JP2008525514A5 - - Google Patents

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Publication number

JP2008525514A5

JP2008525514A5 JP2007548751A JP2007548751A JP2008525514A5 JP 2008525514 A5 JP2008525514 A5 JP 2008525514A5 JP 2007548751 A JP2007548751 A JP 2007548751A JP 2007548751 A JP2007548751 A JP 2007548751A JP 2008525514 A5 JP2008525514 A5 JP 2008525514A5

Authority

JP

Japan

Prior art keywords

lipid

composition according

composition

group

helper

Prior art date

2005-12-27

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Granted

Links

• Espacenet
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• 239000000203 mixture Substances 0.000 claims 67
• 150000002632 lipids Chemical class 0.000 claims 63
• 108020004707 nucleic acids Proteins 0.000 claims 19
• 102000039446 nucleic acids Human genes 0.000 claims 19
• 150000007523 nucleic acids Chemical class 0.000 claims 19
• 150000001875 compounds Chemical class 0.000 claims 17
• YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 claims 11
• CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 claims 11
• 229940106189 ceramide Drugs 0.000 claims 11
• ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 claims 11
• VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 claims 11
• 125000005647 linker group Chemical group 0.000 claims 9
• -1 polypropylene Polymers 0.000 claims 7
• 108091030071 RNAI Proteins 0.000 claims 5
• 108020004459 Small interfering RNA Proteins 0.000 claims 5
• 210000004027 cell Anatomy 0.000 claims 5
• 230000009368 gene silencing by RNA Effects 0.000 claims 5
• 244000089409 Erythrina poeppigiana Species 0.000 claims 4
• 235000009776 Rathbunia alamosensis Nutrition 0.000 claims 4
• 239000012528 membrane Substances 0.000 claims 4
• 238000000034 method Methods 0.000 claims 4
• 101150054147 sina gene Proteins 0.000 claims 4
• BKHMAOXOKNEKHL-NNJYRKLXSA-N (5s)-2,3,5-triamino-8-(diaminomethylideneamino)-n-hexadecyl-n-[(z)-octadec-9-enyl]-4-oxooctanamide;trihydrochloride Chemical compound Cl.Cl.Cl.CCCCCCCCCCCCCCCCN(C(=O)C(N)C(N)C(=O)[C@@H](N)CCCNC(N)=N)CCCCCCCC\C=C/CCCCCCCC BKHMAOXOKNEKHL-NNJYRKLXSA-N 0.000 claims 3
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 3
• 102000053642 Catalytic RNA Human genes 0.000 claims 3
• 108090000994 Catalytic RNA Proteins 0.000 claims 3
• 108020004414 DNA Proteins 0.000 claims 3
• 125000000129 anionic group Chemical group 0.000 claims 3
• 230000000692 anti-sense effect Effects 0.000 claims 3
• 108091092562 ribozyme Proteins 0.000 claims 3
• 102000040650 (ribonucleotides)n+m Human genes 0.000 claims 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 2
• 108091023037 Aptamer Proteins 0.000 claims 2
• 102000053602 DNA Human genes 0.000 claims 2
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
• 229920002472 Starch Polymers 0.000 claims 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 2
• 230000002378 acidificating effect Effects 0.000 claims 2
• 150000001450 anions Chemical class 0.000 claims 2
• 125000004432 carbon atom Chemical group C* 0.000 claims 2
• 239000003795 chemical substances by application Substances 0.000 claims 2
• MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims 2
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
• 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
• 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
• 108090000765 processed proteins & peptides Proteins 0.000 claims 2
• 235000018102 proteins Nutrition 0.000 claims 2
• 108090000623 proteins and genes Proteins 0.000 claims 2
• 102000004169 proteins and genes Human genes 0.000 claims 2
• 229920002477 rna polymer Polymers 0.000 claims 2
• 239000002904 solvent Substances 0.000 claims 2
• 235000019698 starch Nutrition 0.000 claims 2
• 239000008107 starch Substances 0.000 claims 2
• VHAZCTYLSXXYPK-YKOZOZHESA-N (2S,8S)-2,6,8-triamino-11-(diaminomethylideneamino)-N-dodecyl-7-oxo-N-tetradecylundecanamide trihydrochloride Chemical compound Cl.Cl.Cl.CCCCCCCCCCCCCCN(CCCCCCCCCCCC)C(=O)[C@@H](N)CCCC(N)C(=O)[C@@H](N)CCCNC(N)=N VHAZCTYLSXXYPK-YKOZOZHESA-N 0.000 claims 1
• VQTHDGIYEUWNQH-YSYGPASPSA-N (5S)-2,3,5-triamino-8-(diaminomethylideneamino)-N-dodecyl-4-oxo-N-tetradecyloctanamide trihydrochloride Chemical compound Cl.Cl.Cl.CCCCCCCCCCCCCCN(CCCCCCCCCCCC)C(=O)C(N)C(N)C(=O)[C@@H](N)CCCNC(N)=N VQTHDGIYEUWNQH-YSYGPASPSA-N 0.000 claims 1
• LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 claims 1
• MWRBNPKJOOWZPW-NYVOMTAGSA-N 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-NYVOMTAGSA-N 0.000 claims 1
• XLPHMKQBBCKEFO-DHYROEPTSA-N 2-azaniumylethyl [(2r)-2,3-bis(3,7,11,15-tetramethylhexadecanoyloxy)propyl] phosphate Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)CC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CC(C)CCCC(C)CCCC(C)CCCC(C)C XLPHMKQBBCKEFO-DHYROEPTSA-N 0.000 claims 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
• 101001007348 Arachis hypogaea Galactose-binding lectin Proteins 0.000 claims 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 1
• QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 claims 1
• 108091034117 Oligonucleotide Proteins 0.000 claims 1
• 239000004743 Polypropylene Substances 0.000 claims 1
• 108091081021 Sense strand Proteins 0.000 claims 1
• 108091027076 Spiegelmer Proteins 0.000 claims 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 1
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 1
• 239000004480 active ingredient Substances 0.000 claims 1
• 125000002252 acyl group Chemical group 0.000 claims 1
• 125000000217 alkyl group Chemical group 0.000 claims 1
• 239000012736 aqueous medium Substances 0.000 claims 1
• 210000000170 cell membrane Anatomy 0.000 claims 1
• 239000000470 constituent Substances 0.000 claims 1
• 239000006185 dispersion Substances 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 210000001163 endosome Anatomy 0.000 claims 1
• 235000013922 glutamic acid Nutrition 0.000 claims 1
• 239000004220 glutamic acid Substances 0.000 claims 1
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims 1
• 210000005260 human cell Anatomy 0.000 claims 1
• 238000001727 in vivo Methods 0.000 claims 1
• 239000002479 lipoplex Substances 0.000 claims 1
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
• 210000004962 mammalian cell Anatomy 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• 230000007935 neutral effect Effects 0.000 claims 1
• 125000001117 oleyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N ornithyl group Chemical group N[C@@H](CCCN)C(=O)O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims 1
• 229960003330 pentetic acid Drugs 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• 150000003904 phospholipids Chemical class 0.000 claims 1
• 108091033319 polynucleotide Proteins 0.000 claims 1
• 102000040430 polynucleotide Human genes 0.000 claims 1
• 239000002157 polynucleotide Substances 0.000 claims 1
• 229920001155 polypropylene Polymers 0.000 claims 1
• 102000004196 processed proteins & peptides Human genes 0.000 claims 1
• 150000003431 steroids Chemical class 0.000 claims 1
• 230000005945 translocation Effects 0.000 claims 1