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11. 发明授权

US07201907B1 Attenuated human-bovine chimeric parainfluenza virus(PIV) vaccines 有权
标题翻译：减毒的人 - 牛嵌合副流感病毒（PIV）疫苗
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。

12. 发明授权

US06923971B2 Respiratory syncytial virus vaccines expressing protective antigens from promoter-proximal genes 失效
标题翻译：呼吸道合胞病毒疫苗从启动子近端基因表达保护性抗原
公开(公告)号：US06923971B2
公开(公告)日：2005-08-02
申请号：US09887469
申请日：2001-06-22
申请人： Christine D. Krempl , Peter L. Collins , Brian R. Murphy , Ursula Buchholz , Stephen S. Whitehead
发明人： Christine D. Krempl , Peter L. Collins , Brian R. Murphy , Ursula Buchholz , Stephen S. Whitehead
IPC分类号： A61K39/155 , C12N7/00 , C12N7/01 , C12Q1/70
CPC分类号： C12N7/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , C12N2760/18521 , C12N2760/18534 , C12N2760/18543
摘要： Recombinant respiratory syncytial virus (RSV) having the position of genes shifted within the genome or antigenome of the recombinant virus are constructed by insertion, deletion or rearrangement of genes or genome segments within the recombinant genome or antigenome and are useful for eliciting an anti-RSV immune response. Shifting the position of genes in this manner provides for a selected increase or decrease in expression of the gene. In one embodiment, expression of RSV glycoproteins is upregulated by shifting one or more glycoprotein-encoding genes to a more promoter-proximal position. Genes of interest for manipulation to create gene position-shifted RSV include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or a genome segment that may be part of a gene or extragenic. Additional mutations and nucleotide modifications are provided within gene position-shifted RSV to yield desired phenotypic and structural effects.
摘要翻译：具有在重组病毒的基因组或反向原核基因内移位的基因位置的重组呼吸道合胞病毒（RSV）通过在重组基因组或反向原核基因组内的基因或基因组片段的插入，缺失或重排而构建，并且可用于引发抗RSV 免疫反应。以这种方式转移基因的位置提供了基因表达的选择性增加或减少。在一个实施方案中，通过将一个或多个编码糖蛋白的基因移位到更多的启动子近端位置来上调RSV糖蛋白的表达。用于产生基因位置偏移RSV的操作感兴趣的基因包括NS1，NS2，N，P，M，SH，M2（ORF1），M2（ORF2），L，F或G基因中的任何一个或可能成为基因的一部分或非原生质体。在基因位置偏移RSV中提供了额外的突变和核苷酸修饰，以产生所需的表型和结构效应。

13. 发明授权

US06713066B1 Production of attenuated respiratory syncytial virus vaccines involving modification of M2 ORF2 有权
标题翻译：涉及M2 ORF2修饰的减毒呼吸道合胞病毒疫苗的生产
公开(公告)号：US06713066B1
公开(公告)日：2004-03-30
申请号：US09611829
申请日：2000-07-07
申请人： Peter L. Collins , Brian R. Murphy , Alison Bermingham
发明人： Peter L. Collins , Brian R. Murphy , Alison Bermingham
IPC分类号： A61K3912
CPC分类号： C07K14/005 , A61K39/00 , A61K2039/5254 , C12N7/00 , C12N2760/18522 , C12N2760/18543 , C12N2760/18561
摘要： Recombinant respiratory syncytial virus (RSV) are provided in which expression of the second translational open reading frame encoded by the M2 gene (M2ORF2) is reduced or ablated to yield novel RSV vaccine candidates. Expression of M2 ORF2 is reduced or ablated by modifying a recombinant RSV genome or antigenome to incorporate a frame shift mutation, or one or more stop codons in M2 ORF2. Alternatively, M2 ORF2 is deleted in whole or in part to render the M2-2 protein partially or entirely non-functional or to disrupt its expression altogether. M2 ORF2 deletion and knock out mutants possess highly desirable phenotypic characteristics for vaccine development. These changes specify one or more desired phenotypic changes in the resulting virus or subviral particle. Vaccine candidates are generated that show a change in mRNA transcription, genomic or antigenomic RNA replication, viral growth characteristics, viral antigen expression, viral plaque size, and/or a change in cytopathogenicity. In addition, M2-2 knock out or deletion virus exhibits increased levels of synthesis of viral proteins in cell culture, providing an enriched source of viral antigen or protein for purification and use as a noninfectious subunit vaccine.
摘要翻译：提供了重组呼吸道合胞病毒（RSV），其中由M2基因（M2ORF2）编码的第二翻译开放阅读框的表达被减少或消融以产生新的RSV疫苗候选物。 M2 ORF2的表达通过修饰重组RSV基因组或抗原组合来结合帧移位突变或M2 ORF2中的一个或多个终止密码子来减少或消除。或者，M2 ORF2全部或部分缺失，以使M2-2蛋白部分或完全不起作用或完全破坏其表达。 M2 ORF2缺失和敲除突变体对于疫苗开发具有非常需要的表型特征。这些变化指定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mRNA转录，基因组或反基因组RNA复制，病毒生长特征，病毒抗原表达，病毒斑块大小和/或细胞致病性变化的变化。此外，M2-2敲除或缺失病毒在细胞培养物中表现出增加的病毒蛋白质合成水平，提供用于纯化和用作非感染性亚单位疫苗的病毒抗原或蛋白质的丰富来源。

14. 发明申请

US20130052718A1 ATTENUATED HUMAN PARAINFLUENZA VIRUS, METHODS AND USES THEREOF 有权
标题翻译：衰老的人类流行性感冒病毒，其方法和用途
公开(公告)号：US20130052718A1
公开(公告)日：2013-02-28
申请号：US13501447
申请日：2006-01-10
申请人： Mario H. Skiadopoulos , Peter L. Collins , Sheila Nolan
发明人： Mario H. Skiadopoulos , Peter L. Collins , Sheila Nolan
IPC分类号： C12N7/04 , C12N7/01
CPC分类号： C07K14/005 , A61K2039/5254 , A61K2039/5256 , C12N7/00 , C12N15/86 , C12N2760/18722 , C12N2760/18743 , C12N2760/18761
摘要： The invention provides self replicating infectious recombinant paramyxoviruses. The recombinant paramyxovirus preferably have one or more attenuating mutations. In some embodiments, the recombinant paramyxovirus has a separate variant polynucleotide encoding a P protein and a separate monocistronic polynucleotide encoding a V protein. In some embodiments, recombinant paramyxovirus have at least one temperature sensitive mutation and one non-temperature sensitive mutation. Also provided are compositions and methods for using the recombinant paramyxoviruses as described herein.
摘要翻译：本发明提供了自我复制的感染性重组副粘病毒。重组副粘病毒优选具有一个或多个减毒突变。在一些实施方案中，重组副粘病毒具有编码P蛋白的单独变体多核苷酸和编码V蛋白的分离的单顺反子多核苷酸。在一些实施方案中，重组副粘病毒具有至少一个温度敏感突变和一个非温度敏感突变。还提供了使用如本文所述的重组副粘病毒的组合物和方法。

15. 发明申请

US20110189232A1 RECOMBINANT HUMAN PARAINFLUENZA TYPE 1 VIRUSES (HPIV1s) CONTAINING MUTATIONS IN OR DELETION OF THE C PROTEIN ARE ATTENUATED IN AFRICAN GREEN MONKEYS AND IN CILIATED HUMAN AIRWAY EPITHELIAL CELLS AND ARE POTENTIAL VACCINE CANDIDATES FOR HPIV1 审中-公开
标题翻译：包含非蛋白绿色猴子和CILIA人类航空上皮细胞中C蛋白质突变或残留的重组人类亚型流感病毒1型病毒（HPIV1）和HPIV1潜在的候选药物候选物
公开(公告)号：US20110189232A1
公开(公告)日：2011-08-04
申请号：US13001710
申请日：2009-07-01
申请人： Emmalene Bartlett , Peter L. Collins , Mario H. Skiadopoulos , Brian R. Murphy
发明人： Emmalene Bartlett , Peter L. Collins , Mario H. Skiadopoulos , Brian R. Murphy
IPC分类号： A61K39/155 , C12N7/04 , C12N15/63 , C07H21/00 , C12N5/10 , A61P37/04 , A61P31/14
CPC分类号： C12N7/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/543 , C12N2760/18634 , C12N2760/18661
摘要： Two recently characterized live attenuated HPIV1 vaccine candidates, rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HN-T553ALΔ1710-11, which contain temperature sensitive (ts) attenuating (att) and non-ts att mutations, were evaluated in a Human Airway Epithelium (HAE) model culture system and in vivo in African Green monkeys (AGM). The vaccine candidates were highly restricted in growth in HAE at permissive (32° C.) and restrictive (37° C.) temperatures. The viruses grew slightly better at 37° C. than at 32° C., and rHPIV1-CR84G/Δ170HNT553A-LY942A was less attenuated than rHPIV1-CR84G/Δ170HNT553ALΔ1710-11. The level of replication in HAE correlated with that observed in African Green monkeys, suggesting that the HAE model is useful as a tool for pre-clinical evaluation of HPIV1 vaccines. A live attenuated HPIV1 vaccine candidate having a normal P/C gene structure of overlapping P and C open reading frames, but does not express any functional C protein, is found to highly attenuated in AGMs, and provides a significant immune response in AGMs.
摘要翻译：两个最近出现的活的减毒HPIV1疫苗候选物，rHPIV1-CR84G /＆Dgr; 170HNT553ALY942A和rHPIV1-CR84G /＆Dgr; 170HN-T553AL＆Dgr; 1710-11，其含有温度敏感（ts）减毒（att）和非ts att突变在人类气道上皮（HAE）模型培养系统和非洲绿猴（AGM）体内评估。疫苗候选物在允许（32℃）和限制性（37℃）温度下HAE的生长受到高度限制。病毒在37℃比在32℃生长稍微好一些，而rHPIV1-CR84G / Dgr; 170HNT553A-LY942A比rHPIV1-CR84G / Dgr; 170HNT553AL＆Dgr; 1710-11弱得多。 HAE中的复制水平与非洲绿猴中观察到的水平相关，表明HAE模型可用作HPIV1疫苗临床前评估的工具。被发现在AGM中高度减毒的具有重叠P和C开放阅读框但不表达任何功能性C蛋白的正常P / C基因结构的活的减毒的HPIV1疫苗候选物在AGM中提供显着的免疫应答。

16. 发明授权

US07846455B2 Attenuated chimeric respiratory syncytial virus 有权
标题翻译：减毒嵌合呼吸道合胞病毒
公开(公告)号：US07846455B2
公开(公告)日：2010-12-07
申请号：US10722000
申请日：2003-11-25
申请人： Peter L. Collins , Brian R. Murphy , Stephen S. Whitehead
发明人： Peter L. Collins , Brian R. Murphy , Stephen S. Whitehead
IPC分类号： A61K39/155 , A61K39/12 , C12N7/00 , C12N7/01 , C12N7/04
CPC分类号： C07K14/005 , A61K39/00 , A61K2039/5254 , C12N7/00 , C12N2760/18522 , C12N2760/18543 , C12N2760/18561
摘要： Chimeric respiratory syncytial virus (RSV) and vaccine compositions thereof are produced by introducing one or more heterologous gene(s) or gene segment(s) from one RSV subgroup or strain into a recipient RSV backround of a different subgroup or strain. The resulting chimeric RSV virus or subviral particle is infectious and attenuated, preferably by introduction of selected mutations specifying attenuated phenotypes into a chimeric genome or antigenome to yield, for example, temperature sensitive (ts) and/or cold adapted (ca) vaccine strains. Alternatively, chimeric RSV and vaccine compositions thereof incorporate other mutations specifying desired structural and/or phenotypic characteristics in an infectious chimeric RSV. Such chimeric RSV incorporate desired mutations specified by insertion, deletion, substitution or rearrangement of one or more selected nucleotide sequence(s), gene(s), or gene segment(s) in a chimeric RSV clone. This provides a method for development of novel vaccines against diverse RSV strains by using a common attenuated backbone as a vector to express protective antigens of heterologous strains. The immune system of an individual is stimulated to induce protection against natural RSV infection, preferably in a multivalent manner to achieve protection against multiple RSV strains and/or subgroups.
摘要翻译：嵌合呼吸道合胞病毒（RSV）及其疫苗组合物通过将一个或多个异源基因或基因区段从一个RSV亚组或菌株引入不同亚组或菌株的受体RSV背景中而产生。所得到的嵌合RSV病毒或亚病毒颗粒是感染性和减毒性的，优选通过将指定减毒表型的选定突变引入到嵌合基因组或反基因组中以产生例如温度敏感（ts）和/或冷适应（ca）疫苗株。或者，嵌合RSV及其疫苗组合物掺入在感染性嵌合RSV中指定所需结构和/或表型特征的其它突变。这种嵌合RSV包含通过嵌合RSV克隆中的一个或多个选定的核苷酸序列，基因或基因片段的插入，缺失，取代或重排而指定的所需突变。这提供了通过使用共同的减毒骨架作为表达异源株的保护性抗原的载体来开发针对不同RSV菌株的新型疫苗的方法。刺激个体的免疫系统以诱导针对天然RSV感染的保护，优选以多价方式实现针对多个RSV菌株和/或亚组的保护。

17. 发明授权

US07842798B2 Production of attenuated, human-bovine chimeric respiratory syncytial virus vaccines 失效
标题翻译：减毒，人 - 牛嵌合呼吸道合胞病毒疫苗的生产
公开(公告)号：US07842798B2
公开(公告)日：2010-11-30
申请号：US11203620
申请日：2005-08-11
申请人： Ursula Buchholz , Peter L. Collins , Brian R. Murphy , Stephen S. Whitehead , Christine D. Krempl
发明人： Ursula Buchholz , Peter L. Collins , Brian R. Murphy , Stephen S. Whitehead , Christine D. Krempl
IPC分类号： C07H21/00 , A61K39/155
CPC分类号： C12N7/00 , A61K39/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/544 , C07K14/005 , C07K2319/00 , C12N15/86 , C12N2760/18522 , C12N2760/18534 , C12N2760/18543 , C12N2760/18561 , C12N2840/203
摘要： Chimeric human-bovine respiratory syncytial virus (RSV) are infectious and attenuated in humans and other mammals and useful in vaccine formulations for eliciting an anti-RSV immune response. Also provided are isolated polynucleotide molecules and vectors incorporating a chimeric RSV genome or antigenome which includes a partial or complete human or bovine RSV “background” genome or antigenome combined or integrated with one or more heterologous gene(s) or genome segment(s) of a different RSV strain. In preferred aspects of the invention, chimeric RSV incorporate a partial or complete bovine RSV background genome or antigenome combined with one or more heterologous gene(s) or genome segment(s) from a human RSV. A variety of additional mutations and nucleotide modifications are provided within the human-bovine chimeric RSV of the invention to yield desired phenotypic and structural effects.
摘要翻译：嵌合人 - 牛呼吸道合胞病毒（RSV）在人类和其他哺乳动物中具有感染性和减毒性，并且可用于引发抗RSV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RSV基因组或抗原组的载体，其包括部分或完整的人或牛RSV“背景”基因组或与一个或多个异源基因或基因组片段不同的RSV菌株。在本发明的优选方面，嵌合RSV包含与来自人RSV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牛RSV背景基因组或反义基因组。在本发明的人 - 牛嵌合RSV内提供了多种额外的突变和核苷酸修饰，以产生所需的表型和结构效果。

18. 发明授权

US07662397B2 Respiratory syncytial virus vaccines expressing protective antigens from promoter-proximal genes 有权
标题翻译：呼吸道合胞病毒疫苗从启动子近端基因表达保护性抗原
公开(公告)号：US07662397B2
公开(公告)日：2010-02-16
申请号：US11054343
申请日：2005-02-08
申请人： Christine D. Krempl , Peter L. Collins , Brian R. Murphy , Ursula Buchholz , Stephen S. Whitehead
发明人： Christine D. Krempl , Peter L. Collins , Brian R. Murphy , Ursula Buchholz , Stephen S. Whitehead
IPC分类号： A61K39/155 , A61K39/12
CPC分类号： C07K14/005 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/543 , C12N7/00 , C12N15/86 , C12N2760/18522 , C12N2760/18534 , C12N2760/18543 , C12N2760/18561 , C12N2760/18622
摘要： Recombinant respiratory syncytial virus (RSV) having the position of genes shifted within the genome or antigenome of the recombinant virus are infectious and attenuated in humans and other mammals. Gene shifted RSV are constructed by insertion, deletion or rearrangement of genes or genome segments within the recombinant genome or antigenome and are useful in vaccine formulations for eliciting an anti-RSV immune response. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant RSV genome or antigenome wherein a gene or gene segment is shifted to a more promoter-proximal or promoter-distal position within the genome or antigenome compared to a wild type position of the gene in the RSV gene map. Shifting the position of genes in this manner provides for a selected increase or decrease in expression of the gene, depending on the nature and degree of the positional shift.
摘要翻译：重组呼吸道合胞病毒（RSV）具有在重组病毒的基因组或反向基因组内移位的基因位置，在人和其他哺乳动物中具有传染性和减毒性。通过在重组基因组或反向原核基因组内的基因或基因组片段的插入，缺失或重排构建基因转移的RSV，并且可用于引发抗RSV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重组RSV基因组或反基因组的载体，其中与基因组或基因片段中的基因的野生型位置相比，基因或基因片段转移到基因组或反基因组内的更多启动子近端或启动子远端位置 RSV基因图。以这种方式移动基因的位置提供基因的选择性增加或降低，这取决于位置偏移的性质和程度。

19. 发明授权

US07632508B2 Attenuated human-bovine chimeric parainfluenza virus (PIV) vaccines 有权
标题翻译：减毒的人 - 牛嵌合副流感病毒（PIV）疫苗
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。

20. 发明授权

US07585667B2 Negative strand RNA virus replicon 有权
标题翻译：负链RNA病毒复制子
公开(公告)号：US07585667B2
公开(公告)日：2009-09-08
申请号：US10560655
申请日：2004-06-14
申请人： Paul D. Olivo , Peter L. Collins , Mark E. Peeples
发明人： Paul D. Olivo , Peter L. Collins , Mark E. Peeples
IPC分类号： C12N15/86 , C12N7/01 , C12N15/45
CPC分类号： C12N7/00 , A61K2039/5256 , C12N15/86 , C12N2760/18543 , C12N2760/18562 , C12N2760/20222
摘要： The present invention relates to non-cytopathic negative-strand RNA virus replicons, and methods of making and using the replicons and replicon systems.
摘要翻译：本发明涉及非细胞病变负链RNA病毒复制子，以及制备和使用复制子和复制子系统的方法。

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