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1. 发明申请

US20080057063A1 Antibodies Directed to AlphaVBeta6 and Uses Thereof 审中-公开
标题翻译：针对AlphaVBeta6的抗体及其用途
公开(公告)号：US20080057063A1
公开(公告)日：2008-03-06
申请号：US11833486
申请日：2007-08-03
申请人： Julie Rinkenberger , Ian Foltz , Avril Alfred , Simon Barry , Vahe Bedian
发明人： Julie Rinkenberger , Ian Foltz , Avril Alfred , Simon Barry , Vahe Bedian
IPC分类号： A61K39/395 , A61P43/00 , C07K16/18 , C12N15/00 , C12N15/11 , C12N5/06 , C12P21/04
CPC分类号： C07K16/2839 , A61K2039/505 , C07K2317/21 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , C12N5/0686 , C12N2501/998
摘要： Targeted binding agents, such antibodies directed to the antigen αVβ6 and uses of such agents are described. In particular, fully human monoclonal antibodies directed to the antigen αVβ6 are disclosed. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3 are disclosed. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also disclosed.
摘要翻译：描述了靶向结合剂，针对抗原αVβ6的这种抗体及其用途。特别地，公开了针对抗原αVβ6的完全人单克隆抗体。编码的核苷酸序列和包含重链和轻链免疫球蛋白分子的氨基酸序列，特别是对应于跨越框架区和/或互补决定区（CDR）的连续重链和轻链序列的序列，特别是从FR1至FR4或CDR1至CDR3 被披露。还公开了表达这种免疫球蛋白分子和单克隆抗体的杂交瘤或其它细胞系。

2. 发明授权

US08398975B2 Antibodies directed to αVβ6 and uses thereof 有权
标题翻译：针对αV和bgr的抗体6及其用途
公开(公告)号：US08398975B2
公开(公告)日：2013-03-19
申请号：US12782335
申请日：2010-05-18
申请人： Julie Rinkenberger , Ian Foltz , Avril Alfred , Simon Thomas Barry , Vahe Bedian
发明人： Julie Rinkenberger , Ian Foltz , Avril Alfred , Simon Thomas Barry , Vahe Bedian
IPC分类号： A61K39/395 , C07K16/00 , C07K16/46 , C07K16/28
CPC分类号： C07K16/2839 , A61K2039/505 , C07K2317/21 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , C12N5/0686 , C12N2501/998
摘要： Targeted binding agents, such antibodies directed to the antigen αVβ6 and uses of such agents are described. In particular, fully human monoclonal antibodies directed to the antigen αVβ6 are disclosed. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3 are disclosed. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also disclosed.
摘要翻译：描述了靶向结合剂，针对抗原αV和bgr的这种抗体以及这些药剂的用途。特别地，公开了针对抗原αV和bgr的完全人单克隆抗体。编码的核苷酸序列和包含重链和轻链免疫球蛋白分子的氨基酸序列，特别是对应于跨越框架区和/或互补决定区（CDR）的连续重链和轻链序列的序列，特别是从FR1至FR4或CDR1至CDR3 被披露。还公开了表达这种免疫球蛋白分子和单克隆抗体的杂交瘤或其它细胞系。

3. 发明申请

US20100240100A1 HUMAN ANTIBODIES THAT HAVE MN BINDING AND CELL ADHESION-NEUTRALIZING ACTIVITY 审中-公开
标题翻译：具有MN结合和细胞粘附中和活性的人抗体
公开(公告)号：US20100240100A1
公开(公告)日：2010-09-23
申请号：US12330504
申请日：2008-12-08
申请人： Toshihiko Takeuchi , Nathalie Dubois-Stringfellow , John E. Murphy , Julie Rinkenberger
发明人： Toshihiko Takeuchi , Nathalie Dubois-Stringfellow , John E. Murphy , Julie Rinkenberger
IPC分类号： C12P21/00 , C07H21/04 , C12N15/74 , C12N5/10
CPC分类号： C07K16/3038 , A61K2039/505 , C07K16/18 , C07K2317/565 , C07K2317/732
摘要： The invention is composed of monoclonal human MN antibodies or MN antibody fragments that target the GEEDLP repeat within the proteoglycan domain. The proteoglycan domain of the MN cell surface protein contains four of these identical GEEDLP repeats. Binding to the desired epitope is verified by competition ELISA, where ELISA signal can be attenuated by co-incubation with a peptide containing this repeat (PGEEDLPGEEDLP). This inhibition of binding can also be verified using Biacore assays, where binding of desired antibodies to immobilized MN or proteoglycan peptides can be inhibited by the peptide repeat. In addition to binding to the peptide repeat, human anti-MN antibodies can inhibit the cell adhesion of CGL-1 cells to MN coated plastic plates. Human anti-MN antibodies have been used to diagnose and quantify MN expression in cancer cells and tumors using FACS and immunohistochemical methods. An example is also provided where a human anti-MN IgG1 mediates tumor cell lysis though antibody-dependent cell-mediated cytotoxicity. Therefore, these antibodies will be useful for the treatment of cancers in which MN is upregulated or can be useful for the diagnosis of cancers in which MN is upregulated.
摘要翻译：本发明由针对蛋白多糖结构域内的GEEDLP重复的单克隆人MN抗体或MN抗体片段组成。 MN细胞表面蛋白的蛋白多糖结构域包含四个这些相同的GEEDLP重复序列。通过竞争ELISA验证与所需表位的结合，其中ELISA信号可以通过与含有该重复的肽（PGEEDLPGEEDLP）共孵育来减毒。还可以使用Biacore分析验证这种结合抑制，其中所需抗体与固定化的MN或蛋白聚糖肽的结合可被肽重复抑制。除了结合肽重复之外，人抗MN抗体可以抑制CGL-1细胞对MN涂覆的塑料板的细胞粘附。已经使用人抗MN抗体来诊断和定量癌细胞和肿瘤中的MN表达，使用FACS和免疫组织化学方法。还提供了一种实例，其中人抗MN IgG1通过抗体依赖性细胞介导的细胞毒性介导肿瘤细胞裂解。因此，这些抗体可用于治疗其中MN被上调的癌症或可用于诊断MN被上调的癌症。

4. 发明授权

US07462696B2 Human antibodies that have MN binding and cell adhesion-neutralizing activity 有权
标题翻译：具有MN结合和细胞粘附中和活性的人抗体
公开(公告)号：US07462696B2
公开(公告)日：2008-12-09
申请号：US10273541
申请日：2002-10-18
申请人： Toshihiko Takeuchi , Nathalie Dubois-Stringfellow , John E. Murphy , Julie Rinkenberger
发明人： Toshihiko Takeuchi , Nathalie Dubois-Stringfellow , John E. Murphy , Julie Rinkenberger
IPC分类号： C07K16/46 , C07K16/24
CPC分类号： C07K16/3038 , A61K2039/505 , C07K16/18 , C07K2317/565 , C07K2317/732
摘要： The invention is composed of monoclonal human MN antibodies or MN antibody fragments that target the GEEDLP (SEQ ID NO: 118) repeat within the proteoglycan domain. The proteoglycan domain of the MN cell surface protein contains four of these identical GEEDLP (SEQ ID NO: 118) repeats. Binding to the desired epitope is verified by competition ELISA, where ELISA signal can be attenuated by co-incubation with a peptide containing this repeat (PGEEDLPGEEDLP (SEQ ID NO: 119)). This inhibition of binding can also be verified using Biacore assays, where binding of desired antibodies to immobilized MN or proteoglycan peptides can be inhibited by the peptide repeat. In addition to binding to the peptide repeat, human anti-MN antibodies can inhibit the cell adhesion of CGL-1 cells to MN coated plastic plates. Human anti-MN antibodies have been used to diagnose and quantify MN expression in cancer cells and tumors using FACS and immunohistochemical methods. An example is also provided where a human anti-MN IgG1 mediates tumor cell lysis though antibody-dependent cell-mediated cytotoxicity. Therefore, these antibodies will be useful for the treatment of cancers in which MN is upregulated or can be useful for the diagnosis of cancers in which MN is upregulated.
摘要翻译：本发明由针对蛋白多糖结构域内的GEEDLP（SEQ ID NO：118）重复的单克隆人MN抗体或MN抗体片段组成。 MN细胞表面蛋白的蛋白聚糖结构域包含四个这些相同的GEEDLP（SEQ ID NO：118）重复序列。通过竞争ELISA验证与所需表位的结合，其中ELISA信号可以通过与含有该重复的肽（PGEEDLPGEEDLP（SEQ ID NO：119））共孵育来减毒。还可以使用Biacore分析验证这种结合抑制，其中所需抗体与固定化的MN或蛋白聚糖肽的结合可被肽重复抑制。除了结合肽重复之外，人抗MN抗体可以抑制CGL-1细胞对MN涂覆的塑料板的细胞粘附。已经使用人抗MN抗体来诊断和定量癌细胞和肿瘤中的MN表达，使用FACS和免疫组织化学方法。还提供了一种实例，其中人抗MN IgG1通过抗体依赖性细胞介导的细胞毒性介导肿瘤细胞裂解。因此，这些抗体可用于治疗其中MN被上调的癌症或可用于诊断MN被上调的癌症。

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