HRP20210256T1 - Genetski modificirani mišji receptor t-stanice - Google Patents
Genetski modificirani mišji receptor t-stanice Download PDFInfo
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- HRP20210256T1 HRP20210256T1 HRP20210256TT HRP20210256T HRP20210256T1 HR P20210256 T1 HRP20210256 T1 HR P20210256T1 HR P20210256T T HRP20210256T T HR P20210256TT HR P20210256 T HRP20210256 T HR P20210256T HR P20210256 T1 HRP20210256 T1 HR P20210256T1
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- 108091008874 T cell receptors Proteins 0.000 title claims 6
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 title claims 6
- 241000699670 Mus sp. Species 0.000 title 1
- 241000283984 Rodentia Species 0.000 claims 29
- 210000004027 cell Anatomy 0.000 claims 24
- 210000001744 T-lymphocyte Anatomy 0.000 claims 21
- 108090000623 proteins and genes Proteins 0.000 claims 21
- 238000012217 deletion Methods 0.000 claims 14
- 230000037430 deletion Effects 0.000 claims 14
- 238000000034 method Methods 0.000 claims 7
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 4
- 150000007523 nucleic acids Chemical group 0.000 claims 4
- 239000000427 antigen Substances 0.000 claims 3
- 108091007433 antigens Proteins 0.000 claims 3
- 102000036639 antigens Human genes 0.000 claims 3
- 238000000338 in vitro Methods 0.000 claims 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims 2
- GTJASUYQSYEAFD-NPRBSQQLSA-N 102643-50-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)N)[C@@H](C)O)C1=CC=CC=C1 GTJASUYQSYEAFD-NPRBSQQLSA-N 0.000 claims 1
- 108700042077 T-Cell Receptor beta Genes Proteins 0.000 claims 1
- 238000010367 cloning Methods 0.000 claims 1
- 210000001671 embryonic stem cell Anatomy 0.000 claims 1
- 210000005260 human cell Anatomy 0.000 claims 1
- 210000001161 mammalian embryo Anatomy 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 108010050138 synthetic joining segment peptide Proteins 0.000 claims 1
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- A—HUMAN NECESSITIES
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- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
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- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
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- C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
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- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
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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
- 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
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
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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
- A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
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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
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
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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
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0387—Animal model for diseases of the immune system
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- C12N2800/00—Nucleic acids vectors
- C12N2800/20—Pseudochromosomes, minichrosomosomes
- C12N2800/204—Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC
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- C12N2800/00—Nucleic acids vectors
- C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
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- Micro-Organisms Or Cultivation Processes Thereof (AREA)
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Claims (17)
1. Izolirana stanica glodavca, naznačena time, da obuhvaća:
najmanje jedan nepreuređeni Vα-segment varijabilne regije ljudske T-stanice i najmanje jedan nepreuređeni Jα-segment varijabilne regije ljudske T-stanice, koji su operabilno povezani s konstantnim genskim TCRα-slijedom glodavca, na endogenom varijabilnom genskom TCRα-lokusu glodavca, i/ili
najmanje jedan nepreuređeni Vβ-segment varijabilne regije ljudske T-stanice, najmanje jedan nepreuređeni Dβ-segment varijabilne regije ljudske T-stanice, i najmanje jedan nepreuređeni Jβ-segment varijabilne regije ljudske T-stanice, koji su operabilno povezani s konstantnim genskim TCRβ-slijedom glodavca, na endogenom varijabilnom genskom TCRβ-lokusu glodavca,
pri čemu su nepreuređeni segmenti varijabilne regije ljudske T-stanice sposobni za preuređivanje u T-stanici, u svrhu tvorbe gena koji kodiraju varijabilne domene receptora ljudske T-stanice, koje se specifično vežu na antigen od interesa.
2. Izolirana stanica glodavca prema patentnom zahtjevu 1, naznačena time, da stanica glodavca sadrži deleciju odabranu iz skupine koja se sastoji od (a) delecije svih endogenih genskih Vα-segmenata, (b) delecije svih endogenih genskih Jα-segmenata, i (c) njihove kombinacije i/ili time, da stanica glodavca sadrži deleciju odabranu iz skupine koja se sastoji od (a) delecije svih endogenih genskih Vβ-segmenata, (b) delecije svih endogenih genskih Dβ-segmenata, (c) delecije svih endogenih genskih Jβ-segmenata, i (d) njihove kombinacije.
3. Izolirana stanica glodavca prema bilo kojem od patentnih zahtjeva 1 do 2, naznačena time, da stanica jest matična stanica embrija.
4. Izolirana T-stanica glodavca, naznačena time, da na endogenom varijabilnom genskom TCRα-lokusu, sadrži preuređeni ljudski TCR Vα/Jα-slijed i/ili na endogenom varijabilnom genskom TCRβ-lokusu, sadrži preuređeni ljudski TCR Vβ/Dβ/Jβ-slijed, gdje T-stanica eksprimira receptor T-stanice koji sadrži varijabilnu ljudsku TCRα-domenu operabilno povezanu s konstantnom TCRα-regijom glodavca, i/ili varijabilnu ljudsku TCRβ-domenu operativno povezanu s konstantnom TCRβ-regijom glodavca, na svojoj staničnoj površini.
5. Izolirana T-stanica glodavca prema patentnom zahtjevu 4, naznačena time, da T-stanica jest CD4+ T-stanica, CD8+ T-stanica, hibridom ili kvadrom izveden iz CD4+ T-stanice, ili hibridom ili kvadrom izveden iz CD8+ T-stanice.
6. Izolirana stanica ili T-stanica glodavca prema bilo kojem od patentnih zahtjeva 1 do 5, naznačena time, da glodavac je štakor.
7. Izolirana stanica ili T-stanica glodavca prema bilo kojem od patentnih zahtjeva 1 do 5, naznačena time, da glodavac je miš.
8. Sustav in vitro, naznačen time, da sadrži stanicu u skladu s bilo kojim od patentnih zahtjeva 1 do 7.
9. Stanični kompleks in vitro, naznačen time, da obuhvaća prvu stanicu u skladu s bilo kojim od patentnih zahtjeva 4 do 7 i drugu stanicu, pri čemu je druga stanica antigen koji predstavlja stanicu koja eksprimira ljudsku ili humaniziranu MHC molekulu.
10. Stanični kompleks in vitro prema patentnom zahtjevu 9, naznačen time, da druga stanica je ljudska stanica ili stanica glodavca.
11. Postupak proizvodnje genetski modificiranog glodavca, naznačen time, da obuhvaća:
modificiranje endogenog varijabilnog genskog TCRα-lokusa glodavca, u svrhu obuhvaćanja najmanje jednog nepreuređenog Vα-segmenta varijabilne regije ljudske T-stanice i najmanje jednog nepreuređenog Jα-segmenta varijabilne regije ljudske T-stanice, koji su operabilno povezani s konstantnim genskim TCRα-slijedom glodavca, i/ili
modificiranje endogenog varijabilnog genskog TCRβ-lokusa glodavca, u svrhu obuhvaćanja najmanje jednog nepreuređenog Vβ-segmenta varijabilne regije ljudske T-stanice, najmanje jednog nepreuređenog Dβ-segmenta varijabilne regije ljudske T-stanice, i najmanje jednog nepreuređenog Jβ-segmenta varijabilne regije ljudske T-stanice, koji su operabilno povezani s konstantnim genskim TCRβ-slijedom glodavca,
pri čemu su nepreuređeni segmenti varijabilne regije ljudske T-stanice sposobni za preuređivanje u svrhu tvorbe gena koji kodiraju varijabilne
domene receptora ljudske T-stanice, uključujući domene koje se specifično vežu na antigen od interesa.
12. Postupak prema patentnom zahtjevu 11, naznačen time, da glodavac sadrži deleciju odabranu iz skupine koja se sastoji od (a) delecije svih endogenih genskih Vα-segmenata, (b) delecije svih endogenih genskih Jα-segmenata, i (c) njihove kombinacije i/ili time, da glodavac sadrži deleciju odabranu iz skupine koja se sastoji od (a) delecije svih endogenih genskih Vβ-segmenata, (b) delecije svih endogenih genskih Dβ-segmenata, (c) delecije svih endogenih genskih Jβ-segmenata, i (d) njihove kombinacije.
13. Postupak prema bilo kojem od patentnih zahtjeva 11 do 12, naznačen time, da glodavac je štakor.
14. Postupak prema bilo kojem od patentnih zahtjeva 11 do 12, naznačen time, da glodavac je miš.
15. Postupak prema patentnom zahtjevu 14, naznačen time, da se modifikacija radi u samo jednoj ES stanici, i samo jedna ES stanica se uvodi u embrij miša u svrhu stvaranja miša.
16. Postupak za dobivanje slijeda nukleinske kiseline koji kodira ljudsku varijabilnu TCR-domenu, naznačen time, da obuhvaća:
određivanje slijeda nukleinske kiseline ljudske varijabilne TCR-regije koja je eksprimirana pomoću izolirane stanice glodavca u skladu s bilo kojim od patentnih zahtjeva 4 do 7.
17. Postupak za proizvodnju receptora T-stanice, naznačen time, da obuhvaća:
dobivanje izolirane stanice glodavca u skladu s bilo kojim od patentnih zahtjeva 4 do 7;
izoliranje slijeda nukleinske kiseline koji kodira barem ljudsku varijabilnu TCR-domenu koja je eksprimirana pomoću izolirane stanice glodavca;
kloniranje slijeda nukleinske kiseline u nukleotidni konstrukt, i ekspresija u stanici navedenog receptora T-stanice.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161552582P | 2011-10-28 | 2011-10-28 | |
| US201261621198P | 2012-04-06 | 2012-04-06 | |
| US201261700908P | 2012-09-14 | 2012-09-14 | |
| EP18176096.8A EP3424947B1 (en) | 2011-10-28 | 2012-10-26 | Genetically modified t cell receptor mice |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20210256T1 true HRP20210256T1 (hr) | 2021-04-02 |
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ID=47178340
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20181626TT HRP20181626T1 (hr) | 2011-10-28 | 2018-10-10 | Genetski modificirani miševi receptora t-stanice (tcr-miševi) |
| HRP20210256TT HRP20210256T1 (hr) | 2011-10-28 | 2021-02-15 | Genetski modificirani mišji receptor t-stanice |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20181626TT HRP20181626T1 (hr) | 2011-10-28 | 2018-10-10 | Genetski modificirani miševi receptora t-stanice (tcr-miševi) |
Country Status (25)
| Country | Link |
|---|---|
| US (4) | US9113616B2 (hr) |
| EP (3) | EP2771357B1 (hr) |
| JP (7) | JP6254528B2 (hr) |
| KR (5) | KR102321909B1 (hr) |
| CN (5) | CN107858332A (hr) |
| AU (5) | AU2012327204B2 (hr) |
| BR (1) | BR112014009203B1 (hr) |
| CA (1) | CA2853707A1 (hr) |
| CY (2) | CY1120945T1 (hr) |
| DK (2) | DK3424947T3 (hr) |
| ES (2) | ES2858978T3 (hr) |
| HK (1) | HK1198171A1 (hr) |
| HR (2) | HRP20181626T1 (hr) |
| HU (1) | HUE053444T2 (hr) |
| IL (3) | IL274914B2 (hr) |
| IN (1) | IN2014CN03890A (hr) |
| LT (2) | LT2771357T (hr) |
| MX (1) | MX353134B (hr) |
| PL (2) | PL3424947T3 (hr) |
| PT (2) | PT3424947T (hr) |
| RS (2) | RS61455B1 (hr) |
| RU (1) | RU2661106C2 (hr) |
| SG (2) | SG10201914043XA (hr) |
| SI (2) | SI2771357T1 (hr) |
| WO (1) | WO2013063361A1 (hr) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9113616B2 (en) * | 2011-10-28 | 2015-08-25 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice having humanized TCR variable genes |
| CN103212064B (zh) * | 2012-01-19 | 2016-02-17 | 中国科学院上海巴斯德研究所 | 磷酸化途径相关因子在调控调节性t细胞功能中的应用 |
| JP6275120B2 (ja) | 2012-04-25 | 2018-02-07 | 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． | 大きい標的化ベクターによるヌクレアーゼ媒介標的化 |
| GB2508414A (en) * | 2012-11-30 | 2014-06-04 | Max Delbrueck Centrum | Tumour specific T cell receptors (TCRs) |
| US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
| ES2888250T3 (es) | 2013-04-16 | 2022-01-03 | Regeneron Pharma | Modificación direccionada del genoma de rata |
| KR101773782B1 (ko) | 2013-12-11 | 2017-09-01 | 리제너론 파마슈티칼스 인코포레이티드 | 게놈의 표적화된 변형을 위한 방법 및 조성물 |
| PL3152312T3 (pl) | 2014-06-06 | 2020-08-10 | Regeneron Pharmaceuticals, Inc. | Sposoby i kompozycje do modyfikowania docelowego locus |
| WO2015196051A1 (en) | 2014-06-19 | 2015-12-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized programmed cell death 1 gene |
| RS58009B1 (sr) | 2014-06-26 | 2019-02-28 | Regeneron Pharma | Postupci i supstance za ciljane genetske modifikacije i načini upotrebe |
| RU2017113134A (ru) | 2014-09-19 | 2018-10-19 | Регенерон Фармасьютикалз, Инк. | Химерные антигенные рецепторы |
| PL3221457T3 (pl) | 2014-11-21 | 2019-09-30 | Regeneron Pharmaceuticals, Inc. | Sposoby i kompozycje do celowanej modyfikacji genetycznej z zastosowaniem sparowanych przewodników RNA |
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