DK2296672T3 - Konditioneret medium af leverforløberceller - Google Patents

Konditioneret medium af leverforløberceller Download PDF

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DK2296672T3
DK2296672T3 DK09761761.7T DK09761761T DK2296672T3 DK 2296672 T3 DK2296672 T3 DK 2296672T3 DK 09761761 T DK09761761 T DK 09761761T DK 2296672 T3 DK2296672 T3 DK 2296672T3
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pharmaceutical composition
cells
growth factor
human
conditioned medium
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DK09761761.7T
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Valentina Fonsato
Ciro Tetta
Giovanni Camussi
Sanchez Maria Beatriz Herrera
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Fresenius Medical Care De Gmbh
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/37Digestive system
    • A61K35/407Liver; Hepatocytes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
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    • A61K38/1703Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • AHUMAN NECESSITIES
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    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177Receptors; Cell surface antigens; Cell surface determinants
    • A61K38/1793Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
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    • A61K38/18Growth factors; Growth regulators
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    • A61K38/18Growth factors; Growth regulators
    • A61K38/1858Platelet-derived growth factor [PDGF]
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • A61K38/1858Platelet-derived growth factor [PDGF]
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    • A61K38/19Cytokines; Lymphokines; Interferons
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    • A61K38/19Cytokines; Lymphokines; Interferons
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Claims (15)

1. Fremgangsmåde til fremstilling af et konditioneret medium, omfattende trinene: (i) dyrkning af fuldt udviklede leverafledede humane modne hepatocytter i et celledyrkningsmedium indtil død af modne hepatocytter og udvælgelse af en population af overlevende celler med epiteloid morfologi, (ii) ekspandering af populationen af overlevende celler med epiteloid morfologi ved dyrkning i et serumholdigt, glukoseholdigt dyrkningsmedium suppleret med hEGF (human epitelial vækstfaktor) og bFGF (basal fibroblast vækstfaktor), og omfattende almindelige uorganiske salte, aminosyrer og vitaminer nødvendige for væksten af pattedyrceller, og (iii) udskillelse af cellerne fra celledyrkningsmediet.
2. Fremgangsmåde ifølge krav 1, hvori de modne hepatocytter fryses i et serumholdigt dyrkningsmedium under tilstedeværelse af et kuldebeskyttende middel og derefter optøs før dyrkning ifølge trin (i).
3. Fremgangsmåde ifølge krav 1 eller 2, hvori dyrkningsmediet omfatter alpha-MEM suppleret med humanalbumin af GMP-kvalitet.
4. Konditioneret medium, der kan fremskaffes ved dyrkning af en pluripotent forløbercellelinie af human lever, kendetegnet ved, at det er frit for celler og yderligere kendetegnet ved, at det omfatter en blanding af mindst hepatocytvækstfak-tor (FHGF), interleukin 6 (IL-6), interleukin 8 (IL-8) og vaskulær endotelial vækstfaktor (VEGF).
5. Konditioneret mediumsammensætning ifølge krav 4, som kan fremskaffes ved fremgangsmåden ifølge ethvert af krav 1 til 3.
6. Farmaceutisk sammensætning omfattende en farmaceutisk effektiv mængde af det konditionerede medium ifølge krav 4 eller 5.
7. Farmaceutisk sammensætning omfattende en farmaceutisk effektiv mængde af en blanding af mindst hepatocytvækstfaktor (FIGF), interleukin 6 (IL-6), interleukin 8 (IL-8) og vaskulær endotelial vækstfaktor (VEGF) i en koncentration i området fra 10 til 400 ng/ml.
8. Farmaceutisk sammensætning ifølge krav 7, hvori blandingen yderligere omfatter makrofagstimulerende protein (MSP) i en farmaceutisk aktiv mængde.
9. Farmaceutisk sammensætning ifølge krav 7 eller 8, hvori hepatocytvækstfakto-ren (HGF) er i en koncentration fra 1 til 100 ng/ml, interleukin 6 (IL-6) er i en koncentration fra 10 til 200 ng/ml, interleukin 8 (IL-8) er i en koncentration lig med eller højere end 35 ng/ml.
10. Farmaceutisk sammensætning ifølge krav 8 eller 9, hvori det makrofagstimulerende protein (MSP) er i en koncentration i området fra 1 til 100 pg/ml.
11. Koncentreret farmaceutisk sammensætning bestående af den farmaceutiske sammensætning ifølge krav 9 eller 10 koncentreret mindst 5 gange, fortrinsvis mindst 10 gange, mere foretrukket mindst 20 gange, endda mere foretrukket mindst 25 gange.
12. Fortyndet farmaceutisk sammensætning bestående af den farmaceutiske sammensætning ifølge krav 9 eller 10 fortyndet mindst 5 gange, fortrinsvis mindst 10 gange, mere foretrukket mindst 20 gange, endda mere foretrukket mindst 25 gange.
13. Farmaceutisk sammensætning ifølge ethvert af krav 6 til 12 til anvendelse ved behandling af organskade eller -svigt.
14. Farmaceutisk sammensætning til anvendelse ifølge krav 13, hvori organet er lever eller nyre.
15. Farmaceutisk sammensætning til anvendelse ifølge krav 13 eller 14, som er fremstillet som et medikament egnet til at indgive en dosis hepatocytvækstfaktor (HGF) i området 0,01 til 1 mg/kg, en dosis interleukin 6 (IL-6) i området 0,01 til 1 mg/kg, en dosis interleukin 9 (IL-8) i området 0,01 til 1 mg/kg og valgfrit en dosis vaskulær endotelial vækstfaktor (VEGF) i området mellem 0,01 til 1 mg/kg.
DK09761761.7T 2008-06-11 2009-06-11 Konditioneret medium af leverforløberceller DK2296672T3 (da)

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Application Number Priority Date Filing Date Title
EP08010651 2008-06-11
PCT/EP2009/057232 WO2009150199A1 (en) 2008-06-11 2009-06-11 Conditioned medium of liver progenitor cells

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US (2) US10456425B2 (da)
EP (1) EP2296672B1 (da)
JP (1) JP5632833B2 (da)
CN (2) CN103800895B (da)
BR (1) BRPI0909866B1 (da)
CA (1) CA2727392C (da)
DK (1) DK2296672T3 (da)
ES (1) ES2556630T3 (da)
HU (1) HUE028676T2 (da)
PL (1) PL2296672T3 (da)
PT (1) PT2296672E (da)
WO (1) WO2009150199A1 (da)

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FR2912916B1 (fr) * 2007-02-26 2009-05-22 Oreal Composition cosmetique ou dermatologique comprenant un milieu de culture cellulaire

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