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1. 发明申请

US20180193477A1 DRUG-CONJUGATED BI-SPECIFIC ANTIGEN-BINDING CONSTRUCTS 审中-公开
公开(公告)号：US20180193477A1
公开(公告)日：2018-07-12
申请号：US15741984
申请日：2016-07-15
申请人： Zymeworks Inc.
发明人： Gordon Yiu Kon Ng , Leonard G. Presta , Thomas Spreter Von Kreudenstein
IPC分类号： A61K47/68 , A61P35/00 , A61P35/02 , A61P35/04 , C07K16/28 , A61K51/10 , C07K16/32 , A61K45/06 , A61K39/395 , C07K16/46
CPC分类号： A61K47/6803 , A61K39/3955 , A61K39/39558 , A61K45/06 , A61K47/6811 , A61K47/6817 , A61K47/6835 , A61K47/6849 , A61K47/6855 , A61K47/6869 , A61K47/6879 , A61K51/1027 , A61K51/103 , A61K51/1042 , A61K51/1051 , A61K51/1072 , A61K2039/505 , A61K2039/572 , A61P35/00 , A61P35/02 , A61P35/04 , C07K16/28 , C07K16/2803 , C07K16/2809 , C07K16/2863 , C07K16/32 , C07K16/46 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/33 , C07K2317/52 , C07K2317/524 , C07K2317/526 , C07K2317/53 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/71 , C07K2317/73 , C07K2317/75 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C07K2317/94 , C07K2319/00 , C40B40/02 , C40B40/08
摘要： Bispecific antigen-binding constructs e.g., antibodies conjugated to drugs (ADCs), which bind CD3 and other cell-surface target antigen such as tumor antigens e.g., CD19, CDH3, HER2, HER3 and EGFR antigens and methods of use are disclosed.

2. 发明申请

US20160297891A1 METHODS USING MONOVALENT ANTIGEN BINDING CONSTRUCTS TARGETING HER2 审中-公开
标题翻译：使用单一抗原结合方法来对付HER2
公开(公告)号：US20160297891A1
公开(公告)日：2016-10-13
申请号：US15036175
申请日：2014-11-13
申请人： Zymeworks Inc.
发明人： Gordon Yiu Kon Ng , Nina E. Weisser , Grant Raymond Wickman
IPC分类号： C07K16/32 , A61K39/395 , C07K16/30
CPC分类号： C07K16/32 , A61K39/39558 , A61K47/6855 , A61K2039/505 , A61K2039/507 , C07K16/30 , C07K16/3069 , C07K2317/24 , C07K2317/30 , C07K2317/52 , C07K2317/524 , C07K2317/526 , C07K2317/53 , C07K2317/55 , C07K2317/56 , C07K2317/622 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C07K2317/94
摘要： Provided herein are methods of use and treatment using a first or a first and second monovalent antigen-binding constructs targeting HER2. The monovalent antigen-binding constructs can include at least one antigen-binding polypeptide comprising a heavy chain variable domain, wherein the antigen-bind polypeptide specifically binds HER2; and a heterodimeric Fc, the Fc comprising at least two CH3 sequences, wherein the Fc is coupled, with or without a linker, to the antigen-binding polypeptide.
摘要翻译：本文提供了使用靶向HER2的第一或第一和第一单价抗原结合构建体的使用和治疗方法。一价抗原结合构建体可以包括至少一种包含重链可变结构域的抗原结合多肽，其中所述抗原结合多肽特异性结合HER2; 和异二聚体Fc，所述Fc包含至少两个CH3序列，其中所述Fc与或不具有接头偶联至所述抗原结合多肽。

3. 发明授权

US11325981B2 Bispecific antigen-binding constructs targeting Her2 有权
公开(公告)号：US11325981B2
公开(公告)日：2022-05-10
申请号：US16011048
申请日：2018-06-18
申请人： Zymeworks Inc.
发明人： Nina E. Weisser , Gordon Yiu Kon Ng , Grant Raymond Wickman , Surjit Bhimarao Dixit , Eric Escobar-Cabrera , Mario Sanches
IPC分类号： C07K16/32 , A61K39/395 , A61K47/68 , A61K45/06 , C07K16/30 , G01N33/574 , A61K39/00
摘要： Provided herein are biparatopic antigen-binding constructs that specifically bind HER2. The biparatopic antigen-binding constructs comprise one antigen-binding moiety that binds to ECD2 of HER2, a second antigen-binding moiety that binds to ECD4 of HER2, and an Fc. At least one of the antigen-binding moieties is an scFv. The biparatopic antigen-binding constructs can be used in the treatment of cancer.

4. 发明申请

US20210189001A1 METHODS OF USING BISPECIFIC ANTIGEN-BINDING CONSTRUCTS TARGETING HER2 有权
公开(公告)号：US20210189001A1
公开(公告)日：2021-06-24
申请号：US17033441
申请日：2020-09-25
申请人： Zymeworks Inc.
发明人： Grant Raymond Wickman , Gordon Yiu Kon Ng , Nina E. Weisser
IPC分类号： C07K16/32 , A61K47/68 , A61K39/395 , C07K16/28
摘要： Described herein methods of using antigen-binding constructs to treat HER2+ tumors in a subject such as breast, lung, or head and neck tumors. In some aspects, the tumor volume in the subject after receiving at least seven doses of the antigen binding construct is less than the tumor volume of a control subject receiving an equivalent amount of trastuzumab. In some aspects, the survival of the subject receiving the antigen binding construct is increased as compared to a control subject receiving an equivalent amount of a non-specific control antibody or as compared to a control subject not receiving treatment.

5. 发明授权

US10358479B2 Multivalent heteromultimer scaffold design and constructs 有权
公开(公告)号：US10358479B2
公开(公告)日：2019-07-23
申请号：US15001078
申请日：2016-01-19
申请人： Zymeworks Inc.
发明人： Surjit Bhimarao Dixit , Igor Edmondo Paolo D'Angelo , Mario Sanches , Gordon Yiu Kon Ng
IPC分类号： A61K38/38 , C07K14/76 , C07K1/00 , C07K14/00 , C07K16/00 , C07K17/00 , C07K14/765 , C07K16/28 , C07K14/485 , C07K14/605 , C07K16/40
摘要： Provided herein are multifunctional heteromultimer proteins. In specific embodiments is a heteromultimer comprising: at least two polypeptide constructs, each polypeptide construct comprising at least one cargo polypeptide attached to a transporter polypeptide, said transporter polypeptides derived from a monomeric native protein such that said monomeric constructs associate to form the heteromultimer and said transporter polypeptides associate to form a quasi-native structure of the monomeric native protein or analog thereof. These therapeutically novel molecules encompass heteromultimers comprising constructs that function as scaffolds for the conjugation or fusion of therapeutic molecular entities (cargo polypeptides) resulting in the creation of bispecific or multivalent molecular species. Provided herein is a method for creation of bispecific or multivalent molecular species.

6. 发明申请

US20170355779A1 METHODS OF USING BISPECIFIC ANTIGEN-BINDING CONSTRUCTS TARGETING HER2 审中-公开
公开(公告)号：US20170355779A1
公开(公告)日：2017-12-14
申请号：US15526888
申请日：2015-11-26
申请人： Zymeworks Inc.
发明人： Grant Raymond Wickman , Gordon Yiu Kon Ng , Nina E. Weisser
IPC分类号： C07K16/32 , A61K39/395 , A61K47/68 , C07K16/28
CPC分类号： C07K16/32 , A61K39/395 , A61K47/6803 , A61K47/6855 , A61K47/6869 , A61K47/6879 , A61K2039/505 , C07K16/28 , C07K2317/24 , C07K2317/31 , C07K2317/41 , C07K2317/522 , C07K2317/526 , C07K2317/55 , C07K2317/622 , C07K2317/64 , C07K2317/72 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C07K2317/94
摘要： Described herein methods of using antigen-binding constructs to treat HER2+ tumors in a subject such as breast, lung, or head and neck tumors. In some aspects, the tumor volume in the subject after receiving at least seven doses of the antigen binding construct is less than the tumor volume of a control subject receiving an equivalent amount of trastuzumab. In some aspects, the survival of the subject receiving the antigen binding construct is increased as compared to a control subject receiving an equivalent amount of a non-specific control antibody or as compared to a control subject not receiving treatment.

7. 发明申请

US20160355588A1 Bispecific CD3 and CD19 Antigen Binding Constructs 审中-公开
标题翻译：双特异性CD3和CD19抗原结合构建体
公开(公告)号：US20160355588A1
公开(公告)日：2016-12-08
申请号：US14903184
申请日：2014-07-11
申请人： ZYMEWORKS INC.
发明人： Gordon Yiu Kon Ng , Surjit Bhimarao Dixit , Thomas Spreter von Kreudenstein
IPC分类号： C07K16/28 , C07K16/30 , G01N33/68 , A61K47/48
CPC分类号： C07K16/2809 , A61K47/48561 , A61K47/6849 , A61K2039/505 , C07K16/2803 , C07K16/2887 , C07K16/30 , C07K16/468 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/526 , C07K2317/55 , C07K2317/565 , C07K2317/622 , C07K2317/624 , C07K2317/64 , C07K2317/76 , C07K2317/90 , G01N33/6872 , G01N2333/70503 , G01N2333/7051
摘要： Bispecific antigen binding constructs are described that bind to CD3 and CD19 or CD20 antigens.
摘要翻译：描述了结合CD3和CD19或CD20抗原的双特异性抗原结合构建体。

8. 发明授权

US09499634B2 Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells 有权
标题翻译：在哺乳动物细胞中高效制备高纯度不对称抗体的方法和方法
公开(公告)号：US09499634B2
公开(公告)日：2016-11-22
申请号：US13927065
申请日：2013-06-25
申请人： Zymeworks Inc.
发明人： Surjit Bhimarao Dixit , Gordon Yiu Kon Ng , Thomas Spreter Von Kreudenstein
IPC分类号： C12N5/07 , C07K16/46 , C07K16/32 , C12P21/00
CPC分类号： C07K16/46 , C07K16/32 , C07K2317/14 , C07K2317/41 , C07K2317/52 , C07K2317/526 , C07K2317/64 , C12P21/005
摘要： The present invention provides a process and methods for producing asymmetric antibodies in a mammalian expression system. The asymmetric antibodies are transiently or stably expressed and in cells that stably express the asymmetric antibody, following a rapid 2-step process of stable pool to clone, a highly pure asymmetric antibody expressing clone can be identified at a success frequency that permits for screening of tens of clones rather than thousands. The asymmetric antibodies are produced at a high titre and with a high level of purity with no contaminating homodimer antibodies following protein A purification with a step yield of near 100%. Typical downstream purification processes employ standard hydrophobic interaction chromatography (HIC) and/or cation exchange (CEX) resins and the antibody is stable within a wide dynamic range of buffer pH (4-8) and within the requirements for manufacturing antibodies for pre-clinical and clinical applications.
摘要翻译：本发明提供了在哺乳动物表达系统中产生不对称抗体的方法和方法。不稳定抗体瞬时或稳定地表达，并且在稳定表达不对称抗体的细胞中，在稳定的克隆克隆的快速2步骤过程之后，可以以成功频率鉴定出高纯度的不对称抗体表达克隆，其允许筛选数十个克隆而不是数千个。不对称抗体以高滴度产生，具有高水平的纯度，在蛋白A纯化后没有污染的同二聚体抗体，步骤收率接近100％。典型的下游纯化方法采用标准疏水相互作用层析（HIC）和/或阳离子交换（CEX）树脂，并且抗体在宽动态范围的缓冲液pH（4-8）内稳定，并且在制备用于临床前的抗体的要求内和临床应用。

9. 发明申请

US20230118302A1 BISPECIFIC ANTIGEN BINDING CONSTRUCTS TARGETING HER2 有权
公开(公告)号：US20230118302A1
公开(公告)日：2023-04-20
申请号：US17728491
申请日：2022-04-25
申请人： Zymeworks Inc.
发明人： Nina E. Weisser , Gordon Yiu Kon Ng , Grant Raymond Wickman , Surjit Bhimarao Dixit , Eric Escobar-Cabrera , Mario Sanches
IPC分类号： C07K16/32 , A61K47/68 , A61K39/395 , A61K45/06 , C07K16/30 , G01N33/574
摘要： Provided herein are biparatopic antigen-binding constructs that specifically bind HER2. The biparatopic antigen-binding constructs comprise one antigen-binding moiety that binds to ECD2 of HER2, a second antigen-binding moiety that binds to ECD4 of HER2, and an Fc. At least one of the antigen-binding moieties is an scFv. The biparatopic antigen-binding constructs can be used in the treatment of cancer.

10. 发明申请

US20210317212A1 Bispecific Asymmetric Heterodimers Comprising Anti-CD3 Constructs 有权
公开(公告)号：US20210317212A1
公开(公告)日：2021-10-14
申请号：US17207526
申请日：2021-03-19
申请人： ZYMEWORKS INC.
发明人： Gordon Yiu Kon Ng , Surjit Bhimarao Dixit , Thomas Spreter von Kreudenstein , Nina E. Weisser
IPC分类号： C07K16/28 , C07K16/32
摘要： Disclosed herein are isolated multi-specific heteromultimer constructs that bind to CD3 expressed on T-cells and to an antigen expressed on B-cells. The multi-specific heteromultimer constructs are capable of bridging T- and B-cells and mediating killing of B-cells. The multi-specific heteromultimer constructs are based on a heterodimeric Fc scaffold or on a segmented albumin scaffold. Also disclosed herein are multi-specific heteromultimer constructs that bind to HER2 and HER3.

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