HRP20140949T1 - Nukleinska kiselina koja sadrži ili kodira histonsku strukturu peteljka-omäśa i poli(a) sekvencu ili poliadenilacijski signal za poveä†anje ekspresije kodiranog proteina - Google Patents
Nukleinska kiselina koja sadrži ili kodira histonsku strukturu peteljka-omäśa i poli(a) sekvencu ili poliadenilacijski signal za poveä†anje ekspresije kodiranog proteina Download PDFInfo
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- HRP20140949T1 HRP20140949T1 HRP20140949AT HRP20140949T HRP20140949T1 HR P20140949 T1 HRP20140949 T1 HR P20140949T1 HR P20140949A T HRP20140949A T HR P20140949AT HR P20140949 T HRP20140949 T HR P20140949T HR P20140949 T1 HRP20140949 T1 HR P20140949T1
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- 150000007523 nucleic acids Chemical class 0.000 title claims 20
- 108020004707 nucleic acids Proteins 0.000 title claims 18
- 102000039446 nucleic acids Human genes 0.000 title claims 18
- 108010033040 Histones Proteins 0.000 title claims 10
- 108090000623 proteins and genes Proteins 0.000 title claims 8
- 102000004169 proteins and genes Human genes 0.000 title claims 8
- 108091034057 RNA (poly(A)) Proteins 0.000 title claims 3
- 230000008488 polyadenylation Effects 0.000 title claims 3
- 108091007433 antigens Proteins 0.000 claims 23
- 102000036639 antigens Human genes 0.000 claims 23
- 239000000427 antigen Substances 0.000 claims 21
- 125000003729 nucleotide group Chemical group 0.000 claims 16
- 239000002773 nucleotide Substances 0.000 claims 10
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims 8
- 230000000295 complement effect Effects 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 230000003612 virological effect Effects 0.000 claims 6
- 150000003838 adenosines Chemical class 0.000 claims 5
- 230000001580 bacterial effect Effects 0.000 claims 5
- 201000010099 disease Diseases 0.000 claims 5
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims 4
- 102000053642 Catalytic RNA Human genes 0.000 claims 4
- 108090000994 Catalytic RNA Proteins 0.000 claims 4
- 108091026890 Coding region Proteins 0.000 claims 4
- 208000035473 Communicable disease Diseases 0.000 claims 4
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 claims 4
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims 4
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims 4
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical group O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims 4
- 229940029575 guanosine Drugs 0.000 claims 4
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- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims 2
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- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims 2
- 230000000172 allergic effect Effects 0.000 claims 2
- 208000010668 atopic eczema Diseases 0.000 claims 2
- 230000001363 autoimmune Effects 0.000 claims 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims 2
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- 208000032625 disorder of ear Diseases 0.000 claims 2
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- 230000007813 immunodeficiency Effects 0.000 claims 2
- 101150091879 neo gene Proteins 0.000 claims 2
- 230000001717 pathogenic effect Effects 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 208000023504 respiratory system disease Diseases 0.000 claims 2
- 208000017520 skin disease Diseases 0.000 claims 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims 1
- 108091035707 Consensus sequence Proteins 0.000 claims 1
- 208000017701 Endocrine disease Diseases 0.000 claims 1
- 102000048120 Galactokinases Human genes 0.000 claims 1
- 108700023157 Galactokinases Proteins 0.000 claims 1
- 102100027685 Hemoglobin subunit alpha Human genes 0.000 claims 1
- 108091005902 Hemoglobin subunit alpha Proteins 0.000 claims 1
- 102100039869 Histone H2B type F-S Human genes 0.000 claims 1
- 101001035372 Homo sapiens Histone H2B type F-S Proteins 0.000 claims 1
- 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 claims 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 claims 1
- 206010061598 Immunodeficiency Diseases 0.000 claims 1
- 108060001084 Luciferase Proteins 0.000 claims 1
- 239000005089 Luciferase Substances 0.000 claims 1
- 108091008874 T cell receptors Proteins 0.000 claims 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 239000013566 allergen Substances 0.000 claims 1
- 230000002009 allergenic effect Effects 0.000 claims 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims 1
- 208000016097 disease of metabolism Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000030172 endocrine system disease Diseases 0.000 claims 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 claims 1
- 230000002538 fungal effect Effects 0.000 claims 1
- 230000003308 immunostimulating effect Effects 0.000 claims 1
- 108020004999 messenger RNA Proteins 0.000 claims 1
- 208000030159 metabolic disease Diseases 0.000 claims 1
- 235000016709 nutrition Nutrition 0.000 claims 1
- 208000030212 nutrition disease Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 229940104230 thymidine Drugs 0.000 claims 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims 1
- 229940045145 uridine Drugs 0.000 claims 1
- 229940075420 xanthine Drugs 0.000 claims 1
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- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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Claims (16)
1. Sekvenca nukleinske kiselina koja sadrži ili kodira
a) kodirajuće područje koje kodira terapeutski aktivni protein ili peptid, adjuvantni protein, antigen, tumorski antigen, patogeni antigen, životinjski antigen, virusni antigen, protozoalni antigen, bakterijski antigen, alergeni antigen, autoimuni antigen, alergen, protutijelo, imunostimulatorni protein ili peptid, ili antigen-specifični receptor T-stanica; pod uvjetom da kodirajuće područje ne kodira histonske proteine, reporterske proteine odabrane od EGFP i Luciferaze i označavajuće ili selekcijske proteine odabrane od alfa-Globina, galaktokinaze i ksantin:gvanin fosforibozil transferaze,
b) barem jedan histon peteljka-omča, i
c) poli(A) sekvencu ili poliadenilacijski signal,
naznačena time da je za uporabu za povećanje ekspresije navedenog proteina koji kodira kodirajuće područje kako je definirano u (a) za liječenje kanceroznih bolesti, zaraznih bolesti, autoimunih bolesti, alergija ili alergijskih bolesti, monogenetskih bolesti, genetskih bolesti, kardiovaskularnih bolesti, neuronskih bolesti, bolesti dišnog sustava, bolesti probavnog sustava, kožnih bolesti, muskuloskeletalnih poremećaja, poremećaja vezivnog tkiva, imunodeficijencija, endokrinih, prehrambenih i metaboličkih bolesti, očnih bolesti ili bolesti uha.
2. Nukleinska kiselina za uporabu prema zahtjevu 1 naznačena time da je za liječenje virusnih, bakterijskih ili protozooloških zaraznih bolesti.
3. Nukleinska kiselina za uporabu prema zahtjevu 1 ili 2, naznačena time da nukleinska kiselina ne sadrži jednu ili dvije ili barem jednu ili sve osim jedne ili sve komponente skupine koja sadrži: sekvencu koja kodira ribozim ili samostalno-spajajući ribozim, sekvencu virusne nukleinske kiseline, signal za procesiranje histona peteljka-omča, naročito sekvencu za procesiranje signala histona peteljka-omča dobivenu iz mišjeg histon gena H2A614, Neo gen, inaktiviranu sekvencu promotora i inaktiviranu sekvencu pojačivača.
4. Nukleinska kiselina za uporabu prema zahtjevu 1 do 3, naznačena time da nukleinska kiselina ne sadrži ribozim, poželjno samostalno-spajajući ribozim, te jedan iz skupine koja sadrži: Neo gen, inaktiviranu sekvencu promotora, inaktiviranu sekvencu pojačivača, signal za procesiranje histona peteljka-omča, naročito sekvencu za procesiranje signala histona peteljka-omča dobivenu iz mišjeg histon gena H2A614.
5. Nukleinska kiselina za uporabu prema zahtjevu 1 do 4, naznačena time da je nukleinska kiselina RNK, poželjno mRNK.
6. Nukleinska kiselina za uporabu prema bilo kojem zahtjevu 1 do 5, naznačena time da je barem jedan histon peteljka-omča odabran iz slijedećih formula (I) ili (II):
formula (I) (peteljka-omča sekvenca bez graničnih elemenata peteljke):
[image]
formula (II) (peteljka-omča sekvenca sa graničnim elementima peteljke):
[image]
pri čemu:
granični elementi N1-6 peteljka1 ili peteljka2 su uzastopna sekvenca od 1 do 6,
poželjno od 2 do 6, poželjnije od 2 do 5, čak poželjnije od 3 do 5, najpoželjnije od 4 do 5 ili 5 N, pri čemu svaki N je neovisno od drugog izabran od nukleotida odabranog od A, U, T, G i C, ili njegovog nukleotidnog analoga;
peteljka1 [N0-2GN3-5] je reverzno komplementarna ili djelomično reverzno komplementarna sa elementom peteljka2, te je uzastopna sekvenca od između 5 do 7 nukleotida;
pri čemu N0-2 je uzastopna sekvenca od 0 do 2, poželjno od 0 do 1, poželjnije od 1 N, pri čemu svaki N je neovisno od drugog izabran od nukleotida odabranog od A, U, T, G i C ili njegovog nukleotidnog analoga;
pri čemu N3-5 je uzastopna sekvenca od 3 do 5, poželjno od 4 do 5, poželjnije od 4 N, pri čemu svaki N je neovisno od drugog izabran od nukleotida odabranog od A, U, T, G i C ili njegovog nukleotidnog analoga, te
pri čemu G je gvanozin ili njegov analog, te može biti proizvoljno zamijenjen sa citidinom ili njegovim analogom, uz uvjet da je njegov komplementarni nukleotid citidin u peteljki2 zamijenjen sa gvanozinom;
omča sekvence [N0-4(U/T)N0-4] je smještena između elemenata peteljka1 i peteljka2, te je uzastopna sekvenca od 3 do 5 nukleotida, poželjnije od 4 nukleotida; pri čemu je svaki N0-4 neovisan od druge uzastopne sekvence od 0 do 4, poželjno od 1 do 3, poželjnije od 1 do 2 N, pri čemu svaki N je neovisno od drugog izabran od nukleotida odabranog od A, U, T, G i C ili njegovog nukleotidnog analoga; i
pri čemu U/T predstavlja uridin, ili proizvoljno timidin;
peteljka2 [N3-5CN0-2] je reverzno komplementarna ili djelomično reverzno komplementarna sa elementom peteljka1, te je uzastopna sekvenca od između 5 do 7 nukleotida;
pri čemu N3-5 je uzastopna sekvenca od 3 do 5, poželjno od 4 do 5, poželjnije sa 4 N, pri čemu svaki N je neovisno od drugog izabran od nukleotida odabranog od A, U, T, G i C ili njegovog nukleotidnog analoga;
pri čemu N0-2 je uzastopna sekvenca od 0 do 2, poželjno od 0 do 1, poželjnije sa 1 N, pri čemu svaki N je neovisno od drugog izabran od nukleotida odabranog od A, U, T, G i C ili njegovog nukleotidnog analoga; i
pri čemu C je citidin ili njegov analog, te može biti proizvoljno zamijenjen sa gvanozinom ili njegovim analogom uz uvjet da je njegov komplementarni nukleotid gvanozin u peteljki1 zamijenjen sa citidinom;
pri čemu
peteljka1 i peteljka2 su sposobni za međusobno bazno uparivanje i za formiranje reverzno komplementarne sekvence, pri čemu se bazno uparivanje može dogoditi između peteljka1 i peteljka2, ili
za formiranje djelomično reverzno komplementarne sekvence, pri čemu se nepotpuno bazno uparivanje može dogoditi između peteljka1 i peteljka2.
7. Nukleinska kiselina za uporabu prema zahtjevu 6, naznačena time da je barem jedan histon peteljka-omča odabran od barem jednog sa slijedećim formulama (Ia) ili (IIa):
[image]
formula (Ia) (peteljka-omča sekvenca bez graničnih elemenata peteljke)
[image]
formula (IIa) (peteljka-omča sekvenca sa graničnim elementima peteljke)
8. Nukleinska kiselina za uporabu prema bilo kojem zahtjevu 1 do 7, naznačena time da poli(A) sekvenca sadrži sekvencu od oko 25 do oko 400 adenozin nukleotida, poželjno sekvencu od oko 50 do oko 400 adenozin nukleotida, poželjnije sekvencu od oko 50 do oko 300 adenozin nukleotida, čak još poželjnije sekvencu od oko 50 do oko 250 adenozin nukleotida, najpoželjnije sekvencu od oko 60 do oko 250 adenozin nukleotida.
9. Nukleinska kiselina za uporabu prema bilo kojem zahtjevu 1 do 7, naznačena time da poliadenilacijski signal sadrži konsenzus sekvencu NNUANA, poželjno AAUAAA ili AUUAAA.
10. Nukleinska kiselina za uporabu prema bilo kojem zahtjevu 1 do 9, naznačena time da nukleinska kiselina je monocistronska, bicistronska ili čak multicistronska nukleinska kiselina.
11. Farmaceutski pripravak koji sadrži nukleinsku kiselinu kako je opisana u bilo kojem zahtjevu od 1 do 10 za uporabu za povećanje ekspresije proteina kodiranog s kodirajućom regijom navedene nukleinske kiseline kako je definirano u bilo kojem zahtjevu od 1 do 10 naznačen time da je za liječenje kanceroznih bolesti, zaraznih bolesti, autoimunih bolesti, alergija ili alergijskih bolesti, monogenetskih bolesti, genetskih bolesti, kardiovaskularnih bolesti, neuronskih bolesti, bolesti dišnog sustava, bolesti probavnog sustava, kožnih bolesti, muskuloskeletalnih poremećaja, poremećaja vezivnog tkiva, imunodeficijencija, endokrinih, prehrambenih i metaboličkih bolesti, očnih bolesti ili bolesti uha.
12. Farmaceutski pripravak za uporabu prema zahtjevu 11 naznačen time da sadrži farmaceutski prihvatljiv nosač.
13. Farmaceutski pripravak za uporabu prema zahtjevu 11 ili 12 naznačen time da je za liječenje virusnih, bakterijskih ili protozooloških zaraznih bolesti.
14. Cjepivo koje sadrži nukleinsku kiselina prema bilo kojem zahtjevu od 1 do 13 koja kodira proteinski antigen ili sadrži proteinski antigen za uporabu za povećanje ekspresije navedenog proteinskog antigena naznačeno time da je za liječenje kanceroznih bolesti, zaraznih bolesti, alergija ili alergijskih bolesti ili autoimunih bolesti.
15. Cjepivo za uporabu prema zahtjevu 14 naznačeno time da je za liječenje virusnih, bakterijskih ili protozooloških zaraznih bolesti.
16. Cjepivo za uporabu prema zahtjevu 14 ili 15, naznačeno time da antigen je odabran od tumorskih antigena, alergijskih antigena, auto-imunih vlastitih-antigena, patogenih antigena, virusnih antigena, bakterijskih antigena, gljivičnih antigena, protozooloških antigena, životinjskih antigena, ili alergijskih antigena.
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| PCT/EP2010/004998 WO2012019630A1 (en) | 2010-08-13 | 2010-08-13 | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded protein |
| PCT/EP2011/004077 WO2012019780A1 (en) | 2010-08-13 | 2011-08-12 | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded protein |
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| DK2831241T3 (da) | 2012-03-27 | 2017-11-06 | Curevac Ag | Kunstige nukleinsyremolekyler til forbedret protein- eller peptidekspression. |
| ES2719598T3 (es) | 2012-05-25 | 2019-07-11 | Curevac Ag | Inmovilización reversible y/o liberación controlada de ácidos nucleicos contenidos en nanopartículas mediante revestimientos poliméricos (biodegradables) |
| WO2014081507A1 (en) | 2012-11-26 | 2014-05-30 | Moderna Therapeutics, Inc. | Terminally modified rna |
| BR112016001192A2 (pt) | 2013-08-21 | 2017-08-29 | Curevac Ag | Vacina contra a raiva |
| ES2747762T3 (es) | 2013-08-21 | 2020-03-11 | Curevac Ag | Vacuna contra el virus respiratorio sincitial (RSV) |
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2010
- 2010-08-13 WO PCT/EP2010/004998 patent/WO2012019630A1/en active Application Filing
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2011
- 2011-08-12 JP JP2013523537A patent/JP5860464B2/ja active Active
- 2011-08-12 RS RS20140608A patent/RS53593B1/en unknown
- 2011-08-12 EP EP14002182.5A patent/EP2796557A1/en not_active Withdrawn
- 2011-08-12 MX MX2013001182A patent/MX342933B/es active IP Right Grant
- 2011-08-12 SI SI201130279T patent/SI2603590T1/sl unknown
- 2011-08-12 BR BR112013003378A patent/BR112013003378A2/pt not_active Application Discontinuation
- 2011-08-12 DK DK11745701.0T patent/DK2603590T3/da active
- 2011-08-12 CA CA2801218A patent/CA2801218C/en active Active
- 2011-08-12 US US13/321,474 patent/US9234013B2/en active Active
- 2011-08-12 RU RU2013110779/10A patent/RU2583295C2/ru active
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- 2011-08-12 WO PCT/EP2011/004077 patent/WO2012019780A1/en active Application Filing
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- 2011-08-12 CN CN201180039309.6A patent/CN103068987B/zh active Active
- 2011-08-12 PT PT117457010T patent/PT2603590E/pt unknown
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- 2011-08-12 KR KR1020137005831A patent/KR101720063B1/ko active IP Right Grant
- 2011-08-12 ES ES11745701.0T patent/ES2525556T3/es active Active
- 2011-08-12 AU AU2011289021A patent/AU2011289021B2/en active Active
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2014
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- 2015-11-18 US US14/945,349 patent/US9839697B2/en active Active
- 2015-12-18 JP JP2015247498A patent/JP2016041080A/ja not_active Withdrawn
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