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1. 发明申请

WO2006012641A3 METHODS FOR DETECTING AND TREATING AUTOIMMUNE DISORDERS 审中-公开
标题翻译：检测和治疗自身免疫性疾病的方法
公开(公告)号：WO2006012641A3
公开(公告)日：2007-12-13
申请号：PCT/US2005026915
申请日：2005-07-29
申请人： UNIV OREGON HEALTH & SCIENCE , US GOV VETERANS AFFAIRS , IMMUNE RESPONSE CORP INC , VANDENBARK ARTHUR A , OFFNER HALINA , BARTHOLOMEW RICHARD
发明人： VANDENBARK ARTHUR A , OFFNER HALINA , BARTHOLOMEW RICHARD
IPC分类号： A01N37/18 , A61K49/00
CPC分类号： A61K39/0008 , A61K2039/55566 , C07K14/7051 , G01N33/564 , A61K2300/00
摘要： The present disclosure relates to methods for inhibiting an autoimmune disease by administering to a subject a therapeutically effective amount of a composition that increases FOXP3 expression, thereby inhibiting the autoimmune disease. Further disclosed herein are methods for detecting in a subject an autoimmune disease or a predisposition to an autoimmune disease, and methods for assessing the efficacy of a therapy for an autoimmune disease.
摘要翻译：本公开涉及通过向受试者施用治疗有效量的增加FOXP3表达的组合物从而抑制自身免疫疾病来抑制自身免疫疾病的方法。本文进一步公开的是用于在受试者中检测自身免疫性疾病或自身免疫性疾病的倾向的方法，以及用于评估自身免疫性疾病治疗功效的方法。

2. 发明申请

WO2012056407A8 ANTIBODIES WHICH BIND SOLUBLE T-CELL RECEPTOR LIGANDS 审中-公开
标题翻译：抗体可溶性T细胞受体配体
公开(公告)号：WO2012056407A8
公开(公告)日：2012-07-12
申请号：PCT/IB2011054775
申请日：2011-10-26
申请人： TECHNION RES & DEV FOUNDATION , UNIV OREGON HEALTH & SCIENCE , US DEPT VETERANS AFFAIRS , REITER YORAM , DAHAN RONY , VANDENBARK ARTHUR A
发明人： REITER YORAM , DAHAN RONY , VANDENBARK ARTHUR A
IPC分类号： C07K16/28
CPC分类号： C07K16/2809 , C07K16/2833 , G01N33/564
摘要： Provided are isolated high affinity entities which comprise an antigen binding domain which specifically binds a soluble T-cell receptor ligand comprising a two- domain beta1-alpha1 of a major histocompatibility complex (MHC) class II, wherein said antigen binding domain does not bind a complex comprising a four-domain alpha1-beta1/alpha2-beta2 MHC class II. Also provided are methods and kits using same for detecting and sequestering soluble two-domain T cell receptor ligands in a sample.
摘要翻译：提供了分离的高亲和力实体，其包含特异性结合可溶性T细胞受体配体的抗原结合结构域，所述可溶性T细胞受体配体包含II类主要组织相容性复合体（MHC）的二结构域β1-α1，其中所述抗原结合结构域不结合复合物包含四结构域α1-β1/α2-β2MHC II类。还提供了使用其在样品中检测和螯合可溶性双结构域T细胞受体配体的方法和试剂盒。

3. 发明申请

WO2005044982A2 MONOMERIC RECOMBINANT MHC MOLECULES USEFUL FOR MANIPULATION OF ANTIGEN-SPECIFIC T CELLS 审中-公开
标题翻译：用于控制抗原特异性T细胞的单体重组MHC分子
公开(公告)号：WO2005044982A2
公开(公告)日：2005-05-19
申请号：PCT/US2004029096
申请日：2004-09-07
申请人： UNIV OREGON HEALTH & SCIENCE , BURROWS GREGORY G , VANDENBARK ARTHUR A
发明人： BURROWS GREGORY G , VANDENBARK ARTHUR A
IPC分类号： A61K38/16 , A61K39/00 , A61K39/395 , C07H21/04 , C07K14/74 , C12N20060101 , C12N5/08 , C12Q1/68 , C12N
CPC分类号： C07K14/705 , A61K39/0008 , C12N15/62 , C12N15/86
摘要： The present invention provides, in particular embodiments, for modified recombinant T cell receptor (TCR) ligands (RTLs) comprising a MHC class I or MHC class II component. The modified RTLs have redesigned surface features that preclude or reduce aggregation, wherein the modified molecules retain the ability to bind Ag-peptides, target antigen-specific T cells, inhibit T cell proliferation in an Ag-specific manner and have utility to treat, inter alia, autoimmune disease and other conditions mediated by antigen-specific T cells in vivo.
摘要翻译：本发明在特定实施方案中提供了包含MHC I类或II类MHC组分的修饰重组T细胞受体（TCR）配体（RTL）。修饰的RTL具有重新设计的排除或减少聚集的表面特征，其中修饰的分子保留结合Ag-肽，靶抗原特异性T细胞，以Ag特异性方式抑制T细胞增殖的能力，并且具有治疗，特别是自身免疫性疾病和其它由抗原特异性T细胞在体内介导的病症。

4. 发明申请

WO2006102170A2 RECOMBINANT MHC MOLECULES USEFUL FOR MANIPULATION OF ANTIGEN-SPECIFIC T CELLS 审中-公开
标题翻译：用于控制抗原特异性T细胞的重组MHC分子
公开(公告)号：WO2006102170A2
公开(公告)日：2006-09-28
申请号：PCT/US2006009884
申请日：2006-03-16
申请人： UNIV OREGON HEALTH SCIENCES , OFFNER HALINA , VANDENBARK ARTHUR A , BURROWS GREGORY G
发明人： OFFNER HALINA , VANDENBARK ARTHUR A , BURROWS GREGORY G
IPC分类号： C07K14/74
CPC分类号： A61K39/0008 , A61K38/00 , A61K47/6425 , A61K47/646 , C07K14/70539 , C07K2319/00
摘要： Two-domain MHC polypeptides are useful for modulating activities of antigen- specific T-cells, including for modulating pathogenic potential and effects of antigen- specific T-cells. Exemplary MHC class II-based recombinant T-cell ligands (RTLs) of the invention include covalently linked ßl and al domains, and MHC class I-based molecules that comprise covalently linked al and a2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, to modulate T-cell activity, including by regulatory switching of T-cell cytokine and adhesion molecule expression, to treat conditions mediated by antigen- specific T-cells, to treat or prevent autoimmune or neurodegenerative diseases, to protect axons, and to prevent or reverse demyelination.
摘要翻译：双域MHC多肽可用于调节抗原特异性T细胞的活性，包括调节致病潜力和抗原特异性T细胞的作用。本发明的示例性基于MHC II类的重组T细胞配体（RTL）包括共价连接的β1和α1结构域，以及包含共价连接的a1和a2结构域的基于MHC I类的分子。这些多肽还可以包括共价连接的抗原决定簇，毒性部分和/或可检测的标记。所公开的多肽可用于靶向抗原特异性T细胞，并且除其他外，可用于检测和纯化抗原特异性T细胞，诱导或激活T细胞以调节T细胞活性，包括通过T细胞细胞因子和粘附分子表达的调节转换来治疗由抗原特异性T细胞介导的病症，治疗或预防自身免疫或神经变性疾病，保护轴突，以及预防或逆转脱髓鞘。

5. 发明申请

WO2012103365A1 RECOMBINANT T CELL LIGANDS AND ANTIBODIES THAT BIND B CELLS FOR THE TREATMENT OF AUTOIMMUNE DISEASES 审中-公开
标题翻译：重组T细胞配体和结合B细胞治疗自身免疫疾病的抗体
公开(公告)号：WO2012103365A1
公开(公告)日：2012-08-02
申请号：PCT/US2012022770
申请日：2012-01-26
申请人： UNIV OREGON HEALTH & SCIENCE , US DEPT VETERANS AFFAIRS , HUAN JIANYA , VANDENBARK ARTHUR A
发明人： HUAN JIANYA , VANDENBARK ARTHUR A
IPC分类号： A61K38/17 , A61K39/00 , A61K39/395 , A61P37/02
CPC分类号： A61K39/0008 , A61K39/3955 , A61K45/06 , A61K2039/505 , A61K2039/605 , C07K16/2887 , A61K2300/00
摘要： Methods are disclosed for treating or inhibiting an autoimmune disease in a subject. In some embodiments, the disclosed methods include administering to the subject a therapeutically effective amount of one or more Major Histocompatibility Complex (MHC) molecules including covalently linked first, second and third domains; wherein the first domain is an MHC class II ß1 domain and the second domain is an MHC class H al domain, wherein the amino terminus of the al domain is covalently linked to the carboxy terminus of the ß1 domain; or wherein the first domain is an MHC class I al domain and the second domain is an MHC class I a2 domain, wherein the amino terminus of the a2 domain is covalently linked to the carboxy terminus of the al domain; and wherein the third domain is covalently linked to the first domain and comprises an antigen associated with the autoimmune disorder. The method also includes administering a therapeutically effective amount of one or more antibodies that bind to B cells, for example an antibody that specifically binds CD20. In specific non-limiting examples, the autoimmune disease is multiple sclerosis or rheumatoid arthritis.
摘要翻译：公开了用于治疗或抑制受试者中的自身免疫疾病的方法。在一些实施方案中，公开的方法包括向受试者施用治疗有效量的一种或多种包括共价连接的第一，第二和第三结构域的主要组织相容性复合体（MHC）分子; 其中所述第一结构域是MHC II类β1结构域而所述第二结构域是MHCHalα结构域，其中所述α1结构域的氨基末端共价连接至所述β1结构域的羧基末端; 或其中所述第一结构域是MHC I类α1结构域并且所述第二结构域是MHC I类α2结构域，其中所述α2结构域的氨基末端共价连接至所述α1结构域的羧基末端; 并且其中所述第三结构域共价连接至所述第一结构域并且包含与所述自身免疫病症相关的抗原。该方法还包括施用治疗有效量的一种或多种结合B细胞的抗体，例如特异性结合CD20的抗体。在具体的非限制性实例中，自身免疫性疾病是多发性硬化症或类风湿性关节炎。

6. 发明申请

WO2006010020A3 T CELL HYBRIDOMAS 审中-公开
标题翻译： T细胞杂交瘤
公开(公告)号：WO2006010020A3
公开(公告)日：2007-03-01
申请号：PCT/US2005024320
申请日：2005-07-07
申请人： UNIV OREGON HEALTH & SCIENCE , CHOU YUAN K , VANDENBARK ARTHUR A , BURROWS GREGORY G
发明人： CHOU YUAN K , VANDENBARK ARTHUR A , BURROWS GREGORY G
IPC分类号： C12N5/00 , C12N5/0783
CPC分类号： C12N5/0636 , C12N5/16 , C12N2503/00
摘要： The present invention provides T cell hybridomas and related compositions and assay systems for investigative, diagnostic, and therapeutic use in modulating T cell receptor (TCR)-mediated immune response. The T cell hybridomas of the invention are typically constructed by fusing a naïve or early central memory T cell isolated from a mammalian subject with an immortalizing fusion partner (e.g. mammalian lymphoid tumor cell) to yield clonal T cell hybrids. The resulting T cell hybridomas exhibit antigen (Ag)-specific proliferation responsiveness over a background level of proliferation of the hybridomas. These hybridomas are useful for screening, identifying, and characterizing T cell immune modulatory agents, for example recombinant T cell receptor ligands (RTLs) and other agents that can modulate TCR-mediated T cell immune responses. Ag-specific proliferative response profiles exhibited by the T cell hybridomas of the invention show sufficient amplitude, sensitivity and fidelity to distinguish and/or quantify the presence and/or activity of a test RTL or other test modulatory agent in screening and sensitivity assays employing the hybridomas. These and other aspects of the invention yield powerful tools and methods for developing and characterizing novel RTLs and other immune modulatory agents for use in treating immune disorders, including a wide range of autoimmune diseases, in mammals.
摘要翻译：本发明提供用于调节，诊断和治疗用途的T细胞杂交瘤以及用于调节T细胞受体（TCR）介导的免疫应答的相关组合物和测定系统。本发明的T细胞杂交瘤通常通过将从哺乳动物受试者分离的初始或早期中央记忆T细胞与永生化融合配偶体（例如哺乳动物淋巴样肿瘤细胞）融合而构建，以产生克隆T细胞杂交体。所得的T细胞杂交瘤在杂交瘤的增殖的背景水平上表现出抗原（Ag）特异性增殖反应性。这些杂交瘤可用于筛选，鉴定和表征T细胞免疫调节剂，例如重组T细胞受体配体（RTL）和可调节TCR介导的T细胞免疫应答的其它试剂。本发明的T细胞杂交瘤显示的Ag特异性增殖反应谱在筛选和敏感性测定中显示足够的幅度，灵敏度和保真度以区分和/或定量测试RTL或其他测试调节剂的存在和/或活性杂交瘤。本发明的这些和其它方面产生用于开发和表征用于哺乳动物治疗免疫疾病（包括广泛的自身免疫性疾病）的新型RTL和其它免疫调节剂的有力工具和方法。

7. 发明申请

WO2013103816A8 PARTIAL MHC CONSTRUCTS AND METHODS OF USE 审中-公开
标题翻译：部分MHC结构及其使用方法
公开(公告)号：WO2013103816A8
公开(公告)日：2014-06-26
申请号：PCT/US2013020287
申请日：2013-01-04
申请人： UNIV OREGON HEALTH & SCIENCE , US DEPT VETERANS AFFAIRS
发明人： VANDENBARK ARTHUR A , BURROWS GREGORY G , MEZA-ROMERO ROBERTO , BENEDEK GIL , ANDREW SHAYNE , MOONEY JEFFERY
IPC分类号： A61K39/00 , C07K14/74
CPC分类号： C07K14/705 , A61K39/0008 , A61K2039/605 , C07K14/70539 , C07K2319/74 , C12Q1/6881 , G01N33/56977 , G01N2333/70596 , G01N2500/04 , G01N2500/10
摘要： Disclosed herein are isolated major histocompatibility complex (MHC) class II al domain polypeptides and methods of use. In some embodiments, the isolated polypeptide comprises or consists of an MHC class H al domain polypeptide (or portion thereof) and does not include an MHC class II α2, &bgr;1, or &bgr;2 domain. The disclosed MHC class H al domain polypeptides are of use in treating or inhibiting disorders in a subject, such as inflammatory and/or autoimmune disorders. Also disclosed are methods of evaluating efficacy of treatment or optimizing treatment of a subject with a polypeptide including an MHC class II al domain polypeptide (or portion thereof) or a polypeptide including an MHC class II al domain and &bgr;1 domain (such as a &bgr;1α1 RTL).
摘要翻译：本文公开了分离的主要组织相容性复合体（MHC）II类域多肽和使用方法。在一些实施方案中，分离的多肽包含或由MHC类H区域多肽（或其部分）组成，并且不包括MHC II类α2，bgr1，或bgr2结构域。所公开的MHC类H领域多肽可用于治疗或抑制受试者中的疾病，例如炎性和/或自身免疫性疾病。还公开了评估治疗或优化用包含MHC II类域多肽（或其部分）或包含MHC II类结构域和第1结构域的多肽的多肽治疗受试者的功效的方法（例如＆bgr;1α1RTL）。

8. 发明申请

WO2006023598A2 PROSTATE-SPECIFIC ANTIGEN-DERIVED MHC CLASS II-RESTRICTED PEPTIDES AND THEIR USE IN VACCINES TO TREAT OR PREVENT PROSTATE CANCER 审中-公开
标题翻译：前列腺特异性抗原衍生的MHC II类限制性肽及其在疫苗中的用途，以治疗或预防前列腺癌
公开(公告)号：WO2006023598A2
公开(公告)日：2006-03-02
申请号：PCT/US2005029320
申请日：2005-08-19
申请人： UNIV MARYLAND , ALEXANDER RICHARD B , KLYUSHEENKOYA ELENA N , VANDENBARK ARTHUR A , LINK JASON
发明人： ALEXANDER RICHARD B , KLYUSHEENKOYA ELENA N , VANDENBARK ARTHUR A , LINK JASON
CPC分类号： A61K39/0011 , A61K38/00 , A61K45/06 , A61K2039/5154 , A61K2039/5158 , A61K2039/53 , A61K2039/55566 , C12N9/6445
摘要： The present invention relates to immunogenic peptides derived from human prostate cancer antigen (PSA-derived peptides) and their use as vaccines to treat or prevent prostate cancer. The invention is also related to dendritic cells from a patient having prostate cancer, which dendritic cells have been exposed to one or more PSA-derived peptides, and their use to treat or prevent prostate cancer in the patient. The invention is also directed to T-cells from a patient which cells are specific for PSA-activated peptide(s), and their uses to treat or prevent prostate cancer.
摘要翻译：本发明涉及源自人前列腺癌抗原（PSA衍生肽）的免疫原性肽及其作为治疗或预防前列腺癌的疫苗的用途。本发明还涉及来自患有前列腺癌的患者的树突状细胞，该树突状细胞暴露于一种或多种PSA衍生的肽，以及它们在患者体内治疗或预防前列腺癌的用途。本发明还涉及来自患者的T细胞，其中细胞对PSA活化肽是特异性的，以及它们用于治疗或预防前列腺癌的用途。

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