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1. 发明授权

US06245331B1 Early detection of mycobacterial disease 失效
标题翻译：早期发现分枝杆菌病
公开(公告)号：US06245331B1
公开(公告)日：2001-06-12
申请号：US09001984
申请日：1997-12-31
申请人： Suman Laal , Susan Zolla-Pazner , John T. Belisle
发明人： Suman Laal , Susan Zolla-Pazner , John T. Belisle
IPC分类号： A61K3940
CPC分类号： G01N33/5695 , C07K16/1289
摘要： A number of protein and glycoprotein antigens secreted by Mycobacterium. tuberculosis (Mt) have been identified as “early” Mt antigens on the basis early antibodies present in subjects infected with Mt prior to the development of detectable clinical disease. These early Mt antigens, in particular an 88 kDa secreted protein having a pI of about 5.2 present in Mt lipoarabinomannan-free culture filtrate, a protein characterized as Mt antigen 85C; a protein characterized as Mt antigen MPT51, a glycoprotein characterized as Mt antigen MPT32; and a 49 kDa protein having a pI of about 5.1, are useful in immunoassay methods for early, rapid detection of TB in a subject. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mt antigen, an early Mt antibody, and immune complexes thereof. For the first time, a surrogate marker is available for inexpensive screening of individuals at heightened risk for developing TB, in particular HIV-1 infected subjects and other immunocompromised individuals.
摘要翻译：许多由分枝杆菌分泌的蛋白质和糖蛋白抗原。在发现可检测的临床疾病之前，基于在感染Mt的受试者中存在的早期抗体，已经将结核病（Mt）鉴定为“早期”Mt抗原。这些早期的Mt抗原，特别是一种具有约5.2的pI约为5.2的88kDa分泌蛋白，存在于无脂质阿拉伯聚糖的培养滤液中，以Mt抗原85C为特征的蛋白质; 特征为Mt抗原MPT51的蛋白质，以Mt抗原MPT32为特征的糖蛋白; 和具有约5.1的pI的49kDa蛋白质可用于在受试者中早期，快速检测TB的免疫测定方法。还提供了用于检测早期Mt抗原，早期Mt抗体及其免疫复合物的抗原组合物，试剂盒和方法。第一次，替代标记可用于廉价筛选个体，发展结核病风险增加，特别是HIV-1感染的受试者和其他免疫受损的个体。

2. 发明申请

US20110104194A1 IMMUNODOMINANT MYCOBACTERIUM TUBERCULOSIS PEPTIDES FROM CELL WALL PROTEINS FOR EARLY DIAGNOSIS AND IMMUNIZATION 有权
标题翻译：从细胞壁蛋白中免疫组织化学检测细胞膜蛋白，用于早期诊断和免疫
公开(公告)号：US20110104194A1
公开(公告)日：2011-05-05
申请号：US12988595
申请日：2009-04-20
申请人： Suman Laal , Susan Zolla-Pazner
发明人： Suman Laal , Susan Zolla-Pazner
IPC分类号： A61K39/04 , C07K7/08 , C07K7/06 , C07K19/00 , C07K14/35 , G01N33/68 , C12Q1/02 , A61P31/06 , A61P37/04
CPC分类号： G01N33/5695 , C07K14/35 , G01N2333/35 , G01N2469/20
摘要： A number of peptide epitopes and fragments from three Mycobacterium tuberculosis (Mtb) cell wall proteins have been identified as early antigens that induce antibodies early during Mtb infection in humans. The proteins are Proline-Threonine Repetitive Protein (PTRP), PE-PGRS51, and LipC. These peptides, alone or in mixtures, or as parts of fusion polypeptides or peptide multimers, are useful as antigens for serological detection of early in infection by detecting the presence of early antibodies against these proteins, thereby permitting earlier diagnosis of Mtb infection than was heretofore possible by conventional means. The above peptides and other peptide-based compositions are also used as immunogens for inclusion in TB vaccines. Also provided are methods for early diagnosis of Mtb infection and for immunizing a subject to prevent or treat Mtb infections and tuberculosis.
摘要翻译：已经将来自三种结核分枝杆菌（Mtb）细胞壁蛋白质的许多肽表位和片段鉴定为在人类Mtb感染期间早期诱导抗体的早期抗原。蛋白质是脯氨酸 - 苏氨酸重复蛋白（PTRP），PE-PGRS51和LipC。这些肽单独或混合，或作为融合多肽或肽多聚体的部分，可用作抗原，用于通过检测针对这些蛋白质的早期抗体的存在来检测早期感染的血清学检测，从而允许早期诊断Mtb感染比以前可能通过常规手段。上述肽和其它基于肽的组合物也被用作包含在结核病疫苗中的免疫原。还提供了早期诊断Mtb感染和免疫受试者以预防或治疗Mtb感染和结核病的方法。

3. 发明授权

US07807182B2 Early detection of mycobacterial disease using peptides 有权
标题翻译：使用肽的早期检测分枝杆菌病
公开(公告)号：US07807182B2
公开(公告)日：2010-10-05
申请号：US10210884
申请日：2002-08-02
申请人： Suman Laal , Susan Zolla-Pazner , John T. Belisle
发明人： Suman Laal , Susan Zolla-Pazner , John T. Belisle
IPC分类号： A61K39/04 , A61K39/38 , A61K39/02
CPC分类号： C07K16/1289 , C07K14/36 , G01N33/5695 , G01N2469/20
摘要： A number of protein and glycoprotein antigens secreted by Mycobacterium tuberculosis (Mtb) have been identified as “early” Mtb antigens on the basis early antibodies present in subjects infected with Mtb prior to the development of detectable clinical disease. Epitope-bearing peptide fragments of these early Mtb antigens, in particular of an 88 kDa secreted protein, GlcB (SEQ ID NO:106) and of Mtb antigen MPT51 (SEQ ID NO:107) have been identified. These peptides, variants thereof, peptide multimers thereof that include two or more repeats of one or more of the peptides, and fusion polypeptides that include early Mtb antigenic proteins, peptides or both, are useful in immunoassay methods for early, rapid detection of TB in a subject. Preferred immunoassays detect the antibodies in the subject's urine. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mtb antibodies. The antigenic proteins and peptides are also used in vaccine compositions.
摘要翻译：在发展可检测的临床疾病之前，以分子结核分枝杆菌（Mtb）分泌的许多蛋白质和糖蛋白抗原已经被鉴定为在Mtb感染的受试者中存在的早期抗体的“早期”Mtb抗原。已经鉴定了这些早期Mtb抗原，特别是88kDa分泌蛋白，GlcB（SEQ ID NO：106）和Mtb抗原MPT51（SEQ ID NO：107）的表位携带肽片段。这些肽，其变体，包括一个或多个肽的两个或更多个重复的肽多聚体，以及包括早期Mtb抗原性蛋白质，肽或两者的融合多肽在免疫测定方法中可用于早期，快速检测TB 课程。优选的免疫测定法检测受试者尿液中的抗体。还提供了用于检测早期Mtb抗体的抗原组合物，试剂盒和方法。抗原蛋白和肽也用于疫苗组合物中。

4. 发明申请

US20090280140A1 Early detection of mycobacterial disease using peptides 有权
标题翻译：使用肽的早期检测分枝杆菌病
公开(公告)号：US20090280140A1
公开(公告)日：2009-11-12
申请号：US10210884
申请日：2002-08-02
申请人： Suman Laal , Susan Zolla-Pazner , John T. Belisle
发明人： Suman Laal , Susan Zolla-Pazner , John T. Belisle
IPC分类号： A61K39/04 , G01N33/53 , C12Q1/04 , A61P31/06
CPC分类号： C07K16/1289 , C07K14/36 , G01N33/5695 , G01N2469/20
摘要： A number of protein and glycoprotein antigens secreted by Mycobacterium tuberculosis (Mtb) have been identified as “early” Mtb antigens on the basis early antibodies present in subjects infected with Mtb prior to the development of detectable clinical disease. Epitope-bearing peptide fragments of these early Mtb antigens, in particular of an 88 kDa secreted protein, GlcB (SEQ ID NO:106) and of Mtb antigen MPT51 (SEQ ID NO:107) have been identified. These peptides, variants thereof, peptide multimers thereof that include two or more repeats of one or more of the peptides, and fusion polypeptides that include early Mtb antigenic proteins, peptides or both, are useful in immunoassay methods for early, rapid detection of TB in a subject. Preferred immunoassays detect the antibodies in the subject's urine. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mtb antibodies. The antigenic proteins and peptides are also used in vaccine compositions.
摘要翻译：在发展可检测的临床疾病之前，以分子结核分枝杆菌（Mtb）分泌的许多蛋白质和糖蛋白抗原已经被鉴定为在Mtb感染的受试者中存在的早期抗体的“早期”Mtb抗原。已经鉴定了这些早期Mtb抗原，特别是88kDa分泌蛋白，GlcB（SEQ ID NO：106）和Mtb抗原MPT51（SEQ ID NO：107）的表位携带肽片段。这些肽，其变体，包括一个或多个肽的两个或更多个重复的肽多聚体和包括早期Mtb抗原性蛋白质，肽或两者的融合多肽在用于早期，快速检测TB中的免疫测定方法中是有用的课程。优选的免疫测定法检测受试者尿液中的抗体。还提供了用于检测早期Mtb抗体的抗原组合物，试剂盒和方法。抗原蛋白和肽也用于疫苗组合物中。

5. 发明授权

US09335325B2 Immunodominant Mycobacterium tuberculosis peptides from cell wall proteins for early diagnosis and immunization 有权
标题翻译：来自细胞壁蛋白的免疫显性结核分枝杆菌肽用于早期诊断和免疫
公开(公告)号：US09335325B2
公开(公告)日：2016-05-10
申请号：US12988595
申请日：2009-04-20
申请人： Suman Laal , Susan Zolla-Pazner
发明人： Suman Laal , Susan Zolla-Pazner
IPC分类号： A61K39/04 , A61K39/00 , A61K39/02 , G01N33/569 , C07K14/35
CPC分类号： G01N33/5695 , C07K14/35 , G01N2333/35 , G01N2469/20
摘要： A number of peptide epitopes and fragments from three Mycobacterium tuberculosis (Mtb) cell wall proteins have been identified as early antigens that induce antibodies early during Mtb infection in humans. The proteins are Proline-Threonine Repetitive Protein (PTRP), PE-PGRS51, and LipC. These peptides, alone or in mixtures, or as parts of fusion polypeptides or peptide multimers, are useful as antigens for serological detection of early in infection by detecting the presence of early antibodies against these proteins, thereby permitting earlier diagnosis of Mtb infection than was heretofore possible by conventional means. The above peptides and other peptide-based compositions are also used as immunogens for inclusion in TB vaccines. Also provided are methods for early diagnosis of Mtb infection and for immunizing a subject to prevent or treat Mtb infections and tuberculosis.
摘要翻译：已经将来自三种结核分枝杆菌（Mtb）细胞壁蛋白质的许多肽表位和片段鉴定为在人类Mtb感染期间早期诱导抗体的早期抗原。蛋白质是脯氨酸 - 苏氨酸重复蛋白（PTRP），PE-PGRS51和LipC。这些肽单独或混合，或作为融合多肽或肽多聚体的部分，可用作抗原，用于通过检测针对这些蛋白质的早期抗体的存在来检测早期感染的血清学检测，从而允许早期诊断Mtb感染比以前可能通过常规手段。上述肽和其它基于肽的组合物也被用作包含在结核病疫苗中的免疫原。还提供了早期诊断Mtb感染和免疫受试者以预防或治疗Mtb感染和结核病的方法。

6. 发明授权

US07745141B2 Mycobacterial proteins as early antigens for serodiagnosis and vaccines 有权
标题翻译：分枝杆菌蛋白作为血清学诊断和疫苗的早期抗原
公开(公告)号：US07745141B2
公开(公告)日：2010-06-29
申请号：US10481563
申请日：2001-06-21
申请人： Suman Laal , Susan Zolla-Pazner
发明人： Suman Laal , Susan Zolla-Pazner
IPC分类号： G01N33/53 , A61K39/04 , A61K39/02
CPC分类号： G01N33/5695
摘要： A number of protein and glycoprotein antigens secreted by, or expressed on the surface of, Mycobacterium tuberculosis (Mtb) have been identified as “early” Mtb antigens on the basis of antibodies present in subjects infected with Mtb prior to the development of detectable clinical disease. PirG protein encoded by the Mtb gene Rv3810, PE-PGRS protein encoded by the Mtb gene Rv3367, PTRP protein encoded by the Mtb gene Rv0538) and MtrA protein encoded by the Mtb gene Rv3246c, or epitopes of these proteins, are useful in immunoassay methods or T cell assays for early, rapid detection of TB in a subject. Preferred immunoassays detect antibodies in the urine. Also provided are antigenic compositions, kits and methods useful for detecting these early Mtb antigens and early Mtb antibodies specific for them. Vaccine compositions comprising the foregoing antigens or epitopes are also disclosed.
摘要翻译：在发现可检测的临床疾病之前，基于在Mtb感染的受试者中存在的抗体，许多由结核分枝杆菌（Mtb）表达分泌或表达的蛋白质和糖蛋白抗原已被鉴定为“早期”Mtb抗原。由Mtb基因Rv3810编码的PirG蛋白，由Mtb基因Rv3367编码的PE-PGRS蛋白，由Mtb基因Rv0538编码的PTRP蛋白）和由Mtb基因Rv3246c编码的MtrA蛋白或这些蛋白质的表位可用于免疫测定方法或T细胞测定法用于早期，快速检测受试者的结核病。优选的免疫测定法检测尿液中的抗体。还提供了用于检测这些早期Mtb抗原和对其特异的早期Mtb抗体的抗原组合物，试剂盒和方法。还公开了包含前述抗原或表位的疫苗组合物。

7. 发明申请

US20050084904A1 Mycobacterial proteins as early antigens for serodiagnosis and vaccines 有权
标题翻译：分枝杆菌蛋白作为血清学诊断和疫苗的早期抗原
公开(公告)号：US20050084904A1
公开(公告)日：2005-04-21
申请号：US10481563
申请日：2001-06-21
申请人： Suman Laal , Susan Zolla-Pazner
发明人： Suman Laal , Susan Zolla-Pazner
IPC分类号： G01N33/569 , G01N33/53
CPC分类号： G01N33/5695
摘要： In view of the paucity of human material available to study the immunological events occurring after inhalation of virulent bacilli, but prior to development of clinical TB, the present invention is based in part on studies of aerosol infected rabbits. The present inventors reasoned that by 3-5 weeks post-infection, the sera from infected rabbits would contain antibodies to the antigens being expressed by the in vivo bacteria.
摘要翻译：鉴于可用于研究吸入有毒性杆菌之后但在临床TB发展之前发生的免疫学事件的人类材料的缺乏，本发明部分基于气雾感染的兔子的研究。本发明人认为，感染后3-5周，来自感染的兔子的血清将含有由体内细菌表达的抗原的抗体。

8. 发明授权

US06506384B1 Early detection of mycobacterial disease 有权
标题翻译：早期发现分枝杆菌病
公开(公告)号：US06506384B1
公开(公告)日：2003-01-14
申请号：US09396347
申请日：1999-09-14
申请人： Suman Laal , Susan Zolla-Pazner , John T. Belisle
发明人： Suman Laal , Susan Zolla-Pazner , John T. Belisle
IPC分类号： A61K3940
CPC分类号： C07K16/1289 , G01N33/5695
摘要： A number of protein and glycoprotein antigens secreted by Mycobacterium. tuberculosis (Mt) have been identified as “early” Mt antigens on the basis early antibodies present in subjects infected with Mt prior to the development of detectable clinical disease. These early Mt antigens, in particular an 88 kDa secreted protein having a pI of about 5.2 and the sequence of SEQ ID NO:106, which is present in Mt lipoarabinomannan-free culture filtrate, a protein characterized as Mt antigen 85C; a protein characterized as Mt antigen MPT51, a glycoprotein characterized as Mt antigen MPT32; and a 49 kDa protein having a pI of about 5.1, are useful in immunoassay methods for early, rapid detection of TB in a subject. Preferred immunoassays detect the antibodies in the subject's urine. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mt antigen, an early Mt antibody, and immune complexes thereof. For the first time, a surrogate marker is available for inexpensive screening of individuals at heightened risk for developing advanced TB, in particular HIV-1 infected subjects and other immunocompromised individuals.
摘要翻译：许多由分枝杆菌分泌的蛋白质和糖蛋白抗原。在发现可检测的临床疾病之前，基于在感染Mt的受试者中存在的早期抗体，已经将结核病（Mt）鉴定为“早期”Mt抗原。这些早期的Mt抗原，特别是具有约5.2的pI约为88kDa的88kDa的分泌蛋白和存在于无脂肪阿拉伯聚糖的培养滤液中的SEQ ID NO：106的序列，以Mt抗原85C为特征的蛋白质; 特征为Mt抗原MPT51的蛋白质，以Mt抗原MPT32为特征的糖蛋白; 和具有约5.1的pI的49kDa蛋白质可用于在受试者中早期，快速检测TB的免疫测定方法。优选的免疫测定法检测受试者尿液中的抗体。还提供了用于检测早期Mt抗原，早期Mt抗体及其免疫复合物的抗原组合物，试剂盒和方法。第一次，替代标记可用于廉价筛选个体，发展成为晚期结核病，特别是HIV-1感染的受试者和其他免疫受损的个体。

9. 发明申请

US20080171345A1 BIOMARKERS OF TUBERCULOSIS THAT DISTINGUISH DISEASE CATEGORIES: USE AS SERODIAGNOSTIC ANTIGENS 有权
标题翻译：辨证性疾病的结核菌生物标志物：用作血清抗原
公开(公告)号：US20080171345A1
公开(公告)日：2008-07-17
申请号：US11837264
申请日：2007-08-10
申请人： John T. BELISLE , Mark J. Sartain , Suman Laal
发明人： John T. BELISLE , Mark J. Sartain , Suman Laal
IPC分类号： G01N33/554 , C07K14/00
CPC分类号： C07K14/35 , G01N33/5695
摘要： Mycobacterial proteins from culture filtrate or cytosol are disclosed as being useful B cell antigens for early diagnosis of mycobacterial disease, particularly in humans. These proteins include four that had not previously been recognized as B cell antigens (LppZ protein encoded by Mtb gene Rv3006; SodC protein encoded by Mtb gene Rv0432; BfrB protein encoded by Mtb gene Rv3841 and TrxC protein encoded byMtb gene Rv3914). Antigenic compositions include these proteins and/or peptide fragments thereof, in various combinations with each other or with one or more of a set of 10 additional Mtb proteins known to be antigens (in paricular early antigens. Methods and kits for using these antigenic composition for early diagnosis of mycobacterial infection and disease are also disclosed.
摘要翻译：公开了来自培养滤液或细胞溶质的分枝杆菌蛋白质作为用于早期诊断分枝杆菌病，特别是人类的有用的B细胞抗原。这些蛋白质包括以前未被认定为B细胞抗原的四种（Mtb基因Rv3006编码的LppZ蛋白;由Mtb基因Rv0432编码的SodC蛋白;由Mtb基因Rv3841编码的BfrB蛋白和由Mtb基因Rv3914编码的TrxC蛋白）。抗原组合物包括这些蛋白质和/或其肽片段，其彼此具有各种组合，或与已知为抗原的10种另外的Mtb蛋白质的一种或多种组合（在特异性早期抗原中）。使用这些抗原组合物的方法和试剂盒还公开了分枝杆菌感染和疾病的早期诊断。

10. 发明授权

US07776341B2 Biomarkers of tuberculosis that distinguish disease categories: use as serodiagnostic antigens 有权
标题翻译：结核病生物标志物区分疾病类别：用作血清诊断抗原
公开(公告)号：US07776341B2
公开(公告)日：2010-08-17
申请号：US11837264
申请日：2007-08-10
申请人： John T. Belisle , Mark J. Sartain , Suman Laal
发明人： John T. Belisle , Mark J. Sartain , Suman Laal
IPC分类号： A61K39/04 , A61K39/00 , A61K39/02
CPC分类号： C07K14/35 , G01N33/5695
摘要： Mycobacterial proteins from culture filtrate or cytosol are disclosed as being useful B cell antigens for early diagnosis of mycobacterial disease, particularly in humans. These proteins include four that had not previously been recognized as B cell antigens (LppZ protein encoded by Mtb gene Rv3006; SodC protein encoded by Mtb gene Rv0432; BfrB protein encoded by Mtb gene Rv3841 and TrxC protein encoded by Mtb gene Rv3914). Antigenic compositions include these proteins and/or peptide fragments thereof, in various combinations with each other or with one or more of a set of 10 additional Mtb proteins known to be antigens (in particular early antigens. Methods and kits for using these antigenic composition for early diagnosis of mycobacterial infection and disease are also disclosed.
摘要翻译：公开了来自培养滤液或细胞溶质的分枝杆菌蛋白质作为用于早期诊断分枝杆菌病，特别是人类的有用的B细胞抗原。这些蛋白质包括以前未被认定为B细胞抗原的四种（Mtb基因Rv3006编码的LppZ蛋白; Mtb基因Rv0432编码的SodC蛋白;由Mtb基因Rv3841编码的BfrB蛋白和由Mtb基因Rv3914编码的TrxC蛋白）。抗原组合物包括彼此各种组合的这些蛋白质和/或其肽片段，或与一组已知为抗原的10种另外的Mtb蛋白质（特别是早期抗原）中的一种或多种组合使用这些抗原组合物的方法和试剂盒还公开了分枝杆菌感染和疾病的早期诊断。

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