HRP20201873T1 - Sredstva i postupci za liječenje hbv-a - Google Patents
Sredstva i postupci za liječenje hbv-a Download PDFInfo
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- HRP20201873T1 HRP20201873T1 HRP20201873TT HRP20201873T HRP20201873T1 HR P20201873 T1 HRP20201873 T1 HR P20201873T1 HR P20201873T T HRP20201873T T HR P20201873TT HR P20201873 T HRP20201873 T HR P20201873T HR P20201873 T1 HRP20201873 T1 HR P20201873T1
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- Prior art keywords
- hepatitis
- virus
- envelope protein
- protein
- small
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- 238000000034 method Methods 0.000 title claims 11
- 241000700721 Hepatitis B virus Species 0.000 claims 45
- 101710147732 Small envelope protein Proteins 0.000 claims 27
- 101710132601 Capsid protein Proteins 0.000 claims 24
- 101710091045 Envelope protein Proteins 0.000 claims 20
- 101710188315 Protein X Proteins 0.000 claims 20
- 102100021696 Syncytin-1 Human genes 0.000 claims 20
- 238000002255 vaccination Methods 0.000 claims 20
- 101710084021 Large envelope protein Proteins 0.000 claims 18
- 241001183012 Modified Vaccinia Ankara virus Species 0.000 claims 17
- 239000002671 adjuvant Substances 0.000 claims 14
- 239000000427 antigen Substances 0.000 claims 14
- 125000003275 alpha amino acid group Chemical group 0.000 claims 12
- 230000002163 immunogen Effects 0.000 claims 9
- 239000000203 mixture Substances 0.000 claims 9
- 238000012217 deletion Methods 0.000 claims 7
- 230000037430 deletion Effects 0.000 claims 7
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 claims 6
- 102100025221 CD70 antigen Human genes 0.000 claims 5
- 102000004169 proteins and genes Human genes 0.000 claims 5
- 108090000623 proteins and genes Proteins 0.000 claims 5
- 229960005486 vaccine Drugs 0.000 claims 5
- 102000002689 Toll-like receptor Human genes 0.000 claims 4
- 108020000411 Toll-like receptor Proteins 0.000 claims 4
- 239000000556 agonist Substances 0.000 claims 4
- PDXMFTWFFKBFIN-XPWFQUROSA-N cyclic di-AMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]3[C@@H](O)[C@H](N4C5=NC=NC(N)=C5N=C4)O[C@@H]3COP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 PDXMFTWFFKBFIN-XPWFQUROSA-N 0.000 claims 4
- 238000007918 intramuscular administration Methods 0.000 claims 4
- 239000003446 ligand Substances 0.000 claims 4
- 150000007523 nucleic acids Chemical group 0.000 claims 4
- 208000002672 hepatitis B Diseases 0.000 claims 3
- 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
- 108091034117 Oligonucleotide Proteins 0.000 claims 2
- 241000607142 Salmonella Species 0.000 claims 2
- 108010008038 Synthetic Vaccines Proteins 0.000 claims 2
- 229940124615 TLR 7 agonist Drugs 0.000 claims 2
- 229940124614 TLR 8 agonist Drugs 0.000 claims 2
- 230000002238 attenuated effect Effects 0.000 claims 2
- 230000003308 immunostimulating effect Effects 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 229940124551 recombinant vaccine Drugs 0.000 claims 2
- 238000007920 subcutaneous administration Methods 0.000 claims 2
- 102100037435 Antiviral innate immune response receptor RIG-I Human genes 0.000 claims 1
- 101710127675 Antiviral innate immune response receptor RIG-I Proteins 0.000 claims 1
- 241000894006 Bacteria Species 0.000 claims 1
- 101710094648 Coat protein Proteins 0.000 claims 1
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 101710125418 Major capsid protein Proteins 0.000 claims 1
- 201000005505 Measles Diseases 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 101710141454 Nucleoprotein Proteins 0.000 claims 1
- 101710083689 Probable capsid protein Proteins 0.000 claims 1
- 229940123384 Toll-like receptor (TLR) agonist Drugs 0.000 claims 1
- 241000700605 Viruses Species 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- PKFDLKSEZWEFGL-MHARETSRSA-N c-di-GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]3[C@@H](O)[C@H](N4C5=C(C(NC(N)=N5)=O)N=C4)O[C@@H]3COP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 PKFDLKSEZWEFGL-MHARETSRSA-N 0.000 claims 1
- 210000004899 c-terminal region Anatomy 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 102000053826 human CD70 Human genes 0.000 claims 1
- GKTNLYAAZKKMTQ-UHFFFAOYSA-N n-[bis(dimethylamino)phosphinimyl]-n-methylmethanamine Chemical compound CN(C)P(=N)(N(C)C)N(C)C GKTNLYAAZKKMTQ-UHFFFAOYSA-N 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 239000002245 particle Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims 1
- 229930182490 saponin Natural products 0.000 claims 1
- 150000007949 saponins Chemical class 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 241000701161 unidentified adenovirus Species 0.000 claims 1
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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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/29—Hepatitis virus
- A61K39/292—Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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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- A61K2039/55505—Inorganic adjuvants
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- A61K2039/55511—Organic adjuvants
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
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- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
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Claims (16)
1. Rekombinantni vektor cijepljenja koji ekspresira
a) protein ovojnice (HBs-antigen) iz hepatitis B virusa serotipa adw, pri čemu je protein ovojnice poželjno mali ili veliki protein ovojnice iz hepatitis B virusa genotipa A serotipa adw, pri čemu je mali ili veliki protein ovojnice poželjno mali protein ovojnice; i
b) jezgreni protein (HBc-antigen) iz hepatitis B virusa serotipa ayw, pri čemu je jezgreni protein poželjno iz hepatitis B virusa genotipa D serotipa ayw;
i barem jedno od sljedećeg:
c) imunogenski protein ovojnice (HBs-antigen) iz hepatitis B virusa koji ima barem 90 % identiteta sekvence poput sekvence aminokiseline navedene u SEQ ID NO: 1; i/ili
d) imunogenski jezgreni protein (HBc-antigen) iz hepatitis B virusa koji ima barem 90 % identiteta sekvence poput sekvence aminokiseline navedene u SEQ ID NO: 2; i/ili
e) imunogenska RT domena polimeraze iz hepatitis B virusa koji ima barem 90 % identiteta sekvence poput sekvence aminokiseline navedene u SEQ ID NO: 3.
2. Rekombinantni vektor cijepljenja prema zahtjevu 1,
(I) pri čemu HBs-antigen u (c) i/ili HBc-antigen u (d) je(su) iz hepatitis B virusa genotipa C;
(II) pri čemu imunogenski HBs-antigen u (c) ima barem 90 % identiteta sekvence poput sekvence aminokiseline navedene u SEQ ID NO: 4 i/ili imunogenski HBc-antigen u (d) ima barem 90 % identiteta sekvence poput sekvence aminokiseline navedene u SEQ ID NO: 5 i/ili imunogenska RT domena polimeraze u (e) ima barem 90 % identiteta sekvence poput sekvence aminokiseline navedene u SEQ ID NO: 6;
(III) pri čemu je jezgreni protein iz hepatitis B virusa serotipa ayw u (b) C-terminalni krnji jezgreni protein koji sadrži ili se sastoji od aminokiselina 1-149 HBc-antigena iz hepatitis B virusa genotipa D serotipa ayw;
(IV) koji dalje ekspresira
(f) CD70, pri čemu je CD70 poželjno humani CD70 ili pri čemu CD70 poželjno ima barem 90 % identiteta sekvence poput sekvence aminokiseline navedene u SEQ ID NO: 26;
(V) pri čemu je rekombinantni vektor cijepljenja virus, čestica poput virusa ili bakterija; ili
(VI) pri čemu je rekombinantni vektor atenuirani soj Salmonelle, CMV-, VSV-bazirani vektor, adenovirusni vektor ili vektor ospica.
3. Rekombinantni vektor cijepljenja prema zahtjevu 1 ili 2, pri čemu je rekombinantni vektor cijepljenja MVA virus,
(I) pri čemu poželjno barem jedna, poželjno barem dvije, poželjno barem tri, poželjno barem četiri, poželjno pet sekvenca nukleinske kiseline koja/e kodira(ju) za (a), (b), (c), (d), i/ili (e) je(su) poželjno sadržane u jednoj ekspresijskoj kazeti, pri čemu ekspresijska kazeta poželjno kodira za sekvencu aminokiseline navedenu u SEQ ID NO: 7;
(II) pri čemu je barem jedna od nukleinskih kiselina koje kodiraju za (a), (b), (c), (d), i/ili (e) je(su) poželjno pod kontrolom poksviralnog promotora, pri čemu je poksviralni promotor poželjno P7.5 ili PH5, pri čemu ekspresijska kazeta poželjno kodira za sekvencu aminokiseline navedenu u SEQ ID NO: 7; ili
(III) pri čemu je sekvenca nukleinske kiseline koja kodira barem jedan od (a), (b), (c), (d), i/ili (e) poželjno umetnuta u deleciju I (del I), deleciju II (del II), deleciju III (del III), deleciju IV (del IV), deleciju V (del V), ili deleciju VI (del VI), poželjno deleciju III (del III) MVA genoma.
4. MVA virus koji espresira
(a) protein ovojnice (HBs-antigen) iz hepatitis B virusa serotipa adw, pri čemu je protein ovojnice poželjno mali ili veliki protein ovojnice iz hepatitis B virusa genotipa A serotipa adw, pri čemu je mali ili veliki protein ovojnice poželjno mali protein ovojnice;
i MVA virus koji ekspresira
(b) jezgreni protein (HBc-antigen) hepatitis B virusa serotipa ayw, pri čemu je jezgreni protein poželjno iz hepatitis B virusa genotipa D serotipa ayw;
za uporabu u postupku cijepljenja protiv hepatitisa B, pri čemu postupak sadrži:
(i) primjenu na subjektu
(a') proteina ovojnice iz hepatitis B virusa serotipa adw, pri čemu je protein ovojnice poželjno mali ili veliki protein ovojnice iz hepatitis B virusa genotipa A serotipa adw, pri čemu je mali ili veliki protein ovojnice poželjno mali protein ovojnice; i/ili
(b') jezgrenog proteina (HBc-antigen) iz hepatitis B virusa serotipa ayw, pri čemu je jezgreni protein poželjno iz hepatitis B virusa genotipa D serotipa ayw; i
(ii) primjenu MVA virusa koji ekspresira (a) i MVA virusa koji ekspresira (b) na subjektu.
5. MVA virus za uporabu prema zahtjevu 4, pri čemu MVA virus koji ekspresira (a) i/ili MVA virus koji ekspresira (b) dalje ekspresira CD70.
6. MVA virus koji ekspresira
(a) protein ovojnice (HBs-antigen) iz hepatitis B virusa serotipa adw, pri čemu je protein ovojnice poželjno mali ili veliki protein ovojnice iz hepatitis B virusa genotipa A serotipa adw, pri čemu je mali ili veliki protein ovojnice poželjno mali protein ovojnice; i
(b) jezgreni protein (HBc-antigen) iz hepatitis B virusa serotipa ayw, pri čemu je jezgreni protein poželjno iz hepatitis B virusa genotipa D serotipa ayw;
za uporabu u postupku cijepljenja protiv hepatitisa B, pri čemu postupak sadrži:
(i) primjenu na subjektu
(a') proteina ovojnice iz hepatitis B virusa serotipa adw, pri čemu je protein ovojnice poželjno mali ili veliki protein ovojnice iz hepatitis B virusa genotipa A serotipa adw, pri čemu je mali ili veliki protein ovojnice poželjno mali protein ovojnice; i/ili
(b') jezgrenog proteina (HBc-antigen) iz hepatitis B virusa serotipa ayw, pri čemu je jezgreni protein poželjno iz hepatitis B virusa genotipa D serotipa ayw; i
(ii) primjenu MVA virusa na subjektu.
7. MVA virus za uporabu prema zahtjevu 6, pri čemu MVA virus dalje ekspresira CD70.
8. Rekombinantni vektor cijepljenja prema zahtjevu 3 za uporabu u liječenju ili cijepljenju.
9. Rekombinantni vektor cijepljenja za uporabu prema zahtjevu 8 pri čemu je uporaba postupak cijepljenja protiv hepatitisa B, pri čemu uporaba sadrži
(i) primjenu na subjektu
(a') proteina ovojnice iz hepatitis B virusa serotipa adw, pri čemu je protein ovojnice poželjno mali ili veliki protein ovojnice iz hepatitis B virusa genotipa A serotipa adw, pri čemu je mali ili veliki protein ovojnice poželjno mali protein ovojnice; i/ili
(b') jezgrenog proteina (HBc-antigen) iz hepatitis B virusa serotipa ayw, pri čemu je jezgreni protein poželjno iz hepatitis B virusa genotipa D serotipa ayw; i
(ii) primjenu MVA virusa na subjektu.
10. MVA virus ili rekombinantni vektor cijepljenja za uporabu prema bilo kojem od zahtjeva 4 do 9,
(I) pri čemu je postupak cijepljenja postupak za terapijsko cijepljenje;
(II) pri čemu (i) postupka cijepljenja je pripremni korak i (ii) postupka cijepljenja je korak docjepljivanja;
(III) pri čemu su protein ovojnice i/ili jezgreni protein u (i) primijenjeni istodobno s barem jednim adjuvansom, pri čemu je adjuvans poželjno odabran od skupine koja se sastoji od poli[di(natrij karboksilatetilfenoksi)]fosfazena (PCEP), imuno stimulirajućeg oligonukleotida, agonista toll like (TLR) receptora, saponina ili njihovih kombinacija, pri čemu je TLR agonist poželjno TLR 3 agonist, TLR 4 agonist, TLR 7 agonist, TLR 8 agonist, ili TLR 9 agonist, i pri čemu je imuno stimulirajući oligonukleotid poželjno poli I/C, CpG, RIG-I ligand, STING ligand, ciklički di-AMP, ciklički di-CMP, ciklički di-GMP, TLR 7 agonist, TLR 8 agonist, CTA1DD, ili dmLT, pri čemu je adjuvans poželjno PCEP i/ili CpG adjuvans ili pri čemu je adjuvans poželjno ciklički di-AMP;
(IV) pri čemu je (i) izveden barem oko 1 dan prije izvođenja (ii), poželjno barem oko 5 dana, poželjno barem oko 1 tjedna, poželjno oko 1 tjedna do 8 tjedana, poželjno oko 2 tjedna do oko 5 tjedana, poželjno oko 3 tjedna do oko 4 tjedna; ili
(V) pri čemu postupak cijepljenja dalje sadrži nakon (i) i prije (ii):
(i') primjenu na subjektu
(a') proteina ovojnice iz hepatitis B virusa genotipa A, pri čemu je protein ovojnice poželjno mali ili veliki protein ovojnice iz hepatitis B virusa genotipa A serotipa adw, pri čemu je mali ili veliki protein ovojnice poželjno mali protein ovojnice; i/ili
(b') jezgrenog proteina (HBc-antigen) iz hepatitis B virusa genotipa D, pri čemu je jezgreni protein poželjno iz hepatitis B virusa genotipa D serotipa ayw
pri čemu je (i') poželjno korak docjepljivanja, pri čemu je (i) poželjno izveden barem 1 dan prije izvođenja (i'), poželjno barem oko 5 dana, poželjno barem oko 1 tjedna, poželjno oko 1 tjedna do 8 tjedana, poželjno oko 2 tjedna do oko 5 tjedana, poželjno oko 3 tjedna do oko 4 tjedna, i pri čemu je (i') poželjno izveden barem 1 dan prije izvođenja (ii), poželjno barem oko 5 dana, poželjno barem oko 1 tjedna, poželjno oko 1 tjedna do 8 tjedana, poželjno oko 2 tjedna do oko 5 tjedana, poželjno oko 3 tjedna do oko 4 tjedna; ili
11. MVA virus za uporabu prema bilo kojem od zahtjeva 4 do 10, pri čemu je primjena parenteralna ili mukozalnim putem,
(I) pri čemu je primjena poželjno intramuskularna, i pri čemu korak (i) i/ili (i') sadrži primjenu adjuvansa, pri čemu adjuvans sadrži ciklički di-AMP; ili
(II) pri čemu je primjena poželjno potkožna ili intramuskularna, i pri čemu korak (i) i/ili (i') sadrži primjenu adjuvansa, pri čemu adjuvans sadrži poli I/C ili RIG-I-ligandu.
12. Cjepivo ili farmaceutski sastav koji sadrži rekombinantni vektor cijepljenja ili MVA virus prema bilo kojem od zahtjeva 1 do 3.
13. Cjepivo prema zahtjevu 12, pri čemu rekombinantni vektor cijepljenja je rekombinantni vektor cijepljenja prema zahtjevu 3 ili rekombinantni vektor cijepljenja prema zahtjevu 1 koji je atenuirani soj Salmonelle, ili pri čemu je cjepivo parenteralno ili mukozalno cjepivo.
14. Komplet koji sadrži:
(i) proteinski sastav koji sadrži:
(a) protein ovojnice iz hepatitis B virusa genotipa A, pri čemu je protein ovojnice poželjno mali ili veliki protein ovojnice iz hepatitis B virusa genotipa A serotipa adw, pri čemu je mali ili veliki protein ovojnice poželjno mali protein ovojnice; i/ili
(b) jezgreni protein (HBc-antigen) iz hepatitis B virusa genotipa D, pri čemu je jezgreni protein poželjno iz hepatitis B virusa genotipa D serotipa ayw;
(ii) cjepivo prema bilo kojem od zahtjeva 12 ili 13.
15. Komplet prema zahtjevu 14,
(I) pri čemu je proteinski sastav prikladan za parenteralnu primjenu, pri čemu sastav poželjno sadrži barem jedan adjuvans koji je PCEP i/ili CpG adjuvans;
(II) pri čemu je proteinski sastav prikladan za mukozalnu primjenu, pri čemu sastav poželjno sadrži adjuvans odabran od skupine koja se sastoji od CTA1DD, dmLT, PCEP, poli I/C, RIG-I-liganda, cdi-AMP, c-di-CMP i c-diGMP ili njihovih kombinacija;
(III) pri čemu je proteinski sastav prikladan za intramuskularnu primjenu, pri čemu sastav poželjno sadrži barem jedan adjuvans koji je ciklički di-AMP; ili
(IV) pri čemu je proteinski sastav prikladan za potkožnu ili intramuskularnu primjenu, pri čemu sastav poželjno sadrži barem jedan adjuvans koji je poli I/C.
16. Ekspresijska kazeta koja sadrži nukleinske kiseline koje kodiraju:
(a) protein ovojnice (HBs-antigen) iz hepatitis B virusa serotipa adw, pri čemu je protein ovojnice poželjno mali ili veliki protein ovojnice iz hepatitis B virusa genotipa A serotipa adw, pri čemu je mali ili veliki protein ovojnice poželjno mali protein ovojnice; i
b) jezgreni protein (HBc-antigen) iz hepatitis B virusa serotipa ayw, pri čemu je jezgreni protein poželjno iz hepatitis B virusa genotipa D serotipa ayw;
i barem jedno od idućeg:
(c) imunogenski protein ovojnice (HBs-antigen) hepatitis B virusa koji ima barem 90 % identiteta sekvence poput sekvence aminokiseline navedene u SEQ ID NO: 1; i/ili
d) imunogenski jezgreni protein (HBc-antigen) hepatitis B virusa koji ima barem 90 % identiteta sekvence poput sekvence aminokiseline navedene u SEQ ID NO: 2; i/ili
e) imunogenska RT domena polimeraze iz hepatitis B virusa koji ima barem 90 % identiteta sekvence poput sekvence aminokiseline navedene u SEQ ID NO: 3.
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| JOP20200092A1 (ar) | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها |
| US11052148B2 (en) * | 2016-05-30 | 2021-07-06 | Geo Vax, Inc. | Compositions and methods for generating an immune response to hepatitis B virus |
| KR102672900B1 (ko) * | 2016-09-01 | 2024-06-10 | (주)아모레퍼시픽 | 2,4-디클로로-a-(3,4-디하이드로-4-옥소-2(1H)-퀴나졸리닐리덴)-β-옥소-벤젠프로판니트릴을 포함하는 멜라닌 증진용 조성물 |
| JP2020516673A (ja) * | 2017-04-18 | 2020-06-11 | アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | Ｂ型肝炎ウイルス（ｈｂｖ）感染を有する対象を処置する方法 |
| US11324820B2 (en) | 2017-04-18 | 2022-05-10 | Alnylam Pharmaceuticals, Inc. | Methods for the treatment of subjects having a hepatitis b virus (HBV) infection |
| TWI801377B (zh) | 2017-04-18 | 2023-05-11 | 美商阿尼拉製藥公司 | 治療具有ｂ型肝炎病毒（ｈｂｖ）感染之個體之方法 |
| US20210147807A1 (en) * | 2017-06-14 | 2021-05-20 | Helmholtz Zentrum Munchen - Deutsches Forschungszentrum Fur Gesundheit Und Umwelt (Gmbh) | Methods for purifying endoderm and pancreatic endoderm cells derived from human embryonic stem cells |
| GB201721068D0 (en) * | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B immunisation regimen and compositions |
| GB201721069D0 (en) * | 2017-12-15 | 2018-01-31 | Glaxosmithkline Biologicals Sa | Hepatitis B Immunisation regimen and compositions |
| MX2020006471A (es) * | 2017-12-19 | 2020-09-22 | Janssen Sciences Ireland Unlimited Co | Metodos y composiciones para inducir una respuesta inmune contra el virus de hepatitis b (hbv). |
| US11492623B2 (en) | 2018-08-13 | 2022-11-08 | Alnylam Pharmaceuticals, Inc. | Hepatitis B virus (HBV) dsRNA agent compositions and methods of use thereof |
| CN113271969A (zh) * | 2018-09-20 | 2021-08-17 | 萨斯喀彻温大学 | 粘膜粘附脂质递送系统 |
| CN113939527A (zh) * | 2019-01-11 | 2022-01-14 | 新加坡科技研究局 | Hla-a*11:01限制性乙型肝炎病毒(hbv)肽用于鉴别hbv特异性cd8+ t细胞的用途 |
| CN113573730A (zh) * | 2019-03-05 | 2021-10-29 | 葛兰素史密斯克莱生物公司 | 乙型肝炎免疫方案和组合物 |
| WO2020210628A1 (en) * | 2019-04-10 | 2020-10-15 | Emv Enhance (Hk) Limited | Compositions and methods for improving vaccination of hyporesponsive individuals |
| JP2022545530A (ja) * | 2019-08-29 | 2022-10-27 | ブイアイアール バイオテクノロジー インコーポレイテッド | Ｂ型肝炎ウイルスワクチン |
| EP4074334A1 (en) * | 2019-12-13 | 2022-10-19 | Grand Theravac Life Science (Nanjing) Co., Ltd. | Pharmaceutical composition and use thereof |
| AU2021220991A1 (en) * | 2020-02-14 | 2022-09-29 | Geovax, Inc. | Vaccines and uses thereof to induce an immune response to SARS-CoV2 |
| TW202216190A (zh) * | 2020-07-08 | 2022-05-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | 抗hbv之rna複製子疫苗 |
| WO2023085956A1 (en) * | 2021-11-09 | 2023-05-19 | Avalia Immunotherapies Limited | Novel therapeutic vaccines |
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| WO2009056535A2 (en) * | 2007-10-29 | 2009-05-07 | Genimmune N.V. | Methods and kits for inducing a ctl response using a prime boost regimen |
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| KR101281098B1 (ko) * | 2011-06-30 | 2013-07-02 | 주식회사 녹십자 | Ｂ형 간염 바이러스 표면 항원상의 에피토프 및 이의 용도 |
| AU2015259470A1 (en) * | 2014-05-16 | 2016-11-10 | Yale University | Virus like vesicles (VLVs) based vaccines to prevent or treat chronic hepatitis B virus (HBV) infection |
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| PT3402888T (pt) | 2020-12-04 |
| HUE052104T2 (hu) | 2021-04-28 |
| US10912827B2 (en) | 2021-02-09 |
| DK3402888T3 (da) | 2020-11-30 |
| SI3402888T1 (sl) | 2021-02-26 |
| CN109154004B (zh) | 2023-06-06 |
| RU2018114308A (ru) | 2020-02-13 |
| PL3402888T3 (pl) | 2021-04-19 |
| EP3402888A1 (en) | 2018-11-21 |
| US20190030158A1 (en) | 2019-01-31 |
| RU2018114308A3 (hr) | 2020-02-13 |
| EP3402888B1 (en) | 2020-08-26 |
| AU2017207764A1 (en) | 2018-05-10 |
| BR112018013387A2 (pt) | 2019-03-06 |
| JP6743154B2 (ja) | 2020-08-19 |
| SG11201805229YA (en) | 2018-07-30 |
| RU2740802C2 (ru) | 2021-01-21 |
| CN116732101A (zh) | 2023-09-12 |
| AU2017207764B2 (en) | 2023-04-27 |
| ZA201802644B (en) | 2023-07-26 |
| KR20180100228A (ko) | 2018-09-07 |
| WO2017121791A1 (en) | 2017-07-20 |
| JP2019505205A (ja) | 2019-02-28 |
| IL260525B (en) | 2022-02-01 |
| RS61118B1 (sr) | 2020-12-31 |
| CA3002508A1 (en) | 2017-07-20 |
| ES2834698T3 (es) | 2021-06-18 |
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