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1. 发明申请

WO2011015347A1 VACCINE COMPOSITION COMPRISING 5'-CAP MODIFIED RNA 审中-公开
标题翻译：包含5'-CAP修饰的RNA的真菌组合物
公开(公告)号：WO2011015347A1
公开(公告)日：2011-02-10
申请号：PCT/EP2010/004760
申请日：2010-08-03
申请人： BIONTECH AG , JOHANNES GUTENBERG-UNIVERSITÄT MAINZ , UNIWERSYTET WARSZAWSKI , SAHIN, Ugur , KUHN, Andreas , DARZYNKIEWICZ, Edward , JEMIELITY, Jacek , KOWALSKA, Joanna
发明人： SAHIN, Ugur , KUHN, Andreas , DARZYNKIEWICZ, Edward , JEMIELITY, Jacek , KOWALSKA, Joanna
IPC分类号： A61K48/00 , C12N5/16
CPC分类号： A61K39/00 , A61K2039/5154 , A61K2039/53
摘要： The present invention relates to modification of RNA with 5 '-cap analogs in order to improve the stability and increase the expression of said RNA, in particular in immature antigen presenting cells. The present invention provides a vaccine composition comprising said stabilized RNA, immature antigen presenting cells comprising said stabilized RNA, and methods for stimulating and/or activating immune effector cells and for inducing an immune response in an individual using said stabilized RNA.
摘要翻译：本发明涉及用5'-cap类似物修饰RNA，以提高所述RNA的稳定性和增加表达，特别是在未成熟抗原呈递细胞中。本发明提供一种疫苗组合物，其包含所述稳定的RNA，包含所述稳定的RNA的未成熟抗原呈递细胞，以及用于使用所述稳定的RNA刺激和/或激活免疫效应细胞并诱导个体的免疫应答的方法。

2. 发明申请

WO2009149253A3 MRNA CAP ANALOGS 审中-公开
公开(公告)号：WO2009149253A3
公开(公告)日：2009-12-10
申请号：PCT/US2009/046249
申请日：2009-06-04
申请人： UNIWERSYTET WARSZAWSKI , BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICAL COLLEGE , KOWALSKA, Joanna , JEMIELITY, Jacek , DARZYNKIEWICZ, Edward , RHOADS, Robert, E. , LUKASZEWICZ, Maciej , ZUBEREK, Joanna
发明人： KOWALSKA, Joanna , JEMIELITY, Jacek , DARZYNKIEWICZ, Edward , RHOADS, Robert, E. , LUKASZEWICZ, Maciej , ZUBEREK, Joanna
IPC分类号： C07H21/00 , C07H21/02
摘要： Dinucleotide cap analogs are disclosed, modified at different phosphate positions with a boranophosphate group or a phosphoroselenoate group. The analogs are useful as reagents in the preparation of capped mRNAs and have increased stability both in vitro and in vivo . They may be used as inhibitors of cap-dependent translation. Optionally, the boranophosphate or phosphoroselenoate group has a 2'-O or 3'-O-alkyl group, preferably a methyl group, producing analogs called BH 3 -ARCAs or Se-ARCAs. ARCAs may be modified with α-, β-, or γ-boranophosphate or phosphoroselenoate groups.

3. 发明申请

WO2008157688A2 SYNTHESIS AND USE OF ANTI-REVERSE PHOSPHOROTHIOATE ANALOGS OF THE MESSENGER RNA CAP 审中-公开
标题翻译：信使RNA抗体的反向磷酸酯类似物的合成和使用
公开(公告)号：WO2008157688A2
公开(公告)日：2008-12-24
申请号：PCT/US2008/067494
申请日：2008-06-19
申请人： BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICAL COLLEGE , JEMIELITY, Jacek , GRUDZIEN-NOGALSKA, Ewa, M. , KOWALSKA, Joanna , DARZYNKIEWICZ, Edward , RHOADS, Robert, E.
发明人： JEMIELITY, Jacek , GRUDZIEN-NOGALSKA, Ewa, M. , KOWALSKA, Joanna , DARZYNKIEWICZ, Edward , RHOADS, Robert, E.
IPC分类号： C07H19/207
CPC分类号： C07H19/207 , C12P19/34 , C12P21/02
摘要： New RNA cap analogs are disclosed containing one or more phosphorothioates groups. The analogs also contain modifications at the 2'- O position of 7-methylguanosine that prevent them from being incorporated in the reverse orientation during in vitro synthesis of mRNA and that hence are "anti-reverse cap analogs" (ARCAs). The ARCA modification ensures that the S atom is precisely positioned within the active sites of cap-binding proteins in both the translational and decapping machinery. The new S-ARCA analogs are resistant to in vivo decapping enzymes. Some S-ARCAs have a higher affinity for eIF4E than the corresponding analogs not containing a phosphorothioate group. When mRNAs containing the various S-ARCAs are introduced into cultured cells, some are translated as much as five¬ fold more efficiently than mRNAs synthesized with the conventional analog m 7 GpppG.
摘要翻译：公开了含有一个或多个硫代磷酸酯基团的新的RNA帽类似物。类似物还含有在7-甲基鸟苷的2'-O位置上的修饰，这些修饰使得它们在体外合成mRNA期间以相反方向并入，因此是“抗反向帽类似物”（ARCAs）。 ARCA修饰确保S原子精确定位于翻译和去盖机器中帽结合蛋白的活性位点。新的S-ARCA类似物对体内脱色酶具有抗性。一些S-ARCAs对eIF4E具有比不含硫代磷酸酯基团的相应类似物更高的亲和力。当含有各种S-ARCAs的mRNA被引入培养的细胞中时，有一些mRNA比用常规的模拟m7GpppG合成的mRNA翻译高5倍。

4. 发明公开

EP2461833A1 VACCINE COMPOSITION COMPRISING 5'-CAP MODIFIED RNA 有权转让
标题翻译：与5“帽修饰的RNA疫苗组合物
公开(公告)号：EP2461833A1
公开(公告)日：2012-06-13
申请号：EP10742752.8
申请日：2010-08-03
申请人： Biontech AG , Johannes- Gutenberg-Universität Mainz , Uniwersytet Warszawski
发明人： SAHIN, Ugur , KUHN, Andreas , DARZYNKIEWICZ, Edward , JEMIELITY, Jacek , KOWALSKA, Joanna
IPC分类号： A61K48/00 , C12N5/16
CPC分类号： A61K39/00 , A61K2039/5154 , A61K2039/53
摘要： The present invention relates to modification of RNA with 5 '-cap analogs in order to improve the stability and increase the expression of said RNA, in particular in immature antigen presenting cells. The present invention provides a vaccine composition comprising said stabilized RNA, immature antigen presenting cells comprising said stabilized RNA, and methods for stimulating and/or activating immune effector cells and for inducing an immune response in an individual using said stabilized RNA.

5. 发明授权

EP2461833B1 VACCINE COMPOSITION COMPRISING 5'-CAP MODIFIED RNA 有权转让
标题翻译：与5“帽修饰的RNA疫苗组合物
公开(公告)号：EP2461833B1
公开(公告)日：2014-10-08
申请号：EP10742752.8
申请日：2010-08-03
申请人： BioNTech AG , TRON - Translationale Onkologie an der Universitätsmedizin der Johannes Gutenberg- Universität Mainz gemeinnützige GmbH , Uniwersytet Warszawski
发明人： SAHIN, Ugur , KUHN, Andreas , DARZYNKIEWICZ, Edward , JEMIELITY, Jacek , KOWALSKA, Joanna
IPC分类号： A61K48/00 , C12N5/16
CPC分类号： A61K39/00 , A61K2039/5154 , A61K2039/53

6. 发明申请

WO2018015845A1 NOVEL PHOSPHOTRIAZOLE MRNA 5'-END CAP ANALOGS, COMPOSITION COMPRISING THE SAME, RNA MOLECULE INCORPORATING THE SAME, USES THEREOF AND METHOD OF SYNTHESIZING RNA MOLECULE, PROTEIN OR PEPTIDE 审中-公开
标题翻译：新型磷酸三唑类MRNA 5'-末端类似物，包含其的组合物，包含其的RNA分子，其用途和合成RNA分子，蛋白质或肽的方法
公开(公告)号：WO2018015845A1
公开(公告)日：2018-01-25
申请号：PCT/IB2017/054221
申请日：2017-07-12
申请人： UNIWERSYTET WARSZAWSKI
发明人： WALCZAK, Sylwia , KOWALSKA, Joanna , JEMIELITY, Jacek
IPC分类号： C07H21/02 , C07H21/04 , C12N15/67 , A61K31/7084
摘要： The object of the invention is a compound of formula (I), or a stereoisomer or salt thereof, wherein R 1 and R 2 are selected from the group consisting of N, N+-CH 3 , N + -C 2 H 5 , N + -C 3 H 8 , N + - C 4 H 5 , N + -CH 2 C 6 H 5 wherein at least one of R 1 , R 2 is not N. n and m are independently chosen from the group consisting of 0, 1 and 2; X is selected from the group consisting of O, NH, S, CH 2 k is 1 or 2 Y is either void or selected from the group of -CH 2 -, -CH 2 CH 2 -, -CH 2 O-, -CH 2 S-, -CH 2 NH-, - CH 2 CH 2 O-, -CH 2 CH 2 NH-, -CH 2 CH 2 S- R 3 , R 4 , R 5 , R 6 are selected from the group consisting of H, OH, OCH 3 , or OCH 2 CH 3 ; wherein R 3 and R 4 may be the same or different; R 5 and R 6 may be the same or different; if either of R 3 , R 4 is different than OH than R 5 and R 6 are both OH; if either of R 5 , R 6 is different than OH than R 3 and R 4 are both OH. The object of the invention is also a composition comprising the compound of the invention, an RNA molecule incorporating the same, uses thereof and a method of synthesizing, in vitro or in vivo , the RNA molecule, as well as a method of synthesizing a protein or peptide in vitro , or in vivo or in cultured cells, said method comprising translating the RNA molecule.
摘要翻译：本发明的目的是式（I）的化合物或其立体异构体或其盐，其中R 1和R 2为选自N，N + -CH 3，N +， - N 2，N 5，N + N + 3，N + 8，N + 4-C 4 H _{; 其中R 3和R 4可以相同或不同; R 5和R 6可以相同或不同; 如果R 3，R 4中的任一个与OH不同于OH，则R 5和R 6都是OH; 如果R 5，R 6中的任何一个与OH不同于OH，则R 3和R 4都是OH。本发明的目的还在于一种组合物，其包含本发明的化合物，掺入其的RNA分子，其用途以及体内或体外合成的方法，，RNA分子以及在体外或体内或在培养细胞中合成蛋白质或肽的方法，所述方法包括翻译RNA分子。 / p>}

7. 发明申请

WO2021162567A1 NOVEL MRNA 5'-END CAP ANALOGS, RNA MOLECULE INCORPORATING THE SAME, USES THEREOF AND METHOD OF SYNTHESIZING RNA MOLECULE OR PEPTIDE 审中-公开
公开(公告)号：WO2021162567A1
公开(公告)日：2021-08-19
申请号：PCT/PL2021/050007
申请日：2021-02-12
申请人： UNIWERSYTET WARSZAWSKI , EXPLORNA THERAPEUTICS SP. Z O. O.
发明人： WARMIŃSKI, Macin , SIKORSKI, Paweł , KOWALSKA, Joanna , JEMIELITY, Jacek
IPC分类号： C07H21/04 , C12N15/113 , C12P19/34
摘要： The invention relates to new mRNA 5' end cap analogs, RNA molecules containing them, their uses and methods for their in vitro synthesis, as well as a method for protein or peptide synthesis in vitro or in cell cultures, which method encompases translation of the RNA molecule.

8. 发明申请

WO2022191725A1 N-(2-AMINOETHYL)MORPHOLINE-BASED RNA ANALOGS, METHOD FOR THE PREPARATION AND USE THEREOF 审中-公开
公开(公告)号：WO2022191725A1
公开(公告)日：2022-09-15
申请号：PCT/PL2022/050013
申请日：2022-03-10
申请人： UNIWERSYTET WARSZAWSKI
发明人： MAMOT, Adam , SIKORSKI, Paweł , KOWALSKA, Joanna , JEMIELITY, Jacek
IPC分类号： C07H21/02 , C07H1/00 , C09B23/04 , C09B11/28 , C09B15/00 , C07D495/04 , C07D311/82 , C07D311/90 , C07D403/14 , C09B11/08 , C09B11/245 , C09B23/06 , C09B23/083
摘要： The subject of the invention is RNA analogs of formula 1, their preparation and application, inter alia, in microscopic observations, study of the gene expression process and monitoring of enzyme activity. wherein R1 is an (oligo)nucleotide containing group, R2 is a nucleobase, R3 is a functional group.

9. 发明申请

WO2021162566A1 NOVEL MRNA 5'-END CAP ANALOGS MODIFIED WITHIN PHOSPHATE RESIDUES, RNA MOLECULE INCORPORATING THE SAME, USES THEREOF AND METHOD OF SYNTHESIZING RNA MOLECULE OR PEPTIDE 审中-公开
公开(公告)号：WO2021162566A1
公开(公告)日：2021-08-19
申请号：PCT/PL2021/050006
申请日：2021-02-12
申请人： UNIWERSYTET WARSZAWSKI , EXPLORNA THERAPEUTICS SP. Z O. O.
发明人： WARMIŃSKI, Macin , SIKORSKI, Paweł , KOWALSKA, Joanna , JEMIELITY, Jacek
IPC分类号： C07H21/04 , C12N15/113 , C12P19/34
摘要： The invention relates to new 5'mRNA end cap analogs, RNA molecules containing them, their uses and methods for their in vitro synthesis, as well as a method for protein or peptide synthesis in vitro or in cell cultures, which method translates the RNA molecule.

10. 发明申请

WO2017130151A1 5'-PHOSPHOROTHIOLATE MRNA 5'-END (CAP) ANALOGS, MRNA COMPRISING THE SAME, METHOD OF OBTAINING AND USES THEREOF 审中-公开
标题翻译： 5'-PHOSPHOROTHIOLATE MRNA 5'-END（CAP）类似物，包含其的MRNA，获得和使用它们的方法
公开(公告)号：WO2017130151A1
公开(公告)日：2017-08-03
申请号：PCT/IB2017/050447
申请日：2017-01-27
申请人： UNIWERSYTET WARSZAWSKI
发明人： JEMIELITY, Jacek , FAC-DĄBROWSKA, Kaja , WOJTCZAK, Błażej , BARANOWSKI, Marek , NOWICKA, Anna , KOWALSKA, Joanna , SIKORSKI, Paweł , WARMIŃSKI, Marcin
IPC分类号： C07H21/00 , A61K31/7084 , A61K31/7115 , A61K31/712 , A61K31/7125 , C07H21/02 , A61P21/00
CPC分类号： C07H21/00 , A61K31/7084 , A61K31/7115 , A61K31/712 , A61K31/7125 , C07H21/02
摘要： The present invention relates to nucleotides, analogs of mRNA 5'-end (cap) containing sulfur atom at the position 5' of 7-methylguanosine nucleoside. The disclosed compounds are recognized (bound and non-hydrolyzed) by DcpS enzyme (Decapping Scavenger), and thus may find therapeutic use as inhibitors thereof. DcpS is cap-specific enzyme with pyrophosphatase activity, which was identified as a therapeutic target in the treatment of spinal muscular atrophy (SMA). Some of the compounds disclosed have additional modifications in the phosphate chain, wh ich modulate their affinity for DcpS enzyme. The present invention also relates to mRNAs modified at the 5' end with mRNA 5'-end (cap) analogs containing 5'- phosphorothiolate moiety, which mRNAs have an increased stability and translational activity in cellular conditions, to a method of their preparation, their uses, and to a pharmaceutical formulation containing them, wherein L 1 and L 2 are independently selected from the group comprising O and S, wherein at least one of L 1 and L 2 is not O.
摘要翻译：本发明涉及在7-甲基鸟苷核苷的5'位置含有硫原子的mRNA 5'-末端（帽）的核苷酸，类似物。所公开的化合物被DcpS酶（去除捕获剂）识别（结合和未水解），因此可以作为其抑制剂发现治疗用途。 DcpS是具有焦磷酸酶活性的帽特异性酶，其被确定为治疗脊髓性肌萎缩（SMA）的治疗靶标。所公开的一些化合物在磷酸链中具有另外的修饰，其调节它们对DcpS酶的亲和力。本发明还涉及在5'末端用含有5'-硫代磷酸酯部分的mRNA5'-末端（帽）类似物修饰的mRNA，所述mRNA在细胞条件下具有增加的稳定性和翻译活性，涉及它们的制备方法，它们的用途以及含有它们的药物制剂，其中L 1和L 2独立地选自O和S，其中L ^{1 和L ^{2 不是O.}}

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