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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.

4. 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.

5. 发明授权

US10947319B2 Bispecific antigen-binding constructs targeting HER2 有权
公开(公告)号：US10947319B2
公开(公告)日：2021-03-16
申请号：US15036176
申请日：2014-11-27
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.

6. 发明申请

US20150125449A1 Single-Arm Monovalent Antibody Constructs and Uses Thereof 审中-公开
标题翻译：单臂单价抗体构建体及其用途
公开(公告)号：US20150125449A1
公开(公告)日：2015-05-07
申请号：US14399789
申请日：2013-05-08
申请人： Zymeworks Inc.
发明人： Gordon Yiu Kon Ng , Surjit Bhimarao Dixit , Thomas Spreter Von Kreudenstein
IPC分类号： C07K16/30 , A61K47/48 , A61K39/395
CPC分类号： C07K16/32 , A61K39/39558 , A61K47/6803 , A61K47/6855 , A61K2039/505 , C07K16/3015 , C07K2317/35 , C07K2317/41 , C07K2317/51 , C07K2317/515 , C07K2317/52 , C07K2317/526 , C07K2317/55 , C07K2317/622 , C07K2317/64 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C07K2317/94 , C12P21/02
摘要： Provided herein are monovalent antibody constructs. In specific embodiments is a monovalent antibody construct comprising: an antigen-binding polypeptide construct which monovalently binds an antigen; and a dimeric Fc polypeptide construct comprising a CH3 domain, said construct comprising two monomeric Fc polypeptides, wherein one said monomeric Fc polypeptide is fused to at least one polypeptide from the antigen-binding polypeptide construct. These therapeutically novel molecules encompass monovalent constructs that display an increase in binding density and Bmax (maximum binding at a target to antibody ratio of 1:1) to a target cell displaying said antigen as compared to a corresponding monospecific bivalent antibody construct with two antigen binding regions. Provided herein are methods for creation of monovalent antibody constructs that shows superior effector efficacy as compared to the corresponding bivalent antibody construct at equimolar concentrations. Provided herein are methods for creation of monovalent antibody constructs that unexpectedly inhibit tumor cell growth and can be internalized and show greater efficacy compared to a bivalent antibody construct at equimolar saturating concentrations. Provided are monovalent antibody constructs for the treatment of HER2 expressing diseases.
摘要翻译：本文提供单价抗体构建体。在具体实施方案中是单价抗体构建体，其包含：单价结合抗原的抗原结合多肽构建体; 和包含CH3结构域的二聚Fc多肽构建体，所述构建体包含两个单体Fc多肽，其中一个所述单体Fc多肽与来自抗原结合多肽构建体的至少一种多肽融合。与具有两个抗原结合的相应的单特异性二价抗体构建体相比，这些治疗性新颖的分子包括显示结合密度和Bmax（目标与抗体比1:1的最大结合）与显示所述抗原的靶细胞的增加的单价构建体地区。本文提供了用于产生与等摩尔浓度相对于相应的二价抗体构建体相比优异的效应子功效的单价抗体构建体的方法。本文提供用于产生意想不到地抑制肿瘤细胞生长并且可以内化的单价抗体构建体的方法，并且在等摩尔饱和浓度下与二价抗体构建体相比显示更大的功效。提供用于治疗HER2表达疾病的单价抗体构建体。

7. 发明授权

US11248037B2 Multivalent heteromultimer scaffold design and constructs 有权
公开(公告)号：US11248037B2
公开(公告)日：2022-02-15
申请号：US16417969
申请日：2019-05-21
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： C07K14/765 , C07K16/28 , C07K14/76 , C07K16/00 , 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.

8. 发明申请

US20200297862A1 METHODS OF USING BISPECIFIC ANTIGEN-BINDING CONSTRUCTS TARGETING HER2 审中-公开
公开(公告)号：US20200297862A1
公开(公告)日：2020-09-24
申请号：US16088761
申请日：2017-04-25
申请人： Zymeworks Inc.
发明人： Gordon Yiu Kon Ng
IPC分类号： A61K47/68 , A61K47/65 , A61K39/395 , A61K45/06 , A61P35/00
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.

9. 发明申请

US20190248897A1 Bispecific Asymmetric Heterodimers Comprising Anti-CD3 Constructs 审中-公开
公开(公告)号：US20190248897A1
公开(公告)日：2019-08-15
申请号：US16256824
申请日：2019-01-24
申请人： Zymeworks Inc.
发明人： Gordon Yiu Kon Ng , Surjit Bhimarao Dixit , Thomas Spreter von Kruedenstein , Nina E. Weisser
IPC分类号： C07K16/28 , C07K16/32
CPC分类号： C07K16/2809 , C07K16/2803 , C07K16/2887 , C07K16/32 , C07K2317/31 , C07K2317/35 , C07K2317/52 , C07K2317/524 , C07K2317/526 , C07K2317/528 , C07K2317/622 , C07K2317/64 , C07K2317/71 , C07K2317/72 , C07K2317/73 , C07K2317/732 , C07K2317/74 , C07K2317/92 , C07K2317/94 , C07K2319/31
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.

10. 发明授权

US10273303B2 Monovalent antigen binding constructs targeting EGFR and/or HER2 and uses thereof 有权
公开(公告)号：US10273303B2
公开(公告)日：2019-04-30
申请号：US15036174
申请日：2014-11-13
申请人： Zymeworks Inc.
发明人： Gordon Yiu Kon Ng , Peter Wing Yiu Chan , Grant Raymond Wickman
IPC分类号： A61K39/395 , C07K16/28 , C07K16/32 , A61K47/68 , A61K39/00
摘要： Provided herein are monovalent antigen-binding constructs targeting EGFR and/or 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 EGFR and/or HER2; and a heterodimeric Fc domain, the Fc domain comprising at least two CH3 domains, wherein the Fc domain is coupled, with or without a linker, to the antigen-binding polypeptide. Also provided are methods of making the constructs and methods of using the constructs.

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