JP6422441B2 - 遺伝学的に修飾された非ヒト動物およびその使用法 - Google Patents

遺伝学的に修飾された非ヒト動物およびその使用法 Download PDF

Info

Publication number
JP6422441B2
JP6422441B2 JP2015540872A JP2015540872A JP6422441B2 JP 6422441 B2 JP6422441 B2 JP 6422441B2 JP 2015540872 A JP2015540872 A JP 2015540872A JP 2015540872 A JP2015540872 A JP 2015540872A JP 6422441 B2 JP6422441 B2 JP 6422441B2
Authority
JP
Japan
Prior art keywords
human
cells
mouse
nucleic acid
genetically modified
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2015540872A
Other languages
English (en)
Japanese (ja)
Other versions
JP2015534819A5 (enExample
JP2015534819A (ja
Inventor
リチャード フラベル
リチャード フラベル
ティル ストロウィッグ
ティル ストロウィッグ
マルクス ジー． マンツ
マルクス ジー． マンツ
チアラ ボルソッティ
チアラ ボルソッティ
マダブ ドダプカル
マダブ ドダプカル
アンドリュー ジェイ． マーフィー
アンドリュー ジェイ． マーフィー
ショーン スティーブンズ
ショーン スティーブンズ
ジョージ ディー． ヤンコポーロス
ジョージ ディー． ヤンコポーロス
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yale University
Regeneron Pharmaceuticals Inc
Original Assignee
Yale University
Regeneron Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yale University, Regeneron Pharmaceuticals Inc filed Critical Yale University
Publication of JP2015534819A publication Critical patent/JP2015534819A/ja
Publication of JP2015534819A5 publication Critical patent/JP2015534819A5/ja
Application granted granted Critical
Publication of JP6422441B2 publication Critical patent/JP6422441B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0276—Knock-out vertebrates
    • 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
    • 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
    • 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
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • 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
    • A01K2207/12—Animals modified by administration of exogenous cells
    • 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
    • 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
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A01K2217/052—Animals comprising random inserted nucleic acids (transgenic) inducing gain of function
    • 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
    • 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
    • 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
    • A01K2267/01—Animal expressing industrially exogenous proteins
    • 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
    • A01K2267/0331—Animal model for proliferative diseases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
    • A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
    • 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
    • C07K14/524—Thrombopoietin, i.e. C-MPL ligand
    • 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
    • C07K14/53—Colony-stimulating factor [CSF]
    • C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
    • 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]
    • C07K14/5403—IL-3
    • 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]
    • C07K14/5412—IL-6
    • 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
    • C12N2015/8527—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic for producing animal models, e.g. for tests or diseases
    • C12N2015/8572—Animal models for proliferative diseases, e.g. comprising an oncogene

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Environmental Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Veterinary Medicine (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Public Health (AREA)
  • Endocrinology (AREA)
  • Epidemiology (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • Pathology (AREA)
  • General Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
JP2015540872A 2012-11-05 2013-11-05 遺伝学的に修飾された非ヒト動物およびその使用法 Active JP6422441B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261722437P 2012-11-05 2012-11-05
US61/722,437 2012-11-05
PCT/US2013/068569 WO2014071397A2 (en) 2012-11-05 2013-11-05 Genetically modified non-human animals and methods of use thereof

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2018194712A Division JP6772234B2 (ja) 2012-11-05 2018-10-16 遺伝学的に修飾された非ヒト動物およびその使用法

Publications (3)

Publication Number Publication Date
JP2015534819A JP2015534819A (ja) 2015-12-07
JP2015534819A5 JP2015534819A5 (enExample) 2016-12-22
JP6422441B2 true JP6422441B2 (ja) 2018-11-14

Family

ID=49876957

Family Applications (5)

Application Number Title Priority Date Filing Date
JP2015540872A Active JP6422441B2 (ja) 2012-11-05 2013-11-05 遺伝学的に修飾された非ヒト動物およびその使用法
JP2018194712A Active JP6772234B2 (ja) 2012-11-05 2018-10-16 遺伝学的に修飾された非ヒト動物およびその使用法
JP2020165884A Active JP7105844B2 (ja) 2012-11-05 2020-09-30 遺伝学的に修飾された非ヒト動物およびその使用法
JP2022111649A Active JP7579304B2 (ja) 2012-11-05 2022-07-12 遺伝学的に修飾された非ヒト動物およびその使用法
JP2024187836A Pending JP2025010204A (ja) 2012-11-05 2024-10-25 遺伝学的に修飾された非ヒト動物およびその使用法

Family Applications After (4)

Application Number Title Priority Date Filing Date
JP2018194712A Active JP6772234B2 (ja) 2012-11-05 2018-10-16 遺伝学的に修飾された非ヒト動物およびその使用法
JP2020165884A Active JP7105844B2 (ja) 2012-11-05 2020-09-30 遺伝学的に修飾された非ヒト動物およびその使用法
JP2022111649A Active JP7579304B2 (ja) 2012-11-05 2022-07-12 遺伝学的に修飾された非ヒト動物およびその使用法
JP2024187836A Pending JP2025010204A (ja) 2012-11-05 2024-10-25 遺伝学的に修飾された非ヒト動物およびその使用法

Country Status (19)

Country Link
US (5) US9901082B2 (enExample)
EP (5) EP4389764A3 (enExample)
JP (5) JP6422441B2 (enExample)
KR (5) KR102402806B1 (enExample)
CN (3) CN108401987B (enExample)
AU (3) AU2013337242B2 (enExample)
CA (1) CA2887706C (enExample)
DK (4) DK3308641T3 (enExample)
ES (4) ES2983031T3 (enExample)
FI (1) FI3939423T3 (enExample)
IL (5) IL311744B2 (enExample)
MX (3) MX370856B (enExample)
MY (1) MY175400A (enExample)
NO (1) NO2946162T3 (enExample)
NZ (3) NZ631614A (enExample)
PT (4) PT3556206T (enExample)
RU (1) RU2673156C2 (enExample)
SG (2) SG10201707449TA (enExample)
WO (1) WO2014071397A2 (enExample)

Families Citing this family (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
ES2700852T3 (es) 2009-10-06 2019-02-19 Regeneron Pharma Ratones modificados genéticamente e injerto
DK3375284T3 (da) 2011-02-15 2023-06-12 Univ Yale Humaniserede M-CSF-mus og anvendelser deraf
EP4193834B1 (en) * 2012-09-07 2025-05-14 Yale University Methods of using genetically modified mice
KR102402806B1 (ko) 2012-11-05 2022-05-30 리제너론 파마슈티칼스 인코포레이티드 유전자 변형된 비-인간 동물 및 그것의 사용 방법
CA2900832A1 (en) 2013-02-20 2014-08-28 Regeneron Pharmaceuticals, Inc. Mice expressing humanized t-cell co-receptors
WO2014130667A1 (en) 2013-02-22 2014-08-28 Regeneron Pharmaceuticals, Inc. Mice expressing humanized major histocompatibility complex
LT3175706T (lt) 2013-09-23 2019-02-25 Regeneron Pharmaceuticals, Inc. Gyvūnai, išskyrus žmogų, turintys humanizuotą signalą reguliuojančio baltymo geną
RU2674910C2 (ru) 2013-10-15 2018-12-13 Регенерон Фармасьютикалс, Инк. Животные с гуманизированным геном il-15
WO2015077071A1 (en) 2013-11-19 2015-05-28 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized b-cell activating factor gene
US20150143559A1 (en) 2013-11-19 2015-05-21 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized a proliferation-inducing ligand gene
KR102439412B1 (ko) 2014-04-08 2022-09-02 리제너론 파아마슈티컬스, 인크. 인간화된 Fc-감마 수용체를 갖는 비-인간 동물
CA2946881A1 (en) 2014-04-28 2015-11-05 Recombinetics, Inc. Multiplex gene editing in swine
CA3225091A1 (en) 2014-05-05 2015-11-12 Regeneron Pharmaceuticals, Inc. Humanized c5 and c3 animals
NO2785538T3 (enExample) 2014-05-07 2018-08-04
RU2711744C1 (ru) 2014-05-19 2020-01-21 Ридженерон Фармасьютикалз, Инк. Генетически модифицированные животные, отличные от человека, экспрессирующие epo человека
RS60097B1 (sr) 2014-06-19 2020-05-29 Regeneron Pharma Ne-humane životinje koje imaju humanizovani gen za programiranu ćelijsku smrt 1
CA2967823A1 (en) 2014-11-24 2016-06-02 Regeneron Pharmaceuticals, Inc. Non-human animals expressing humanized cd3 complex
SMT201900178T1 (it) * 2014-12-05 2019-05-10 Regeneron Pharma Animali diversi dall’uomo aventi un gruppo umanizzato del gene 47 di differenziazione
IL282649B (en) 2014-12-09 2022-07-01 Regeneron Pharma Non-human animals with a humanized gene for differentiation cluster 274
WO2016137841A1 (en) * 2015-02-26 2016-09-01 William Paterson University Of New Jersey Transgenic mice
RS64540B1 (sr) 2015-04-06 2023-09-29 Regeneron Pharma Imunski odgovori posredovani humanizovanim t ćelijama kod ne-humanih životinja
WO2016168212A1 (en) * 2015-04-13 2016-10-20 Regeneron Pharmaceuticals, Inc. Humanized sirpa-il15 knockin mice and methods of use thereof
PL3376857T3 (pl) 2015-11-20 2021-09-13 Regeneron Pharmaceuticals, Inc. Zwierzęta inne niż człowiek posiadające humanizowany gen aktywacji limfocytów 3
EP3422845B1 (en) 2016-02-29 2021-06-02 Regeneron Pharmaceuticals, Inc. Rodents having a humanized tmprss gene
EP4056031A1 (en) * 2016-08-11 2022-09-14 The Jackson Laboratory Methods and compositions relating to improved human red blood cell survival in genetically modified immunodeficient non-human animals
JOP20190009A1 (ar) 2016-09-21 2019-01-27 Alx Oncology Inc أجسام مضادة ضد بروتين ألفا منظم للإشارات وطرق استخدامها
US20190320633A1 (en) * 2016-11-30 2019-10-24 The Jackson Laboratory Humanized mouse model with improved human innate immune cell development
WO2018157058A1 (en) * 2017-02-27 2018-08-30 Regeneron Pharmaceuticals, Inc. Non-human animal models of retinoschisis
CN107115424B (zh) * 2017-05-09 2018-05-29 江西樟树市正康医药生物科技有限公司 改变酸性体质保钙及清热解毒的中药组合物及制备方法
RU2019140867A (ru) * 2017-05-12 2021-06-15 Зе Джексон Лаборатори Nsg мыши, не имеющие mhc класса i и класса ii
BR112020003609A2 (pt) 2017-09-29 2020-09-01 Regeneron Pharmaceuticals, Inc. sistema e método para formar uma emulsão
US11712026B2 (en) 2017-10-18 2023-08-01 The Jackson Laboratory Murine-MHC-deficient HLA-transgenic nod-mouse models for T1D therapy development
CN116064611A (zh) 2017-11-30 2023-05-05 瑞泽恩制药公司 包含人源化trkb基因座的非人动物
BR112020018927A2 (pt) 2018-03-21 2021-01-05 ALX Oncology Inc. Anticorpos contra proteína alfa reguladora de sinal e métodos de uso
CN116420679B (zh) 2018-03-26 2025-10-03 瑞泽恩制药公司 用于测试治疗剂的人源化啮齿动物
WO2020018511A1 (en) 2018-07-16 2020-01-23 Regeneron Pharmaceuticals, Inc. Non-human animal models of ditra disease and uses thereof
US12331320B2 (en) 2018-10-10 2025-06-17 The Research Foundation For The State University Of New York Genome edited cancer cell vaccines
CN111057721B (zh) * 2018-10-12 2021-03-16 百奥赛图(北京)医药科技股份有限公司 人源化IL-4和/或IL-4Rα改造动物模型的制备方法及应用
CN111172190B (zh) * 2018-12-25 2021-07-30 百奥赛图江苏基因生物技术有限公司 人源化细胞因子csf2基因改造非人动物的构建方法及应用
AU2020253532B2 (en) 2019-04-04 2024-06-20 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized coagulation factor 12 locus
CN113874510A (zh) 2019-06-04 2021-12-31 瑞泽恩制药公司 包括具有β滑移突变的人源化TTR基因座的非人动物和使用方法
US11622547B2 (en) 2019-06-07 2023-04-11 Regeneran Pharmaceuticals, Inc. Genetically modified mouse that expresses human albumin
US20220354098A1 (en) * 2019-07-17 2022-11-10 Yale University Genetically Modified Non-Human Animals and Methods of Use Thereof
CN111304246B (zh) * 2019-12-17 2021-05-04 百奥赛图江苏基因生物技术有限公司 一种人源化细胞因子动物模型、制备方法及应用
EP4087392A4 (en) * 2020-01-10 2024-02-21 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. GENETICALLY MODIFIED NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC MHC PROTEIN COMPLEX
US10973908B1 (en) 2020-05-14 2021-04-13 David Gordon Bermudes Expression of SARS-CoV-2 spike protein receptor binding domain in attenuated salmonella as a vaccine
AU2021347320A1 (en) 2020-09-24 2023-05-11 The Jackson Laboratory Humanized mouse models for assessing immune cell therapy
JP2024512702A (ja) 2021-03-31 2024-03-19 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 Ｔｃｒβレパートリーの改善された多様性を伴うヒト化細胞免疫系の構成要素を含む、遺伝的に改変されたマウス
CN116918767A (zh) * 2022-04-07 2023-10-24 上海立迪生物技术股份有限公司 一种人all小鼠原位pdox模型的建立方法及应用
CN116918766A (zh) * 2022-04-07 2023-10-24 上海立迪生物技术股份有限公司 一种人aml小鼠原位pdox模型的建立方法及应用
CN119654068A (zh) 2022-07-19 2025-03-18 瑞泽恩制药公司 转基因动物模型及其模拟人类免疫系统的用途
AU2024304358A1 (en) 2023-06-16 2025-11-06 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
WO2025171307A1 (en) 2024-02-08 2025-08-14 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
WO2025212991A1 (en) 2024-04-05 2025-10-09 Regeneron Pharmaceuticals, Inc. Rodent models of disease
WO2025250495A1 (en) * 2024-05-28 2025-12-04 Regeneron Pharmaceuticals, Inc. Acceleration of human hepatocyte engraftment in humanized liver animals by supplementing paracrine ligands or agonists that activate human liver regeneration signals

Family Cites Families (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4870009A (en) 1982-11-22 1989-09-26 The Salk Institute For Biological Studies Method of obtaining gene product through the generation of transgenic animals
US4736866B1 (en) 1984-06-22 1988-04-12 Transgenic non-human mammals
US5573930A (en) 1985-02-05 1996-11-12 Cetus Oncology Corporation DNA encoding various forms of colony stimulating factor-1
WO1988003173A2 (en) 1986-10-24 1988-05-05 Cetus Corporation New forms of colony stimulating factor-1
ATE119197T1 (de) 1987-12-23 1995-03-15 Univ Leland Stanford Junior Schimäre immunkompromittierende säugetiere und ihre verwendung.
JP2981486B2 (ja) 1988-06-14 1999-11-22 メディカル・バイオロジー・インスティチュート 哺乳動物の免疫系研究方法
JP2935511B2 (ja) * 1989-10-20 1999-08-16 忠三 岸本 ヒトｉｌ―６レセプターの製造方法
US5849288A (en) 1990-01-15 1998-12-15 Yeda Research And Development Co. Ltd. Method for production of monoclonal antibodies in chimeric mice or rats having xenogeneic antibody-producing cells
EP0438053B1 (en) 1990-01-15 1999-06-16 Yeda Research And Development Company Limited Durable engraftment and development of human hematopoietic lineages in normal mammals
US5652373A (en) 1990-01-15 1997-07-29 Yeda Research And Development Co. Ltd. Engraftment and development of xenogeneic cells in normal mammals having reconstituted hematopoetic deficient immune systems
CA2063408A1 (en) 1990-05-03 1991-11-04 Susan Mayo Human lymphoid tissue in an immunocompromised host
EP0484512A4 (en) 1990-05-25 1993-05-05 Systemix, Inc. Human peripheral blood cells in an immunocompromised host
US5633426A (en) 1990-05-25 1997-05-27 Systemix, Inc. In vivo use of human bone marrow for investigation and production
EP0571525A1 (en) 1991-02-11 1993-12-01 OMMAYA, Ayub K. Spinal fluid driven artificial organ
US5222982A (en) 1991-02-11 1993-06-29 Ommaya Ayub K Spinal fluid driven artificial organ
EP0517199A1 (en) 1991-06-04 1992-12-09 Yeda Research And Development Company, Ltd. Durable engraftment of human tissue and cells in normal mammals
WO1993005796A1 (en) 1991-09-19 1993-04-01 The Scripps Research Institute Method for producing human antibodies in a non-human animal, and animals therefor
EP0539970B1 (en) 1991-10-30 1999-05-26 Idemitsu Kosan Company Limited Methods for producing human lymphocytes and human monoclonal antibodies, and human monoclonal antibodies produced thereby
US6353150B1 (en) 1991-11-22 2002-03-05 Hsc Research And Development Limited Partnership Chimeric mammals with human hematopoietic cells
WO1993018144A1 (en) 1992-03-05 1993-09-16 The Trustees Of Columbia University Of The City Of New York Recombination activating gene deficient animal
US5866757A (en) 1992-06-02 1999-02-02 Yeda Research And Development Co. Ltd. Engraftment and development of xenogeneic cells in normal mammals having reconstituted hematopoetic deficient immune systems
US6018096A (en) 1993-05-03 2000-01-25 Surrogen, Inc. Animal model for engraftment, proliferation and differentiation of human hematopoietic stem cells
US5663481A (en) 1993-08-06 1997-09-02 Mount Sinai Hospital Corporation Animal model of the human immune system
CA2195678A1 (en) 1994-07-27 1996-02-08 Joseph A. Borkowski Bradykinin b2 receptor modified transgenic non-human animals
US6455756B1 (en) 1994-08-12 2002-09-24 Novartis Ag Long term xenogeneic myeloid and lymphoid cell production in chimeric immunocompromised mice
US7273753B2 (en) 1996-08-02 2007-09-25 Center Of Blood Research Purification and uses of dendritic cells and monocytes
US6248721B1 (en) 1997-04-09 2001-06-19 Lung-Ji Chang Method of using mouse model for evaluation of HIV vaccines
CA2284689C (en) 1997-04-09 2009-10-06 Lung-Ji Chang Animal model for evaluation of vaccines
GB2337755B (en) * 1998-05-29 2003-10-29 Secr Defence Virus vaccine
CA2382383A1 (en) 1999-08-31 2001-03-08 Genencor International, Inc. Transgenic mammal capable of facilitating production of donor-specific functional immunity
US20030028911A1 (en) 1999-08-31 2003-02-06 Manley Huang Transgenic mammal capable of facilitating production of donor-specific functional immunity
WO2001042484A1 (en) * 1999-12-09 2001-06-14 Human Genome Sciences, Inc. Il-6 like polynucleotide
WO2002022786A1 (en) 2000-09-14 2002-03-21 Genetrol Biotherapeutics, Inc. Method and cell composition for screening compounds for anti-inflammatory activity
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
KR101015913B1 (ko) * 2001-07-10 2011-02-23 존슨 앤드 존슨 리서치 피티와이 리미티드 조혈모세포의 유전적 변이 치료 방법 및 변이 세포의 용도
US20030124091A1 (en) * 2001-10-26 2003-07-03 Large Scale Biology Corporation Endothelial cell derived hematopoietic growth factor
JP4087338B2 (ja) 2001-11-15 2008-05-21 キリンファーマ株式会社 キメラ非ヒト動物
JPWO2004005496A1 (ja) 2002-07-05 2005-11-04 麒麟麦酒株式会社 臍帯血、骨髄、末梢血等に含まれる新規な未分化幹細胞集団
CN101250553A (zh) 2002-07-13 2008-08-27 上海医学遗传研究所 一种促人血小板生成素表达载体及其构建方法
JP2005537805A (ja) 2002-09-09 2005-12-15 カリフォルニア インスティチュート オブ テクノロジー ヒト化マウスを作成するための方法および組成物
EP1418185A1 (en) 2002-11-11 2004-05-12 Aventis Pharma Deutschland GmbH Use of EDG2 receptor in an animal model of heart failure
DE60322426D1 (enExample) 2002-12-16 2008-09-04 Genentech Inc
US7632810B2 (en) * 2003-03-12 2009-12-15 Genentech, Inc. Compositions with hematopoietic and immune activity
EP1598364A1 (en) * 2004-05-21 2005-11-23 AGIRx Limited Chimerical soluble hyper IL-11 receptor and use thereof
PT2767161T (pt) 2004-10-19 2018-04-20 Regeneron Pharma Método para gerar um animal homozigótico para uma modificação genética
US7759541B2 (en) * 2004-12-13 2010-07-20 Iti Life Sciences Transgenic animals for assessing drug metabolism and toxicity
GB2434578A (en) 2006-01-26 2007-08-01 Univ Basel Transgenic animals
ES2618787T5 (es) 2006-04-25 2022-10-21 Univ California Administración de factores de crecimiento para el tratamiento de trastornos del SNC
EP1878342A1 (en) 2006-07-13 2008-01-16 Institut Pasteur Immunodeficient mice transgenic for HLA class I and HLA class II molecules and their uses
US20080081064A1 (en) 2006-09-28 2008-04-03 Surmodics, Inc. Implantable Medical Device with Apertures for Delivery of Bioactive Agents
WO2008069659A1 (en) 2006-12-05 2008-06-12 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Improved xenogenic immune system in a non-human mammal
AU2008262487B2 (en) 2007-05-23 2013-10-31 Sangamo Therapeutics, Inc. Methods and compositions for increased transgene expression
GB0718029D0 (en) 2007-09-14 2007-10-24 Iti Scotland Ltd Two step cluster deletion and humanisation
WO2009042917A1 (en) 2007-09-28 2009-04-02 The General Hospital Corporation Methods and compositions for antibody production
EP2257250A2 (en) 2008-01-29 2010-12-08 Gilbert H. Kliman Drug delivery devices, kits and methods therefor
SG175127A1 (en) * 2009-04-13 2011-11-28 Apceth Gmbh & Co Kg Engineered mesenchymal stem cells and method of using same to treat tumors
US20120251528A1 (en) 2009-06-29 2012-10-04 Leskov Ilya B Non-Human Mammal Model Of Human Hematopoietic Cancer
JP2012531896A (ja) * 2009-06-29 2012-12-13 チェン，チンフェン ヒト化非ヒト哺乳動物を製造する方法
RU2425880C2 (ru) 2009-07-30 2011-08-10 Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН Способ получения трансгенных мышей
ES2700852T3 (es) 2009-10-06 2019-02-19 Regeneron Pharma Ratones modificados genéticamente e injerto
SG181690A1 (en) * 2009-12-21 2012-07-30 Regeneron Pharma Humanized fcy r mice
US9402377B2 (en) 2010-09-20 2016-08-02 Yale University Human SIRPAalpha transgenic animals and their methods of use
WO2012051572A1 (en) 2010-10-15 2012-04-19 Massachusetts Institute Of Technology A humanized non-human mammal model of malaria and uses thereof
DK3375284T3 (da) 2011-02-15 2023-06-12 Univ Yale Humaniserede M-CSF-mus og anvendelser deraf
RS55949B1 (sr) * 2011-10-28 2017-09-29 Regeneron Pharmaeuticals Inc Humanizovani il-6 i il-6 receptor
EP4193834B1 (en) 2012-09-07 2025-05-14 Yale University Methods of using genetically modified mice
KR102402806B1 (ko) 2012-11-05 2022-05-30 리제너론 파마슈티칼스 인코포레이티드 유전자 변형된 비-인간 동물 및 그것의 사용 방법
LT3175706T (lt) 2013-09-23 2019-02-25 Regeneron Pharmaceuticals, Inc. Gyvūnai, išskyrus žmogų, turintys humanizuotą signalą reguliuojančio baltymo geną
RU2674910C2 (ru) 2013-10-15 2018-12-13 Регенерон Фармасьютикалс, Инк. Животные с гуманизированным геном il-15
RU2711744C1 (ru) 2014-05-19 2020-01-21 Ридженерон Фармасьютикалз, Инк. Генетически модифицированные животные, отличные от человека, экспрессирующие epo человека
WO2016168212A1 (en) 2015-04-13 2016-10-20 Regeneron Pharmaceuticals, Inc. Humanized sirpa-il15 knockin mice and methods of use thereof

Also Published As

Publication number Publication date
NZ724353A (en) 2022-05-27
RU2018140189A3 (enExample) 2022-05-04
PT3556206T (pt) 2021-08-24
US10785968B2 (en) 2020-09-29
US20180049413A1 (en) 2018-02-22
PT3939423T (pt) 2024-05-29
US11778995B2 (en) 2023-10-10
EP3556206B1 (en) 2021-06-02
RU2015121195A (ru) 2016-12-27
IL311744A (en) 2024-05-01
AU2013337242A1 (en) 2015-04-30
HK1210380A1 (en) 2016-04-22
HK1253909A1 (en) 2019-07-05
FI3939423T3 (fi) 2024-05-23
DK3308641T3 (da) 2019-10-07
EP2914102A2 (en) 2015-09-09
ES2884598T3 (es) 2021-12-10
MY175400A (en) 2020-06-24
IL258968B (en) 2019-10-31
AU2013337242B2 (en) 2019-04-04
KR20220075242A (ko) 2022-06-07
DK3556206T3 (da) 2021-08-09
EP3308641B1 (en) 2019-07-03
CN114766432A (zh) 2022-07-22
KR20210087567A (ko) 2021-07-12
AU2019204775B2 (en) 2021-10-21
US20240099278A1 (en) 2024-03-28
IL238478A0 (en) 2015-06-30
KR20150081285A (ko) 2015-07-13
EP2914102B1 (en) 2017-10-18
CN104918483B (zh) 2018-05-11
AU2019204775A1 (en) 2019-07-25
ES2655442T3 (es) 2018-02-20
CA2887706A1 (en) 2014-05-08
KR102768101B1 (ko) 2025-02-18
EP4389764A2 (en) 2024-06-26
JP2025010204A (ja) 2025-01-20
JP2019037238A (ja) 2019-03-14
IL311744B1 (en) 2025-06-01
US20210100228A1 (en) 2021-04-08
JP7105844B2 (ja) 2022-07-25
EP3939423B1 (en) 2024-03-06
IL270124B2 (en) 2023-06-01
RU2673156C2 (ru) 2018-11-22
ES2748662T3 (es) 2020-03-17
DK3939423T3 (da) 2024-05-06
SG11201502685XA (en) 2015-05-28
EP3939423A1 (en) 2022-01-19
IL270124A (enExample) 2019-12-31
US20160366862A1 (en) 2016-12-22
US9986724B2 (en) 2018-06-05
MX2015005654A (es) 2016-04-28
KR20220148307A (ko) 2022-11-04
JP2021010371A (ja) 2021-02-04
NZ631614A (en) 2016-10-28
EP3308641A1 (en) 2018-04-18
JP7579304B2 (ja) 2024-11-07
MX377561B (es) 2025-03-10
MX370856B (es) 2020-01-08
US20140134662A1 (en) 2014-05-15
IL299887A (en) 2023-03-01
KR102402806B1 (ko) 2022-05-30
SG10201707449TA (en) 2017-10-30
KR102649893B1 (ko) 2024-03-25
IL270124B1 (enExample) 2023-02-01
CN108401987A (zh) 2018-08-17
MX2020012427A (es) 2022-06-08
PT2914102T (pt) 2018-01-15
KR102458016B1 (ko) 2022-10-25
US9901082B2 (en) 2018-02-27
WO2014071397A3 (en) 2014-06-26
CN114766432B (zh) 2024-08-02
AU2022200302B2 (en) 2025-04-10
JP6772234B2 (ja) 2020-10-21
DK2914102T3 (en) 2017-12-11
EP4389764A3 (en) 2024-08-14
PT3308641T (pt) 2019-10-24
IL299887B2 (en) 2024-09-01
RU2018140189A (ru) 2018-12-10
IL258968A (en) 2018-06-28
CN108401987B (zh) 2022-04-29
EP3556206A1 (en) 2019-10-23
IL299887B1 (en) 2024-05-01
CA2887706C (en) 2022-08-02
KR102275412B1 (ko) 2021-07-12
NO2946162T3 (enExample) 2018-06-09
KR20240042142A (ko) 2024-04-01
AU2022200302A1 (en) 2022-02-10
IL311744B2 (en) 2025-10-01
MX2019015882A (es) 2020-02-07
JP2022132376A (ja) 2022-09-08
WO2014071397A2 (en) 2014-05-08
NZ749626A (en) 2023-11-24
CN104918483A (zh) 2015-09-16
JP2015534819A (ja) 2015-12-07
IL238478B (en) 2018-05-31
ES2983031T3 (es) 2024-10-21

Similar Documents

Publication Publication Date Title
JP7105844B2 (ja) 遺伝学的に修飾された非ヒト動物およびその使用法
HK40111833A (en) Genetically modified non-human animals and methods of use thereof
HK40068456B (en) Genetically modified non-human animals and methods of use thereof
HK40068456A (en) Genetically modified non-human animals and methods of use thereof
HK40016315B (en) Genetically modified non-human animals and methods of use thereof
HK40016315A (en) Genetically modified non-human animals and methods of use thereof
HK1253909B (en) Immunodeficient, genetically modified rodent and methods of use thereof
HK1210380B (en) Genetically modified non-human animals and methods of use thereof

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20150409

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20150611

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20161101

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20161101

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20171012

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20180110

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20180406

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20180919

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20181016

R150 Certificate of patent or registration of utility model

Ref document number: 6422441

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250