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1.发明授权Use of recombinant live-attenuated parainfluenza virus (PIV) as a vector to protect against disease caused by PIV and respiratory syncytial virus (RSV) 有权使用重组减毒副流感病毒（PIV）作为载体，以防止由PIV和呼吸道合胞病毒（RSV）引起的疾病公开(公告)号：US07314631B1
公开(公告)日：2008-01-01
申请号：US09458813
申请日：1999-12-10
IPC分类号： A61K39/155 , C12N7/00
CPC分类号： C12N15/86 , A61K39/12 , A61K39/155 , A61K39/165 , A61K2039/5254 , A61K2039/5256 , A61K2039/70 , C07K14/005 , C12N2760/18422 , C12N2760/18434 , C12N2760/18634 , C12N2760/18643 , C12N2760/18734
摘要： Chimeric parainfluenza viruses (PIVs) are provided that incorporate a PIV vector genome or antigenome and one or more antigenic determinant(s) of a heterologous PIV or non-PIV pathogen. These chimeric viruses are infectious and attenuated in humans and other mammals and are useful in vaccine formulations for eliciting and immune responses against one or more PIVs, or against a PIV and non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric PIV genome or antigenome which includes a partial or complete PIV vector genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) encoding antigenic determinant(s) of a heterologous PIV or non-PIV pathogen. In preferred aspects of the invention, chimeric PIV incorporate a partial or complete human PIV vector genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a heterologous PIV or non-PIV pathogen, wherein the chimeric virus is attenuated for use as a vaccine agent by any of a variety of mutations and nucleotide modifications introduced into the chimeric genome or antigenome.
摘要翻译： 提供了嵌合副流感病毒（PIV），其包含PIV载体基因组或反义基因组以及异源PIV或非PIV病原体的一个或多个抗原决定簇。 这些嵌合病毒在人类和其他哺乳动物中是感染性和减毒性的，并且可用于针对一种或多种PIV或针对PIV和非PIV病原体的引发和免疫应答的疫苗制剂。 还提供了分离的多核苷酸分子和掺入嵌合PIV基因组或抗原组的载体，其包括与编码抗原决定簇的一个或多个异源基因或基因组片段组合或整合的部分或完整PIV载体基因组或反义基因， 的异源PIV或非PIV病原体。 在本发明的优选方面，嵌合PIV掺入与来自异源PIV或非PIV病原体的一个或多个异源基因或基因组片段组合的部分或完整的人PIV载体基因组或反向异构体，其中所述嵌合病毒 通过引入到嵌合基因组或反基因组中的各种突变和核苷酸修饰中的任一种减毒用作疫苗剂。
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2.发明授权Use of recombinant parainfluenza viruses (PIVs) as vectors to protect against infection and disease caused by PIV and other human pathogens 有权使用重组副流感病毒（PIVs）作为载体，以防止由PIV和其他人类病原体引起的感染和疾病公开(公告)号：US07192593B2
公开(公告)日：2007-03-20
申请号：US09733692
申请日：2000-12-08
申请人： Brian R. Murphy , Peter L. Collins , Alexander C. Schmidt , Anna P. Durbin , Mario H. Skiadopoulos , Tao Tao
发明人： Brian R. Murphy , Peter L. Collins , Alexander C. Schmidt , Anna P. Durbin , Mario H. Skiadopoulos , Tao Tao
IPC分类号： A61K39/12 , A61K39/155
CPC分类号： C07K14/005 , A61K39/00 , A61K2039/5256 , C12N15/86 , C12N2760/18422 , C12N2760/18622 , C12N2760/18643
摘要： Chimeric parainfluenza viruses (PIVs) incorporate a PIV vector genome or antigenome and one or more antigenic determinant(s) of a heterologous PIV or non-PIV pathogen. These chimeric viruses are infectious and attenuated in humans and other mammals and are useful in vaccine formulations for eliciting an immune responses against one or more PIVs, or against a PIV and non-PIV pathogen. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric Ply genome or antigenome which includes a partial or complete PIV vector genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) encoding antigenic determinant(s) of a heterologous PIV or non-PIV pathogen.
摘要翻译： 嵌合型副流感病毒（PIV）掺入PIV载体基因组或反向原子团以及异源PIV或非PIV病原体的一个或多个抗原决定簇。 这些嵌合病毒在人和其他哺乳动物中是感染性和减毒性的，并且可用于引发针对一种或多种PIV或针对PIV和非PIV病原体的免疫应答的疫苗制剂中。 还提供了分离的多核苷酸分子和掺入嵌合Ply基因组或反向基团的载体，其包括与编码抗原决定簇的一个或多个异源基因或基因组片段组合或整合的部分或完整PIV载体基因组或反义基因， 的异源PIV或非PIV病原体。
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3.发明授权公开(公告)号：US07632508B2
公开(公告)日：2009-12-15
申请号：US11324284
申请日：2006-01-04
申请人： Alexander C. Schmidt , Mario H. Skiadopoulos , Peter L. Collins , Brian R. Murphy , Jane E. Bailly , Anna P. Durbin
发明人： Alexander C. Schmidt , Mario H. Skiadopoulos , Peter L. Collins , Brian R. Murphy , Jane E. Bailly , Anna P. Durbin
IPC分类号： A61K39/12 , A61K39/155
CPC分类号： C12N7/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/543 , A61K2039/544 , C12N2760/18634 , C12N2760/18661
摘要： Chimeric human-bovine parainfluenza viruses (PIVs) are infectious and attenuated in humans and other mammals and useful individually or in combination in vaccine formulations for eliciting an immune response to PIV or other pathogens. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric PIV genome or antigenome which includes a partial or complete human or bovine PIV “background” genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) of a different PIV. Chimeric human-bovine PIV of the invention include a partial or complete “background” PIV genome or antigenome derived from or patterned after a human or bovine PIV virus combined with one or more heterologous gene(s) or genome segment(s) of a different pathogen, including different PIV virus to form the human-bovine chimeric PIV genome or antigenome.
摘要翻译： 嵌合人 - 牛副流感病毒（PIV）在人类和其他哺乳动物中是感染性和减毒性的，并且在疫苗制剂中单独使用或组合用于引发对PIV或其它病原体的免疫应答。 还提供了分离的多核苷酸分子和掺入嵌合PIV基因组或抗原组的载体，其包括部分或完整的人或牛PIV“背景”基因组或反基因组，其与一个或多个异源基因或基因组片段组合或整合， 不同的PIV。 本发明的嵌合人牛PIV包括部分或完整的“背景”PIV基因组或反义基因组，其衍生自或构图在人或牛PIV病毒与一个或多个异源基因或不同基因组的基因组片段组合 病原体，包括不同的PIV病毒，以形成人 - 牛嵌合PIV基因组或抗原组。
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4.发明申请PRODUCTION OF ATTENUATED NEGATIVE STRANDED RNA VIRUS VACCINES FROM CLONED NUCLEOTIDE SEQUENCES 审中-公开从克隆核苷酸序列中产生衰减的病毒RNA病毒疫苗公开(公告)号：US20090081728A1
公开(公告)日：2009-03-26
申请号：US12136765
申请日：2008-06-10
CPC分类号： A61K39/155 , A61K39/12 , A61K2039/5254 , A61K2039/543 , A61K2039/544 , C12N7/00 , C12N2760/18534 , C12N2760/18561 , C12N2760/18634
摘要： Attenuated, recombinant negative stranded RNA viruses suitable for vaccine use are produced from one or more isolated polynucleotide molecules encoding the virus. A recombinant genome or antigenome of the subject virus is modified to encode a mutation within a recombinant protein of the virus at one or more amino acid positions(s) corresponding to a site of an attenuating mutation in a heretologous, mutant negative stranded RNA virus. A similar attenuating mutation as identified in the heterologous negative stranded RNA virus is thus incorporated at a corresponding site within the recombinant virus to confer an attenuated phenotype on the recombinant virus. The attenuating mutation incorporated in the recombinant virus may be identical or conservative in relation to the attenuating mutation identified in the heterologous, mutant virus. By the transfer of mutations into recombinant negative stranded RNA viruses in this matter, candidate vaccine viruses are engineered to elicit a desired immune response against a subject virus in a host susceptible to infection thereby.
摘要翻译： 减毒，从编码病毒的一个或多个分离的多核苷酸分子产生适合疫苗使用的重组负链RNA病毒。 修饰受试病毒的重组基因组或反基因组，以在对应于本体异质突变体负链RNA病毒中的减毒突变位点的一个或多个氨基酸位置上编码病毒重组蛋白内的突变。 因此，在异源负链RNA病毒中鉴定的类似的减毒突变被并入重组病毒中的相应位点，以在重组病毒上赋予减毒表型。 结合在重组病毒中的减毒突变可以与异源突变病毒中鉴定的减毒突变相同或保守。 通过将突变转移到重组负链RNA病毒中，候选疫苗病毒被工程化以在由此感染的宿主中引发针对受试者病毒的所需免疫应答。
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5.发明申请PRODUCTION OF ATTENUATED NEGATIVE STRANDED RNA VIRUS VACCINES FROM CLONED NUCLEOTIDE SEQUENCES 审中-公开从克隆核苷酸序列中产生衰减的病毒RNA病毒疫苗公开(公告)号：US20120064569A9
公开(公告)日：2012-03-15
申请号：US12136765
申请日：2008-06-10
CPC分类号： A61K39/155 , A61K39/12 , A61K2039/5254 , A61K2039/543 , A61K2039/544 , C12N7/00 , C12N2760/18534 , C12N2760/18561 , C12N2760/18634
摘要： Attenuated, recombinant negative stranded RNA viruses suitable for vaccine use are produced from one or more isolated polynucleotide molecules encoding the virus. A recombinant genome or antigenome of the subject virus is modified to encode a mutation within a recombinant protein of the virus at one or more amino acid positions(s) corresponding to a site of an attenuating mutation in a heretologous, mutant negative stranded RNA virus. A similar attenuating mutation as identified in the heterologous negative stranded RNA virus is thus incorporated at a corresponding site within the recombinant virus to confer an attenuated phenotype on the recombinant virus. The attenuating mutation incorporated in the recombinant virus may be identical or conservative in relation to the attenuating mutation identified in the heterologous, mutant virus. By the transfer of mutations into recombinant negative stranded RNA viruses in this matter, candidate vaccine viruses are engineered to elicit a desired immune response against a subject virus in a host susceptible to infection thereby.
摘要翻译： 减毒，从编码病毒的一个或多个分离的多核苷酸分子产生适合疫苗使用的重组负链RNA病毒。 修饰受试病毒的重组基因组或反基因组，以在对应于本体异质突变体负链RNA病毒中的减毒突变位点的一个或多个氨基酸位置上编码病毒重组蛋白内的突变。 因此，在异源负链RNA病毒中鉴定的类似的减毒突变被并入重组病毒中的相应位点，以在重组病毒上赋予减毒表型。 结合在重组病毒中的减毒突变可以与异源突变病毒中鉴定的减毒突变相同或保守。 通过将突变转移到重组负链RNA病毒中，候选疫苗病毒被工程化以在由此感染的宿主中引发针对受试者病毒的所需免疫应答。
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6.发明授权Production of attenuated parainfluenza virus vaccines from cloned nucleotide sequences 失效从克隆的核苷酸序列产生减毒副流感病毒疫苗公开(公告)号：US07208161B1
公开(公告)日：2007-04-24
申请号：US09083793
申请日：1998-05-22
IPC分类号： A61K39/155 , C12N7/00
CPC分类号： C07K16/1027 , A61K39/00 , A61K2039/5254 , C07K14/005 , C07K2319/00 , C12N7/00 , C12N2760/18622 , C12N2760/18643 , C12N2760/18661
摘要： Isolated polynucleotide molecules provide recombinant PIV genomes and antigenomes for production of recombinant PIV vaccines. The recombinant genome or antigenome can be expressed with a nucleoprotein (N), phosphoprotein (P), and a large (L) polymerase protein to produce isolated infectious PIV particles. The recombinant PIV genome and antigenome can be modified to produce desired changes, for example to incorporate attenuating mutations from biologically derived PIV mutants or to create chimeric PIV clones, to generate attenuated, immunogenic viruses for vaccine use.
摘要翻译： 分离的多核苷酸分子提供用于重组PIV疫苗生产的重组PIV基因组和抗原单体。 可以用核蛋白（N），磷酸化蛋白（P）和大的（L）聚合酶蛋白来表达重组基因组或反基因组以产生分离的感染性PIV颗粒。 可以修饰重组PIV基因组和反义基因组以产生所需的变化，例如从生物衍生的PIV突变体引入减毒突变或产生嵌合PIV克隆，以产生用于疫苗使用的减毒的免疫原性病毒。
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7.发明授权公开(公告)号：US07201907B1
公开(公告)日：2007-04-10
申请号：US09586479
申请日：2000-06-01
申请人： Alexander C. Schmidt , Mario H. Skiadopoulos , Peter L. Collins , Brian R. Murphy , Jane E. Bailly , Anna P. Durbin
发明人： Alexander C. Schmidt , Mario H. Skiadopoulos , Peter L. Collins , Brian R. Murphy , Jane E. Bailly , Anna P. Durbin
IPC分类号： A61K39/12 , A61K39/155
CPC分类号： C12N7/00 , A61K39/12 , A61K39/155 , A61K2039/525 , A61K2039/5254 , A61K2039/5256 , A61K2039/543 , C12N2760/18634 , C12N2760/18643 , C12N2760/18645 , C12N2760/18661 , C12N2810/6072
摘要： Chimeric human-bovine parainfluenza viruses (PIVs) are infectious and attenuated in humans and other mammals and useful individually or in combination in vaccine formulations for eliciting an anti-PIV immune response or as vectors for introducing heterologous genes into a host. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric PIV genome or antigenome which includes a partial or complete human or bovine PIV “background” genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) of a different PIV. Chimeric human-bovine PIV of the invention include a partial or complete “background” PIV genome or antigenome derived from or patterned after a human or bovine PIV virus combined with one or more heterologous gene(s) or genome segment(s) of a different PIV virus to form the human-bovine chimeric PIV genome or antigenome.
摘要翻译： 嵌合人 - 牛副流感病毒（PIV）在人类和其他哺乳动物中具有感染性和减毒性，并且在疫苗制剂中单独使用或组合用于引发抗PIV免疫应答或作为将异源基因导入宿主的载体。 还提供了分离的多核苷酸分子和掺入嵌合PIV基因组或抗原组的载体，其包括部分或完整的人或牛PIV“背景”基因组或反基因组，其与一个或多个异源基因或基因组片段组合或整合， 不同的PIV。 本发明的嵌合人牛PIV包括部分或完整的“背景”PIV基因组或反义基因组，其衍生自或构图在人或牛PIV病毒与一个或多个异源基因或不同基因组的基因组片段组合 PIV病毒形成人 - 牛嵌合PIV基因组或抗原组。
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8.发明授权Recombinant parainfluenza virus vaccines attenuated by deletion or ablation of a non-essential gene 有权重组副流感病毒疫苗通过非必需基因的缺失或消融而减弱公开(公告)号：US06410023B1
公开(公告)日：2002-06-25
申请号：US09350821
申请日：1999-07-09
IPC分类号： A61K3912
CPC分类号： C12N7/00 , A61K39/00 , A61K2039/522 , C07K14/005 , C12N2760/18622 , C12N2760/18643 , C12N2760/18661
摘要： Recombinant parainfluenza virus (PIV) are provided in which expression of the C, D and/or V translational open reading frame(s) (ORFs) is reduced or ablated to yield novel PIV vaccine candidates. Expression of the C, D and/or V ORF(s) is reduced or ablated by modifying a recombinant PIV genome or antigenome, for example by introduction of a stop codon, by a mutation in an RNA editing site, by a mutation that alters the amino acid specified by an initiation codon, or by a frame shift mutation in the targeted ORF(s). Alternatively, the C, D and/or V ORF(s) is deleted in whole or in part to render the protein(s) encoded thereby partially or entirely non-functional or to disrupt protein expression altogether. C, D and/or V ORF(s) deletion and knock out mutants possess highly desirable phenotypic characteristics for vaccine development. These deletion and knock out mutations changes specify one or more desired phenotypic changes in the resulting virus or subviral particle. Vaccine candidates are generated that show a change in viral growth characteristics, attenuation, plaque size, and/or a change in cytopathogenicity, among other novel phenotypes. A variety of additional mutations and nucleotide modifications are provided within the C, D and/or V ORF(s) deletion or ablation mutant PIV of the invention to yield desired phenotypic and structural effects.
摘要翻译： 提供了重组副流感病毒（PIV），其中C，D和/或V翻译开放阅读框（ORF）的表达被降低或消融以产生新型PIV疫苗候选物。 C，D和/或V ORF的表达通过修饰重组PIV基因组或反义基因组，例如通过引入终止密码子，通过RNA编辑位点中的突变，通过改变的突变来降低或消除 由起始密码子指定的氨基酸或靶向ORF中的帧位移突变。 或者，全部或部分删除C，D和/或V ORF，以使由此编码的蛋白质部分或完全不起作用或完全破坏蛋白质表达。 C，D和/或V ORF（s）缺失和敲除突变体对疫苗开发具有非常需要的表型特征。 这些缺失和敲除突变变化指定了所得病毒或亚病毒颗粒中的一种或多种期望的表型变化。 产生疫苗候选物，其显示病毒生长特征，衰减，斑块大小和/或细胞致病性变化以及其他新型表型之间的变化。 本发明的C，D和/或V ORF缺失或消融突变体PIV中提供了多种其它突变和核苷酸修饰，以产生所需的表型和结构效果。
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