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    T cell receptor-like antibodies specific for a WTI peptide presented by HLA-A2
    1.
    发明授权
    T cell receptor-like antibodies specific for a WTI peptide presented by HLA-A2 有权

    公开(公告)号：US10858444B2

    公开(公告)日：2020-12-08

    申请号：US16055535

    申请日：2018-08-06

    申请人： Memorial Sloan Kettering Cancer Center ,  Eureka Therapeutics, Inc.

    发明人： David Scheinberg ,  Tao Dao ,  Cheng Liu ,  Su Yan

    IPC分类号： A61K39/00 ,  C07K16/32 ,  A61K47/68 ,  C07K16/28 ,  C07K16/18 ,  G01N33/574

    摘要： The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

    T cell receptor-like antibodies specific for a WTI peptide presented by HLA-A2
    2.
    发明授权
    T cell receptor-like antibodies specific for a WTI peptide presented by HLA-A2 有权
    由HLA-A2呈递的WTI肽特异的T细胞受体样抗体

    公开(公告)号：US09540448B2

    公开(公告)日：2017-01-10

    申请号：US14724155

    申请日：2015-05-28

    申请人： MEMORIAL SLOAN KETTERING CANCER CENTER ,  EUREKA THERAPEUTICS, INC.

    发明人： David Scheinberg ,  Tao Dao ,  Cheng Liu ,  Su Yan

    IPC分类号： A61K39/395 ,  C07K16/32 ,  A61K47/48 ,  C07K16/28 ,  G01N33/574 ,  C07K16/18 ,  A61K39/00

    CPC分类号： C07K16/32 ,  A61K47/6849 ,  A61K47/6851 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/2833 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/732 ,  G01N33/5748

    摘要： The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

    摘要翻译： 本发明提供特异性结合Wilms肿瘤蛋白（WT1）的抗原结合蛋白，包括针对WT1的人源化，嵌合和完全人抗体，抗体片段，嵌合抗原受体（CAR），融合蛋白及其缀合物。 抗原结合蛋白和抗体结合HLA-A0201限制性WT1肽。 此类抗体，片段，融合蛋白及其结合物可用于治疗WT1相关癌症，包括例如乳腺癌，卵巢癌，前列腺癌，慢性骨髓性白血病，多发性骨髓瘤，急性淋巴细胞性白血病（ALL），急性骨髓/ 骨髓性白血病（AML）和骨髓增生异常综合征（MDS）。 在更具体的实施方案中，抗WT1 / A抗体可以包含设计用于改善蛋白质稳定性，抗体结合和/或表达水平的一个或多个框架区氨基酸取代。

    ANTI-WT1/HLA BI-SPECIFIC ANTIBODY
    4.
    发明申请
    ANTI-WT1/HLA BI-SPECIFIC ANTIBODY 审中-公开
    ANTI-WT1 / HLA BI特异性抗体

    公开(公告)号：US20160280796A1

    公开(公告)日：2016-09-29

    申请号：US15034782

    申请日：2014-11-07

    申请人： MEMORIAL SLOAN-KETTERING CANCER CENTER ,  EUREKA THERAPEUTICS, INC.

    发明人： David Scheinberg ,  Jingyi Xiang ,  Tao Dao ,  Su Yan ,  Cheng Liu

    IPC分类号： C07K16/32 ,  C07K16/28

    CPC分类号： C07K16/32 ,  A61K2039/505 ,  C07K16/2809 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2317/73

    摘要： Disclosed herein is a bi-specific form of a T cell receptor mimic (TCRm) mAb with reactivity to human immune effector cell antigen and a WT1 peptide/HLA-A epitope. This antibody selectively bound to leukemias and solid tumor cells expressing WT1 and HLA-A as well as activated resting human T cells to release interferon-(IFN-γ) and to kill the target cancer cells in vitro. Importantly, the antibody mediated autologous T cell proliferation and directed potent cytotoxicity against fresh ovarian cancer cells. Therapeutic activity in vivo of the antibody was demonstrated in NOD SCID SCID Yc* (NSG) mice with three different human cancers expressing WT1/HLA-A2 including disseminated Ph+ acute lymphocytic leukemia (ALL), disseminated acute myeloid leukemia, and peritoneal mesothelioma. In both of the leukemia xenograft models, mice that received the antibody and T cells also showed longer survival and delayed limb paralysis. Also provided are methods for stimulating a primary T cell response comprising stimulating cytotoxic T cells against a first tumor antigen and a secondary T cell response comprising stimulating effector T cells and/or memory T cells against a first tumor antigen and/or against a second tumor antigen using the bi-specific antibodies described herein.

    摘要翻译： 本文公开了与人免疫效应细胞抗原和WT1肽/ HLA-A表位具有反应性的T细胞受体模拟物（TCRm）mAb的双特异性形式。 该抗体选择性结合表达WT1和HLA-A的白血病和实体肿瘤细胞以及活化的休息的人T细胞以释放干扰素（IFN-γ）并在体外杀死靶癌细胞。 重要的是，抗体介导的自体T细胞增殖和对新鲜卵巢癌细胞的有力的细胞毒性。 在具有表达WT1 / HLA-A2的三种不同人类癌症的NOD SCID SCID Yc *（NSG）小鼠中证实了抗体的治疗活性，包括播散性Ph +急性淋巴细胞性白血病（ALL），弥散性急性骨髓性白血病和腹膜间皮瘤。 在两种白血病异种移植模型中，接受抗体和T细胞的小鼠也显示较长的存活期和延迟的肢体麻痹。 还提供了用于刺激原代T细胞应答的方法，包括刺激针对第一肿瘤抗原的细胞毒性T细胞和辅助T细胞应答，包括针对第一肿瘤抗原和/或针对第二肿瘤刺激效应T细胞和/或记忆T细胞 使用本文所述的双特异性抗体。

    Anti-WT1/HLA bi-specific antibody
    5.
    发明授权
    Anti-WT1/HLA bi-specific antibody 有权

    公开(公告)号：US10239952B2

    公开(公告)日：2019-03-26

    申请号：US15034782

    申请日：2014-11-07

    申请人： MEMORIAL SLOAN-KETTERING CANCER CENTER ,  EUREKA THERAPEUTICS, INC.

    发明人： David Scheinberg ,  Jingyi Xiang ,  Tao Dao ,  Su Yan ,  Cheng Liu

    IPC分类号： A61K39/00 ,  C07K16/32 ,  C07K16/28

    摘要： Disclosed herein is a bi-specific form of a T cell receptor mimic (TCRm) mAb with reactivity to human immune effector cell antigen and a WT1 peptide/HLA-A epitope. This antibody selectively bound to leukemias and solid tumor cells expressing WT1 and HLA-A as well as activated resting human T cells to release interferon-(IFN-γ) and to kill the target cancer cells in vitro. Importantly, the antibody mediated autologous T cell proliferation and directed potent cytotoxicity against fresh ovarian cancer cells. Therapeutic activity in vivo of the antibody was demonstrated in NOD SCID SCID Yc*(NSG) mice with three different human cancers expressing WT1/HLA-A2 including disseminated Ph+ acute lymphocytic leukemia (ALL), disseminated acute myeloid leukemia, and peritoneal mesothelioma. In both of the leukemia xenograft models, mice that received the antibody and T cells also showed longer survival and delayed limb paralysis. Also provided are methods for stimulating a primary T cell response comprising stimulating cytotoxic T cells against a first tumor antigen and a secondary T cell response comprising stimulating effector T cells and/or memory T cells against a first tumor antigen and/or against a second tumor antigen using the bi-specific antibodies described herein.

    T cell receptor-like antibodies specific for a WTI peptide presented by HLA-A2
    6.
    发明授权
    T cell receptor-like antibodies specific for a WTI peptide presented by HLA-A2 有权

    公开(公告)号：US10040865B2

    公开(公告)日：2018-08-07

    申请号：US15364953

    申请日：2016-11-30

    申请人： MEMORIAL SLOAN KETTERING CANCER CENTER ,  EUREKA THERAPEUTICS, INC.

    发明人： David Scheinberg ,  Tao Dao ,  Cheng Liu ,  Su Yan

    IPC分类号： A61K39/00 ,  C07K16/32 ,  C07K16/28 ,  G01N33/574 ,  C07K16/18 ,  A61K47/68

    摘要： The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

    T CELL RECEPTOR-LIKE ANTIBODIES SPECIFIC FOR A WTI PEPTIDE PRESENTED BY HLA-A2
    7.
    发明申请
    T CELL RECEPTOR-LIKE ANTIBODIES SPECIFIC FOR A WTI PEPTIDE PRESENTED BY HLA-A2 有权
    T细胞受体 - HLA-A2提供的WTI肽特异性抗体

    公开(公告)号：US20150259436A1

    公开(公告)日：2015-09-17

    申请号：US14724155

    申请日：2015-05-28

    申请人： Memorial Sloan Kettering Cancer Center ,  Eureka Therapeutics, Inc.

    发明人： David Scheinberg ,  Tao Dao ,  Cheng Liu ,  Su Yan

    IPC分类号： C07K16/32 ,  A61K47/48

    CPC分类号： C07K16/32 ,  A61K47/6849 ,  A61K47/6851 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/2833 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/732 ,  G01N33/5748

    摘要： The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

    摘要翻译： 本发明提供特异性结合Wilms肿瘤蛋白（WT1）的抗原结合蛋白，包括针对WT1的人源化，嵌合和完全人抗体，抗体片段，嵌合抗原受体（CAR），融合蛋白及其缀合物。 抗原结合蛋白和抗体结合HLA-A0201限制性WT1肽。 此类抗体，片段，融合蛋白及其结合物可用于治疗WT1相关癌症，包括例如乳腺癌，卵巢癌，前列腺癌，慢性骨髓性白血病，多发性骨髓瘤，急性淋巴细胞性白血病（ALL），急性骨髓/ 骨髓性白血病（AML）和骨髓增生异常综合征（MDS）。 在更具体的实施方案中，抗WT1 / A抗体可以包含设计用于改善蛋白质稳定性，抗体结合和/或表达水平的一个或多个框架区氨基酸取代。