HRP20231412T1 - Uređaj za kontrolu temperature, pogon za obradu površina, proizvodni pogon i postupak za proizvodnju proizvoda - Google Patents
Uređaj za kontrolu temperature, pogon za obradu površina, proizvodni pogon i postupak za proizvodnju proizvoda Download PDFInfo
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- HRP20231412T1 HRP20231412T1 HRP20231412TT HRP20231412T HRP20231412T1 HR P20231412 T1 HRP20231412 T1 HR P20231412T1 HR P20231412T T HRP20231412T T HR P20231412TT HR P20231412 T HRP20231412 T HR P20231412T HR P20231412 T1 HRP20231412 T1 HR P20231412T1
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- hypertension
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- dsrna agent
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- 102000004881 Angiotensinogen Human genes 0.000 title claims 8
- 108090001067 Angiotensinogen Proteins 0.000 title claims 8
- 238000000034 method Methods 0.000 title claims 3
- 239000000203 mixture Substances 0.000 title claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 20
- 150000003839 salts Chemical class 0.000 claims 18
- 206010020772 Hypertension Diseases 0.000 claims 11
- 239000008194 pharmaceutical composition Substances 0.000 claims 11
- 230000002401 inhibitory effect Effects 0.000 claims 4
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 4
- 208000001362 Fetal Growth Retardation Diseases 0.000 claims 3
- 206010070531 Foetal growth restriction Diseases 0.000 claims 3
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 claims 3
- 108091081021 Sense strand Proteins 0.000 claims 3
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 3
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 208000035475 disorder Diseases 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 208000030941 fetal growth restriction Diseases 0.000 claims 3
- 239000003446 ligand Substances 0.000 claims 3
- 229940124597 therapeutic agent Drugs 0.000 claims 3
- 101150070360 Agt gene Proteins 0.000 claims 2
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims 2
- 206010019708 Hepatic steatosis Diseases 0.000 claims 2
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical group CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims 2
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims 2
- 102100028255 Renin Human genes 0.000 claims 2
- 108090000783 Renin Proteins 0.000 claims 2
- 201000003099 Renovascular Hypertension Diseases 0.000 claims 2
- 206010042957 Systolic hypertension Diseases 0.000 claims 2
- 229940083712 aldosterone antagonist Drugs 0.000 claims 2
- 229940126905 angiotensin receptor-neprilysin inhibitor Drugs 0.000 claims 2
- 230000000692 anti-sense effect Effects 0.000 claims 2
- 230000035487 diastolic blood pressure Effects 0.000 claims 2
- 239000002308 endothelin receptor antagonist Substances 0.000 claims 2
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 2
- 239000002773 nucleotide Substances 0.000 claims 2
- 125000003729 nucleotide group Chemical group 0.000 claims 2
- 230000035488 systolic blood pressure Effects 0.000 claims 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
- 206010002383 Angina Pectoris Diseases 0.000 claims 1
- 208000006179 Aortic Coarctation Diseases 0.000 claims 1
- 206010003210 Arteriosclerosis Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 239000005485 Azilsartan Substances 0.000 claims 1
- VYCMAAOURFJIHD-PJNXIOHISA-N BQ 123 Chemical compound N1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](CC(O)=O)NC(=O)[C@H]1CC1=CNC2=CC=CC=C12 VYCMAAOURFJIHD-PJNXIOHISA-N 0.000 claims 1
- 239000002083 C09CA01 - Losartan Substances 0.000 claims 1
- 239000002080 C09CA02 - Eprosartan Substances 0.000 claims 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims 1
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 1
- 206010007558 Cardiac failure chronic Diseases 0.000 claims 1
- 208000031229 Cardiomyopathies Diseases 0.000 claims 1
- 206010009807 Coarctation of the aorta Diseases 0.000 claims 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
- 208000032781 Diabetic cardiomyopathy Diseases 0.000 claims 1
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 1
- 206010012758 Diastolic hypertension Diseases 0.000 claims 1
- 229940097420 Diuretic Drugs 0.000 claims 1
- 208000007530 Essential hypertension Diseases 0.000 claims 1
- 208000004930 Fatty Liver Diseases 0.000 claims 1
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- 208000002705 Glucose Intolerance Diseases 0.000 claims 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims 1
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- 206010055171 Hypertensive nephropathy Diseases 0.000 claims 1
- 206010049079 Labile hypertension Diseases 0.000 claims 1
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 1
- FJHHZXWJVIEFGJ-UHFFFAOYSA-N N-(3-methoxy-5-methyl-2-pyrazinyl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]-3-pyridinesulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C=2OC=NN=2)C=C1 FJHHZXWJVIEFGJ-UHFFFAOYSA-N 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010030043 Ocular hypertension Diseases 0.000 claims 1
- 239000005480 Olmesartan Substances 0.000 claims 1
- 206010033307 Overweight Diseases 0.000 claims 1
- 208000001647 Renal Insufficiency Diseases 0.000 claims 1
- 201000004239 Secondary hypertension Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 201000009594 Systemic Scleroderma Diseases 0.000 claims 1
- 206010042953 Systemic sclerosis Diseases 0.000 claims 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 1
- 239000000464 adrenergic agent Substances 0.000 claims 1
- 239000000674 adrenergic antagonist Substances 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 239000002170 aldosterone antagonist Substances 0.000 claims 1
- 239000002160 alpha blocker Substances 0.000 claims 1
- 229960002414 ambrisentan Drugs 0.000 claims 1
- OUJTZYPIHDYQMC-LJQANCHMSA-N ambrisentan Chemical compound O([C@@H](C(OC)(C=1C=CC=CC=1)C=1C=CC=CC=1)C(O)=O)C1=NC(C)=CC(C)=N1 OUJTZYPIHDYQMC-LJQANCHMSA-N 0.000 claims 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 1
- 230000001327 anti-mineralocorticoid effect Effects 0.000 claims 1
- 208000007474 aortic aneurysm Diseases 0.000 claims 1
- 208000011775 arteriosclerosis disease Diseases 0.000 claims 1
- 229950010993 atrasentan Drugs 0.000 claims 1
- MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 claims 1
- KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 claims 1
- 229960002731 azilsartan Drugs 0.000 claims 1
- 239000002876 beta blocker Substances 0.000 claims 1
- 229940097320 beta blocking agent Drugs 0.000 claims 1
- 229960003065 bosentan Drugs 0.000 claims 1
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 claims 1
- 239000000480 calcium channel blocker Substances 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 208000033679 diabetic kidney disease Diseases 0.000 claims 1
- 239000002934 diuretic Substances 0.000 claims 1
- 230000001882 diuretic effect Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 229940100321 entresto Drugs 0.000 claims 1
- 229960004563 eprosartan Drugs 0.000 claims 1
- OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 claims 1
- 208000010706 fatty liver disease Diseases 0.000 claims 1
- 230000004761 fibrosis Effects 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 206010061989 glomerulosclerosis Diseases 0.000 claims 1
- ZASXKEGREHRXDL-CAWNUZPDSA-H hexasodium;4-[[(2s,4r)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoate;(2s)-3-methyl-2-[pentanoyl-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]amino]butanoate;pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].C1=CC(C[C@H](C[C@@H](C)C(=O)OCC)NC(=O)CCC([O-])=O)=CC=C1C1=CC=CC=C1.C1=CC(C[C@H](C[C@@H](C)C(=O)OCC)NC(=O)CCC([O-])=O)=CC=C1C1=CC=CC=C1.C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C([O-])=O)=CC=C1C1=CC=CC=C1C1=NN=N[N-]1.C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C([O-])=O)=CC=C1C1=CC=CC=C1C1=NN=N[N-]1 ZASXKEGREHRXDL-CAWNUZPDSA-H 0.000 claims 1
- 208000015210 hypertensive heart disease Diseases 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- 201000006370 kidney failure Diseases 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 229960004773 losartan Drugs 0.000 claims 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 claims 1
- 229960001039 macitentan Drugs 0.000 claims 1
- JGCMEBMXRHSZKX-UHFFFAOYSA-N macitentan Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCCC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 JGCMEBMXRHSZKX-UHFFFAOYSA-N 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 239000002394 mineralocorticoid antagonist Substances 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- TUYWTLTWNJOZNY-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-propan-2-ylpyridine-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C2=NNN=N2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=N1 TUYWTLTWNJOZNY-UHFFFAOYSA-N 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 claims 1
- 229960005117 olmesartan Drugs 0.000 claims 1
- 230000001314 paroxysmal effect Effects 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 208000007232 portal hypertension Diseases 0.000 claims 1
- 230000035935 pregnancy Effects 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 208000002815 pulmonary hypertension Diseases 0.000 claims 1
- 239000000018 receptor agonist Substances 0.000 claims 1
- 229940044601 receptor agonist Drugs 0.000 claims 1
- 239000002461 renin inhibitor Substances 0.000 claims 1
- 229940086526 renin-inhibitors Drugs 0.000 claims 1
- 208000015658 resistant hypertension Diseases 0.000 claims 1
- 229920002477 rna polymer Polymers 0.000 claims 1
- 229940100334 sacubitril / valsartan Drugs 0.000 claims 1
- 229960002578 sitaxentan Drugs 0.000 claims 1
- PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 claims 1
- 231100000240 steatosis hepatitis Toxicity 0.000 claims 1
- 230000003637 steroidlike Effects 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- 229950000584 tezosentan Drugs 0.000 claims 1
- -1 thymidine-glycol nucleic acid Chemical class 0.000 claims 1
- 229960004699 valsartan Drugs 0.000 claims 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 claims 1
- 229940124549 vasodilator Drugs 0.000 claims 1
- 239000003071 vasodilator agent Substances 0.000 claims 1
- 230000002861 ventricular Effects 0.000 claims 1
- 229950003684 zibotentan Drugs 0.000 claims 1
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Claims (12)
1. Agens koji je dvolančana ribonukleinska kiselina (dsRNK), ili njegova sol, za inhibiranje ekspresije angiotenzinogena (AGT), pri čemu dsRNK agens, ili njegova sol, sadrži smisleni lanac i antismisleni lanac koji formiraju dvolančanu regiju, pri čemu smisleni lanac sadrži nukleotidnu sekvencu 5’-gsuscaucCfaCfAfAfugagaguaca-3’ (SEQ ID NO:482), a antismisleni lanac sadrži nukleotidnu sekvencu 5’- usGfsuac(Tgn)cucauugUfgGfaugacsgsa-3’ (SEQ ID NO:666),
gdje a, g, c i u su 2'-O-metil (2'-OMe) A, G, C i U, tim redom; Af, Gf, Cf i Uf su 2'-fluoro A, G, C i U, tim redom; s je fosforotioatna veza; a (Tgn) je S-izomer timidin-glikolne nukleinske kiseline (GNA), i dalje sadrži ligand koji je derivat N-acetilgalaktozamina (GalNAc).
2. dsRNK agens, ili njegova sol, prema patentnom zahtjevu 1, gdje je ligand:
(i) konjugiran na 3' kraj smislenog lanca dsRNK agensa, ili njegove soli;
i/ili
(ii) derivat N-acetilgalaktozamina (GalNAc), koji je
[image]
dalje opcionalno, pri čemu je dsRNK agens, ili njegova sol, konjugiran s ligandom kao što je prikazano na sljedećoj shemi
[image]
a, gdje X je O ili S; ili
(iv) jedan ili više GalNAc derivata, vezanih preko monovalentnog, dvovalentnog ili trovalentnog razgranatog povezivača.
3. Izolirana stanica koja sadrži dsRNK agens, ili njegovu sol, prema patentnom zahtjevu 1 ili 2.
4. Farmaceutski sastav za inhibiranje ekspresije gena koji kodira AGT, koja sadrži dsRNK agens, ili njegovu sol, prema patentnom zahtjevu 1 ili 2.
5. Farmaceutski sastav koji sadrži dsRNK agens, ili njegovu sol, prema patentnom zahtjevu 1 ili 2, i lipidnu formulaciju.
6. In vitro postupak inhibiranja ekspresije AGT gena u ćeliji, postupak koji obuhvaća dovođenje stanice u kontakt sa dsRNK agensom, ili njegovom soli, prema patentnom zahtjevu 1 ili 2, ili farmaceutskim sastavom prema patentnom zahtjevu 4 ili 5, čime se inhibira ekspresija AGT gena u stanici.
7. dsRNK agens, ili njegova sol, prema patentnom zahtjevu 1 ili 2, ili farmaceutski sastav prema patentnom zahtjevu 4 ili 5, za upotrebu u liječenju subjekta koji ima poremećaj povezan sa AGT.
8. dsRNK agens, ili njegova sol, ili farmaceutski sastav za upotrebu prema patentnom zahtjevu 7, pri čemu je subjektu postavljena dijagnoza poremećaja povezanog sa AGT,
opcionalno, pri čemu je poremećaj povezan sa AGT izabran iz grupe koju čine visok krvni tlak, hipertenzija, granična hipertenzija, primarna hipertenzija, sekundarna hipertenzija, izolirana sistolna ili dijastolna hipertenzija, hipertenzija povezana s trudnoćom, dijabetska hipertenzija, rezistentna hipertenzija, refraktorna hipertenzija, paroksizmalna hipertenzija, renovaskularna hipertenzija, Goldblatova hipertenzija, hipertenzija povezana s niskom aktivnošću renina ili koncentracijom renina u plazmi, očna hipertenzija, glaukom, plućna hipertenzija, portalna hipertenzija, sistemska venska hipertenzija, sistolna hipertenzija, labilna hipertenzija; hipertenzivna bolest srca, hipertenzivna nefropatija, ateroskleroza, arterioskleroza, vaskulopatija, dijabetska nefropatija, dijabetska retinopatija, kronična srčana insuficijencija, kardiomiopatija, dijabetska kardiomiopatija, glomeruloskleroza, koarktacija aorte, aneurizma aorte, ventrikularna fibroza, insuficijencija srca, infarkt miokarda, angina, moždani udar, bubrežna bolest, bubrežna insuficijencija, sistemska skleroza, intrauterini zastoj rasta (IUGR), ograničenje rasta fetusa, gojaznost, steatoza jetre/masna jetra, nealkoholni steatohepatitis (NASH), bolest nealkoholne masne jetre (NAFLD); intolerancija na glukozu, dijabetes tipa 2 (dijabetes nezavisan od insulina) i metabolički sindrom.
9. dsRNK agens, ili njegova sol, ili farmaceutski sastav, za upotrebu prema patentnom zahtjevu 7 ili 8, pri čemu dovođenje stanice u kontakt sa dsRNK agensom, ili njegovom soli, ili farmaceutskim sastavom, inhibira ekspresiju AGT za najmanje 50%, 60%, 70 %, 80%, 90%, 95%.
10. dsRNK agens, ili njegova sol, ili farmaceutski sastav, za upotrebu prema bilo kojem od patentnih zahtjeva 7-9, pri čemu subjekt:
(i) ima sistolični krvni tlak od najmanje 130 mm Hg ili dijastolni krvni tlak od najmanje 80 mm Hg;
(ii) ima sistolični krvni tlak od najmanje 140 mm Hg i dijastolni krvni tlak od najmanje 80 mm Hg;
(iii) čovjek je; i/ili
(iv) dio je grupe podložne osjetljivosti na sol, prekomjerne je težine, gojazan je ili je u trudnoći.
11. dsRNK agens, ili njegova sol, ili farmaceutski sastav za upotrebu prema bilo kojem od patentnih zahtjeva 7-10, pri čemu se dsRNK agens daje subjektu u dozi od oko 0,01 mg/kg do oko 50 mg/kg, i/ili pri čemu se dsRNK agens, ili njegova sol, ili farmaceutski sastav, daju subkutano; i/ili
pri čemu se subjektu daje dodatni terapijski agens za liječenje hipertenzije, opcionalno, pri čemu je dodatni terapijski agens:
(a) izabran iz grupe koju čine diuretik, inhibitor angiotenzin konvertujućeg enzima (ACE), antagonista receptora angiotenzina II, beta-blokator, vazodilatator, blokator kalcijevih kanala, antagonista aldosterona, alfa2-agonista, inhibitor renina, alfa-blokator, adrenergički agens perifernog djelovanja, selektivni djelomičan agonista D1 receptora, neselektivni alfa-adrenergički antagonista, sintetički, steroidni antimineralokortikoidni agens, inhibitori angiotenzinskog receptora-neprilizina (ARNi), Entresto®, sakubitril/valsartan; ili antagonista endotelinskog receptora (ERA), sitaksentan, ambrisentan, atrasentan, BQ-123, zibotentan, bosentan, macitentan i tezosentan; kombinacija bilo kojih od prethodno navedenih; i terapijski agens za hipertenziju formuliran kao kombinacija agenasa; ili
(b) sadrži antagonistu receptora angiotenzina II, dodatno opcionalno, pri čemu je antagonista receptora angiotenzina II izabran iz grupe koju čine losartan, valsartan, olmesartan, eprosartan i azilsartan.
12. Komplet koji sadrži dsRNK agens, ili njegovu sol, prema patentnom zahtjevu 1 ili 2, ili farmaceutski sastav prema patentnom zahtjevu 4 ili 5.
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PCT/US2019/032150 WO2019222166A1 (en) | 2018-05-14 | 2019-05-14 | Angiotensinogen (agt) irna compositions and methods of use thereof |
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Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX2016015126A (es) | 2014-05-22 | 2017-02-23 | Alnylam Pharmaceuticals Inc | Composiciones de angiotensinogeno (agt) arni y metodos de uso de las mismas. |
TW202016304A (zh) | 2018-05-14 | 2020-05-01 | 美商阿尼拉製藥公司 | 血管收縮素原(AGT)iRNA組成物及其使用方法 |
KR20220115946A (ko) * | 2019-11-13 | 2022-08-19 | 알닐람 파마슈티칼스 인코포레이티드 | 안지오텐시노겐 (agt) 관련 장애를 치료하기 위한 방법 및 조성물 |
WO2021231552A1 (en) * | 2020-05-12 | 2021-11-18 | Duke University | Compositions and methods for controlling blood pressure |
IL310295A (en) * | 2021-08-04 | 2024-03-01 | Alnylam Pharmaceuticals Inc | iRNA compositions and methods for silencing angiotensinogen (AGT) |
CA3238317A1 (en) | 2021-11-19 | 2023-05-25 | Xiaoyan LIN | Sirna targeting angiotensinogen and pharmaceutical use of sirna |
WO2023138650A1 (zh) * | 2022-01-20 | 2023-07-27 | 上海拓界生物医药科技有限公司 | 一种dsRNA、其应用及制备方法 |
WO2023155909A1 (zh) * | 2022-02-18 | 2023-08-24 | 南京明德新药研发有限公司 | 三氮唑核苷类似物及其作为嵌入基团的应用 |
US20240041913A1 (en) * | 2022-04-01 | 2024-02-08 | Adarx Pharmaceuticals, Inc. | Angiotensinogen-modulating compositions and methods of use thereof |
WO2023208128A1 (zh) * | 2022-04-29 | 2023-11-02 | 南京明德新药研发有限公司 | 一类含核苷酸类似物的双链RNAi类似物的缀合物 |
CN117264948B (zh) * | 2022-06-14 | 2024-05-10 | 广州必贝特医药股份有限公司 | 抑制血管紧张素原基因表达的RNAi抑制剂及其应用 |
WO2024013334A1 (en) * | 2022-07-15 | 2024-01-18 | Silence Therapeutics Gmbh | Nucleic acids for inhibiting expression of agt in a cell |
WO2024031101A1 (en) * | 2022-08-05 | 2024-02-08 | Sanegene Bio Usa Inc. | Double stranded rna targeting angiotensinogen (agt) and methods of use thereof |
Family Cites Families (231)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
US4476301A (en) | 1982-04-29 | 1984-10-09 | Centre National De La Recherche Scientifique | Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon |
JPS5927900A (ja) | 1982-08-09 | 1984-02-14 | Wakunaga Seiyaku Kk | 固定化オリゴヌクレオチド |
FR2540122B1 (fr) | 1983-01-27 | 1985-11-29 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application |
US4605735A (en) | 1983-02-14 | 1986-08-12 | Wakunaga Seiyaku Kabushiki Kaisha | Oligonucleotide derivatives |
US4948882A (en) | 1983-02-22 | 1990-08-14 | Syngene, Inc. | Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis |
US4824941A (en) | 1983-03-10 | 1989-04-25 | Julian Gordon | Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems |
US4587044A (en) | 1983-09-01 | 1986-05-06 | The Johns Hopkins University | Linkage of proteins to nucleic acids |
US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
US5118802A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside |
US5550111A (en) | 1984-07-11 | 1996-08-27 | Temple University-Of The Commonwealth System Of Higher Education | Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof |
FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
US5430136A (en) | 1984-10-16 | 1995-07-04 | Chiron Corporation | Oligonucleotides having selectably cleavable and/or abasic sites |
US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
US5258506A (en) | 1984-10-16 | 1993-11-02 | Chiron Corporation | Photolabile reagents for incorporation into oligonucleotide chains |
US4828979A (en) | 1984-11-08 | 1989-05-09 | Life Technologies, Inc. | Nucleotide analogs for nucleic acid labeling and detection |
FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4762779A (en) | 1985-06-13 | 1988-08-09 | Amgen Inc. | Compositions and methods for functionalizing nucleic acids |
US5130300A (en) | 1986-03-07 | 1992-07-14 | Monsanto Company | Method for enhancing growth of mammary parenchyma |
US5317098A (en) | 1986-03-17 | 1994-05-31 | Hiroaki Shizuya | Non-radioisotope tagging of fragments |
JPS638396A (ja) | 1986-06-30 | 1988-01-14 | Wakunaga Pharmaceut Co Ltd | ポリ標識化オリゴヌクレオチド誘導体 |
US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
US4904582A (en) | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
AU598946B2 (en) | 1987-06-24 | 1990-07-05 | Howard Florey Institute Of Experimental Physiology And Medicine | Nucleoside derivatives |
US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
US4924624A (en) | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
US5188897A (en) | 1987-10-22 | 1993-02-23 | Temple University Of The Commonwealth System Of Higher Education | Encapsulated 2',5'-phosphorothioate oligoadenylates |
US5525465A (en) | 1987-10-28 | 1996-06-11 | Howard Florey Institute Of Experimental Physiology And Medicine | Oligonucleotide-polyamide conjugates and methods of production and applications of the same |
DE3738460A1 (de) | 1987-11-12 | 1989-05-24 | Max Planck Gesellschaft | Modifizierte oligonukleotide |
FR2623508B1 (fr) | 1987-11-20 | 1990-04-20 | Commissariat Energie Atomique | Proteine basique denommee phospholipase a2 isolee de venin de serpent de la famille des elapides et sa sequence en amino-acides, derives et fragments de ladite proteine, leur procede d'obtention, compositions therapeutiques et agents de diagnostic contenant ladite proteine et/ou ses derives et/ou ses fragments |
US5082830A (en) | 1988-02-26 | 1992-01-21 | Enzo Biochem, Inc. | End labeled nucleotide probe |
EP0406309A4 (en) | 1988-03-25 | 1992-08-19 | The University Of Virginia Alumni Patents Foundation | Oligonucleotide n-alkylphosphoramidates |
US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
US5109124A (en) | 1988-06-01 | 1992-04-28 | Biogen, Inc. | Nucleic acid probe linked to a label having a terminal cysteine |
US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
US5262536A (en) | 1988-09-15 | 1993-11-16 | E. I. Du Pont De Nemours And Company | Reagents for the preparation of 5'-tagged oligonucleotides |
US5512439A (en) | 1988-11-21 | 1996-04-30 | Dynal As | Oligonucleotide-linked magnetic particles and uses thereof |
US5457183A (en) | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
US5599923A (en) | 1989-03-06 | 1997-02-04 | Board Of Regents, University Of Tx | Texaphyrin metal complexes having improved functionalization |
US5391723A (en) | 1989-05-31 | 1995-02-21 | Neorx Corporation | Oligonucleotide conjugates |
US4958013A (en) | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
US5744101A (en) | 1989-06-07 | 1998-04-28 | Affymax Technologies N.V. | Photolabile nucleoside protecting groups |
US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
US5451463A (en) | 1989-08-28 | 1995-09-19 | Clontech Laboratories, Inc. | Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides |
US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
US5254469A (en) | 1989-09-12 | 1993-10-19 | Eastman Kodak Company | Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures |
US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
WO1991006556A1 (en) | 1989-10-24 | 1991-05-16 | Gilead Sciences, Inc. | 2' modified oligonucleotides |
US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
US5292873A (en) | 1989-11-29 | 1994-03-08 | The Research Foundation Of State University Of New York | Nucleic acids labeled with naphthoquinone probe |
US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
CA2029273A1 (en) | 1989-12-04 | 1991-06-05 | Christine L. Brakel | Modified nucleotide compounds |
US5486603A (en) | 1990-01-08 | 1996-01-23 | Gilead Sciences, Inc. | Oligonucleotide having enhanced binding affinity |
US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
US5852188A (en) | 1990-01-11 | 1998-12-22 | Isis Pharmaceuticals, Inc. | Oligonucleotides having chiral phosphorus linkages |
US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5578718A (en) | 1990-01-11 | 1996-11-26 | Isis Pharmaceuticals, Inc. | Thiol-derivatized nucleosides |
US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
US7037646B1 (en) | 1990-01-11 | 2006-05-02 | Isis Pharmaceuticals, Inc. | Amine-derivatized nucleosides and oligonucleosides |
US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
US6783931B1 (en) | 1990-01-11 | 2004-08-31 | Isis Pharmaceuticals, Inc. | Amine-derivatized nucleosides and oligonucleosides |
US5214136A (en) | 1990-02-20 | 1993-05-25 | Gilead Sciences, Inc. | Anthraquinone-derivatives oligonucleotides |
AU7579991A (en) | 1990-02-20 | 1991-09-18 | Gilead Sciences, Inc. | Pseudonucleosides and pseudonucleotides and their polymers |
US5321131A (en) | 1990-03-08 | 1994-06-14 | Hybridon, Inc. | Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling |
US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
DE69032425T2 (de) | 1990-05-11 | 1998-11-26 | Microprobe Corp., Bothell, Wash. | Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden |
US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
ATE154246T1 (de) | 1990-07-27 | 1997-06-15 | Isis Pharmaceuticals Inc | Nuklease resistente, pyrimidin modifizierte oligonukleotide, die die gen-expression detektieren und modulieren |
US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
US5688941A (en) | 1990-07-27 | 1997-11-18 | Isis Pharmaceuticals, Inc. | Methods of making conjugated 4' desmethyl nucleoside analog compounds |
US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
US5218105A (en) | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
HU217036B (hu) | 1990-08-03 | 1999-11-29 | Sanofi | Eljárás génexpresszió gátlására alkalmas vegyületek előállítására |
US5245022A (en) | 1990-08-03 | 1993-09-14 | Sterling Drug, Inc. | Exonuclease resistant terminally substituted oligonucleotides |
US5512667A (en) | 1990-08-28 | 1996-04-30 | Reed; Michael W. | Trifunctional intermediates for preparing 3'-tailed oligonucleotides |
US5214134A (en) | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
US5561225A (en) | 1990-09-19 | 1996-10-01 | Southern Research Institute | Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages |
EP0549686A4 (en) | 1990-09-20 | 1995-01-18 | Gilead Sciences Inc | Modified internucleoside linkages |
US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
WO1992008728A1 (en) | 1990-11-08 | 1992-05-29 | Hybridon, Inc. | Incorporation of multiple reporter groups on synthetic oligonucleotides |
GB9100304D0 (en) | 1991-01-08 | 1991-02-20 | Ici Plc | Compound |
US7015315B1 (en) | 1991-12-24 | 2006-03-21 | Isis Pharmaceuticals, Inc. | Gapped oligonucleotides |
US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
US5371241A (en) | 1991-07-19 | 1994-12-06 | Pharmacia P-L Biochemicals Inc. | Fluorescein labelled phosphoramidites |
US5571799A (en) | 1991-08-12 | 1996-11-05 | Basco, Ltd. | (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response |
ES2103918T3 (es) | 1991-10-17 | 1997-10-01 | Ciba Geigy Ag | Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios. |
US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
DE69233087T2 (de) | 1991-11-22 | 2003-12-24 | Affymetrix Inc N D Ges D Staat | Verfahren zur Herstellung von Polymerarrays |
US6235887B1 (en) | 1991-11-26 | 2001-05-22 | Isis Pharmaceuticals, Inc. | Enhanced triple-helix and double-helix formation directed by oligonucleotides containing modified pyrimidines |
US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
US6277603B1 (en) | 1991-12-24 | 2001-08-21 | Isis Pharmaceuticals, Inc. | PNA-DNA-PNA chimeric macromolecules |
EP0618925B2 (en) | 1991-12-24 | 2012-04-18 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides |
US5565552A (en) | 1992-01-21 | 1996-10-15 | Pharmacyclics, Inc. | Method of expanded porphyrin-oligonucleotide conjugate synthesis |
US5595726A (en) | 1992-01-21 | 1997-01-21 | Pharmacyclics, Inc. | Chromophore probe for detection of nucleic acid |
FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
DE4203923A1 (de) | 1992-02-11 | 1993-08-12 | Henkel Kgaa | Verfahren zur herstellung von polycarboxylaten auf polysaccharid-basis |
US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
EP0577558A2 (de) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
US5272250A (en) | 1992-07-10 | 1993-12-21 | Spielvogel Bernard F | Boronated phosphoramidate compounds |
EP0786522A2 (en) | 1992-07-17 | 1997-07-30 | Ribozyme Pharmaceuticals, Inc. | Enzymatic RNA molecules for treatment of stenotic conditions |
US6346614B1 (en) | 1992-07-23 | 2002-02-12 | Hybridon, Inc. | Hybrid oligonucleotide phosphorothioates |
US5374525A (en) | 1992-09-30 | 1994-12-20 | University Of Utah Research Foundation | Methods to determine predisposition to hypertension and association of variant angiotensinogen gene and hypertension |
US5574142A (en) | 1992-12-15 | 1996-11-12 | Microprobe Corporation | Peptide linkers for improved oligonucleotide delivery |
US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
AU6449394A (en) | 1993-03-30 | 1994-10-24 | Sterling Winthrop Inc. | Acyclic nucleoside analogs and oligonucleotide sequences containing them |
HU9501974D0 (en) | 1993-03-31 | 1995-09-28 | Sterling Winthrop Inc | Oligonucleotides with amide linkages replacing phosphodiester linkages |
DE4311944A1 (de) | 1993-04-10 | 1994-10-13 | Degussa | Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen |
US5955591A (en) | 1993-05-12 | 1999-09-21 | Imbach; Jean-Louis | Phosphotriester oligonucleotides, amidites and method of preparation |
US6015886A (en) | 1993-05-24 | 2000-01-18 | Chemgenes Corporation | Oligonucleotide phosphate esters |
US6294664B1 (en) | 1993-07-29 | 2001-09-25 | Isis Pharmaceuticals, Inc. | Synthesis of oligonucleotides |
US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
AU678085B2 (en) | 1993-11-16 | 1997-05-15 | Genta Incorporated | Synthetic oligomers having chirally pure phosphonate internucleosidyl linkages mixed with non-phosphonate internucleosidyl linkages |
US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
US5599922A (en) | 1994-03-18 | 1997-02-04 | Lynx Therapeutics, Inc. | Oligonucleotide N3'-P5' phosphoramidates: hybridization and nuclease resistance properties |
US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
US5625050A (en) | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
US6054299A (en) | 1994-04-29 | 2000-04-25 | Conrad; Charles A. | Stem-loop cloning vector and method |
US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
US5597696A (en) | 1994-07-18 | 1997-01-28 | Becton Dickinson And Company | Covalent cyanine dye oligonucleotide conjugates |
US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
US5580731A (en) | 1994-08-25 | 1996-12-03 | Chiron Corporation | N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith |
US5556752A (en) | 1994-10-24 | 1996-09-17 | Affymetrix, Inc. | Surface-bound, unimolecular, double-stranded DNA |
US6608035B1 (en) | 1994-10-25 | 2003-08-19 | Hybridon, Inc. | Method of down-regulating gene expression |
US6166197A (en) | 1995-03-06 | 2000-12-26 | Isis Pharmaceuticals, Inc. | Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions |
WO1996027606A1 (en) | 1995-03-06 | 1996-09-12 | Isis Pharmaceuticals, Inc. | Improved process for the synthesis of 2'-o-substituted pyrimidines and oligomeric compounds therefrom |
US5645620A (en) | 1995-05-25 | 1997-07-08 | Foster Wheeler Development Corp. | System for separating particulates and condensable species from a gas stream |
US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
US5545531A (en) | 1995-06-07 | 1996-08-13 | Affymax Technologies N.V. | Methods for making a device for concurrently processing multiple biological chip assays |
US6160109A (en) | 1995-10-20 | 2000-12-12 | Isis Pharmaceuticals, Inc. | Preparation of phosphorothioate and boranophosphate oligomers |
US5854033A (en) | 1995-11-21 | 1998-12-29 | Yale University | Rolling circle replication reporter systems |
US6444423B1 (en) | 1996-06-07 | 2002-09-03 | Molecular Dynamics, Inc. | Nucleosides comprising polydentate ligands |
US6639062B2 (en) | 1997-02-14 | 2003-10-28 | Isis Pharmaceuticals, Inc. | Aminooxy-modified nucleosidic compounds and oligomeric compounds prepared therefrom |
US6576752B1 (en) | 1997-02-14 | 2003-06-10 | Isis Pharmaceuticals, Inc. | Aminooxy functionalized oligomers |
US6172209B1 (en) | 1997-02-14 | 2001-01-09 | Isis Pharmaceuticals Inc. | Aminooxy-modified oligonucleotides and methods for making same |
US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
US6287591B1 (en) | 1997-05-14 | 2001-09-11 | Inex Pharmaceuticals Corp. | Charged therapeutic agents encapsulated in lipid particles containing four lipid components |
EP2341058A3 (en) | 1997-09-12 | 2011-11-23 | Exiqon A/S | Oligonucleotide Analogues |
US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
US6528640B1 (en) | 1997-11-05 | 2003-03-04 | Ribozyme Pharmaceuticals, Incorporated | Synthetic ribonucleic acids with RNAse activity |
US6617438B1 (en) | 1997-11-05 | 2003-09-09 | Sirna Therapeutics, Inc. | Oligoribonucleotides with enzymatic activity |
US6320017B1 (en) | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
US7273933B1 (en) | 1998-02-26 | 2007-09-25 | Isis Pharmaceuticals, Inc. | Methods for synthesis of oligonucleotides |
US7045610B2 (en) | 1998-04-03 | 2006-05-16 | Epoch Biosciences, Inc. | Modified oligonucleotides for mismatch discrimination |
US6531590B1 (en) | 1998-04-24 | 2003-03-11 | Isis Pharmaceuticals, Inc. | Processes for the synthesis of oligonucleotide compounds |
US6867294B1 (en) | 1998-07-14 | 2005-03-15 | Isis Pharmaceuticals, Inc. | Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages |
BR9914772A (pt) | 1998-10-09 | 2001-12-11 | Ingene Inc | Conjunto de elementos genéticos, vetor, célulahospedeira, conjunto para a produção de umasequência de ácido nucléico, método para aprodução in vivo ou in vitro de uma sequência deácido nucléico, transcrição de cdna, molécula deácido nucléico inibidor, transcrição de mrna,molécula heteroduplex e composiçãofarmacêutica |
AU6298899A (en) | 1998-10-09 | 2000-05-01 | Ingene, Inc. | Production of ssdna (in vivo) |
US6465628B1 (en) | 1999-02-04 | 2002-10-15 | Isis Pharmaceuticals, Inc. | Process for the synthesis of oligomeric compounds |
US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
PT1178999E (pt) | 1999-05-04 | 2007-06-26 | Santaris Pharma As | Análogos de l-ribo-lna |
US6525191B1 (en) | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
US6593466B1 (en) | 1999-07-07 | 2003-07-15 | Isis Pharmaceuticals, Inc. | Guanidinium functionalized nucleotides and precursors thereof |
US6147200A (en) | 1999-08-19 | 2000-11-14 | Isis Pharmaceuticals, Inc. | 2'-O-acetamido modified monomers and oligomers |
US20030113330A1 (en) | 1999-11-08 | 2003-06-19 | Uhal Bruce D. | Methods for treating pulmonary fibrosis |
AU2001227965A1 (en) | 2000-01-21 | 2001-07-31 | Geron Corporation | 2'-arabino-fluorooligonucleotide n3'-p5'phosphoramidates: their synthesis and use |
WO2002028875A2 (en) | 2000-10-04 | 2002-04-11 | Cureon A/S | Improved synthesis of purine locked nucleic acid analogues |
US7176303B2 (en) | 2003-11-06 | 2007-02-13 | Isis Pharmaceuticals, Inc. | Modulation of STAT5 expression |
AU2003254334A1 (en) | 2002-07-10 | 2004-02-02 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Rna-interference by single-stranded rna molecules |
US6878805B2 (en) | 2002-08-16 | 2005-04-12 | Isis Pharmaceuticals, Inc. | Peptide-conjugated oligomeric compounds |
WO2004044136A2 (en) | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2’-modified nucleosides for use in gene modulation |
WO2004041889A2 (en) | 2002-11-05 | 2004-05-21 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
ATE555118T1 (de) | 2003-08-28 | 2012-05-15 | Takeshi Imanishi | Neue synthetische nukleidsäuren vom typ mit quervernetzter n-o-bindung |
US7858769B2 (en) | 2004-02-10 | 2010-12-28 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using multifunctional short interfering nucleic acid (multifunctional siNA) |
ES2381201T3 (es) | 2005-03-31 | 2012-05-24 | Calando Pharmaceuticals, Inc. | Inhibidores de la subunidad 2 de la ribonucleótido-reductasa y utilizaciones de los mismos |
EP1937312B1 (en) | 2005-08-30 | 2016-06-29 | Ionis Pharmaceuticals, Inc. | Chimeric oligomeric compounds for modulation of splicing |
JP5342881B2 (ja) | 2006-01-27 | 2013-11-13 | アイシス ファーマシューティカルズ, インコーポレーテッド | 6−修飾された二環式核酸類似体 |
US7569686B1 (en) | 2006-01-27 | 2009-08-04 | Isis Pharmaceuticals, Inc. | Compounds and methods for synthesis of bicyclic nucleic acid analogs |
WO2007091269A2 (en) | 2006-02-08 | 2007-08-16 | Quark Pharmaceuticals, Inc. | NOVEL TANDEM siRNAS |
CN101460178B (zh) | 2006-04-07 | 2016-12-07 | 艾德拉药物股份有限公司 | 用于tlr7和tlr8的稳定化的免疫调节性rna(simra)化合物 |
AU2007249349B2 (en) | 2006-05-11 | 2012-03-08 | Isis Pharmaceuticals, Inc. | 5'-Modified bicyclic nucleic acid analogs |
US20100105134A1 (en) | 2007-03-02 | 2010-04-29 | Mdrna, Inc. | Nucleic acid compounds for inhibiting gene expression and uses thereof |
MX2009012568A (es) | 2007-05-22 | 2009-12-08 | Mdrna Inc | Oligonucleotidos de acido ribonucleico sustituidos con hidroximetilo y complejos de acido ribonucleico. |
US8278425B2 (en) | 2007-05-30 | 2012-10-02 | Isis Pharmaceuticals, Inc. | N-substituted-aminomethylene bridged bicyclic nucleic acid analogs |
EP2173760B2 (en) | 2007-06-08 | 2015-11-04 | Isis Pharmaceuticals, Inc. | Carbocyclic bicyclic nucleic acid analogs |
CN101796062B (zh) | 2007-07-05 | 2014-07-30 | Isis制药公司 | 6-双取代双环核酸类似物 |
AU2008279509B2 (en) | 2007-07-09 | 2011-07-21 | Idera Pharmaceuticals, Inc. | Stabilized immune modulatory RNA (SIMRA) compounds |
CA2910760C (en) | 2007-12-04 | 2019-07-09 | Muthiah Manoharan | Targeting lipids |
CN102119217B (zh) | 2008-04-15 | 2015-06-03 | 普洛体维生物治疗公司 | 用于核酸递送的新型制剂 |
WO2010042749A2 (en) | 2008-10-08 | 2010-04-15 | Chimeros Inc. | Chimeric therapeutics, compositions, and methods for using same |
CA2744093A1 (en) | 2008-12-03 | 2010-06-10 | Marina Biotech, Inc. | Una oligomer structures for therapeutic agents |
EP2438168B1 (en) | 2009-06-01 | 2020-02-12 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotides for multivalent rna interference, compositions and methods of use thereof |
TR201811076T4 (tr) | 2009-06-10 | 2018-08-27 | Arbutus Biopharma Corp | Geliştirilmiş lipit formulasyonu. |
NZ597504A (en) | 2009-06-15 | 2013-10-25 | Alnylam Pharmaceuticals Inc | Lipid formulated dsrna targeting the pcsk9 gene |
US9512164B2 (en) | 2009-07-07 | 2016-12-06 | Alnylam Pharmaceuticals, Inc. | Oligonucleotide end caps |
WO2011005860A2 (en) | 2009-07-07 | 2011-01-13 | Alnylam Pharmaceuticals, Inc. | 5' phosphate mimics |
WO2011031520A1 (en) | 2009-08-27 | 2011-03-17 | Idera Pharmaceuticals, Inc. | Composition for inhibiting gene expression and uses thereof |
WO2011139710A1 (en) | 2010-04-26 | 2011-11-10 | Marina Biotech, Inc. | Nucleic acid compounds with conformationally restricted monomers and uses thereof |
WO2012177949A2 (en) | 2011-06-21 | 2012-12-27 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibition of expression of protein c (proc) genes |
AU2012304358B2 (en) | 2011-09-07 | 2017-07-20 | Marina Biotech Inc. | Synthesis and uses of nucleic acid compounds with conformationally restricted monomers |
KR102095699B1 (ko) | 2011-11-18 | 2020-04-02 | 알닐람 파마슈티칼스 인코포레이티드 | 트랜스티레틴(TTR) 관련 질병을 치료하기 위한 RNAi 제제, 조성 및 그의 사용방법 |
US9127274B2 (en) | 2012-04-26 | 2015-09-08 | Alnylam Pharmaceuticals, Inc. | Serpinc1 iRNA compositions and methods of use thereof |
JP2016522674A (ja) | 2012-05-16 | 2016-08-04 | ラナ セラピューティクス インコーポレイテッド | 遺伝子発現を調節するための組成物及び方法 |
ES2773489T3 (es) | 2012-07-27 | 2020-07-13 | Ionis Pharmaceuticals Inc | Modulación de enfermedades relacionadas con el sistema renina-angiotensina (RAS) mediante angiotensinógenos |
EP2992009B1 (en) | 2013-05-01 | 2020-06-24 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating apolipoprotein (a) expression |
CN113018307A (zh) * | 2013-05-22 | 2021-06-25 | 阿尔尼拉姆医药品有限公司 | SERPINA1 iRNA组合物及其使用方法 |
MX2016015126A (es) | 2014-05-22 | 2017-02-23 | Alnylam Pharmaceuticals Inc | Composiciones de angiotensinogeno (agt) arni y metodos de uso de las mismas. |
EP3262181B1 (en) | 2015-02-23 | 2024-04-10 | Ionis Pharmaceuticals, Inc. | Method for solution phase detritylation of oligomeric compounds |
WO2016196111A1 (en) | 2015-06-01 | 2016-12-08 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting angiotensinogen (agt) and methods of use thereof |
BR112018005223B1 (pt) * | 2015-10-08 | 2022-08-09 | Ionis Pharmaceuticals, Inc | Compostos, uso dos mesmos, e composição farmacêutica |
TW202016304A (zh) | 2018-05-14 | 2020-05-01 | 美商阿尼拉製藥公司 | 血管收縮素原(AGT)iRNA組成物及其使用方法 |
KR20220115946A (ko) | 2019-11-13 | 2022-08-19 | 알닐람 파마슈티칼스 인코포레이티드 | 안지오텐시노겐 (agt) 관련 장애를 치료하기 위한 방법 및 조성물 |
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