HRP20171761T1 - Genetski modificirani miš s glavnim kompleksom histokompatibilnosti - Google Patents
Genetski modificirani miš s glavnim kompleksom histokompatibilnosti Download PDFInfo
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- HRP20171761T1 HRP20171761T1 HRP20171761TT HRP20171761T HRP20171761T1 HR P20171761 T1 HRP20171761 T1 HR P20171761T1 HR P20171761T T HRP20171761T T HR P20171761TT HR P20171761 T HRP20171761 T HR P20171761T HR P20171761 T1 HRP20171761 T1 HR P20171761T1
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- mouse
- polypeptide
- human
- rodent
- microglobulin
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- 108700018351 Major Histocompatibility Complex Proteins 0.000 title claims 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 title claims 2
- 241000699670 Mus sp. Species 0.000 title 1
- 229920001184 polypeptide Polymers 0.000 claims 46
- 108090000765 processed proteins & peptides Proteins 0.000 claims 46
- 102000004196 processed proteins & peptides Human genes 0.000 claims 46
- 241000283984 Rodentia Species 0.000 claims 30
- 239000002773 nucleotide Substances 0.000 claims 27
- 125000003729 nucleotide group Chemical group 0.000 claims 27
- 108010081355 beta 2-Microglobulin Proteins 0.000 claims 19
- 102000015736 beta 2-Microglobulin Human genes 0.000 claims 17
- 101000937544 Homo sapiens Beta-2-microglobulin Proteins 0.000 claims 6
- 241001529936 Murinae Species 0.000 claims 6
- 101000937526 Mus musculus Beta-2-microglobulin Proteins 0.000 claims 5
- 108700043516 mouse H-2Kb Proteins 0.000 claims 5
- 230000001105 regulatory effect Effects 0.000 claims 5
- 102000025850 HLA-A2 Antigen Human genes 0.000 claims 4
- 108010074032 HLA-A2 Antigen Proteins 0.000 claims 4
- 230000001086 cytosolic effect Effects 0.000 claims 4
- 108700024394 Exon Proteins 0.000 claims 3
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 3
- 108010075704 HLA-A Antigens Proteins 0.000 claims 2
- 102000011786 HLA-A Antigens Human genes 0.000 claims 2
- 210000001161 mammalian embryo Anatomy 0.000 claims 2
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 claims 1
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 claims 1
- 108010058607 HLA-B Antigens Proteins 0.000 claims 1
- 108010052199 HLA-C Antigens Proteins 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 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
-
- 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
-
- 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
- A01K2217/15—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
- A01K2267/03—Animal model, e.g. for test or diseases
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Environmental Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Engineering & Computer Science (AREA)
- Animal Husbandry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Cell Biology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Claims (38)
1. Glodavac koji na lokusu endogenog glavnog sustava tkivne podudarnosti (MHC I) ima nukleotidni slijed kojim se kodira kimerni MHC I polipeptid čovjeka/glodavca,
pri čemu se ljudski dio kimernog polipeptida sastoji od domena ljudskog MHC I polipeptida α1, α2, i α3,
pri čemu se dio glodavca kimernog polipeptida sastoji od transmembranske i citoplazmatske domene endogenog polipeptida glodavca MHC I i
pri čemu glodavac izražava kimerni MHC I polipeptid čovjeka/glodavca.
2. U glodavca iz zahtjeva 1. glodavac ne izražava domene α1, α2, i α3 endogenog MHC I polipeptida iz endogenog MHC I lokusa glodavca.
3. Glodavac iz zahtjeva 1. ili zahtjeva 2. pri čemu je nukleotidni slijed operabilno povezan s endogenim regulatornim elementima glodavca.
4. Glodavac iz bilo kojeg od prethodnih zahtjeva, pri čemu se ljudski dio kimernog polipeptida sastoji od vodećeg ljudskog slijeda.
5. Glodavac iz bilo kojeg od prethodnih zahtjeva, pri čemu je ljudski MHC I polipeptid odabran iz grupe koja se sastoji od HLA-A, HLA-B i HLA-C.
6. Glodavac iz bilo kojeg od prethodnih zahtjeva, pri čemu je glodavac miš.
7. Miš iz zahtjeva 6. pri čemu je endogeni lokus mišji lokus H-2K.
8. Miš iz zahtjeva 7. pri čemu je endogeni MHC I polipeptid glodavca H-2K.
9. Miš iz zahtjeva 6. na endogenom lokusu H-2K sadrži nukleotidni slijed kojim se kodira kimerni ljudski/mišji MHC I polipeptid,
pri čemu se ljudski dio kimernog polipeptida sastoji od domena α1, α2 i α3 ljudskog polipeptida HLA-A2, a mišji se dio sastoji od transmembranske i citoplazmatske domene mišjeg H-2K polipeptida i
pri čemu miš izražava kimerni HLA-A2/H-2K polipeptid.
10. U miša iz zahtjeva 9. miš ne izražava domene α1, α2, i α3 mišjeg H-2K polipeptida iz endogenog H-2K lokusa.
11. Miš iz zahtjeva 9. ili 10. pri čemu se ljudski dio kimernog polipeptida sastoji od vodećeg ljudskog slijeda.
12. Miš iz bilo kojeg zahtjeva 9. – 11. pri čemu je nukleotidni slijed operabilno povezan s endogenim regulatornim elementima miša.
13. Miš iz bilo kojeg zahtjeva 9. – 12. pri čemu je HLA-A2 polipeptid HLA-A2.1 polipeptid.
14. Miš iz bilo kojeg zahtjeva 9. – 13. pri čemu je mišji H-2K lokus H-2Kb lokus.
15. Metoda kojom se izmjenjuje mišji MHC I lokus kako bi se izrazio kimerni ljudski/mišji MHC I polipeptid, pri čemu se metoda sastoji od zamjene nukleotidnog slijeda kojim se kodiraju domene α1, α2 i α3 na endogenom MHC I lokusu mišjeg MHC I polipeptida nukleotidnim slijedom kojim se kodiraju domene α1, α2 i α3 ljudskog MHC I polipeptida, pri čemu miš izražava transmembranske i citoplazmatske domene mišjeg MHC I polipeptida.
16. Metoda iz zahtjeva 15., pri čemu miš ne izražava domene α1, α2, i α3 mišjeg MHC I polipeptida iz endogenog mišjeg MHC I lokusa.
17. Metoda iz zahtjeva 15. ili zahtjeva 16. pri čemu je mišji MHC I lokus H-2K lokus, a mišji MHC I polipeptid H-2K polipeptid.
18. Metoda iz bilo kojeg zahtjeva 15. – 17. pri čemu je ljudski MHC I polipeptid HLA-A polipeptid.
19. Metoda iz bilo kojeg zahtjeva 15. – 18. gdje se zamjena vrši na jednoj ES stanici, a ta se jedna ES stanica uvodi u mišji embrij kako bi nastao miš.
20. Glodavac koji prema bilo kojem od zahtjeva 1. – 14. nadalje na endogenom lokusu β2 mikroglobulina glodavca sadrži nukleotidni slijed kojim se kodira polipeptid koji sadrži ljudski slijed aminokiselina β2 mikroglobulina, pri čemu glodavac izražava ljudski ili humanizirani polipeptid β2 mikroglobulina.
21. U glodavca iz zahtjeva 20. glodavac ne izražava funkcionalni endogeni polipeptid β2 mikroglobulina iz endogenog lokusa β2 mikroglobulina glodavca.
22. Glodavac iz zahtjeva 20. ili zahtjeva 21. pri čemu je nukleotidni slijed operabilno povezan s endogenim regulatornim elementima β2 mikroglobulina glodavca.
23. Glodavac iz bilo kojeg od zahtjeva 20. – 22. pri čemu nukleotidni slijed sadrži nukleotidni slijed koji je izložen od eksona 2. do eksona 4. ljudskog gena β2 mikroglobulina.
24. Glodavac iz bilo kojeg od zahtjeva 20. – 23. pri čemu nukleotidni slijed sadrži nukleotidne sljedove koji su izloženi u eksonima 2., 3. i 4. ljudskog gena β2 mikroglobulina.
25. Glodavac iz bilo kojeg od zahtjeva 20. – 24. pri čemu nukleotidni slijed nadalje sadrži nukleotidni slijed koji je izložen u eksonu 1. gena β2 mikroglobulina glodavca.
26. Glodavac iz bilo kojeg od zahtjeva 20. – 25., pri čemu je glodavac miš.
27. Metoda prema bilo kojem od zahtjeva 15. – 19., pri čemu metoda dodatno sadrži izmjenu mišjeg lokusa β2 mikroglobulina kako bi izražavao ljudski ili humanizirani polipeptid β2 mikroglobulina tako da se na endogenom mišjem lokusu β2 mikroglobulina nukleotidni slijed kojim se kodira mišji polipeptid β2 mikroglobulina zamijeni nukleotidnim slijedom kojim se kodira ljudski ili humanizirani polipeptid β2 mikroglobulina.
28. Metoda iz zahtjeva 27. pri čemu miš ne izražava funkcionalni mišji polipeptid β2 mikroglobulina iz endogenog lokusa β2 mikroglobulina.
29. Metoda iz zahtjeva 27. ili 28. pri čemu nukleotidni slijed kojim se kodira ljudski ili humanizirani polipeptid β2 mikroglobulina sadrži nukleotidni slijed koji je izložen od eksona 2. do eksona 4. ljudskog gena β2 mikroglobulina.
30. Metoda iz bilo kojeg zahtjeva 27. – 29. pri čemu nukleotidni slijed kojim se kodira ljudski ili humanizirani polipeptid β2 mikroglobulina sadrži nukleotidne sljedove koji su izloženi u eksonima 2., 3. i 4. ljudskog gena β2 mikroglobulina.
31. Metoda iz bilo kojeg od zahtjeva 27. – 30. pri čemu izmijenjeni lokus zadržava nukleotidni slijed eksona 1. mišjeg gena β2 mikroglobulina.
32. Metoda iz bilo kojeg zahtjeva 27. – 31. gdje se zamjena vrši na jednoj ES stanici, a ta se jedna ES stanica uvodi u mišji embrij kako bi nastao miš.
33. Genom miša iz zahtjeva 9. sastoji se od:
prvog nukleotidnog slijeda kojim se kodira kimerni ljudski/mišji MHC I polipeptid, pri čemu se ljudski dio kimernog polipeptida sastoji od domena α1, α2 i α3 ljudskog HLA-A2, a mišji se dio sastoji od transmembranske i citoplazmatske domene mišjeg H-2K, i
drugog nukleotidnog slijeda kojim se kodira ljudski ili humanizirani polipeptid β2 mikroglobulina,
pri čemu se prvi nukleotidni slijed nalazi na endogenom H-2K lokus, a drugi se nukleotidni slijed nalazi na endogenom mišjem lokusu β2 mikroglobulina te
pri čemu miš izražava kimerni ljudski/mišji MHC I polipeptid i ljudski ili humanizirani polipeptid β2 mikroglobulina.
34. Miš iz zahtjeva 33. pri čemu miš ne izražava endogene mišje polipeptide H-2K i β2 mikroglobulina iz njihovih endogenih lokusa.
35. Miš iz zahtjeva 33. i 34., pri čemu je prvi nukleotidni slijed operabilno povezan s endogenim mišjim H-2K regulatornim elementima, a drugi je nukleotidni slijed operabilno povezan s endogenim mišjim regulatornim elementima β2 mikroglobulina.
36. Miš iz bilo kojeg od zahtjeva 33. – 35. pri čemu drugi nukleotidni slijed sadrži nukleotidni slijed koji je izložen od eksona 2. do eksona 4. ljudskog gena β2 mikroglobulina.
37. Miš iz bilo kojeg od zahtjeva 33. – 36. pri čemu drugi nukleotidni slijed sadrži nukleotidne sljedove koji su izloženi u eksonima 2., 3. i 4. ljudskog gena β2 mikroglobulina.
38. Miš iz bilo kojeg od zahtjeva 33. – 37. pri čemu se u izražavanju ljudskog ili humaniziranog polipeptida β2 mikroglobulina povećava izražavanje kimernog ljudskog/mišjeg MHC I polipeptida u usporedbi s izražavanjem kimernog ljudskog/mišjeg MHC I polipeptida gdje ne dolazi do izražavanja ljudskog ili humaniziranog polipeptida β2 mikroglobulina.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161552582P | 2011-10-28 | 2011-10-28 | |
| US201161552587P | 2011-10-28 | 2011-10-28 | |
| US201261700908P | 2012-09-14 | 2012-09-14 | |
| EP12787255.4A EP2770821B1 (en) | 2011-10-28 | 2012-10-26 | Genetically modified major histocompatibility complex mice |
| PCT/US2012/062042 WO2013063346A1 (en) | 2011-10-28 | 2012-10-26 | Genetically modified major histocompatibility complex mice |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20171761T1 true HRP20171761T1 (hr) | 2017-12-29 |
Family
ID=47178940
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20171761TT HRP20171761T1 (hr) | 2011-10-28 | 2017-11-15 | Genetski modificirani miš s glavnim kompleksom histokompatibilnosti |
| HRP20191420 HRP20191420T1 (hr) | 2011-10-28 | 2019-08-06 | Miševi koji su genetski modificirani s glavnim histokompatibilnim kompleksom |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20191420 HRP20191420T1 (hr) | 2011-10-28 | 2019-08-06 | Miševi koji su genetski modificirani s glavnim histokompatibilnim kompleksom |
Country Status (25)
| Country | Link |
|---|---|
| US (3) | US9615550B2 (hr) |
| EP (4) | EP4311833A3 (hr) |
| JP (4) | JP6154391B2 (hr) |
| KR (3) | KR101921126B1 (hr) |
| CN (3) | CN104039132B9 (hr) |
| AU (3) | AU2012324016C1 (hr) |
| BR (1) | BR112014009259A2 (hr) |
| CA (2) | CA3074400A1 (hr) |
| CY (2) | CY1119657T1 (hr) |
| DK (2) | DK2770821T3 (hr) |
| ES (3) | ES2962287T3 (hr) |
| HK (2) | HK1200272A1 (hr) |
| HR (2) | HRP20171761T1 (hr) |
| HU (2) | HUE045879T2 (hr) |
| IL (3) | IL232097A (hr) |
| LT (2) | LT2770821T (hr) |
| MX (2) | MX355725B (hr) |
| MY (2) | MY164836A (hr) |
| NZ (1) | NZ734532A (hr) |
| PL (2) | PL2770821T3 (hr) |
| PT (2) | PT3262932T (hr) |
| RS (2) | RS59082B1 (hr) |
| SG (2) | SG10201603188SA (hr) |
| SI (2) | SI2770821T1 (hr) |
| WO (1) | WO2013063346A1 (hr) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG10201600965YA (en) | 2011-10-28 | 2016-03-30 | Regeneron Pharma | Humanized il-6 and il-6 receptor |
| US9591835B2 (en) | 2011-10-28 | 2017-03-14 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| HUE045478T2 (hu) | 2013-02-20 | 2019-12-30 | Regeneron Pharma | Humanizált T-sejt koreceptorokat expresszáló egerek |
| JP6444321B2 (ja) * | 2013-02-22 | 2018-12-26 | 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． | ヒト化主要組織適合性遺伝子複合体を発現するマウス |
| US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
| KR102313053B1 (ko) * | 2013-03-11 | 2021-10-18 | 리제너론 파아마슈티컬스, 인크. | 키메라 주요 조직적합성 복합체(ｍｈｃ) 제ｉ 부류 분자를 발현하는 유전자전이 마우스 |
| RS64573B1 (sr) | 2013-09-23 | 2023-10-31 | Regeneron Pharma | Ne-humana životinja sa humanizovanim signalno-regulatornim proteinskim genom |
| SI3138397T1 (sl) | 2013-10-15 | 2019-04-30 | Regeneron Pharmaceuticals, Inc. | Humanizirane živali IL-15 |
| EP3058819B1 (en) * | 2013-10-18 | 2021-05-19 | Taiho Pharmaceutical Co., Ltd. | Hla class i expressing non-human animal |
| ES2794942T3 (es) | 2014-04-08 | 2020-11-19 | Regeneron Pharma | Animales no humanos que tienen receptores Fc-gamma humanizados |
| RU2020103811A (ru) | 2014-05-05 | 2020-02-18 | Регенерон Фармасьютикалз, Инк. | Гуманизированные животные по с5 и с3 |
| NO2785538T3 (hr) | 2014-05-07 | 2018-08-04 | ||
| RU2735958C2 (ru) | 2014-06-19 | 2020-11-11 | Регенерон Фармасьютикалз, Инк. | Животные, отличные от человека, имеющие гуманизированный ген 1 запрограммированной гибели клеток |
| WO2016044745A1 (en) | 2014-09-19 | 2016-03-24 | Regeneron Pharmaceuticals, Inc. | Chimeric antigen receptors |
| RU2020122439A (ru) | 2014-11-24 | 2020-09-24 | Регенерон Фармасьютикалз, Инк. | Не относящиеся к человеку животные, экспрессирующие гуманизированный комплекс cd3 |
| US20160345549A1 (en) | 2014-12-05 | 2016-12-01 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized cluster of differentiation 47 gene |
| PT3230320T (pt) * | 2014-12-09 | 2021-01-08 | Regeneron Pharma | Animais não humanos tendo um gene do cluster humanizado de diferenciação 274 |
| WO2016094679A1 (en) | 2014-12-10 | 2016-06-16 | Regents Of The University Of Minnesota | Genetically modified cells, tissues, and organs for treating disease |
| HRP20231039T1 (hr) | 2015-04-06 | 2023-12-22 | Regeneron Pharmaceuticals, Inc. | Imunosni odgovori posredovani humaniziranim t stanicama kod ne-humanih životinja |
| JP6752221B2 (ja) * | 2015-04-13 | 2020-09-09 | 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ｓｉｒｐａ−ｉｌ１５ノックインマウス及びその使用方法 |
| KR102454546B1 (ko) | 2015-11-20 | 2022-10-14 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 림프구 활성화 유전자 3을 갖는 비인간 동물 |
| KR102493894B1 (ko) | 2016-02-29 | 2023-01-31 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 tmprss 유전자를 갖는 설치류 |
| SI3462853T1 (sl) | 2016-06-03 | 2023-05-31 | Regeneron Pharmaceuticals, Inc. | Glodavci, ki izražajo eksogeno terminalno deoksinukleotidiltransferazo |
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