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1. 发明授权

US06268411B1 Use of multivalent chimeric peptide-loaded, MHC/ig molecules to detect, activate or suppress antigen-specific T cell-dependent immune responses 有权
标题翻译：使用多价嵌合肽加载的MHC / ig分子检测，激活或抑制抗原特异性T细胞依赖性免疫应答
公开(公告)号：US06268411B1
公开(公告)日：2001-07-31
申请号：US09150622
申请日：1998-09-10
申请人： Jonathan Schneck , Drew Pardoll , Sean O'Herrin , Jill Slansky , Tim Greten
发明人： Jonathan Schneck , Drew Pardoll , Sean O'Herrin , Jill Slansky , Tim Greten
IPC分类号： C07K16100
CPC分类号： A61K39/385 , A61K38/00 , A61K39/00 , A61K47/6425 , A61K47/6811 , A61K2035/124 , A61K2039/5154 , A61K2039/5158 , A61K2039/605 , A61K2039/6056 , C07K14/005 , C07K14/7051 , C07K14/70539 , C07K2319/00 , C07K2319/30 , C12N2710/14143 , C12N2740/13022 , C12N2740/14022 , C12N2760/16122 , C12N2760/16134
摘要： To increase the effective affinity of soluble analogs of peptide/MHC molecules for their cognate ligands, divalent peptide/MHC complexes were constructed. Using a recombinant DNA strategy, DNA encoding the MHC class I was ligated to DNA coding for murine Ig heavy chain. MHC/Ig complexes were exploited to homogeneously load with peptides of interest. The results of flow cytometry demonstrated that the pepMHC/Ig complexes bound specifically with high affinity to cells bearing their cognate receptors. pepMHC/Ig complexes are also useful in modulating effector functions of antigen-specific T cells. These pepMHC/Ig complexes are useful for studying TCR/MHC interactions and lymphocyte tracking and have uses as specific regulators of immune responses.
摘要翻译：为了增加肽/ MHC分子的可溶性类似物对其同源配体的有效亲和力，构建了二价肽/ MHC复合物。使用重组DNA策略，将编码MHC I类的DNA连接到编码鼠Ig重链的DNA上。利用MHC / Ig复合物均匀加载感兴趣的肽。流式细胞仪的结果表明，具有高亲和力的pepMHC / Ig复合物特异性结合携带其同源受体pepMHC / Ig复合物的细胞也可用于调节抗原特异性T细胞的效应子功能。这些pepMHC / Ig复合物可用于研究TCR / MHC相互作用和淋巴细胞跟踪，并将其用作免疫应答的特异性调节物。

2. 发明授权

US06734013B2 Use of multivalent chimeric peptide-loaded, MHC/Ig molecules to detect, activate or suppress antigen-specific T cell-dependent immune responses 有权
标题翻译：使用多价嵌合肽负载的MHC / Ig分子来检测，激活或抑制抗原特异性T细胞依赖性免疫应答
公开(公告)号：US06734013B2
公开(公告)日：2004-05-11
申请号：US09789720
申请日：2001-02-22
申请人： Jonathan Schneck , Drew Pardoll , Sean O'Herrin , Jill Slansky , Tim Greten
发明人： Jonathan Schneck , Drew Pardoll , Sean O'Herrin , Jill Slansky , Tim Greten
IPC分类号： C12N1563
CPC分类号： A61K39/385 , A61K38/00 , A61K39/00 , A61K47/6425 , A61K47/6811 , A61K2035/124 , A61K2039/5154 , A61K2039/5158 , A61K2039/605 , A61K2039/6056 , C07K14/005 , C07K14/7051 , C07K14/70539 , C07K2319/00 , C07K2319/30 , C12N2710/14143 , C12N2740/13022 , C12N2740/14022 , C12N2760/16122 , C12N2760/16134
摘要： To increase the effective affinity of soluble analogs of peptide/MHC molecules for their cognate ligands, divalent peptide/MHC complexes were constructed. Using a recombinant DNA strategy, DNA encoding the MHC class I was ligated to DNA coding for murine Ig heavy chain. MHC/Ig complexes were exploited to homogeneously load with peptides of interest. The results of flow cytometry demonstrated that the pepMHC/Ig complexes bound specifically with high affinity to cells bearing their cognate receptors. pepMHC/Ig complexes are also useful in modulating effector functions of antigen-specific T cells. These pepMHC/Ig complexes are useful for studying TCR/MHC interactions and lymphocyte tracking and have uses as specific regulators of immune responses.
摘要翻译：为了增加肽/ MHC分子的可溶性类似物对其同源配体的有效亲和力，构建了二价肽/ MHC复合物。使用重组DNA策略，将编码MHC I类的DNA连接到编码鼠Ig重链的DNA上。利用MHC / Ig复合物均匀加载感兴趣的肽。流式细胞术的结果表明，MHC / Ig复合物特异性结合具有高亲和力的细胞携带其同源受体。 MHC / Ig复合物也可用于调节抗原特异性T细胞的效应子功能。这些MHC / Ig复合物可用于研究TCR / MHC相互作用和淋巴细胞跟踪，并且具有用作免疫应答的特异性调节物。

3. 发明申请

US20110243967A1 MOLECULAR COMPLEXES WHICH MODIFY IMMUNE RESPONSES 审中-公开
标题翻译：修饰免疫应答的分子复合物
公开(公告)号：US20110243967A1
公开(公告)日：2011-10-06
申请号：US13156964
申请日：2011-06-09
申请人： Jonathan Schneck , Sean O'Herrin , Michael S. Lebowitz , Abdel Hamad
发明人： Jonathan Schneck , Sean O'Herrin , Michael S. Lebowitz , Abdel Hamad
IPC分类号： A61K39/395 , G01N33/53 , C12N5/0783 , A61P37/08 , A61P37/06 , A61P31/00
CPC分类号： C07K14/7051 , A61K38/00 , A61K39/00 , A61K2039/605 , A61K2039/6056 , C07K14/70539 , C07K2319/00 , C07K2319/30 , C12N2799/026
摘要： Extracellular domains of transmembrane heterodimeric proteins, particularly T cell receptor and major histocompatibility complex proteins, can be covalently linked to the heavy and light chains of immunoglobulin molecules to provide soluble multivalent molecular complexes with high affinity for their cognate ligands. The molecular complexes can be used, inter alia, to detect and regulate antigen-specific T cells and as therapeutic agents for treating disorders involving immune system regulation, such as allergies, autoimmune diseases, tumors, infections, and transplant rejection.
摘要翻译：跨膜异二聚体蛋白质的细胞外结构域，特别是T细胞受体和主要的组织相容性复合物蛋白质，可以与免疫球蛋白分子的重链和轻链共价连接，从而为其同源配体提供高亲和力的可溶性多价分子复合物。分子复合物尤其可用于检测和调节抗原特异性T细胞和用作治疗涉及免疫系统调节的疾病的治疗剂，例如过敏，自身免疫性疾病，肿瘤，感染和移植排斥。

4. 发明授权

US06458354B1 Molecular complexes which modify immune responses 有权
标题翻译：改变免疫应答的分子复合物
公开(公告)号：US06458354B1
公开(公告)日：2002-10-01
申请号：US09668143
申请日：2000-09-25
申请人： Jonathan Schneck , Sean O'Herrin , Michael S. Lebowitz , Abdel Hamad
发明人： Jonathan Schneck , Sean O'Herrin , Michael S. Lebowitz , Abdel Hamad
IPC分类号： A61K39395
CPC分类号： C07K14/70539 , A61K38/00 , A61K39/00 , A61K2039/605 , A61K2039/6056 , C07K14/7051 , C07K2319/00 , C07K2319/30 , C12N2799/026
摘要： Extracellular domains of transmembrane heterodimeric proteins, particularly T cell receptor and major histocompatibility complex proteins, can be covalently linked to the heavy and light chains of immunoglobulin molecules to provide soluble multivalent molecular complexes with high affinity for their cognate ligands. The molecular complexes can be used, inter alia, to detect and regulate antigen-specific T cells and as therapeutic agents for treating disorders involving immune system regulation, such as allergies, autoimmune diseases, tumors, infections, and transplant rejection.
摘要翻译：跨膜异二聚体蛋白质的细胞外结构域，特别是T细胞受体和主要的组织相容性复合物蛋白质，可以与免疫球蛋白分子的重链和轻链共价连接，从而为其同源配体提供高亲和力的可溶性多价分子复合物。分子复合物尤其可用于检测和调节抗原特异性T细胞和用作治疗涉及免疫系统调节的疾病的治疗剂，例如过敏，自身免疫性疾病，肿瘤，感染和移植排斥。

5. 发明授权

US06448071B1 Soluble divalent and multivalent heterodimeric analogs of proteins 有权
标题翻译：蛋白质的可溶性二价和多价异二聚体类似物
公开(公告)号：US06448071B1
公开(公告)日：2002-09-10
申请号：US09324782
申请日：1999-06-03
申请人： Jonathan Schneck , Sean O'Herrin
发明人： Jonathan Schneck , Sean O'Herrin
IPC分类号： C12N1563
CPC分类号： C07K14/7051 , A61K38/00 , A61K39/00 , A61K2039/605 , A61K2039/6056 , C07K14/70539 , C07K2319/00 , C07K2319/30 , C12N2799/026
摘要： Specificity in immune responses is in part controlled by the selective interaction of T cell receptors with their cognate ligands, peptide/MHC molecules. The discriminating nature of this interaction makes these molecules, in soluble form, good candidates for selectively regulating immune responses. Attempts to exploit soluble analogs of these proteins has been hampered by the intrinsic low avidity of these molecules for their ligands. To increase the avidity of soluble analogs for their cognates to biologically relevant levels, divalent peptide/MHC complexes or T cell receptors (superdimers) were constructed. Using a recombinant DNA strategy, DNA encoding either the MHC class II/peptide or TCR heterodimers was ligated to DNA coding for murine Ig heavy and light chains. These constructs were subsequently expressed in a baculovirus expression system. Enzyme-linked immunosorbant assays (ELISA) specific for the Ig and polymorphic determinants of either the TCR or MHC fraction of the molecule indicated that infected insect cells secreted approximately 1 &mgr;g/ml of soluble, conformationally intact chimeric superdimers. SDS PAGE gel analysis of purified protein showed that expected molecular weight species. The results of flow cytometry demonstrated that the TCR and class II chimeras bound specifically with high avidity to cells bearing their cognate receptors. These superdimers will be useful for studying TCR/MHC interactions, liymphocyte tracking, identifying new antigens, and have possible uses as specific regulators of immune responses.
摘要翻译：免疫应答的特异性部分由T细胞受体与其同源配体，肽/ MHC分子的选择性相互作用控制。这种相互作用的区别性质使得这些分子以可溶形式是选择性调节免疫应答的良好候选物。利用这些蛋白质的可溶性类似物的尝试受到这些分子对其配体的固有低亲合力的阻碍。为了将可溶性类似物的同源物的亲合力提高到生物相关水平，构建了二价肽/ MHC复合物或T细胞受体（superdimers）。使用重组DNA策略，将编码MHC II类/肽或TCR异源二聚体的DNA连接到编码鼠Ig重链和轻链的DNA。这些构建体随后在杆状病毒表达系统中表达。对分子的TCR或MHC级分的Ig和多态性决定簇特异的酶联免疫吸附测定（ELISA）表明感染的昆虫细胞分泌约1μg/ ml的可溶性，构象完整的嵌合超聚体。纯化蛋白的SDS PAGE凝胶分析显示预期的分子量物种。流式细胞术的结果表明，TCR和II类嵌合体具有高亲和力特异性结合携带其同源受体的细胞。这些超模对于研究TCR / MHC相互作用，淋巴细胞跟踪，鉴定新抗原以及可能用作免疫应答的特异性调节剂将是有用的。

6. 发明申请

US20120141482A1 MOLECULAR COMPLEXES WHICH MODIFY IMMUNE RESPONSES 审中-公开
标题翻译：修饰免疫应答的分子复合物
公开(公告)号：US20120141482A1
公开(公告)日：2012-06-07
申请号：US13369429
申请日：2012-02-09
申请人： Jonathan Schneck , Sean O'Herrin , Michael S. Lebowitz , Abdel Hamad
发明人： Jonathan Schneck , Sean O'Herrin , Michael S. Lebowitz , Abdel Hamad
IPC分类号： A61K39/395 , G01N21/64 , G01N33/566 , C12N5/0783 , A61P37/08 , A61P31/00
CPC分类号： C07K14/7051 , A61K38/00 , A61K39/00 , A61K2039/605 , A61K2039/6056 , C07K14/70539 , C07K2319/00 , C07K2319/30 , C12N2799/026
摘要： Extracellular domains of transmembrane heterodimeric proteins, particularly T cell receptor and major histocompatibility complex proteins, can be covalently linked to the heavy and light chains of immunoglobulin molecules to provide soluble multivalent molecular complexes with high affinity for their cognate ligands. The molecular complexes can be used, inter alia, to detect and regulate antigen-specific T cells and as therapeutic agents for treating disorders involving immune system regulation, such as allergies, autoimmune diseases, tumors, infections, and transplant rejection.
摘要翻译：跨膜异二聚体蛋白质的细胞外结构域，特别是T细胞受体和主要的组织相容性复合物蛋白质，可以与免疫球蛋白分子的重链和轻链共价连接，从而为其同源配体提供高亲和力的可溶性多价分子复合物。分子复合物尤其可用于检测和调节抗原特异性T细胞和用作治疗涉及免疫系统调节的疾病的治疗剂，例如过敏，自身免疫性疾病，肿瘤，感染和移植排斥。

7. 发明授权

US6140113A Polynucleotides encoding molecular complexes which modify immune responses 失效
标题翻译：编码分子复合物的多核苷酸修饰免疫应答
公开(公告)号：US6140113A
公开(公告)日：2000-10-31
申请号：US63276
申请日：1998-04-21
申请人： Jonathan Schneck , Sean O'Herrin , Michael S. Lebowitz , Abdel Hamad
发明人： Jonathan Schneck , Sean O'Herrin , Michael S. Lebowitz , Abdel Hamad
IPC分类号： A61K38/00 , A61K39/00 , B60R19/18 , B60R19/24 , C07K14/725 , C07K14/74 , C12P21/08 , C12N15/63 , C07H21/00 , C12N5/10 , C12N15/09 , C12N15/66
CPC分类号： C07K14/7051 , C07K14/70539 , A61K2039/605 , A61K2039/6056 , A61K38/00 , A61K39/00 , C07K2319/00 , C07K2319/30 , C12N2799/026
摘要： Polynucleotides encode soluble, multivalent molecular complexes which modify immune responses, and host cells comprise such polynucleotides. The molecular complexes comprise extracellular domains of transmembrane heterodimeric proteins, particularly T cell receptor and major histocompatibility complex proteins, which are covalently linked to the heavy and light chains of immunoglobulin molecules to provide soluble multivalent molecular complexes with high affinity for their cognate ligands. The molecular complexes can be used, inter alia, to detect and regulate antigen-specific T cells and as therapeutic agents for treating disorders involving immune system regulation, such as allergies, autoimmune diseases, tumors, infections, and transplant rejection.
摘要翻译：多核苷酸编码改变免疫应答的可溶性多价分子复合物，宿主细胞包含这样的多核苷酸。分子复合物包括跨膜异二聚体蛋白的细胞外结构域，特别是T细胞受体和主要组织相容性复合蛋白，其与免疫球蛋白分子的重链和轻链共价连接以提供对其同源配体具有高亲和力的可溶性多价分子复合物。分子复合物尤其可用于检测和调节抗原特异性T细胞和用作治疗涉及免疫系统调节的疾病的治疗剂，例如过敏，自身免疫性疾病，肿瘤，感染和移植排斥。

8. 发明授权

US07973137B1 Cell compositions comprising molecular complexes that modify immune responses 有权
标题翻译：包含修饰免疫应答的分子复合物的细胞组合物
公开(公告)号：US07973137B1
公开(公告)日：2011-07-05
申请号：US09642660
申请日：2000-08-22
申请人： Jonathan Schneck , Sean O'Herrin , Michael S. Lebowitz , Abdel Hamad
发明人： Jonathan Schneck , Sean O'Herrin , Michael S. Lebowitz , Abdel Hamad
IPC分类号： C12P21/08
CPC分类号： C07K14/7051 , A61K38/00 , A61K39/00 , A61K2039/605 , A61K2039/6056 , C07K14/70539 , C07K2319/00 , C07K2319/30 , C12N2799/026
摘要： Compositions comprising a cell in which a molecular complex with high affinity for its cognate ligand is bound to the surface of the cell are provided. To form the molecular complexes, extracellular domains of transmembrane heterodimeric proteins, particularly T cell receptor and major histocompatibility complex proteins, can be covalently linked to the heavy and light chains of immunoglobulin molecules. The molecular complexes can be used, inter alia, to detect and regulate antigen-specific T cells and as therapeutic agents for treating disorders involving immune system regulation, such as allergies, autoimmune diseases, tumors, infections, and transplant rejection. Optionally, identical antigenic peptides can be bound to each ligand binding site of a molecular complex.
摘要翻译：提供了包含细胞的组合物，其中与其同源配体具有高亲和力的分子复合物结合于细胞表面。为了形成分子复合物，跨膜异二聚体蛋白的细胞外结构域，特别是T细胞受体和主要组织相容性复合蛋白，可以与免疫球蛋白分子的重链和轻链共价连接。分子复合物尤其可用于检测和调节抗原特异性T细胞和用作治疗涉及免疫系统调节的疾病的治疗剂，例如过敏，自身免疫性疾病，肿瘤，感染和移植排斥。任选地，相同的抗原肽可以结合到分子复合物的每个配体结合位点。

9. 发明授权

US6015884A Soluble divalent and multivalent heterodimeric analogs of proteins 失效
标题翻译：蛋白质的可溶性二价和多价异二聚体类似物
公开(公告)号：US6015884A
公开(公告)日：2000-01-18
申请号：US828712
申请日：1997-03-28
申请人： Jonathan Schneck , Sean O'Herrin
发明人： Jonathan Schneck , Sean O'Herrin
IPC分类号： C12N15/09 , A61K38/00 , A61K39/00 , A61K39/395 , A61P37/00 , C07K14/725 , C07K14/74 , C07K16/18 , C07K19/00 , C12N5/10 , C12N15/62 , C12P21/02 , C12P21/08 , G01N33/531 , C07K16/00
CPC分类号： C07K14/7051 , C07K14/70539 , A61K2039/605 , A61K2039/6056 , A61K38/00 , A61K39/00 , C07K2319/00 , C07K2319/30 , C12N2799/026
摘要： Specificity in immune responses is in part controlled by the selective interaction of T cell receptors with their cognate ligands, peptide/MHC molecules. The discriminating nature of this interaction makes these molecules, in soluble form, good candidates for selectively regulating immune responses. Attempts to exploit soluble analogs of these proteins has been hampered by the intrinsic low avidity of these molecules for their ligands. To increase the avidity of soluble analogs for their cognates to biologically relevant levels, divalent peptide/MHC complexes or T cell receptors (superdimers) were constructed. Using a recombinant DNA strategy, DNA encoding either the MHC class II/peptide or TCR heterodimers was ligated to DNA coding for murine Ig heavy and light chains. These constructs were subsequently expressed in a baculovirus expression system. Enzyme-linked immunosorbant assays (ELISA) specific for the Ig and polymorphic determinants of either the TCR or MHC fraction of the molecule indicated that infected insect cells secreted approximately 1 .mu.g/ml of soluble, conformationally intact chimeric superdimers. SDS PAGE gel analysis of purified protein showed that expected molecular weight species. The results of flow cytometry demonstrated that the TCR and class II chimeras bound specifically with high avidity to cells bearing their cognate receptors. These superdimers will be useful for studying TCR/MHC interactions, lymphocyte tracking, identifying new antigens, and have possible uses as specific regulators of immune responses.
摘要翻译：免疫应答的特异性部分由T细胞受体与其同源配体，肽/ MHC分子的选择性相互作用控制。这种相互作用的区别性质使得这些分子以可溶形式是选择性调节免疫应答的良好候选物。利用这些蛋白质的可溶性类似物的尝试受到这些分子对其配体的固有低亲合力的阻碍。为了将可溶性类似物的同源物的亲合力提高到生物相关水平，构建了二价肽/ MHC复合物或T细胞受体（superdimers）。使用重组DNA策略，将编码MHC II类/肽或TCR异源二聚体的DNA连接到编码鼠Ig重链和轻链的DNA。这些构建体随后在杆状病毒表达系统中表达。特异于分子的TCR或MHC级分的Ig和多态性决定簇的酶联免疫吸附测定（ELISA）表明感染的昆虫细胞分泌约1μg/ ml的可溶性，构象完整的嵌合超聚体。纯化蛋白的SDS PAGE凝胶分析显示预期的分子量物种。流式细胞术的结果表明，TCR和II类嵌合体具有高亲和力特异性结合携带其同源受体的细胞。这些超模对于研究TCR / MHC相互作用，淋巴细胞跟踪，鉴定新抗原以及可能用作免疫应答的特异性调节剂将是有用的。

10. 发明申请

US20110300168A1 COMPOSITIONS AND METHODS FOR INDUCING AN IMMUNE RESPONSE AGAINST INFLUENZA ANTIGENS 审中-公开
标题翻译：诱导针对流感抗体的免疫应答的组合物和方法
公开(公告)号：US20110300168A1
公开(公告)日：2011-12-08
申请号：US13099514
申请日：2011-05-03
申请人： Jonathan Schneck , Mathias Oelke
发明人： Jonathan Schneck , Mathias Oelke
IPC分类号： A61K39/135 , A61P31/16
CPC分类号： A61K39/145 , A61K39/12 , A61K2039/55 , C12N2760/16134
摘要： This disclosure provides compositions and methods for inducing an immune response against influenza antigens, for example in elderly populations, as well as a sensitive artificial antigen presenting cell (aAPC) stimulation assay that can be used for expansion and analysis of multiple antigen specific T cell populations simultaneously.
摘要翻译：本公开提供了用于诱导针对流感抗原的免疫应答的组合物和方法，例如在老年人群中，以及敏感的人造抗原呈递细胞（aAPC）刺激测定法，其可用于扩增和分析多种抗原特异性T细胞群体同时。

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