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    Cell free T cell antigen receptor beta chain and its clinical utilities
    1.
    发明授权
    Cell free T cell antigen receptor beta chain and its clinical utilities 失效
    无细胞T细胞抗原受体β链及其临床应用

    公开(公告)号：US5436319A

    公开(公告)日：1995-07-25

    申请号：US312167

    申请日：1994-09-26

    申请人： Patrick C. Kung ,  Stephen H. Ip ,  Michael C. Brown

    发明人： Patrick C. Kung ,  Stephen H. Ip ,  Michael C. Brown

    IPC分类号： A61K38/17 ,  A61K39/00 ,  C07K14/725 ,  C07K16/28

    CPC分类号： C07K16/2809 ,  C07K14/7051 ,  G01N33/56972 ,  A61K38/00 ,  A61K39/00 ,  G01N2333/7051 ,  Y10S530/83

    摘要： Cell-free or released T cell antigen receptors, immunoassays which allow the detection of the released T cell antigen receptor in cell culture supernatants, cell lysates, and biological fluids, as well as diagnostic and therapeutic compositions and methods for monitoring and treating certain diseases or disorders which elicit or involve a T cell response are described. The released T cell antigen receptors described herein differ from the cell membrane bound antigen receptors and appear to exist in a variety of forms, some of which may be complexed with other T cell determinants such as the T3 antigen. Despite the size heterogeneity of the released T cell antigen receptors or receptor/complexes, these may be reliably identified using anti-receptor antibodies, including, but not limited to, anti-major framework, anti-minor frarmework and anti-clonotypic antibodies which define particular epitopes of the released T cell receptor or receptor/complex. The immunoassays described herein may be used to test for the presence of the released receptor or receptor/complex in biological samples and may be used to diagnose or monitor patients with disorders or diseases that elicit or involve T cell response who exhibit elevated serum level of the receptor or receptor/complex. In addition, the cell free T cell antigen receptors themselves may be used diagnostically and/or therapeutically for diseases or conditions that are not easily addressed using immunoglobulins.

    摘要翻译： 无细胞或释放的T细胞抗原受体，允许检测细胞培养物上清液，细胞裂解物和生物流体中释放的T细胞抗原受体的免疫测定，以及用于监测和治疗某些疾病的诊断和治疗组合物和方法， 描述引起或涉及T细胞应答的病症。 本文所述释放的T细胞抗原受体不同于细胞膜结合的抗原受体，并且似乎以多种形式存在，其中一些可与其它T细胞决定簇如T3抗原复合。 尽管释放的T细胞抗原受体或受体/复合物的大小异质性，但可以使用抗受体抗体可靠地鉴定这些抗体，所述抗受体抗体包括但不限于抗主要框架，抗小细胞体系和抗克隆型抗体 释放的T细胞受体或受体/复合物的特异性表位。 本文描述的免疫测定可用于测试生物样品中释放的受体或受体/复合物的存在，并且可用于诊断或监测引起或涉及T细胞应答的患者，所述疾病或疾病表现出升高的血清水平 受体或受体/复合物。 此外，无细胞的T细胞抗原受体本身可以在诊断和/或治疗上用于使用免疫球蛋白不容易解决的疾病或病症。

    Therapeutic and diagnostic methods using soluble T cell surface molecules
    3.
    发明授权
    Therapeutic and diagnostic methods using soluble T cell surface molecules 失效
    使用可溶性T细胞表面分子的治疗和诊断方法

    公开(公告)号：US5292636A

    公开(公告)日：1994-03-08

    申请号：US434398

    申请日：1989-11-09

    申请人： Patrick C. Kung ,  Stephen H. Ip ,  Michael C. Brown ,  Linda A. MacKeen

    发明人： Patrick C. Kung ,  Stephen H. Ip ,  Michael C. Brown ,  Linda A. MacKeen

    IPC分类号： C07K16/28 ,  G01N33/564 ,  G01N33/566 ,  G01N33/569 ,  G01N33/571 ,  G01N33/574 ,  G01N33/68 ,  G01N33/543 ,  G01N33/577

    CPC分类号： C07K16/2812 ,  C07K16/2815 ,  G01N33/564 ,  G01N33/566 ,  G01N33/56972 ,  G01N33/56977 ,  G01N33/56983 ,  G01N33/56988 ,  G01N33/571 ,  G01N33/57407 ,  G01N33/57423 ,  G01N33/57488 ,  G01N33/6869 ,  G01N33/6893 ,  G01N2333/71 ,  G01N2333/715 ,  G01N2800/102 ,  G01N2800/245 ,  Y10S435/974 ,  Y10S435/975 ,  Y10S436/811 ,  Y10S436/813

    摘要： The present invention is directed to the measurement of soluble T cell growth factor receptors, soluble T cell differentiation antigens, or related soluble molecules or fragments thereof, and the use of such measurements in the diagnosis, staging, and therapy of diseases and disorders. Specific embodiments involve the diagnosis and monitoring of therapy using absolute values of such soluble molecules. Further embodiments involve detecting a change in the levels of such soluble molecules, in the diagnosis and therapy of diseases and disorders. In specific embodiments, measurements of interleukin-2 receptor levels can be made to detect lung cancer, or to stage squamous cell lung carcinoma. In other embodiments, detection of increases in both soluble IL2R and creatinine in the body fluid of a transplant patient can be used to differentially diagnose renal allograft rejection from infection. The invention is also directed to methods for measurement of soluble CD4 antigens, which measurements can be used, in a specific embodiment, to diagnose a state of immune activation, to diagnose rheumatoid arthritis, to monitor therapeutic efficacy (e.g. of AIDS treatments), or to stage adult T cell leukemia in a patient. In another aspect, the invention relates to the detection, staging, and monitoring of therapy of diseases and disorders by measuring a plurality of soluble T cell markers.

    摘要翻译： 本发明涉及可溶性T细胞生长因子受体，可溶性T细胞分化抗原或相关的可溶性分子或其片段的测量，以及在疾病和病症的诊断，分期和治疗中使用这些测量。 具体实施方案涉及使用这种可溶性分子的绝对值来诊断和监测治疗。 进一步的实施方案涉及在疾病和病症的诊断和治疗中检测这些可溶性分子的水平的变化。 在具体实施方案中，可以测量白细胞介素-2受体水平以检测肺癌或鳞状细胞肺癌。 在其它实施方案中，检测移植患者的体液中可溶性IL2R和肌酐的增加可用于差异性诊断感染的肾同种异体移植排斥反应。 本发明还涉及用于测量可溶性CD4抗原的方法，在具体实施方案中可以使用测量来诊断免疫激活的状态，诊断类风湿性关节炎，以监测治疗功效（例如AIDS治疗）或 在患者中分期成年T细胞白血病。 另一方面，本发明涉及通过测量多种可溶性T细胞标记来检测，分期和监测疾病和病症的治疗。

    Monoclonal antibodies reactive with defined regions of the T cell antigen receptor
    7.
    发明授权
    Monoclonal antibodies reactive with defined regions of the T cell antigen receptor 失效
    与T细胞抗原受体的限定区域反应的单克隆抗体

    公开(公告)号：US06171799B2

    公开(公告)日：2001-01-09

    申请号：US08450275

    申请日：1995-05-25

    申请人： Robert V. Skibbens ,  Larry D. Henry ,  Charles W. Rittershaus ,  Wei-Tao Tian ,  Stephen H. Ip ,  Patrick C. Kung ,  Mary Ellen Snider ,  Jone-Long Ko ,  Nancy L. Wood

    发明人： Robert V. Skibbens ,  Larry D. Henry ,  Charles W. Rittershaus ,  Wei-Tao Tian ,  Stephen H. Ip ,  Patrick C. Kung ,  Mary Ellen Snider ,  Jone-Long Ko ,  Nancy L. Wood

    IPC分类号： G01N3353

    CPC分类号： C07K16/2809 ,  A61K38/00 ,  A61K2039/505 ,  C07K2317/74 ,  Y10S436/804 ,  Y10S436/811

    摘要： The present invention relates to monoclonal antibodies which recognize defined regions of the T-cell receptor (TCR). In a specific embodiment, the invention provides monoclonal antibodies which are reactive with a constant region of the alpha chain of the TCR. In particular embodiments, the invention relates to two monoclonal antibodies, termed &agr;F1 and &agr;F2, which react with two different epitopes on the framework region of the &agr; monomer of the TCR molecule. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the beta chain of the TCR. In particular, the invention provides two monoclonal antibodies, termed W112 and 2D1, which react with &bgr; chain variable regions V&bgr;5.3 and V&bgr;8.1, respectively. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the delta chain of the TCR. In particular, the invention provides monoclonal antibody &dgr;TCS1, isotype IgG2a. The monoclonal antibodies of the invention have value in diagnosis and therapy and are useful tools for study of the immune system.

    摘要翻译： 本发明涉及识别T细胞受体（TCR）的限定区域的单克隆抗体。 在具体实施方案中，本发明提供了与TCR的α链的恒定区反应的单克隆抗体。 在具体实施方案中，本发明涉及称为αF1和αF2的两种单克隆抗体，其与TCR分子的α单体的框架区上的两个不同表位反应。 在另一个具体实施方案中，本发明涉及与TCR的β链的可变区反应的单克隆抗体。 特别地，本发明提供两种分别与β链可变区Vbeta5.3和Vbeta8.1反应的单克隆抗体，称为W112和2D1。 在另一个具体实施方案中，本发明涉及与TCR的δ链的可变区反应的单克隆抗体。 特别地，本发明提供单克隆抗体deltaTCS1，同种型IgG2a。 本发明的单克隆抗体在诊断和治疗中具有价值，并且是免疫系统研究的有用工具。

    Monoclonal antibodies reactive with an epitope of a V.beta.3.1 variable region of a T cell receptor
    9.
    发明授权
    Monoclonal antibodies reactive with an epitope of a V.beta.3.1 variable region of a T cell receptor 失效
    与T细胞受体的Vβ1A可变区的表位反应的单克隆抗体

    公开(公告)号：US5766947A

    公开(公告)日：1998-06-16

    申请号：US938906

    申请日：1992-08-31

    申请人： Charles W. Rittershaus ,  Patrick C. Kung ,  Nancy Jones

    发明人： Charles W. Rittershaus ,  Patrick C. Kung ,  Nancy Jones

    IPC分类号： G01N33/564 ,  A61K35/12 ,  A61K38/00 ,  A61K39/00 ,  A61K39/395 ,  A61K51/00 ,  A61P29/00 ,  A61P37/00 ,  C07K16/28 ,  C12N5/20 ,  C12N15/02 ,  C12N15/09 ,  C12P21/08 ,  C12R1/91 ,  G01N33/577 ,  C07K16/46 ,  C12N5/12

    CPC分类号： C07K16/2809 ,  A61K2039/505 ,  A61K38/00 ,  Y10S514/825 ,  Y10S530/809

    摘要： The invention is directed to monoclonal antibodies reactive with a member of the V.beta.3 family variable region of the beta chain of the TCR. More particularly, the invention provides for detection of the V.beta.3.1 subfamily. In a specific embodiment the invention provides for detection of V.beta.3.1, without cross-reacting with other V.beta.3 family variable regions. In a specific embodiment, the monoclonal antibodies of the invention do not react with V.beta.3.2. In particular, the invention provides monoclonal antibodies, termed 5E4 and 8F10, which react with the variable region of a member of the V.beta.3 family. In various embodiments of the invention, these antibodies, or fragments or derivatives thereof, can be used to bind with a member of the V.beta.3 family TCR variable region amino acid sequences, either as part of an intact TCR or peptide, or T cell-surface molecule, or a fragment thereof. The monoclonal antibodies are useful for diagnosis and therapy of autoimmune disease, in particular rheumatoid arthritis.

    摘要翻译： 本发明涉及与TCR的β链的Vβ3家族可变区的成员反应的单克隆抗体。 更具体地，本发明提供了Vβ3.1亚家族的检测。 在具体实施方案中，本发明提供了Vβ3.1的检测，而不与其他Vβ3家族可变区交叉反应。 在具体实施方案中，本发明的单克隆抗体不与Vβ2.2反应。 特别地，本发明提供了称为5E4和8F10的单克隆抗体，其与Vβ3家族的成员的可变区发生反应。 在本发明的各种实施方案中，这些抗体或其片段或衍生物可用于与Vβ3家族TCR可变区氨基酸序列的成员结合，作为完整TCR或肽或T细胞的一部分 表面分子或其片段。 单克隆抗体可用于诊断和治疗自身免疫性疾病，特别是类风湿性关节炎。

    Hybrid cell line for producing monoclonal antibody to a human monocyte antigen, antibody, and methods
    10.
    发明授权
    Hybrid cell line for producing monoclonal antibody to a human monocyte antigen, antibody, and methods 失效
    用于产生人单核细胞抗原的单克隆抗体的杂交细胞系，抗体和方法

    公开(公告)号：US5196310A

    公开(公告)日：1993-03-23

    申请号：US389246

    申请日：1989-08-03

    申请人： Patrick C. Kung ,  Gideon Goldstein

    发明人： Patrick C. Kung ,  Gideon Goldstein

    IPC分类号： A61K38/00 ,  C07K16/28

    CPC分类号： C07K16/28 ,  A61K38/00

    摘要： Hybrid cell line for production of monoclonal antibody to an antigen found on normal human monocytes and granulocytes. The hybrid is formed by fusing splenocytes from immunized BALB/cJ mice with P3X63Ag8U1 myeloma cells. Diagnostic and therapeutic uses of the monoclonal antibody are also disclosed.

    摘要翻译： 用于在正常人单核细胞和粒细胞上发现的抗原的单克隆抗体的杂交细胞系。 通过将来自免疫的BALB / cJ小鼠的脾细胞与P3X63Ag8U1骨髓瘤细胞融合来形成杂交体。 还公开了单克隆抗体的诊断和治疗用途。