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    • 6. 发明申请
      US20090023226A1 Variant Integrin Polypeptides and Uses Thereof 有权
    • Variant Integrin Polypeptides and Uses Thereof
    • 变体整合素多肽及其用途
    • US20090023226A1
    • 2009-01-22
    • US12021074
    • 2008-01-28
    • M. Amin Arnaout , Rui Li , Jian-Ping Xiong
    • M. Amin Arnaout , Rui Li , Jian-Ping Xiong
    • G01N33/566 , C07K16/18
    • C07K14/70553 , A61K38/00 , C07K14/70546 , C07K16/2845
    • Polypeptides comprising all or part of a variant integrin α subunit A domain and its flanking region are described. In solution or in membrane-associated form, the A domain polypeptides of the invention exists predominantly in a high affinity conformation. In the polypeptides of the invention, referred to as variant integrin polypeptides, a crucial isoleucine or glutamic acid residue is altered. For example, the glutamic acid can be either deleted or replaced with different amino acids residue, e.g., glutamine, aspartic acid, or alanine The variant integrin polypeptides of the invention selectively impair binding of activation-dependent ligands, but not independent ligands. They are useful in screening assays for the identification of molecules that enhance binding of variant polypeptides with impaired binding. In addition, they are useful in distinguishing between activation-dependent ligands and activation-independent ligands. They are also useful for generating antibodies, e.g., monoclonal antibodies, which bind to the impaired form of an integrin. Some such antibodies recognize an epitope that is either not present or not accessible on an integrin that is in the high affinity conformation. The variant integrin polypeptides of the invention can be derived from any integrin α subunit that could be used therapeutically.
    • 描述了包含全部或部分变体整联蛋白α亚基A结构域及其侧翼区的多肽。 在溶液或膜相关形式中，本发明的A结构域多肽主要存在于高亲和力构象中。 在本发明的多肽中，称为变体整联蛋白多肽，关键的异亮氨酸或谷氨酸残基被改变。 例如，谷氨酸可被删除或被不同氨基酸残基替代，例如谷氨酰胺，天冬氨酸或丙氨酸。本发明的变体整联蛋白多肽选择性地损害活化依赖性配体但不是独立配体的结合。 它们可用于鉴定增强变异多肽与受损结合的结合的分子的筛选分析。 此外，它们可用于区分活化依赖性配体和与激活无关的配体。 它们也可用于产生结合受损形式的整联蛋白的抗体，例如单克隆抗体。 一些这样的抗体识别在高亲和力构象的整联蛋白上不存在或不可接近的表位。 本发明的变体整联蛋白多肽可以衍生自可以在治疗上使用的任何整联蛋白α亚基。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
    • 7. 发明授权
      US07323552B2 Variant integrin polypeptides and uses thereof 失效
    • Variant integrin polypeptides and uses thereof
    • 变体整联蛋白多肽及其用途
    • US07323552B2
    • 2008-01-29
    • US10144259
    • 2002-05-10
    • M. Amin Arnaout , Rui Li , Jian-Ping Xiong
    • M. Amin Arnaout , Rui Li , Jian-Ping Xiong
    • C07K1/107 , A61K38/04 , G01N33/53
    • C07K14/70553 , A61K38/00 , C07K14/70546 , C07K16/2845
    • Polypeptides comprising all or part of a variant integrin α subunit A domain and its flanking region are described. In solution or in membrane-associated form, the A domain polypeptides of the invention exists predominantly in a high affinity conformation. In the polypeptides of the invention, referred to as variant integrin polypeptides, a crucial isoleucine or glutamic acid residue is altered. For example, the glutamic acid can be either deleted or replaced with different amino acids residue, e.g., glutamine, aspartic acid, or alanine The variant integrin polypeptides of the invention selectively impair binding of activation-dependent ligands, but not independent ligands. They are useful in screening assays for the identification of molecules that enhance binding of variant polypeptides with impaired binding. In addition, they are useful in distinguishing between activation-dependent ligands and activation-independent ligands. They are also useful for generating antibodies, e.g., monoclonal antibodies, which bind to the impaired form of an integrin. Some such antibodies recognize an epitope that is either not present or not accessible on an integrin that is in the high affinity conformation. The variant integrin polypeptides of the invention can be derived from any integrin α subunit that could be used therapeutically.
    • 描述了包含全部或部分变体整联蛋白α亚基A结构域及其侧翼区的多肽。 在溶液或膜相关形式中，本发明的A结构域多肽主要存在于高亲和力构象中。 在本发明的多肽中，称为变体整联蛋白多肽，关键的异亮氨酸或谷氨酸残基被改变。 例如，谷氨酸可被删除或被不同氨基酸残基替代，例如谷氨酰胺，天冬氨酸或丙氨酸。本发明的变体整联蛋白多肽选择性地损害活化依赖性配体但不是独立配体的结合。 它们可用于鉴定增强变异多肽与受损结合的结合的分子的筛选分析。 此外，它们可用于区分活化依赖性配体和与激活无关的配体。 它们也可用于产生结合受损形式的整联蛋白的抗体，例如单克隆抗体。 一些这样的抗体识别在高亲和力构象的整联蛋白上不存在或不可接近的表位。 本发明的变体整联蛋白多肽可以衍生自可以在治疗上使用的任何整联蛋白α亚基。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Espacenet 法律信息 同族专利 专利引用
    • 10. 发明授权
      US07064180B2 High affinity integrin polypeptides and uses thereof 失效
    • High affinity integrin polypeptides and uses thereof
    • US07064180B2
    • 2006-06-20
    • US09758493
    • 2001-01-11
    • M. Amin Arnaout , Rui Li , Jian-Ping Xiong
    • M. Amin Arnaout , Rui Li , Jian-Ping Xiong
    • A61K38/04
    • C07K14/70553 , A61K38/00 , C07K16/2845
    • Polypeptides comprising all or part of a variant integrin α subunit A domain or a variant integrin β subunit A-like domain are described. In solution or in membrane-associated form, the A domain or the A-like domain of the polypeptides of the invention exists predominantly in a high affinity conformation. In the polypeptides of the invention, referred to as variant integrin polypeptides, a crucial isoleucine residue (described in greater detail below) is absent. The isoleucine can be either deleted or replaced with different amino acids residue, preferably a smaller or less hydrophobic amino acid residue, e.g., alanine or glycine. Because the variant integrin polypeptides of the invention exist in solution or in membrane-associated form predominantly in a high affinity conformation, they are useful in screening assays for the identification of molecules that bind to (and/or mediate the activity of) an integrin. They are also useful for generating antibodies, e.g., monoclonal antibodies, which bind to the high affinity form of an integrin. Some such antibodies recognize an epitope that is either not present or not accessible on an integrin that is in a lower affinity conformation. The variant integrin polypeptides of the invention can be derived from any integrin α subunit or any integrin β subunit and could be used therapeutically. The variant integrin polypeptides preferably include a ligand-binding portion of an A-domain or an A-like domain.
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Espacenet 法律信息 同族专利 专利引用
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