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1.发明授权Humanized anti-tag-72 monoclonal antibodies using human subgroup 4 kappa light chains 失效人源化抗标签72单克隆抗体，使用人亚组4 kappa轻链公开(公告)号：US06495137B1
公开(公告)日：2002-12-17
申请号：US08961309
申请日：1997-10-30
申请人： Peter S. Mezes , Ruth A. Richard , Kimberly S. Johnson , Jeffrey Schlom , Syed V. S. Kashmiri , Liming Shu , Eduardo A. Padlan
发明人： Peter S. Mezes , Ruth A. Richard , Kimberly S. Johnson , Jeffrey Schlom , Syed V. S. Kashmiri , Liming Shu , Eduardo A. Padlan
IPC分类号： A61K39395
CPC分类号： C07K16/30 , A61K2039/505 , C07K2317/21 , C07K2317/24 , C07K2317/56 , C07K2317/622 , Y10S530/866 , Y10S530/867
摘要： Novel composite and humanized anti-TAG-72 monoclonal antibodies, antibody fragments, and derivatives thereof using human subgroup IV kappa light chain framework regions.
摘要翻译： 使用人亚组IVκ轻链框架区的新型复合和人源化抗TAG-72单克隆抗体，抗体片段及其衍生物。
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2.发明授权Composite antibodies of humanized human subgroup IV light chain capable of binding to TAG-72 有权能够结合TAG-72的人源化人亚组IV轻链的复合抗体公开(公告)号：US07179899B2
公开(公告)日：2007-02-20
申请号：US10255478
申请日：2002-09-25
申请人： Peter S. Mezes , Ruth A. Richard , Kimberly S. Johnson , Jeffrey Schlom , Syed V. S. Kashmiri , Liming Shu , Eduardo A. Padlan
发明人： Peter S. Mezes , Ruth A. Richard , Kimberly S. Johnson , Jeffrey Schlom , Syed V. S. Kashmiri , Liming Shu , Eduardo A. Padlan
IPC分类号： C07H21/04
CPC分类号： C07K16/30 , A61K2039/505 , C07K2317/21 , C07K2317/24 , C07K2317/56 , C07K2317/622 , Y10S530/866 , Y10S530/867
摘要： Novel composite and humanized anti-TAG-72 monoclonal antibodies, antibody fragments, and derivatives thereof using human subgroup IV kappa light chain framework regions.
摘要翻译： 使用人亚组IVκ轻链框架区的新型复合和人源化抗TAG-72单克隆抗体，抗体片段及其衍生物。
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公开(公告)号：US5892019A
公开(公告)日：1999-04-06
申请号：US299999
申请日：1994-09-01
申请人： Jeffrey Schlom , Syed V. S. Kashmiri , Liming Shu
发明人： Jeffrey Schlom , Syed V. S. Kashmiri , Liming Shu
CPC分类号： C07K16/30 , A61K47/48569 , C07K2317/732 , C07K2319/00
摘要： Construction of a single gene encoding a signal-chain immunoglobulin-like molecule is described. This single-gene approach circumvents inefficiencies inherent in delivering two genes into a mammalian cell and in the assembly of a functional immunoglobulin molecule. It also facilitates ex vivo transfection of cells for gene-therapy protocols. The single-chain protein comprises the heavy- and light-chain variable (V.sub.H and V.sub.L) domains of a monoclonal antibody covalently joined through a short linker peptide, while the carboxyl end of a V domain is linked to the amino terminus of a human constant region such as .gamma.1 Fc, through the hinge region. The single-chain protein assembles into a dimeric molecule of .apprxeq.120 kDa and is secreted into the culture fluid. The single-chain immunoglobulin-like protein shows similar antigen binding affinity to that of chimeric or parental antibody and mediates ADCC. This single-gene construct approach provides a way of generating an immunoglobulin-like molecule which retains the specificity, binding properties, and cytolytic activity of a parental monoclonal antibody, and thus is a useful therapeutic and diagnostic reagent against a range of antigens, such as human carcinomas.
摘要翻译： 描述编码信号链免疫球蛋白样分子的单个基因的构建。 这种单基因方法规避了将两个基因递送到哺乳动物细胞中以及在功能性免疫球蛋白分子的组装中固有的低效率。 它还有助于体外转染细胞用于基因治疗方案。 单链蛋白质包含通过短接头肽共价连接的单克隆抗体的重链和轻链可变（VH和VL）结构域，而V结构域的羧基末端连接到人类常数的氨基末端 区域，如γ1 Fc，通过铰链区。 单链蛋白质组装成约120kDa的二聚体分子，并分泌到培养液中。 单链免疫球蛋白样蛋白显示出与嵌合抗体或亲本抗体相似的抗原结合亲和力并介导ADCC。 该单基因构建方法提供了产生免疫球蛋白样分子的方法，其保留亲本单克隆抗体的特异性，结合特性和溶细胞活性，因此是针对一系列抗原的有用的治疗和诊断试剂，例如 人类癌。
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4.发明授权Methods to determine immunogenicity of humanized anti-tag 72 CC49 antibodies 失效确定人源化抗标签72 CC49抗体免疫原性的方法公开(公告)号：US08535890B2
公开(公告)日：2013-09-17
申请号：US13039171
申请日：2011-03-02
IPC分类号： G01N33/53
CPC分类号： C07K16/30 , A61K51/1045 , A61K2039/505 , C07K2317/24 , C07K2317/55 , C07K2317/622 , C07K2317/92
摘要： The present disclosure provides humanized CC49 monoclonal antibodies that bind TAG-72 with high binding affinity and that are minimally immunogenic. In one embodiment, a humanized CC49 antibody includes a non-conservative amino acid substitution in a light chain complementarity determining region 3 of the CC49 antibody. In a further embodiment, the humanized CC49 antibody includes a non-conservative substitution of a first residue in a light chain complementarity determining region 3 and a substitution of a second residue in a complementarity determining region of the humanized CC49 antibody. In several of the embodiments, methods are disclosed for the use of a humanized CC49 antibody.
摘要翻译： 本公开提供以高结合亲和力结合TAG-72并且是免疫原性最小的人源化CC49单克隆抗体。 在一个实施方案中，人源化CC49抗体包括CC49抗体的轻链互补决定区3中的非保守氨基酸取代。 在另一个实施方案中，人源化CC49抗体包括轻链互补决定区3中的第一残基的非保守取代和人源化CC49抗体的互补决定区的第二残基的取代。 在几个实施方案中，公开了使用人源化CC49抗体的方法。
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公开(公告)号：US07919607B2
公开(公告)日：2011-04-05
申请号：US12474221
申请日：2009-05-28
CPC分类号： C07K16/30 , A61K51/1045 , A61K2039/505 , C07K2317/24 , C07K2317/55 , C07K2317/622 , C07K2317/92
摘要： The present disclosure provides humanized CC49 monoclonal antibodies that bind TAG-72 with high binding affinity and that are minimally immunogenic. In one embodiment, a humanized CC49 antibody includes a non-conservative amino acid substitution in a light chain complementarity determining region 3 of the CC49 antibody. In a further embodiment, the humanized CC49 antibody includes a non-conservative substitution of a first residue in a light chain complementarity determining region 3 and a substitution of a second residue in a complementarity determining region of the humanized CC49 antibody. In several of the embodiments, methods are disclosed for the use of a humanized CC49 antibody in the detection or treatment of a tumor in a subject. Also disclosed is a kit including the humanized CC49 antibody described herein.
摘要翻译： 本公开提供以高结合亲和力结合TAG-72并且是免疫原性最小的人源化CC49单克隆抗体。 在一个实施方案中，人源化CC49抗体包括CC49抗体的轻链互补决定区3中的非保守氨基酸取代。 在另一个实施方案中，人源化CC49抗体包括轻链互补决定区3中的第一残基的非保守取代和人源化CC49抗体的互补决定区的第二残基的取代。 在几个实施方案中，公开了使用人源化CC49抗体检测或治疗受试者的肿瘤的方法。 还公开了包含本文所述的人源化CC49抗体的试剂盒。
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公开(公告)号：US07763719B2
公开(公告)日：2010-07-27
申请号：US11776437
申请日：2007-07-11
IPC分类号： C07H21/04
CPC分类号： A61K49/0002 , A61K38/00 , A61K51/1045 , A61K2039/505 , C07K16/30 , C07K16/3046 , C07K16/4208 , C07K2317/24 , C07K2317/565 , C07K2317/76 , C07K2317/92 , C12N2799/026 , G01N33/5743
摘要： The invention is directed towards mouse-human chimeric variants of CC49 monoclonal antibodies with minimal murine content. A first aspect of the invention provides CDR variants of humanized monoclonal antibody (HuCC49) in which less than all six (three heavy chain and three light chain) Complementarity Determining Regions (CDRs) of CC49 are present. A second aspect of the invention provides SDR variants of humanized monoclonal antibody (HuCC49) in which only Specificity Determining Regions (SDRs) of at least one CDR from CC49 are present. The invention is also directed towards biotechnological methods of making the variants and therapeutic methods of using the variants.
摘要翻译： 本发明针对具有最小鼠含量的CC49单克隆抗体的小鼠 - 人嵌合变体。 本发明的第一方面提供了存在CC49的全部六（三个重链和三个轻链）互补决定区（CDR）的人源化单克隆抗体（HuCC49）的CDR变体。 本发明的第二方面提供了仅存在来自CC49的至少一个CDR的特异性确定区（SDR）的人源化单克隆抗体（HuCC49）的SDR变体。 本发明还涉及制备使用变体的变体和治疗方法的生物技术方法。
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公开(公告)号：US07256004B2
公开(公告)日：2007-08-14
申请号：US10927433
申请日：2004-08-25
IPC分类号： G01N33/53
CPC分类号： A61K49/0002 , A61K38/00 , A61K51/1045 , A61K2039/505 , C07K16/30 , C07K16/3046 , C07K16/4208 , C07K2317/24 , C07K2317/565 , C07K2317/76 , C07K2317/92 , C12N2799/026 , G01N33/5743
摘要： The invention is directed towards mouse-human chimeric variants of CC49 monoclonal antibodies with minimal murine content. A first aspect of the invention provides CDR variants of humanized monoclonal antibody (HuCC49) in which less than all six (three heavy chain and three light chain) Complementarity Determining Regions (CDRs) of CC49 are present. A second aspect of the invention provides SDR variants of humanized monoclonal antibody (HuCC49) in which only Specificity Determining Regions (SDRs) of at least one CDR from CC49 are present. The invention is also directed towards biotechnological methods of making the variants and therapeutic methods of using the variants.
摘要翻译： 本发明针对具有最小鼠含量的CC49单克隆抗体的小鼠 - 人嵌合变体。 本发明的第一方面提供了存在CC49的全部六（三个重链和三个轻链）互补决定区（CDR）的人源化单克隆抗体（HuCC49）的CDR变体。 本发明的第二方面提供了仅存在来自CC49的至少一个CDR的特异性确定区（SDR）的人源化单克隆抗体（HuCC49）的SDR变体。 本发明还涉及制备使用变体的变体和治疗方法的生物技术方法。
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8.发明授权Nucleic acid molecules encoding minimally immunogenic variants of SDR-grafted humanized antibody CC49 有权编码SDR移植的人源化抗体CC49的最低免疫原性变体的核酸分子公开(公告)号：US07915396B2
公开(公告)日：2011-03-29
申请号：US12544978
申请日：2009-08-20
CPC分类号： C07K16/465 , C07K16/30 , C07K2317/565 , C07K2317/567 , C07K2317/92
摘要： Humanized anti-TAG-72 CC49 monoclonal antibodies are disclosed herein. The antibodies include a light chain Complementarity Determining Region (L-CDR)1, a L-CDR2, and a L-CDR3; and a heavy chain Complementarity Determining Region (H-CDR)1, a H-CDR2, and a H-CDR3 from humanized antibody HuCC49V10. The L-CDR1, L-CDR2, L-CDR3 are within a HuCC49V10 light chain framework region that includes the corresponding amino acid from LEN at position 5, 19, 21, and 106 in the light chain. The H-CDR1, H-CDR2, and H-CDR3 are within a heavy chain HuCC49V10 framework comprising a human 21/28′ CL residue at positions 20, 38, 48, 66, 67, 69, and 80 in the heavy chain. These humanized CC49 antibodies retain binding affinity for TAG-72 and have reduced immunogenicity, as compared to a parental HuCC49V10 antibody. Methods are disclosed herein for using these antibodies in the treatment or diagnosis of a tumor, such as a carcinoma, expressing TAG-72.
摘要翻译： 本文公开了人源化抗TAG-72 CC49单克隆抗体。 抗体包括轻链互补决定区（L-CDR）1，L-CDR2和L-CDR3; 和来自人源化抗体HuCC49V10的重链互补决定区（H-CDR）1，H-CDR2和H-CDR3。 L-CDR1，L-CDR2，L-CDR3位于HuCC49V10轻链框架区内，其包含轻链中位置5,19,21和106处的LEN的相应氨基酸。 H-CDR1，H-CDR2和H-CDR3在重链HuCC49V10框架内，包含重链中20,38,48,66,67,69和80位的人21 / 28'CL残基。 与亲本的HuCC49V10抗体相比，这些人源化CC49抗体对TAG-72保留结合亲和力并具有降低的免疫原性。 本文公开了使用这些抗体来治疗或诊断表达TAG-72的肿瘤例如癌症的方法。
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公开(公告)号：US08029788B2
公开(公告)日：2011-10-04
申请号：US12819920
申请日：2010-06-21
IPC分类号： A61K39/395 , A61K39/00
CPC分类号： A61K49/0002 , A61K38/00 , A61K51/1045 , A61K2039/505 , C07K16/30 , C07K16/3046 , C07K16/4208 , C07K2317/24 , C07K2317/565 , C07K2317/76 , C07K2317/92 , C12N2799/026 , G01N33/5743
摘要： The invention is directed towards mouse-human chimeric variants of CC49 monoclonal antibodies with minimal murine content. A first aspect of the invention provides CDR variants of humanized monoclonal antibody (HuCC49) in which less than all six (three heavy chain and three light chain) Complementarity Determining Regions (CDRs) of CC49 are present. A second aspect of the invention provides SDR variants of humanized monoclonal antibody (HuCC49) in which only Specificity Determining Regions (SDRs) of at least one CDR from CC49 are present. The invention is also directed towards biotechnological methods of making the variants and therapeutic methods of using the variants.
摘要翻译： 本发明针对具有最小鼠含量的CC49单克隆抗体的小鼠 - 人嵌合变体。 本发明的第一方面提供了存在CC49的全部六（三个重链和三个轻链）互补决定区（CDR）的人源化单克隆抗体（HuCC49）的CDR变体。 本发明的第二方面提供了仅存在来自CC49的至少一个CDR的特异性确定区（SDR）的人源化单克隆抗体（HuCC49）的SDR变体。 本发明还涉及制备使用变体的变体和治疗方法的生物技术方法。
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10.发明授权Minimally immunogenic variants of SDR-grafted humanized antibody CC49 and their use 失效SDR移植的人源化抗体CC49的最小免疫原性变体及其用途公开(公告)号：US07589181B2
公开(公告)日：2009-09-15
申请号：US10570220
申请日：2004-08-27
IPC分类号： C12P21/08 , C07K16/00 , G01N33/574 , A61K39/395 , C07H21/04
CPC分类号： C07K16/465 , C07K16/30 , C07K2317/565 , C07K2317/567 , C07K2317/92
摘要： Humanized anti-TAG-72 CC49 monoclonal antibodies are disclosed herein. The antibodies include a light chain Complementarity Determining Region (L-CDR)1, a L-CDR2, and a L-CDR3; and a heavy chain Complementarity Determining Region (H-CDR)1, a H-CDR2, and a H-CDR3 from humanized antibody HuCC49V10. The L-CDR1, L-CDR2, L-CDR3 are within a HuCC49V10 light chain framework region that includes the corresponding amino acid from LEN at position 5, 19, 21, and 106 in the light chain. The H-CDR1, H-CDR2, and H-CDR3 are within a heavy chain HuCC49V10 framework comprising a human 21/28′ CL residue at positions 20, 38, 48, 66, 67, 69, and 80 in the heavy chain. These humanized CC49 antibodies retain binding affinity for TAG-72 and have reduced immunogenicity, as compared to a parental HuCC49V10 antibody. Methods are disclosed herein for using these antibodies in the treatment or diagnosis of a tumor, such as a carcinoma, expressing TAG-72.
摘要翻译： 本文公开了人源化抗TAG-72 CC49单克隆抗体。 抗体包括轻链互补决定区（L-CDR）1，L-CDR2和L-CDR3; 和来自人源化抗体HuCC49V10的重链互补决定区（H-CDR）1，H-CDR2和H-CDR3。 L-CDR1，L-CDR2，L-CDR3位于HuCC49V10轻链框架区内，其包含轻链中位置5,19,21和106处的LEN的相应氨基酸。 H-CDR1，H-CDR2和H-CDR3在重链HuCC49V10框架内，包含重链中20,38,48,66,67,69和80位的人21 / 28'CL残基。 与亲本的HuCC49V10抗体相比，这些人源化CC49抗体对TAG-72保留结合亲和力并具有降低的免疫原性。 本文公开了使用这些抗体来治疗或诊断表达TAG-72的肿瘤例如癌症的方法。
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