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公开(公告)号：US09409976B2
公开(公告)日：2016-08-09
申请号：US13763398
申请日：2013-02-08
CPC分类号： C07K16/18 , C07K16/28 , C07K16/3061 , C07K2317/33 , C07K2317/734 , C07K2317/92
摘要： The present disclosure relates to Cell Death Inducing Molecule (“CDIM”) binding proteins and pharmaceutical compositions thereof. Particularly, the disclosure provides CDIM binding proteins that are useful in the selective depleting and killing of B cells, including neoplastic B cells as well as neoplastic cells that are not of B-cell origin that express CDIM-like antigens. In addition, the disclosure encompasses polynucleotides encoding the disclosed antigen binding proteins, and expression systems for producing the same. Further the present disclosure encompasses methods of treating patients with B cell proliferative- and mediated diseases by administering the CDIM binding proteins as well as diagnostic assays for identifying proteins that bind to CDIM. The disclosure further contemplates diagnostic assays for identifying patient populations that can be treated with the CDIM binding proteins.
摘要翻译： 本公开涉及细胞死亡诱导分子（“CDIM”）结合蛋白及其药物组合物。 特别地，本公开提供了可用于选择性消耗和杀死B细胞的CDIM结合蛋白，所述B细胞包括肿瘤性B细胞以及不具有表达CDIM样抗原的B细胞来源的肿瘤细胞。 此外，本公开包括编码所公开的抗原结合蛋白的多核苷酸，以及用于制备其的表达系统。 此外，本公开包括通过施用CDIM结合蛋白来治疗患有B细胞增殖和介导的疾病的患者的方法以及用于鉴定结合CDIM的蛋白质的诊断测定法。 本公开进一步考虑用于鉴定可用CDIM结合蛋白治疗的患者群体的诊断测定。
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公开(公告)号：US20140044739A1
公开(公告)日：2014-02-13
申请号：US13763398
申请日：2013-02-08
IPC分类号： C07K16/18
CPC分类号： C07K16/18 , C07K16/28 , C07K16/3061 , C07K2317/33 , C07K2317/734 , C07K2317/92
摘要： The present disclosure relates to Cell Death Inducing Molecule (“CDIM”) binding proteins and pharmaceutical compositions thereof. Particularly, the disclosure provides CDIM binding proteins that are useful in the selective depleting and killing of B cells, including neoplastic B cells as well as neoplastic cells that are not of B-cell origin that express CDIM-like antigens. In addition, the disclosure encompasses polynucleotides encoding the disclosed antigen binding proteins, and expression systems for producing the same. Further the present disclosure encompasses methods of treating patients with B cell proliferative- and mediated diseases by administering the CDIM binding proteins as well as diagnostic assays for identifying proteins that bind to CDIM. The disclosure further contemplates diagnostic assays for identifying patient populations that can be treated with the CDIM binding proteins.
摘要翻译： 本公开涉及细胞死亡诱导分子（“CDIM”）结合蛋白及其药物组合物。 特别地，本公开提供了可用于选择性消耗和杀死B细胞的CDIM结合蛋白，所述B细胞包括肿瘤性B细胞以及不具有表达CDIM样抗原的B细胞来源的肿瘤细胞。 此外，本公开包括编码所公开的抗原结合蛋白的多核苷酸，以及用于制备其的表达系统。 此外，本公开包括通过施用CDIM结合蛋白来治疗患有B细胞增殖和介导的疾病的患者的方法以及用于鉴定结合CDIM的蛋白质的诊断测定法。 本公开进一步考虑用于鉴定可用CDIM结合蛋白治疗的患者群体的诊断测定。
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3.发明授权Triple gradient process for recovering nucleated fetal cells from maternal blood 失效从母体血液中回收有核胎儿细胞的三重梯度过程
公开(公告)号：US5275933A
公开(公告)日：1994-01-04
申请号：US951628
申请日：1992-09-25
CPC分类号： G01N33/5002 , Y10S436/811
摘要： Nucleated fetal cells such as nucleated fetal red blood cells are separated from maternal blood with a discontinuous triple gradient gel and centrifugation. Nucleated fetal red blood cells are collected at an interface between a gel layer having a density in the range of from 1.105 to 1.110 g/mL and the second layer having a density in the range of from 1.075 to 1.085 g/mL, and maternal granulocytes are collected at an interface between a gel layer having a density in the range of from 1.115 to 1.125 g/mL and a layer having a density in the range of from 1.105 to 1.110 g/mL. This allows separation of fetal cells for testing from the maternal blood rather than the placenta or amniotic fluid, reducing the risk of sample collection and facilitating routine testing of fetal cells for evidence of genetic defects.
摘要翻译： 通过不连续的三重梯度凝胶和离心将成核的胎儿细胞如成核胎儿红细胞与母体血液分离。 在密度为1.105至1.110μg/ mL的凝胶层和密度为1.075至1.085g / mL的第二层和母体粒细胞之间的界面收集成核胎儿红细胞 在密度在1.115至1.125g / mL范围内的凝胶层和密度在1.105至1.110g / mL范围内的界面处收集。 这允许分离胎儿细胞用于测试与母体血液而不是胎盘或羊水，降低样品收集的风险，并促进胎儿细胞的常规检测以证明遗传缺陷。
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公开(公告)号：US08377435B2
公开(公告)日：2013-02-19
申请号：US11267935
申请日：2005-11-04
IPC分类号： A61K39/395 , A61K39/00 , C07K16/00 , C12P21/08
CPC分类号： C07K16/2896 , A61K31/475 , A61K31/704 , A61K38/50 , A61K39/3955 , A61K39/39558 , A61K2039/505 , C07K16/28 , C07K2317/21
摘要： Compositions and methods for inducing cell membrane wounding, cell permeabilization and cell killing are provided. The composition comprises a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell. Preferably, the cell surface antigen is associated with the cytoskeleton of the cell. A preferred polyvalent agent is an IgM, and enhanced cell wounding and killing can be provided by the addition of a crosslinking agent. At sublethal concentrations in vivo, the cell wounding antibodies permeabilize cells and dramatically enhance response to chemotherapeutic agents, even in patients refractory to the chemotherapeutic agents.
摘要翻译： 提供诱导细胞膜损伤，细胞透化和细胞杀伤的组合物和方法。 该组合物包含与存在于细胞表面上的高度表达的细胞表面抗原结合的多价试剂。 优选地，细胞表面抗原与细胞的细胞骨架相关联。 优选的多价试剂是IgM，并且可以通过加入交联剂来提供增强的细胞伤口和杀伤。 在体内亚致死浓度下，细胞损伤抗体透化细胞，并显着增强对化学治疗剂的反应，即使在化疗药物难治的患者中也是如此。
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5.发明授权Method of killing B-cells in a complement independent and an ADCC independent manner using antibodies which specifically bind CDIM 失效使用特异性结合CDIM的抗体以补体独立和ADCC独立的方式杀死B细胞的方法
公开(公告)号：US5417972A
公开(公告)日：1995-05-23
申请号：US101436
申请日：1993-08-02
IPC分类号： A61K38/00 , C07K16/28 , C07K16/30 , A61K39/395
CPC分类号： C07K16/3061 , C07K16/28 , A61K38/00 , C07K2317/73
摘要： Methods are provided for inducing cell death in B-cells, including neoplastic B-cells, by employing reagents that bind to a B-cell epitope. Particularly, antibodies specific for the marker can be administered to a host to induce death in B-cells to which the antibodies bind or can be used in ex vivo clinical situations to selectively remove B-cells. A B-cell specific oligosaccharide epitope useful as a B-cell marker has been identified. The ligand being recognized on B lymphocytes has no apparent similarities to any of the known pan-B cells markers. In addition, proteins which specifically bind the disclosed epitope are provided. Human monoclonal antibody 216, which recognizes this B-cell epitope, is cytotoxic to B-cells and binds all CD19.sup.+ and CD20.sup.+ B lymphocytes in human peripheral blood and spleen. Furthermore, MAb 216 does not distinguish B cells by the isotype expressed, binding IgG.sup.+ and IgM.sup.+ cells with equal intensity, and also bind all B cells regardless of their CD5 expression. Methods to inhibit neoplastic B-cell growth by administering a B-cell-cytotoxic protein are presented. These products and methods find use in diagnosis and therapy.
摘要翻译： 提供了通过使用与B细胞表位结合的试剂来诱导B细胞（包括肿瘤性B细胞）中的细胞死亡的方法。 特别地，可以向宿主施用对标记物特异性的抗体，以在抗体结合或可用于离体临床情况的B细胞中诱导死亡以选择性去除B细胞。 已经鉴定了可用作B细胞标记的B细胞特异性寡糖表位。 在B淋巴细胞上识别的配体与任何已知的泛-B细胞标记物没有明显的相似性。 此外，提供了特异性结合公开的表位的蛋白质。 识别该B细胞表位的人单克隆抗体216对B细胞具有细胞毒性，并结合人外周血和脾中的所有CD19 +和CD20 + B淋巴细胞。 此外，MAb 216不区分B细胞的同种型表达，结合IgG +和IgM +细胞具有相同的强度，并且还结合所有B细胞，而不管其CD5表达。 提出了通过施用B细胞 - 细胞毒素蛋白抑制肿瘤性B细胞生长的方法。 这些产品和方法可用于诊断和治疗。
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公开(公告)号：US5593676A
公开(公告)日：1997-01-14
申请号：US394673
申请日：1995-02-23
IPC分类号： A61K38/00 , C07K16/28 , C07K16/30 , A61K39/395
CPC分类号： C07K16/3061 , C07K16/28 , A61K38/00 , C07K2317/73
摘要： Methods are provided for inducing cell death in B-cells, including neoplastic B-cells, by employing reagents that bind to a B-cell epitope. Particularly, antibodies specific for the marker can be administered to a host to induce death in B-cells to which the antibodies bind or can be used in ex vivo clinical situations to selectively remove B-cells. A B-cell specific oligosaccharide epitope useful as a B-cell marker has been identified. The ligand being recognized on B lymphocytes has no apparent similarities to any of the known pan-B cells markers. In addition, proteins which specifically bind the disclosed epitope are provided. Human monoclonal antibody 216, which recognizes this B-cell epitope, is cytotoxic to B-cells and binds all CD19.sup.+ and CD20.sup.+ B lymphocytes in human peripheral blood and spleen. Furthermore, MAb 216 does not distinguish B cells by the isotype expressed, binding IgG.sup.+ and IgM.sup.+ cells with equal intensity, and also bind all B cells regardless of their CD5 expression. Methods to inhibit neoplastic B-cell growth by administering a B-cell-cytotoxic protein are presented. These products and methods find use in diagnosis and therapy.
摘要翻译： 提供了通过使用与B细胞表位结合的试剂来诱导B细胞（包括肿瘤性B细胞）中的细胞死亡的方法。 特别地，可以向宿主施用对标记物特异性的抗体，以在抗体结合或可用于离体临床情况的B细胞中诱导死亡以选择性去除B细胞。 已经鉴定了可用作B细胞标记的B细胞特异性寡糖表位。 在B淋巴细胞上识别的配体与任何已知的泛-B细胞标记物没有明显的相似性。 此外，提供了特异性结合公开的表位的蛋白质。 识别该B细胞表位的人单克隆抗体216对B细胞具有细胞毒性，并结合人外周血和脾中的所有CD19 +和CD20 + B淋巴细胞。 此外，MAb 216不区分B细胞的同种型表达，结合IgG +和IgM +细胞具有相同的强度，并且还结合所有B细胞，而不管其CD5表达。 提出了通过施用B细胞 - 细胞毒素蛋白抑制肿瘤性B细胞生长的方法。 这些产品和方法可用于诊断和治疗。
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7.发明授权Triple gradient process with antibody panning to recover nucleated fetal cells from maternal blood 失效三重梯度过程与抗体淘选从母体血液回收有核的胎儿细胞
公开(公告)号：US5437987A
公开(公告)日：1995-08-01
申请号：US077295
申请日：1993-06-14
CPC分类号： G01N33/5002 , Y10S436/811
摘要： A method for separating nucleated fetal red blood cells and nucleated fetal cells and maternal granular sites from maternal blood is achieved by applying maternal blood to a triple gradient gel, isolating nucleated fetal cells from the gel and binding the isolated fetal cells to a solid support by means of an anti-i antibody bound to the solid support. The separated fetal cells can then be subjected to analysis for fetal sex or genetic disorders.
摘要翻译： 通过将母体血液应用于三重梯度凝胶，从凝胶中分离成核胎儿细胞并将分离的胎儿细胞与固体支持物结合，从而实现从母体血液中分离有核的胎儿红细胞和有核胎儿细胞和母体粒细胞的方法 与固体支持物结合的抗-I抗体的方法。 然后分离的胎儿细胞可以进行胎儿性别或遗传疾病的分析。
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公开(公告)号：US5185270A
公开(公告)日：1993-02-09
申请号：US282426
申请日：1988-12-12
CPC分类号： G01N33/689 , G01N33/76 , G01N2800/368 , Y10S436/814
摘要： A method for determining normal intrauterine pregnancy during the first 20 weeks of pregnancy comprises obtaining a test sample; and determining the presence of a fetal restricted antigen in the sample. The test sample is removed the vaginal cavity in the vicinity of the cervical canal and/or the cervical os. One fetal restricted antigen is fetal fibronectin.In one embodiment of this invention, the test sample is contacted with an insoluble support to which anti-(fetal restricted antigen) antibody is adhered, and the fetal restricted antigen binding to the support is determined. Alternatively, the test sample is contacted with an insoluble support to which is adhered an antibody which binds a class of substances including the fetal restricted antigen; and the fetal restricted antigen binding to the support is determined. Reagents and reagent kits are also included.
摘要翻译： 妊娠前20周确定正常子宫内孕的方法包括获得试验样品; 并确定样品中胎儿限制性抗原的存在。 将测试样品移除在子宫颈管和/或子宫颈附近的阴道腔。 一种胎儿限制性抗原是胎儿纤连蛋白。 在本发明的一个实施方案中，将测试样品与抗（胎儿限制性抗原）抗体所粘附的不溶性支持物接触，并确定与载体结合的胎儿限制性抗原。 或者，将测试样品与不溶性载体接触，所述不溶性载体附着有结合一类物质（包括胎儿限制性抗原）的抗体; 确定与载体结合的胎儿限制性抗原。 还包括试剂和试剂盒。
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公开(公告)号：US5426046A
公开(公告)日：1995-06-20
申请号：US112048
申请日：1993-08-25
CPC分类号： C07K16/1203 , A61K38/00
摘要： A human monoclonal antibody, C5, specific for lipid A of the endotoxin core of Gram-negative bacteria and the hybridoma cell line which produces the antibody. The monoclonal antibody is produced by the fusion of lipid A sensitized lymphocytes and an appropriate fusion partner.
摘要翻译： 对革兰氏阴性细菌的内毒素核心的脂质A和产生抗体的杂交瘤细胞系特异性的人单克隆抗体C5。 单克隆抗体通过融合脂质A致敏淋巴细胞和合适的融合配偶体产生。
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公开(公告)号：US5236846A
公开(公告)日：1993-08-17
申请号：US732364
申请日：1991-07-18
IPC分类号： G01N33/68
CPC分类号： G01N33/689 , G01N2800/368
摘要： A method for determining ectopic pregnancy in pregnant persons comprises obtaining a test sample; and determining the absence of a fetal restricted antigen in the sample. The sample is obtained from the vaginal cavity in the vicinity of the cervical canal or the cervical os. One fetal restricted antigen is fetal fibronectin. In one embodiment of this invention, the sample is contacted with an insoluble support to which anti-(fetal restricted antigen) antibody is adhered, and the fetal restricted antigen binding to the support is determined. Alternatively, a class of substances of which the fetal restricted antigen is a member is captured with a general binding antibody such as an anti-(fibronectin) antibody; an anti-(fetal restricted antigen) antibody such as anti-(fetal fibronectin) antibody is bound to the support; and the absence of binding with fetal restricted antigen is determined. Competition or sandwich assay procedures can be used. Reagents and reagent kits are also included.
摘要翻译： 用于确定孕妇异位妊娠的方法包括获得测试样品; 并确定样品中不存在胎儿限制性抗原。 样品从宫颈管或宫颈口附近的阴道腔获得。 一种胎儿限制性抗原是胎儿纤连蛋白。 在本发明的一个实施方案中，将样品与抗（胎儿限制性抗原）抗体所粘附的不溶性载体接触，并确定与载体结合的胎儿限制性抗原。 或者，用一般结合抗体如抗（纤连蛋白）抗体捕获一类胎儿限制性抗原成员的物质; 抗（胎儿限制性抗原）抗体如抗（胎儿纤连蛋白）抗体与载体结合; 并确定与胎儿限制性抗原不结合。 可以使用竞争或三明治测定程序。 还包括试剂和试剂盒。
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