HRP20180506T1 - Pripravci i postupci za inhibiranje endogenih imunoglobinskih gena i proizvodnju transgenskih humanih idiotipnih protutijela - Google Patents
Pripravci i postupci za inhibiranje endogenih imunoglobinskih gena i proizvodnju transgenskih humanih idiotipnih protutijela Download PDFInfo
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- HRP20180506T1 HRP20180506T1 HRP20180506TT HRP20180506T HRP20180506T1 HR P20180506 T1 HRP20180506 T1 HR P20180506T1 HR P20180506T T HRP20180506T T HR P20180506TT HR P20180506 T HRP20180506 T HR P20180506T HR P20180506 T1 HRP20180506 T1 HR P20180506T1
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- 238000000034 method Methods 0.000 title claims abstract 16
- 230000009261 transgenic effect Effects 0.000 title claims abstract 15
- 108090000623 proteins and genes Proteins 0.000 title claims 6
- 230000002401 inhibitory effect Effects 0.000 title 1
- 239000000203 mixture Substances 0.000 title 1
- 241001465754 Metazoa Species 0.000 claims abstract 8
- 210000004027 cell Anatomy 0.000 claims 7
- 210000004602 germ cell Anatomy 0.000 claims 7
- 210000001161 mammalian embryo Anatomy 0.000 claims 7
- 210000000287 oocyte Anatomy 0.000 claims 6
- 230000010354 integration Effects 0.000 claims 4
- 230000006801 homologous recombination Effects 0.000 claims 2
- 238000002744 homologous recombination Methods 0.000 claims 2
- 230000001939 inductive effect Effects 0.000 claims 2
- 230000001105 regulatory effect Effects 0.000 claims 2
- 101150097493 D gene Proteins 0.000 claims 1
- 230000007018 DNA scission Effects 0.000 claims 1
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 claims 1
- 101150008942 J gene Proteins 0.000 claims 1
- 241001504654 Mustela nivalis Species 0.000 claims 1
- 241000283984 Rodentia Species 0.000 claims 1
- 101150117115 V gene Proteins 0.000 claims 1
- 230000001413 cellular effect Effects 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 210000001671 embryonic stem cell Anatomy 0.000 claims 1
- 210000002257 embryonic structure Anatomy 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 230000000415 inactivating effect Effects 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 150000007523 nucleic acids Chemical class 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 230000001360 synchronised effect Effects 0.000 claims 1
- 230000008685 targeting Effects 0.000 claims 1
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- A—HUMAN NECESSITIES
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- A01K67/0276—Knock-out vertebrates
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- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
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Claims (16)
1. Postupak za ciljanu integraciju umjetnog imunoglobulinskog (Ig) mjesta u primateljskoj ne-humanoj zametnoj stanici, oplođenoj jajnoj stanici ili embrijima, koji obuhvaća: uvođenje u ne-ljudsku zametnu stanicu primatelja, gnojivo jajne stanice ili embrij mjesto specifične meganukleaze usmjerene na endogeni Ig lokus i transgenski vektor koji sadrži umjetni Ig lokus tako da umjetni Ig lokus integrira u genom primateljske ne-humane zametne stanice, oplođene oocite ili embrije ciljanom integracijom i zamjenjuje endogeni Ig lokus ili njihove dijelove homolognim rekombinacijom; gdje meganukleaza povećavaju učestalost homologne rekombinacije kroz dvostruko DNA cijepanje.
2. Postupak sukladno patentnom zahtjevu 1, naznačena time, da je meganukleaza osigurana u konstruktu ekspresije koju je moguće regulirati.
3. Postupak sukladno patentnom zahtjevu 2, naznačena time, da je meganukleaza operativno povezana s inducibilnim promotorom.
4. Postupak sukladno bilo kojem od patentnih zahtjeva 1 do 3, naznačen time, što se nadalje sastoji od odabira stanice u kojoj je umjetni Ig lokus integriran na ciljano mjesto i u kojem su regulativni konstrukti ekspresije meganukleaze integrirani u genom.
5. Postupak sukladno patentnom zahtjevu 4, naznačena time, da nadalje uključuje spajanje odabrane stanice sa stanicom za nuklearnu prijenosnu jedinicu koja nije ljudska, totipotentna i sposobna za tvorbu funkcionalnog novorođenog tkiva, kako bi se dobila rezultirajuća stanica.
6. Postupak sukladno patentnom zahtjevu 4 ili 5, naznačena time, da je enukleizirana stanična jedinica nuklearnog prijenosa oocit ili embrionalna matična stanica.
7. Postupak sukladno bilo kojem od patentnih zahtjeva 4 do 6, naznačen time, da nadalje sadrži:
I. Injektirane odabrane stanice u razvoj ne-ljudskog embrija; ili
II. kultiviranje rezultirajuće stanice u odgovarajućem mediju i prenošenje u nastalu stanicu u sinkronizirani primatelj za generiranje transgenične ne-humane životinje.
8. Postupak sukladno bilo kojem prethodnom patentnom zahtjevu, naznačen time, da umjetni Ig lokus sadrži fragmente ljudskih i ne-humanih Ig-lokusa.
9. Postupak sukladno bilo kojem prethodnom patentnom zahtjevu, naznačen time, da umjetni Ig lokus sadrži najmanje jedan segment humanog V gena.
10. Postupak sukladno bilo kojem prethodnom patentnom zahtjevu, naznačen time, da umjetni Ig lokus obuhvaća više segmenata imunoglobulinskog gena, pri čemu segmenti gena sadrže najmanje jedan segment genske regije V, jedan ili više segmenata J, jedan ili više segmenata gena D i jednu ili više konstanta regijskih gena.
11. Postupak sukladno bilo kojem prethodnom patentnom zahtjevu, naznačen time, da ciljana sekvenca meganukleaze je prisutna u ili proksimalno za segmente gena odabranih od: J segment gena; i genski segment konstantne regije.
12. Postupak sukladno bilo kojem prethodnom patentnom zahtjevu, naznačen time, da sukladno bilo kojem prethodnom patentnom zahtjevu, nadalje obuhvaća uporabu druge meganukleaze, pri čemu druga meganukleaza prepoznaje drugu ciljnu sekvencu meganukleaze prisutnu u ili proksimalnom endogenom Ig lokusu i selektivno cijepa endogeni Ig lokus zajedno s prvom meganukazom, ali na mjestu različitom od prve meganukleaze, čime se inaktivira najmanje jedan endogeni Ig lokus
13. Transgenska ne-humana životinja, koja se može dobiti metodom sukladno zahtjevu 9, naznačena time, da životinja sadrži:
I. najmanje jedan regulirabilni konstrukt genomskog meganukleaza ekspresije; i
II. umjetni Ig lokus koji zamjenjuje endogeni Ig lokus;
pri čemu je životinja sposobna proizvesti protutijelo koje ima ljudski idiotip.
14. Transgenska životinja sukladno patentnog zahtjevu 13, naznačena time, da je ta životinja odabrana između ptice, glodara, i lasice.
15. Transgenska životinja sukladno patentnom zahtjevu 14, naznačeno time, da je ta životinja štakor.
16. In vitro primjena transgenskog vektora za ciljanu integraciju,
pri čemu transgeni vektor sadrži induskcijsku ekspresijsku kontrolnu regiju koju je moguće
koja je operabilno povezana s nukleinskom kiselinom koja kodira mjesno specifičnu meganukleazu koja cilja endogeni Ig lokus, pri čemu uporaba obuhvaća:
uvođenje transgeničnog vektora u primateljsku ne-ljudsku zametnu stanicu, oplođene oocite ili embrij tako da se transgenski vektor integrira u genom zametne stanice, oplođene oocite ili embrija; i uvođenje transgenskog vektora koji sadrži umjetni Ig lokus u primateljsku ne-humanu zametnu stanicu, oplođeno oocite ili embrij, tako da se umjetni lokus integrira u genom primateljske ne-humane zametne stanice, oplođene oocite ili embrija ciljanom integracijom
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Application Number | Priority Date | Filing Date | Title |
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US94161907P | 2007-06-01 | 2007-06-01 | |
US4432408P | 2008-04-11 | 2008-04-11 | |
EP12187787.2A EP2602323B1 (en) | 2007-06-01 | 2008-05-30 | Compositions and methods for inhibiting endogenous immunoglobin genes and producing transgenic human idiotype antibodies |
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HRP20180506T1 true HRP20180506T1 (hr) | 2018-05-04 |
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HRP20180506TT HRP20180506T1 (hr) | 2007-06-01 | 2018-03-27 | Pripravci i postupci za inhibiranje endogenih imunoglobinskih gena i proizvodnju transgenskih humanih idiotipnih protutijela |
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US (6) | US8703485B2 (hr) |
EP (4) | EP3382022A1 (hr) |
JP (6) | JP5823690B2 (hr) |
KR (4) | KR101886610B1 (hr) |
CN (1) | CN101784664B (hr) |
AT (1) | ATE522611T1 (hr) |
AU (1) | AU2008259939B2 (hr) |
CA (2) | CA2688834C (hr) |
CY (1) | CY1120383T1 (hr) |
DK (3) | DK2152880T3 (hr) |
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HK (1) | HK1135138A1 (hr) |
HR (1) | HRP20180506T1 (hr) |
HU (1) | HUE037302T2 (hr) |
IL (2) | IL202302A (hr) |
LT (1) | LT2602323T (hr) |
NZ (1) | NZ581396A (hr) |
PL (3) | PL2602323T3 (hr) |
PT (3) | PT2336329E (hr) |
SG (2) | SG182144A1 (hr) |
SI (1) | SI2602323T1 (hr) |
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Families Citing this family (98)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2008512987A (ja) | 2004-07-22 | 2008-05-01 | エラスムス・ユニヴァーシティ・メディカル・センター・ロッテルダム | 結合分子 |
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