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1. 发明授权

US08221759B2 Neutralizing monoclonal antibodies to respiratory syncytial virus 有权
标题翻译：呼吸道合胞病毒的中和单克隆抗体
公开(公告)号：US08221759B2
公开(公告)日：2012-07-17
申请号：US13250357
申请日：2011-09-30
申请人： Glenn R. Pilkington , Page S. Gilmour , Robert M. Chanock , James E. Crowe, Jr. , Brian R. Murphy
发明人： Glenn R. Pilkington , Page S. Gilmour , Robert M. Chanock , James E. Crowe, Jr. , Brian R. Murphy
IPC分类号： A61K39/42
CPC分类号： C07K16/1027 , A61K38/00 , A61K39/00 , A61K48/00 , A61K51/1006 , A61K2039/505 , C07K2317/21 , C07K2317/55 , C07K2317/565 , G01N33/56983
摘要： The present invention relates to the identification and cloning of a novel neutralizing human monoclonal antibody to the Respiratory Syncytial Virus. The invention provides such antibodies, fragments of such antibodies retaining RSV-binding ability, chimeric antibodies retaining RSV-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Finally, the invention provides for diagnostic and therapeutic methods employing the antibodies and nucleic acids of the invention.
摘要翻译：本发明涉及鉴定和克隆呼吸道合胞病毒的新型中和人单克隆抗体。本发明提供了这样的抗体，保留RSV结合能力的这些抗体片段，保留RSV结合能力的嵌合抗体以及包含这种抗体的药物组合物。本发明还提供了编码本发明的抗体的分离的核酸和用其转化的宿主细胞。最后，本发明提供了使用本发明的抗体和核酸的诊断和治疗方法。

2. 发明申请

US20120064569A9 PRODUCTION OF ATTENUATED NEGATIVE STRANDED RNA VIRUS VACCINES FROM CLONED NUCLEOTIDE SEQUENCES 审中-公开
标题翻译：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
申请人： Brian R. Murphy , Peter L. Collins , Anna P. Durbin , Mario H. Skiadopoulos
发明人： Brian R. Murphy , Peter L. Collins , Anna P. Durbin , Mario H. Skiadopoulos
IPC分类号： C12P21/00 , C12N15/63 , C12N7/01 , C12N15/44
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。

3. 发明授权

US08075903B2 Dengue tetravalent vaccine containing a common 30 nucleotide deletion in the 3′-UTR of dengue types 1, 2, 3, and 4 or antigenic chimeric dengue viruses 1, 2, 3, and 4 有权
标题翻译：登革热四价疫苗，其在登革热类型1,2,3和4的3'-UTR中含有共同的30个核苷酸缺失或抗原嵌合登革热病毒1,2,3和4
公开(公告)号：US08075903B2
公开(公告)日：2011-12-13
申请号：US12398043
申请日：2009-03-04
申请人： Stephen S. Whitehead , Brian R. Murphy , Lewis Markoff , Barry Falgout , Joseph Blaney , Kathryn Hanley
发明人： Stephen S. Whitehead , Brian R. Murphy , Lewis Markoff , Barry Falgout , Joseph Blaney , Kathryn Hanley
IPC分类号： A61K39/295
CPC分类号： C12N7/00 , A61K39/12 , A61K2039/5254 , A61K2039/5256 , A61K2039/70 , C12N2770/24134 , C12N2770/24161 , Y02A50/386
摘要： The invention relates to a dengue virus tetravalent vaccine containing a common 30 nucleotide deletion (Δ30) in the 3′-untranslated region of the genome of dengue virus serotypes 1, 2, 3, and 4, or antigenic chimeric dengue viruses of serotypes 1, 2, 3, and 4.
摘要翻译：本发明涉及登革病毒四价疫苗，其在登革病毒血清型1,2,3和4的基因组的3'非翻译区中含有共同的30个核苷酸缺失（＆Dgr; 30），或血清型的抗原性嵌合登革热病毒 1，2，3和4。

4. 发明授权

US07951383B2 Attenuated parainfluenza virus (PIV) vaccines 有权
标题翻译：减毒副流感病毒（PIV）疫苗
公开(公告)号：US07951383B2
公开(公告)日：2011-05-31
申请号：US11785364
申请日：2007-04-17
申请人： Brian R. Murphy , Peter L. Collins , Mario H. Skiadopoulos
发明人： Brian R. Murphy , Peter L. Collins , Mario H. Skiadopoulos
IPC分类号： A61K39/155 , C12N7/00
CPC分类号： C12N7/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/543 , A61K2039/70 , C07K2319/00 , C12N2760/18434 , C12N2760/18451 , C12N2760/18461 , C12N2760/18634 , C12N2760/18651 , C12N2760/18661 , C12N2760/18671 , C12N2760/18734 , C12N2760/18751 , C12N2760/18761 , C12N2810/60
摘要： The invention provides isolated nucleic acids encoding recombinant genomes or antigenomes of Human Parainfluenza Viruses that are useful as vaccines. The recombinant genomes or antigenomes can be incorporated into expression vectors for production of recombinant viruses in vitro. The invention also provides recombinant Human Parainfluenza viruses having one or more mutations that attenuate replication of the virus in a host.
摘要翻译：本发明提供编码人类副流感病毒的重组基因组或抗原单体的分离的核酸，其可用作疫苗。重组基因组或抗原单体可以并入用于体外重组病毒生产的表达载体中。本发明还提供具有一种或多种突变的重组人副流感病毒，所述突变减弱病毒在宿主中的复制。

5. 发明申请

US20100330120A1 HUMAN PARAINFLUENZA VIRUSES HAVING SEPARATED P AND C GENES 审中-公开
标题翻译：具有分离的P和C基因的人类流感病毒病毒
公开(公告)号：US20100330120A1
公开(公告)日：2010-12-30
申请号：US12599095
申请日：2008-05-08
申请人： Peter L. Collins , Brian R. Murphy , Mario H. Skiadopoulos , Emmalene J. Bartlett , Alexander C. Schmidt , Ann-Marie M. Cruz
发明人： Peter L. Collins , Brian R. Murphy , Mario H. Skiadopoulos , Emmalene J. Bartlett , Alexander C. Schmidt , Ann-Marie M. Cruz
IPC分类号： A61K39/155 , C12N7/01 , C07H21/04 , C12N7/04 , A61P37/04 , A61P31/14
CPC分类号： C12N7/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/543 , C12N15/86 , C12N2760/18634 , C12N2760/18643 , C12N2760/18661
摘要： The invention provides self replicating infectious recombinant paramyxoviruses where the P and C genes are separated rated. The recombinant paramyxoviruses preferably have one or more attenuating mutations and/or at least one temperature sensitive mutation and one non-temperature sensitive mutation. In some embodiments, the recombinant paramyxovirus has a separate variant polynucleotide encoding a C protein and a separate monocistronic polynucleotide encoding a P protein. 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，其中P和C基因被分级。重组副粘病毒优选具有一个或多个减毒突变和/或至少一个温度敏感突变和一个非温度敏感突变。在一些实施方案中，重组副粘病毒具有编码C蛋白的单独变体多核苷酸和编码P蛋白的分离的单顺反子多核苷酸。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。

6. 发明申请

US20100316670A1 CHIMERIC SLE/DENGUE TYPE 4 ANTIGENIC VIRUSES 审中-公开
标题翻译： CHIMERIC SLE / DENGUE TYPE 4抗原病毒
公开(公告)号：US20100316670A1
公开(公告)日：2010-12-16
申请号：US12664293
申请日：2008-06-10
申请人： Joseph E. Blaney , Brian R. Murphy , Alexander G. Pletnev , Stephen S. Whitehead
发明人： Joseph E. Blaney , Brian R. Murphy , Alexander G. Pletnev , Stephen S. Whitehead
IPC分类号： A61K39/295 , C07H21/00 , C07K14/08 , C12N7/01 , A61P37/04 , A61P31/14
CPC分类号： C12N15/86 , A61K2039/5254 , C12N7/00 , C12N2770/24143 , C12N2770/24161 , Y02A50/386
摘要： Embodiments described herein concern attenuated, St. Louis Encephalitis Virus/dengue virus type 4 antigenic chimeric viruses, which can be used to prepare immunogenic compositions, vaccines, and diagnostic reagents. Methods of making and using the foregoing are provided.
摘要翻译：本文描述的实施方案涉及减毒的圣路易脑炎病毒/登革热病毒4型抗原嵌合病毒，其可用于制备免疫原性组合物，疫苗和诊断试剂。提供制造和使用前述的方法。

7. 发明授权

US07820182B2 Production of attenuated, human-bovine chimeric respiratory syncytial viruses for use in immunogenic compositions 失效
标题翻译：用于免疫原性组合物的减毒的人 - 牛嵌合呼吸道合胞病毒的生产
公开(公告)号：US07820182B2
公开(公告)日：2010-10-26
申请号：US10704116
申请日：2003-11-07
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： A61K39/155 , A61K39/12
CPC分类号： C12N15/86 , A61K39/00 , A61K39/12 , A61K39/155 , A61K2039/5254 , A61K2039/5256 , A61K2039/543 , A61K2039/544 , C07K14/005 , C07K2319/00 , C12N7/00 , C12N2760/18521 , 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 immunogenic compositions 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. Chimeric human-bovine RSV of the invention include a partial or complete “background” RSV genome or antigenome derived from or patterned after a human or bovine RSV strain or subgroup virus combined with one or more heterologous gene(s) or genome segment(s) of a different RSV strain or subgroup virus to form the human-bovine chimeric RSV genome or antigenome. 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. Genes of interest include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or a genome segment including a protein or portion thereof. 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免疫应答的免疫原性组合物。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。本发明的嵌合人类牛RSV包括部分或完整的“背景”RSV基因组或在与一个或多个异源基因或基因组片段组合的人或牛RSV病毒株或亚组病毒之后衍生或构图的部分或完整的“背景” 的不同RSV株或亚组病毒形成人 - 牛嵌合RSV基因组或抗原组。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。感兴趣的基因包括任何NS1，NS2，N，P，M，SH，M2（ORF1），M2（ORF2），L，F或G基因或包含蛋白质或其部分的基因组片段。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。

8. 发明授权

US07744902B2 Respiratory syncytial virus vaccines expressing protective antigens from promotor-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：US07744902B2
公开(公告)日：2010-06-29
申请号：US11033055
申请日：2005-01-10
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
CPC分类号： C07K14/005 , A61K39/00 , A61K2039/5254 , A61K2039/5256 , A61K2039/543 , A61K2039/545 , C07H21/02 , C07K2319/00 , C12N7/00 , C12N15/86 , C12N2760/18522 , C12N2760/18543 , C12N2760/18561 , C12N2760/18562
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. In one embodiment, RSV glycoproteins are 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. A variety of additional mutations and nucleotide modifications are provided within the gene position-shifted RSV of the invention to yield desired phenotypic and structural effects.
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动的基因位置，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。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。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。在本发明的基因位置偏移的RSV中提供了多种另外的突变和核苷酸修饰，以产生所需的表型和结构效应。

9. 发明申请

US20090263424A1 DEVELOPMENT OF MUTATIONS USEFUL FOR ATTENUATING DENGUE VIRUSES AND CHIMERIC DENGUE VIRUSES 有权
标题翻译：开发有用于减少登革热病毒和濒危病毒的突变
公开(公告)号：US20090263424A1
公开(公告)日：2009-10-22
申请号：US12396376
申请日：2009-03-02
申请人： Stephen S. Whitehead , Brian R. Murphy , Kathryn A. Hanley , Joseph E. Blaney
发明人： Stephen S. Whitehead , Brian R. Murphy , Kathryn A. Hanley , Joseph E. Blaney
IPC分类号： A61K39/12
CPC分类号： A61K39/12 , A61K39/295 , A61K2039/5252 , A61K2039/5254 , A61K2039/5256 , A61K2039/54 , A61K2039/575 , A61K2039/70 , C12N7/00 , C12N2770/24121 , C12N2770/24134 , C12N2770/24161 , C12N2770/24162 , C12N2770/24171 , C12Q1/701 , C12Q2600/156 , G01N2333/18 , G01N2500/10 , Y02A50/386
摘要： A menu of mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccines.
摘要翻译：开发了一个突变菜单，可用于微调登革病毒疫苗的衰减和生长特性。

10. 发明申请

US20090110684A1 Neutralizing monoclonal antibodies to respiratory syncytial virus 审中-公开
标题翻译：呼吸道合胞病毒的中和单克隆抗体
公开(公告)号：US20090110684A1
公开(公告)日：2009-04-30
申请号：US12082000
申请日：2008-04-24
申请人： Glenn R. Pilkington , Page S. Gilmour , Robert M. Chanock , James E. Crowe, JR. , Brian R. Murphy
发明人： Glenn R. Pilkington , Page S. Gilmour , Robert M. Chanock , James E. Crowe, JR. , Brian R. Murphy
IPC分类号： A61K39/395 , A61K31/7088 , A61P31/12
CPC分类号： C07K16/1027 , A61K38/00 , A61K39/00 , A61K48/00 , A61K51/1006 , A61K2039/505 , C07K2317/21 , C07K2317/55 , C07K2317/565 , G01N33/56983
摘要： The present invention relates to the identification and cloning of a novel neutralizing human monoclonal antibody to the Respiratory Syncytial Virus. The invention provides such antibodies, fragments of such antibodies retaining RSV-binding ability, chimeric antibodies retaining RSV-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Finally, the invention provides for diagnostic and therapeutic methods employing the antibodies and nucleic acids of the invention.
摘要翻译：本发明涉及鉴定和克隆呼吸道合胞病毒的新型中和人单克隆抗体。本发明提供了这样的抗体，保留RSV结合能力的这些抗体片段，保留RSV结合能力的嵌合抗体以及包含这种抗体的药物组合物。本发明还提供了编码本发明的抗体的分离的核酸和用其转化的宿主细胞。最后，本发明提供了使用本发明的抗体和核酸的诊断和治疗方法。

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