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公开(公告)号：US10517958B2
公开(公告)日：2019-12-31
申请号：US15724763
申请日：2017-10-04
发明人： John Babcook , James R. Rich , Mads Daugaard , Ali El-Salanti
摘要： VAR2CSA-drug conjugates for targeting and inhibiting the growth of cancer cells that have developed resistance to a platinum drug and the use of the conjugates in the treatment of platinum drug-resistant cancers. VAR2CSA-drug conjugates (VDCs) comprise a VAR2CSA polypeptide that is capable of binding to oncofetal chondroitin sulfate (ofCS) and one or more toxins having anti-cancer activity conjugated to the VAR2CSA polypeptide, either directly or via a linker.
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公开(公告)号：US09522876B2
公开(公告)日：2016-12-20
申请号：US14213504
申请日：2014-03-14
申请人： ZYMEWORKS INC.
发明人： Geoffrey C. Winters , Alexander L. Mandel , Bradley J. Hedberg , John Babcook , James R. Rich , Tom Han Hsiao Hsieh , Elyse Marie Josée Bourque
IPC分类号： C07C311/51 , C07C323/67 , C07C381/08 , C07C327/06 , C07C323/12 , C07D207/452 , C07D211/34 , C07D207/08 , C07D333/34 , C07D213/56 , C07D211/60 , C07D213/71 , C07K5/027 , C07K5/065 , A61K38/05 , A61K38/06 , A61K31/445 , A61K39/395 , A61K47/48 , C07K5/02 , C07C317/28 , C07C317/32 , C07C317/50
CPC分类号： C07C311/51 , A61K31/445 , A61K38/05 , A61K38/06 , A61K39/3955 , A61K47/48261 , A61K47/48415 , A61K47/6415 , C07C317/28 , C07C317/32 , C07C317/50 , C07C323/12 , C07C323/67 , C07C327/06 , C07C381/08 , C07C2101/02 , C07C2101/08 , C07C2101/14 , C07C2601/02 , C07C2601/08 , C07C2601/14 , C07D207/08 , C07D207/452 , C07D211/34 , C07D211/60 , C07D213/56 , C07D213/71 , C07D333/34 , C07K5/0205 , C07K5/06078 , Y02A50/385 , Y02A50/414 , Y02A50/423
摘要： Compounds having cytotoxic and/or anti-mitotic activity are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein R1, R2, R3, R4 and R5 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having structure (I).
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公开(公告)号：US10414822B2
公开(公告)日：2019-09-17
申请号：US15872642
申请日：2018-01-16
申请人： ZYMEWORKS INC.
发明人： Geoffrey C. Winters , James R. Rich , Graham Albert Edwin Garnett , Alexander Laurence Mandel , Tom Han Hsiao Hsieh , Elyse Marie Josée Bourque , Stuart Daniel Barnscher
IPC分类号： C07K16/30 , C07K16/32 , C07K16/28 , C07K5/02 , A61K38/00 , A61K38/06 , A61K47/54 , A61K47/68
摘要： Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.
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公开(公告)号：US11000598B2
公开(公告)日：2021-05-11
申请号：US16594728
申请日：2019-10-07
申请人： Zymeworks Inc.
发明人： Kevin Hamblett , Rupert H. Davies , James R. Rich , Gerald J. Rowse , Vincent K. C. Fung , Stuart D. Barnscher
摘要： Anti-HER2 biparatopic antibody-drug conjugates (ADCs) in which the drug is an auristatin analogue and is conjugated to the antibody at a low average drug-to-antibody ratio (DAR), and methods of using the ADCs in the treatment of a HER2-expressing cancer. The low average DAR (
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公开(公告)号：US10675355B2
公开(公告)日：2020-06-09
申请号：US15108258
申请日：2014-12-29
发明人： James R. Rich , John Babcook , Ali El-Salanti , Mads Daugaard , Madeleine Dahlback , Bradley J. Hedberg , Geoffrey C. Winters , Alexander L. Mandel , Elyse Marie Josée Bourque , Tom Han Hsiao Hsieh
IPC分类号： A61K47/64 , C07K14/445 , A61K38/05 , A61K47/54
摘要： VAR2CSA-drug conjugates having biological activity are disclosed. Methods associated with preparation and use of such conjugates, as well as pharmaceutical compositions comprising such conjugates, are also disclosed.
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公开(公告)号：US10450378B2
公开(公告)日：2019-10-22
申请号：US15512030
申请日：2015-09-17
申请人： ZYMEWORKS INC.
发明人： Geoffrey C. Winters , James R. Rich , Graham Albert Edwin Garnett , Alexander Laurence Mandel , Tom Han Hsiao Hsieh , Elyse Marie Josee Bourque , Stuart Daniel Barnscher
IPC分类号： C07K16/30 , C07K16/32 , C07K5/02 , A61K38/00 , A61K38/06 , A61K47/54 , C07K16/28 , A61K47/68
摘要： Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.
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公开(公告)号：US10201614B2
公开(公告)日：2019-02-12
申请号：US14776654
申请日：2014-03-14
申请人： ZYMEWORKS INC.
发明人： Geoffrey C. Winters , Alexander Laurence Mandel , James R. Rich , Bradley John Hedberg , Tom Han Hsiao Hsieh , Elyse Marie Josée Bourque , John Babcook
IPC分类号： C07D211/60 , C07D211/34 , C07D213/56 , C07D213/71 , C07D333/34 , A61K38/06 , A61K31/445 , A61K38/05 , C07C311/51 , C07C323/12 , C07C323/67 , A61K47/48 , A61K39/395 , C07C327/06 , C07C381/08 , C07D207/08 , C07D207/452 , C07K5/02
摘要： Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.
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公开(公告)号：US11560422B2
公开(公告)日：2023-01-24
申请号：US15108247
申请日：2014-12-29
申请人： ZYMEWORKS INC.
发明人： Geoffrey C. Winters , Alexander L. Mandel , Elyse Marie Josée Bourque , James R. Rich , Tom Han Hsiao Hsieh
摘要： Sulfonamide-containing linkage systems for release of payload compounds from an attached targeting moiety in drug conjugates. The conjugates have the formula of [(P)-(L)]m-(T), wherein (P) is a payload compound, (L) is a linker, (T) is a targeting moiety and m is an integer from 1- to 10. Also provided are pharmaceutical compositions comprising such conjugates and there use in treating cancer.
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公开(公告)号：US11208497B2
公开(公告)日：2021-12-28
申请号：US15107884
申请日：2014-12-23
申请人： ZYMEWORKS INC.
摘要： The present disclosure provides light chain polypeptides that include a C-terminal extension, as well as antibodies and antibody conjugates containing such modified light chain polypeptides, where the C-terminal extension includes one or more cysteine residues. Conjugates that include an antibody of the present disclosure conjugated to an agent via the cysteine residue of the C-terminal amino acid extension are also provided. The present disclosure further provides nucleic acids encoding an antibody light chain polypeptide that includes a C-terminal amino acid extension including a cysteine residue. Pharmaceutical compositions including the antibodies or conjugates of the present disclosure are also provided, as are methods of making and use of the modified anti-bodies and conjugates of the present disclosure.
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公开(公告)号：US20210346508A1
公开(公告)日：2021-11-11
申请号：US17210081
申请日：2021-03-23
申请人： Zymeworks Inc.
发明人： Kevin Hamblett , Rupert H. Davies , James R. Rich , Gerald J. Rowse , Vincent K.C. Fung , Stuart D. Barnscher
摘要： Anti-HER2 biparatopic antibody-drug conjugates (ADCs) in which the drug is an auristatin analogue and is conjugated to the antibody at a low average drug-to-antibody ratio (DAR), and methods of using the ADCs in the treatment of a HER2-expressing cancer. The low average DAR (
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