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1. 发明申请

US20170152512A1 IMPROVED NANOPARTICLE TYPE OLIGONUCLEOTIDE STRUCTURE HAVING HIGH EFFICIENCY AND METHOD FOR PREPARING SAME 审中-公开
公开(公告)号：US20170152512A1
公开(公告)日：2017-06-01
申请号：US14902563
申请日：2014-07-04
申请人： BIONEER CORPORATION
发明人： Han Oh Park , Jeiwook Chae , Pyoung Oh Yoon , Boram Han , Gi-Eun Choi , Youngho Ko , Taewoo Kwon , Jae Don Lee , Sun Gi Kim
IPC分类号： C12N15/113 , A61K31/713
CPC分类号： C12N15/113 , A61K9/127 , A61K9/5123 , A61K31/713 , A61K47/54 , A61K47/6935 , C07H21/00 , C12N15/111 , C12N2310/11 , C12N2310/14 , C12N2310/351 , C12N2310/3515 , C12N2320/32 , C12N2330/30 , Y02A50/473
摘要： The present invention relates to an oligonucleotide structure and a method for preparing the same and, more particularly, to an oligonucleotide structure in which a polymer compound is linked to an oligonucleotide via a covalent bond to improve in vivo stability of the oligonucleotide and cellular delivery efficiency of the oligonucleotide; and to a method for preparing the same. The oligonucleotide structure is improved into a homogenous material, thereby solving the problem in material verification due to polydispersion characteristics occurring when a hydrophilic material linked to the oligonucleotide is a synthetic polymer; the oligonucleotide structure is easy to synthesize compared with the existing process; and the size of a double-stranded oligo RNA structure can be accurately adjusted through the control of the repetition number of a hydrophilic material block, and thus, the gene expression regulation function of the oligonucleotide does not deteriorate through the synthesis of the optimized oligonucleotide structure, and the oligonucleotide can be delivered into cells at even a relatively low-concentration dosage. Therefore, the oligonucleotide structure of the present invention can be useful as a novel type oligonucleotide delivery system as well as a tool for treating cancers, infectious diseases, and the like.

2. 发明申请

US20140371432A1 NOVEL OLIGONUCLEOTIDE CONJUGATES AND USE THEREOF 审中-公开
标题翻译：新型寡核苷酸结合物及其用途
公开(公告)号：US20140371432A1
公开(公告)日：2014-12-18
申请号：US14365621
申请日：2012-12-14
申请人： Bioneer Corporation
发明人： Jeiwook Chae , Boram Han , Han-na Kim , Han Oh Park , Pyoung Oh Yoon , Sun Gi Kim , Kwang-Ju Jung , Taewoo Kwon , Jong Deok Choi , Sam Young Lee , Eun-Jung Jung
IPC分类号： A61K47/42 , C12N15/113 , A61K47/22 , A61K31/713
CPC分类号： A61K47/42 , A61K31/713 , A61K47/549 , A61K47/551 , A61K47/60 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/14 , C12N2310/3513 , C12N2310/3515 , C12N2320/32
摘要： The present invention provides a double-stranded RNA structure, which comprises a polymer compound covalently bonded to a double-helix oligo RNA useful for the treatment of diseases, particularly cancer, in order to enhance the delivery of the double-helix oligo RNA, and further comprises a target-specific ligand bonded thereto, a preparation method thereof, and a technique of delivering the double-helix oligo RNA in a target-specific manner using the RNA structure. A nanoparticle composed of the ligand-bonded double-helix oligo RNA structures can efficiently deliver the double-helix oligo RNA to a target, and thus can exhibit the activity of the double-helix oligo RNA even when the double-helix oligo RNA is administered at a relatively low concentration. Also, it can prevent the non-specific delivery of the double-helix oligo RNA into other organs and cells. Accordingly, the ligand-bonded double-stranded RNA structure can be used for the treatment for various diseases, particularly cancer, and can also be effectively used as a new type of double-helix oligo RNA delivery system. Particularly, the ligand-bonded double-stranded RNA structure can be effectively used for the treatment of diseases, including cancer and infectious diseases. Moreover, the present invention relates to a hybrid conjugate, which comprises a hydrophilic material and hydrophobic material bonded to both ends of an antisense oligonucleotide (ASO) by a covalent bond in order to enhance the in vivo stability of the ASO, a method for preparing the hybrid conjugate, and a nanoparticle composed of the conjugates. The ASO-polymer conjugate according to the invention can increase the in vivo stability of the ASO, making it possible to efficiently deliver the therapeutic ASO into cells. Also, the ASO-polymer conjugate can exhibit the activity of the ASO even when it is administered at a relatively low concentration.
摘要翻译：本发明提供双链RNA结构，其包含与用于治疗疾病，特别是癌症的双螺旋寡聚RNA共价键合的高分子化合物，以增强双螺旋寡聚RNA的递送，以及还包括与其键合的靶特异性配体，其制备方法，以及使用RNA结构以目标特异性方式递送双螺旋寡聚RNA的技术。由配体结合的双螺旋寡聚RNA结构组成的纳米粒子可以有效地将双螺旋寡聚RNA递送至靶，因此即使施用双螺旋寡核苷酸RNA也能显示双螺旋寡聚RNA的活性浓度相对较低。此外，它可以防止双螺旋寡聚RNA非特异性递送到其他器官和细胞中。因此，配体键合的双链RNA结构可以用于各种疾病，特别是癌症的治疗，也可以有效地用作新型双螺旋寡聚RNA递送系统。特别地，配体键合的双链RNA结构可以有效地用于治疗包括癌症和感染性疾病在内的疾病。此外，本发明涉及一种杂合缀合物，其包含通过共价键与反义寡核苷酸（ASO）的两端键合的亲水性材料和疏水性材料，以增强ASO的体内稳定性，制备方法杂交缀合物和由缀合物组成的纳米颗粒。根据本发明的ASO-聚合物缀合物可以增加ASO的体内稳定性，使得可以有效地将治疗性ASO递送到细胞中。此外，即使以相对低的浓度施用，ASO-聚合物缀合物也可以表现出ASO的活性。

3. 发明申请

US20160168573A1 LIVER CANCER RELATED GENES-SPECIFIC siRNA, DOUBLE-STRANDED OLIGO RNA MOLECULES COMPRISING THE siRNA, AND COMPOSITION FOR PREVENTING OR TREATING CANCER COMPRISING THE SAME 审中-公开
标题翻译：肝癌相关基因特异性siRNA，包含siRNA的双链寡聚RNA分子，以及用于预防或治疗包含其的癌症的组合物
公开(公告)号：US20160168573A1
公开(公告)日：2016-06-16
申请号：US14902808
申请日：2014-07-09
申请人： BIONEER CORPORATION , SANOFI-AVENTIS KOREA CO., LTD.
发明人： Jeiwook Chae , Han Oh Park , Pyoung Oh Yoon , Boram Han , Han-na Kim , Sung-II Yun , Jun Hong Park , Youngho Ko , Gi-Eun Choi , Junsoo Jung , Jae Eun Kim
IPC分类号： C12N15/113
CPC分类号： C12N15/1135 , A61K9/0019 , A61K9/51 , A61K31/713 , A61K47/60 , C12N2310/14
摘要： There is provided a liver cancer related specific siRNA and high efficiency double-stranded oligo RNA molecules containing the same. The double-stranded oligo RNA molecules have a structure in which hydrophilic and hydrophobic compounds are conjugated to both ends of the double-stranded oligo RNA molecules by a simple covalent bond or a linker-mediated covalent bond in order to be efficiently delivered into cells and may be converted into nanoparticles in an aqueous solution by hydrophobic interactions of the double-stranded oligo RNA molecules. The siRNA contained in the double-stranded oligo RNA molecules may be liver cancer related genes, particularly Gankyrin or BMI-1 specific siRNA.In addition, the present invention relates to a method of preparing the double-stranded oligo RNA molecules, and a pharmaceutical composition for preventing or treating cancer, particularly, liver cancer, containing the double-stranded oligo RNA molecules.
摘要翻译：提供了与相关肝癌相关的特异性siRNA和高效双链寡聚RNA分子。双链寡RNA分子具有通过简单的共价键或连接体介导的共价键将亲水和疏水化合物与双链寡RNA分子的两端缀合以便有效地递送到细胞中的结构，可以通过双链寡聚RNA分子的疏水相互作用在水溶液中转化成纳米颗粒。双链寡核苷酸分子中含有的siRNA可能是肝癌相关基因，特别是Gankyrin或BMI-1特异性siRNA。此外，本发明涉及制备双链寡聚RNA分子的方法和用于预防或治疗含有双链寡RNA分子的癌症，特别是肝癌的药物组合物。

4. 发明授权

US10030243B2 Nanoparticle type oligonucleotide structure having high efficiency and method for preparing same 有权
公开(公告)号：US10030243B2
公开(公告)日：2018-07-24
申请号：US14902563
申请日：2014-07-04
申请人： BIONEER CORPORATION
发明人： Han Oh Park , Jeiwook Chae , Pyoung Oh Yoon , Boram Han , Gi-Eun Choi , Youngho Ko , Taewoo Kwon , Jae Don Lee , Sun Gi Kim
IPC分类号： C12N15/113 , A61K9/51 , A61K48/00 , A61K47/48 , A61K31/713
摘要： The present invention relates to an oligonucleotide structure and a method for preparing the same and, more particularly, to an oligonucleotide structure in which a polymer compound is linked to an oligonucleotide via a covalent bond to improve in vivo stability of the oligonucleotide and cellular delivery efficiency of the oligonucleotide; and to a method for preparing the same. The oligonucleotide structure is improved into a homogenous material, thereby solving the problem in material verification due to polydispersion characteristics occurring when a hydrophilic material linked to the oligonucleotide is a synthetic polymer; the oligonucleotide structure is easy to synthesize compared with the existing process; and the size of a double-stranded oligo RNA structure can be accurately adjusted through the control of the repetition number of a hydrophilic material block, and thus, the gene expression regulation function of the oligonucleotide does not deteriorate through the synthesis of the optimized oligonucleotide structure, and the oligonucleotide can be delivered into cells at even a relatively low-concentration dosage. Therefore, the oligonucleotide structure of the present invention can be useful as a novel type oligonucleotide delivery system as well as a tool for treating cancers, infectious diseases, and the like.

5. 发明申请

US20150005364A1 HIGH-EFFICIENCY NANOPARTICLE-TYPE DOUBLE-HELICAL OLIGO-RNA STRUCTURE AND METHOD FOR PREPARING SAME 有权
标题翻译：高效纳米二型双螺旋OLIGO-RNA结构及其制备方法
公开(公告)号：US20150005364A1
公开(公告)日：2015-01-01
申请号：US14370035
申请日：2013-01-04
申请人： BIONEER CORPORATION
发明人： Jeiwook Chae , Boram Han , Han-na Kim , Han Oh Park
IPC分类号： A61K9/14 , C12N15/113
CPC分类号： A61K9/14 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/14 , C12N2310/3515 , C12N2320/30 , C12N2320/32 , C12N2330/30
摘要： Provided are a double-stranded oligo RNA structure and a method of preparing the same, and more specifically, a double-stranded oligo RNA structure in which a polymer compound is covalently bound to a double-stranded oligo RNA in order to improve stability in vivo and a cell delivery efficiency of the double-stranded oligo RNA, and a method of preparing the same.The double-stranded oligo RNA structure having the optimized structure according to the present invention may not inhibit functions of the double-stranded oligo RNA, but effectively improve stability and cell membrane permeability of the double-stranded oligo RNA, such that the double-stranded oligo RNA may be delivered into the cell even at a low concentration dosage thereof to be significantly used as a tool for treatment of cancer, infectious diseases, and the like, as well as a new delivery system of the double-stranded oligo RNA.
摘要翻译：提供双链寡聚RNA结构及其制备方法，更具体地，其中高分子化合物与双链寡RNA共价结合以提高体内稳定性的双链寡聚RNA结构和双链寡聚RNA的细胞递送效率及其制备方法。具有本发明优化结构的双链寡聚RNA结构可能不抑制双链寡聚RNA的功能，而且可有效提高双链寡RNA的稳定性和细胞膜通透性，使得双链寡聚RNA 寡核苷酸即使以低浓度剂量也可以递送到细胞中，以显着地用作治疗癌症，感染性疾病等的工具，以及双链寡聚RNA的新的递送系统。

6. 发明授权

US10208309B2 Double-stranded oligo RNA targeted to amphiregulin and pharmaceutical composition comprising same for preventing or treating fibrosis or respiratory diseases 有权
公开(公告)号：US10208309B2
公开(公告)日：2019-02-19
申请号：US15301713
申请日：2015-04-06
申请人： Bioneer Corporation
发明人： Jeiwook Chae , Pyoung Oh Yoon , Boram Han , Mi Na Kim , Youngho Ko , Han Oh Park
IPC分类号： C12N15/113
摘要： The present invention relates to a novel siRNA, and a high-efficiency double-stranded oligo RNA structure containing the same, and a nanoparticle containing the high-efficiency double-stranded oligo RNA structure. The double-stranded oligo RNA structure has a structure in which a hydrophilic material and a hydrophobic material are conjugated to both ends of a double-stranded oligo RNA (siRNA) via a simple covalent bond or linker-mediated covalent bond in order to be efficiently delivered into cells, and may be converted into a nanoparticle form in an aqueous solution by hydrophobic interactions of double-stranded oligo RNA structures. It is preferable that the siRNA contained in the double-stranded oligo RNA structure is an siRNA specific for fibrosis or respiratory disease-related gene, particularly, amphiregulin or stratifin.In addition, the present invention relates to a pharmaceutical composition for preventing or treating fibrosis or respiratory diseases, containing an siRNA, a high-efficiency double-stranded oligo RNA structure containing the siRNA, or a nanoparticle containing the high-efficiency double-stranded oligo RNA structure, as an active ingredient.In addition, the present invention relates to a method of preventing or treating fibrosis or respiratory diseases, including administering the pharmaceutical composition for preventing or treating fibrosis or respiratory diseases to a subject in need thereof.

7. 发明申请

US20160145624A1 LIVER CANCER RELATED GENES-SPECIFIC siRNA, DOUBLE-STRANDED OLIGO RNA MOLECULES COMPRISING THE siRNA, AND COMPOSITION FOR PREVENTING OR TREATING CANCER COMPRISING THE SAME 审中-公开
标题翻译：肝癌相关基因特异性siRNA，包含siRNA的双链寡聚RNA分子，以及用于预防或治疗包含其的癌症的组合物
公开(公告)号：US20160145624A1
公开(公告)日：2016-05-26
申请号：US14903043
申请日：2014-07-09
申请人： BIONEER CORPORATION , SANOFI-AVENTIS KOREA CO., LTD.
发明人： Jeiwook Chae , Pyoung Oh Yoon , Han-na Kim , Han Oh Park , Boram Han , Youngho Ko , Gi-Eun Choi , Jae Eun Kim
IPC分类号： C12N15/113 , A61K31/713 , A61K47/48
CPC分类号： C12N15/1137 , A61K9/1075 , A61K31/713 , A61K47/6907 , C12N15/113 , C12N15/1135 , C12N2310/14 , C12N2310/31 , C12N2310/351 , C12N2320/30
摘要： There is provided a liver cancer related specific siRNA and high efficiency double-stranded oligo RNA molecules containing the same. The double-stranded oligo RNA molecules have a structure in which hydrophilic and hydrophobic compounds are conjugated to both ends of the double-stranded oligo RNA molecules by a simple covalent bond or a linker-mediated covalent bond in order to be efficiently delivered into cells and may be converted into nanoparticles in an aqueous solution by hydrophobic interactions of the double-stranded oligo RNA molecules. The siRNA contained in the double-stranded oligo RNA molecules may be liver cancer related genes, particularly ZBTB7A, YAP1 or CHD1L specific siRNA.In addition, the present invention relates to a method of preparing the double-stranded oligo RNA molecules, and a pharmaceutical composition for preventing or treating cancer, particularly, liver cancer, containing the double-stranded oligo RNA molecules.
摘要翻译：提供了与相关肝癌相关的特异性siRNA和高效双链寡聚RNA分子。双链寡RNA分子具有通过简单的共价键或连接体介导的共价键将亲水和疏水化合物与双链寡RNA分子的两端缀合以便有效地递送到细胞中的结构，可以通过双链寡聚RNA分子的疏水相互作用在水溶液中转化成纳米颗粒。双链寡核苷酸分子中包含的siRNA可能是肝癌相关基因，特别是ZBTB7A，YAP1或CHD1L特异性siRNA。此外，本发明涉及制备双链寡聚RNA分子的方法和用于预防或治疗含有双链寡RNA分子的癌症，特别是肝癌的药物组合物。

8. 发明申请

US20160122764A1 RESPIRATORY DISEASE-RELATED GENE SPECIFIC SIRNA, DOUBLE-HELICAL OLIGO RNA STRUCTURE CONTAINING SIRNA, COMPOSITON CONTAINING SAME FOR PREVENTING OR TREATING RESPIRATORY DISEASE 审中-公开
标题翻译：呼吸道疾病相关基因特异性SIRNA，双重HOLICAL OLIGO RNA结构含有SIRNA，含有相同的组合物，用于预防或治疗呼吸道疾病
公开(公告)号：US20160122764A1
公开(公告)日：2016-05-05
申请号：US14902566
申请日：2014-07-04
申请人： BIONEER CORPORATION , YUHAN CORPORATION
发明人： Jeiwook Chae , Han Oh Park , Pyoung Oh Yoon , Boram Han , Mi Na Kim
IPC分类号： C12N15/113
摘要： The present invention relates to a gene specific siRNA related with respiratory diseases, particularly, to a gene specific siRNA related with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease (COPD), and a highly efficient double-helical oligo RNA structure containing the same, wherein the double-helical oligo RNA structure has a structure in which hydrophilic and hydrophobic materials are bonded at the both ends of the double-helical RNA (siRNA) using a simple covalent bond or a linker-mediated covalent bond to be effectively transferred into a cell, and may be converted into nanoparticles by the hydrophobic interaction of the double-helical oligo RNA structure in a solution. It is desirable that the siRNA contained in the double-helical oligo RNA structure is a siRNA specific to a CTGF, Cyr61, or Plekho1, which are genes related with respiratory diseases, particularly idiopathic pulmonary fibrosis and COPD. In addition, the present invention relates to a method for producing the double-helical oligo RNA structure and a pharmaceutical composition containing the double-helical oligo RNA structure for preventing or treating respiratory diseases, particularly idiopathic pulmonary fibrosis and COPD.
摘要翻译：本发明涉及与呼吸系统疾病相关的基因特异性siRNA，特别涉及与特发性肺纤维化和慢性阻塞性肺疾病（COPD）相关的基因特异性siRNA以及含有该特异性siRNA的高效双螺旋寡聚RNA结构，其中双螺旋寡聚RNA结构具有亲水和疏水性材料在双螺旋RNA（siRNA）的两端使用简单共价键或连接体介导的共价键键合以有效转移到细胞中的结构，并且可以通过双螺旋寡聚RNA结构在溶液中的疏水相互作用而转化成纳米颗粒。希望双螺旋寡聚RNA结构中所含的siRNA是与呼吸道疾病，特别是特发性肺纤维化和COPD有关的基因的CTGF，Cyr61或Plekho1特异的siRNA。此外，本发明涉及双螺旋寡聚RNA结构的制造方法和含有预防或治疗呼吸系统疾病，特别是特发性肺纤维化和COPD的双螺旋寡聚RNA结构的药物组合物。

9. 发明授权

US09326941B2 High-efficiency nanoparticle-type double-helical oligo-RNA structure and method for preparing same 有权
标题翻译：高效纳米颗粒型双螺旋寡聚RNA结构及其制备方法
公开(公告)号：US09326941B2
公开(公告)日：2016-05-03
申请号：US14370035
申请日：2013-01-04
申请人： BIONEER CORPORATION
发明人： Jeiwook Chae , Boram Han , Han-na Kim , Han Oh Park
IPC分类号： A61K48/00 , C07H21/02 , C07H21/04 , A61K9/14 , C12N15/11 , C12N15/113
CPC分类号： A61K9/14 , C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/14 , C12N2310/3515 , C12N2320/30 , C12N2320/32 , C12N2330/30
摘要： Provided are a double-stranded oligo RNA structure and a method of preparing the same, and more specifically, a double-stranded oligo RNA structure in which a polymer compound is covalently bound to a double-stranded oligo RNA in order to improve stability in vivo and a cell delivery efficiency of the double-stranded oligo RNA, and a method of preparing the same.The double-stranded oligo RNA structure having the optimized structure according to the present invention may not inhibit functions of the double-stranded oligo RNA, but effectively improve stability and cell membrane permeability of the double-stranded oligo RNA, such that the double-stranded oligo RNA may be delivered into the cell even at a low concentration dosage thereof to be significantly used as a tool for treatment of cancer, infectious diseases, and the like, as well as a new delivery system of the double-stranded oligo RNA.
摘要翻译：提供双链寡聚RNA结构及其制备方法，更具体地，其中高分子化合物与双链寡RNA共价结合以提高体内稳定性的双链寡聚RNA结构和双链寡聚RNA的细胞递送效率及其制备方法。具有本发明优化结构的双链寡聚RNA结构可能不抑制双链寡聚RNA的功能，而且可有效提高双链寡RNA的稳定性和细胞膜通透性，使得双链寡聚RNA 寡核苷酸即使以低浓度剂量也可以递送到细胞中，以显着地用作治疗癌症，感染性疾病等的工具，以及双链寡聚RNA的新的递送系统。

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