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1. 发明申请

WO2009134027A3 ANTI-NUCLEIC ACID ANTIBODY INDUCING CELL DEATH OF CANCER CELLS AND COMPOSITION FOR PREVENTING OR TREATING CANCERS COMPRISING THE SAME 审中-公开
标题翻译：抗核酸抗体诱导癌细胞细胞死亡和组合物，用于预防或治疗包括其的癌症
公开(公告)号：WO2009134027A3
公开(公告)日：2010-01-21
申请号：PCT/KR2009001973
申请日：2009-04-16
申请人： AJOU UNIV IND ACAD COOP FOUND , KWON MYUNG-HEE , KIM YONG-SUNG , JANG JI-YOUNG
发明人： KWON MYUNG-HEE , KIM YONG-SUNG , JANG JI-YOUNG
IPC分类号： A61K39/395 , A61K36/48 , C12N9/12 , C12P21/04
CPC分类号： C07K16/44 , A61K2039/505 , C07K16/30 , C07K2317/622 , C07K2317/73 , C07K2317/77 , C07K2317/82 , C12N9/0002 , C12N9/22
摘要： There are provided an anti-nucleic acid antibody inducing cell death of cancer cells by invading normal cells; and a composition for preventing or treating cancers comprising the anti-nucleic acid antibody, which shows anticancer effect of an anti-nucleic acid antibody that shows cytotoxicity by damaging nucleic acid strands, that is, genetic information of a cancer cell when the anti-nucleic acid antibody, which has binding activity and degrading activity to the nucleic acid strands in cells at the same time, is overexpressed in the cancer cell, or flows in the cancer cell. Therefore, the composition for treating cancers may be useful to induce the selective cell death in cancer cells than in normal cells since the anti-nucleic acid antibody very easily permeates into the cancer cells due to the excellent selectivity, compared to the normal cells.
摘要翻译：提供通过侵入正常细胞诱导癌细胞的细胞死亡的抗核酸抗体; 以及用于预防或治疗包含抗核酸抗体的癌症的组合物，其显示通过损伤核酸链显示细胞毒性的抗核酸抗体的抗癌作用，即抗核酸抗体的抗核酸抗体，即抗核酸抗体的遗传信息同时对细胞中的核酸链具有结合活性和降解活性的酸抗体在癌细胞中过表达，或在癌细胞中流动。因此，与正常细胞相比，用于治疗癌症的组合物可以用于诱导癌细胞中的选择性细胞死亡，因为与正常细胞相比，抗核酸抗体由于优异的选择性而非常容易地渗入癌细胞。

2. 发明申请

WO2010056043A3 CELL-PENETRATING, SEQUENCE-SPECIFIC AND NUCLEIC ACID-HYDROLYZING ANTIBODY, METHOD FOR PREPARING THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME 审中-公开
标题翻译：细胞穿刺，序列特异性和核酸抗氢化抗体，其制备方法和包含其的药物组合物
公开(公告)号：WO2010056043A3
公开(公告)日：2010-10-07
申请号：PCT/KR2009006628
申请日：2009-11-11
申请人： AJOU UNIV IND ACAD COOP FOUND , KIM YONG SUNG , KWON MYUNG HEE , LEE WOO RAM
发明人： KIM YONG SUNG , KWON MYUNG HEE , LEE WOO RAM
IPC分类号： C07K16/00 , C07K16/28
CPC分类号： C07K16/44 , C07K16/32 , C07K2317/34 , C07K2317/569 , C07K2317/73 , C07K2317/77 , C07K2317/82 , C07K2317/92 , C12N9/0002
摘要： Disclosed are a cell-penetrating, base sequence-specific, nucleic acid-hydrolyzing antibody, a method of preparing the same, and a pharmaceutical composition comprising the same. The antibody can be prepared by modifying a particular site of a cell-penetrating, nucleic acid-hydrolyzing antibody which lacks substrate specificity to impart sequence specificity thereto without alteration in nucleic acid-hydrolyzing ability. The antibody, when penetrating into cells by itself or ectopically expressed within cells, binds specifically to single- or double-stranded nucleic acid targets and hydrolyzes them, thus downregulating the expression of the targeted genes.
摘要翻译：披露了细胞穿透性，碱基序列特异性核酸水解抗体，其制备方法和包含其的药物组合物。抗体可以通过修饰缺乏底物特异性的细胞穿透性核酸水解抗体的特定位点来赋予其序列特异性而不改变核酸水解能力来制备。当抗体本身穿透细胞或在细胞内外表达时，该抗体特异性结合于单链或双链核酸靶，并将其水解，从而下调靶基因的表达。

3. 发明申请

WO2010047509A9 ANTI-DR5 ANTIBODY WITH IMPROVED AFFINITY AND STABILITY, AND COMPOSITION FOR CANCER PREVENTION OR TREATMENT INCLUDING SAME 审中-公开
标题翻译：具有改善的亲和力和稳定性的抗DR5抗体，以及用于癌症预防或治疗的组合物，包括相同的
公开(公告)号：WO2010047509A9
公开(公告)日：2010-09-02
申请号：PCT/KR2009006036
申请日：2009-10-20
申请人： AJOU UNIV IND ACAD COOP FOUND , KIM YONG SUNG , KWON MYUNG HEE , LEE SEUNG HYUN , PARK KYUNG JIN
发明人： KIM YONG SUNG , KWON MYUNG HEE , LEE SEUNG HYUN , PARK KYUNG JIN
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00 , C12N15/13
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/56 , C07K2317/565
摘要： The present invention relates to an anti-DR5 antibody with improved affinity and stability that specifically binds to the death receptor 5 (DR5) to destroy cancer cells effectively and the composition for cancer prevention or treatment including the same. The anti-DR5 antibody of the present invention causes mutageneses on the amino acid residues of VH-CDR2 and VH-CDR3 within the heavy chain variable region and the amino acid residue of VL-CDR3 within the light chain variable region of HW1 which is the known anti-DR5 antibody, and replaces the framework within the heavy chain variable region from a VH6 subtype to a VH3 subtype and replaces the framework within the light chain variable region with the framework part of Vk1 or Vk3 so that affinity and stability are improved over the known anti-DR5 antibody, HW1. In addition, the anti-DR5 antibody of the present invention effectively induces cell death with respect to TRAIL-sensitive cancer cells that express DR5 and TRAIL-resistant cancer cells that express DR5 by autophagy so that it may be usefully employed in preventing or treating cancers caused by DR5 expression.
摘要翻译：本发明涉及特异性结合死亡受体5（DR5）以有效破坏癌细胞的具有改善的亲和力和稳定性的抗DR5抗体，并且涉及用于癌症预防或治疗的组合物以及包含其的组合物。本发明的抗DR5抗体对重链可变区内的VH-CDR2和VH-CDR3的氨基酸残基和HW1的轻链可变区内的VL -CDR3的氨基酸残基进行诱变，并将重链可变区内的框架从VH6亚型替换为VH3亚型并用Vk1或Vk3的框架部分置换轻链可变区内的框架，从而改善了亲和性和稳定性已知的抗DR5抗体HW1。此外，本发明的抗DR5抗体相对于表达DR5和TRAIL抗性癌细胞的TRAIL敏感性癌细胞，通过自噬来有效地诱导细胞死亡，从而其可有效用于预防或治疗癌症由DR5表达引起。

4. 发明申请

WO2010056043A2 CELL-PENETRATING, SEQUENCE-SPECIFIC AND NUCLEIC ACID-HYDROLYZING ANTIBODY, METHOD FOR PREPARING THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME 审中-公开
标题翻译：细胞穿透，序列特异性和核酸水解抗体，其制备方法和包含该组合物的药物组合物
公开(公告)号：WO2010056043A2
公开(公告)日：2010-05-20
申请号：PCT/KR2009006628
申请日：2009-11-11
申请人： AJOU UNIV IND ACAD COOP FOUND , KIM YONG SUNG , KWON MYUNG HEE , LEE WOO RAM
发明人： KIM YONG SUNG , KWON MYUNG HEE , LEE WOO RAM
IPC分类号： C07K16/00 , C07K16/28
CPC分类号： C07K16/44 , C07K16/32 , C07K2317/34 , C07K2317/569 , C07K2317/73 , C07K2317/77 , C07K2317/82 , C07K2317/92 , C12N9/0002
摘要： Disclosed are a cell-penetrating, base sequence-specific, nucleic acid-hydrolyzing antibody, a method of preparing the same, and a pharmaceutical composition comprising the same. The antibody can be prepared by modifying a particular site of a cell-penetrating, nucleic acid-hydrolyzing antibody which lacks substrate specificity to impart sequence specificity thereto without alteration in nucleic acid-hydrolyzing ability. The antibody, when penetrating into cells by itself or ectopically expressed within cells, binds specifically to single- or double-stranded nucleic acid targets and hydrolyzes them, thus downregulating the expression of the targeted genes.
摘要翻译：公开了细胞穿透性碱基序列特异性核酸水解抗体，其制备方法以及包含其的药物组合物。抗体可以通过修饰缺乏底物特异性的细胞穿透性核酸水解抗体的特定位点来制备，以赋予其序列特异性而不改变核酸水解能力。当单独穿透细胞或在细胞内异位表达时，抗体特异性结合单链或双链核酸靶标并将其水解，从而下调靶基因的表达。

5. 发明申请

WO2010018950A2 PROTEIN SCAFFOLD LIBRARY BASED ON KRINGLE DOMAIN STRUCTURE AND USES THEREOF 审中-公开
标题翻译：基于结构域的蛋白质SCAFFOLD图书及其用途
公开(公告)号：WO2010018950A2
公开(公告)日：2010-02-18
申请号：PCT/KR2009/004423
申请日：2009-08-07
申请人： AJOU UNIVERSITY INDUSTRY-ACADEMIC COOPERATION FOUNDATION , KIM, Yong-Sung , KWON, Myung-Hee , LEE, Chang-Han
发明人： KIM, Yong-Sung , KWON, Myung-Hee , LEE, Chang-Han
IPC分类号： C40B40/10
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 of 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; 和基于Kringle结构域结构的蛋白质支架变体，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，提供了一种用于构建同 - 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，特别是癌症等的方法和组合物免疫相关疾病，包括：将有效量的相关分子施用于动物，优选人。

6. 发明申请

WO2010018950A3 PROTEIN SCAFFOLD LIBRARY BASED ON KRINGLE DOMAIN STRUCTURE AND USES THEREOF 审中-公开
标题翻译：基于KRINGLE域结构的蛋白质支架库及其应用
公开(公告)号：WO2010018950A3
公开(公告)日：2010-06-03
申请号：PCT/KR2009004423
申请日：2009-08-07
申请人： AJOU UNIV IND ACAD COOP FOUND , KIM YONG-SUNG , KWON MYUNG-HEE , LEE CHANG-HAN
发明人： KIM YONG-SUNG , KWON MYUNG-HEE , LEE CHANG-HAN
IPC分类号： C40B40/10
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 of 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Kringle结构域结构，其包括：在保留Kringle结构域的结构支架很重要的保守氨基酸残基之外的氨基酸残基处诱导人工突变; 以及基于Kringle域结构的蛋白质支架变体，其通过特异性结合靶分子来调节源自蛋白质支架文库的多种靶分子的生物活性。此外，提供了一种构建同型/异型寡聚体的方法，其允许使用接头通过串联组装单体Kringle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移植到具有相同或不同靶标结合特异性的另一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骨架变体，编码蛋白质骨架变体的DNA或用于预防，检测，诊断，治疗或缓解疾病或病症，特别是癌症和其他疾病的方法和组合物包括：将有效量的相关分子给予动物，优选人类。

7. 发明申请

WO2009134027A2 ANTI-NUCLEIC ACID ANTIBODY INDUCING CELL DEATH OF CANCER CELLS AND COMPOSITION FOR PREVENTING OR TREATING CANCERS COMPRISING THE SAME 审中-公开
标题翻译：抗核酸抗体诱导癌细胞细胞死亡和组合物，用于预防或治疗包括其的癌症
公开(公告)号：WO2009134027A2
公开(公告)日：2009-11-05
申请号：PCT/KR2009/001973
申请日：2009-04-16
申请人： AJOU UNIVERSITY INDUSTRY-ACADEMIC COOPERATION FOUNDATION , KWON, Myung-Hee , KIM, Yong-Sung , JANG, Ji-Young
发明人： KWON, Myung-Hee , KIM, Yong-Sung , JANG, Ji-Young
IPC分类号： A61K39/395
CPC分类号： C07K16/44 , A61K2039/505 , C07K16/30 , C07K2317/622 , C07K2317/73 , C07K2317/77 , C07K2317/82 , C12N9/0002 , C12N9/22
摘要： There are provided an anti-nucleic acid antibody inducing cell death of cancer cells by invading normal cells; and a composition for preventing or treating cancers comprising the anti-nucleic acid antibody, which shows anticancer effect of an anti-nucleic acid antibody that shows cytotoxicity by damaging nucleic acid strands, that is, genetic information of a cancer cell when the anti-nucleic acid antibody, which has binding activity and degrading activity to the nucleic acid strands in cells at the same time, is overexpressed in the cancer cell, or flows in the cancer cell. Therefore, the composition for treating cancers may be useful to induce the selective cell death in cancer cells than in normal cells since the anti-nucleic acid antibody very easily permeates into the cancer cells due to the excellent selectivity, compared to the normal cells.
摘要翻译：提供通过侵入正常细胞诱导癌细胞的细胞死亡的抗核酸抗体; 以及用于预防或治疗包含抗核酸抗体的癌症的组合物，其显示通过损伤核酸链显示细胞毒性的抗核酸抗体的抗癌作用，即抗核酸抗体的抗核酸抗体，即抗核酸抗体的遗传信息同时对细胞中的核酸链具有结合活性和降解活性的酸抗体在癌细胞中过表达，或在癌细胞中流动。因此，与正常细胞相比，用于治疗癌症的组合物可以用于诱导癌细胞中的选择性细胞死亡，因为与正常细胞相比，抗核酸抗体由于优异的选择性而非常容易地渗入癌细胞。

8. 发明申请

WO2008004760A1 ANTIBODY SPECIFICALLY BINDING TO DR5 AND COMPOSITION FOR PREVENTING OR TREATING CANCERS COMPRISING THE SAME 审中-公开
标题翻译：抗体特异性结合DR5及其组合物，用于预防或治疗包括其的癌症
公开(公告)号：WO2008004760A1
公开(公告)日：2008-01-10
申请号：PCT/KR2007/002644
申请日：2007-05-31
申请人： AJOU UNIVERSITY INDUSTRY-ACADEMIC COOPERATION FOUNDATION , KYONGGI PROVINCIAL GOVERNOR , KIM, Yong Sung , KWON, Myung Hee , LEE, Seung Hyun , PARK, Kyung Jin , LEE, Hae Won
发明人： KIM, Yong Sung , KWON, Myung Hee , LEE, Seung Hyun , PARK, Kyung Jin , LEE, Hae Won
IPC分类号： C07K16/28 , A61K39/00 , A61P35/00
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/73 , C07K2317/92
摘要： The present invention provides an antibody specifically binding to death receptor 5 (DR5), which is selected from the group consisting of: an antibody comprising a heavy chain variable region (V H ) having the amino acid sequences of SEQ ID NOs: 1 to 3 at complementary determining regions (CDRs) and a light chain variable region (V L ) having the amino acid sequences of SEQ ID NOs: 4 to 6 at CDRs; and an antibody comprising a (V H ) having the amino acid sequences of SEQ ID NOs: 7 to 9 at CDRs and a (V L ) having the amino acid sequences of SEQ ID NOs: 10 to 12 at CDRs, and a composition for preventing or treating a cancer comprising the same. The antibody of the present invention can be effectively used for the prevention or treatment of various cancers, through inducing autophagic cell death of TRAIL-sensitive cancer cells as well as TRAIL-resistant cancer cells by specific binding to DR5.
摘要翻译：本发明提供了与死亡受体5（DR5）特异性结合的抗体，其选自：包含具有氨基酸序列的重链可变区（V H H H）的抗体， SEQ ID NO：1至3在互补决定区（CDR）和轻链可变区（V L L L），其CDR具有SEQ ID NO：4至6的氨基酸序列; 以及包含在CDR中具有SEQ ID NO：7至9的氨基酸序列的（V H H H）的抗体和具有氨基酸序列的（V L L L） CDR中的SEQ ID NO：10至12，以及用于预防或治疗包含该癌症的癌症的组合物。通过特异性结合DR5，本发明的抗体可以通过诱导TRAIL敏感性癌细胞的自噬细胞死亡以及抗TRAIL抗性癌细胞来有效地用于预防或治疗各种癌症。

9. 发明申请

WO2010056043A9 CELL-PENETRATING, SEQUENCE-SPECIFIC AND NUCLEIC ACID-HYDROLYZING ANTIBODY, METHOD FOR PREPARING THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME 审中-公开
公开(公告)号：WO2010056043A9
公开(公告)日：2010-05-20
申请号：PCT/KR2009/006628
申请日：2009-11-11
申请人： AJOU UNIVERSITY INDUSTRY-ACADEMIC COOPERATION FOUNDATION , KIM, Yong Sung , KWON, Myung Hee , LEE, Woo Ram
发明人： KIM, Yong Sung , KWON, Myung Hee , LEE, Woo Ram
IPC分类号： C07K16/00 , C07K16/28
摘要： Disclosed are a cell-penetrating, base sequence-specific, nucleic acid-hydrolyzing antibody, a method of preparing the same, and a pharmaceutical composition comprising the same. The antibody can be prepared by modifying a particular site of a cell-penetrating, nucleic acid-hydrolyzing antibody which lacks substrate specificity to impart sequence specificity thereto without alteration in nucleic acid-hydrolyzing ability. The antibody, when penetrating into cells by itself or ectopically expressed within cells, binds specifically to single- or double-stranded nucleic acid targets and hydrolyzes them, thus downregulating the expression of the targeted genes.

10. 发明申请

WO2010047509A3 ANTI-DR5 ANTIBODY WITH IMPROVED AFFINITY AND STABILITY, AND COMPOSITION FOR CANCER PREVENTION OR TREATMENT INCLUDING SAME 审中-公开
公开(公告)号：WO2010047509A3
公开(公告)日：2010-10-21
申请号：PCT/KR2009006036
申请日：2009-10-20
申请人： AJOU UNIV IND ACAD COOP FOUND , KIM YONG SUNG , KWON MYUNG HEE , LEE SEUNG HYUN , PARK KYUNG JIN
发明人： KIM YONG SUNG , KWON MYUNG HEE , LEE SEUNG HYUN , PARK KYUNG JIN
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00 , C12N15/13
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/56 , C07K2317/565
摘要： The present invention relates to an anti-DR5 antibody with improved affinity and stability that specifically binds to the death receptor 5 (DR5) to destroy cancer cells effectively and the composition for cancer prevention or treatment including the same. The anti-DR5 antibody of the present invention causes mutageneses on the amino acid residues of VH-CDR2 and VH-CDR3 within the heavy chain variable region and the amino acid residue of VL-CDR3 within the light chain variable region of HW1 which is the known anti-DR5 antibody, and replaces the framework within the heavy chain variable region from a VH6 subtype to a VH3 subtype and replaces the framework within the light chain variable region with the framework part of Vk1 or Vk3 so that affinity and stability are improved over the known anti-DR5 antibody, HW1. In addition, the anti-DR5 antibody of the present invention effectively induces cell death with respect to TRAIL-sensitive cancer cells that express DR5 and TRAIL-resistant cancer cells that express DR5 by autophagy so that it may be usefully employed in preventing or treating cancers caused by DR5 expression.

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