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公开(公告)号：US20210353777A1
公开(公告)日：2021-11-18
申请号：US17373950
申请日：2021-07-13
发明人： Robert Yongxin ZHAO , Qingliang YANG , Yuanyuan HUANG , Shun GAI , Linyao ZHAO , Hangbo YE , Huihui GUO , Qianqian TONG , Minjun CAO , Junxiang JIA , Chengyu YANG , Wenjun LI , Xiaomai ZHOU , Hongsheng XIE , Chen LIN , Zhixiang GUO , Zhicang YE
IPC分类号： A61K49/00 , A61K47/68 , C07D417/12 , C07D417/14 , C07D498/18 , C07D513/22 , C07D519/00
摘要： The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.
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公开(公告)号：US20220378951A1
公开(公告)日：2022-12-01
申请号：US17355286
申请日：2021-06-23
发明人： Robert Yongxin ZHAO , Qingliang YANG , Yuanyuan HUANG , Shun GAI , Linyao ZHAO , Hangbo YE , Huihui GUO , Qianqian TONG , Minjun CAO , Junxiang JIA , Chengyu YANG , Wenjun LI , Xiaomai ZHOU , Hongsheng XIE , Chen LIN , Zhixiang GUO , Zhicang YE
IPC分类号： A61K49/00 , A61K47/68 , C07D417/12 , C07D417/14 , C07D498/18 , C07D513/22 , C07D519/00
摘要： The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.
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公开(公告)号：US20210052747A1
公开(公告)日：2021-02-25
申请号：US17093184
申请日：2020-11-09
发明人： Robert Yongxin ZHAO , Qingliang YANG , Yuanyuan HUANG , Shun GAI , Linyao ZHAO , Hangbo YE , Huihui GUO , Qianqian TONG , Minjun CAO , Junxiang JIA , Chengyu YANG , Wenjun LI , Xiaomai ZHOU , Hongsheng XIE , Chen LIN , Zhixiang GUO , Zhicang YE
IPC分类号： A61K49/00 , A61K47/68 , C07D417/12 , C07D417/14 , C07D498/18 , C07D513/22 , C07D519/00
摘要： The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)-or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.
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公开(公告)号：US20210346523A1
公开(公告)日：2021-11-11
申请号：US17373987
申请日：2021-07-13
发明人： Robert Yongxin ZHAO , Qingliang YANG , Yuanyuan HUANG , Shun GAI , Linyao ZHAO , Hangbo YE , Huihui GUO , Qianqian TONG , Minjun CAO , Junxiang JIA , Chengyu YANG , Wenjun LI , Xiaomai ZHOU , Hongsheng XIE , Chen LIN , Zhixiang GUO , Zhicang YE
IPC分类号： A61K49/00 , A61K47/68 , C07D417/12 , C07D417/14 , C07D498/18 , C07D513/22 , C07D519/00
摘要： The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.
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公开(公告)号：US20230115871A1
公开(公告)日：2023-04-13
申请号：US17622360
申请日：2019-06-24
发明人： Robert Yongxin ZHAO , Qingliang YANG , Linyao ZHAO , Yuanyuan HUANG , Hangbo YE , Shun GAI , Junxiang JIA , Lu BAI , Wenjun LI , Zhixiang GUO , Chen LIN , Jun ZHENG , Huihui GUO , Minjun CAO , Xiangfei KONG , Yong DU , Yifang XU , Xiaomai ZHOU , Hongsheng XIE , Xiuzhen ZHANG , Miaomiao CHEN , Xiaolei LIU , Xiang CAI , Binbin CHEN , Yanlei YANG , Lingli ZHANG
IPC分类号： A61K47/68
摘要： The present invention relates to the conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.
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公开(公告)号：US20230057350A1
公开(公告)日：2023-02-23
申请号：US17426813
申请日：2019-01-31
发明人： Robert Yongxin ZHAO , Qingliang YANG , Jun LEI , Yuanyuan HUANG , Linyao ZHAO , Hangbo YE , Shun GAI , Mingjun CAO , Qianqian TONG , Lu BAI , Zhixiang GUO , Chengyu YANG , Xiaomai ZHOU , Hongsheng XIE , Yifang XU , Huihui GUO , Junxiang JIA , Jun ZHENG , Cheng LIN , Xiaotao ZHUO , Wenjun LI , Yong DU , Xiangfei KONG , Binbin CHEN , Yanlei YANG , Yanhong TONG , Xiaoxiao CHEN , Yanhua LI , Xiuzheng ZHANG , Juan LAI
摘要： Provided herein is the conjugation of an amanita toxin compound to a cell-binding molecule with branched linkers for having better targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of an amanita molecule to a cell-binding ligand, as well as methods of using the conjugate in targets treatment of cancer, infection and autoimmune disease.
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公开(公告)号：US20220313836A1
公开(公告)日：2022-10-06
申请号：US17835081
申请日：2022-06-08
发明人： Yongxin Robert ZHAO , Qingliang YANG , Yuanyuan HUANG , Shun GAI , Hangbo YE , Linyao ZHAO , Chengyu YANG , Huihui GUO , Xiaomai ZHOU , Hongsheng XIE , Haifeng ZHU , Yifang XU , Qianqian TONG , Junxiang JIA , Minjun CAO , Wenjun LI , Shuihong GAO , Zhixiang GUO , Lu BAI , Chen LI , Yanlei YANG , Chunyan WANG , Zhichang YE
IPC分类号： A61K47/68
摘要： The present invention relates to linkers having a group of propiolyl, substituted acryl (acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.
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公开(公告)号：US20210169896A1
公开(公告)日：2021-06-10
申请号：US17256034
申请日：2018-07-05
发明人： Robert Yongxin ZHAO , Xiaotao ZHUO , Qingliang YANG , Linyao ZHAO , Yuanyuan HUANG , Hangbo YE , Chengyu YANG , Jun LEI , Shun GAI , Huihui GUO , Junxiang JIA , Lu BAI , Hongsheng XIE , Xiaomai ZHOU , Zhixiang GUO , Wenjun LI , Mingjun CAO , Jun ZHENG , Zhicang YE , Yanlei YANG
IPC分类号： A61K31/5517 , C07D519/00 , A61K45/06 , A61K47/55 , A61K47/68 , A61K47/54 , A61P35/00
摘要： The present invention relates to novel cross-linked cytotoxic agents, pyrrolobenzodiazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.
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公开(公告)号：US20200276261A1
公开(公告)日：2020-09-03
申请号：US16759175
申请日：2017-12-31
发明人： Robert Yongxin ZHAO , Qingliang YANG , Yuanyuan HUANG , Linyao ZHAO , Shun GAI , Hangbo YE , Jun LEI , Yifang XU , Mingjun CAO , Huihui GUO , Junxiang JIA , Qianqian TONG , Wenjun LI , Xiaomai ZHOU , Hongsheng XIE , Lu BAI , Xiang CAI , Xiaotao ZHUO , Xiuzheng ZHANG , Jun ZHENG
摘要： The present invention relates to the conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.
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公开(公告)号：US20230010108A1
公开(公告)日：2023-01-12
申请号：US17284091
申请日：2018-10-12
发明人： Robert Yongxin ZHAO , Qingliang YANG , Yuanyuan HUANG , Linyao ZHAO , Hangbo YE , Xiaotao ZHUO , Chengyu YANG , Jun LEI , Yifang XU , Huihui GUO , Wenjun LI , Shun GAI , Lu BAI , Zhixiang GUO , Junxiang JIA , Jun ZHENG , Xiaomai ZHOU , Hongsheng XIE , Qianqian TONG , Mingjun CHAO , Yanhong TONG , Zhicang YE , Chen LIN , Yanlei YANG , Binbin CHEN
IPC分类号： C07D403/12 , C07D417/12 , C07D413/14 , C07D417/14 , C07D403/14 , C07D498/22 , C07D498/12 , A61K47/54 , A61K45/06 , A61K47/68
摘要： The present invention relates to a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (a dual-linker) containing a 2,3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.
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