公开(公告)号：US12084510B2

公开(公告)日：2024-09-10

申请号：US16797364

申请日：2020-02-21

申请人： GILEAD SCIENCES, INC. ,  NATIONAL RESEARCH COUNCIL OF CANADA

发明人： Ilia Alexandre Tikhomirov ,  Maria L. Jaramillo ,  Maureen D. O'Connor-McCourt ,  Traian Sulea ,  Renald Gilbert ,  Bruno Gaillet ,  Jason Baardsnes ,  Myriam Banville ,  Suzanne Grothe

IPC分类号： C07K16/30 ,  C07K16/28

CPC分类号： C07K16/30 ,  C07K16/2863 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567

摘要： Herein described are antibodies to epidermal growth factor receptor (EGER) having an EGER binding affinity that is sufficient to kill disease cells presenting EGFR at high density, but is insufficient for binding to normal cells. A therapeutic effect is thus achieved while avoiding adverse events that result from unintended binding to normal cells.

公开(公告)号：US20190194349A1

公开(公告)日：2019-06-27

申请号：US16237363

申请日：2018-12-31

申请人： National Research Council of Canada

发明人： Ilia Alexandre Tikhomirov ,  Maria L. Jaramillo ,  Maureen D. O'Connor-McCourt ,  Traian Sulea ,  Renald Gilbert ,  Bruno Gaillet ,  Jason Baardsnes ,  Myriam Banville

IPC分类号： C07K16/32

CPC分类号： C07K16/32 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/92

摘要： An erbB2 antibody is provided that binds preferentially to disease cells having an erbB2 density greater than a normal erbB2 density. The erbB2 antibody comprises a heavy chain and a light chain. Each chain has a constant region and a variable region. Each variable region comprises framework regions and complementarity determining regions (CDRs), wherein the CDRs have an amino acid sequence set forth below: For the heavy chain: CDR1 GFNIKDTYIH (SEQ ID No. 1) CDR2 RIYPTNGY57TR59YADSVKG (SEQ ID No. 2) CDR3 WGGDGFYAMDY (SEQ ID No. 3). For the light chain: CDR1 RASQDVN30TAVA (SEQ ID No. 4) CDR2 SASF53LYS (SEQ ID No. 5) CDR3 QQHY92TTPPT (SEQ ID NO. 6). At least one of Y57, R59, N30, F53, and Y92 is substituted by an amino acid that confers on said antibody a reduced erbB2 binding affinity (Kd) that is in the range from 0.1 nM to 100 nM. The substitution is other than N30A, F53N, Y92A and Y92F when there is a single substitution in the antibody light chain.

公开(公告)号：US20130266564A1

公开(公告)日：2013-10-10

申请号：US13992051

申请日：2011-12-02

申请人： National Research Council of Canada ,  YM Biosciences Inc.

发明人： Maria L. Jaramillo ,  Maureen D. O'Connor-McCourt ,  Traian Sulea ,  Ronald Gilbert ,  Bruno Gaillet ,  Jason Baardsnes ,  Myriam Banville ,  Ilia Tikhomirov

IPC分类号： C07K16/32

CPC分类号： C07K16/32 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/92

摘要： An erbB2 antibody is provided that binds preferentially to disease cells having an erbB2 density greater than a normal erbB2 density. The erbB2 antibody comprises a heavy chain and a light chain. Each chain has a constant region and a variable region. Each variable region comprises framework regions and complementarity determining regions (CDRs), wherein the CDRs have an amino acid sequence set forth below: For the heavy chain: CDR1 GFNIKDTYIH (SEQ ID No. 1) CDR2 RIYPTNGY57TR59 YADSVKG (SEQ ID No. 2) CDR3 WGGDGFYAMDY (SEQ ID No. 3) For the light chain: CDR1 RASQDVN30TAVA (SEQ ID No. 4) CDR2 SASF53LYS (SEQ ID No. 5) CDR3 QQHY92TTPPT (SEQ ID No. 6). At least one of Y57, R59, N30, F53, and Y92 is substituted by an amino acid that confers on said antibody a reduced erbB2 binding affinity (Kd) that is in the range from 0.1 nM to 100 nM. The substitution is other than N30A, F53N, Y92A and Y92F when there is a single substitution in the antibody light chain.

摘要翻译： 提供了erbB2抗体优先结合具有大于正常erbB2密度的erbB2密度的疾病细胞。 erbB2抗体包含重链和轻链。 每个链具有恒定区和可变区。 每个可变区包括框架区和互补决定区（CDR），其中CDR具​​有如下所示的氨基酸序列：对于重链：CDR1 GFNIKDTYIH（SEQ ID No.1）CDR2 RIYPTNGY57TR59 YADSVKG（SEQ ID No.2） CDR3 WGGDGFYAMDY（SEQ ID No.3）对于轻链：CDR1 RASQDVN30TAVA（SEQ ID No.4）CDR2SASF53LYS（SEQ ID No.5）CDR3 QQHY92TTPPT（SEQ ID No.6）。 Y57，R59，N30，F53和Y92中的至少一个被赋予所述抗体的氨基酸取代在0.1nM至100nM范围内的降低的erbB2结合亲和力（Kd）。 当抗体轻链中存在单一取代时，取代不是N30A，F53N，Y92A和Y92F。