公开(公告)号：US08492343B2

公开(公告)日：2013-07-23

申请号：US13058810

申请日：2009-08-07

申请人： Yong-Sung Kim ,  Myung-Hee Kwon ,  Chang-Han Lee

发明人： Yong-Sung Kim ,  Myung-Hee Kwon ,  Chang-Han Lee

IPC分类号： A61K38/00 ,  A61P35/00 ,  C12Q1/68 ,  C12N15/74 ,  C12N1/20

CPC分类号： C12N15/1044 ,  C40B40/10

摘要： There are provided a Kringle domain structure, comprising: inducing artificial mutations at amino acid residues except for conserved amino acid residues that are important to maintain the structural scaffold of a Kringle domain; and protein scaffold variants, based on the Kringle domain structure, which modulate the biological activities of a variety of target molecules derived from the protein scaffold library by specifically binding to the target molecules. Also, there is provided a method for constructing homo-/hetero-oligomers which allow multi-specificity binding to multiple targets by the tandem assembly monomeric Kringle domain variants using a linker. Additionally, there is provided a method for preparing multispecific monomers and multivalent monomers by grafting target-binding loops of a Kringle domain variant into non-binding loops of another Kringle domain variant with the same or different target binding specificity. Furthermore, a protein scaffold variant based on the Kringle domain structure that specifically binds to target molecules, DNA encoding the protein scaffold variant, or a method and composition for prevention, detection, diagnosis, treatment or relieving diseases or disorders, particularly cancers and other immune-related diseases, comprising: administering an effective amount of the related molecule to animals, preferably human.

摘要翻译： 提供了一种Kringle结构域结构，其包括：除了保持Kringle结构域的结构支架重要的保守氨基酸残基之外，在氨基酸残基处诱导人工突变; 和蛋白质支架变体，其基于Kringle结构域结构，其通过特异性结合靶分子来调节衍生自蛋白质支架文库的各种靶分子的生物学活性。 此外，提供了一种构建同 - 异寡聚物的方法，其允许使用接头通过串联组装单体Kringle结构域变体多特异性结合多个靶标。 另外，提供了通过将Kringle结构域变体的靶结合环转移到具有相同或不同靶结合特异性的另一个Kringle结构域变体的非结合环中来制备多特异性单体和多价单体的方法。 此外，基于特异性结合靶分子的Kringle结构域结构的蛋白质支架变体，编码蛋白质支架变体的DNA，或用于预防，检测，诊断，治疗或缓解疾病或病症，特别是癌症和其他免疫的方法和组合物 相关疾病，包括：向动物，优选人类施用有效量的相关分子。

公开(公告)号：US20120021993A1

公开(公告)日：2012-01-26

申请号：US13058810

申请日：2009-08-07

申请人： Yong-Sung Kim ,  Myung-Hee Kwon ,  Chang-Han Lee

发明人： Yong-Sung Kim ,  Myung-Hee Kwon ,  Chang-Han Lee

IPC分类号： A61K38/17 ,  C40B40/10 ,  A61P35/00 ,  C07K14/47 ,  C07K1/107 ,  A61P37/06 ,  C40B50/06 ,  C40B30/04

CPC分类号： C12N15/1044 ,  C40B40/10

摘要： There are provided a Kringle domain structure, comprising: inducing artificial mutations at amino acid residues except for conserved amino acid residues that are important to maintain the structural scaffold of a Kringle domain; and protein scaffold variants, based on the Kringle domain structure, which modulate the biological activities of a variety of target molecules derived from the protein scaffold library by specifically binding to the target molecules. Also, there is provided a method for constructing homo-/hetero-oligomers which allow multi-specificity binding to multiple targets by the tandem assembly monomeric Kringle domain variants using a linker. Additionally, there is provided a method for preparing multispecific monomers and multivalent monomers by grafting target-binding loops of a Kringle domain variant into non-binding loops of another Kringle domain variant with the same or different target binding specificity. Furthermore, a protein scaffold variant based on the Kringle domain structure that specifically binds to target molecules, DNA encoding the protein scaffold variant, or a method and composition for prevention, detection, diagnosis, treatment or relieving diseases or disorders, particularly cancers and other immune-related diseases, comprising: administering an effective amount of the related molecule to animals, preferably human.

摘要翻译： 提供了一种Kringle结构域结构，其包括：除了保持Kringle结构域的结构支架重要的保守氨基酸残基之外，在氨基酸残基处诱导人工突变; 和蛋白质支架变体，其基于Kringle结构域结构，其通过特异性结合靶分子来调节衍生自蛋白质支架文库的各种靶分子的生物学活性。 此外，提供了一种构建同 - 异寡聚物的方法，其允许使用接头通过串联组装单体Kringle结构域变体多特异性结合多个靶标。 另外，提供了通过将Kringle结构域变体的靶结合环转移到具有相同或不同靶结合特异性的另一个Kringle结构域变体的非结合环中来制备多特异性单体和多价单体的方法。 此外，基于特异性结合靶分子的Kringle结构域结构的蛋白质支架变体，编码蛋白质支架变体的DNA，或用于预防，检测，诊断，治疗或缓解疾病或病症，特别是癌症和其他免疫的方法和组合物 相关疾病，包括：向动物，优选人类施用有效量的相关分子。