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1. 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.

2. 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.

3. 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.

4. 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。

5. 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。

6. 发明授权

US06767545B2 Pseudomonas treatment composition and method 失效
标题翻译：假单胞菌治疗组合物及方法
公开(公告)号：US06767545B2
公开(公告)日：2004-07-27
申请号：US09865159
申请日：2001-05-24
申请人： Randall T. Irvin , Randy J. Read , Bart Hazes , Wah Y. Wong , Sastry A. Parimi , Linda M. G. Glasier
发明人： Randall T. Irvin , Randy J. Read , Bart Hazes , Wah Y. Wong , Sastry A. Parimi , Linda M. G. Glasier
IPC分类号： A61K3902
CPC分类号： A61K38/164 , C07K14/21 , C07K2319/00
摘要： A composition and method for treating or preventing infection by Pseudomonas aeruginosa is disclosed. The composition includes a P. aeruginosa pilin peptide modified to prevent oligomerization of the pilin. The method involves administered the composition to a person infected with Pseudomonas are at risk of such infection.
摘要翻译：公开了一种用于治疗或预防铜绿假单胞菌感染的组合物和方法。该组合物包括经改良的铜绿假单胞菌肽蛋白肽，以防止皮林的低聚。该方法包括将组合物给予感染了假单胞菌的人患有这种感染的风险。

7. 发明授权

US06342233B1 Pseudomonas treatment composition and method 失效
标题翻译：假单胞菌治疗组合物及方法
公开(公告)号：US06342233B1
公开(公告)日：2002-01-29
申请号：US09329884
申请日：1999-06-11
申请人： Randall T. Irvin , Randy J. Read , Bart Hazes , Wah Y. Wong , Sastry A. Parimi , Linda M. G. Glasier
发明人： Randall T. Irvin , Randy J. Read , Bart Hazes , Wah Y. Wong , Sastry A. Parimi , Linda M. G. Glasier
IPC分类号： A61K39108
CPC分类号： A61K38/164 , C07K14/21 , C07K2319/00
摘要： A composition and method for treating or preventing infection by Pseudomonas aeruginosa is disclosed. The composition includes a P. aeruginosa pilin peptide modified to prevent oligomerization of the pilin. The method involves administered the composition to a person infected with Pseudomonas are at risk of such infection.
摘要翻译：公开了一种用于治疗或预防铜绿假单胞菌感染的组合物和方法。该组合物包括经改良的铜绿假单胞菌肽蛋白肽，以防止皮林的低聚。该方法包括将组合物给予感染了假单胞菌的人患有这种感染的风险。

8. 发明授权

US5962423A Treatment of bacterial dysentery 失效
标题翻译：治疗细菌性痢疾
公开(公告)号：US5962423A
公开(公告)日：1999-10-05
申请号：US130495
申请日：1998-08-07
申请人： David R. Bundle , Pavel Kitov , Randy J. Read , Hong Ling , Glen Armstrong
发明人： David R. Bundle , Pavel Kitov , Randy J. Read , Hong Ling , Glen Armstrong
IPC分类号： A61K47/48 , C07H3/04 , C07H3/06 , A61K31/70 , A61K31/74 , A61K31/745 , A61K31/785
CPC分类号： C07H3/06 , A61K47/48192 , C07H3/04 , Y10S424/16
摘要： Compounds which bind to shiga-like toxins (SLT) associated with enteric E. coli infection, compositions including the compounds, methods for the neutralization of (SLT) in a patient, and methods for the diagnosis of enteric E. coli infection are disclosed. The compounds include a core molecule bound to a plurality of linker arms, which in turn are bound to a plurality of bridging moieties, which in turn are bound to two or three di- or tri-saccharide moieties. The di- or tri-saccharide moieties themselves are active in binding to the SLTs. The presence of a plurality of bridged dimers of the di- and tri-saccharides is responsible for the increased binding affinity of the compounds relative to the di- and tri-saccharides themselves. The compounds, when administered in a timely fashion to a patient suffering from enteric E. coli infection, inhibit progression of this infection into hemolytic uremic syndrome (HUS).
摘要翻译：公开了结合与肠道大肠杆菌感染相关的志贺样毒素（SLT）的化合物，包括该化合物的组合物，患者中的（SLT）的方法以及肠道大肠杆菌感染的诊断方法。化合物包括与多个连接臂结合的核心分子，其又结合到多个桥连部分，其又结合到两个或三个二糖或三糖部分上。二糖或三糖部分本身具有活性的结合SLT。二糖和三糖的多个桥连二聚体的存在导致化合物相对于二糖和三糖本身增加的结合亲和力。当及时给予患有肠道大肠杆菌感染的患者时，这些化合物抑制该感染进入溶血性尿毒症综合征（HUS）。

9. 发明授权

US06310043B1 Treatment of bacterial infections 失效
标题翻译：细菌感染的治疗
公开(公告)号：US06310043B1
公开(公告)日：2001-10-30
申请号：US09317290
申请日：1999-05-24
申请人： David R. Bundle , Pavel Kitov , Randy J. Read , Hong Ling , Glen Armstrong
发明人： David R. Bundle , Pavel Kitov , Randy J. Read , Hong Ling , Glen Armstrong
IPC分类号： A61K3170
CPC分类号： C07H15/04 , A61K47/549 , A61K47/59 , C07H3/04 , C07H3/06 , Y10S424/16
摘要： Compounds which bind to toxins associated with enteric bacterial infection, compositions including the compounds, methods for the neutralization of toxins in a patient, and methods for the diagnosis of bacterial and viral infections are disclosed. Toxins which can be bound by the compounds include pentameric toxins, for example SLTs, such as those from salmonella, camylobacter and other bacteria, verotoxins from E. coli, cholera toxin, clostridium difficile toxins A and B, bacterial pili from enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) and viral lectins such as viral hemagglutinins. The compounds include a core molecule bound to a plurality of linker arms, which in turn are bound to a plurality of bridging moieties, which in turn are bound to at least one, and preferably, two or more ligands which bind to the toxin. The presence of a plurality of bridged dimers of the ligands is responsible for the increased binding affinity of the compounds relative to the ligands themselves. In one embodiment, the compounds, when administered in a timely fashion to a patient suffering from enteric E. coli infection, inhibit progression of this infection into hemolytic uremic syndrome (HUS).
摘要翻译：公开了结合与肠细菌感染相关的毒素的化合物，包括该化合物的组合物，用于中和患者中的毒素的方法，以及诊断细菌和病毒感染的方法。可以被化合物结合的毒素包括五聚体毒素，例如SLT，例如来自沙门氏菌属，弯孢杆菌属和其他细菌的那些，来自大肠杆菌的肠毒素，霍乱毒素，艰难梭菌毒素A和B，来自肠致病性大肠杆菌的细菌（EPEC）和肠毒素性大肠杆菌（ETEC）和病毒凝集素如病毒血凝素。化合物包括与多个连接臂结合的核心分子，其又结合到多个桥连部分，其又结合至少一个，优选两个或更多个与毒素结合的配体。配体的多个桥连二聚体的存在导致化合物相对于配体本身的增加的结合亲和力。在一个实施方案中，当及时给予患有肠道大肠杆菌感染的患者时，化合物抑制该感染进入溶血性尿毒综合征（HUS）。

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