HRP20201684T1 - Tri-segmentirani arenavirusi kao vektori cjepiva - Google Patents
Tri-segmentirani arenavirusi kao vektori cjepiva Download PDFInfo
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- HRP20201684T1 HRP20201684T1 HRP20201684TT HRP20201684T HRP20201684T1 HR P20201684 T1 HRP20201684 T1 HR P20201684T1 HR P20201684T T HRP20201684T T HR P20201684TT HR P20201684 T HRP20201684 T HR P20201684T HR P20201684 T1 HRP20201684 T1 HR P20201684T1
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- arenavirus
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- 241000712891 Arenavirus Species 0.000 title claims 57
- 229960005486 vaccine Drugs 0.000 title claims 2
- 239000013598 vector Substances 0.000 title claims 2
- 108700026244 Open Reading Frames Proteins 0.000 claims 32
- 239000002245 particle Substances 0.000 claims 31
- 239000000427 antigen Substances 0.000 claims 14
- 102000036639 antigens Human genes 0.000 claims 14
- 108091007433 antigens Proteins 0.000 claims 14
- 108020005345 3' Untranslated Regions Proteins 0.000 claims 11
- 108020003589 5' Untranslated Regions Proteins 0.000 claims 11
- 108090000623 proteins and genes Proteins 0.000 claims 8
- 241000700605 Viruses Species 0.000 claims 6
- 108010043121 Green Fluorescent Proteins Proteins 0.000 claims 4
- 102000004144 Green Fluorescent Proteins Human genes 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 239000005090 green fluorescent protein Substances 0.000 claims 4
- 208000015181 infectious disease Diseases 0.000 claims 4
- 230000002458 infectious effect Effects 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 239000002299 complementary DNA Substances 0.000 claims 3
- 102000004169 proteins and genes Human genes 0.000 claims 3
- 108010054624 red fluorescent protein Proteins 0.000 claims 3
- 230000003362 replicative effect Effects 0.000 claims 3
- 108020004635 Complementary DNA Proteins 0.000 claims 2
- 241000701022 Cytomegalovirus Species 0.000 claims 2
- 102100039793 E3 ubiquitin-protein ligase RAG1 Human genes 0.000 claims 2
- 101001065501 Escherichia phage MS2 Lysis protein Proteins 0.000 claims 2
- 241000711549 Hepacivirus C Species 0.000 claims 2
- 101000744443 Homo sapiens E3 ubiquitin-protein ligase RAG1 Proteins 0.000 claims 2
- 241000701085 Human alphaherpesvirus 3 Species 0.000 claims 2
- 241000725303 Human immunodeficiency virus Species 0.000 claims 2
- 241000712899 Lymphocytic choriomeningitis mammarenavirus Species 0.000 claims 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 claims 2
- 239000013566 allergen Substances 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 108091006047 fluorescent proteins Proteins 0.000 claims 2
- 102000034287 fluorescent proteins Human genes 0.000 claims 2
- 238000005215 recombination Methods 0.000 claims 2
- 230000006798 recombination Effects 0.000 claims 2
- 201000008827 tuberculosis Diseases 0.000 claims 2
- 108020004414 DNA Proteins 0.000 claims 1
- 108010086140 Interferon alpha-beta Receptor Proteins 0.000 claims 1
- 102000007438 Interferon alpha-beta Receptor Human genes 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 claims 1
- 208000037581 Persistent Infection Diseases 0.000 claims 1
- 108091023045 Untranslated Region Proteins 0.000 claims 1
- 239000013604 expression vector Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 108010077753 type II interferon receptor Proteins 0.000 claims 1
- 230000003612 virological effect Effects 0.000 claims 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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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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- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5254—Virus avirulent or attenuated
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5256—Virus expressing foreign proteins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
- A61K2039/572—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/10011—Arenaviridae
- C12N2760/10021—Viruses as such, e.g. new isolates, mutants or their genomic sequences
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- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/10011—Arenaviridae
- C12N2760/10034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/10011—Arenaviridae
- C12N2760/10041—Use of virus, viral particle or viral elements as a vector
- C12N2760/10043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/10011—Arenaviridae
- C12N2760/10061—Methods of inactivation or attenuation
- C12N2760/10062—Methods of inactivation or attenuation by genetic engineering
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/80—Vectors comprising a special translation-regulating system from vertebrates
- C12N2840/85—Vectors comprising a special translation-regulating system from vertebrates mammalian
Claims (24)
1. Čestica tri-segmentiranog zaraznog replicirajućeg arenavirusa koja obuhvaća jedan L segment i dva S segmenta, pri čemu je jedan od dva S segmenta odabran iz skupine koja se sastoji od:
(i) S segmenta, pri čemu je ORF (Otvoreni okvir čitanja (engl. open reading frame)) kodiranja NP-a pod kontrolom arenavirus 5' UTR-a (netranslatirana regija (engl. untranslated region);
(ii) S segmenta, pri čemu je ORF kodiranja Z proteina pod kontrolom arenavirus 5' UTR-a;
(iii) S segmenta, pri čemu je ORF kodiranja L proteina pod kontrolom arenavirus 5' UTR-a;
(iv) S segmenta, pri čemu je ORF kodiranja GP-a pod kontrolom arenavirus 3' UTR-a;
(v) S segmenta, pri čemu je ORF kodiranja L-a pod kontrolom arenavirus 3' UTR-a; i
(vi) S segmenta, pri čemu je ORF kodiranja Z proteina pod kontrolom arenavirus 3' UTR-a,
pri čemu čestica tri-segmentiranog virusa obuhvaća dva heterologna ORF-a.
2. Čestica tri-segmentiranog zaraznog replicirajućeg arenavirusa koja obuhvaća dva L segmenta i jedan S segment, pri čemu je jedan od dva L segmenta odabran iz skupine koja se sastoji od:
(i) L segmenta, pri čemu je ORF kodiranja GP-a pod kontrolom arenavirus 5' UTR-a;
(ii) L segmenta, pri čemu je ORF kodiranja NP-a pod kontrolom arenavirus 5' UTR-a;
(iii) L segmenta, pri čemu je ORF kodiranja L proteina pod kontrolom arenavirus 5' UTR-a;
(iv) L segmenta, pri čemu je ORF kodiranja GP-a pod kontrolom arenavirus 3' UTR-a;
(v) L segmenta, pri čemu je ORF kodiranja NP-a pod kontrolom arenavirus 3' UTR-a; i
(vi) L segmenta, pri čemu je ORF kodiranja Z proteina pod kontrolom arenavirus 3' UTR-a,
pri čemu čestica tri-segmentiranog virusa obuhvaća dva heterologna ORF-a.
3. Čestica tri-segmentiranog arenavirusa prema zahtjevu 1, naznačena time da među-segmentna rekombinacija dvaju S segmenata, koja spaja dva ORF-a arenavirusa na samo jednom umjesto dva odvojena segmenta, stavlja izvan snage aktivnost nositelja virusa.
4. Čestica tri-segmentiranog arenavirusa prema zahtjevu 2, naznačena time da među-segmentna rekombinacija dvaju L segmenata, koja spaja dva ORF-a arenavirusa na samo jednom umjesto dva odvojena segmenta, stavlja izvan snage aktivnost nositelja virusa.
5. Čestica tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 1 do 4, naznačena time da reprodukcija čestice tri-segmentiranog arenavirusa ne dovodi do replicirajuće bi-segmentirane viralne čestice nakon 70 dana stalne infekcije kod miševa kojima nedostaje tip I interferon receptor, tip II interferon receptor i gen koji aktivira rekombinaciju 1 (RAG1) i bivajući inficirani s 104 PFU čestice tri-segmentiranog arenavirusa.
6. Čestica tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 1 do 5, naznačena time da je arenavirus 3' UTR 3' UTR arenavirus S Segmenta ili arenavirus L segmenta, i naznačena time da je arenavirus 5' UTR 5' UTR arenavirus S segmenta ili arenavirus L segmenta.
7. Čestica tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 1, 3, 5 i 6, naznačena time da dva S segmenta obuhvaćaju dva heterologna ORF-a.
8. Čestica tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 2, 4, 5 i 6, naznačena time da dva L segmenta obuhvaćaju dva heterologna ORF-a.
9. Čestica tri-segmentiranog arenavirusa prema zahtjevu 7 ili 8, naznačena time da barem jedan heterologni ORF kodira antigen (i) dobiven od infektivnog organizma, tumora ili alergena; ili (ii) odabran od antigena virusa humane imunodeficijencije, antigena virusa hepatitisa C, antigena virusa varicella-zoster, antigena citomegalovirusa, antigena tuberkuloze (mycobacterium tuberculosis), i antigena povezanih s tumorima.
10. Čestica tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 1 do 9, naznačena time da barem jedan heterologan ORF kodira fluorescentni protein.
11. Čestica tri-segmentiranog arenavirusa prema zahtjevu 10, naznačena time da je fluorescentni protein zeleni fluorescentni protein (GFP) ili crveni fluorescentni protein (RFP).
12. Čestica tri-segmentiranog arenavirusa prema zahtjevu 11, naznačena time da dva heterologna ORF-a svaki kodiraju GFP.
13. Čestica tri-segmentiranog arenavirusa prema zahtjevu 11, naznačena time da jedan heterologni ORF kodira GFP i jedan heterologni ORF kodira RFP.
14. Čestica tri-segmentiranog arenavirusa prema zahtjevu 1, naznačena time da je prvi S segment projektiran za nošenje ORF kodirajućeg GP-a u položaju pod kontrolom arenavirus 3' UTR-a i heterologni ORF koji kodira prvi gen od interesa u položaju pod kontrolom arenavirus 5' UTR-a i drugi S segment je projektiran za nošenje ORF kodirajućeg NP-a u položaju pod kontrolom arenavirus 3' UTR-a i heterologni ORF koji kodira drugi gen od interesa u položaju pod kontrolom arenavirus 5' UTR-a.
15. Čestica tri-segmentiranog arenavirusa prema zahtjevu 1, naznačena time da je prvi S segment projektiran za nošenje ORF kodirajućeg GP-a u položaju pod kontrolom arenavirus 5' UTR-a i heterologni ORF koji kodira prvi gen od interesa u položaju pod kontrolom arenavirus 3' UTR-a i drugi S segment je projektiran za nošenje ORF kodirajućeg NP-a u položaju pod kontrolom arenavirus 5' UTR-a i heterologni ORF koji kodira drugi gen od interesa u položaju pod kontrolom arenavirus 3' UTR-a.
16. Čestica tri-segmentiranog arenavirusa prema zahtjevu 14 ili 15, naznačena time da gen od interesa kodira antigen (i) dobiven od infektivnog organizma, tumora ili alergena; ili (ii) odabran od antigena virusa humane imunodeficijencije, antigena virusa hepatitisa C, antigena virusa varicella-zoster, antigena citomegalovirusa, antigena tuberkuloze (mycobacterium tuberculosis), i antigena povezanih s tumorima.
17. Čestica tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 1 do 16, naznačena time da je čestica tri-segmentiranog arenavirusa dobivena od LCMV (Limfocitni koriomeningitis; engl. Lymphocytic choriomeningitis virus).
18. cDNK genoma čestice tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 1 do 17.
19. DNK ekspresijski vektor koji obuhvaća cDNK prema zahtjevu 18.
20. Stanica domaćin koja obuhvaća česticu tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 1 do 17, cDNK prema zahtjevu 18, ili vektor prema zahtjevu 19.
21. Metoda generiranja čestice tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 1, 3 i 5, naznačena time da metoda obuhvaća:
(i) prijenos jedne ili više cDNK s jednim L segmentom i dva S segmenta u stanicu domaćina;
(ii) održavanje stanice domaćina u uvjetima prikladnim za formiranje virusa; i
(iii) prikupljanje čestice arenavirusa.
22. Metoda generiranja čestice tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 2, 4 i 5, naznačena time da metoda obuhvaća:
(i) prijenos jedne ili više cDNK s dva L segmenta i jednim S segmentom u stanicu domaćina;
(ii) održavanje stanice domaćina u uvjetima prikladnim za formiranje virusa; i
(iii) prikupljanje čestice arenavirusa.
23. Cjepivo koje obuhvaća česticu tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 1 do 17 i farmaceutski prihvatljiv nosač.
24. Farmaceutski sastav koji obuhvaća česticu tri-segmentiranog arenavirusa prema bilo kojem od zahtjeva 1 do 17 i farmaceutski prihvatljiv nosač.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462079493P | 2014-11-13 | 2014-11-13 | |
EP15794900.9A EP3218504B1 (en) | 2014-11-13 | 2015-11-12 | Tri-segmented arenaviruses as vaccine vectors |
PCT/EP2015/076458 WO2016075250A1 (en) | 2014-11-13 | 2015-11-12 | Tri-segmented arenaviruses as vaccine vectors |
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HRP20201684T1 true HRP20201684T1 (hr) | 2020-12-25 |
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HRP20201684TT HRP20201684T1 (hr) | 2014-11-13 | 2020-10-19 | Tri-segmentirani arenavirusi kao vektori cjepiva |
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US (3) | US10722564B2 (hr) |
EP (2) | EP3778903A1 (hr) |
JP (3) | JP6805139B2 (hr) |
CN (1) | CN107223130A (hr) |
AU (2) | AU2015345080B2 (hr) |
CA (1) | CA2967720C (hr) |
CY (1) | CY1123339T1 (hr) |
DK (1) | DK3218504T3 (hr) |
ES (1) | ES2811093T3 (hr) |
HK (1) | HK1244034A1 (hr) |
HR (1) | HRP20201684T1 (hr) |
HU (1) | HUE051390T2 (hr) |
LT (1) | LT3218504T (hr) |
PL (1) | PL3218504T3 (hr) |
PT (1) | PT3218504T (hr) |
RS (1) | RS60937B1 (hr) |
SI (1) | SI3218504T1 (hr) |
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Families Citing this family (24)
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EP4186978A1 (en) | 2007-12-27 | 2023-05-31 | Universität Zürich | Replication-defective arenavirus vectors |
AU2014359276B2 (en) | 2013-12-03 | 2021-01-28 | Hookipa Biotech Gmbh | CMV vaccines |
RS60937B1 (sr) | 2014-11-13 | 2020-11-30 | Univ Geneve | Tri-segmentirani arenavirusi kao vektori za vakcinu |
JP7098330B2 (ja) * | 2015-06-10 | 2022-07-11 | ホオキパ バイオテック ジーエムビーエイチ | Hpvワクチン |
WO2018045029A1 (en) * | 2016-09-02 | 2018-03-08 | The United States Of America, As Represented By The Secretary Of The Army | Pan south american arenavirus live attenuated vaccine |
AU2016348675B2 (en) * | 2015-11-04 | 2022-11-17 | Hookipa Biotech Gmbh | Vaccines against Hepatitis B virus |
PL3373959T3 (pl) * | 2015-11-12 | 2022-10-24 | Hookipa Biotech Gmbh | Cząstki arenawirusa jako szczepionki przeciwrakowe |
US20200206334A1 (en) | 2016-11-04 | 2020-07-02 | Hookipa Biotech Gmbh | Replication-deficient arenavirus particles and tri-segmented arenavirus particles as cancer vaccines |
WO2018185307A1 (en) | 2017-04-07 | 2018-10-11 | Hookipa Biotech Ag | Arenavirus particles to treat solid tumors |
US11021692B2 (en) | 2017-12-19 | 2021-06-01 | Janssen Sciences Ireland Unlimited Company | Hepatitis B virus (HBV) vaccines and uses thereof |
CN108611310A (zh) * | 2018-04-28 | 2018-10-02 | 中国药科大学 | 一种重组Hsp65与STEAP1186-193融合蛋白的基因工程菌的构建 |
CN108977434A (zh) * | 2018-07-03 | 2018-12-11 | 张罗 | 鼻腔脱落细胞rna的提取方法 |
AU2020297011A1 (en) * | 2019-06-18 | 2022-02-10 | Janssen Sciences Ireland Unlimited Company | Arenavirus vectors for hepatitis B virus (HBV) vaccines and uses thereof |
KR20220047277A (ko) | 2019-07-16 | 2022-04-15 | 길리애드 사이언시즈, 인코포레이티드 | Hiv 백신, 및 이의 제조 및 사용 방법 |
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CA2967720A1 (en) | 2016-05-19 |
US10722564B2 (en) | 2020-07-28 |
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HUE051390T2 (hu) | 2021-03-01 |
RS60937B1 (sr) | 2020-11-30 |
ES2811093T3 (es) | 2021-03-10 |
AU2015345080B2 (en) | 2022-01-27 |
AU2015345080A1 (en) | 2017-06-01 |
JP2021045154A (ja) | 2021-03-25 |
US20240082376A1 (en) | 2024-03-14 |
AU2022200061A1 (en) | 2022-02-03 |
JP6805139B2 (ja) | 2020-12-23 |
CN107223130A (zh) | 2017-09-29 |
WO2016075250A1 (en) | 2016-05-19 |
US20170319673A1 (en) | 2017-11-09 |
CA2967720C (en) | 2024-01-02 |
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