HRP20210824T1 - Neljudske životinje koje imaju humanizirani gen 3 za aktiviranje limfocita - Google Patents
Neljudske životinje koje imaju humanizirani gen 3 za aktiviranje limfocita Download PDFInfo
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- HRP20210824T1 HRP20210824T1 HRP20210824TT HRP20210824T HRP20210824T1 HR P20210824 T1 HRP20210824 T1 HR P20210824T1 HR P20210824T T HRP20210824T T HR P20210824TT HR P20210824 T HRP20210824 T HR P20210824T HR P20210824 T1 HRP20210824 T1 HR P20210824T1
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- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 title claims 13
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 title 1
- 241001465754 Metazoa Species 0.000 title 1
- 101100510617 Caenorhabditis elegans sel-8 gene Proteins 0.000 claims 62
- 241000283984 Rodentia Species 0.000 claims 49
- 229920001184 polypeptide Polymers 0.000 claims 44
- 108090000765 processed proteins & peptides Proteins 0.000 claims 44
- 102000004196 processed proteins & peptides Human genes 0.000 claims 44
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims 9
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims 9
- 238000000034 method Methods 0.000 claims 9
- 108700024394 Exon Proteins 0.000 claims 6
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 claims 5
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 5
- 229940079593 drug Drugs 0.000 claims 5
- 230000003834 intracellular effect Effects 0.000 claims 5
- 102000048362 human PDCD1 Human genes 0.000 claims 4
- 102000017578 LAG3 Human genes 0.000 claims 3
- 101150030213 Lag3 gene Proteins 0.000 claims 3
- 150000001413 amino acids Chemical class 0.000 claims 3
- 230000008685 targeting Effects 0.000 claims 3
- 230000000259 anti-tumor effect Effects 0.000 claims 2
- 239000012634 fragment Substances 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
- 210000001161 mammalian embryo Anatomy 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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- 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
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- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
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- A01K67/0276—Knock-out vertebrates
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Claims (17)
1. Glodavac, naznačen time što mu genom sadrži humanizirani gen Lag-3 na lokusu endogenog Lag-3, gdje navedeni glodavac sadrži humanizirani polipeptid Lag-3 iz navedenog humaniziranog gena Lag-3, gdje navedeni humanizirani polipeptid Lag-3 sadrži: izvanstanični dio koji sadrži prve dvije N-terminalne imunoglobulinu (Ig) slične domene ljudskog polipeptida LAG-3 i posljednje dvije Ig-u slične domene endogenog polipeptida Lag-3; transmembransku domenu endogenog polipeptida Lag-3; i unutarstaničnu domenu endogenog polipeptida Lag-3; i gdje je navedeni glodavac miš ili štakor.
2. Glodavac, naznačen time što mu genom sadrži humanizirani gen Lag-3 na lokusu endogenog Lag-3, gdje navedeni glodavac sadrži humanizirani polipeptid Lag-3 iz navedenog humaniziranog gena Lag-3, gdje navedeni humanizirani polipeptid Lag-3 sadrži prve dvije N-terminalne Ig-u slične domene ljudskog polipeptida LAG-3; gdje humanizirani gen Lag-3 sadrži eksone 1, 5, 6, 7 i 8 endogenog Lag-3; i gdje je navedeni glodavac miš ili štakor.
3. Glodavac u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2, naznačen time što
(a) humanizirani polipeptid Lag-3 sadrži aminokiseline 29-260 ljudskog polipeptida LAG-3; i/ili
(b) glodavac dodatno sadrži humanizirani polipeptid PD-1, gdje navedeni humanizirani polipeptid PD-1 sadrži izvanstanični dio ljudskog polipeptida PD-1 i unutarstanični dio endogenog polipeptida PD-1, gdje izborno
humanizirani polipeptid PD-1 dodatno sadrži transmembranski dio endogenog polipeptida PD-1; i/ili
humanizirani polipeptid PD-1 sadrži aminokiseline 35-145 navedenog ljudskog polipeptida PD-1.
4. Glodavac u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2, naznačen time što je humanizirani gen Lag-3 operabilno spojen s glodavačkim promotorom Lag-3, gdje izborno:
glodavački promotor Lag-3 je endogeni glodavački promotor Lag-3; i/ili
humanizirani gen Lag-3 sadrži eksone 2-4 ljudskog gena LAG-3.
5. Glodavac u skladu s patentnim zahtjevom 4, naznačen time što genom glodavca dodatno sadrži humanizirani gen Pdcd1 koji je operabilno spojen s glodavačkim promotorom Pdcd1 i kodira navedeni humanizirani polipeptid PD-1, gdje izborno:
(a) glodavački promotor Pdcd1 je endogeni glodavački promotor Pdcd1; i/ili
(b) humanizirani gen Pdcd1 sadrži eksone 1, 4 i 5 endogenog Pdcd1, te sadrži ekson 3 endogenog Pdcd1 u cijelosti ili djelomično.
6. Glodavac u skladu s patentnim zahtjevom 5, naznačen time što ljudski dio humaniziranog gena Pdcd1 sadrži ekson 2 ljudskog gena PDCD1, gdje izborno humanizirani gen Pdcd1 dodatno sadrži ekson 3 ljudskog PDCD1 u cijelosti ili djelomično.
7. Humanizirani polipeptid Lag-3, naznačen time što ga proizvodi glodavac u skladu s bilo kojim od patentnih zahtjeva 1-6.
8. Izolirana stanica ili tkivo, naznačeni time što su izolirana stanica ili tkivo glodavca u skladu s bilo kojim od patentnih zahtjeva 1-6.
9. Glodavačka embrijska matična (ES) stanica, naznačena time što njezin genom sadrži humanizirani gen Lag-3 na endogenom lokusu Lag-3 koji kodira humanizirani polipeptid Lag-3, gdje navedeni humanizirani polipeptid Lag-3 sadrži: izvanstanični dio koji sadrži prve dvije N-terminalne Ig-u slične domene ljudskog polipeptida LAG-3 i posljednje dvije Ig-u slične domene endogenog polipeptida Lag-3; transmembransku domenu endogenog polipeptida Lag-3; i unutarstaničnu domenu endogenog glodavačkog polipeptida Lag-3; gdje je humanizirani gen Lag-3 operabilno spojen s glodavačkim promotorom Lag-3, i gdje je navedena glodavačka ES stanica mišja ili štakorska ES stanica.
10. Glodavačka embrijska matična (ES) stanica, naznačena time što njezin genom sadrži humanizirani gen Lag-3 na lokusu endogenog Lag-3 koji kodira humanizirani polipeptid Lag-3, gdje navedeni humanizirani polipeptid Lag-3 sadrži: prve dvije N-terminalne Ig-u slične domene ljudskog polipeptida LAG-3; gdje humanizirani gen Lag-3 sadrži eksone 1, 5, 6, 7 i 8 endogenog Lag-3; gdje je humanizirani gen Lag-3 operabilno spojen s glodavačkim promotorom Lag-3; i gdje je navedena glodavačka ES stanica mišja ili štakorska ES stanica.
11. Glodavački embrij, naznačen time što ga se dobiva iz ES stanice u skladu s patentnim zahtjevom 9 ili patentnim zahtjevom 10.
12. Postupak dobivanja glodavca, naznačen time što se sastoji u:
modificiranju genoma glodavca tako da sadrži humanizirani gen Lag-3 na lokusu endogenog Lag-3, gdje je navedeni humanizirani gen operabilno spojen s glodavačkim promotorom Lag-3, čime se dobije navedeni glodavac, gdje navedeni glodavac sadrži humanizirani polipeptid Lag-3 iz navedenog humaniziranog gena Lag-3, gdje navedeni humanizirani polipeptid Lag-3 sadrži: izvanstanični dio koji sadrži prve dvije N-terminalne Ig-u slične domene ljudskog polipeptida LAG-3 i posljednje dvije Ig-u slične domene endogenog polipeptida Lag-3; transmembransku domenu endogenog polipeptida Lag-3; i unutarstaničnu domenu endogenog polipeptida Lag-3; i gdje je navedeni glodavac miš ili štakor.
13. Postupak dobivanja glodavca, naznačen time što se sastoji u:
modificiranju genoma glodavca tako da sadrži humanizirani gen Lag-3 na lokusu endogenog Lag-3, gdje je navedeni humanizirani gen operabilno spojen s glodavačkim promotorom Lag-3, čime se dobije navedeni glodavac, gdje navedeni glodavac sadrži humanizirani polipeptid Lag-3 iz navedenog humaniziranog gena Lag-3, gdje navedeni humanizirani polipeptid Lag-3 sadrži: prve dvije N-terminalne Ig-u slične domene ljudskog polipeptida LAG-3; i gdje humanizirani gen Lag-3 sadrži eksone 1, 5, 6, 7 i 8 endogenog Lag-3; i gdje je navedeni glodavac miš ili štakor.
14. Postupak u skladu s patentnim zahtjevom 12 ili patentnim zahtjevom 13, naznačen time što je glodavački promotor Lag-3 endogeni glodavački promotor Lag-3.
15. Postupak u skladu s bilo kojim od patentnih zahtjeva 12-14, naznačen time što se postupak sastoji u:
a) integriranju genomskog fragmenta u endogeni gen Lag-3 u glodavačku ES stanicu, gdje navedeni genomski fragment sadrži nukleotidni slijed koji kodira prve dvije N-terminalne Ig-u slične domene navedenog ljudskog polipeptida LAG-3, čime se dobije genetički modificirana glodavačka embrijska matična stanica; i
b) stvaranju glodavca uz upotrebu genetički modificirane glodavačke ES stanice iz (a).
16. Postupak u skladu s bilo kojim od patentnih zahtjeva 12-15, naznačen time što:
(a) humanizirani gen Lag-3 sadrži eksone 2-4 ljudskog gena LAG-3; ili humanizirani gen Lag-3 kodira u najmanju ruku aminokiseline 29-260 navedenog ljudskog polipeptida LAG-3; i/ili
(b) postupak dodatno uključuje modificiranje genoma glodavca tako da sadrži humanizirani gen Pdcd1 koji kodira humanizirani polipeptid PD-1 koji sadrži izvanstanični dio ljudskog polipeptida PD-1 i unutarstanični dio endogenog polipeptida PD-1.
17. Postupak procjenjivanja antitumorske djelotvornosti ili farmakokinetičkih svojstava lijeka koji cilja na ljudski LAG-3, naznačen time što se postupak sastoji u koracima:
primjene lijeka na glodavcu u skladu s bilo kojim od patentnih zahtjeva 1-6; i
provođenja ispitivanja kako bi se odredilo jedno ili više antitumorskih svojstava lijeka koji cilja na ljudski LAG-3, gdje izborno:
(a) lijek koji cilja na ljudski LAG-3 je protutijelo protiv Lag-3; i/ili
(b) lijek koji cilja na ljudski LAG-3 se primjenjuje na glodavcu intravenski, intraperitonealno ili supkutano.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562258181P | 2015-11-20 | 2015-11-20 | |
| US201662370430P | 2016-08-03 | 2016-08-03 | |
| PCT/US2016/062733 WO2017087780A1 (en) | 2015-11-20 | 2016-11-18 | Non-human animals having a humanized lymphocyte-activation gene 3 |
| EP16810152.5A EP3376857B1 (en) | 2015-11-20 | 2016-11-18 | Non-human animals having a humanized lymphocyte-activation gene 3 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20210824T1 true HRP20210824T1 (hr) | 2021-07-09 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20210824TT HRP20210824T1 (hr) | 2015-11-20 | 2021-05-21 | Neljudske životinje koje imaju humanizirani gen 3 za aktiviranje limfocita |
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| Country | Link |
|---|---|
| US (3) | US10306874B2 (hr) |
| EP (1) | EP3376857B1 (hr) |
| JP (1) | JP6997708B2 (hr) |
| KR (1) | KR102454546B1 (hr) |
| CN (1) | CN108366548B (hr) |
| AU (1) | AU2016358101B2 (hr) |
| BR (1) | BR112018010158A2 (hr) |
| CA (1) | CA3003786C (hr) |
| CY (1) | CY1124171T1 (hr) |
| DK (1) | DK3376857T3 (hr) |
| ES (1) | ES2872799T3 (hr) |
| HK (1) | HK1253683A1 (hr) |
| HR (1) | HRP20210824T1 (hr) |
| HU (1) | HUE054612T2 (hr) |
| IL (1) | IL258841B (hr) |
| LT (1) | LT3376857T (hr) |
| MX (1) | MX2018005389A (hr) |
| NZ (1) | NZ742447A (hr) |
| PL (1) | PL3376857T3 (hr) |
| PT (1) | PT3376857T (hr) |
| RS (1) | RS61866B1 (hr) |
| RU (1) | RU2745403C2 (hr) |
| SG (1) | SG11201803409UA (hr) |
| SI (1) | SI3376857T1 (hr) |
| WO (1) | WO2017087780A1 (hr) |
| ZA (1) | ZA201802717B (hr) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2015360667B2 (en) | 2014-12-09 | 2021-09-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized cluster of differentiation 274 gene |
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