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1. 发明授权

US08802640B2 Oligonucleotides for RNA interference and biological applications thereof 有权
标题翻译：用于RNA干扰的寡核苷酸及其生物应用
公开(公告)号：US08802640B2
公开(公告)日：2014-08-12
申请号：US11921089
申请日：2006-06-01
申请人： Jean-Paul Behr , Anne-Laure Bolcato Bellemin , Patrick Erbacher
发明人： Jean-Paul Behr , Anne-Laure Bolcato Bellemin , Patrick Erbacher
IPC分类号： C07H21/00
CPC分类号： C12N15/113 , A61K31/713 , A61K47/34 , C12N15/111 , C12N2310/14 , C12N2310/51 , C12N2320/30 , C12N2320/51 , C12N2320/52
摘要： The invention relates to compositions comprising double-stranded oligonucleotides of identical or different sequences and/or length, said oligonucleotides having sequences 3′N1N2 . . . Ni-1Ni . . . Nj5′ wherein—3′Ni . . . Nj5′ is half of a double-stranded 19-28mer oligonucleotide of sequence complementary to a target nucleic acid sequence present in a living cell, and—3′N1 . . . Ni-15′ is a 3-50mer overhang of sequence allowing oligomerization of said double-stranded oligonucleotide. Compositions of transfection comprising said oligonucleotide compositions and there used for therapeutical application.
摘要翻译：本发明涉及包含相同或不同序列和/或长度的双链寡核苷酸的组合物，所述寡核苷酸具有序列3'N1N2。。。 Ni-1Ni。。。 Nj5'其中3'Ni。。。 Nj5'是与存在于活细胞中的靶核酸序列互补的序列的双链19-28mer寡核苷酸和-3'N1的一半。。。 Ni-15'是允许所述双链寡核苷酸低聚的序列的3-50mer突出端。包含所述寡核苷酸组合物并用于治疗应用的转染组合物。

2. 发明授权

US06013240A Nucleic acid containing composition, preparation and uses of same 失效
标题翻译：含有核酸的组合物，其制备及用途
公开(公告)号：US06013240A
公开(公告)日：2000-01-11
申请号：US765679
申请日：1997-02-28
申请人： Jean-Paul Behr , Barbara Demeneix , Franck Lezoualch , Mojgan Mergny , Daniel Scherman , Otmane Boussif
发明人： Jean-Paul Behr , Barbara Demeneix , Franck Lezoualch , Mojgan Mergny , Daniel Scherman , Otmane Boussif
IPC分类号： C12N15/00 , A61K9/00 , A61K31/66 , A61K31/70 , A61K38/00 , A61K39/395 , A61K47/48 , A61K48/00 , A61P31/04 , A61P31/12 , A61P35/00 , C07H21/04 , C12N15/88 , A61K9/127
CPC分类号： C12N15/88 , A61K47/48192
摘要： Compositions containing one or more nucleic acids and cationic polymers, and their use in gene therapy, particularly for in vivo nucleic acid transfer.
摘要翻译： PCT No.PCT / FR95 / 00914 Sec。 371日期1997年2月28日 102（e）1997年2月28日PCT PCT 1995年7月7日PCT公布。公开号WO96 / 02655 日期1996年2月1日含有一种或多种核酸和阳离子聚合物的组合物及其在基因治疗中的用途，特别是用于体内核酸转移。

3. 发明授权

US5171678A Lipopolyamines, their preparation and their use 失效
标题翻译：氯丙胺，他们的制备及其使用
公开(公告)号：US5171678A
公开(公告)日：1992-12-15
申请号：US509788
申请日：1990-04-17
申请人： Jean-Paul Behr , Jean-Philippe Loeffler
发明人： Jean-Paul Behr , Jean-Philippe Loeffler
IPC分类号： C07C229/00 , C07C233/00 , C07C235/00 , C07C237/22 , C07F9/10 , C12N15/00
CPC分类号： C07C237/22 , A61K47/48053 , C07C237/06 , C07C271/22 , C07F9/10
摘要： New lipopolyamines of general formula (I), their salts, their preparation and their use. ##STR1## n=1 to 5 and m=2 to 6; R represents a radical ##STR2## (R.sub.1 and R.sub.2 : aliphatic radical containing 12 to 22 carbon atoms; R: hydrogen atom or alkyl radical optionally substituted with phenyl), or a radical ##STR3## (X=CH.sub.2, CO; R.sub.3 and R.sub.4 aliphatic radical containing 11 to 21 carbon atoms), their preparation and their use.The lipopolyamines of general formula (I) are especially useful as vectors for the transfection of eukaryotic cells.
摘要翻译：新的通式（I）的脂多胺，其盐，其制备及其用途。（I）n = 1〜5，m = 2〜6; R表示基团（R1和R2：含有12-22个碳原子的脂族基团; R：氢原子或任选被苯基取代的烷基）或基团（X = CH 2，CO; R 3和R 4 含有11〜21个碳原子的脂族基团），它们的制备及其用途。通式（I）的脂多胺特别可用作转染真核细胞的载体。

4. 发明授权

US10927371B2 Cationic siRNAs, synthesis and use for RNA interference 有权
公开(公告)号：US10927371B2
公开(公告)日：2021-02-23
申请号：US12735595
申请日：2009-01-30
申请人： France Jean-Paul Behr , Mitsuharu Kotera , Nadege Pfender , Jean-Serge Remy
发明人： France Jean-Paul Behr , Mitsuharu Kotera , Nadege Pfender , Jean-Serge Remy
IPC分类号： C12N15/11
摘要： The invention relates to cationic siRNAs, characterized in that they are double-stranded RNA fragments, grafted to the ends of which are oligocations, the number of cationic charges grafted being comparable to or greater than that of the anionic charges carried by the internucleoside phosphates of the RNA strands.

5. 发明授权

US08399422B2 Compositions for transfection of oligonucleotides active for gene silencing and their biological and therapeutical applications 有权
标题翻译：用于转染活性基因沉默寡核苷酸的组合物及其生物学和治疗应用
公开(公告)号：US08399422B2
公开(公告)日：2013-03-19
申请号：US12226027
申请日：2007-04-05
申请人： Patrick Neuberg , Anne-Laure Bolcato Bellemin , Jean-Paul Behr , Patrick Erbacher
发明人： Patrick Neuberg , Anne-Laure Bolcato Bellemin , Jean-Paul Behr , Patrick Erbacher
IPC分类号： A61K48/00
CPC分类号： A61K48/0025 , A61K9/1271 , A61K31/4164 , A61K31/4184 , A61K31/7088 , A61K48/00 , A61K48/0033 , C12N15/88
摘要： The invention relates to compositions of transfection comprising an oligonucleotide and an amphiphilic cationic molecule of formula (I) wherein, —X is N—R1, S or O, R1 being a C1-C4 alkyl radical or an hydroxylated C3-C6 alkyl radical, R2 and R3, identical or different, represent H or a C1-C4 alkyl radical, or R2 and R3 are linked together to form a saturated or unsaturated cycle or a heterocycle having 5 or 6 elements, E is a C1-C5 alkyl spacer, R4 and R5, identical or different, represent saturated or unsaturated, linear or branched, C10-C36 hydrocarbon or fluorocarbon chains, optionally comprising C3-C6 cycloalkyl, A− is a biocompatible anion. The invention relates to compositions active for oligonucleotides delivery into eukaryotic cells in culture, ex vivo or in vivo. The invention relates to compositions of transfection comprising an oligonucleotide active for RNA interference. Such compositions can be used as tools for biological studies or as drugs for therapies.
摘要翻译：本发明涉及包含寡核苷酸和式（I）的两亲性阳离子分子的转染组合物，其中-X是N-R 1，S或O，R 1是C 1 -C 4烷基或羟基化的C 3 -C 6烷基， R2和R3相同或不同，表示H或C1-C4烷基，或R2和R3连接在一起形成饱和或不饱和的环或具有5或6个元素的杂环，E是C1-C5烷基间隔基， R 4和R 5相同或不同，表示任选包含C 3 -C 6环烷基的饱和或不饱和的直链或支链C 10 -C 36烃或碳氟化合物链，A-是生物相容的阴离子。本发明涉及在培养，离体或体内的寡核苷酸递送至真核细胞中活性的组合物。本发明涉及包含对RNA干扰有活性的寡核苷酸的转染组合物。这样的组合物可以用作生物学研究的工具或用于治疗的药物。

6. 发明申请

US20110118331A1 CATIONIC SIRNAS, SYNTHESIS AND USE FOR RNA INTERFERENCE 审中-公开
标题翻译：阳离子SIRNAS，RNA干扰的合成和使用
公开(公告)号：US20110118331A1
公开(公告)日：2011-05-19
申请号：US12735595
申请日：2009-01-30
申请人： France Jean-Paul Behr , Mitsuharu Kotera , Nadege Pfender , Jean-Serge Remy
发明人： France Jean-Paul Behr , Mitsuharu Kotera , Nadege Pfender , Jean-Serge Remy
IPC分类号： C07H21/02 , A61K31/7105
CPC分类号： C12N15/111 , C12N2310/14 , C12N2310/351 , C12N2320/32
摘要： The invention relates to cationic siRNAs, characterized in that they are double-stranded RNA fragments, grafted to the ends of which are oligocations, the number of cationic charges grafted being comparable to or greater than that of the anionic charges carried by the internucleoside phosphates of the RNA strands.
摘要翻译：本发明涉及阳离子siRNA，其特征在于它们是双链RNA片段，其末端接枝为寡聚物，所接枝的阳离子电荷的数目与由磷酸核苷间磷酸酯所携带的阴离子电荷相当或更大 RNA链。

7. 发明申请

US20090069262A1 Cationic Oligonucleotides, Automated Methods for Preparing Same and Their Uses 有权
标题翻译：阳离子寡核苷酸，自动制备方法及其用途
公开(公告)号：US20090069262A1
公开(公告)日：2009-03-12
申请号：US12086599
申请日：2006-12-14
申请人： Jean-Paul Behr , Mitsuharu Kotera , Benedicte Pons , Emilie Voirin , Jean-Serge Remy
发明人： Jean-Paul Behr , Mitsuharu Kotera , Benedicte Pons , Emilie Voirin , Jean-Serge Remy
IPC分类号： A61K31/7088 , C07H21/00 , C07H21/04 , C07H21/02 , C12Q1/68
CPC分类号： C07F9/22 , A61K47/59 , A61K48/0041 , C07H21/00 , C12N15/88
摘要： The invention relates to oligonucleotide-oligocation molecules AiBjH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein. Ai is an i-mer oligonucleotide residue, with i=5 to 50, where nucleotide A is an oligomer with naturally or non naturally occurring nucleobases and/or pentafuranosyl groups and/or native phosphodiester bonds, for example selected from the group comprising deoxyribo, ribo, locked (LNA) nucleotides as well as their chemical modifications or substitutions such as phosphorothioate, 2′-fluoro, 2′-O-alkyl, or a marker group such as a fluorescent agent, Bj is a j-mer organic oligocation moiety, with j=1 to 50, where B is selected from the group comprising .—HPO3—R1—(X—R2n)n1—X—R3—O—, where R1, R2n and R3, identical or different, are lower alkylene, X is NH or NC(NH2)2, n varies from 1 to 5 and n1=2 to 20, .—HPO3—R4—CH(R5X1)—R6—O—, where R4 is lower alkylene, R5 and R6, identical or different, are lower alkylene and X1 is putrescine, spermidine or spermine residue, .—HPO3—R7-(aa)n2-R8—O—, where R7 is lower alkylene and R8 is lower alkylene, serine, a natural aminoalcohol, (aa)n2 is a peptide containing natural aminoacids with cationic side chains, such as Arginine, Lysine, Ornithine, -Histidine, Diaminopropionic acid and n2=2 to 20.
摘要翻译：本发明涉及可通过自动亚磷酰胺化学合成寡核苷酸寡聚分子AiBjH，其具有寡核苷酸部分A 1和寡聚部分B 1，其中。 Ai是i = 5至50的i-mer寡核苷酸残基，其中核苷酸A是具有天然或非天然存在的核碱基和/或五呋喃糖基和/或天然磷酸二酯键的寡聚体，例如选自脱氧核糖，核苷酸，锁定（LNA）核苷酸以及它们的化学修饰或取代，例如硫代磷酸酯，2'-氟，2'-O-烷基或诸如荧光剂的标记基团，Bj是j-mer有机寡核苷酸部分，其中B选自包含-HPO 3 -R 1（X-R 2n）n1-X-R 3 -O-的基团，其中R 1，R 2n和R 3相同或不同，为低级亚烷基，X为NH或NC（NH 2）2，n为1至5，n 1 = 2至20，...-HPO 3 -R 4 -CH（R5X1）-R6-O-，其中R4为低级亚烷基，R5和R6，相同或不同的是低级亚烷基，X 1是腐胺，亚精胺或精胺残基。-HPO3-R7-（aa）n2-R8-O-，其中R7是低级亚烷基，R8是低级亚烷基，丝氨酸，天然氨基醇，（aa）n2是肽c 使用阳离子侧链，如精氨酸，赖氨酸，鸟氨酸，组氨酸，二氨基丙酸，n2 = 2〜20。

8. 发明授权

US09090648B2 Cationic oligonucleotides, automated methods for preparing same and their uses 有权
标题翻译：阳离子寡核苷酸，自动制备方法及其用途
公开(公告)号：US09090648B2
公开(公告)日：2015-07-28
申请号：US12086599
申请日：2006-12-14
申请人： Jean-Paul Behr , Mitsuharu Kotera , Bénédicte Pons , Emilie Voirin , Jean-Serge Remy
发明人： Jean-Paul Behr , Mitsuharu Kotera , Bénédicte Pons , Emilie Voirin , Jean-Serge Remy
IPC分类号： C07H21/00 , A61K47/00 , A61K47/48 , A61K48/00
CPC分类号： C07F9/22 , A61K47/59 , A61K48/0041 , C07H21/00 , C12N15/88
摘要： The invention relates to oligonucleotide-oligocation molecules AiBjH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein •Ai is an i-mer oligonucleotide residue, with i=5 to 50, where nucleotide A is an oligomer with naturally or non naturally occurring nucleobases and/or pentafuranosyl groups and/or native phosphodiester bonds, for example selected from the group comprising deoxyribo, ribo, locked (LNA) nucleotides as well as their chemical modifications or substitutions such as phosphorothioate, 2′-fluoro, 2′-O-alkyl, or a marker group such as a fluorescent agent, •Bj is a j-mer organic oligocation moiety, with j=1 to 50, where B is selected from the group comprising •—HPO3—R1—(X—R2n)n1—X—R3—O—, where R1, R2n and R3, identical or different, are lower alkylene, X is NH or NC(NH2)2, n varies from 1 to 5 and n1=2 to 20, •—HPO3—R4—CH(R5X1)—R6—O—, where R4 is lower alkylene, R5 and R6, identical or different, are lower alkylene and X1 is putrescine, spermidine or spermine residue, •—HPO3—R7-(aa)n2-R8—O—, where R7 is lower alkylene and R8 is lower alkylene, serine, a natural aminoalcohol, (aa)n2 is a peptide containing natural aminoacids with cationic side chains, such as Arginine, Lysine, Ornithine, -Histidine, Diaminopropionic acid and n2=2 to 20.
摘要翻译：本发明涉及可通过具有寡核苷酸部分A 1和寡核苷酸部分B 1的自动亚磷酰胺化学合成的寡核苷酸寡聚分子AiBjH，其中·Ai是i = 5〜50的i-mer寡核苷酸残基，其中核苷酸A为低聚物与天然或非天然存在的核碱基和/或五五烷酰基基团和/或天然磷酸二酯键，例如选自脱氧核糖核酸，核糖体，锁定（LNA）核苷酸以及它们的化学修饰或取代，例如硫代磷酸酯，氟，2'-O-烷基或标记基团如荧光剂，Bj是j-mer有机寡核苷酸部分，j = 1-50，其中B选自-HPO 3 -R 1 - （X-R2n）n1-X-R3-O-，其中R1，R2n和R3相同或不同，为低级亚烷基，X为NH或NC（NH2）2，n为1至5，n1 = 2 至20，-HPO 3 -R 4 -CH（R5X1）-R6-O-，其中R4较低亚烷基，R 5和R 6相同或不同，为低级亚烷基，X 1为腐胺，亚精胺或精胺残基，-HPO3-R7-（aa）n2-R8-O-，其中R7为低级亚烷基，R8为低级亚烷基，丝氨酸，天然氨基醇，（aa）n2是含有阳离子侧链的天然氨基酸的肽，例如精氨酸，赖氨酸，鸟氨酸，组氨酸，二氨基丙酸，n2 = 2〜20。

9. 发明申请

US20100048672A1 COMPOSITIONS FOR TRANSFECTION OF OLIGONUCLEOTIDES ACTIVE FOR GENE SILENCING AND THEIR BIOLOGICAL AND THERAPEUTICAL APPLICATIONS 有权
标题翻译：用于转基因沉默的寡核苷酸组合物及其生物和治疗应用
公开(公告)号：US20100048672A1
公开(公告)日：2010-02-25
申请号：US12226027
申请日：2007-04-05
申请人： Patrick Neuberg , Anne-Laure Bolcato Bellemin , Jean-Paul Behr , Patrick Erbacher
发明人： Patrick Neuberg , Anne-Laure Bolcato Bellemin , Jean-Paul Behr , Patrick Erbacher
IPC分类号： A61K48/00 , C12N15/00 , A61P35/00 , A61P31/12 , A61P33/00 , C07D233/56 , C07D235/08 , C07H21/04
CPC分类号： A61K48/0025 , A61K9/1271 , A61K31/4164 , A61K31/4184 , A61K31/7088 , A61K48/00 , A61K48/0033 , C12N15/88
摘要： The invention relates to compositions of transfection comprising an oligonucleotide and an amphiphilic cationic molecule of formula (I) wherein, —X is N—R1, S or O, R1 being a C1-C4 alkyl radical or an hydroxylated C3-C6 alkyl radical, R2 and R3, identical or different, represent H or a C1-C4 alkyl radical, or R2 and R3 are linked together to form a saturated or unsaturated cycle or a heterocycle having 5 or 6 elements, E is a C1-C5 alkyl spacer, R4 and R5, identical or different, represent saturated or unsaturated, linear or branched, C10-C36 hydrocarbon or fluorocarbon chains, optionally comprising C3-C6 cycloalkyl, A- is a biocompatible anion. The invention relates to compositions active for oligonucleotides delivery into eukaryotic cells in culture, ex vivo or in vivo. The invention relates to compositions of transfection comprising an oligonucleotide active for RNA interference. Such compositions can be used as tools for biological studies or as drugs for therapies.
摘要翻译：本发明涉及包含寡核苷酸和式（I）的两亲性阳离子分子的转染组合物，其中-X是N-R 1，S或O，R 1是C 1 -C 4烷基或羟基化的C 3 -C 6烷基， R2和R3相同或不同，表示H或C1-C4烷基，或R2和R3连接在一起形成饱和或不饱和的环或具有5或6个元素的杂环，E是C1-C5烷基间隔基， R 4和R 5相同或不同，表示任选包含C 3 -C 6环烷基的饱和或不饱和的直链或支链C 10 -C 36烃或碳氟化合物链，A-是生物相容的阴离子。本发明涉及在培养，离体或体内的寡核苷酸递送至真核细胞中活性的组合物。本发明涉及包含对RNA干扰有活性的寡核苷酸的转染组合物。这样的组合物可以用作生物学研究的工具或用于治疗的药物。

10. 发明申请

US20080153772A1 Oligonucleotides For Rna Interference and Biological Applications Thereof 有权
标题翻译：寡核苷酸用于Rna干扰和生物应用
公开(公告)号：US20080153772A1
公开(公告)日：2008-06-26
申请号：US11921089
申请日：2006-06-01
申请人： Jean-Paul Behr , Anne-Laure Bolcato Bellemin , Patrick Erbacher
发明人： Jean-Paul Behr , Anne-Laure Bolcato Bellemin , Patrick Erbacher
IPC分类号： A61K31/713 , C07H21/00 , C12P19/34 , C12N5/02 , A61P31/12
CPC分类号： C12N15/113 , A61K31/713 , A61K47/34 , C12N15/111 , C12N2310/14 , C12N2310/51 , C12N2320/30 , C12N2320/51 , C12N2320/52
摘要： The invention relates to compositions comprising double-stranded oligonucleotides of identical or different sequences and/or length, said oligonucleotides having sequences 3′N1N2 . . . Ni−1Ni . . . Nj5′ wherein—3Ni . . . Nj5′ is half of a double-stranded 19-28 mer oligonucleotide of sequence complementary to a target nucleic acid sequence present in a living cell, and—3′N1 . . . Ni−15′ is a 3-50 mer overhang of sequence allowing oligomerisation of said double-stranded oligonucleotide. Compositions of transfection comprising said oligonucleotide compositions and there used for therapeutical application.
摘要翻译：本发明涉及包含相同或不同序列和/或长度的双链寡核苷酸的组合物，所述寡核苷酸具有序列“N”N 1 N 2 N 2 >。。。 N 1-N 1 N 2。。。其中 - N 3 N 1 - - - - - - - - - - - - - - 。。 N'是与存在于活细胞中的靶核酸序列互补的序列的双链19-28mer寡核苷酸的一半，而< 3'N 1 。。。 N 1 -I 5'是序列的3-50个突出端，允许所述双链寡核苷酸的低聚。包含所述寡核苷酸组合物并用于治疗应用的转染组合物。

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