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公开(公告)号：US20190144563A1
公开(公告)日：2019-05-16
申请号：US16055535
申请日：2018-08-06
Inventor： David SCHEINBERG , Tao DAO , Cheng LIU , Su YAN
IPC: C07K16/32 , A61K47/68 , C07K16/28 , C07K16/18 , G01N33/574
Abstract: 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.
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公开(公告)号：US20180134804A1
公开(公告)日：2018-05-17
申请号：US15710384
申请日：2017-09-20
Inventor： David A. SCHEINBERG , Tao DAO , Cheng LIU
CPC classification number: C07K16/40 , A61K39/0011 , A61K47/6871 , C07K16/2809 , C07K2317/14 , C07K2317/21 , C07K2317/31 , C07K2317/34 , C07K2317/54 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/622 , C07K2317/732 , C07K2317/92 , C07K2319/70
Abstract: Antigen binding proteins specific for an HLA-A2 restricted Ras peptide are disclosed. The antigen binding proteins encompass antibodies in a variety of forms, including full-length antibodies, substantially intact antibodies, Fab fragments, F(ab′)2 fragments, and single chain Fv fragments. Fusion proteins, such as scFv fusions with immunoglobulin or T-cell receptor domains, and bispecific antibodies incorporating the specificity of the antigen binding region for each peptide are also contemplated by the disclosure. Furthermore, immunoconjugates may include antibodies to which is linked a radioisotope, fluorescent or other detectable marker, cytotoxin, or other molecule are also encompassed by the disclosure. Among other things, immunoconjugates can be used for delivery of an agent to elicit a therapeutic effect or to facilitate an immune effector function.
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公开(公告)号：US20210332150A9
公开(公告)日：2021-10-28
申请号：US15710384
申请日：2017-09-20
Inventor： David A. SCHEINBERG , Tao DAO , Cheng LIU
Abstract: Antigen binding proteins specific for an HLA-A2 restricted Ras peptide are disclosed. The antigen binding proteins encompass antibodies in a variety of forms, including full-length antibodies, substantially intact antibodies, Fab fragments, F(ab′)2 fragments, and single chain Fv fragments. Fusion proteins, such as scFv fusions with immunoglobulin or T-cell receptor domains, and bispecific antibodies incorporating the specificity of the antigen binding region for each peptide are also contemplated by the disclosure. Furthermore, immunoconjugates may include antibodies to which is linked a radioisotope, fluorescent or other detectable marker, cytotoxin, or other molecule are also encompassed by the disclosure. Among other things, immunoconjugates can be used for delivery of an agent to elicit a therapeutic effect or to facilitate an immune effector function.
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公开(公告)号：US20210163624A1
公开(公告)日：2021-06-03
申请号：US17085234
申请日：2020-10-30
Inventor： David SCHEINBERG , Tao DAO , Cheng LIU , Su YAN
IPC: C07K16/32 , A61K47/68 , C07K16/28 , C07K16/18 , G01N33/574
Abstract: 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.
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公开(公告)号：US20220267420A1
公开(公告)日：2022-08-25
申请号：US16970332
申请日：2019-02-14
Inventor： David A. SCHEINBERG , Cheng LIU , Zhiyuan YANG , Lianxing LIU , Shaohua Xu , Pei WANG , Yiyang XU
IPC: C07K16/18 , C07K14/725 , C07K14/74 , C07K14/705 , C12N5/0783
Abstract: Provided herein are compositions, kits, and methods for manufacturing cells for adoptive cell therapy comprising (a) an engineered receptor, vector encoding an engineered receptor, or engineered immune cell expressing such engineered receptor or comprising such vector; and (b) a Fox P3 targeting agent.
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公开(公告)号：US20160369006A1
公开(公告)日：2016-12-22
申请号：US15101273
申请日：2014-11-07
Inventor： David SCHEINBERG , Nicholas VEOMETT , Hong LIU , Jingyi XIANG , Cheng LIU , Tao DAO , Heather Adkins HUET
CPC classification number: C07K16/32 , A61K2039/505 , C07K16/2833 , C07K16/3015 , C07K16/3046 , C07K16/3069 , C07K2317/32 , C07K2317/34 , C07K2317/41 , C07K2317/565 , C07K2317/72 , C07K2317/732 , C07K2317/92 , C07K2317/94
Abstract: The present disclosure relates to an anti-WT-1/HLA/A2 antibody with enhanced antibody dependent cell-mediated cytotoxicity (ADCC) function due to altered Fc glycosylation. The antibody, which has reduced fucose and/or galactose, was compared to its normally glycosylated counterpart in binding assays, in vitro ADCC assays, and mesothelioma and leukemia therapeutic models and pharmacokinetic studies in mice. The antibody with normal glycosylation mediated ADCC against hematopoietic and solid tumor cells at concentrations below 1 μg/ml, but the reduced fucosylated antibody was about 5-10 fold more potent in vitro against multiple cancer cell lines, was more potent in vivo against JMN mesothelioma, and effective against SET2 AML and fresh ALL xenografts. ESKM had a shortened half-life (4.9 vs 6.5 days), but an identical biodistribution pattern in C57BL6/J mice. At therapeutic doses of ESKM, there was no difference in half-life or biodistribution in HLA-A2.1+ transgenic mice compared to the parent strain. Importantly, therapeutic doses of ESKM in these mice caused no depletion of total WBCs or hematopoietic stem cells, or pathologic tissue damage.
Abstract translation: 本公开涉及由于改变的Fc糖基化而具有增强的抗体依赖性细胞介导的细胞毒性（ADCC）功能的抗WT-1 / HLA / A2抗体。 将具有降低的岩藻糖和/或半乳糖的抗体与结合测定中的通常糖基化的对应物，体外ADCC测定和间皮瘤和白血病治疗模型和小鼠中的药代动力学研究进行比较。 具有正常糖基化的抗体对低于1μg/ ml的造血和实体肿瘤细胞介导的ADCC的抗体，但是减少的岩藻糖基化抗体在体外对多种癌细胞系有效约5-10倍，在体内对JMN间皮瘤有更强的作用 ，对抗SET2 AML和新鲜ALL异种移植物有效。 ESKM具有缩短的半衰期（4.9 vs 6.5天），但在C57BL6 / J小鼠中具有相同的生物分布模式。 在治疗剂量的ESKM中，与亲本菌株相比，HLA-A2.1 +转基因小鼠的半衰期或生物分布没有差异。 重要的是，这些小鼠的治疗剂量的ESKM不会造成总WBCs或造血干细胞或病理组织损伤的消耗。
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公开(公告)号：US20220235143A1
公开(公告)日：2022-07-28
申请号：US17609053
申请日：2020-05-07
Inventor： David SPRIGGS , Dharmarao THAPI , Su YAN , Cheng LIU
IPC: C07K16/30 , A61K47/68 , A61P35/00 , C12N5/0783 , A61K35/17 , A61K39/395 , G01N33/574 , A61K51/10 , C07K16/28 , C07K14/705 , C07K14/725 , A61K38/17 , A61P35/04
Abstract: Provided herein are compositions, methods, and uses involving anti-Mucin-16 (MUC16) agents that immunospecifically bind an epitope of Mucin-16 (MUC16). Also provided herein are uses and methods for managing, treating, or preventing disorders, such as cancer and diseases associated with positive MUC16 expression.
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公开(公告)号：US20180127502A1
公开(公告)日：2018-05-10
申请号：US15849107
申请日：2017-12-20
Inventor： Renier J. BRENTJENS , Hollie Jaine JACKSON , Cheng LIU
CPC classification number: C07K16/2818 , A61K35/17 , A61K38/00 , A61K39/39558 , A61K47/6849 , A61K48/00 , A61K2035/124 , A61K2039/505 , A61K2039/507 , A61P35/00 , C07K14/70503 , C07K14/7051 , C07K16/2803 , C07K16/30 , C07K2317/21 , C07K2317/54 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/73 , C07K2317/75 , C07K2317/76 , C07K2319/03 , C12N2740/10043 , A61K2300/00
Abstract: The present application provides anti-PD-1 antigen-binding proteins or a fragment thereof, as well as nucleic acids encoding anti-PD-1 antigen-binding proteins or CAR T cells expressing such antigen-binding protein or fragment. Also provided are methods of regulating T cells or treating patients using such constructs or cells.
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公开(公告)号：US20200031927A1
公开(公告)日：2020-01-30
申请号：US16484451
申请日：2018-02-26
Inventor： Katharine HSU , Nai-Kong V. Cheung , Su YAN , Yiyang XU , Jingyi XIANG , Cheng LIU
IPC: C07K16/28 , A61P35/02 , A61K45/06 , A61K39/395 , A61K47/68
Abstract: The disclosure provides antibody agents that bind to inhibitory human killer immunoglobulin-like receptors (KIRs). Particular antibody agents of the disclosure include antibody agents that bind to KIR3DL1 (also known as CD158e). Also provided are related nucleic acids, vectors, compositions and methods of using KIR-binding antibody agents of the present technology.
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公开(公告)号：US20180360880A1
公开(公告)日：2018-12-20
申请号：US15613638
申请日：2018-01-19
Inventor： Renier J. Brentjens , Eric L. SMITH , Cheng LIU
IPC: A61K35/17 , C07K14/725 , C07K14/705 , C07K16/28 , A61P35/00
Abstract: The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target B cell maturation antigen (BMCA), and immunoresponsive cells comprising such CARs. The presently disclosed BMCA-specific CARs have enhanced immune-activating properties, including anti-tumor activity.
