DK2134853T3 - Glykosylering af molekyler - Google Patents

Glykosylering af molekyler Download PDF

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DK2134853T3
DK2134853T3 DK08776351.2T DK08776351T DK2134853T3 DK 2134853 T3 DK2134853 T3 DK 2134853T3 DK 08776351 T DK08776351 T DK 08776351T DK 2134853 T3 DK2134853 T3 DK 2134853T3
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protein
cell
glycosylation
cells
altered
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Nico Luc Marc Callewaert
Wouter Vervecken
De Pourcq Karen Jacqueline Marcel
Steven Christian Jozef Geysens
Mouna Guerfal
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Oxyrane Uk Ltd
Univ Gent
Vib Vzw
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    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
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    • C12N9/2465—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1) acting on alpha-galactose-glycoside bonds, e.g. alpha-galactosidase (3.2.1.22)
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Claims (15)

1. Fremgangsmåde til fremstilling afen ændret N-glykosyleringsform af et målprotein, hvilken fremgangsmåde omfatter: A) at tilvejebringe en Yarrowia lipolytica-celle, der er gensplejset til at omfatte overekspression af Yarrowia lipolytica-MNN4, og indføre i cellen en nukleinsyre, der koder for et målprotein, hvor cellen producerer målproteinet i ændret N-glykosyleringsform; eller B) at tilvejebringe en Yarrowia lipolytica-celle, der er gensplejset til at omfatte overekspression af en biologisk aktiv variant af Yarrowia lipolytica-MNN4, og indføre i cellen en nukleinsyre, der koder for et målprotein, hvor cellen producerer målproteinet i ændret N-glykosyleringsform, hvor mindst 80 % af N-glycanerne af målproteinet er phosphorylerede.
2. Fremgangsmåde ifølge krav 1, hvor målproteinet er et pattedyrsprotein eller et fusionsprotein, der omfatter pattedyrsproteinet.
3. Fremgangsmåde ifølge krav 1 eller 2, hvor målproteinet er et humant protein eller et fusionsprotein, der omfatter det humane protein.
4. Fremgangsmåde ifølge krav 3, hvor den ændrede N-glykosyleringsform af proteinet er en form, der kan behandle en lidelse hos mennesker.
5. Fremgangsmåde ifølge krav 4, hvor lidelsen er en lysosomal lagringssygdom.
6. Fremgangsmåde ifølge krav 5, hvor den lysosomale lagringslidelse er Gau-chers sygdom, Tay-Sachs sygdom, Pompes sygdom, Niemann-Pick-sygdom eller Fabrys sygdom.
7. Fremgangsmåde ifølge et hvilket som helst af de foregående krav, hvor målproteinet er et lysosomalt protein, en vækstfaktor, et cytokin, et kemokin, et antistof eller antigenbindende fragment deraf; eller er et fusionsprotein omfattende et hvilket som helst af de førnævnte.
8. Fremgangsmåde ifølge et hvilket som helst af de foregående krav, hvor målproteinet er udvalgt fra gruppen bestående af glucocerebrosidase, galactoce-rebrosidase, alpha-galactosidase, alpha-L-iduronidase, beta-D-galactosidase, beta-glucosidase, beta-hexosam in idase, beta-D-mannosidase, alpha-L-fuco-sidase, arylsulfatase B, arylsulfatase A, alpha-N-acteylgalactosaminidase, aspartylglucosaminidase, iduronat-2-sulfatase, alpha-glucosaminid-N-acetyl-transferase, beta-D-glucoronidase, hyaluronidase, alpha-L-mannosidase, al-pha-neuraminidase, phosphotransferase, syrelipase, syre-ceram idase, sphinogmyelinase, thioesterase, cathepsin K og lipoproteinlipase; eller er et fusionsprotein omfattende et hvilket som helst af de førnævnte.
9. Fremgangsmåde ifølge et hvilket som helst af de foregående krav, hvor cellen yderligere er gensplejset til at have nedgang i eller en mangel på mindst en N-glykosyleringsaktivitet.
10. Fremgangsmåde ifølge krav 9, hvor cellen omfatter en nedgang i eller en mangel på OCH1-aktivitet.
11. Fremgangsmåde ifølge et hvilket som helst af de foregående krav, hvor N-glykosyleringsformen af målproteinet er homogen eller i det væsentlige homogen.
12. Fremgangsmåde ifølge et hvilket som helst af de foregående krav, omfattende trinnet at isolere målproteinet i biologisk aktiv form.
13. Fremgangsmåde ifølge krav 12, yderligere omfattende trinnet at danne en farmaceutisk sammensætning omfattende en terapeutisk virksom mængde af målproteinet og en eller flere excipienser, adjuvanser, bærere og/eller fortyndingsmidler.
14. Fremgangsmåde ifølge krav 13, hvor sammensætningen er til anvendelse til behandling af en lidelse som beskrevet i et hvilket som helst af kravene 4 til 6.
15. Yarrowia lipolytica-celle, hvor cellen er en celle som beskrevet i et hvilket som helst af kravene 1 til 11.
DK08776351.2T 2007-04-03 2008-04-03 Glykosylering af molekyler DK2134853T3 (da)

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US90990407P 2007-04-03 2007-04-03
US94021207P 2007-05-25 2007-05-25
PCT/IB2008/001814 WO2008120107A2 (en) 2007-04-03 2008-04-03 Glycosylation of molecules

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EP (4) EP2134853B1 (da)
JP (3) JP5967861B2 (da)
KR (3) KR101811057B1 (da)
CN (2) CN104480140B (da)
CA (3) CA3069431A1 (da)
DK (2) DK2134853T3 (da)
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