Method of killing B cells using antibodies which bind CDIM
    1.
    发明授权
    Method of killing B cells using antibodies which bind CDIM 失效
    使用结合CDIM的抗体杀死B细胞的方法

    公开(公告)号:US5593676A

    公开(公告)日:1997-01-14

    申请号:US394673

    申请日:1995-02-23

    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。

    ENHANCED B CELL CYTOTOXICITY OF CDIM BINDING ANTIBODY
    2.
    发明申请
    ENHANCED B CELL CYTOTOXICITY OF CDIM BINDING ANTIBODY 审中-公开
    CDIM结合抗体的增强B细胞的细胞毒性

    公开(公告)号:US20100322849A1

    公开(公告)日:2010-12-23

    申请号:US12490296

    申请日:2009-06-23

    摘要: Formulations and methods of treating human patients suffering from a condition characterized by lymphoid cancer, autoimmune disease or B cell hyperproliferation are disclosed, the treatment comprising administering (1) a cytotoxic amount of an antibody having specific binding for CDIM epitopes on a B cell, and (2) a cytotoxic agent, including a chemotherapeutic agent, radioactive isotope, cytotoxic antibody, immunoconjugate, ligand conjugate, immunosuppressant, cell growth regulator and/or inhibitor, toxin, or mixtures thereof, including agents that disrupt the cytoskeleton of B cells, particularly vinca alkaloids or colchicine.

    摘要翻译: 公开了治疗患有以淋巴癌,自身免疫疾病或B细胞过度增殖为特征的病症的患者的制剂和方法,所述方法包括在B细胞上施用(1)细胞毒性量的具有CDIM表位特异性结合的抗体,以及 (2)细胞毒剂,包括化学治疗剂,放射性同位素,细胞毒性抗体,免疫缀合物,配体结合物,免疫抑制剂,细胞生长调节剂和/或抑制剂,毒素或其混合物,包括破坏B细胞的细胞骨架的试剂,特别是 长春花生物碱或秋水仙碱。

    ENHANCED B CELL CYTOTOXICITY OF CDIM BINDING ANTIBODY
    3.
    发明申请
    ENHANCED B CELL CYTOTOXICITY OF CDIM BINDING ANTIBODY 审中-公开
    CDIM结合抗体的增强B细胞的细胞毒性

    公开(公告)号:US20120237441A9

    公开(公告)日:2012-09-20

    申请号:US12490296

    申请日:2009-06-23

    摘要: Formulations and methods of treating human patients suffering from a condition characterized by lymphoid cancer, autoimmune disease or B cell hyperproliferation are disclosed, the treatment comprising administering (1) a cytotoxic amount of an antibody having specific binding for CDIM epitopes on a B cell, and (2) a cytotoxic agent, including a chemotherapeutic agent, radioactive isotope, cytotoxic antibody, immunoconjugate, ligand conjugate, immunosuppressant, cell growth regulator and/or inhibitor, toxin, or mixtures thereof, including agents that disrupt the cytoskeleton of B cells, particularly vinca alkaloids or colchicine.

    摘要翻译: 公开了治疗患有以淋巴癌,自身免疫疾病或B细胞过度增殖为特征的病症的患者的制剂和方法,所述方法包括在B细胞上施用(1)细胞毒性量的具有CDIM表位特异性结合的抗体,以及 (2)细胞毒剂,包括化学治疗剂,放射性同位素,细胞毒性抗体,免疫缀合物,配体结合物,免疫抑制剂,细胞生长调节剂和/或抑制剂,毒素或其混合物,包括破坏B细胞的细胞骨架的试剂,特别是 长春花生物碱或秋水仙碱。

    Triple gradient process for recovering nucleated fetal cells from
maternal blood
    4.
    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

    IPC分类号: G01N33/50 A01N1/02

    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。

    CDIM binding proteins and uses thereof
    5.
    发明授权
    CDIM binding proteins and uses thereof 有权
    CDIM结合蛋白及其用途

    公开(公告)号:US09409976B2

    公开(公告)日:2016-08-09

    申请号:US13763398

    申请日:2013-02-08

    IPC分类号: C07K16/18 C07K16/28 C07K16/30

    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。

    Antibody induced cell membrane wounding
    6.
    发明授权
    Antibody induced cell membrane wounding 有权
    抗体诱导细胞膜受伤

    公开(公告)号:US08377435B2

    公开(公告)日:2013-02-19

    申请号:US11267935

    申请日:2005-11-04

    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。

    Method of killing B-cells in a complement independent and an ADCC
independent manner using antibodies which specifically bind CDIM
    7.
    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

    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。

    CDIM Binding Proteins And Uses Thereof
    8.
    发明申请
    CDIM Binding Proteins And Uses Thereof 有权
    CDIM结合蛋白及其用途

    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

    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。