HRP20231400T1 - Kelirani fosforotioirani polimeri nukleinskih kiselina, namijenjeni upotrebi u kombinaciji s inhibitorom hbv polimeraze u liječenju infekcija virusima hepatitisa b i hepatitisa d - Google Patents
Kelirani fosforotioirani polimeri nukleinskih kiselina, namijenjeni upotrebi u kombinaciji s inhibitorom hbv polimeraze u liječenju infekcija virusima hepatitisa b i hepatitisa d Download PDFInfo
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- 108020004707 nucleic acids Proteins 0.000 title claims 14
- 150000007523 nucleic acids Chemical class 0.000 title claims 14
- 102000039446 nucleic acids Human genes 0.000 title claims 14
- 229920000642 polymer Polymers 0.000 title claims 14
- 108700024845 Hepatitis B virus P Proteins 0.000 title claims 6
- 229940123066 Polymerase inhibitor Drugs 0.000 title claims 4
- 208000002672 hepatitis B Diseases 0.000 title 1
- 208000029570 hepatitis D virus infection Diseases 0.000 title 1
- 238000002360 preparation method Methods 0.000 claims 28
- 239000003795 chemical substances by application Substances 0.000 claims 14
- 125000003729 nucleotide group Chemical group 0.000 claims 13
- 150000004697 chelate complex Chemical class 0.000 claims 9
- 108091034117 Oligonucleotide Proteins 0.000 claims 8
- 239000002773 nucleotide Substances 0.000 claims 8
- 238000012986 modification Methods 0.000 claims 6
- 230000004048 modification Effects 0.000 claims 6
- 208000003322 Coinfection Diseases 0.000 claims 5
- 208000015181 infectious disease Diseases 0.000 claims 5
- 239000002777 nucleoside Substances 0.000 claims 5
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 5
- 238000009169 immunotherapy Methods 0.000 claims 3
- 150000003291 riboses Chemical class 0.000 claims 3
- STGXGJRRAJKJRG-JDJSBBGDSA-N (3r,4r,5r)-5-(hydroxymethyl)-3-methoxyoxolane-2,4-diol Chemical compound CO[C@H]1C(O)O[C@H](CO)[C@H]1O STGXGJRRAJKJRG-JDJSBBGDSA-N 0.000 claims 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 2
- HSBKFSPNDWWPSL-VDTYLAMSSA-N 4-amino-5-fluoro-1-[(2s,5r)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@@H]1C=C[C@H](CO)O1 HSBKFSPNDWWPSL-VDTYLAMSSA-N 0.000 claims 2
- JXQUAHHUSMJUFV-HZPZRMRQSA-N 9-[2-[[(2r,4s)-4-(3-chlorophenyl)-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl]methoxy]ethyl]purin-6-amine;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1([C@@H]2CCO[P@](O2)(=O)COCCN2C=3N=CN=C(C=3N=C2)N)=CC=CC(Cl)=C1 JXQUAHHUSMJUFV-HZPZRMRQSA-N 0.000 claims 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims 2
- VFCYZPOEGWLYRM-QCZKYFFMSA-N [(2s,3r,5s)-5-(4-amino-2-oxopyrimidin-1-yl)-2-(hydroxymethyl)oxolan-3-yl] (2s)-2-amino-3-methylbutanoate Chemical compound O1[C@@H](CO)[C@H](OC(=O)[C@@H](N)C(C)C)C[C@H]1N1C(=O)N=C(N)C=C1 VFCYZPOEGWLYRM-QCZKYFFMSA-N 0.000 claims 2
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 claims 2
- 229960003205 adefovir dipivoxil Drugs 0.000 claims 2
- 239000000443 aerosol Substances 0.000 claims 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims 2
- 229910052791 calcium Inorganic materials 0.000 claims 2
- 239000011575 calcium Substances 0.000 claims 2
- 229960005338 clevudine Drugs 0.000 claims 2
- GBBJCSTXCAQSSJ-XQXXSGGOSA-N clevudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1[C@H](F)[C@@H](O)[C@H](CO)O1 GBBJCSTXCAQSSJ-XQXXSGGOSA-N 0.000 claims 2
- 229950006528 elvucitabine Drugs 0.000 claims 2
- 229960000980 entecavir Drugs 0.000 claims 2
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 claims 2
- 238000001802 infusion Methods 0.000 claims 2
- 238000001990 intravenous administration Methods 0.000 claims 2
- 238000010253 intravenous injection Methods 0.000 claims 2
- 229960001627 lamivudine Drugs 0.000 claims 2
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims 2
- 229910052749 magnesium Inorganic materials 0.000 claims 2
- 239000011777 magnesium Substances 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 238000010254 subcutaneous injection Methods 0.000 claims 2
- 239000007929 subcutaneous injection Substances 0.000 claims 2
- 229960005311 telbivudine Drugs 0.000 claims 2
- IQFYYKKMVGJFEH-CSMHCCOUSA-N telbivudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 IQFYYKKMVGJFEH-CSMHCCOUSA-N 0.000 claims 2
- 229960003560 tenofovir alafenamide fumarate Drugs 0.000 claims 2
- SVUJNSGGPUCLQZ-FQQAACOVSA-N tenofovir alafenamide fumarate Chemical compound OC(=O)\C=C\C(O)=O.O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1.O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1 SVUJNSGGPUCLQZ-FQQAACOVSA-N 0.000 claims 2
- 229960004693 tenofovir disoproxil fumarate Drugs 0.000 claims 2
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 claims 2
- 229950002819 valtorcitabine Drugs 0.000 claims 2
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/7088—Compounds having three or more nucleosides or nucleotides
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1131—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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Claims (20)
1. Pripravak, koji sadrži prvo farmaceutski prihvatljivo sredstvo, koje sadrži kelatni kompleks najmanje jednog fosforotioiranog polimera nukleinske kiseline (NAP) s drugim farmaceutski prihvatljivim sredstvom, koje sadrži najmanje jedan nukleozidni/nukleotidni analog kao inhibitor HBV polimeraze, namijenjen upotrebi u postupku liječenja infekcije s HBV ili suinfekcije s HBV/HDV kod subjekta u odsutnosti imunoterapije.
2. Pripravak, koji sadrži prvo farmaceutski prihvatljivo sredstvo, koje sadrži kelatni kompleks jednog ili više polimera nukleinskih kiselina (NAP), koje se bira između sljedećeg:
SEQ ID NO: 2;
SEQ ID NO: 10;
SEQ ID NO: 13;
SEQ ID NO: 1, 3-9, 11, 12 i 14-20;
fosforotioiranog oligonukleotida, dugog od 20-120 nukleotida, koji sadrži ponavljanja slijeda AC;
fosforotioiranog oligonukleotida, dugog od 20-120 nukleotida, koji sadrži ponavljanja slijeda CA;
fosforotioiranog oligonukleotida, dugog od 20-120 nukleotida, koji sadrži ponavljanja slijeda TG; i
fosforotioiranog oligonukleotida, dugog od 20-120 nukleotida, koji sadrži ponavljanja slijeda GT;
s drugim farmaceutski prihvatljivim sredstvom, koje sadrži jedno ili više od sljedećeg:
lamivudina;
adefovir dipivoksila;
entekavira;
telbivudina;
tenofovir dizoproksil-fumarata;
entricitabina;
klevudina;
bezifovira;
tenofovir alafenamid-fumarata;
AGX-1009;
elvucitabina;
lagociklovir-valaktata;
pradefovir-mesilata;
valtorcitabina; i
bilo kojeg nukleozidnog/nukleotidnog analoga koji inhibira HBV polimerazu,
namijenjen upotrebi u postupku liječenja infekcije s HBV ili suinfekcije s HBV/HDV u odsutnosti imunoterapije.
3. Pripravak koji se sastoji od prvog farmaceutski prihvatljivog sredstva, koje se sastoji od kelatnog kompleksa najmanje jednog fosforotioiranog polimera nukleinske kiseline (NAP) s drugim farmaceutski prihvatljivim sredstvom, koje se sastoji od najmanje jednog nukleozidnog/nukleotidnog analoga kao inhibitora HBV polimeraze, pogodnog za liječenje infekcije s HBV ili suinfekcije s HBV/HDV kod subjekta.
4. Pripravak koji se sastoji od prvog farmaceutski prihvatljivog sredstva, koje se sastoji od kelatnog kompleksa jednog ili više polimera nukleinskih kiselina (NAP), koje se bira između sljedećeg:
SEQ ID NO: 2;
SEQ ID NO: 10;
SEQ ID NO: 13;
SEQ ID NO: 1,3-9, 11, 12 i 14-20;
fosforotioiranog oligonukleotida, dugog od 20-120 nukleotida, koji sadrži ponavljanja slijeda AC;
fosforotioiranog oligonukleotida, dugog od 20-120 nukleotida, koji sadrži ponavljanja slijeda CA;
fosforotioiranog oligonukleotida, dugog od 20-120 nukleotida, koji sadrži ponavljanja slijeda TG; i
fosforotioiranog oligonukleotida, dugog od 20-120 nukleotida, koji sadrži ponavljanja slijeda GT;
s drugim farmaceutski prihvatljivim sredstvom, koje se sastoji od jednog ili više od sljedećeg:
lamivudina;
adefovir dipivoksila;
entekavira;
telbivudina;
tenofovir dizoproksil-fumarata;
entricitabina;
klevudina;
bezifovira;
tenofovir alafenamid-fumarata;
AGX-1009;
elvucitabina;
lagociklovir-valaktata;
pradefovir-mesilata;
valtorcitabina; i
bilo kojeg nukleozidnog/nukleotidnog analoga koji inhibira HBV polimerazu,
pogodan za liječenje infekcije s HBV ili suinfekcije s HBV/HDV.
5. Pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 1 ili 2 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-4, pri čemu polimer nukleinske kiseline dodatno sadrži najmanje jednu modifikaciju riboze na položaju 2’.
6. Pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 1-2 ili 5 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-5, pri čemu polimer nukleinske kiseline dodatno sadrži sve riboze koje imaju modifikaciju na položaju 2’.
7. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-2 ili 5-6 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-6, pri čemu polimer nukleinske kiseline dodatno sadrži najmanje jednu 2’-O-metilriboznu modifikaciju.
8. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-2 ili 5-7 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-7, pri čemu polimer nukleinske kiseline dodatno sadrži sve riboze koje imaju 2’-O-metilnu modifikaciju.
9. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-2 ili 5-8 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-8, pri čemu polimer nukleinske kiseline dodatno sadrži najmanje jedan 5’-metilcitozin.
10. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-2 ili 5-9 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-9, pri čemu polimer nukleinske kiseline dodatno sadrži sve citozine prisutne kao 5’-metilcitozin.
11. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-2 ili 5-10 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-10, pri čemu polimer nukleinske kiseline dodatno sadrži najmanje jednu 2’-O-metilriboznu modifikaciju i najmanje jedan 5’-metilcitozin.
12. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-2 ili 5-11 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-11, pri čemu polimer nukleinske kiseline dodatno sadrži sve riboze koje imaju 2’-O-metilnu modifikaciju, a svi citozini su prisutni kao 5’-metilcitozin.
13. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-2 ili 5-12 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-12, pri čemu je kelatni kompleks kelatni kompleks s kalcijem, ili kelatni kompleks s magnezijem, ili kelatni kompleks s kalcijem i magnezijem.
14. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-2 ili 5-13 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-13, pri čemu su navedeno prvo i drugo farmaceutski prihvatljivo sredstvo formulirana u isti farmaceutski pripravak, ili u zasebnim farmaceutskim pripravcima.
15. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-2 ili 5-13 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-13, pri čemu:
a) navedeno prvo i drugo farmaceutski prihvatljivo sredstvo su formulirana za istodobnu primjenu, ili
b) navedeno prvo i drugo farmaceutski prihvatljivo sredstvo se primjenjuje različitim načinima.
16. Pripravak namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-2 ili 5-15 ili pripravak u skladu s bilo kojim od patentnih zahtjeva 3-15, pri čemu su navedeno prvo i drugo farmaceutski prihvatljivo sredstvo formulirana za primjenu uz upotrebu jednog ili više od sljedećeg: oralnog unosa, inhaliranja aerosola, supkutane injekcije, intravenske injekcije i intravenske infuzije.
17. Pripravak u skladu s bilo kojim od patentnih zahtjeva 3-16, namijenjen upotrebi u terapiji.
18. Prvo farmaceutski prihvatljivo sredstvo, koje sadrži kelatni kompleks najmanje jednog fosforotioiranog polimera nukleinske kiseline s drugim farmaceutski prihvatljivim sredstvom, koje sadrži najmanje jedan nukleozidni/nukleotidni analog kao inhibitor HBV polimeraze, namijenjen upotrebi u postupku liječenja infekcije s HBV ili suinfekcije s HBV/HDV kod subjekta u odsutnosti imunoterapije.
19. Prvo i drugo farmaceutski prihvatljivo sredstvo, namijenjeno upotrebi u skladu s patentnim zahtjevom 18, pri čemu prvo ili drugo farmaceutski prihvatljivo sredstvo dodatno definiraju značajke navedene u skladu s bilo kojim od patentnih zahtjeva 4 do 14.
20. Prvo i drugo farmaceutski prihvatljivo sredstvo, namijenjeno upotrebi u skladu s patentnim zahtjevom 18 ili 19, pri čemu se postupak sastoji u primjeni prvog i drugog farmaceutski prihvatljivog sredstva:
a) istodobno ili različitim načinom, ili
b) uz upotrebu jednog ili više od sljedećeg: oralnog unosa, inhaliranja aerosola, supkutane injekcije, intravenske injekcije i intravenske infuzije.
Applications Claiming Priority (4)
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| US201462022846P | 2014-07-10 | 2014-07-10 | |
| US201462091943P | 2014-12-15 | 2014-12-15 | |
| EP15818148.7A EP3166615B1 (en) | 2014-07-10 | 2015-07-07 | Chelated phosphorotiotated nucleic acid polymers for use in combination with a hbv polymerase inhibitor for the treatment of hepatitis b and hepatitis d virus infections |
| PCT/CA2015/050626 WO2016004525A1 (en) | 2014-07-10 | 2015-07-07 | Methods for the treatment of hepatitis b and hepatitis d virus infections |
Publications (1)
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| HRP20231400T1 true HRP20231400T1 (hr) | 2024-02-16 |
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| HRP20231400TT HRP20231400T1 (hr) | 2014-07-10 | 2015-07-07 | Kelirani fosforotioirani polimeri nukleinskih kiselina, namijenjeni upotrebi u kombinaciji s inhibitorom hbv polimeraze u liječenju infekcija virusima hepatitisa b i hepatitisa d |
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| EP (1) | EP3166615B1 (hr) |
| JP (2) | JP2017521433A (hr) |
| KR (2) | KR20170029577A (hr) |
| CN (2) | CN113750112A (hr) |
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| BR (1) | BR112017000320B1 (hr) |
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| CL (1) | CL2017000008A1 (hr) |
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| EC (1) | ECSP16097355A (hr) |
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| IL (1) | IL249660B (hr) |
| LT (1) | LT3166615T (hr) |
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| MX (1) | MX2017000053A (hr) |
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| SI (1) | SI3166615T1 (hr) |
| TW (1) | TWI766831B (hr) |
| WO (1) | WO2016004525A1 (hr) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200147124A1 (en) * | 2018-11-08 | 2020-05-14 | Aligos Therapeutics, Inc. | S-antigen transport inhibiting oligonucleotide polymers and methods |
| US11166976B2 (en) | 2018-11-08 | 2021-11-09 | Aligos Therapeutics, Inc. | S-antigen transport inhibiting oligonucleotide polymers and methods |
| WO2021119325A1 (en) * | 2019-12-12 | 2021-06-17 | Aligos Therapeutics, Inc. | S-antigen transport inhibiting oligonucleotide polymers and methods |
| WO2021223398A1 (zh) * | 2020-05-07 | 2021-11-11 | 西安新通药物研究股份有限公司 | 治疗肝病的晶型及其应用 |
| CN113637030A (zh) * | 2020-05-07 | 2021-11-12 | 西安新通药物研究股份有限公司 | 甲磺酸帕拉德福韦b晶型及其应用 |
| CN114057816A (zh) * | 2020-07-30 | 2022-02-18 | 浙江柏拉阿图医药科技有限公司 | 富含腺嘌呤硫代磷酸酯化寡核苷酸及其抗肝炎病毒的应用 |
| EP4247393A1 (en) * | 2020-11-20 | 2023-09-27 | Aligos Therapeutics, Inc. | Conjugates of s-antigen transport inhibiting oligonucleotide polymers having enhanced liver targeting |
| WO2022133230A1 (en) | 2020-12-18 | 2022-06-23 | Janssen Pharmaceuticals, Inc. | Combination therapy for treating hepatitis b virus infection |
| WO2022152869A1 (en) | 2021-01-15 | 2022-07-21 | Janssen Sciences Ireland Unlimited Company | Use of oligonucleotides for individuals with hepatic impairment |
| WO2022261046A1 (en) * | 2021-06-07 | 2022-12-15 | Antios Therapeutics, Inc. | Compositions and methods of treating hepatitis d and hepatitis b/hepatitis d co-infections with phosphoramidate clevudine prodrugs |
| CA3224600A1 (en) | 2021-07-09 | 2023-01-12 | Glaxosmithkline Intellectual Property (No.3) Limited | Use of oligonucleotides for individuals with renal impairment |
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| US5482836A (en) * | 1993-01-14 | 1996-01-09 | The Regents Of The University Of California | DNA purification by triplex-affinity capture and affinity capture electrophoresis |
| WO2004024919A1 (en) | 2002-09-13 | 2004-03-25 | Replicor, Inc. | Non-sequence complementary antiviral oligonucleotides |
| US9474793B2 (en) * | 2005-02-22 | 2016-10-25 | The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Vaccines and methods for prevention and treatment of drug-resistant HIV-1 and hepatitis B virus |
| PT2605794T (pt) | 2010-08-20 | 2016-10-25 | Replicor Inc | Complexos de quelato de oligonucleótido |
| WO2012058210A1 (en) * | 2010-10-29 | 2012-05-03 | Merck Sharp & Dohme Corp. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA) |
| WO2012075114A2 (en) * | 2010-12-01 | 2012-06-07 | Ablitech, Inc. | Nucleic acid-polymer conjugates and uses thereof |
| CA2873529C (en) | 2012-05-18 | 2020-08-18 | Replicor Inc. | Oligonucleotide chelate complex-polypeptide compositions and methods |
| IN2015DN01087A (hr) | 2012-08-30 | 2015-06-26 | Replicor Inc |
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2015
- 2015-07-07 HR HRP20231400TT patent/HRP20231400T1/hr unknown
- 2015-07-07 DK DK15818148.7T patent/DK3166615T3/da active
- 2015-07-07 CA CA2954182A patent/CA2954182C/en active Active
- 2015-07-07 KR KR1020177003538A patent/KR20170029577A/ko active Application Filing
- 2015-07-07 WO PCT/CA2015/050626 patent/WO2016004525A1/en active Application Filing
- 2015-07-07 ES ES15818148T patent/ES2963814T3/es active Active
- 2015-07-07 CN CN202111146395.2A patent/CN113750112A/zh active Pending
- 2015-07-07 LT LTEPPCT/CA2015/050626T patent/LT3166615T/lt unknown
- 2015-07-07 FI FIEP15818148.7T patent/FI3166615T3/fi active
- 2015-07-07 CN CN201580037179.0A patent/CN106659730A/zh active Pending
- 2015-07-07 MX MX2017000053A patent/MX2017000053A/es unknown
- 2015-07-07 SI SI201531976T patent/SI3166615T1/sl unknown
- 2015-07-07 PT PT158181487T patent/PT3166615T/pt unknown
- 2015-07-07 MY MYPI2017700005A patent/MY178087A/en unknown
- 2015-07-07 HU HUE15818148A patent/HUE064449T2/hu unknown
- 2015-07-07 KR KR1020237015821A patent/KR20230070330A/ko active IP Right Grant
- 2015-07-07 SG SG11201700073PA patent/SG11201700073PA/en unknown
- 2015-07-07 BR BR112017000320-1A patent/BR112017000320B1/pt active IP Right Grant
- 2015-07-07 JP JP2017501004A patent/JP2017521433A/ja active Pending
- 2015-07-07 EA EA201790160A patent/EA036745B1/ru unknown
- 2015-07-07 PL PL15818148.7T patent/PL3166615T3/pl unknown
- 2015-07-07 RS RS20231031A patent/RS64833B1/sr unknown
- 2015-07-07 AU AU2015286199A patent/AU2015286199B2/en active Active
- 2015-07-07 EP EP15818148.7A patent/EP3166615B1/en active Active
- 2015-07-07 MD MDA20170014A patent/MD4760C8/ro active IP Right Grant
- 2015-07-08 US US14/794,129 patent/US9603865B2/en active Active
- 2015-07-13 TW TW104122636A patent/TWI766831B/zh active
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2016
- 2016-12-20 IL IL249660A patent/IL249660B/en unknown
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2017
- 2017-01-03 EC ECIEPI201697355A patent/ECSP16097355A/es unknown
- 2017-01-03 DO DO2017000002A patent/DOP2017000002A/es unknown
- 2017-01-03 CL CL2017000008A patent/CL2017000008A1/es unknown
- 2017-01-03 PH PH12017500010A patent/PH12017500010A1/en unknown
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2020
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