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11. 发明授权

US10239952B2 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.

12. 发明授权

US10040865B2 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.

13. 发明申请

US20150259436A1 T CELL RECEPTOR-LIKE ANTIBODIES SPECIFIC FOR A WTI PEPTIDE PRESENTED BY HLA-A2 有权
标题翻译： 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。

14. 发明申请

US20140271644A1 COMBINATION/ADJUVANT THERAPY FOR WT-1-POSITIVE DISEASE 审中-公开
标题翻译：用于WT-1阳性疾病的组合/辅助治疗
公开(公告)号：US20140271644A1
公开(公告)日：2014-09-18
申请号：US14211435
申请日：2014-03-14
申请人： Memorial Sloan-Kettering Cancer Center
发明人： David Scheinberg , Leonid Dubrovsky
IPC分类号： A61K39/395 , A61K31/506
CPC分类号： A61K39/39558 , A61K31/506 , A61K45/06 , A61K2039/505 , C07K16/2833 , C07K16/30 , C07K2317/32 , C07K2317/732 , A61K2300/00
摘要： In an attempt to improve primary disease responsiveness and/or to overcome resistant disease, the present disclosure provides a method for treating or inhibiting the proliferation of a WT-1-dependent cancer comprising providing to a subject in need thereof a therapeutically effective amount of a tyrosine kinase inhibitor along with an anti-WT-1/HLA antibody, that is, an antibody that specifically binds to a peptide of Wilms' tumor protein (WT-1) presented on the surface of the cancer cells in an HLA-restricted fashion.
摘要翻译：为了提高初级疾病反应性和/或克服耐药性疾病，本公开提供了治疗或抑制WT-1依赖性癌症增殖的方法，包括向有需要的受试者提供治疗有效量的酪氨酸激酶抑制剂以及抗WT-1 / HLA抗体，即以HLA限制性方式特异性结合存在于癌细胞表面上的Wilms肿瘤蛋白（WT-1）的肽的抗体。

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