JP2015501844A5 - - Google Patents

Info

Publication number

JP2015501844A5

JP2015501844A5 JP2014547454A JP2014547454A JP2015501844A5 JP 2015501844 A5 JP2015501844 A5 JP 2015501844A5 JP 2014547454 A JP2014547454 A JP 2014547454A JP 2014547454 A JP2014547454 A JP 2014547454A JP 2015501844 A5 JP2015501844 A5 JP 2015501844A5

Authority

JP

Japan

Prior art keywords

lipid

modified mrna

peg

formulation

dlin

Prior art date

2012-12-14

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.)

Pending

Links

• Espacenet
• Global Dossier
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• 238000000034 method Methods 0.000 claims 31
• 150000002632 lipids Chemical class 0.000 claims 26
• 108020004999 messenger RNA Proteins 0.000 claims 24
• 239000000203 mixture Substances 0.000 claims 15
• 238000009472 formulation Methods 0.000 claims 10
• 239000002105 nanoparticle Substances 0.000 claims 10
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical class C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 8
• 230000000799 fusogenic effect Effects 0.000 claims 6
• 230000000144 pharmacologic effect Effects 0.000 claims 6
• 229920000642 polymer Polymers 0.000 claims 5
• 229920001184 polypeptide Polymers 0.000 claims 5
• 102000004196 processed proteins & peptides Human genes 0.000 claims 5
• 108090000765 processed proteins & peptides Proteins 0.000 claims 5
• 102000009123 Fibrin Human genes 0.000 claims 4
• 108010073385 Fibrin Proteins 0.000 claims 4
• BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims 4
• 235000012000 cholesterol Nutrition 0.000 claims 4
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
• 150000002148 esters Chemical class 0.000 claims 4
• 229950003499 fibrin Drugs 0.000 claims 4
• 230000004048 modification Effects 0.000 claims 4
• 238000012986 modification Methods 0.000 claims 4
• NRLNQCOGCKAESA-KWXKLSQISA-N [(6z,9z,28z,31z)-heptatriaconta-6,9,28,31-tetraen-19-yl] 4-(dimethylamino)butanoate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCCC(OC(=O)CCCN(C)C)CCCCCCCC\C=C/C\C=C/CCCCC NRLNQCOGCKAESA-KWXKLSQISA-N 0.000 claims 3
• 239000000017 hydrogel Substances 0.000 claims 3
• 239000004005 microsphere Substances 0.000 claims 3
• 239000008194 pharmaceutical composition Substances 0.000 claims 3
• 210000002966 serum Anatomy 0.000 claims 3
• NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 claims 2
• RVHYPUORVDKRTM-UHFFFAOYSA-N 1-[2-[bis(2-hydroxydodecyl)amino]ethyl-[2-[4-[2-[bis(2-hydroxydodecyl)amino]ethyl]piperazin-1-yl]ethyl]amino]dodecan-2-ol Chemical compound CCCCCCCCCCC(O)CN(CC(O)CCCCCCCCCC)CCN(CC(O)CCCCCCCCCC)CCN1CCN(CCN(CC(O)CCCCCCCCCC)CC(O)CCCCCCCCCC)CC1 RVHYPUORVDKRTM-UHFFFAOYSA-N 0.000 claims 2
• HXVVOLDXHIMZJZ-UHFFFAOYSA-N 3-[2-[2-[2-[bis[3-(dodecylamino)-3-oxopropyl]amino]ethyl-[3-(dodecylamino)-3-oxopropyl]amino]ethylamino]ethyl-[3-(dodecylamino)-3-oxopropyl]amino]-n-dodecylpropanamide Chemical compound CCCCCCCCCCCCNC(=O)CCN(CCC(=O)NCCCCCCCCCCCC)CCN(CCC(=O)NCCCCCCCCCCCC)CCNCCN(CCC(=O)NCCCCCCCCCCCC)CCC(=O)NCCCCCCCCCCCC HXVVOLDXHIMZJZ-UHFFFAOYSA-N 0.000 claims 2
• -1 cationic lipid Chemical class 0.000 claims 2
• 229920001577 copolymer Polymers 0.000 claims 2
• 201000010099 disease Diseases 0.000 claims 2
• 208000035475 disorder Diseases 0.000 claims 2
• 208000015181 infectious disease Diseases 0.000 claims 2
• 210000004962 mammalian cell Anatomy 0.000 claims 2
• 239000003894 surgical glue Substances 0.000 claims 2
• UTAIYTHAJQNQDW-KQYNXXCUSA-N 1-methylguanosine Chemical compound C1=NC=2C(=O)N(C)C(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O UTAIYTHAJQNQDW-KQYNXXCUSA-N 0.000 claims 1
• UVBYMVOUBXYSFV-XUTVFYLZSA-N 1-methylpseudouridine Chemical compound O=C1NC(=O)N(C)C=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UVBYMVOUBXYSFV-XUTVFYLZSA-N 0.000 claims 1
• UVBYMVOUBXYSFV-UHFFFAOYSA-N 1-methylpseudouridine Natural products O=C1NC(=O)N(C)C=C1C1C(O)C(O)C(CO)O1 UVBYMVOUBXYSFV-UHFFFAOYSA-N 0.000 claims 1
• LRFJOIPOPUJUMI-KWXKLSQISA-N 2-[2,2-bis[(9z,12z)-octadeca-9,12-dienyl]-1,3-dioxolan-4-yl]-n,n-dimethylethanamine Chemical compound CCCCC\C=C/C\C=C/CCCCCCCCC1(CCCCCCCC\C=C/C\C=C/CCCCC)OCC(CCN(C)C)O1 LRFJOIPOPUJUMI-KWXKLSQISA-N 0.000 claims 1
• JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 claims 1
• JTMZHHMIEMBYNV-VITAEQTISA-N 2-amino-9-[(2r,3r,4s,5r)-2-azido-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@]1(N=[N+]=[N-])O[C@H](CO)[C@@H](O)[C@H]1O JTMZHHMIEMBYNV-VITAEQTISA-N 0.000 claims 1
• BGTXMQUSDNMLDW-AEHJODJJSA-N 2-amino-9-[(2r,3s,4r,5r)-3-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@]1(O)F BGTXMQUSDNMLDW-AEHJODJJSA-N 0.000 claims 1
• ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 claims 1
• ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 claims 1
• HCAJQHYUCKICQH-VPENINKCSA-N 8-Oxo-7,8-dihydro-2'-deoxyguanosine Chemical compound C1=2NC(N)=NC(=O)C=2NC(=O)N1[C@H]1C[C@H](O)[C@@H](CO)O1 HCAJQHYUCKICQH-VPENINKCSA-N 0.000 claims 1
• 241000180579 Arca Species 0.000 claims 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
• 108090000790 Enzymes Proteins 0.000 claims 1
• 102000004190 Enzymes Human genes 0.000 claims 1
• 108010049003 Fibrinogen Proteins 0.000 claims 1
• 102000008946 Fibrinogen Human genes 0.000 claims 1
• 102000001554 Hemoglobins Human genes 0.000 claims 1
• 108010054147 Hemoglobins Proteins 0.000 claims 1
• UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims 1
• 229930010555 Inosine Natural products 0.000 claims 1
• RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims 1
• 229930185560 Pseudouridine Natural products 0.000 claims 1
• PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 claims 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 1
• 108090000190 Thrombin Proteins 0.000 claims 1
• WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 claims 1
• 239000000872 buffer Substances 0.000 claims 1
• DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 claims 1
• 229910052791 calcium Inorganic materials 0.000 claims 1
• 239000011575 calcium Substances 0.000 claims 1
• BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 claims 1
• 150000001720 carbohydrates Chemical class 0.000 claims 1
• 235000014633 carbohydrates Nutrition 0.000 claims 1
• 125000002091 cationic group Chemical group 0.000 claims 1
• 210000004027 cell Anatomy 0.000 claims 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 230000000694 effects Effects 0.000 claims 1
• 238000005538 encapsulation Methods 0.000 claims 1
• 229940088598 enzyme Drugs 0.000 claims 1
• 239000005038 ethylene vinyl acetate Substances 0.000 claims 1
• 229940012952 fibrinogen Drugs 0.000 claims 1
• 239000000499 gel Substances 0.000 claims 1
• 239000003292 glue Substances 0.000 claims 1
• 229940029575 guanosine Drugs 0.000 claims 1
• 238000005534 hematocrit Methods 0.000 claims 1
• 238000000338 in vitro Methods 0.000 claims 1
• 229960003786 inosine Drugs 0.000 claims 1
• 239000002502 liposome Substances 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• 150000002772 monosaccharides Chemical class 0.000 claims 1
• GLGLUQVVDHRLQK-WRBBJXAJSA-N n,n-dimethyl-2,3-bis[(z)-octadec-9-enoxy]propan-1-amine Chemical compound CCCCCCCC\C=C/CCCCCCCCOCC(CN(C)C)OCCCCCCCC\C=C/CCCCCCCC GLGLUQVVDHRLQK-WRBBJXAJSA-N 0.000 claims 1
• 239000002953 phosphate buffered saline Substances 0.000 claims 1
• 229960000502 poloxamer Drugs 0.000 claims 1
• 229920001983 poloxamer Polymers 0.000 claims 1
• 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 claims 1
• PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 claims 1
• 239000000565 sealant Substances 0.000 claims 1
• 239000011780 sodium chloride Substances 0.000 claims 1
• 239000000243 solution Substances 0.000 claims 1
• 229940124597 therapeutic agent Drugs 0.000 claims 1
• 229960004072 thrombin Drugs 0.000 claims 1