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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。

3. 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。

4. 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。

5. 发明授权

US08465920B2 Method for hybridizing nucleic acids 有权
标题翻译：核酸杂交方法
公开(公告)号：US08465920B2
公开(公告)日：2013-06-18
申请号：US12735261
申请日：2008-09-12
申请人： Nathalie Lenne , Patrick Erbacher
发明人： Nathalie Lenne , Patrick Erbacher
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6832 , C12Q2525/113 , C12Q2563/113 , C12Q2525/119
摘要： The invention relates to a method for manipulating, isolating, detecting or amplifying a target nucleic acid in a sample by hybridization with an oligonucleotide-oligocation conjugate, comprising allowing said nucleic acid to react with an oligonucleotide-oligocation conjugate comprising at least A1 and Bj linked together directly or via a linker, wherein. A, is an i-mer oligonucleotides, with i=3 to 50, where Ai is an oligomer with naturally or non naturally occurring nucleobases and/or pentafuranosyl groups and/or native phosphodiester bonds, optionally comprising a marker group. Bj is a j-mer organic oligocation moiety, with j=1 to 50, where B is —HPO3—R1—(NH—R2)n—NH—R3—O—, where R1, R2 and R3 are lower alkylene, identical or different, NH—R2 moieties being identical or different when n is >1; HPO3—R1—CH(X)—R3—O—, where Ri and R3, identical or different, are lower alkylene and X is putrescine, spermidine or spermine residue.
摘要翻译：本发明涉及通过与寡核苷酸寡核苷酸缀合物杂交来操纵，分离，检测或扩增样品中的靶核酸的方法，包括使所述核酸与包含至少A1和Bj连接的寡核苷酸寡核苷酸轭合物反应一起直接或通过连接体，其中。 A是i = 3至50的i-mer寡核苷酸，其中A 1是具有天然或非天然存在的核碱基和/或五五烷酰基基团和/或天然磷酸二酯键的寡聚体，任选地包含标记基团。 Bj是j-1有机寡核苷酸部分，其中B = -HPO 3 -R1-（NH-R 2）n -NH-R 3 -O-，其中R 1，R 2和R 3为低级亚烷基，相同或不同的NH-R 2部分在n> 1时相同或不同; HPO 3 -R 1 -CH（X）-R 3 -O-，其中R 1和R 3相同或不同，为低级亚烷基，X为腐胺，亚精胺或精胺残基。

6. 发明申请

US20100297756A1 MEANS FOR DELIVERY OF NUCLEIC ACIDS ACTIVE FOR GENE SILENCING USING SYNTHETIC POLYMERS 审中-公开
标题翻译：使用合成聚合物输送用于基因沉默的核酸的方法
公开(公告)号：US20100297756A1
公开(公告)日：2010-11-25
申请号：US12735031
申请日：2008-12-12
申请人： Abdennajj Adib , Patrick Erbacher , Fabrice Stock , Nadia Hafdi
发明人： Abdennajj Adib , Patrick Erbacher , Fabrice Stock , Nadia Hafdi
IPC分类号： C12N5/071 , C12N15/79 , C07C229/00
CPC分类号： A61K48/0041 , C12N15/111 , C12N15/87 , C12N2310/14 , C12N2320/32
摘要： The invention relates to a composition useful as transfection agent, comprising polyamines modified by aromatic amino acids and small double-strand or single-strand RNA active for RNA interference.
摘要翻译：本发明涉及可用作转染剂的组合物，其包含由芳族氨基酸修饰的多胺和用于RNA干扰的小双链或单链RNA。

7. 发明授权

US5595897A Polylysine conjugates 失效
标题翻译：聚赖氨酸共轭物
公开(公告)号：US5595897A
公开(公告)日：1997-01-21
申请号：US288681
申请日：1994-08-10
申请人： Patrick Midoux , Patrick Erbacher , Annie-Claude Roche-Degremont , Michel Monsigny
发明人： Patrick Midoux , Patrick Erbacher , Annie-Claude Roche-Degremont , Michel Monsigny
IPC分类号： A61K47/48 , C12N15/87 , C07K1/00 , C07K1/107 , C12N15/00 , C12N15/88
CPC分类号： C12N15/87 , A61K47/48315
摘要： The invention concerns a complex between at least one negatively charged nucleic acid and at least one positively charged polymeric conjugate, the link between the nucleic acid and the polymeric conjugate being electrostatic in nature, the polymeric conjugate containing a polymer formed from monomer components having free NH.sub.3.sup.+ functions of the aforementioned components and being as follows:--the free NH.sub.3.sup.+ functions from the aforementioned components are substituted in a ratio of at least 10%, advantageously from 45% to 70%, particularly 60%, by noncharged residues leading to a reduction of positive charges in comparison to the same nonsubstituted polymeric conjugate, facilitating the release of nucleic acid by the dissociation of the complex,--the aforementioned residues possess in addition the following properties:.fwdarw.they contain at least one hydroxyl group,.fwdarw.they do not correspond to a recognition signal recognized by a cellular membrane receptor,--the free NH.sub.3.sup.+ functions from the above mentioned components and/or the hydroxyl groups of the above mentioned residues are also able to be substituted by at least one molecule which constitutes a recognition signal recognized by a cellular membrane receptor, under the condition that the polymeric conjugate contains at least 30% free NH.sub.3.sup.+ functions.
摘要翻译：本发明涉及至少一个带负电荷的核酸和至少一个带正电荷的聚合物缀合物之间的复合物，核酸和聚合物缀合物之间的连接本质上是静电的，所述聚合物缀合物含有由具有游离NH 3+的单体组分形成的聚合物，上述组分的功能如下： - 上述组分的游离NH 3+官能团以至少10％，有利地为45％至70％，特别是60％的比例被非电荷残基取代，导致降低与相同的非取代的聚合物缀合物相比，正电荷有利于通过络合物的解离释放核酸，上述残基另外具有以下性质： - >它们含有至少一个羟基， - >它们不对应于由细胞膜受体识别的识别信号， - 来自a的游离NH 3+功能所述提及的组分和/或上述残基的羟基也能够被至少一种构成由细胞膜受体识别的识别信号的分子取代，条件是聚合物缀合物含有至少30％的游离 NH3 +功能。

8. 发明申请

US20110091935A1 PRODUCTION OF RECOMBINANT PROTEINS IN SYNTHETIC MEDIUM 审中-公开
标题翻译：合成培养基中重组蛋白的生产
公开(公告)号：US20110091935A1
公开(公告)日：2011-04-21
申请号：US12975788
申请日：2010-12-22
申请人： Patrick Erbacher , Abdennaji Adib
发明人： Patrick Erbacher , Abdennaji Adib
IPC分类号： C12P21/02
CPC分类号： C12N5/0018 , C12N2510/02
摘要： The invention relates to a method for the production of recombinant proteins by eucaryotic cells in synthetic culture media, wherein said eucaryotic cells are transfected with a composition comprising a synthetic transfection reagent based on a polyhydroxylated polyalkyleneimine.
摘要翻译：本发明涉及通过合成培养基中的真核细胞生产重组蛋白的方法，其中所述真核细胞用包含基于多羟基化聚亚烷基亚胺的合成转染试剂的组合物转染。

9. 发明申请

US20100311056A1 METHOD FOR HYBRIDIZING NUCLEIC ACIDS 有权
标题翻译：用于杂交核酸的方法
公开(公告)号：US20100311056A1
公开(公告)日：2010-12-09
申请号：US12735261
申请日：2008-09-12
申请人： Nathalie Lenne , Patrick Erbacher
发明人： Nathalie Lenne , Patrick Erbacher
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6832 , C12Q2525/113 , C12Q2563/113 , C12Q2525/119
摘要： The invention relates to a method for manipulating, isolating, detecting or amplifying a target nucleic acid in a sample by hybridization with an oligonucleotide-oligocation conjugate, comprising allowing said nucleic acid to react with an oligonucleotide-oligocation conjugate comprising at least A1 and Bj linked together directly or via a linker, wherein. A, is an i-mer oligonucleotides, with i=3 to 50, where Ai is an oligomer with naturally or non naturally occurring nucleobases and/or pentafuranosyl groups and/or native phosphodiester bonds, optionally comprising a marker group. Bj is a j-mer organic oligocation moiety, with j=1 to 50, where B is —HPO3—R1—(NH—R2)n—NH—R3—O—, where R1, R2 and R3 are lower alkylene, identical or different, NH—R2 moieties being identical or different when n is >1; HPO3—R1—CH(X)—R3—O—, where Ri and R3, identical or different, are lower alkylene and X is putrescine, spermidine or spermine residue.
摘要翻译：本发明涉及通过与寡核苷酸寡聚轭合物杂交来操纵，分离，检测或扩增样品中的靶核酸的方法，包括使所述核酸与至少包含A1和Bj连接的寡核苷酸寡聚轭合物反应一起直接或通过连接体，其中。 A是i = 3至50的i-mer寡核苷酸，其中A 1是具有天然或非天然存在的核碱基和/或五五烷酰基基团和/或天然磷酸二酯键的寡聚体，任选地包含标记基团。 Bj是j-1有机寡核苷酸部分，其中B = -HPO 3 -R1-（NH-R 2）n -NH-R 3 -O-，其中R 1，R 2和R 3为低级亚烷基，相同或不同的NH-R 2部分在n> 1时相同或不同; HPO 3 -R 1 -CH（X）-R 3 -O-，其中R 1和R 3相同或不同，为低级亚烷基，X为腐胺，亚精胺或精胺残基。

10. 发明申请

US20100197888A1 Method for Manufacturing Linear Polyethylenimine (PEI) for Transfection Purpose and Linear PEI Obtained with Such Method 审中-公开
标题翻译：制造用于转染目的的线性聚乙烯亚胺（PEI）和用这种方法获得的线性PEI的方法
公开(公告)号：US20100197888A1
公开(公告)日：2010-08-05
申请号：US12671312
申请日：2008-07-31
申请人： Abdennaji Adib , Fabrice Stock , Patrick Erbacher
发明人： Abdennaji Adib , Fabrice Stock , Patrick Erbacher
IPC分类号： C08G73/06
CPC分类号： C08G73/0233 , C12N15/87
摘要： The invention concerns a method of synthesising and preparing linear polyethylenimine (PEI) for use as a transfection vector, and the product obtained with such a method. It comprises drying a monomer 2-ethyl-2-oxazoline and polymerising said monomer for obtaining poly (2-ethyl-2-oxazoline) (PEOX) by: using acetonitrile as solvent, adding a dried initiator of the reaction of polymerisation, and mixing them altogether, purifying said obtained PEOX by evaporation, while performing at least three times successive washing/precipitation steps with methanol and diethyl ether and corresponding filtrations, in order to obtain (i), by performing 1H-NMR tests, correct identification of said PEOX polymer, confirmation of absence of monomer to a level 23,000 Da and polydispersity (Mw/Mn) of said PEOX
摘要翻译：本发明涉及一种合成和制备用作转染载体的线性聚乙烯亚胺（PEI）的方法，以及用这种方法获得的产品。它包括干燥单体2-乙基-2-恶唑啉并使所述单体聚合以获得聚（2-乙基-2-恶唑啉）（PEOX）：通过使用乙腈作为溶剂，加入干燥的聚合反应引发剂和混合它们一起通过蒸发纯化所获得的PEOX，同时用甲醇和二乙醚进行至少三次连续的洗涤/沉淀步骤和相应的过滤，以获得（i）通过进行1H-NMR测试，正确鉴定所述PEOX 聚合物，确认不存在单体至<1.0％的水平，并且确认溶剂不存在至<5.0％的水平，和（ii）通过进行凝胶渗透色谱法，分子量（Mw）> 23,000Da的平均值和多分散性所述PEOX <1.5的Mw / Mn）水解所述PEOX。

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