DK1554375T3 - Adenovirus som eksprimerer gener i omvendt rækkefølge og anvendelse deraf - Google Patents
Adenovirus som eksprimerer gener i omvendt rækkefølge og anvendelse deraf Download PDFInfo
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- DK1554375T3 DK1554375T3 DK03753560.6T DK03753560T DK1554375T3 DK 1554375 T3 DK1554375 T3 DK 1554375T3 DK 03753560 T DK03753560 T DK 03753560T DK 1554375 T3 DK1554375 T3 DK 1554375T3
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- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10332—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
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Claims (62)
1. Adenovirus, som eksprimerer et E1 B55kD protein og et E4orf6 protein før et E1A12S protein, hvor adenovirusset omfatter i det mindste én nucleinsyre, som koder for et E1A12S protein, hvor eksprimeringen af E1A12S proteinet sker under styring af en promotor og er styret af den promotor, hvor promotoren er forskellig fra den promotor, som styrer eksprimeringen af proteinet i en vildtype adenovirus, hvor promotoren er valgt fra gruppen bestående af tumorspecifikke promotorer, organspecifikke promotorer, vævsspecifikke promotorer, heterologe promotorer og adenovirale promotorer, hvor den adenovirale promotor er forskellig fra E1A promotoren, hvor adenovirussen er repli-kations-deficient, men replikerer i celler, som omfatter YB-1 i cellekernen eller som omfatter dereguleret YB-1 i cytoplasmaet, hvor dereguleret YB-1 er ét, som foreligger i en form, som er kvantitativt forskellig fra dette i en ikke-tumorcelle.
2. Adenovirus ifølge krav 1, kendetegnet ved, at eksprimeringen af E1B55kD proteinet er styret af en promotor, hvor promotoren er valgt fra gruppen bestående af tumorspecifikke promotorer, organspecifikke promotorer, vævsspecifikke promotorer, heterologe promotorer og adenovirale promotorer, hvor den adenovirale promotor er forskellige fra E1B promotoren.
3. Advenovirus ifølge ethvert af kravene 1 til 2, kendetegnet ved, at eksprimeringen af E4orf6 proteinet er styret af en promotor, hvor promotoren er valgt fra gruppen bestående af tumorspecifikke promotorer, organspecifikke promotorer, vævsspecifikke promotorer, heterologe promotorer og adenovirale promotorer, hvor den adenovirale promotor er forskellige fra E4 promotoren.
4. Adenovirus ifølge ethvert af kravene 2 og 3, hvor den adenovirale promotor er E1A promotoren.
5. Adenovirus ifølge ethvert af kravene 2 til 4, kendetegnet ved, at promotoren, som styrer eksprimeringen af E1A12S proteinet er YB-1 styret eller kan styres af YB-1.
6. Adenovirus ifølge ethvert af kravene 2 til 5, kendetegnet ved, at promotoren, som styrer eksprimeringen E1A12S proteinet er den adenovirale E2-late-promotor.
7. Adenovirus ifølge ethvert af kravene 1 til 6, kendetegnet ved, at E4orf6 proteinet og E1 B55kD proteinet er under kontrol af den samme eller en fælles promotor.
8. Adenovirus ifølge ethvert af kravene 1 til 7, kendetegnet ved, at nucleinsyren i adenovirussen omfatter i det mindste én funktionel inaktiv adenoviral region, hvor regionen er valgt fra gruppen bestående af E1-regionen, E3-regionen, E4-regionen og kombinationer deraf.
9. Advenovirus ifølge krav 8, kendetegnet ved, at regionen er E1-regionen.
10. Advenovirus ifølge ethvert af kravene 8 eller 9, kendetegnet ved, at regionen er E3-regionen.
11. Advenovirus ifølge ethvert af kravene 8 til 10, kendetegnet ved, at regionen er E4-regionen.
12. Advenovirus ifølge ethvert af kravene 8 til 11, kendetegnet ved, at regionen omfatter E1-regionen, E3-regionen og E4-regionen.
13. Advenovirus ifølge ethvert af kravene 1 til 12, kendetegnet ved, at adenovirussen omfatter en nucleinsyre, hvor nucleinsyren koder for YB-1.
14. Advenovirus ifølge krav 13, kendetegnet ved, at nucleinsyren, som koder for YB-1, er under styring af en promotor, hvor promotoren er E2-late-promotoren.
15. Advenovirus ifølge ethvert af kravene 13 eller 14, kendetegnet ved, at nuclein-syren, som koder for YB-1, er under styring af en promotor, hvor promotoren er afhængig af YB-1 eller er styret af YB-1.
16. Advenovirus ifølge ethvert af kravene 13 til 15, kendetegnet ved, at nucleinsyren, som koder for YB-1, er en del af en ekspressionskassette, som omfatter en nukleinsyre, som koder for et E1A12S protein.
17. Advenovirus ifølge krav 16, kendetegnet ved, at nucleinsyren, som koder for E1A12S proteinet, er separeret fra nucleinsyren, som koder for YB-1, med en IRES sekvens.
18. Advenovirus ifølge ethvert af kravene 1 til 17, kendetegnet ved, at nucleinsyren, som koder for E4orf6 proteinet, og nucleinsyren, som koder for E1B55kD proteinet, er indeholdt i en ekspressionskassette.
19. Advenovirus ifølge krav 18, kendetegnet ved, at nucleinsyren, som koder for E4orf6 proteinet, og nucleinsyren, som koder for E1B55kD proteinet, er separerede fra hinanden af en IRES sekvens.
20. Advenovirus ifølge ethvert af kravene 18 og 19, kendetegnet ved, at ekspressionskassettens promotor er valgt fra gruppen bestående af tumorspecifikke promotorer, organspecifikke promotorer, vævsspecifikke promotorer, heterologe promotorer og adenovirale promotorer, hvor de adenovirale promotorer er forskellige fra E4 promotoren og E1B promotoren.
21. Advenovirus ifølge ethvert af kravene 1 til 20, kendetegnet ved, at advenovirussen omfatter en ekspressionskassette omfattende en promotor og en nucleinsyresekvens, hvor nucleinsyresekvensen er valgt fra gruppen bestående af aptamere, ribozymer, aptazymer, antisense-molekyler og siRNA.
22. Advenovirus ifølge ethvert af kravene 1 til 20, kendetegnet ved, at adenovirussen omfatter en ekspressionskassette omfattende en promotor og en nucleinsyresekvens, hvor nucleinsyresekvensen er en kodende nucleinsyre, hvor nucleinsyren koder for et molekyle valgt fra gruppen bestående af peptider, polypeptider, proteiner, anticaliner, antistoffer og antistoffragmenter.
23. Advenovirus ifølge ethvert af kravene 1 til 20, kendetegnet ved, at adenovirussen omfatter en ekspressionskassette omfattende en promotor og en nucleinsyresekvens, hvor nucleinsyresekvensen er valgt fra gruppen bestående af apoptose-inducerende gener, prodrug-gener, proteaseinhibitorer, tumorundertrykkende gener, cytokiner og angiogeneseinhibitorer.
24. Advenovirus ifølge ethvert af kravene 1 til 23, kendetegnet ved, at adenovirussen er en rekombinant adenovirus.
25. Advenovirus ifølge ethvert af kravene 1 til 24, kendetegnet ved, at advenovirussen er en mutant adenovirus.
26. Advenovirus ifølge ethvert af kravene 1 til 25, kendetegnet ved, at cellerne indeholder YB-1 i kernen uafhængigt af cellecyclusen.
27. Nucleinsyre, som koder for en adenovirus ifølge ethvert af kravene 1 til 26.
28. Vektor omfattende en nucleinsyre ifølge krav 27.
29. Vektor ifølge krav 28, kendetegnet ved, at vektoren er en ekspressionsvektor.
30. Celle omfattende en adenovirus ifølge ethvert af kravene 1 til 26 og/eller en nucleinsyre ifølge krav 27 og/eller en vektor ifølge krav 28 eller 29.
31. Celle ifølge krav 30, kendetegnet ved, at cellen er en mammal celle.
32. Celle ifølge krav 31, kendetegnet ved, at den mammalle celle er valgt fra gruppen af celler fra mus, rotter, marsvin, svin, får, geder, kvæg, heste, hunde, katte og menneske.
33. Anvendelse af en adenovirus ifølge ethvert af kravene 1 til 26, af en nucleinsyre ifølge krav 27, af en vektor ifølge ethvert af kravene 28 eller 29, eller af en celle ifølge ethvert af kravene 30 til 32, til in vitro replikation af adenovirus.
34. Anvendelse af en adenovirus ifølge ethvert af kravene 1 til 26, af en nucleinsyre ifølge krav 27, af en vektor ifølge ethvert af kravene 28 eller 29, eller af en celle ifølge ethvert af kravene 30 til 32, til in vitro fremstilling af adenovirus.
35. Anvendelse af en adenovirus ifølge ethvert af kravene 1 til 26, af en nucleinsyre ifølge krav 27, af en vektor ifølge ethvert af kravene 28 eller 29, eller af en celle ifølge ethvert af kravene 30 til 32 til in vitro ekspression af gener.
36. Anvendelse ifølge krav 35, kendetegnet ved, at generne er gener, som promoverer cellelyse.
37. Anvendelse af en adenovirus ifølge ethvert af kravene 1 til 26, af en nucleinsyre ifølge krav 27, af en vektor ifølge ethvert af kravene 28 eller 29, eller af en celle ifølge ethvert af kravene 30 til 32 til fremstillingen af et medikament.
38. Anvendelse ifølge krav 37, kendetegnet ved, at medikamentet er til behandlingen af tumorsygdomme.
39. Anvendelse ifølge krav 38, kendetegnet ved, at tumorsygdommen er valgt fra gruppen bestående af maligne sygdomme, cancer, cancersygdomme og tumorer.
40. Anvendelse ifølge krav 39, kendetegnet ved, at tumoren er valgt fra gruppen bestående af solide, ikke-solide, maligne og benigne tumorer.
41. anvendelse ifølge ethvert af kravene 38 til 40, kendetegnet ved, at i det mindste en del af cellerne, som danner tumoren, har YB-1 i kernen.
42. Anvendelse ifølge krav 41, kendetegnet ved, at cellerne har YB-1 i kernen uafhængigt af cellecyklusen.
43. Anvendelse ifølge ethvert af kravene 38 til 42, kendetegnet ved, at i det mindste en del af de tumordannende celler omfatter dereguleret YB-1, hvor det deregulerede YB-1 er ét, som foreligger i en form, som er kvantitativt og kvalitativt forskellig fra denne i en ikke-tumorcelle.
44. Anvendelse ifølge ethvert af kravene 38 til 43, kendetegnet ved, at i det mindste en del af de tumordannende celler er Rb-positive eller Rb-negative.
45. Anvendelse ifølge ethvert af kravene 38 til 43, kendetegnet ved, at i det mindste en del af de tumordannende celler udviser resistens imod et antitumormiddel.
46. Anvendelse ifølge krav 45, kendetegnet ved, at resistensen er en multiresistens.
47. Anvendelse ifølge ethvert af kravene 45 eller 46, kendetegnet ved, at antitumormidlet er et cytostatikum.
48. Anvendelse ifølge ethvert af kravene 38 til 43, kendetegnet ved, at i det mindste en del af de tumordannende celler er resistente, hvor resistensen er forårsaget af bestråling.
49. Anvendelse ifølge ethvert af kravene 38 til 48, kendetegnet ved, at medikamentet er til en patient, som har adskillige celler, hvor cellerne er celler som beskrevet i ethvert af kravene 41 til 48.
50. Anvendelse ifølge ethvert af kravene 38 til 49, kendetegnet ved, at medikamentet omfatter i det mindste ét yderligere farmaceutisk aktivt middel.
51. Anvendelse ifølge ethvert af kravene 38 til 49, kendetegnet ved, at medikamentet indgives eller skal indgives med et yderligere farmaceutisk aktivt middel.
52. Anvendelse ifølge krav 50 eller 51, kendetegnet ved, at det yderligere farmaceutisk aktive middel er valgt fra gruppen bestående af cytokiner, metalproteinaseinhibitorer, angioneseinhibitorer, cytostatika, tyrosinkinaseinhibitorer og cellecyclusinhibitorer.
53. Anvendelse ifølge ethvert af kravene 38 til 49, kendetegnet ved, at medikamentet indgives før, under eller efter bestråling.
54. Anvendelse ifølge krav 53, kendetegnet ved, at bestrålingen tilføres med henblik på behandlingen af en tumor.
55. Anvendelse ifølge ethvert af kravene 38 til 54, kendetegnet ved, at cellen eller organismen, som skal behandles, underkastes en foranstaltning, hvor foranstaltningen er valgt fra gruppen bestående af bestråling, indgivelse af cytostatika og hypertermi.
56. Anvendelse ifølge ethvert af kravene 38 til 55, kendetegnet ved, at foranstaltningen anvendes lokalt eller systemisk.
57. Anvendelse ifølge ethvert af de foregående krav, kendetegnet ved, at bestrålingen anvender højenergistråling.
58. Anvendelse ifølge krav 57, kendetegnet ved, at bestrålingen er én, som anvendes ved behandlingen af tumorsygdomme.
59. Anvendelse af en adenovirus ifølge ethvert af kravene 1 til 26, af en nucleinsyre ifølge krav 27, af en vektor ifølge ethvert af kravene 28 eller 29, eller er en celle ifølge ethvert af kravene 30 til 32, til fremstillingen af et medikament til behandlingen af en tumorsygdom, kendetegnet ved, at tumorsygdommen er valgt fra gruppen bestående af brysttumorer, knogletumorer, mavetumorer, tarmtumorer, galdeblæretumorer, pan-kreastumorer, levertumorer, nyretumorer, hjernetumorer, ovarietumorer, hudtumorer og hudvedhængstumorer, hoved- og halstumorer, uterus tumorer, synoviale tumorer, laryn-geale tumorer, øsophageale tumorer, linguale tumorer og prostatatumorer.
60. Anvendelse af en adenovirus ifølge ethvert af kravene 1 til 26, af en nukleinsyre ifølge krav 27, af en vektor ifølge ethvert af kravene 28 eller 29, eller af en celle ifølge ethvert af kravene 30 til 32, til fremstillingen af et medikament til behandlingen af en tumorsygdom, hvor den tumorspecifikke promotor er en promotor, som er specifik for den tumor, for hvilken medikamentet anvendes.
61. Farmaceutisk sammensætning omfattende en adenovirus ifølge ethvert af kravene 1 til 26, en nucleinsyre ifølge krav 27, en vektor ifølge ethvert af kravene 28 eller 29 eller en celle ifølge ethvert af kravene 30 til 32, og eventuelt et farmaceutisk egnet bærestof.
62. Advenovirus ifølge ethvert af kravene 1 til 26 til anvendelse ved en fremgangsmåde til behandlingen af en tumorsygdom.
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| PCT/EP2003/005583 WO2003099859A2 (de) | 2002-05-27 | 2003-05-27 | Neue verwendung von adenoviren und dafür codierenden nukleinsäuren |
| PCT/EP2003/011427 WO2004035616A2 (de) | 2002-10-15 | 2003-10-15 | Adenovirus mit umgekehrter reihenfolge der expression von genen und verwendung davon |
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| AU2003222427B8 (en) * | 2000-11-17 | 2010-04-29 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same |
| US8071740B2 (en) | 2000-11-17 | 2011-12-06 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same for regulation of angiogenesis |
| MXPA04003514A (es) | 2001-10-19 | 2004-07-23 | Vascular Biogenics Ltd | Construcciones de polinucleotidos, composiciones farmaceuticas y metodos para reducir la regulacion dirigida de angionesis y terapia anticancer. |
| AU2003242585A1 (en) | 2002-05-27 | 2003-12-12 | Per Sonne Holm | Novel use of adenoviruses and nucleic acids coding therefor |
| JP2007511211A (ja) | 2003-11-14 | 2007-05-10 | ホルム，ペル・ゾンネ | アデノウイルスおよびそれをコードしている核酸の新たな使用 |
| KR101527213B1 (ko) * | 2004-12-31 | 2015-06-09 | 페르 손네 홀름 | 동물 세포에서 다중 내성을 역전시키기 위한 방법 |
| CA2610360A1 (en) * | 2004-12-31 | 2006-07-06 | Per Sonne Holm | E1-minus adenoviruses and use thereof |
| KR100747646B1 (ko) * | 2005-02-25 | 2007-08-08 | 연세대학교 산학협력단 | 데코린 유전자를 포함하는 유전자 전달 시스템 및 이를 포함하는 약제학적 항종양 조성물 |
| WO2012022496A2 (en) | 2010-08-19 | 2012-02-23 | Per Sonne Holm | Method for killing tumor stem cells |
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| US20060057113A1 (en) | 2006-03-16 |
| WO2004035616A2 (de) | 2004-04-29 |
| EP1554375A2 (de) | 2005-07-20 |
| AU2010257327A1 (en) | 2011-01-13 |
| MXPA05004074A (es) | 2005-09-20 |
| EP1554375B1 (de) | 2018-08-22 |
| ZA200502680B (en) | 2005-11-30 |
| SG165168A1 (en) | 2010-10-28 |
| US8951772B2 (en) | 2015-02-10 |
| AU2010257327C1 (en) | 2012-02-16 |
| PL219321B1 (pl) | 2015-04-30 |
| AU2010257327B2 (en) | 2011-09-29 |
| WO2004035616A3 (de) | 2004-05-27 |
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