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1. 发明授权

US07662575B2 Use of cross-protection to identify novel vaccine candidates for infectious agents 失效
标题翻译：使用交叉保护来鉴定感染因子的新型候选疫苗
公开(公告)号：US07662575B2
公开(公告)日：2010-02-16
申请号：US11979173
申请日：2007-10-31
申请人： Christopher Sikora , Bradley Berger , John Cherwonogrodzky
发明人： Christopher Sikora , Bradley Berger , John Cherwonogrodzky
IPC分类号： C12Q1/00
CPC分类号： A61K39/02 , A61K2039/52 , C07K14/195 , G01N2469/20 , Y02A50/405
摘要： This invention discloses methods for identifying Francisella tularensis vaccine candidates. It enables identification of novel vaccine candidates and quality assurance for vaccine batches, assessment of protection in vaccinates and identification of the infecting agent in vaccinates. Mice were first vaccinated with Brucella abortus O-polysaccharide (OPS) vaccine. These animals were then given 10 LD50s of F. tularensis live vaccine strain (LVS). Sixty percent (60%) of the vaccinated mice survived the multiple lethal doses. Sera were collected from these surviving mice and the antibodies were used to probe supernatant and cell lysates of live F. tularensis LVS cultures. Several F. tularensis components were identified only by the noted “survivor” antisera. Of these identified proteins, enzyme digestions and chemical oxidation suggest post-translational modifications of some proteins e.g. a 52 kDa glycoprotein, a 45 kDa lipoprotein and a 19 kDa nucleoprotein. The 52 kDa component caused nitrous oxide induction in tissue cultures at low concentrations, cell death at high concentrations. Vaccination with this gave partial protection while addition of other components acted synergistically to give enhanced protection from 250 LD50s of F. tularensis LVS.
摘要翻译：本发明公开了用于鉴定土拉弗朗西丝杆菌疫苗候选物的方法。它能够识别新型疫苗候选物和疫苗批次的质量保证，疫苗接种中的保护评估和疫苗接种中感染剂的鉴定。首先用Brucella abortus O-polysaccharide（OPS）疫苗接种小鼠。然后给予这些动物10只LD50的土拉曼杆菌活疫苗株（LVS）。接种疫苗的小鼠中有60％（60％）存活多次致死剂量。从这些存活的小鼠中收集血清，并使用抗体来探测活的土拉氏木霉LVS培养物的上清液和细胞裂解物。几种罗非鱼片组分仅由所述的“幸存者”抗血清鉴定。在这些鉴定的蛋白质中，酶消化和化学氧化表明某些蛋白质的翻译后修饰，例如一个52 kDa的糖蛋白，一个45 kDa的脂蛋白和一个19 kDa的核蛋白。 52 kDa组分在低浓度组织培养物中引起氧化亚氮诱导，高浓度细胞死亡。用这种疫苗接种给予部分保护，而加入其他成分则协同作用，从而提高了对土拉氏杆菌LVS的250 LD50的保护。

2. 发明授权

US07323180B2 Use of cross-protection to identify novel vaccine candidates for infectious agents 有权
标题翻译：使用交叉保护来鉴定感染因子的新型候选疫苗
公开(公告)号：US07323180B2
公开(公告)日：2008-01-29
申请号：US10762241
申请日：2004-01-23
申请人： Christopher Sikora , Bradley Berger , John Cherwonogrodzky
发明人： Christopher Sikora , Bradley Berger , John Cherwonogrodzky
IPC分类号： A61K39/02
CPC分类号： A61K39/02 , A61K2039/52 , C07K14/195 , G01N2469/20 , Y02A50/405
摘要： This invention discloses methods for identifying Francisella tularensis vaccine candidates. It enables identification of novel vaccine candidates and quality assurance for vaccine batches, assessment of protection in vaccinates and identification of the infecting agent in vaccinates. Mice were first vaccinated with Brucella abortus O-polysaccharide (OPS) vaccine. These animals were then given 10 LD50s of F. tularensis live vaccine strain (LVS). Sixty percent (60%) of the vaccinated mice survived the multiple lethal doses. Sera were collected from these surviving mice and the antibodies were used to probe supernatant and cell lysates of live F. tularensis LVS cultures. Several F. tularensis components were identified only by the noted “survivor” antisera. Of these identified proteins, enzyme digestions and chemical oxidation suggest post-translational modifications of some proteins e.g. a 52 kDa glycoprotein, a 45 kDa lipoprotein and a 19 kDa nucleoprotein. The 52 kDa component caused nitrous oxide induction in tissue cultures at low concentrations, cell death at high concentrations. Vaccination with this gave partial protection while addition of other components acted synergistically to give enhanced protection from 250 LD50s of F. tularensis LVS.
摘要翻译：本发明公开了用于鉴定土拉弗朗西丝杆菌疫苗候选物的方法。它能够识别新型疫苗候选物和疫苗批次的质量保证，疫苗接种中的保护评估和疫苗接种中感染剂的鉴定。首先用Brucella abortus O-polysaccharide（OPS）疫苗接种小鼠。然后给予这些动物10欧拉土拉氏杆菌活疫苗株（LVS）50。接种疫苗的小鼠中有60％（60％）存活多次致死剂量。从这些存活的小鼠中收集血清，并使用抗体来探测活的土拉氏木霉LVS培养物的上清液和细胞裂解物。几种罗非鱼片组分仅由所述的“幸存者”抗血清鉴定。在这些鉴定的蛋白质中，酶消化和化学氧化表明某些蛋白质的翻译后修饰，例如一个52 kDa的糖蛋白，一个45 kDa的脂蛋白和一个19 kDa的核蛋白。 52 kDa组分在低浓度组织培养物中引起氧化亚氮诱导，高浓度细胞死亡。用这种疫苗接种给予部分保护，而添加其它成分的作用是协同作用，以增强对土拉氏木霉LVS的250 LD 50的保护。

3. 发明申请

US20080153108A1 Use of cross-protection to identify novel vaccine candidates for infectious agents 审中-公开
公开(公告)号：US20080153108A1
公开(公告)日：2008-06-26
申请号：US11979174
申请日：2007-10-31
申请人： Christopher Sikora , Bradley Berger , John Cherwonogrodzky
发明人： Christopher Sikora , Bradley Berger , John Cherwonogrodzky
IPC分类号： G01N33/53 , G01N33/68
CPC分类号： A61K39/02 , A61K2039/52 , C07K14/195 , G01N2469/20 , Y02A50/405
摘要： This invention discloses methods for identifying Francisella tularensis vaccine candidates. It enables identification of novel vaccine candidates and quality assurance for vaccine batches, assessment of protection in vaccinates and identification of the infecting agent in vaccinates. Mice were first vaccinated with Brucella abortus O-polysaccharide (OPS) vaccine. These animals were then given 10 LD50s of F. tularensis live vaccine strain (LVS). Sixty percent (60%) of the vaccinated mice survived the multiple lethal doses. Sera were collected from these surviving mice and the antibodies were used to probe supernatant and cell lysates of live F. tularensis LVS cultures. Several F. tularensis components were identified only by the noted “survivor” antisera. Of these identified proteins, enzyme digestions and chemical oxidation suggest post-translational modifications of some proteins e.g. a 52 kDa glycoprotein, a 45 kDa lipoprotein and a 19 kDa nucleoprotein. The 52 kDa component caused nitrous oxide induction in tissue cultures at low concentrations, cell death at high concentrations. Vaccination with this gave partial protection while addition of other components acted synergistically to give enhanced protection from 250 LD50s of F. tularensis LVS.

4. 发明授权

US07579182B2 Use of cross-protection to identify novel vaccine candidates for infectious agents 失效
标题翻译：使用交叉保护来鉴定感染因子的新型候选疫苗
公开(公告)号：US07579182B2
公开(公告)日：2009-08-25
申请号：US11979172
申请日：2007-10-31
申请人： Christopher Sikora , Bradley Berger , John Cherwonogrodzky
发明人： Christopher Sikora , Bradley Berger , John Cherwonogrodzky
IPC分类号： C12N1/00
CPC分类号： A61K39/02 , A61K2039/52 , C07K14/195 , G01N2469/20 , Y02A50/405
摘要： This invention discloses methods for identifying Francisella tularensis vaccine candidates. It enables identification of novel vaccine candidates and quality assurance for vaccine batches, assessment of protection in vaccinates and identification of the infecting agent in vaccinates. Mice were first vaccinated with Brucella abortus O-polysaccharide (OPS) vaccine. These animals were then given 10 LD50s of F. tularensis live vaccine strain (LVS). Sixty percent (60%) of the vaccinated mice survived the multiple lethal doses. Sera were collected from these surviving mice and the antibodies were used to probe supernatant and cell lysates of live F. tularensis LVS cultures. Several F. tularensis components were identified only by the noted “survivor” antisera. Of these identified proteins, enzyme digestions and chemical oxidation suggest post-translational modifications of some proteins e.g. a 52 kDa glycoprotein, a 45 kDa lipoprotein and a 19 kDa nucleoprotein. The 52 kDa component caused nitrous oxide induction in tissue cultures at low concentrations, cell death at high concentrations. Vaccination with this gave partial protection while addition of other components acted synergistically to give enhanced protection from 250 LD50s of F. tularensis LVS.
摘要翻译：本发明公开了用于鉴定土拉弗朗西丝杆菌疫苗候选物的方法。它能够识别新型疫苗候选物和疫苗批次的质量保证，疫苗接种中的保护评估和疫苗接种中感染剂的鉴定。首先用Brucella abortus O-polysaccharide（OPS）疫苗接种小鼠。然后给予这些动物10只LD50的土拉曼杆菌活疫苗株（LVS）。接种疫苗的小鼠中有60％（60％）存活多次致死剂量。从这些存活的小鼠中收集血清，并使用抗体来探测活的土拉氏木霉LVS培养物的上清液和细胞裂解物。几种罗非鱼片组分仅由所述的“幸存者”抗血清鉴定。在这些鉴定的蛋白质中，酶消化和化学氧化表明某些蛋白质的翻译后修饰，例如一个52 kDa的糖蛋白，一个45 kDa的脂蛋白和一个19 kDa的核蛋白。 52 kDa组分在低浓度组织培养物中引起氧化亚氮诱导，高浓度细胞死亡。用这种疫苗接种给予部分保护，而加入其他成分则协同作用，从而提高了对土拉氏杆菌LVS的250 LD50的保护。

5. 发明申请

US20080102088A1 Use of cross-protection to identify novel vaccine candidates for infectious agents 失效
公开(公告)号：US20080102088A1
公开(公告)日：2008-05-01
申请号：US11979172
申请日：2007-10-31
申请人： Christopher Sikora , Bradley Berger , John Cherwonogrodzky
发明人： Christopher Sikora , Bradley Berger , John Cherwonogrodzky
IPC分类号： A61K39/00 , A61P43/00 , C12P21/04
CPC分类号： A61K39/02 , A61K2039/52 , C07K14/195 , G01N2469/20 , Y02A50/405
摘要： This invention discloses methods for identifying Francisella tularensis vaccine candidates. It enables identification of novel vaccine candidates and quality assurance for vaccine batches, assessment of protection in vaccinates and identification of the infecting agent in vaccinates. Mice were first vaccinated with Brucella abortus O-polysaccharide (OPS) vaccine. These animals were then given 10 LD50s of F. tularensis live vaccine strain (LVS). Sixty percent (60%) of the vaccinated mice survived the multiple lethal doses. Sera were collected from these surviving mice and the antibodies were used to probe supernatant and cell lysates of live F. tularensis LVS cultures. Several F. tularensis components were identified only by the noted “survivor” antisera. Of these identified proteins, enzyme digestions and chemical oxidation suggest post-translational modifications of some proteins e.g. a 52 kDa glycoprotein, a 45 kDa lipoprotein and a 19 kDa nucleoprotein. The 52 kDa component caused nitrous oxide induction in tissue cultures at low concentrations, cell death at high concentrations. Vaccination with this gave partial protection while addition of other components acted synergistically to give enhanced protection from 250 LD50s of F. tularensis LVS.

6. 发明授权

US06221386B1 Use of virulence factors of pathogens to improve liposomal delivery of therapeutic agents 有权
标题翻译：使用病原体的毒力因子来改善治疗剂的脂质体递送
公开(公告)号：US06221386B1
公开(公告)日：2001-04-24
申请号：US09251304
申请日：1999-02-17
申请人： John Cherwonogrodzky , Jonathan P. Wong , Vincent L. Dininno
发明人： John Cherwonogrodzky , Jonathan P. Wong , Vincent L. Dininno
IPC分类号： A61K9127
CPC分类号： A61K9/127 , A61K47/61 , A61K47/6911 , Y10S424/812 , Y10S436/829 , Y10S514/885
摘要： Liposome encapsulated antibiotic therapy has limited application against infectious organisms, which can sequester in non-phagocytic cells. Virulence factors of these infectious organisms, for example bacterial components, when used in the formulation of liposomes can enhance the effectiveness of liposomes as delivery systems in the treatment of disease. In this manner, multi-functional liposomes can be developed to treat target diseases. In addition to serving as antibiotic delivery systems, such liposomes also have an immunization effect. Thus, the liposomes can be used for both the prevention and treatment of diseases.
摘要翻译：脂质体包裹的抗生素治疗对感染性生物的应用有限，可以在非吞噬细胞中螯合。当用于脂质体制剂时，这些感染性生物体（例如细菌成分）的毒力因子可增强作为治疗疾病的递送系统的脂质体的有效性。以这种方式，可以开发多功能脂质体来治疗目标疾病。除了作为抗生素递送系统之外，这样的脂质体还具有免疫作用。因此，脂质体可以用于预防和治疗疾病。

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