HRP20220616T1 - Genetski modificirani miš koji eksprimira kimerne molekule glavnog kompleksa histokompatibilnosti (mhc) ii - Google Patents
Genetski modificirani miš koji eksprimira kimerne molekule glavnog kompleksa histokompatibilnosti (mhc) ii Download PDFInfo
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- HRP20220616T1 HRP20220616T1 HRP20220616TT HRP20220616T HRP20220616T1 HR P20220616 T1 HRP20220616 T1 HR P20220616T1 HR P20220616T T HRP20220616T T HR P20220616TT HR P20220616 T HRP20220616 T HR P20220616T HR P20220616 T1 HRP20220616 T1 HR P20220616T1
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- Prior art keywords
- mhc
- rodent
- human
- polypeptide
- chimeric
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- 108700018351 Major Histocompatibility Complex Proteins 0.000 title 1
- 241000699670 Mus sp. Species 0.000 title 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 title 1
- 241000283984 Rodentia Species 0.000 claims 43
- 229920001184 polypeptide Polymers 0.000 claims 32
- 108090000765 processed proteins & peptides Proteins 0.000 claims 32
- 102000004196 processed proteins & peptides Human genes 0.000 claims 32
- 238000000034 method Methods 0.000 claims 10
- 239000002773 nucleotide Substances 0.000 claims 8
- 125000003729 nucleotide group Chemical group 0.000 claims 8
- 101100263837 Bovine ephemeral fever virus (strain BB7721) beta gene Proteins 0.000 claims 7
- 101100316840 Enterobacteria phage P4 Beta gene Proteins 0.000 claims 7
- 101150087698 alpha gene Proteins 0.000 claims 7
- 239000000427 antigen Substances 0.000 claims 7
- 108091007433 antigens Proteins 0.000 claims 7
- 102000036639 antigens Human genes 0.000 claims 7
- 108010046732 HLA-DR4 Antigen Proteins 0.000 claims 5
- 210000004027 cell Anatomy 0.000 claims 4
- 230000001086 cytosolic effect Effects 0.000 claims 4
- 230000001105 regulatory effect Effects 0.000 claims 4
- 108010010378 HLA-DP Antigens Proteins 0.000 claims 2
- 102000015789 HLA-DP Antigens Human genes 0.000 claims 2
- 108010062347 HLA-DQ Antigens Proteins 0.000 claims 2
- 108091008874 T cell receptors Proteins 0.000 claims 2
- 230000005867 T cell response Effects 0.000 claims 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims 2
- 230000028993 immune response Effects 0.000 claims 2
- 108010067802 HLA-DR alpha-Chains Proteins 0.000 claims 1
- 108010053491 HLA-DR beta-Chains Proteins 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 150000007523 nucleic acids Chemical group 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
Classifications
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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
- 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
-
- 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
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0271—Chimeric vertebrates, e.g. comprising exogenous cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70539—MHC-molecules, e.g. HLA-molecules
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- 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
-
- 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
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- 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
-
- 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
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (10)
1. Postupak za identifikaciju antigena koji generira CD4+ odgovor T stanice kod čovjeka, naznačen time, da obuhvaća:
izlaganje glodavca navodnom antigenu,
omogućavanje glodavcu da generira imunosni odgovor,
otkrivanje CD4+ odgovora T stanice koja je specifična za antigen; i
identifikaciju antigena,
pri čemu glodavac sadrži:
(i) na endogenom MHC II α genskom lokusu, nukleotidni slijed koji kodira kimerni ljudski/glodavački MHC II α polipeptid, i
(ii) na endogenom MHC II β genskom lokusu, nukleotidni slijed koji kodira kimerni ljudski/glodavački MHC II β polipeptid,
pri čemu ljudski dio kimernog ljudskog/glodavačkog MHC II α polipeptida, sadrži ljudske MHC II α1 i α2 domene, i ljudski dio kimernog ljudskog/glodavačkog MHC II β polipeptida, sadrži ljudske MHC II β1 i β2 domene,
dok glodavac eksprimira funkcionalni kimerni MHC II kompleks koji sadrži kimerni ljudski/glodavački MHC II α polipeptid i kimerni ljudski/glodavački MHC II β polipeptid, na površini stanice glodavca.
2. Postupak za identifikaciju varijabilne domene receptora T stanice koji prepoznaje antigen koji je predstavljen u kontekstu ljudskog MHC II, naznačen time, da obuhvaća:
izlaganje glodavca antigenu,
omogućavanje glodavcu da generira imunosni odgovor, i
izoliranje iz glodavca slijeda nukleinske kiseline koji kodira varijabilnu domenu receptora T stanice koji se veže na MHC II ograničeni antigen,
pri čemu glodavac sadrži:
(i) na endogenom MHC II α genskom lokusu, nukleotidni slijed koji kodira kimerni ljudski/glodavački MHC II α polipeptid, i
(ii) na endogenom MHC II β genskom lokusu, nukleotidni slijed koji kodira kimerni ljudski/glodavački MHC II β polipeptid,
pri čemu ljudski dio kimernog ljudskog/glodavačkog MHC II α polipeptida, sadrži ljudske MHC II α1 i α2 domene, i ljudski dio kimernog ljudskog/glodavačkog MHC II β polipeptida, sadrži ljudske MHC II β1 i β2 domene,
dok glodavac eksprimira funkcionalni kimerni MHC II kompleks koji sadrži kimerni ljudski/glodavački MHC II α polipeptid i kimerni ljudski/glodavački MHC II β polipeptid, na površini stanice glodavca.
3. Postupak prema patentnom zahtjevu 1 ili zahtjevu 2, naznačen time, da se nukleotidni slijed koji kodira kimerni ljudski/glodavački MHC II α polipeptid, eksprimira pod reguliranim upravljanjem endogenog glodavačkog MHC II α promotora i regulacijskih elemenata, i nukleotidni slijed koji kodira kimerni ljudski/glodavački MHC II β polipeptid se eksprimira pod reguliranim upravljanjem endogenog glodavačkog MHC II β promotora i regulacijskih elemenata.
4. Postupak prema patentnom zahtjevu 1 ili zahtjevu 2, naznačen time, da glodavački dio kimernog ljudskog/glodavačkog MHC II α polipeptida, sadrži transmembransku i citoplazmatsku domenu endogenog glodavačkog MHC II α polipeptida, i glodavački dio kimernog ljudskog/glodavačkog MHC II β polipeptida, sadrži transmembransku i citoplazmatsku domenu endogenog glodavačkog MHC II β polipeptida.
5. Postupak prema patentnom zahtjevu 1 ili zahtjevu 2, naznačen time, da ljudski dio kimernog ljudskog/glodavačkog MHC II α polipeptida, kodira genski lanac HLA razreda II α odabranog iz skupine koju čine HLA-DR α genski lanac, HLA-DQ α genski lanac, i HLA-DP α genski lanac, i ljudski dio kimernog ljudskog/glodavačkog MHC II β polipeptida, kodira genski lanac HLA razreda II β odabranog iz skupine koju čine HLA-DR β genski lanac, HLA-DQ β genski lanac, i HLA-DP β genski lanac.
6. Postupak prema patentnom zahtjevu 5, naznačen time, da ljudski dio kimernog ljudskog/glodavačkog MHC II α polipeptida, kodira putem ljudskog HLA-DR4 α genskog lanca, i ljudski dio kimernog ljudskog/glodavačkog MHC II β polipeptida, kodira HLA-DR4 β genski lanac.
7. Postupak prema patentnom zahtjevu 7, naznačen time, da glodavac jest miš.
8. Postupak prema patentnom zahtjevu 1 ili zahtjevu 2, naznačen time, da glodavac je miš i da se glodavačke dijelove kimernih MHC II α i β polipeptida kodiraju mišji H-2E α i β gena.
9. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da glodavac je miš koji na endogenom mišjem MHC II lokusu sadrži prvi nukleotidni slijed koji kodira kimerni ljudski/mišji MHC II α polipeptid i drugi nukleotidni slijed koji kodira kimerni ljudski/mišji MHC II β polipeptid,
pri čemu ljudski dio kimernog MHC II α polipeptida sadrži α1 i α2 domene koje kodirana ljudski HLA-DR4 α genski lanca, i ljudski dio kimernog MHC II β polipeptida sadrži β1 i β2 domene koje kodira ljudski HLA-DR4 β genski lanac,
dok mišji dio kimernog MHC II α polipeptida, sadrži transmembransku i citoplazmatsku domenu mišjeg H-2E α lanca, i mišji dio kimernog MHC II β polipeptida, sadrži transmembransku i citoplazmatsku domenu mišjeg H-2E β lanca,
i pritom miš eksprimira funkcionalni kimerni kompleks HLA-DR4/H-2E MHC II koji sadrži kimerni ljudski/mišji MHC II α polipeptid i kimerni ljudski/mišji MHC II β polipeptid, na površini mišje stanice.
10. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da glodavac na površini stanice ne eksprimira funkcionalne endogene MHC II polipeptide sa njihovih endogenih glodavačkih MHC II lokusa.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161552584P | 2011-10-28 | 2011-10-28 | |
| EP19189533.3A EP3590332B1 (en) | 2011-10-28 | 2012-10-26 | Genetically modified mice expressing chimeric major histocompatibility complex (mhc) ii molecules |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20220616T1 true HRP20220616T1 (hr) | 2022-06-24 |
Family
ID=47430036
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20220616TT HRP20220616T1 (hr) | 2011-10-28 | 2012-10-26 | Genetski modificirani miš koji eksprimira kimerne molekule glavnog kompleksa histokompatibilnosti (mhc) ii |
| HRP20171327TT HRP20171327T1 (hr) | 2011-10-28 | 2017-09-04 | Genetski modificirani miševi s ekspresijom kimernih molekula s glavnim sustavom tkivne podudarnosti (mhc) skupine ii |
| HRP20200305TT HRP20200305T1 (hr) | 2011-10-28 | 2020-02-24 | Genetski modificirani miševi koji eksprimiraju kimerne molekule glavnog histokompatibilnog kompleksa (mhc) ii |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20171327TT HRP20171327T1 (hr) | 2011-10-28 | 2017-09-04 | Genetski modificirani miševi s ekspresijom kimernih molekula s glavnim sustavom tkivne podudarnosti (mhc) skupine ii |
| HRP20200305TT HRP20200305T1 (hr) | 2011-10-28 | 2020-02-24 | Genetski modificirani miševi koji eksprimiraju kimerne molekule glavnog histokompatibilnog kompleksa (mhc) ii |
Country Status (25)
| Country | Link |
|---|---|
| US (6) | US8847005B2 (hr) |
| EP (4) | EP2770822B9 (hr) |
| JP (2) | JP6285361B2 (hr) |
| KR (2) | KR101926442B1 (hr) |
| CN (3) | CN108401986B (hr) |
| AU (4) | AU2012327205B2 (hr) |
| BR (1) | BR112014009941B1 (hr) |
| CA (1) | CA2852962C (hr) |
| CY (2) | CY1119283T1 (hr) |
| DK (3) | DK2770822T3 (hr) |
| ES (3) | ES2914374T3 (hr) |
| HK (2) | HK1196999A1 (hr) |
| HR (3) | HRP20220616T1 (hr) |
| HU (2) | HUE034374T2 (hr) |
| IL (3) | IL231895B (hr) |
| IN (1) | IN2014CN03892A (hr) |
| LT (3) | LT2770822T (hr) |
| MX (1) | MX355726B (hr) |
| PL (3) | PL2770822T3 (hr) |
| PT (3) | PT3590332T (hr) |
| RS (3) | RS63220B1 (hr) |
| RU (1) | RU2660564C2 (hr) |
| SG (3) | SG10201510056SA (hr) |
| SI (3) | SI2770822T1 (hr) |
| WO (1) | WO2013063340A1 (hr) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2008054865A2 (en) | 2006-04-26 | 2008-05-08 | L-3 Communications Security And Detection Systems, Inc. | Multi-source surveillance systems |
| KR101926442B1 (ko) | 2011-10-28 | 2018-12-12 | 리제너론 파아마슈티컬스, 인크. | 키메라 주요 조직적합성 복합체 （ｍｈｃ） ｉｉ 분자들을 발현하는 유전자 변형된 마우스 |
| EP2818478B1 (en) | 2011-10-28 | 2017-02-01 | Regeneron Pharmaceuticals, Inc. | Humanized IL-6 and IL-6 receptor |
| US9043996B2 (en) | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| EP2958938B1 (en) | 2013-02-20 | 2019-04-17 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized t-cell co-receptors |
| SI2958937T1 (sl) * | 2013-02-22 | 2018-12-31 | Regeneron Pharmaceuticals, Inc. | Miš, ki izraža humanizirani poglavitni histokompatibilnostni kompleks |
| US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
| CN105208855B (zh) * | 2013-03-11 | 2018-04-27 | 瑞泽恩制药公司 | 表达嵌合的主要组织相容性复合物(mhc)ii类分子的转基因小鼠 |
| IL297607B2 (en) | 2013-09-23 | 2024-01-01 | Regeneron Pharma | Non-human animals with a humanized gene for SIGNAL-REGULATORY PROTEIN |
| KR102376041B1 (ko) * | 2013-10-15 | 2022-03-18 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화된 il-15 동물 |
| SG11201604886WA (en) | 2014-04-08 | 2016-07-28 | Regeneron Pharma | Non-human animals having humanized fc-gamma receptors |
| NO2785538T3 (hr) | 2014-05-07 | 2018-08-04 | ||
| EP3157956B1 (en) * | 2014-06-19 | 2020-02-05 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized programmed cell death 1 gene |
| AU2015317370A1 (en) | 2014-09-19 | 2017-03-23 | Regeneron Pharmaceuticals, Inc. | Chimeric antigen receptors |
| LT3689140T (lt) | 2014-11-24 | 2022-08-25 | Regeneron Pharmaceuticals, Inc. | Gyvūnai, išskyrus žmones, ekspresuojantys humanizuotą cd3 kompleksą |
| FI3850946T3 (fi) | 2014-12-05 | 2023-12-28 | Regeneron Pharma | Ei-ihmiseläimiä, joilla on humanisoitu erilaistumisklusterin 47 geeni |
| AU2016246698B2 (en) | 2015-04-06 | 2022-06-02 | Regeneron Pharmaceuticals, Inc. | Humanized T cell mediated immune responses in non-human animals |
| MX2018005389A (es) | 2015-11-20 | 2018-09-05 | Regeneron Pharma | Animales no humanos que tienen un gen 3 de activacion linfocitaria humanizado. |
| EP3411392B1 (en) * | 2016-02-04 | 2021-12-29 | Regeneron Pharmaceuticals, Inc. | Non-human animals having an engineered angptl8 gene |
| CN109068621B (zh) | 2016-02-29 | 2021-07-20 | 再生元制药公司 | 具有人源化的tmprss基因的啮齿类动物 |
| CN116458475A (zh) | 2016-06-03 | 2023-07-21 | 瑞泽恩制药公司 | 表达外源末端脱氧核苷酸转移酶的非人动物 |
| JP7361031B2 (ja) | 2017-11-30 | 2023-10-13 | 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 | ヒト化ｔｒｋｂ遺伝子座を含む非ヒト動物 |
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| KR20210004994A (ko) | 2018-03-26 | 2021-01-13 | 리제너론 파마슈티칼스 인코포레이티드 | 치료제를 시험하기 위한 인간화된 설치류 |
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