 ,  A61K39/12 ,  A61K39/385 ,  A61K39/39 ,  A61K2039/545 ,  A61K2039/55516 ,  A61K2039/6043 ,  A61K2039/70 ,  C07K14/005 ,  C07K14/35 ,  C07K2319/03 ,  C07K2319/20 ,  C07K2319/21 ,  C07K2319/35 ,  C07K2319/40 ,  C07K2319/50 ,  C07K2319/735 ,  C07K2319/75 ,  C12N15/62 ,  C12N2740/16222 ,  C12N2740/16234

摘要： The present invention relates to stress proteins and methods of modulating an individual's immune response. In particular, it relates to the use of such stress proteins in immune therapy and prophylaxis, which results in an induction or enhancement of an individual's immune response and as an immunotherapeutic agent which results in a decrease of an individual's immune response to his or her own cells. The present invention also relates to compositions comprising a stress protein joined to another component, such as a fusion protein in which a stress protein is fused to an antigen. Further, the present invention relates to a method of generating antibodies to a substance using a conjugate comprised of a stress protein joined to the substance.