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1. 发明申请

US20120088815A1 Modified Oligonucleotide and Its Preparation and Application 有权
标题翻译：改性寡核苷酸及其制备及应用
公开(公告)号：US20120088815A1
公开(公告)日：2012-04-12
申请号：US13262702
申请日：2010-03-30
申请人： Zicai Liang
发明人： Zicai Liang
IPC分类号： A61K31/713 , G01N33/48 , C07H1/00 , C07H21/00 , C12N5/07
CPC分类号： C12N15/111 , A61K31/7115 , A61K31/712 , A61K31/7125 , A61K31/713 , A61K48/00 , C12N15/113 , C12N2310/322 , C12N2320/51 , C12N2310/3525
摘要： The present invention relates to a modified oligonucleotide, its preparation and application. The invention enables stabilizing the oligonucleotide by introducing a relatively small amount of modified nucleotide at specific UA/UA and/or CA/UG and/or UG/CA site of the oligonucleotide, therefore to decrease the modification-related cytotoxicity and compromising effects on the biological activity.
摘要翻译：本发明涉及修饰的寡核苷酸，其制备和应用。本发明可通过在寡核苷酸的特定UA / UA和/或CA / UG和/或UG / CA位点引入相对少量的修饰的核苷酸来稳定寡核苷酸，从而降低与修饰相关的细胞毒性和对生物活性。

2. 发明授权

US08653252B2 Short interfering RNA (siRNA) analogues 有权
标题翻译：短干扰RNA（siRNA）类似物
公开(公告)号：US08653252B2
公开(公告)日：2014-02-18
申请号：US10550152
申请日：2004-03-22
申请人： Joachim Elmén , Claes Wahlestedt , Zicai Liang , Anders Malling Sørensen , Henrik Ørum , Troels Koch
发明人： Joachim Elmén , Claes Wahlestedt , Zicai Liang , Anders Malling Sørensen , Henrik Ørum , Troels Koch
IPC分类号： C07H21/04 , C12N15/113
CPC分类号： C12N15/1131 , A61K38/00 , A61K38/09 , A61K38/2013 , A61K38/212 , A61K38/31 , C12N15/111 , C12N15/1135 , C12N2310/14 , C12N2310/315 , C12N2310/3231 , C12N2310/3233 , C12N2310/3341 , C12N2310/53 , C12N2320/51 , C12N2330/30 , Y02A50/465 , A61K2300/00
摘要： The present invention is directed to novel double-stranded short interfering (siRNA) analogues comprising locked nucleic acid (LNA) monomers. Such compounds induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). The compounds disclosed herein has improved properties compared to non-modified siRNAs and may, accordingly, be useful as therapeutic agents, e.g., in the treatment of various cancer forms. More particularly, the present invention is directed to siRNA analogues comprising a sense strand and an antisense strand, wherein each strand comprises 12-35 nucleotides and wherein the siRNA analogues comprise at least one locked nucleic acid (LNA) monomer.
摘要翻译：本发明涉及包含锁定核酸（LNA）单体的新型双链短干扰（siRNA）类似物。这种化合物通过称为RNA干扰（RNAi）的方法在许多生物体中诱导序列特异性的转录后基因沉默。本文公开的化合物与未修饰的siRNA相比具有改善的性质，因此可用作治疗剂，例如用于治疗各种癌症形式。更具体地，本发明涉及包含有义链和反义链的siRNA类似物，其中每条链包含12-35个核苷酸，并且其中siRNA类似物包含至少一个锁定核酸（LNA）单体。

3. 发明申请

US20100317714A1 COMPLEX MOLECULE INTERFERING THE EXPRESSION OF TARGET GENES AND ITS PREPARING METHODS 审中-公开
标题翻译：复合分子干扰目标基因的表达及其制备方法
公开(公告)号：US20100317714A1
公开(公告)日：2010-12-16
申请号：US12745322
申请日：2008-11-28
申请人： Zhen Xi , Zicai Liang , Liqiang Cao , Junbin Zhang , Jinyu Huang
发明人： Zhen Xi , Zicai Liang , Liqiang Cao , Junbin Zhang , Jinyu Huang
IPC分类号： A61K31/7088 , C07H21/02 , C07K2/00 , A61P7/00
CPC分类号： C12N15/111 , C12N2310/14 , C12N2310/318 , C12N2310/532
摘要： The present invention provides a complex molecule interfering the expression of target genes and the methods for preparing the complex molecule, wherein the complex molecule contains two siRNA strands X1 and X2 having at least 80% complementarity, the 5′ end of X1 and 3′ end of X2 are linked through non-nucleic acid molecule L1, the 5′ end of X2 and 3′ end of X1 are linked through non-nucleic acid molecule L2. Since both 5′ and 3′ ends of two siRNA strands X1 and X2 of the complex molecule according to the present invention are linked through non-nucleic acid molecules, it is not easy to unwind and degraded for the siRNA strands, and therefore the chemical stability of siRNA and the remaining time in the blood are greatly improved. After being administered, the Dicer enzyme in the cells is utilized to release the locked siRNAs from the complex molecules, and after unwinding, the antisense strand of the siRNA is released from the double-stranded siRNA to inhibit the expression of the target genes.
摘要翻译：本发明提供了干扰靶基因表达的复合分子和制备复合分子的方法，其中复合分子含有两个具有至少80％互补性的siRNA链X1和X2，X1和3'末端的5'末端的X2通过非核酸分子L1连接，X2的5'端和X1的3'末端通过非核酸分子L2连接。由于根据本发明的复合分子的两个siRNA链X1和X2的5'和3'末端都通过非核酸分子连接，所以对于siRNA链来说不容易退化和降解，因此化学 siRNA的稳定性和血液中的剩余时间大大提高。在施用后，细胞中的Dicer酶用于从复合分子中释放锁定的siRNA，并且在解开后，从双链siRNA释放siRNA的反义链以抑制靶基因的表达。

4. 发明授权

US08846895B2 Double-stranded RNA molecules with stability in mammalian body fluid, preparation and application thereof 有权
标题翻译：哺乳动物体液中具有稳定性的双链RNA分子，其制备和应用
公开(公告)号：US08846895B2
公开(公告)日：2014-09-30
申请号：US13582936
申请日：2011-03-29
申请人： Quan Du , Zicai Liang
发明人： Quan Du , Zicai Liang
IPC分类号： C07H21/04 , C07H21/02 , C12Q1/68 , A61K48/00
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/51
摘要： The present invention discloses preparation and application of double-stranded RNA molecules stable in mammalian body fluids. The mammalian-body-fluid-stable RNA molecules disclosed in the present invention are comprised of only unmodified nucleotides. For the first time, the present invention discloses the applications of mammalian-body-fluid-stable RNA molecules for immunotherapy and siRNA drug development.
摘要翻译：本发明公开了哺乳动物体液中稳定的双链RNA分子的制备和应用。本发明中公开的哺乳动物体液稳定的RNA分子仅由未修饰的核苷酸组成。本发明首次公开了哺乳动物体液稳定的RNA分子在免疫治疗和siRNA药物开发中的应用。

5. 发明申请

US20130065940A1 DOUBLE-STRANDED RNA MOLECULES WITH STABILITY IN MAMMALIAN BODY FLUID, PREPARATION AND APPLICATION THEREOF 有权
标题翻译：具有稳定性的双链RNA分子在马马里兰体液中的制备和应用
公开(公告)号：US20130065940A1
公开(公告)日：2013-03-14
申请号：US13582936
申请日：2011-03-29
申请人： Quan Du , Zicai Liang
发明人： Quan Du , Zicai Liang
IPC分类号： A61K31/713 , C12N5/071 , C07H21/02 , C07H1/00
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/51
摘要： The present invention discloses preparation and application of double-stranded RNA molecules stable in mammalian body fluids. The mammalian-body-fluid-stable RNA molecules disclosed in the present invention are comprised of only unmodifide nucleotides. For the first time, the present invention discloses the applications of mammalian-body-fluid-stable RNA molecules for immunotherapy and siRNA drug development.
摘要翻译：本发明公开了哺乳动物体液中稳定的双链RNA分子的制备和应用。本发明中公开的哺乳动物体液稳定的RNA分子仅由未修饰的核苷酸组成。本发明首次公开了哺乳动物体液稳定的RNA分子在免疫治疗和siRNA药物开发中的应用。

6. 发明授权

US08754058B2 Inhibitors of FAM3B gene, inhibitor compositions, inhibiting methods and applications of inhibitors in preparing pharmaceuticals 有权
标题翻译： FAM3B基因的抑制剂，抑制剂组成，抑制剂在制备药物中的抑制方法和应用
公开(公告)号：US08754058B2
公开(公告)日：2014-06-17
申请号：US13498717
申请日：2010-11-26
申请人： Youfei Guan , Zicai Liang
发明人： Youfei Guan , Zicai Liang
IPC分类号： C12N15/11 , C12Q1/68
CPC分类号： C12N15/1136 , A61K31/7088 , A61K31/7105 , A61K31/711 , A61K31/7115 , A61K31/712 , A61K31/7125 , A61K31/713 , A61K2039/505 , C07K16/18 , C12N2310/14 , C12N2310/31 , C12N2310/321
摘要： Inhibitors that can inhibit expression of FAM3B gene to reduce the levels of expression products, or can combine the expression products to reduce the activity of promoting lipid synthesis of FAM3B gene product are provided, wherein the inhibitors are one or more inhibitors selected from the group consisting of small interfering RNAs, antisense oligonucleotides, antibodies against FAM3B proteins and active organic compounds. Cells, vectors or inhibitor compositions, comprising such inhibitors, methods for inhibiting expression of FAM3B gene or inhibiting the activity of promoting lipid synthesis of FAM3B gene product using the inhibitors are provided. Methods for treating diseases mediated by expression of FAM3B gene using such inhibitors and uses of the inhibitors in preparing pharmaceuticals for preventing and/or treating the disease mediated by FAM3B gene expression are also provided.
摘要翻译：提供可以抑制FAM3B基因表达以降低表达产物水平的抑制剂，或可以组合表达产物以降低促进FAM3B基因产物的脂质合成的活性，其中所述抑制剂是一种或多种选自以下的抑制剂：小干扰RNA，反义寡核苷酸，抗FAM3B蛋白和活性有机化合物的抗体。提供了包含这些抑制剂的细胞，载体或抑制剂组合物，使用抑制剂抑制FAM3B基因表达或抑制促进FAM3B基因产物的脂质合成活性的方法。还提供了使用这种抑制剂治疗由FAM3B基因表达介导的疾病的方法以及抑制剂在制备用于预防和/或治疗由FAM3B基因表达介导的疾病的药物中的用途。

7. 发明授权

US08563710B2 Modified oligonucleotide and its preparation and application 有权
标题翻译：改性寡核苷酸及其制备及应用
公开(公告)号：US08563710B2
公开(公告)日：2013-10-22
申请号：US13262702
申请日：2010-03-30
申请人： Zicai Liang
发明人： Zicai Liang
IPC分类号： C07H21/04
CPC分类号： C12N15/111 , A61K31/7115 , A61K31/712 , A61K31/7125 , A61K31/713 , A61K48/00 , C12N15/113 , C12N2310/322 , C12N2320/51 , C12N2310/3525
摘要： The present invention relates to a modified oligonucleotide, its preparation and application. The invention eables stabilizing the oligonucleotide by introducing a relatively small amount of modified nucleotide at specific UA/UA and/or CA/UG and/or UG/CA site of the oligonucleotide, therefore to decrease the modification-related cytotoxicity and compromising effects on the biological activity.
摘要翻译：本发明涉及修饰的寡核苷酸，其制备和应用。本发明通过在寡核苷酸的特定UA / UA和/或CA / UG和/或UG / CA位点引入相对少量的修饰的核苷酸来稳定寡核苷酸，从而降低与修饰相关的细胞毒性和对生物活性。

8. 发明申请

US20100009856A1 Randomized dna libraries and double-stranded rna libraries, use and method of production thereof 审中-公开
标题翻译：随机dna文库和双链rna文库，其使用及其生产方法
公开(公告)号：US20100009856A1
公开(公告)日：2010-01-14
申请号：US10517324
申请日：2003-06-23
申请人： Zicai Liang , Hong-Yan Zhang , Meihong Cheng , Yan Shen
发明人： Zicai Liang , Hong-Yan Zhang , Meihong Cheng , Yan Shen
IPC分类号： C40B30/00 , C40B40/08 , C07H21/04 , C07H21/02
CPC分类号： C12N15/1093 , C12N15/111 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2330/31
摘要： This invention relates to DNA libraries based on plasmid or viral vectors that can express double-stranded RNA of 10-30 base pairs in length with all possible sequences, where each of the double stranded RNA is formed by a single RNA molecule in the form of hairpin, or formed by two separate RNA molecules with different 3′-overhangs. Each single member in such a DNA library encodes all components of a double stranded RNA as specified above. Such a library can be used in screening for double stranded RNA species that can induce a given phenotype without prior knowledge of their target genes. This invention further relates to a method to generate such a DNA library.
摘要翻译：本发明涉及基于质粒或病毒载体的DNA文库，其可以表达长度为10-30个碱基对的所有可能序列的双链RNA，其中每个双链RNA由单个RNA分子形成，其形式为发夹，或由具有不同3'-突出端的两个分开的RNA分子形成。这样的DNA文库中的每个单个成员编码如上所述的双链RNA的所有组分。这样的文库可用于筛选双链RNA物种，其可以在没有其目标基因的知识的情况下诱导给定的表型。本发明还涉及产生这种DNA文库的方法。

9. 发明授权

US09567364B2 Nucleotide and/or oligonucleotide and preparation process thereof 有权
标题翻译：核苷酸和/或寡核苷酸及其制备方法
公开(公告)号：US09567364B2
公开(公告)日：2017-02-14
申请号：US13811295
申请日：2011-07-20
申请人： Zhen Xi , Zicai Liang , Jinyu Huang
发明人： Zhen Xi , Zicai Liang , Jinyu Huang
IPC分类号： C07H21/02 , C07H21/04 , C07H21/00 , C07H19/04 , C07H19/20 , C07H19/10 , C07H19/048 , C07H19/167
CPC分类号： C07H21/02 , C07H19/10 , C07H19/167 , C07H19/20 , C07H21/04 , Y02P20/55
摘要： Nucleotide and/or oligonucleotide represented by formula (1) and the liquid phase synthesis process thereof. The present invention provides a liquid phase synthesis process for preparing a nucleotide and/or an oligonucleotide, comprising a process for combining the nucleotide and/or oligonucleotide protective groups, in which, under the condition that the 2′-hydroxyl group is protected by a group with a sterically hindered silane structure, the 3′ phosphate group(s) of the nucleotide and/or oligonucleotide is/are directly protected by (a)β-cyanoethyl group(s), and after the β-cyanoethyl group(s) is/are removed, the resulting product can directly participate in the next cycle of synthesis, wherein the synthesis reaction is carried out in a reaction flask or reaction kettle, without being limited by a solid carrier or synthesizer, so that the large scale preparation of oligonucleotides can be achieved.
摘要翻译：由式（1）表示的核苷酸和/或寡核苷酸及其液相合成方法。本发明提供了制备核苷酸和/或寡核苷酸的液相合成方法，包括将核苷酸和/或寡核苷酸保护基组合的方法，其中在2'-羟基被具有空间位阻硅烷结构的基团，核苷酸和/或寡核苷酸的3'磷酸基团被（a）2-氰基乙基直接保护，并且在2-氰基乙基之后，所得产物可以直接参与下一个合成循环，其中合成反应在反应烧瓶或反应釜中进行，而不受固体载体或合成仪的限制，从而大规模制备可以实现寡核苷酸。

10. 发明申请

US20130123482A1 NUCLEOTIDE AND/OR OLIGONUCLEOTIDE AND PREPARATION PROCESS THEREOF 有权
标题翻译：核苷酸和/或寡核苷酸及其制备方法
公开(公告)号：US20130123482A1
公开(公告)日：2013-05-16
申请号：US13811295
申请日：2011-07-20
申请人： Zhen Xi , Zicai Liang , Jinyu Huang
发明人： Zhen Xi , Zicai Liang , Jinyu Huang
IPC分类号： C07H21/02 , C07H21/04
CPC分类号： C07H21/02 , C07H19/10 , C07H19/167 , C07H19/20 , C07H21/04 , Y02P20/55
摘要： Nucleotide and/or oligonucleotide represented by formula (1) and the liquid phase synthesis process thereof. The present invention provides a liquid phase synthesis process for preparing a nucleotide and/or an oligonucleotide, comprising a process for combining the nucleotide and/or oligonucleotide protective groups, in which, under the condition that the 2′-hydroxyl group is protected by a group with a sterically hindered silane structure, the 3′ phosphate group(s) of the nucleotide and/or oligonucleotide is/are directly protected by (a)β-cyanoethyl group(s), and after the β-cyanoethyl group(s) is/are removed, the resulting product can directly participate in the next cycle of synthesis, wherein the synthesis reaction is carried out in a reaction flask or reaction kettle, without being limited by a solid carrier or synthesizer, so that the large scale preparation of oligonucleotides can be achieved.
摘要翻译：由式（1）表示的核苷酸和/或寡核苷酸及其液相合成方法。本发明提供了制备核苷酸和/或寡核苷酸的液相合成方法，包括将核苷酸和/或寡核苷酸保护基组合的方法，其中在2'-羟基被具有空间位阻硅烷结构的基团，核苷酸和/或寡核苷酸的3'磷酸基团被（a）β-氰基乙基直接保护，并且在β-氰基乙基之后，所得产物可以直接参与下一个合成循环，其中合成反应在反应烧瓶或反应釜中进行，而不受固体载体或合成仪的限制，从而大规模制备可以实现寡核苷酸。

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