公开(公告)号：US20250011463A1

公开(公告)日：2025-01-09

申请号：US18640985

申请日：2024-04-19

Applicant: EUREKA THERAPEUTICS, INC.

Inventor： Hong LIU ,  Hongruo YUN ,  Xiaomei GE ,  Zhiyuan YANG ,  Lianxing LIU ,  Pengbo ZHANG ,  Yixiang XU ,  Shan LI ,  Lucas HORAN

IPC: C07K16/30 ,  A61K39/00 ,  A61P35/00 ,  C07K14/705 ,  C07K14/725 ,  C07K16/28 ,  G01N33/574

Abstract: The present application provides constructs comprising an antibody moiety that specifically binds to PSMA (e.g., PSMA expressed on the surface of a cell). Also provided are methods of making and using these constructs.

公开(公告)号：US20240317855A1

公开(公告)日：2024-09-26

申请号：US18593621

申请日：2024-03-01

Applicant: EUREKA THERAPEUTICS, INC.

Inventor： Hong LIU ,  Pengbo ZHANG ,  Lucas HORAN ,  Yiyang XU ,  Binnaz K. STALEY ,  Lianxing LIU ,  Hongruo YUN

IPC: C07K16/28 ,  A61K35/17 ,  A61K38/00 ,  A61K39/00 ,  A61P35/00 ,  C07K14/705 ,  C07K14/725 ,  C07K16/30

CPC classification number: C07K16/2803 ,  A61K35/17 ,  A61P35/00 ,  C07K14/7051 ,  C07K14/70521 ,  C07K14/70578 ,  C07K16/2809 ,  C07K16/2827 ,  C07K16/283 ,  C07K16/2833 ,  C07K16/2887 ,  C07K16/303 ,  A61K38/00 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/522 ,  C07K2317/53 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/02 ,  C07K2319/03 ,  C07K2319/30 ,  C07K2319/33

Abstract: The present application provides immune cells (such as T cells) comprising a chimeric antibody-T cell receptor (TCR) construct (caTCR) and a chimeric signaling receptor (CSR) construct. The caTCR comprises an antigen-binding module that specifically binds to a target antigen and a T cell receptor module (TCRM) capable of recruiting at least one TCR-associated signaling molecule, and the CSR comprises a ligand-binding domain that specifically binds to a target ligand and a co-stimulatory signaling domain capable of providing a stimulatory signal to the immune cell. Also provided are methods of making and using these cells.

公开(公告)号：US20210107992A1

公开(公告)日：2021-04-15

申请号：US16608377

申请日：2018-04-24

Applicant: EUREKA THERAPEUTICS, INC.

Inventor： Pengbo ZHANG ,  Yiyang XU ,  Javier MORALES ,  Yoko NAKANO ,  Hong LIU ,  Jingyi XIANG ,  Timothy ACKER

IPC: C07K16/30 ,  C07K14/705 ,  C07K14/725 ,  G01N33/574 ,  C07K16/28 ,  A61P35/00

Abstract: The present application provides constructs comprising an antibody moiety specifically recognizing Glypican 3 (GPC3), such as a cell surface-bound GPC3. Also provided are methods of making and using these constructs.

公开(公告)号：US20210253665A1

公开(公告)日：2021-08-19

申请号：US17181913

申请日：2021-02-22

Applicant: EUREKA THERAPEUTICS, INC.

Inventor： Jingwei LU ,  Zhiyuan YANG ,  Cheng LIU ,  Hong LIU ,  Yiyang XU ,  Su YAN ,  Vivien Wai-Fan CHAN ,  Lucas HORAN

IPC: C07K14/725 ,  A61K35/17 ,  C12N15/62 ,  A61K38/00 ,  A61P35/00 ,  A61K39/395 ,  C07K16/28

Abstract: The present application provides antibody-TCR chimeric constructs comprising an antibody moiety that specifically binds to a target antigen fused to a TCRM capable of recruiting at least one TCR-associated signaling module. Also provided are methods of making and using these constructs.

公开(公告)号：US20190382504A1

公开(公告)日：2019-12-19

申请号：US15738097

申请日：2016-06-24

Applicant: EUREKA THERAPEUTICS, INC.

Inventor： Cheng LIU ,  Hong LIU ,  Yiyang XU ,  Jingyi XIANG

IPC: C07K16/30 ,  G01N33/574 ,  C07K16/28 ,  C07K16/46 ,  C07K14/725 ,  C07K14/705 ,  A61P35/00

Abstract: The present application provides constructs comprising an antibody moiety that specifically binds to a complex comprising an NY-ESO-1 peptide and an MHC class I protein. Also provided are methods of making and using these constructs.

公开(公告)号：US20160369006A1

公开(公告)日：2016-12-22

申请号：US15101273

申请日：2014-11-07

Applicant: MEMORIAL SLOAN-KETTERING CANCER CENTER ,  EUREKA THERAPEUTICS, INC. ,  NOVARTIS AG

Inventor： David SCHEINBERG ,  Nicholas VEOMETT ,  Hong LIU ,  Jingyi XIANG ,  Cheng LIU ,  Tao DAO ,  Heather Adkins HUET

IPC: C07K16/32 ,  C07K16/30

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。

公开(公告)号：US20220348629A1

公开(公告)日：2022-11-03

申请号：US17716667

申请日：2022-04-08

Applicant: EUREKA THERAPEUTICS, INC.

Inventor： Jingwei LU ,  Zhiyuan YANG ,  Cheng LIU ,  Hong LIU ,  Yiyang XU ,  Su YAN ,  Vivien Wai-Fan CHAN ,  Lucas HORAN

IPC: C07K14/725 ,  A61K35/17 ,  C12N15/62 ,  A61K38/00 ,  A61P35/00 ,  A61K39/395 ,  C07K16/28

Abstract: The present application provides antibody-TCR chimeric constructs comprising an antibody moiety that specifically binds to a target antigen fused to a TCRM capable of recruiting at least one TCR-associated signaling module. Also provided are methods of making and using these constructs.

公开(公告)号：US20210093666A1

公开(公告)日：2021-04-01

申请号：US16608362

申请日：2018-04-24

Applicant: EUREKA THERAPEUTICS, INC.

Inventor： Binnaz K. STALEY ,  Fei XIE ,  Yiyang XU ,  Hong LIU ,  Cheng LIU

IPC: A61K35/17 ,  C07K16/28 ,  C07K16/30 ,  C07K14/725

Abstract: The present application provides immune cells (such as T cells) comprising a chimeric antibody-T cell receptor (TCR) construct (caTCR) and a secretory secondary effector (SSE) construct. The caTCR comprises an antigen-binding module that specifically binds to a target antigen and a T cell receptor module (TCRM) capable of recruiting at least one TCR-associated signaling molecule, and the SSE is capable of enhancing an immune response mediated by the caTCR. Also provided are methods of making and using these cells.

公开(公告)号：US20200115448A1

公开(公告)日：2020-04-16

申请号：US16660515

申请日：2019-10-22

Applicant: EUREKA THERAPEUTICS, INC.

Inventor： Hong LIU ,  Pengbo ZHANG ,  Lucas HORAN ,  Yiyang XU ,  Binnaz K. STALEY ,  Lianxing LIU ,  Hongruo YUN

IPC: C07K16/28 ,  C07K14/725 ,  C07K16/30 ,  A61K35/17 ,  A61P35/00 ,  C07K14/705

Abstract: The present application provides immune cells (such as T cells) comprising a chimeric antibody-T cell receptor (TCR) construct (caTCR) and a chimeric signaling receptor (CSR) construct. The caTCR comprises an antigen-binding module that specifically binds to a target antigen and a T cell receptor module (TCRM) capable of recruiting at least one TCR-associated signaling molecule, and the CSR comprises a ligand-binding domain that specifically binds to a target ligand and a co-stimulatory signaling domain capable of providing a stimulatory signal to the immune cell. Also provided are methods of making and using these cells.

公开(公告)号：US20200087400A1

公开(公告)日：2020-03-19

申请号：US15746367

申请日：2016-07-22

Applicant: EUREKA THERAPEUTICS, INC.

Inventor： Hong LIU ,  Jingyi XIANG ,  Yiyang XU ,  Vivien Wai-Fan CHAN

IPC: C07K16/28 ,  C07K16/30

Abstract: The present application provides constructs comprising an antibody moiety that specifically binds to a complex comprising a PSA peptide and an MHC class I protein. Also provided are methods of making and using these constructs.