DK2007356T3 - Lipoplexformuleringer til specifik indgivelse til vaskulært endothelium - Google Patents
Lipoplexformuleringer til specifik indgivelse til vaskulært endothelium Download PDFInfo
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- DK2007356T3 DK2007356T3 DK07724432.5T DK07724432T DK2007356T3 DK 2007356 T3 DK2007356 T3 DK 2007356T3 DK 07724432 T DK07724432 T DK 07724432T DK 2007356 T3 DK2007356 T3 DK 2007356T3
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- nucleic acid
- lipid
- sirna
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- lipoplex
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Claims (29)
1. Lipidsammensætning indeholdt i og/eller indeholdende et bærestof omfattende a) 50 mol-% fi-arginyl-2,3-diaminopropionsyrc-N-palmityl-N-oleyl-amid trihydrochlorid, fortrinsvis (P-(L-arginyl)-2,3-L-diaminopropionsyre-V-palmityl-jV-olcyl-amid tri-hydrochlorid) b) 48 til 49 mol -% l,2-diphytanoyl-sn-glycero-3-phosphoethanolamin (DPhyPE), og c) 1 til 2 mol-% l,2-distearoyl-sn-glycero-3-phosphoethanolamin-polyethylen-glycol, fortrinsvis N-(carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3 -phosphoethanolami n-natriumsalt hvor lipidsammensætningen indeholdende bærestof har en osmolaritet på ca. 50 til 600 mosmol/kg, fortrinsvis ca. 250 - 350 mosmol/kg og mere fortrinsvis ca. 280 til 320 mosmol/kg, og/eller hvor liposomer dannet af den første lipidbestanddel og/eller én eller begge af hjælperlipidet og den afskærmende forbindelse i bærestoffet har en partikelstørrelse på ca. 30 til 100 nm, og fortrinsvis ca. 40 til 80 nm.
2. Sammensætning ifølge krav 1, hvor osmolariteten overvejende bestemmes af et sukker, hvor sukkeret fortrinsvis er udvalgt fra gruppen omfattende saccharose, trehalose, glucose, galactose, mannose, maltose, lactulose, inulin, raffmose og en hvilken som helst kombination deraf, mere fortrinsvis udvalgt fra gruppen omfattende saccharose, trehalose, inulin, raffmose og en hvilken som helst kombination deraf.
3. Sammensætning ifølge et hvilket som helst af kravene 1 til 2, hvor sammensætningen indeholder én eller flere basiske forbindelser, hvor sådanne basiske forbindelser fortrinsvis er udvalgt lfa gruppen omfattende basic aminosyrer og svage baser.
4. Lipidsammensætning ifølge et hvilket som helst af kravene 1 til 3, hvor lipidsammensætningen omfatter en nukleinsyre, hvor en sådan nukleinsyre fortrinsvis er den yderligere bestanddel.
5. Lipidsammensætning ifølge krav 4, hvor nukleinsyren er udvalgt fra gruppen omfattende RNAi, siRNA, siNA, antisense-nukleinsyre, ribozymer, aptamerer og spiegelmerer.
6. Lipidsammensætning ifølge et hvilket som helst af de foregående krav, hvor sammensætningen omfatter en nukleinsyre og nukleinsyren sammen med liposomet danner et lipoplex.
7. Lipidsammensætning ifølge et hvilket som helst af kravene 1 til 6, hvor koncentrationen af lipideme i bærestoffet er ca. fra 0,01 til 100 mg/ml, fortrinsvis ca. ffa 0,01 til 40 mg/ml og mere fortrinsvis ca. fra 0,01 til 25 mg/ml, hver baseret på den totale mængde lipider tilvejebragt af lipoplexet.
8. Lipidsammensætning ifølge et hvilket som helst af kravene 6 til 7, hvor nukleinsyren er et siRNA og koncentrationen af siRN’et i lipidsammensætningen ca. ca. 0,2 til 0,4 mg/ml, fortrinsvis 0,28 mg/ml, og den totale lipidkoncentration er ca. 1,5 til 2,7 mg/ml, fortrinsvis 2,17 mg/ml.
9. Farmaceutisk sammensætning omfattende en sammensætning ifølge et hvilket som helst af kravene 1 til 8 og eventuelt en farmaceutisk aktiv forbindelse og fortrinsvis et farmaceutisk acceptabelt bærestof.
10. Sammensætning ifølge krav 9, hvor den farmaceutisk aktive forbindelse og/eller den yderligere bestanddel er udvalgt lfa gruppen omfattende peptider, proteiner, oligonukleotider, polynukleotider og nukleinsyrer.
11. Sammensætning ifølge krav 10, hvor nukleinsyren er en funktionel nukleinsyre, hvor den funktionelle nukleinsyre fortrinsvis er udvalgt fra gruppen omfattende RNAi, siRNA, siNA, antisense-nukleinsyre, ribozymer, aptamerer og spiegelmerer.
12. Sammensætning ifølge et hvilket som helst af kravene 1 til 11, hvor PEG-delen tilvejebringer en molekylvægt fra ca. 500 til 10000 Da, mere fortrinsvis fra ca. 2000 til 5000 Da.
13. Sammensætning ifølge et hvilket som helst af kravene 1 til 12, hvor sammensætningen endvidere omfatter en nukleinsyre, fortrinsvis en funktionel nukleinsyre, der mere fortrinsvis er en dobbeltstrenget ribonukleinsyre og mest fortrinsvis en nukleinsyre udvalgt fra gruppen omfattende RNAi, siRNA, siNA, antisense-nukleinsyre og ribozym, hvor molforholdet mellem RNAi og kationisk lipid fortrinsvis er fra ca. 0 til 0,075, fortrinsvis fra ca. 0,02 til 0,05 og endnu mere fortrinsvis 0,037.
14. Lipoplex, der er en sammensætning ifølge et hvilket som helst af kravene 1 til 13 eller indeholdt i en sådan sammensætning, omfattende: a) et positivt ladet liposom bestående af aa) ca. 50 mol-% P-arginyl-2,3-diaminopropionsyre-N-palmityl-N-oleyl-amidtrihydrochlorid, fortrinsvis (P-(L-arginyl)-2,3-L-diaminopropionsyrc-/V-palniityl-/V-olcyl-amid trihydrochlorid) ab) ca. 48 til 49 mol-% l,2-diphytanoyl-sn-glycero-3-phosphoethanolamin (DPhyPE) ac) ca. 1 til 2 mol-% l,2-distearoyl-sn-glycero-3-phosphoethanolamin-polyethylen-glycol, fortrinsvis N-(carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3 -phosphoethanolaminnatriumsalt og b) en funktionel nukleinsyre, fortrinsvis et siRNA.
15. Lipoplex ifølge krav 14, hvor lipoplexets zeta-potentiale er ca. 40 til 55 mV, fortrinsvis ca. 45 til 50 mV.
16. Lipoplex ifølge krav 14 eller 15, hvor lipoplexet har en størrelse på ca. 80 til 200 rnn, fortrinsvis på ca. 100 til 140 nm, og mere fortrinsvis på ca. 110 nm til 130 nm, som bestemt ved QELS.
17. Sammensætning ifølge et hvilket som helst af kravene 1 til 13, hvor sammensætningen omfatter et lipoplex ifølge et hvilket som helst af kravene 14 til 16.
18. Anvendelse af en sammensætning ifølge et hvilket som helst af kravene 1 til 13 og 17 eller af et lipoplex ifølge et hvilket som helst af kravene 14 til 16 til fremstilling af et medikament.
19. Anvendelse ifølge krav 18, hvor medikamentet er til indgivelse af en nukleinsyre, fortrinsvis en funktionel nukleinsyre, til endothelium, fortrinsvis et vaskulært endothelium.
20. Anvendelse ifølge et hvilket som helst af krav 18 og 19, hvor medikamentet er til behandling af en angiogenese-afhængig sygdom.
21. Anvendelse ifølge krav 21, hvor sygdommen er en cancersygdom, mere fortrinsvis en solid tumor.
22. Anvendelse ifølge et hvilket som helst af kravene 18 til 21, hvor medikamentet anvendes i kombination med én eller flere andre terapier.
23. Anvendelse ifølge krav 22, hvor terapien er udvalgt fra gruppen omfattende kemoterapi, kryoterapi, hypertermi, antistofterapi og strålingsterapi.
24. Anvendelse af en sammensætning ifølge et hvilket som helst af kravene 1 til 13 og 17 eller af et lipoplex ifølge et hvilket som helst af kravene 14 til 16, som et overføringsmiddel in vitro.
25. Anvendelse ifølge krav 24, hvor overføringsmidlet overfører en nukleinsyre, hvorved nukleinsyren fortrinsvis er nukleinsyren indeholdt i sammensætningen eller nukleinsyren fortrinsvis er lipoplexets nukleinsyrebestanddel.
26. Anvendelse ifølge krav 25, hvor nukleinsyren er en funktionel nukleinsyre, fortrinsvis et siRNA.
27. Anvendelse ifølge et hvilket som helst af kravene 24 til 26, hvor overføringsmidlet er specifikt for endothelium, fortrinsvis et vaskulært endothelium.
28. Fremgangsmåde in vitro til overføring af en farmaceutisk aktiv forbindelse og/eller en yderligere bestanddel ind i en celle eller gennem en membran, fortrinsvis en cellemembran, hvilken fremgangsmåde omfatter følgende trin: - tilvejebringelse af cellen eller membranen; - tilvejebringelse af en sammensætning ifølge et hvilket som helst af kravene 1 til 13 og 17 eller et lipoplex ifølge et hvilket som helst af kravene 14 til 16, hvor sammensætningen eventuelt omfatter den farmaceutisk aktive forbindelse og/eller den yderligere bestanddel; og etablering af kontakt mellem cellen eller membranen og sammensætningen ifølge et hvilket som helst af kravene 1 til 13 og 17 eller et lipoplex ifølge et hvilket som helst af kravene 14 til 16.
29. Fremgangsmåde ifølge krav 28, hvor fremgangsmåden som yderligere trin omfatter: detektering af den farmaceutisk aktive forbindelse og/eller den yderligere bestanddel i cellen og/eller på den anden side af membranen.
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|---|---|---|---|
| EP06008209 | 2006-04-20 | ||
| PCT/EP2007/003496 WO2007121947A1 (en) | 2006-04-20 | 2007-04-20 | Lipoplex formulations for specific delivery to vascular endothelium |
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| Publication Number | Publication Date |
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| DK2007356T3 true DK2007356T3 (da) | 2015-10-19 |
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| DK07724432.5T DK2007356T3 (da) | 2006-04-20 | 2007-04-20 | Lipoplexformuleringer til specifik indgivelse til vaskulært endothelium |
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| EP (2) | EP2007356B1 (da) |
| JP (4) | JP2009534342A (da) |
| AU (1) | AU2007241370A1 (da) |
| CA (1) | CA2649630C (da) |
| DK (1) | DK2007356T3 (da) |
| ES (1) | ES2549728T3 (da) |
| PL (1) | PL2007356T3 (da) |
| WO (1) | WO2007121947A1 (da) |
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| SG158175A1 (en) * | 2004-12-27 | 2010-01-29 | Silence Therapeutics Ag | Lipid complexes coated with peg and their use |
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2007
- 2007-04-20 EP EP07724432.5A patent/EP2007356B1/en active Active
- 2007-04-20 ES ES07724432.5T patent/ES2549728T3/es active Active
- 2007-04-20 EP EP15161527.5A patent/EP2992875A1/en not_active Withdrawn
- 2007-04-20 JP JP2009505789A patent/JP2009534342A/ja active Pending
- 2007-04-20 PL PL07724432T patent/PL2007356T3/pl unknown
- 2007-04-20 US US12/297,611 patent/US20090074852A1/en not_active Abandoned
- 2007-04-20 WO PCT/EP2007/003496 patent/WO2007121947A1/en not_active Ceased
- 2007-04-20 CA CA2649630A patent/CA2649630C/en not_active Expired - Fee Related
- 2007-04-20 AU AU2007241370A patent/AU2007241370A1/en not_active Abandoned
- 2007-04-20 DK DK07724432.5T patent/DK2007356T3/da active
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2007356B1 (en) | 2015-08-12 |
| AU2007241370A1 (en) | 2007-11-01 |
| ES2549728T3 (es) | 2015-11-02 |
| EP2007356A1 (en) | 2008-12-31 |
| JP2017048223A (ja) | 2017-03-09 |
| JP2014055167A (ja) | 2014-03-27 |
| JP2016121153A (ja) | 2016-07-07 |
| US20090074852A1 (en) | 2009-03-19 |
| JP2009534342A (ja) | 2009-09-24 |
| WO2007121947A1 (en) | 2007-11-01 |
| PL2007356T3 (pl) | 2016-02-29 |
| EP2992875A1 (en) | 2016-03-09 |
| CA2649630C (en) | 2016-04-05 |
| US20170296469A1 (en) | 2017-10-19 |
| CA2649630A1 (en) | 2007-11-01 |
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