DK2908626T3 - Humaniserede IL-15 dyr - Google Patents
Humaniserede IL-15 dyr Download PDFInfo
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- DK2908626T3 DK2908626T3 DK14790452.8T DK14790452T DK2908626T3 DK 2908626 T3 DK2908626 T3 DK 2908626T3 DK 14790452 T DK14790452 T DK 14790452T DK 2908626 T3 DK2908626 T3 DK 2908626T3
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- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5443—IL-15
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
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- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
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- A—HUMAN NECESSITIES
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- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/15—Humanized animals
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
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- A—HUMAN NECESSITIES
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- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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- A01K2267/035—Animal model for multifactorial diseases
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Claims (12)
1. Genetisk modificeret mus, hvis genom omfatter en erstatning i et endogent muse-IL-15 locus, af et musegenomfragment der koder for et modent muse-IL-15 polypeptid, med et humant genomsegment der koder for et modent humant IL-15 polypeptid hvor de humane IL-15 exoner i det humane genomsegment består af humane IL-15 protein kodende exoner 3, 4, 5 og 6 til at danne et humani-seret IL-15 gen, hvor IL-15 exonerne er nummererede med det første kodende exon som exon 1, og hvor det humaniserede IL-15 gen er styret af alle endogene muse-IL-15 opstrømsregulerende elementer i det endogene muse-IL-15 locus.
2. Genetisk modificeret mus ifølge krav 1, hvor det humaniserede IL-15 kodende gen koder for et protein der omfatter aminosyresekvensen med SEQ ID NO: 5.
3. Genetisk modificeret mus ifølge krav 1, hvor det humane genomsegment endvidere omfatter human intron-sekvens opstrøms fra 5' mest human exon og human ikke-protein kodende sekvens nedstrøms fra det humane stop-codon og nedstrøms fra det humane 3' UTR.
4. Fremgangsmåde til fremstilling af en genetisk modificeret mus, omfattende at modificere genomet hos en mus ved at erstatte et musegenomfragment der koder for et modent muse-IL-15 polypeptid i det endogene muse-IL-15 locus med et humant genomsegment der koder for et modent humant IL-15 polypeptid hvor de humane IL-15 exoner i det humane genomsegment består af humane IL-15 protein kodende exoner 3, 4, 5 og 6 til at danne et humaniseret IL-15 gen, hvor IL-15 exonerne er nummererede med det første kodende exon som exon 1, og hvor det humaniserede IL-15 gen er styret af alle endogene muse-IL-15 opstrømsregulerende elementer i det endogene muse-IL-15 locus.
5. Fremgangsmåde ifølge krav 4, hvor det humane genomsegment endvidere omfatter human intron-sekvens opstrøms fra 5' mest human exon og human ikke- protein kodende sekvens nedstrøms fra det humane stop-codon og nedstrøms fra det humane 3' UTR.
6. Fremgangsmåde ifølge krav 4, hvor det humaniserede IL-15 kodende gen koder for et protein der omfatter aminosyresekvensen med SEQ ID NO: 5.
7. Genetisk modificeret mus, hvis genomen omfatter et humaniseret IL-15 gen, hvor det humaniserede IL-15 gen omfatter muse-IL-15 protein kodende exoner 1 og 2 og et humant genomsegment hvor de humane IL-15 exoner i det humane genomsegment består af humane IL-15 protein kodende exoner 3, 4, 5 og 6, hvor IL-15 exonerne er nummererede med det første kodende exon som exon 1, og hvor det humaniserede IL-15 gen er styret af alle muse-IL-15 opstrømsregule-rende elementer fra et endogent muse-IL-15 locus, og det humaniserede IL-15 gen koder for et protein omfattende en moden human IL-15 polypeptidsekvens.
8. Genetisk modificeret mus ifølge krav 7, hvor det humaniserede IL-15 kodende gen koder for et protein der omfatter aminosyresekvensen med SEQ ID NO: 5.
9. Genetisk modificeret mus ifølge krav 7, hvor det humane genomsegment endvidere omfatter human intron-sekvens opstrøms fra 5' mest human exon og human ikke-protein kodende sekvens nedstrøms fra det humane stop-codon og nedstrøms fra det humane 3' UTR.
10. Genetisk modificeret mus ifølge krav 7, hvor det humaniserede IL-15 gen er i en position i musens genom der er en anden end et endogent IL-15 locus.
11. Fremgangsmåde til fremstilling af en genetisk modificeret mus omfattende at introducere i genomet hos en mus et humaniseret IL-15 gen der omfatter muse-IL-15 protein kodende exoner 1 og 2 og et humant genomsegment hvor de humane IL-15 exoner i det humane genomsegment består af humane IL-15 exoner 3,4, 5 og 6, hvor de humane IL-15 exoner er nummererede med det første kodende exon som exon 1, og hvor det humaniserede IL-15 gen er styret af alle muse-IL-15 opstrømregulerende elementer fra et endogent muse-IL-15 locus, og det humaniserede IL-15 gen koder for et protein omfattende en moden human IL-15 polypeptidsekvens.
12. Fremgangsmåde ifølge krav 11, hvor det humaniserede IL-15 gen er inte-greret i genomet i en position der er en anden end et endogent IL-15 locus.
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ES2700852T3 (es) | 2009-10-06 | 2019-02-19 | Regeneron Pharma | Ratones modificados genéticamente e injerto |
SG10202008003VA (en) | 2011-02-15 | 2020-10-29 | Regeneron Pharma | Humanized m-csf mice |
JP6283031B2 (ja) | 2012-09-07 | 2018-02-21 | イエール ユニバーシティ | 遺伝学的に修飾された非ヒト動物およびその使用法 |
CN114766432A (zh) | 2012-11-05 | 2022-07-22 | 再生元制药公司 | 经遗传修饰的非人动物及其使用方法 |
RS58465B1 (sr) | 2013-10-15 | 2019-04-30 | Regeneron Pharma | Humanizovane il-15 životinje |
MX2016014504A (es) | 2014-05-05 | 2017-05-23 | Regeneron Pharma | Animales c5 y c3 humanizados. |
NO2785538T3 (da) | 2014-05-07 | 2018-08-04 | ||
KR20240017405A (ko) | 2014-05-19 | 2024-02-07 | 리제너론 파마슈티칼스 인코포레이티드 | 인간 epo를 발현하는 유전자 변형된 비-인간 동물 |
MX2017007293A (es) | 2014-12-05 | 2018-03-12 | Regeneron Pharma | Animales no humanos que tienen un gen del grupo de diferenciacion 47 humanizado. |
CN115943929A (zh) | 2015-04-13 | 2023-04-11 | 再生元制药公司 | 人源化SIRPα-IL15敲入小鼠及其使用方法 |
JP6843872B2 (ja) | 2016-02-04 | 2021-03-17 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | 操作されたangptl8遺伝子を有する非ヒト動物 |
SG10202001578RA (en) | 2016-02-29 | 2020-04-29 | Regeneron Pharma | Rodents having a humanized tmprss gene |
EP3476865B1 (en) | 2016-06-28 | 2023-09-13 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Method for constructing pd-1 gene-modified humanized animal model and use thereof |
CN107815467B (zh) | 2016-08-31 | 2021-03-16 | 百奥赛图(北京)医药科技股份有限公司 | 人源化基因改造动物模型的制备方法及应用 |
CN107815468B (zh) | 2016-08-31 | 2021-03-16 | 百奥赛图(北京)医药科技股份有限公司 | 人源化基因改造动物模型的制备方法及应用 |
WO2018041121A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric ctla-4 |
WO2018041118A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric pd-l1 |
WO2018041120A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric tigit |
WO2018086594A1 (en) | 2016-11-11 | 2018-05-17 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric tim-3 |
CN108070613B (zh) | 2016-11-11 | 2020-03-13 | 百奥赛图江苏基因生物技术有限公司 | 人源化基因改造动物模型的制备方法及应用 |
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