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11. 发明授权

US5935573A Method of use of an analog of Haemophilus influenzae Hin47 with reduced protease activity 失效
标题翻译：使用具有降低的蛋白酶活性的流感嗜血杆菌Hin47类似物的方法
公开(公告)号：US5935573A
公开(公告)日：1999-08-10
申请号：US482816
申请日：1995-06-07
申请人： Sheena M. Loosmore , Yan-Ping Yang , Pele Chong , Raymond P. Oomen , Michel H. Klein
发明人： Sheena M. Loosmore , Yan-Ping Yang , Pele Chong , Raymond P. Oomen , Michel H. Klein
IPC分类号： A61K39/00 , A61P31/04 , C07K14/285 , C12N9/52 , C12N15/31 , A61K38/48
CPC分类号： C12N9/52 , C07K14/285 , A61K39/00 , C07K2319/00
摘要： An isolated and purified analog of Haemophilus influenzae Hin47 protein has a decreased protease activity which is less than about 10% of that of natural Hin47 protein and preferably substantially the same immunogenic properties as natural Hin47 protein. An isolated an purified nucleic acid molecule encoding the Hin47 analog may be provided in a recombinant plasmid which may be introduced into a cell which is grown to produce the Hin47 analog. Immunogenic compositions comprising the Hin47 analog and the encoding nucleic acid may be formulated as vaccines for in vivo administration to a host, including a human, to confer protection against diseases caused by a bacterial pathogen, including Haemophilus species, such as Haemophilus influenzae, that produces Hin47 protein or a protein capable of inducing antibodies in the host specifically reactive with Hin47 protein. The Hin47 analog and the encoding nucleic acid also may be employed in diagnostic applications.
摘要翻译：分离和纯化的流感嗜血杆菌Hin47蛋白的类似物具有降低的蛋白酶活性，其小于天然Hin47蛋白的约10％，优选与天然Hin47蛋白基本相同的免疫原性。可以在重组质粒中提供分离的纯化的编码Hin47类似物的核酸分子，所述重组质粒可以被引入生长以产生Hin47类似物的细胞中。包含Hin47类似物和编码核酸的免疫原性组合物可以配制成用于体内施用于宿主（包括人）的疫苗，以赋予针对由细菌病原体（例如流感嗜血杆菌）产生的细菌病原体引起的疾病的保护， Hin47蛋白或能够诱导与Hin47蛋白特异性反应的宿主中的抗体的蛋白质。 Hin47类似物和编码核酸也可用于诊断应用。

12. 发明授权

US5656436A Analog of Haemophilus Hin47 with reduced protease activity 失效
标题翻译：具有减少的蛋白酶活性的嗜血杆菌Hin47的类似物
公开(公告)号：US5656436A
公开(公告)日：1997-08-12
申请号：US483859
申请日：1995-06-07
申请人： Sheena M. Loosmore , Yan-Ping Yang , Pele Chong , Raymond P. Oomen , Michel H. Klein
发明人： Sheena M. Loosmore , Yan-Ping Yang , Pele Chong , Raymond P. Oomen , Michel H. Klein
IPC分类号： A61K39/00 , A61P31/04 , C07K14/285 , C12N9/52 , C12N15/31 , G01N33/53 , C12Q1/68 , G01N33/554
CPC分类号： C12N9/52 , C07K14/285 , A61K39/00 , C07K2319/00
摘要： An isolated and purified analog of Haemophilus influenzae Hin47 protein has a decreased protease activity which is less than about 10% of that of natural Hin47 protein and preferably substantially the same immunogenic properties as natural Hin47 protein. An isolated an purified nucleic acid molecule encoding the Hin47 analog may be provided in a recombinant plasmid which may be introduced into a cell which is grown to produce the Hin47 analog. Immunogenic compositions comprising the Hin47 analog and the encoding nucleic acid may be formulated as vaccines for in vivo administration to a host, including a human, to confer protection against diseases caused by a bacterial pathogen, including Haemophilus species, such as Haemophilus influenzae, that produces Hin47 protein or a protein capable of inducing antibodies in the host specifically reactive with Hin47 protein. The Hin47 analog and the encoding nucleic acid also may be employed in diagnostic applications.
摘要翻译：分离和纯化的流感嗜血杆菌Hin47蛋白的类似物具有降低的蛋白酶活性，其小于天然Hin47蛋白的约10％，优选与天然Hin47蛋白基本相同的免疫原性。可以在重组质粒中提供分离的纯化的编码Hin47类似物的核酸分子，所述重组质粒可以被引入生长以产生Hin47类似物的细胞中。包含Hin47类似物和编码核酸的免疫原性组合物可以配制成用于体内施用于宿主（包括人）的疫苗，以赋予针对由细菌病原体（例如流感嗜血杆菌）产生的细菌病原体引起的疾病的保护， Hin47蛋白或能够诱导与Hin47蛋白特异性反应的宿主中的抗体的蛋白质。 Hin47类似物和编码核酸也可用于诊断应用。

13. 发明授权

US6025342A Analog of Haemophilus Hin47 with reduced protease activity 失效
标题翻译：具有减少的蛋白酶活性的嗜血杆菌Hin47的类似物
公开(公告)号：US6025342A
公开(公告)日：2000-02-15
申请号：US74659
申请日：1998-05-08
申请人： Sheena M. Loosmore , Yan-Ping Yang , Pele Chong , Raymond P. Oomen , Michel H. Klein
发明人： Sheena M. Loosmore , Yan-Ping Yang , Pele Chong , Raymond P. Oomen , Michel H. Klein
IPC分类号： A61K39/00 , C07K14/285 , C12N9/52 , C12N15/31 , A61K48/00 , A61K35/00
CPC分类号： C07K14/285 , C12N9/52 , A61K2039/51 , A61K39/00 , C07K2319/00
摘要： An isolated and purified analog of Haemophilus influenza Hin47 protein has a decreased protease activity which is less than about 10% of that of natural Hin47 protein and preferably substantially the same immunogenic properties as natural Hin47 protein. An isolated and purified nucleic acid molecule encoding the Hin47 analog may be provided in a recombinant plasmid which may be introduced into a cell which is grown to produce the Hin47 analog. Immunogenic compositions comprising the Hin47 analog and the encoding nucleic acid may be formulated as vaccines for in vivo administration to a host, including a human, to confer protection against diseases caused by a bacterial pathogen, including Haemophilus species, such as Haemophilus influenzae, that produces Hin47 protein or a protein capable of inducing antibodies in the host specifically reactive with Hin47 protein. The Hin47 analog and the encoding nucleic acid also may be employed in diagnostic applications.
摘要翻译：分离和纯化的嗜血杆菌流感Hin47蛋白的类似物具有降低的蛋白酶活性，其小于天然Hin47蛋白的约10％，优选与天然Hin47蛋白基本相同的免疫原性。编码Hin47类似物的分离和纯化的核酸分子可以在重组质粒中提供，其可以被引入生长以产生Hin47类似物的细胞中。包含Hin47类似物和编码核酸的免疫原性组合物可以配制成用于体内施用于宿主（包括人）的疫苗，以赋予针对由细菌病原体（例如流感嗜血杆菌）产生的细菌病原体引起的疾病的保护， Hin47蛋白或能够诱导与Hin47蛋白特异性反应的宿主中的抗体的蛋白质。 Hin47类似物和编码核酸也可用于诊断应用。

14. 发明授权

US06309649B1 Subunit respiratory syncytial virus vaccine preparation 失效
标题翻译：亚单位呼吸道合胞病毒疫苗的制备
公开(公告)号：US06309649B1
公开(公告)日：2001-10-30
申请号：US09214605
申请日：1999-05-03
申请人： George A. Cates , Sonia E. Sanhueza , Raymond P. Oomen , Michel H. Klein
发明人： George A. Cates , Sonia E. Sanhueza , Raymond P. Oomen , Michel H. Klein
IPC分类号： A61K39155
CPC分类号： C07K14/005 , A61K39/00 , A61K39/12 , A61K39/155 , A61K2039/55505 , A61K2039/55511 , A61K2039/55577 , C07K2319/00 , C12N7/00 , C12N2760/18521 , C12N2760/18522 , C12N2760/18534 , C12N2760/18551 , G01N33/56983
摘要： The fusion (F) protein, attachment (G) protein and matrix (M) protein of respiratory syncytial virus (RSV) are isolated and purified from respiratory syncytial virus by mild detergent extraction of the proteins from concentrated virus, loading the protein onto a hydroxyapatite or other ion-exchange matrix column and eluting the protein using mild salt treatment. The F, G and M proteins, formulated as immunogenic compositions, are safe and highly immunogenic and protect relevant animal models against decreased caused by respiratory syncytial virus infection.
摘要翻译：呼吸道合胞病毒（RSV）的融合（F）蛋白，附着（G）蛋白和基质（M））蛋白从呼吸道合胞病毒中分离并纯化，通过温和洗涤从浓缩病毒中提取蛋白质，将蛋白质加载到羟基磷灰石上或其他离子交换基质柱，并使用温和盐处理洗脱该蛋白质。配制为免疫原性组合物的F，G和M蛋白是安全和高度免疫原性的，并保护相关动物模型免受呼吸道合胞病毒感染引起的降低。

15. 发明授权

US5977304A Modification of pertussis toxin 失效
公开(公告)号：US5977304A
公开(公告)日：1999-11-02
申请号：US467536
申请日：1995-06-06
申请人： Randy J. Read , Penelope E. Stein , Stephen A. Cockle , Raymond P. Oomen , Sheena Loosmore , Michel H. Klein , Glen D. Armstrong , Bart Hazes
发明人： Randy J. Read , Penelope E. Stein , Stephen A. Cockle , Raymond P. Oomen , Sheena Loosmore , Michel H. Klein , Glen D. Armstrong , Bart Hazes
IPC分类号： C07K14/235 , G01N33/566 , G01N33/68 , C07K1/00 , C07H21/04 , C12N1/20 , C12P21/06
CPC分类号： C07K14/235 , G01N33/566 , G01N33/6893
摘要： The three-dimensional structure of crystalline pertussis holotoxin (PT) has been determined by X-ray crystallography. Crystal structures have also been determined for complexes of pertussis toxin with molecules relevant to the biological activity of PT. These three-dimensional structures were analyzed to identify functional amino acids appropriate for modification to alter the biological properties of PT. Similar procedures may be used to predict amino acids which contribute to the toxicity of the holotoxin, to produce immunoprotective, genetically-detoxified analogs of pertussis toxin.

16. 发明授权

US5965385A Modification of pertussis toxin 失效
公开(公告)号：US5965385A
公开(公告)日：1999-10-12
申请号：US467974
申请日：1995-06-06
申请人： Randy J. Read , Penelope E. Stein , Stephen A. Cockle , Raymond P. Oomen , Sheena Loosmore , Michel H. Klein , Glen D. Armstrong , Bart Hazes
发明人： Randy J. Read , Penelope E. Stein , Stephen A. Cockle , Raymond P. Oomen , Sheena Loosmore , Michel H. Klein , Glen D. Armstrong , Bart Hazes
IPC分类号： C07K14/235 , G01N33/566 , G01N33/68 , C12P21/06 , C07H21/04 , C07K1/00 , C12N1/20
CPC分类号： C07K14/235 , G01N33/566 , G01N33/6893
摘要： The three-dimensional structure of crystalline pertussis holotoxin (PT) has been determined by X-ray crystallography. Crystal structures have also been determined for complexes of pertussis toxin with molecules relevant to the biological activity of PT. These three-dimensional structures were analyzed to identify functional amino acids appropriate for modification to alter the biological properties of PT. Similar procedures may be used to predict amino acids which contribute to the toxicity of the holotoxin, to produce immunoprotective, genetically-detoxified analogs of pertussis toxin.

17. 发明授权

US5856122A Modification of pertussis toxin 失效
公开(公告)号：US5856122A
公开(公告)日：1999-01-05
申请号：US292968
申请日：1994-08-22
申请人： Randy J. Read , Penelope E. Stein , Stephen A. Cockle , Raymond P. Oomen , Sheena Loosmore , Michel H. Klein , Glen D. Armstrong , Bart Hazes
发明人： Randy J. Read , Penelope E. Stein , Stephen A. Cockle , Raymond P. Oomen , Sheena Loosmore , Michel H. Klein , Glen D. Armstrong , Bart Hazes
IPC分类号： C07K14/235 , G01N33/566 , G01N33/68 , C12P21/02
CPC分类号： C07K14/235 , G01N33/566 , G01N33/6893
摘要： The three-dimensional structure of crystalline pertussis holotoxin (PT) has been determined by X-ray crystallography. Crystal structures have also been determined for complexes of pertussis toxin with molecules relevant to the biological activity of PT. These three-dimensional structures were analyzed to identify functional amino acids appropriate for modification to alter the biological properties of PT. Similar procedures may be used to predict amino acids which contribute to the toxicity of the holotoxin, to produce immunoprotective, genetically-detoxified analogs of pertussis toxin.

18. 发明授权

US06168928A Modification of pertussis toxin 失效
标题翻译：改变百日咳毒素
公开(公告)号：US06168928A
公开(公告)日：2001-01-02
申请号：US09082514
申请日：1998-05-21
申请人： Randy J. Read , Penelope E. Stein , Stephen A. Cockle , Raymond P. Oomen , Sheena Loosmore , Michel H. Klein , Glen D. Armstrong , Bart Hazes
发明人： Randy J. Read , Penelope E. Stein , Stephen A. Cockle , Raymond P. Oomen , Sheena Loosmore , Michel H. Klein , Glen D. Armstrong , Bart Hazes
IPC分类号： C12N910
CPC分类号： C07K14/235 , G01N33/566 , G01N33/6893
摘要： The three-dimensional structure of crystalline pertussis holotoxin (PT) has been determined by X-ray crystallography. Crystal structures have also been determined for complexes of pertussis toxin with molecules relevant to the biological activity of PT. These three-dimensional structures were analyzed to identify functional amino acids appropriate for modification to alter the biological properties of PT. Similar procedures may be used to predict amino acids which contribute to the toxicity of the holotoxin, to produce immunoprotective, genetically-detoxified analogs of pertussis toxin.
摘要翻译：结晶百日咳全毒素（PT）的三维结构已经通过X射线晶体学确定。也已经确定了百日咳毒素与PT生物活性相关分子的复合物的晶体结构。分析这些三维结构以鉴定适于修饰以改变PT的生物学性质的功能性氨基酸。类似的程序可用于预测有助于全毒素毒性的氨基酸，产生免疫保护，百日咳毒素的遗传解毒类似物。

19. 发明授权

US6020182A Subunit respiratory syncytial virus vaccine preparation 失效
标题翻译：亚单位呼吸道合胞病毒疫苗的制备
公开(公告)号：US6020182A
公开(公告)日：2000-02-01
申请号：US679060
申请日：1996-07-12
申请人： George A. Cates , Sonia E. Sanhueza , Raymond P. Oomen , Michel H. Klein
发明人： George A. Cates , Sonia E. Sanhueza , Raymond P. Oomen , Michel H. Klein
IPC分类号： G01N33/531 , A61K31/00 , A61K39/00 , A61K39/155 , A61P31/00 , A61P31/12 , C07K1/18 , C07K14/135 , C07K16/10 , C12N5/10 , C12N7/00 , C12N7/02 , C12N15/02 , G01N33/569 , C12N7/04
CPC分类号： C07K14/005 , A61K39/12 , A61K39/155 , C12N7/00 , G01N33/56983 , A61K2039/55505 , A61K2039/55511 , A61K2039/55577 , A61K39/00 , C07K2319/00 , C12N2760/18521 , C12N2760/18522 , C12N2760/18534 , C12N2760/18551
摘要： The fusion (F) protein, attachment (G) protein and matrix (M) protein of respiratory syncytial virus (RSV) are isolated and purified from respiratory syncytial virus by mild detergent extraction of the proteins from concentrated virus, loading the protein onto a hydroxyapatite or other ion-exchange matrix column and eluting the protein using mild salt treatment. The F, G and M proteins, formulated as immunogenic compositions, are safe and highly immunogenic and protect relevant animal models against respiratory syncytial virus.
摘要翻译：呼吸道合胞病毒（RSV）的融合（F）蛋白，附着（G）蛋白和基质（M））蛋白从呼吸道合胞病毒中分离并纯化，通过温和洗涤从浓缩病毒中提取蛋白质，将蛋白质加载到羟基磷灰石上或其他离子交换基质柱，并使用温和盐处理洗脱该蛋白质。配制成免疫原性组合物的F，G和M蛋白是安全和高度免疫原性的，并保护针对呼吸道合胞病毒的相关动物模型。

20. 发明授权

US6018022A Modification of pertussis toxin 失效
标题翻译：改变百日咳毒素
公开(公告)号：US6018022A
公开(公告)日：2000-01-25
申请号：US467976
申请日：1995-06-06
申请人： Randy J. Read , Penelope E. Stein , Stephen A. Cockle , Raymond P. Oomen , Sheena Loosmore , Michel H. Klein , Glen D. Armstrong , Bart Hazes
发明人： Randy J. Read , Penelope E. Stein , Stephen A. Cockle , Raymond P. Oomen , Sheena Loosmore , Michel H. Klein , Glen D. Armstrong , Bart Hazes
IPC分类号： C07K14/235 , G01N33/566 , G01N33/68 , C07K1/00 , A61K39/10 , A61K39/108 , C12P21/06
CPC分类号： C07K14/235 , G01N33/566 , G01N33/6893
摘要： The three-dimensional structure of crystalline pertussis holotoxin (PT) has been determined by X-ray crystallography. Crystal structures have also been determined for complexes of pertussis toxin with molecules relevant to the biological activity of PT. These three-dimensional structures were analyzed to identify functional amino acids appropriate for modification to alter the biological properties of PT. Similar procedures may be used to predict amino acids which contribute to the toxicity of the holotoxin, to produce immunoprotective, genetically-detoxified analogs of pertussis toxin.
摘要翻译：结晶百日咳全毒素（PT）的三维结构已经通过X射线晶体学确定。也已经确定了百日咳毒素与PT生物活性相关分子的复合物的晶体结构。分析这些三维结构以鉴定适于修饰以改变PT的生物学性质的功能性氨基酸。类似的程序可用于预测有助于全毒素毒性的氨基酸，产生免疫保护，百日咳毒素的遗传解毒类似物。

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