DK3145307T3 - Genmodificerede ikke-humane dyr, der eksprimerer human epo - Google Patents

Genmodificerede ikke-humane dyr, der eksprimerer human epo Download PDF

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Publication number
DK3145307T3
DK3145307T3 DK15756500.3T DK15756500T DK3145307T3 DK 3145307 T3 DK3145307 T3 DK 3145307T3 DK 15756500 T DK15756500 T DK 15756500T DK 3145307 T3 DK3145307 T3 DK 3145307T3
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Denmark
Prior art keywords
human
rodent
cells
nucleic acid
promoter
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DK15756500.3T
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English (en)
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Andrew J Murphy
Richard Flavell
Liang Shan
Sean Stevens
Markus Manz
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Regeneron Pharma
Univ Yale
Institute For Res In Biomedicine Irb
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Claims (11)

1. Gen modificeret gnaver, omfattende: en nukleinsyresekvens, der koder for et humant erythropoietin-protein (hEPO), hvor nukleinsyren er funktionsmæssigt forbundet med en endogen erythropoietin (EPOJ-gen-promoter ved gnaver-EPO-genlocuset, hvor den funktionsmæssige binding resulterer i en nul-mutation i gnaver-EPO-genet ved gnaver-EPO-genlocuset, og hvor gnaveren eksprimerer yderligere humane proteiner udvalgt fra gruppen bestående af: et hM-CSF-protein, der kodes af en nukleinsyre under styring af en M-csf-pro-moter, hvor /W-csf-promoteren er en endogen gnaver-M-csf-promoter ved gna-ver-M-csf-genlocuset, og hvor gnaveren er heterozygot nul eller homozygot nul for gnaver-M-csf-genet, et hlL3-protein, der kodes af en nukleinsyre under styring af en //-3-promoter, hvor //-3-promoteren er en endogen gnaver-//-3-promoter ved gnaver-1/-3-gen-locuset, og hvor gnaveren er heterozygot nul eller homozygot nul for gnaver-//-3-genet, et hGM-CSF-protein, der kodes af en nukleinsyre under styring af en Gm-csf-promoter, hvor Gm-csf-promoteren er en endogen gnaver-Gm-csf-promoter ved gnaver-Gm-csf-genlocuset, og hvor gnaveren er heterozygot nul eller homozygot nul for gnaver-Gm-csf-genet, et hTPO-protein, der kodes af en nukleinsyre under styring af en TPO-promo-ter, hvor 7"PO-promoteren er en endogen gnaver-7"PO-promoter ved gnaver-7"PO-genlocuset, og hvor gnaveren er heterozygot nul eller homozygot nul for gnaver-TPO-genet, og et hSirpa-protein, der kodes af en nukleinsyre under styring af en Sirpa-pro-moter, hvor S/rpa-promoteren er en endogen gnaver-S/rpa-promoter ved gna-ver-S/rpa-genlocuset, og hvor gnaveren er heterozygot nul eller homozygot nul for gnaver-S/rpa-genet, hvor de humane proteiner indbefatter mindst hTPO, hlL3, hGM-CSF og hSirpa, og hvor gnaveren er immundeficient, og immundefekten er forårsaget af en deficiens med hensyn til både Rag2 og Il2rg.
2. Gnaver ifølge krav 1, hvor gnaveren er heterozygot for allelen omfattende nukleinsyresekvensen, der koder for hEPO'et.
3. Gnaver ifølge krav 1, hvor gnaveren er homozygot for allelen omfattende nukleinsyresekvensen, der koder for hEPO'et.
4. Gnaver ifølge et hvilket som helst af kravene 1-3, hvor nukleinsyresekvensen, der koder for hEPO'et, omfatter en human EPO-genomisk-kodende og -ikke-kodende sekvens.
5. Gnaver ifølge et hvilket som helst af kravene 1-3, hvor nukleinsyresekvensen, der koder for hEPO'et, omfatter en human EPO-cDNA-sekvens.
6. Gnaver ifølge et hvilket som helst af kravene 1 -5, hvor gnaveren er en mus.
7. Gnaver ifølge et hvilket som helst af kravene 1-6, hvor gnaveren yderligere omfatter en indpodning af humane hæmatopoietiske celler.
8. Gnaver ifølge krav 7, hvor de humane hæmatopoietiske celler omfatter en eller flere celler udvalgt fra gruppen bestående af en human CD34-positiv celle, en human hæmatopoietisk stamcelle, en human myeloid precursorcelle, en human erythroid precursorcelle, en human myeloid celle, en human dend-ritisk celle, en human monocyt, en human granulocyt, en human erythrocyt, en human neutrofil, en human mastcelle, en human thymocyt og en human B-lymfocyt.
9. Gnaver ifølge krav 8, hvor gnaveren omfatter clodronat.
10. Gnaver ifølge krav 9, hvor gnaveren yderligere omfatter en infektion med et patogen, der er rettet mod humane celler af erythroid-afstamningen.
11. Gnaver ifølge krav 10, hvor patogenet er udvalgt blandt en Plasmodium sp., Babesia sp. og en Theileri sp.
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KR20250096864A (ko) 2025-06-27
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