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1.发明授权Treatment of retinal disorders with recombinant T cell receptor ligand (RTL) 有权用重组T细胞受体配体（RTL）治疗视网膜疾病公开(公告)号：US09260506B2
公开(公告)日：2016-02-16
申请号：US13441719
申请日：2012-04-06
CPC分类号： C07K14/70539 , A61K38/1774 , A61K39/0005 , A61K39/0008 , A61K2039/605 , C07K2319/00 , C07K2319/32
摘要： Methods are provided for the treatment of a retinal disorder or optic neuritis in a subject. In some embodiments, the methods include administering a therapeutically effective amount of an MHC molecule including covalently linked first, second, and third domains; wherein the first domain is an MHC class II β1 domain and the second domain is an MHC class II α1 domain, wherein the amino terminus of the α1 domain is covalently linked to the carboxy terminus of the β1 domain; or wherein the first domain is an MHC class I α1 domain and the second domain is an MHC class I α2 domain, wherein the amino terminus of the α2 domain is covalently linked to the carboxy terminus of the α1 domain; and wherein the third domain is covalently linked to the first domain and comprises a retinal antigen or an antigen of the central or peripheral nervous system.
摘要翻译： 提供了用于治疗受试者的视网膜病症或视神经炎的方法。 在一些实施方案中，所述方法包括施用治疗有效量的MHC分子，包括共价连接的第一，第二和第三结构域; 其中第一结构域是MHC类II和bgr1结构域，第二结构域是MHC II类α1结构域，其中α1结构域的氨基末端共价连接到第1结构域的羧基末端; 或其中第一结构域是MHC I型α1结构域，第二结构域是MHC I类α2结构域，其中α2结构域的氨基末端与α1结构域的羧基末端共价连接; 并且其中所述第三结构域共价连接到所述第一结构域并且包含视网膜抗原或中枢神经系统或外周神经系统的抗原。
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公开(公告)号：US08685404B2
公开(公告)日：2014-04-01
申请号：US13361720
申请日：2012-01-30
IPC分类号： A61K39/00 , A61K39/385 , A61K38/16
CPC分类号： A61K39/0007 , A61B5/1124 , A61B5/165 , A61B5/168 , A61B5/4803 , A61K39/0013 , A61K45/06 , A61K2039/605 , C07K14/705 , C07K14/70539 , A61K2300/00
摘要： Methods are provided for the treatment of subjects with cognitive or neuropsychiatric impairment induced by substance addiction and for increasing cognitive function in a subject with substance addiction. In some embodiments, the methods include administering to the subject a therapeutically effective amount of a major histocompatibility complex (MHC) molecule including covalently linked first, second, and third domains; wherein the first domain is an MHC class II β1 domain and the second domain is an MHC class II α1 domain; or wherein the first domain is an MHC class I α1 domain and the second domain is an MHC class I α2 domain; and wherein the third domain is covalently linked to the first domain and comprises an antigen of the central or peripheral nervous system.
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公开(公告)号：US08053197B2
公开(公告)日：2011-11-08
申请号：US11658834
申请日：2005-07-29
IPC分类号： G01N33/53
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。
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4.发明授权T-cell antigens, and their use in diagnosis and treatment of T-cell mediated conditions 失效T细胞抗原及其在诊断和治疗T细胞介导的病症中的应用公开(公告)号：US06566082B1
公开(公告)日：2003-05-20
申请号：US08469633
申请日：1995-06-06
IPC分类号： G01N3353
CPC分类号： A61K49/0058 , A61K38/00 , A61K47/6849 , A61K51/1039 , C07K14/70578 , C07K16/2878 , C07K2319/00 , Y10S530/866 , Y10S530/867 , Y10S530/868
摘要： The OX-40 antigen is characterized and claimed together with variants and derivatives thereof. Also described are binding agents for the antigen and the use of these in diagnosis and therapy. Examples of such use include a method for the selective depletion of activated CD4+ T-cells in vivo by using immunotoxins comprising an OX-40 antibody conjugated to a toxic molecule (such as Ricin-A chain). The administration of these specific immunotoxins is used therapeutically to deplete autoimmune reactive CD4+ T-cells which have been implicated in diseases including Multiple Sclerosis, Rheumatoid Arthritis, Sarcoidosis, and Autoimmune Uveitis as well as inflammatory bowel disease and graft-versus-host disease. This type of therapy is also beneficial for eradicating CD4+ T-cell lymphomas and alloreactive CD4+ T-cells involved with a transplantation reaction. The use of the human form of the OX-40 antibody will also help in the early diagnosis of all the diseases mentioned above.
摘要翻译： OX-40抗原与其变体和衍生物一起被表征和要求。 还描述了用于抗原的结合剂和它们在诊断和治疗中的用途。 这种用途的实例包括通过使用包含与毒性分子缀合的OX-40抗体（例如蓖麻毒素A链）的免疫毒素在体内选择性消耗活化的CD4 + T细胞的方法。 这些特异性免疫毒素的施用在治疗上用于消除已涉及包括多发性硬化症，类风湿关节炎，结节病和自身免疫性葡萄膜炎以及炎性肠病和移植物抗宿主病在内的疾病的自身免疫反应性CD4 + T细胞。 这种治疗方法也有利于根除与移植反应相关的CD4 + T细胞淋巴瘤和同种异体反应性CD4 + T细胞。 OX-40抗体的人体形态的使用也有助于早期诊断上述所有疾病。
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5.发明授权Monomeric recombinant MHC molecules useful for manipulation of antigen-specific T cells 有权用于治疗抗原特异性T细胞的单体重组MHC分子公开(公告)号：US08377447B2
公开(公告)日：2013-02-19
申请号：US10936467
申请日：2004-09-07
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。
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6.发明申请T Cell Hybridomas And Related Compositions And Methods For Assaying And Modulating T Cell Receptor-Mediated Immune Responses 审中-公开T细胞杂交瘤和相关组合物和测定和调节T细胞受体介导的免疫应答的方法公开(公告)号：US20100279401A1
公开(公告)日：2010-11-04
申请号：US12527004
申请日：2005-07-07
IPC分类号： C12N5/16
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： 本发明提供了用于调节，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。
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公开(公告)号：US07462486B2
公开(公告)日：2008-12-09
申请号：US10438729
申请日：2003-05-14
申请人： Arthur A. Vandenbark
发明人： Arthur A. Vandenbark
IPC分类号： C12N5/00 , C12N5/02 , A61K38/00 , C07K2/00 , C07K4/00 , C07K5/00 , C07K7/00 , C07K14/00 , C07K16/00 , C07K17/00
CPC分类号： C12Q1/6809 , C12Q1/6883 , C12Q2600/106 , C12Q2600/136 , C12Q2600/158
摘要： A method is disclosed to identify a T cell receptor (TCR) variable (V) peptide of use as a therapeutic agent in a subject. A method is also disclosed for monitoring the efficacy of a T Cell Receptor (TCR) V peptide for the treatment of a subject. In another embodiment, a method is disclosed for selecting a TCR V peptide of use in therapy for a subject having an autoimmune disease.
摘要翻译： 公开了一种用于鉴定受试者中用作治疗剂的T细胞受体（TCR）可变（V）肽的方法。 还公开了一种用于监测T细胞受体（TCR）V肽用于治疗受试者的功效的方法。 在另一个实施方案中，公开了一种用于选择用于具有自身免疫疾病的受试者的治疗中的TCR V肽的方法。
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公开(公告)号：US20170369577A1
公开(公告)日：2017-12-28
申请号：US15629573
申请日：2017-06-21
IPC分类号： C07K16/28
CPC分类号： C07K16/2833 , C07K14/70539 , C07K2319/40
摘要： Disclosed are recombinant CD74 polypeptides mutated relative to the naturally occurring CD74 polypeptides with improved properties such as binding of CD74 ligands such as MIF and RTL1000 as well as polynucleotides that encode the polypeptides, expression vectors comprising the polynucleotides, bacteria that include the expression vectors, and methods of making the recombinant polypeptides.
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9.发明申请MONOMERIC RECOMBINANT MHC MOLECULES USEFUL FOR MANIPULATION OF ANTIGEN-SPECIFIC T-CELLS 有权用于控制特异性T细胞的单体重组MHC分子公开(公告)号：US20130190221A1
公开(公告)日：2013-07-25
申请号：US13731711
申请日：2012-12-31
IPC分类号： C07K14/705
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。
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10.发明授权Method for direct electrical detection of molecules and molecule-molecule interactions 失效直接电子检测分子和分子 - 分子相互作用的方法公开(公告)号：US07732140B2
公开(公告)日：2010-06-08
申请号：US11679126
申请日：2007-02-26
CPC分类号： G01N27/3276
摘要： A method for direct electrical detection of proteins, peptides and the like, and their interactions includes an electrode arrangement, a current/voltage provider, and a circuit analyzer. The electrode arrangement has an interdigitated electrode pair including a first electrode and a second electrode. Coupled to the electrode arrangement is a signal generator adapted to provide a signal (e.g., an alternating current or voltage) having a selected range of frequencies. The analyzer is coupled to the electrode arrangement and is operative to analyze an electrical parameter of the circuit as the signal is applied. An analytic method includes measuring changes in one or more parameters of the circuit over the range of frequencies. By such measurement, the device can determine whether a target moiety has been bound by a probe attached to the electrode(s). The device can also specifically identify the intermolecular system detected, i.e., by “fingerprinting” the electrical response of each molecule or intermolecular complex.
摘要翻译： 用于蛋白质，肽等的直接电检测及其相互作用的方法包括电极装置，电流/电压提供器和电路分析器。 电极布置具有包括第一电极和第二电极的交错电极对。 耦合到电极布置的信号发生器适于提供具有选定频率范围的信号（例如，交流电或电压）。 分析器耦合到电极装置，并且用于在施加信号时分析电路的电参数。 分析方法包括在频率范围内测量电路的一个或多个参数的变化。 通过这样的测量，该装置可以确定目标部分是否已被连接到电极的探针结合。 该装置还可以特异性地识别所检测的分子间系统，即通过“指纹”每个分子或分子间复合物的电响应。
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