HRP20202034T1 - Neljudske životinje s genom za humanizirani diferencijacijski biljeg cd274 - Google Patents
Neljudske životinje s genom za humanizirani diferencijacijski biljeg cd274 Download PDFInfo
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- HRP20202034T1 HRP20202034T1 HRP20202034TT HRP20202034T HRP20202034T1 HR P20202034 T1 HRP20202034 T1 HR P20202034T1 HR P20202034T T HRP20202034T T HR P20202034TT HR P20202034 T HRP20202034 T HR P20202034T HR P20202034 T1 HRP20202034 T1 HR P20202034T1
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- Prior art keywords
- rodent
- polypeptide
- humanized
- gene
- endogenous
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- 108090000623 proteins and genes Proteins 0.000 title claims 12
- 230000004069 differentiation Effects 0.000 title claims 2
- 241001465754 Metazoa Species 0.000 title 1
- 241000283984 Rodentia Species 0.000 claims 49
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 16
- 150000007523 nucleic acids Chemical group 0.000 claims 16
- 229920001184 polypeptide Polymers 0.000 claims 16
- 102000004196 processed proteins & peptides Human genes 0.000 claims 16
- 108090000765 processed proteins & peptides Proteins 0.000 claims 16
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 claims 13
- 210000004027 cell Anatomy 0.000 claims 11
- 102000048776 human CD274 Human genes 0.000 claims 11
- 238000000034 method Methods 0.000 claims 11
- 101150091609 CD274 gene Proteins 0.000 claims 9
- 101100407305 Homo sapiens CD274 gene Proteins 0.000 claims 9
- 230000003834 intracellular effect Effects 0.000 claims 7
- 239000003814 drug Substances 0.000 claims 5
- 229940079593 drug Drugs 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 210000001161 mammalian embryo Anatomy 0.000 claims 3
- 210000001671 embryonic stem cell Anatomy 0.000 claims 2
- 230000004614 tumor growth Effects 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 1
- 238000003782 apoptosis assay Methods 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 230000005522 programmed cell death Effects 0.000 claims 1
- 238000012216 screening Methods 0.000 claims 1
- 210000004881 tumor cell Anatomy 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
- A01K67/027—New breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Humanized animals, e.g. knockin
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/02—Animal zootechnically ameliorated
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; 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
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
Claims (15)
1. Genetički modificirani glodavac čiji genom sadrži gen za humanizirani diferencijacijski biljeg 274 (CD274) koji kodira humanizirani polipeptid liganda 1 za programiranu staničnu smrt (PD-L1) na lokusu endogenog CD274, naznačen time što navedeni gen za humanizirani CD274 sadrži nukleinskokiselinski slijed koji kodira izvanstanični slijed ljudskog polipeptida PD-L1, operabilno vezan na
(i) nukleinskokiselinski slijed koji kodira unutarstanični slijed i transmembranski slijed endogenog glodavačkog polipeptida PD-L1, i
(ii) promotor endogenog glodavačkog CD274;
te što navedeni glodavac eksprimira humanizirani polipeptid PD-L1 na površini stanice navedenog glodavca.
2. Genetički modificirani glodavac u skladu s patentnim zahtjevom 1, naznačen time što nukleinskokiselinski slijed koji kodira unutarstanični slijed i transmembranski slijed endogenog glodavačkog polipeptida PD-L1 sadrži ekson 6, ekson 7, te dio eksona 5 iz gena za endogeni glodavački CD274, gdje gen za humanizirani CD274 može dodatno sadržavati ekson 1 i ekson 2 iz gena za endogeni glodavački CD274.
3. Genetički modificirani glodavac u skladu s patentnim zahtjevom 2, naznačen time što nukleinskokiselinski slijed koji kodira izvanstanični slijed ljudskog polipeptida PD-L1 sadrži ekson 3, ekson 4, te dio eksona 5 iz ljudskog gena CD274.
4. Izolirana glodavačka stanica ili tkivo čiji genom sadrži gen za humanizirani CD274 koji kodira humanizirani PD-L1 polipeptid na lokusu endogenog CD274, naznačeni time što navedeni gen za humanizirani CD274 sadrži nukleinskokiselinski slijed koji kodira izvanstanični slijed ljudskog polipeptida PD-L1, operabilno vezan na
(i) nukleinskokiselinski slijed koji kodira unutarstanični slijed i transmembranski slijed endogenog glodavačkog polipeptida PD-L1, i
(ii) promotor endogenog glodavačkog CD274; i
gdje izolirana glodavačka stanica ili tkivo eksprimira humanizirani polipeptid PD-L1 na površini navedene stanice ili na površini stanice navedenog tkiva.
5. Izolirana glodavačka embrijska matična (ES) stanica čiji genom sadrži gen za humanizirani CD274 koji kodira humanizirani polipeptid PD-L1 na lokusu endogenog CD274, naznačena time što navedeni gen za humanizirani CD274 sadrži nukleinskokiselinski slijed koji kodira izvanstanični slijed ljudskog polipeptida PD-L1, operabilno vezan na
(i) nukleinskokiselinski slijed koji kodira unutarstanični slijed i transmembranski slijed endogenog glodavačkog polipeptida PD-L1, i
(ii) promotor endogenog glodavačkog CD274.
6. Glodavački embrij dobiven iz embrijske matične stanice u skladu s patentnim zahtjevom 5, naznačen time što navedeni embrij sadrži gen za humanizirani CD274 na njegovom lokusu endogenog CD274.
7. Postupak dobivanja genetički modificiranog glodavca, naznačen time što obuhvaća
(a) ubacivanje nukleinskokiselinskog slijeda koji kodira izvanstanični slijed ljudskog polipeptida PD-L1 u gen za endogeni glodavački CD274 u izoliranoj glodavačkoj ES stanici; i
(b) dobivanje glodavca uz pomoć glodavačke ES stanice iz (a), gdje genom glodavca sadrži gen za humanizirani CD274 koji kodira humanizirani polipeptid PD-L1 na lokusu endogenog glodavačkog CD274, gdje navedeni gen za humanizirani CD274 sadrži nukleinskokiselinski slijed koji kodira izvanstanični slijed ljudskog polipeptida PD-L1, operabilno vezan na
(i) nukleinskokiselinski slijed koji kodira unutarstanični slijed i transmembranski slijed endogenog glodavačkog polipeptida PD-L1, i
(ii) promotor endogenog glodavačkog CD274; i
gdje glodavac eksprimira humanizirani polipeptid PD-L1 na površini stanice navedenog glodavca.
8. Postupak dobivanja genetički modificiranog glodavca čiji genom sadrži gen za humanizirani CD274 koji kodira humanizirani polipeptid PD-L1, naznačen time što postupak obuhvaća
modificiranje genoma glodavca tako da modificirani genom sadrži gen za humanizirani CD274 na lokusu endogenog CD274, gdje navedeni gen za humanizirani CD274 sadrži nukleinskokiselinski slijed koji kodira izvanstanični slijed ljudskog polipeptida PD-L1, operabilno vezan na
(i) nukleinskokiselinski slijed koji kodira unutarstanični slijed i transmembranski slijed endogenog glodavačkog polipeptida PD-L1, i
(ii) promotor endogenog glodavačkog CD274; i
gdje glodavac eksprimira humanizirani polipeptid PD-L1 na površini stanice navedenog glodavca.
9. Postupak u skladu s patentnim zahtjevom 7 ili 8, naznačen time što nukleinskokiselinski slijed koji kodira izvanstanični slijed ljudskog polipeptida PD-L1 sadrži ekson 3, ekson 4, te dio eksona 5 iz ljudskog gena CD274.
10. Postupak u skladu s patentnim zahtjevom 7 ili 8, naznačen time što nukleinskokiselinski slijed koji kodira izvanstanični slijed ljudskog polipeptida PD-L1 kodira aminokiseline 19-238 ljudskog polipeptida PD-L1.
11. Postupak u skladu s patentnim zahtjevom 7 ili 8, naznačen time što nukleinskokiselinski slijed koji kodira unutarstanični slijed i transmembranski slijed endogenog glodavačkog polipeptida PD-L1 sadrži ekson 6, ekson 7, te dio eksona 5 iz gena za endogeni glodavački CD274, gdje gen za humanizirani CD274 može dodatno sadržavati ekson 1 i ekson 2 iz gena za endogeni glodavački CD274.
12. Postupak probiranja lijeka koji može liječiti tumor, naznačen time što postupak obuhvaća
(a) primjenu tumorskih stanica na glodavcu u skladu s patentnim zahtjevom 1, gdje je glodavac homozigotan za gen za humanizirani CD274, tako da u glodavcu nastane tumor,
(b) primjenu lijeka na glodavcu iz koraka (a); i
(c) određivanje je li rast tumora smanjen kod glodavca iz koraka (b), gdje lijek koji smanjuje rast tumora može liječiti tumor.
13. Postupak u skladu s patentnim zahtjevom 12, naznačen time što je lijek protutijelo usmjereno protiv ljudskog polipeptida PD-L1.
14. Postupak u skladu s patentnim zahtjevom 12 ili 13, naznačen time što se lijek na glodavcu primijenjuje intravenski, intraperitonealno, intramuskularno ili supkutano.
15. Genetički modificirani glodavac u skladu s bilo kojim od patentnih zahtjeva 1 do 3, izolirana glodavačka stanica ili tkivo u skladu s patentnim zahtjevom 4, izolirana glodavačka embrijska matična stanica u skladu s patentnim zahtjevom 5, glodavački embrij u skladu s patentnim zahtjevom 6, ili postupak u skladu s bilo kojim od patentnih zahtjeva 7 do 14, naznačeni time što je glodavac miš ili štakor.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462089549P | 2014-12-09 | 2014-12-09 | |
| US201562106525P | 2015-01-22 | 2015-01-22 | |
| PCT/US2015/064626 WO2016094481A1 (en) | 2014-12-09 | 2015-12-09 | Non-human animals having a humanized cluster of differentiation 274 gene |
| EP15816631.4A EP3230320B1 (en) | 2014-12-09 | 2015-12-09 | Non-human animals having a humanized cluster of differentiation 274 gene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20202034T1 true HRP20202034T1 (hr) | 2021-02-19 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20202034TT HRP20202034T1 (hr) | 2014-12-09 | 2020-12-18 | Neljudske životinje s genom za humanizirani diferencijacijski biljeg cd274 |
Country Status (23)
| Country | Link |
|---|---|
| US (3) | US9913461B2 (hr) |
| EP (2) | EP3230320B1 (hr) |
| JP (3) | JP2018500896A (hr) |
| KR (2) | KR102316842B1 (hr) |
| CN (2) | CN107257624B (hr) |
| AU (2) | AU2015360667B2 (hr) |
| BR (1) | BR112017011982A2 (hr) |
| CA (1) | CA2968675C (hr) |
| CY (1) | CY1123723T1 (hr) |
| DK (1) | DK3230320T3 (hr) |
| ES (1) | ES2841353T3 (hr) |
| HR (1) | HRP20202034T1 (hr) |
| HU (1) | HUE052606T2 (hr) |
| IL (3) | IL282649B (hr) |
| LT (1) | LT3230320T (hr) |
| MX (1) | MX2017007636A (hr) |
| PT (1) | PT3230320T (hr) |
| RS (1) | RS61218B1 (hr) |
| RU (1) | RU2711729C2 (hr) |
| SG (2) | SG10202100792XA (hr) |
| SI (1) | SI3230320T1 (hr) |
| WO (1) | WO2016094481A1 (hr) |
| ZA (1) | ZA201703263B (hr) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| HUE052606T2 (hu) | 2014-12-09 | 2021-05-28 | Regeneron Pharma | Humanizált differenciációs klaszter 274 génnel rendelkezõ nem humán állatok |
| WO2017087780A1 (en) | 2015-11-20 | 2017-05-26 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized lymphocyte-activation gene 3 |
| WO2017136712A1 (en) | 2016-02-04 | 2017-08-10 | Regeneron Pharmaceuticals, Inc. | Non-human animals having an engineered angptl8 gene |
| AU2017228293B2 (en) | 2016-02-29 | 2023-05-25 | Regeneron Pharmaceuticals, Inc. | Rodents having a humanized Tmprss gene |
| DK3476865T3 (da) | 2016-06-28 | 2023-12-18 | Biocytogen Pharmaceuticals Beijing Co Ltd | Fremgangsmåde til konstruktion af pd-1-gen-modificeret humaniseret dyremodel og anvendelse deraf |
| DK3507373T3 (da) | 2016-08-31 | 2023-10-30 | Biocytogen Pharmaceuticals Beijing Co Ltd | Genetisk modificeret ikke-menneskeligt dyr med human eller kimær pd-l1 |
| 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 |
| CN107815466B (zh) | 2016-08-31 | 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 |
| WO2018041120A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric tigit |
| AU2017367734A1 (en) | 2016-12-01 | 2019-06-20 | Regeneron Pharmaceuticals, Inc. | Radiolabeled anti-PD-l1 antibodies for immuno-PET imaging |
| CN109666701B (zh) * | 2017-10-13 | 2021-08-24 | 百奥赛图(北京)医药科技股份有限公司 | 一种pd-1基因修饰人源化动物模型的构建方法及其应用 |
| WO2019072241A1 (en) * | 2017-10-13 | 2019-04-18 | Beijing Biocytogen Co., Ltd | NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC |
| EP3585164B1 (en) | 2017-11-30 | 2023-12-27 | Regeneron Pharmaceuticals, Inc. | Rats comprising a humanized trkb locus |
| SG11202008620VA (en) | 2018-03-26 | 2020-10-29 | Regeneron Pharma | Humanized rodents for testing therapeutic agents |
| CN112638154B (zh) | 2018-07-16 | 2022-10-18 | 瑞泽恩制药公司 | Ditra疾病的非人动物模型及其用途 |
| CN110846321B (zh) * | 2018-08-21 | 2021-11-19 | 中国科学院动物研究所 | 一种突变基因及其用于构建斑色鱼鳞癣小型猪模型的用途 |
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