公开(公告)号：US20150056145A1

公开(公告)日：2015-02-26

申请号：US14372211

申请日：2013-01-17

Applicant: BIONEER CORPORATION

Inventor： Jeiwook Chae ,  Hyunjin Chung ,  Boreum Lee ,  Han Oh Park

IPC: A61K47/48 ,  C12N15/11 ,  A61K49/18 ,  A61K9/14

CPC classification number: A61K47/48015 ,  A61K9/14 ,  A61K9/5094 ,  A61K9/5115 ,  A61K31/7105 ,  A61K31/713 ,  A61K33/24 ,  A61K47/6923 ,  A61K49/1857 ,  C12N15/11 ,  A61K2300/00

Abstract: Provided are a SAMiRNA-magnetic nanoparticle complex capable of effectively delivering a double-stranded oligo RNA and magnetic nanoparticles into a cell and a composition capable of simultaneously performing diagnosis and therapy of diseases such as cancer, and the like, containing the same. More specifically, provided is the SAMiRNA-magnetic nanoparticle complex consisting of double-stranded oligo RNA-polymer structures in which a hydrophilic material and a second hydrophobic material are bound to the double-stranded oligo RNA by a simple covalent bond or a linker-mediated covalent bond, and the magnetic nanoparticles in which a first hydrophobic material is bound onto a surface of the magnetic material, as a core.The SAMiRNA-magnetic nanoparticle complex may have a homogeneous size by a hydrophobic interaction between the first hydrophobic material of the present invention and the second hydrophobic material of the double-stranded oligo RNA structure.In addition, the hydrophilic material and the second hydrophobic material bound to the double-stranded oligo RNA structure may improve in vivo stability of the double-stranded oligo RNA, an additionally bound ligand may deliver the SAMiRNA-magnetic nanoparticle complex into a target cell even at a relative low concentration of dosage, and the magnetic materials of the magnetic nanoparticles may be used as an imaging agent for diagnosis.

Abstract translation: 提供了能够有效地将双链寡RNA和磁性纳米颗粒递送到细胞中的SAMiRNA-磁性纳米颗粒复合物，以及能够同时进行包含其的癌症等疾病的诊断和治疗的组合物。 更具体地，提供了由双链寡聚RNA结构组成的SAMiRNA-磁性纳米颗粒复合物，其中亲水性材料和第二疏水性材料通过简单的共价键或连接体介导的结合到双链寡聚RNA上 共价键和其中第一疏水性材料结合到磁性材料的表面上的磁性纳米粒子作为核心。 SAMiRNA磁性纳米颗粒复合物可以通过本发明的第一疏水性材料与双链寡聚RNA结构的第二疏水性材料之间的疏水相互作用而具有均匀的尺寸。 此外，与双链寡聚RNA结构结合的亲水性材料和第二疏水性材料可以提高双链寡聚RNA的体内稳定性，附加结合的配体可以将SAMiRNA-磁性纳米颗粒复合体均匀地递送到靶细胞中 在相对低的剂量浓度下，磁性纳米颗粒的磁性材料可以用作诊断的显像剂。

公开(公告)号：US10030243B2

公开(公告)日：2018-07-24

申请号：US14902563

申请日：2014-07-04

Applicant: BIONEER CORPORATION

Inventor： Han Oh Park ,  Jeiwook Chae ,  Pyoung Oh Yoon ,  Boram Han ,  Gi-Eun Choi ,  Youngho Ko ,  Taewoo Kwon ,  Jae Don Lee ,  Sun Gi Kim

IPC: C12N15/113 ,  A61K9/51 ,  A61K48/00 ,  A61K47/48 ,  A61K31/713

Abstract: 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.

公开(公告)号：US20150259690A1

公开(公告)日：2015-09-17

申请号：US14433627

申请日：2013-10-07

Applicant: BIONEER CORPORATION

Inventor： Han-Oh Park ,  Jeiwook Chae ,  Pyoung Oh Yoon

IPC: C12N15/113 ,  A61K31/713 ,  A61K9/51 ,  A61K47/48

CPC classification number: C12N15/1136 ,  A61K9/51 ,  A61K31/713 ,  A61K47/543 ,  A61K47/554 ,  C12N2310/14 ,  C12N2310/312 ,  C12N2310/314 ,  C12N2310/315 ,  C12N2310/3181 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/351 ,  C12N2320/52

Abstract: An amphiregulin-specific double-stranded oligo siRNA structure comprises hydrophilic and hydrophobic compounds bound to the amphiregulin-specific double-stranded oligo siRNA by a simple covalent bond or a linker-mediated covalent bond so as to increase the in vivo stability and intracellular delivery efficiency of the double-stranded oligo siRNA, and to nanoparticles composed of the oligo siRNA structures. The amphiregulin-specific double-stranded oligo siRNA structure can increase the stability of the amphiregulin-specific double-stranded oligo siRNA without impairing the function of the amphiregulin-specific double-stranded oligo siRNA, and at the same time, can efficiently increase the membrane permeability of the double-stranded oligo siRNA. Thus, when the amphiregulin-specific double-stranded oligo siRNA structure is used, the amphiregulin-specific double-stranded oligo siRNA can be efficiently delivered into cells even when it is administered at a relatively low concentration, so that it can be effectively used for the prevention or treatment of respiratory diseases.

Abstract translation: 双调蛋白特异性双链寡核苷酸siRNA结构包含通过简单的共价键或连接体介导的共价键与双调蛋白特异性双链寡核苷酸结合的亲水和疏水化合物，以增加体内稳定性和细胞内递送效率 的双链寡聚siRNA，以及由寡聚siRNA结构构成的纳米颗粒。 双调蛋白特异性双链寡聚siRNA结构可以增加双调蛋白特异性双链寡聚siRNA的稳定性，而不损害双调蛋白特异性双链寡聚siRNA的功能，同时可以有效地增加膜 双链寡聚siRNA的通透性。 因此，当使用双调蛋白特异性双链寡聚siRNA结构时，即使以相对低的浓度给药，也可以将双调蛋白特异性双链寡聚siRNA有效地递送到细胞中，使得其可以有效地用于 预防或治疗呼吸系统疾病。

公开(公告)号：US20150005364A1

公开(公告)日：2015-01-01

申请号：US14370035

申请日：2013-01-04

Applicant: BIONEER CORPORATION

Inventor： Jeiwook Chae ,  Boram Han ,  Han-na Kim ,  Han Oh Park

IPC: A61K9/14 ,  C12N15/113

CPC classification number: A61K9/14 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/3515 ,  C12N2320/30 ,  C12N2320/32 ,  C12N2330/30

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20160168573A1

公开(公告)日：2016-06-16

申请号：US14902808

申请日：2014-07-09

Applicant: BIONEER CORPORATION ,  SANOFI-AVENTIS KOREA CO., LTD.

Inventor： 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: C12N15/113

CPC classification number: C12N15/1135 ,  A61K9/0019 ,  A61K9/51 ,  A61K31/713 ,  A61K47/60 ,  C12N2310/14

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US10208309B2

公开(公告)日：2019-02-19

申请号：US15301713

申请日：2015-04-06

Applicant: Bioneer Corporation

Inventor： Jeiwook Chae ,  Pyoung Oh Yoon ,  Boram Han ,  Mi Na Kim ,  Youngho Ko ,  Han Oh Park

IPC: C12N15/113

Abstract: 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.

公开(公告)号：US20160145624A1

公开(公告)日：2016-05-26

申请号：US14903043

申请日：2014-07-09

Applicant: BIONEER CORPORATION ,  SANOFI-AVENTIS KOREA CO., LTD.

Inventor： Jeiwook Chae ,  Pyoung Oh Yoon ,  Han-na Kim ,  Han Oh Park ,  Boram Han ,  Youngho Ko ,  Gi-Eun Choi ,  Jae Eun Kim

IPC: C12N15/113 ,  A61K31/713 ,  A61K47/48

CPC classification number: C12N15/1137 ,  A61K9/1075 ,  A61K31/713 ,  A61K47/6907 ,  C12N15/113 ,  C12N15/1135 ,  C12N2310/14 ,  C12N2310/31 ,  C12N2310/351 ,  C12N2320/30

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20160122764A1

公开(公告)日：2016-05-05

申请号：US14902566

申请日：2014-07-04

Applicant: BIONEER CORPORATION ,  YUHAN CORPORATION

Inventor： Jeiwook Chae ,  Han Oh Park ,  Pyoung Oh Yoon ,  Boram Han ,  Mi Na Kim

IPC: C12N15/113

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US09326941B2

公开(公告)日：2016-05-03

申请号：US14370035

申请日：2013-01-04

Applicant: BIONEER CORPORATION

Inventor： Jeiwook Chae ,  Boram Han ,  Han-na Kim ,  Han Oh Park

IPC: A61K48/00 ,  C07H21/02 ,  C07H21/04 ,  A61K9/14 ,  C12N15/11 ,  C12N15/113

CPC classification number: A61K9/14 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/3515 ,  C12N2320/30 ,  C12N2320/32 ,  C12N2330/30

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20170152512A1

公开(公告)日：2017-06-01

申请号：US14902563

申请日：2014-07-04

Applicant: BIONEER CORPORATION

Inventor： Han Oh Park ,  Jeiwook Chae ,  Pyoung Oh Yoon ,  Boram Han ,  Gi-Eun Choi ,  Youngho Ko ,  Taewoo Kwon ,  Jae Don Lee ,  Sun Gi Kim

IPC: C12N15/113 ,  A61K31/713

CPC classification number: 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

Abstract: 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.