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1. 发明授权

US07960535B2 Recombinant lipidated PsaA protein, methods of preparation and use 失效
标题翻译：重组脂质化PsaA蛋白，制备和使用方法
公开(公告)号：US07960535B2
公开(公告)日：2011-06-14
申请号：US12619357
申请日：2009-11-16
申请人： Edwin W. Ades , George M. Carlone , Barun K. De , Jacquelyn S. Sampson , Robert C. Huebner
发明人： Edwin W. Ades , George M. Carlone , Barun K. De , Jacquelyn S. Sampson , Robert C. Huebner
IPC分类号： C07H21/02 , C07H21/04 , A61K49/00
CPC分类号： C07K14/3156 , A61K39/00 , C07K2319/00 , Y02A50/401
摘要： The present invention relates to recombinant lipidated PsaA proteins and recombinant constructs from which such lipidated PsaA proteins may be expressed. The invention relates further to lipidated PsaA proteins in which lipidation is effected by the use of a heterologous leader sequence derived from the ospA gene of Borrelia burgdorferi, which leader sequence is joined in translational reading frame with the psaA structural gene. The invention also provides methods of preparation of lipidated PsaA proteins and use of such proteins in immunological compositions. Also provided are vaccines comprising immunogenic lipidated PsaA proteins and methods of use of such vaccines in the prevention and treatment of S. pneumoniae infection.
摘要翻译：本发明涉及重组脂化的PsaA蛋白和重组构建体，其中可以表达这种脂质化的PsaA蛋白。本发明进一步涉及脂质化PsaA蛋白，其中通过使用源自博氏疏螺旋体的ospA基因的异源前导序列来实现脂化，该引导序列与psaA结构基因连接在翻译阅读框中。本发明还提供了脂质化PsaA蛋白的制备方法和这些蛋白质在免疫组合物中的应用。还提供了包含免疫原性脂化PsaA蛋白的疫苗以及这种疫苗在预防和治疗肺炎链球菌感染中的使用方法。

2. 发明申请

US20100260802A1 RECOMBINANT LIPIDATED PsaA PROTEIN, METHODS OF PREPARATION AND USE 失效
标题翻译：重组脂肪酸PsaA蛋白，制备和使用方法
公开(公告)号：US20100260802A1
公开(公告)日：2010-10-14
申请号：US12619357
申请日：2009-11-16
申请人： Edwin W. Ades , George M. Carlone , Barun K. De , Jacquelyn S. Sampson , Robert C. Huebner
发明人： Edwin W. Ades , George M. Carlone , Barun K. De , Jacquelyn S. Sampson , Robert C. Huebner
IPC分类号： A61K39/09 , C07H21/04 , A61P31/04 , C07K14/315 , C12N15/63 , C12P21/00
CPC分类号： C07K14/3156 , A61K39/00 , C07K2319/00 , Y02A50/401
摘要： The present invention relates to recombinant lipidated PsaA proteins and recombinant constructs from which such lipidated PsaA proteins may be expressed. The invention relates further to lipidated PsaA proteins in which lipidation is effected by the use of a heterologous leader sequence derived from the ospA gene of Borrelia burgdorferi, which leader sequence is joined in translational reading frame with the psaA structural gene. The invention also provides methods of preparation of lipidated PsaA proteins and use of such proteins in immunological compositions. Also provided are vaccines comprising immunogenic lipidated PsaA proteins and methods of use of such vaccines in the prevention and treatment of S. pneumoniae infection.
摘要翻译：本发明涉及重组脂化的PsaA蛋白和重组构建体，其中可以表达这种脂质化的PsaA蛋白。本发明进一步涉及脂质化PsaA蛋白，其中通过使用源自博氏疏螺旋体的ospA基因的异源前导序列来实现脂化，该引导序列与psaA结构基因连接在翻译阅读框中。本发明还提供了脂质化PsaA蛋白的制备方法和这些蛋白质在免疫组合物中的应用。还提供了包含免疫原性脂化PsaA蛋白的疫苗以及这种疫苗在预防和治疗肺炎链球菌感染中的使用方法。

3. 发明授权

US07635486B1 Recombinant lipidated PsaA protein, methods of preparation and use 失效
标题翻译：重组脂质化PsaA蛋白，制备和使用方法
公开(公告)号：US07635486B1
公开(公告)日：2009-12-22
申请号：US09600057
申请日：1999-01-14
申请人： Edwin W. Ades , George M. Carlone , Barun K. De , Jacquelyn S. Sampson , Robert C. Huebner
发明人： Edwin W. Ades , George M. Carlone , Barun K. De , Jacquelyn S. Sampson , Robert C. Huebner
IPC分类号： A61K39/02 , A61K45/00 , A61K39/09
CPC分类号： C07K14/3156 , A61K39/00 , C07K2319/00 , Y02A50/401
摘要： The present invention relates to recombinant lipidated PsaA proteins and recombinant constructs from which such lipidated PsaA proteins may be expressed. The invention relates further to lipidated PsaA proteins in which lipidation is effected by the use of a heterologous leader sequence derived from the ospA gene of Borrelia burgdorferi, which leader sequence is joined in translational reading frame with the psaA structural gene. The invention also provides methods of preparation of lipidated PsaA proteins and use of such proteins in immunological compositions. Also provided are vaccines comprising immunogenic lipidated PsaA proteins and methods of use of such vaccines in the prevention and treatment of S. pneumoniae infection.
摘要翻译：本发明涉及重组脂化的PsaA蛋白和重组构建体，其中可以表达这种脂质化的PsaA蛋白。本发明进一步涉及脂质化PsaA蛋白，其中通过使用源自博氏疏螺旋体的ospA基因的异源前导序列来实现脂化，该引导序列与psaA结构基因连接在翻译阅读框中。本发明还提供了脂质化PsaA蛋白的制备方法和这些蛋白质在免疫组合物中的应用。还提供了包含免疫原性脂化PsaA蛋白的疫苗以及这种疫苗在预防和治疗肺炎链球菌感染中的使用方法。

4. 发明授权

US08420107B2 Peptide vaccines against group A streptococci 有权
标题翻译：针对A组链球菌的肽疫苗
公开(公告)号：US08420107B2
公开(公告)日：2013-04-16
申请号：US13427477
申请日：2012-03-22
申请人： Bernard W. Beall , George M. Carlone , Jacquelyn S. Sampson , Edwin W. Ades
发明人： Bernard W. Beall , George M. Carlone , Jacquelyn S. Sampson , Edwin W. Ades
IPC分类号： A61K39/09 , C07K14/315
CPC分类号： A61K39/092 , A61K39/00 , C07K14/001 , C07K14/315 , C07K2319/00
摘要： This invention, in one aspect, relates to synthetic immunoreactive peptides. These peptides are approximately 20-25 amino acids in length which are portions of the N termini of the M proteins of the most prevalent United States (U.S.) Group A Streptococcus (GAS) serotypes. At least some of the synthetic peptides can be recognized by M type-specific antibodies and are capable of eliciting functional opsonic antibodies and/or anti-attachment antibodies without eliciting tissue cross-reactive antibodies. In another aspect, it relates to compositions or vaccines comprising these synthetic serotype-specific peptides, including polypeptides and proteins. The invention may also be isolated antibodies which are raised in response to the peptides, compositions or vaccines. The invention further relates to kits for using the peptides, compositions, or antibodies. In still further aspects, the invention also relates to methods for using the peptides, compositions, vaccines, or antibodies and methods for tailoring vaccines.
摘要翻译：本发明在一个方面涉及合成免疫反应肽。这些肽的长度约为20-25个氨基酸，它们是最流行的美国（A）链球菌（GAS）血清型的M蛋白的N末端的部分。至少一些合成肽可被M型特异性抗体识别，并且能够引发功能性调理抗体和/或抗附着抗体而不引发组织交叉反应性抗体。另一方面，本发明涉及包含这些合成血清型特异性肽（包括多肽和蛋白质）的组合物或疫苗。本发明还可以是响应于肽，组合物或疫苗引起的分离的抗体。本发明还涉及使用肽，组合物或抗体的试剂盒。在另外的方面，本发明还涉及使用肽，组合物，疫苗或抗体的方法和用于定制疫苗的方法。

5. 发明授权

US07883710B2 Peptide vaccines against Group A streptococci 有权
标题翻译：针对A组链球菌的肽疫苗
公开(公告)号：US07883710B2
公开(公告)日：2011-02-08
申请号：US12144461
申请日：2008-06-23
申请人： Bernard W. Beall , George M. Carlone , Jacquelyn S. Sampson , Edwin W. Ades
发明人： Bernard W. Beall , George M. Carlone , Jacquelyn S. Sampson , Edwin W. Ades
IPC分类号： A61K39/09 , C07H21/04 , C07K4/04 , C12P21/06
CPC分类号： A61K39/092 , A61K39/00 , C07K14/001 , C07K14/315 , C07K2319/00
摘要： This invention, in one aspect, relates to synthetic immunoreactive peptides. These peptides are approximately 20-25 amino acids in length which are portions of the N termini of the M proteins of the most prevalent United States (U.S.) Group A Streptococcus (GAS) serotypes. At least some of the synthetic peptides can be recognized by M type-specific antibodies and are capable of eliciting functional opsonic antibodies and/or anti-attachment antibodies without eliciting tissue cross-reactive antibodies. In another aspect, it relates to compositions or vaccines comprising these synthetic serotype-specific peptides, including polypeptides and proteins. The invention may also be isolated antibodies which are raised in response to the peptides, compositions or vaccines. The invention further relates to kits for using the peptides, compositions, or antibodies. In still further aspects, the invention also relates to methods for using the peptides, compositions, vaccines, or antibodies and methods for tailoring vaccines.
摘要翻译：本发明在一个方面涉及合成免疫反应肽。这些肽的长度约为20-25个氨基酸，它们是最流行的美国（A）链球菌（GAS）血清型的M蛋白的N末端的部分。至少一些合成肽可被M型特异性抗体识别，并且能够引发功能性调理抗体和/或抗附着抗体而不引发组织交叉反应性抗体。另一方面，本发明涉及包含这些合成血清型特异性肽（包括多肽和蛋白质）的组合物或疫苗。本发明还可以是响应于肽，组合物或疫苗引起的分离的抗体。本发明还涉及使用肽，组合物或抗体的试剂盒。在另外的方面，本发明还涉及使用肽，组合物，疫苗或抗体的方法和用于定制疫苗的方法。

6. 发明申请

US20110110969A1 PEPTIDE VACCINES AGAINST GROUP A STREPTOCOCCI 审中-公开
标题翻译：肽类疫苗对A组STREPTOCOCCI
公开(公告)号：US20110110969A1
公开(公告)日：2011-05-12
申请号：US12973247
申请日：2010-12-20
申请人： Bernard W. Beall , George M. Carlone , Jacquelyn S. Sampson , Edwin W. Ades
发明人： Bernard W. Beall , George M. Carlone , Jacquelyn S. Sampson , Edwin W. Ades
IPC分类号： A61K39/09 , C07K14/315 , A61P31/04 , A61K39/116
CPC分类号： A61K39/092 , A61K39/00 , C07K14/001 , C07K14/315 , C07K2319/00
摘要： This invention, in one aspect, relates to synthetic immunoreactive peptides. These peptides are approximately 20-25 amino acids in length which are portions of the N termini of the M proteins of the most prevalent United States (U.S.) Group A Streptococcus (GAS) serotypes. At least some of the synthetic peptides can be recognized by M type-specific antibodies and are capable of eliciting functional opsonic antibodies and/or anti-attachment antibodies without eliciting tissue cross-reactive antibodies. In another aspect, it relates to compositions or vaccines comprising these synthetic serotype-specific peptides, including polypeptides and proteins. The invention may also be isolated antibodies which are raised in response to the peptides, compositions or vaccines. The invention further relates to kits for using the peptides, compositions, or antibodies. In still further aspects, the invention also relates to methods for using the peptides, compositions, vaccines, or antibodies and methods for tailoring vaccines.
摘要翻译：本发明在一个方面涉及合成免疫反应肽。这些肽的长度约为20-25个氨基酸，它们是最流行的美国（A）链球菌（GAS）血清型的M蛋白的N末端的部分。至少一些合成肽可被M型特异性抗体识别，并且能够引发功能性调理抗体和/或抗附着抗体而不引发组织交叉反应性抗体。另一方面，本发明涉及包含这些合成血清型特异性肽（包括多肽和蛋白质）的组合物或疫苗。本发明还可以是响应于肽，组合物或疫苗引起的分离的抗体。本发明还涉及使用肽，组合物或抗体的试剂盒。在另外的方面，本发明还涉及使用肽，组合物，疫苗或抗体的方法和用于定制疫苗的方法。

7. 发明授权

US07919104B2 Functional epitopes of Streptococcus pneumoniae PsaA antigen and uses thereof 有权
标题翻译：肺炎链球菌PsaA抗原的功能表位及其用途
公开(公告)号：US07919104B2
公开(公告)日：2011-04-05
申请号：US11992719
申请日：2005-07-29
申请人： Edwin W. Ades , Jacquelyn S. Sampson , Sandra Steiner , George M. Carlone , Joseph J. Caba , GowriSankar Rajam
发明人： Edwin W. Ades , Jacquelyn S. Sampson , Sandra Steiner , George M. Carlone , Joseph J. Caba , GowriSankar Rajam
IPC分类号： A61K39/09 , A61K39/02 , A61K39/38 , A61K38/00 , A01N37/18
CPC分类号： C07K14/3156 , A61K39/00 , A61K2039/505 , Y10S530/825
摘要： Provided is a P4 peptide, which contains functional epitopes of the PsaA protein of Streptococcus pneumoniae, and related methods and compositions. P4 peptide mimetics having a conformational structure identical or similar to the conformation of P4 (e.g., SEQ ID NO: 1 and SEQ ID NO:2) are provided. An antibody that specifically binds to the epitope defined by the disclosed peptides is provided. A P4-specific antibody is PsaA-specific since P4 defines an epitope specific for PsaA. Immunogenic compositions comprising the peptide of SEQ ID NO: 1 and a pharmaceutical carrier or the peptide of SEQ ID NO:2 and a pharmaceutical carrier are also provided. Methods of using the peptides and antibodies of the invention are provided.
摘要翻译：提供了含有肺炎链球菌PsaA蛋白的功能性表位的P4肽及其相关方法和组合物。提供了具有与P4的构象相同或相似的构象结构的P4肽模拟物（例如，SEQ ID NO：1和SEQ ID NO：2）。提供了特异性结合由公开的肽定义的表位的抗体。 P4特异性抗体是PsaA特异性的，因为P4定义了PsaA特异性表位。还提供了包含SEQ ID NO：1的肽和药物载体或SEQ ID NO：2的肽的药物载体的免疫原性组合物。提供使用本发明的肽和抗体的方法。

8. 发明授权

US07501132B2 Multiple antigenic peptides immunogenic against Streptococcus pneumonia 有权
标题翻译：针对肺炎链球菌免疫原性的多种抗原肽
公开(公告)号：US07501132B2
公开(公告)日：2009-03-10
申请号：US11145814
申请日：2005-06-06
申请人： Edwin W. Ades , Scott E. Johnson , Danny L. Jue , Jacquelyn S. Sampson , George M. Carlone
发明人： Edwin W. Ades , Scott E. Johnson , Danny L. Jue , Jacquelyn S. Sampson , George M. Carlone
IPC分类号： A61K39/09 , A61K39/02 , A61K39/38 , A61K39/385 , A61K38/00 , A01N37/18
CPC分类号： C07K7/08 , A61K38/00 , A61K39/00 , C07K14/3156 , Y10S530/806 , Y10S530/825
摘要： The invention provides a nucleic acid encoding the 37-kDa pneumococcal surface adhesion A protein (PsaA) from Streptococcus pneumoniae. Also provided are isolated nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. The invention also provides purified polypeptides encoded by the nucleic acid encoding the 37-kDa protein from and the nucleic acids comprising unique fragment of at least 10 nucleotides of the 37-kDa protein. The invention further provides monoclonal antibodies which selectively bind PsaA. In addition, peptides are provided that immunospecifically bind to the monoclonal antibodies of the invention, and that are immunogenic against Streptococcus pneumoniae infection. Additionally, multiple antigenic peptides that provide protection against S. pneumoniae challenge are provided. These multiple antigen peptides comprise the peptides that immunospecifically bind to the monoclonal antibodies. Also provided are vaccines comprising such immunogenic peptides, and methods of conferring protective immunity against Streptococcus pneumoniae infection by administering therapeutic composition comprising the immunogenic peptides of the invention. Also provided are methods of detecting the presence of Streptococcus pneumoniae in a sample using antibodies or antigens and methods of preventing and treating Streptococcus pneumoniae infection in a subject. In addition, a method of identifying the sequence of a peptide potentially capable of eliciting protective immunity against a pathogenic microorganism is provided.
摘要翻译：本发明提供编码来自肺炎链球菌的37-kDa肺炎球菌表面粘附A蛋白（PsaA）的核酸。还提供了分离的核酸，其包含37-kDa蛋白质的至少10个核苷酸的独特片段。本发明还提供由编码37-kDa蛋白质的核酸编码的纯化多肽和包含37-kDa蛋白质至少10个核苷酸的独特片段的核酸。本发明还提供选择性结合PsaA的单克隆抗体。此外，提供了免疫特异性结合本发明的单克隆抗体并且对肺炎链球菌感染具有免疫原性的肽。另外，提供了提供针对肺炎链球菌攻击的保护的多种抗原肽。这些多重抗原肽包含免疫特异性结合单克隆抗体的肽。还提供了包含这种免疫原性肽的疫苗，以及通过施用包含本发明的免疫原性肽的治疗组合物来赋予对肺炎链球菌感染的保护性免疫的方法。还提供了使用抗体或抗原检测样品中肺炎链球菌存在的方法以及在受试者中预防和治疗肺炎链球菌感染的方法。此外，提供了鉴定潜在地能够引发对病原微生物的保护性免疫的肽的序列的方法。

9. 发明申请

US20080279880A1 PEPTIDE VACCINES AGAINST GROUP A STREPTOCOCCI 有权
标题翻译：肽类疫苗对A组STREPTOCOCCI
公开(公告)号：US20080279880A1
公开(公告)日：2008-11-13
申请号：US12144461
申请日：2008-06-23
申请人： Bernard W. Beall , George M. Carlone , Jacquelyn S. Sampson , Edwin W. Ades
发明人： Bernard W. Beall , George M. Carlone , Jacquelyn S. Sampson , Edwin W. Ades
IPC分类号： A61K39/02 , A61K38/16 , A61K39/095 , A61K39/10 , A61K38/10
CPC分类号： A61K39/092 , A61K39/00 , C07K14/001 , C07K14/315 , C07K2319/00
摘要： This invention, in one aspect, relates to synthetic immunoreactive peptides. These peptides are approximately 20-25 amino acids in length which are portions of the N termini of the M proteins of the most prevalent United States (U.S.) Group A Streptococcus (GAS) serotypes. At least some of the synthetic peptides can be recognized by M type-specific antibodies and are capable of eliciting functional opsonic antibodies and/or anti-attachment antibodies without eliciting tissue cross-reactive antibodies. In another aspect, it relates to compositions or vaccines comprising these synthetic serotype-specific peptides, including polypeptides and proteins. The invention may also be isolated antibodies which are raised in response to the peptides, compositions or vaccines. The invention further relates to kits for using the peptides, compositions, or antibodies. In still further aspects, the invention also relates to methods for using the peptides, compositions, vaccines, or antibodies and methods for tailoring vaccines.
摘要翻译：本发明在一个方面涉及合成免疫反应肽。这些肽的长度约为20-25个氨基酸，它们是最流行的美国（A）链球菌（GAS）血清型的M蛋白的N末端的部分。至少一些合成肽可被M型特异性抗体识别，并且能够引发功能性调理抗体和/或抗附着抗体而不引发组织交叉反应性抗体。另一方面，本发明涉及包含这些合成血清型特异性肽（包括多肽和蛋白质）的组合物或疫苗。本发明还可以是响应于肽，组合物或疫苗引起的分离的抗体。本发明还涉及使用肽，组合物或抗体的试剂盒。在另外的方面，本发明还涉及使用肽，组合物，疫苗或抗体的方法和用于定制疫苗的方法。

10. 发明申请

US20110195075A1 USE OF A PNEUMOCOCCAL P4 PEPTIDE FOR ENHANCING OPSONOPHAGOCYTOSIS IN RESPONSE TO A PATHOGEN 有权
标题翻译：使用肺癌P4肽增强麻醉药对病人的反应
公开(公告)号：US20110195075A1
公开(公告)日：2011-08-11
申请号：US13056522
申请日：2009-07-31
申请人： Edwin W. Ades , Gowrisankar Rajam , Sandra Steiner , George M. Carlone , Nikkol Melnick , Jacquelyn S. Sampson , Joseph E. Martinez , Julie M. Skinner
发明人： Edwin W. Ades , Gowrisankar Rajam , Sandra Steiner , George M. Carlone , Nikkol Melnick , Jacquelyn S. Sampson , Joseph E. Martinez , Julie M. Skinner
IPC分类号： A61K39/42 , A61K39/395 , A61K39/40 , A61K38/16 , A61P31/00
CPC分类号： A61K38/164 , A61K31/00 , A61K31/53 , A61K38/1725 , A61K39/395 , A61K39/40 , A61K39/42 , A61K45/06 , A61K2300/00
摘要： Methods for enhancing opsonophagocytosis of a pathogen of interest are disclosed. The disclosed methods include administering to a subject an isolated P4 peptide, which including the amino acid sequence set forth as SEQ ID NO: 1 and optionally an isolated opsonic antibody or a fragment thereof that specifically binds to an antigen present of the surface of the pathogen of interest. In some examples isolated complement protein or a fragment thereof (for example, a C3a, C3b, iC3b, C3d, C4b, or C5a fragment of a complement protein) is also administering. Compositions contain isolated P4 peptide and one or more isolated opsonic antibodies or a fragment thereof that specifically binds to an antigen present of the surface of a pathogen of interest are also disclosed. In some examples, the compositions also isolated complement protein or fragment thereof, such as one or more of C3a, C3b, iC3b, C3d, C4b, or C5a.
摘要翻译：公开了增加目的病原体的调理吞噬作用的方法。所公开的方法包括向受试者施用分离的P4肽，其包括如SEQ ID NO：1所示的氨基酸序列和任选的特异性结合病原体表面存在的抗原的分离的调理蛋白抗体或其片段出于兴趣。在一些实例中，还施用了分离的补体蛋白或其片段（例如，补体蛋白的C3a，C3b，iC3b，C3d，C4b或C5a片段）。还公开了组合物含有分离的P4肽和一种或多种分离的调理抗体或其特异性结合目的病原体表面存在的抗原的片段。在一些实例中，组合物还分离补体蛋白或其片段，例如C3a，C3b，iC3b，C3d，C4b或C5a中的一种或多种。

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