HRP20151130T1 - Fuzijski protein koji sadrži domenu kaspaze i vezujuä†u domenu nuklearnog hormonskog receptora te uz njega vezani postupci i uporabe - Google Patents

Fuzijski protein koji sadrži domenu kaspaze i vezujuä†u domenu nuklearnog hormonskog receptora te uz njega vezani postupci i uporabe Download PDF

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HRP20151130T1
HRP20151130T1 HRP20151130TT HRP20151130T HRP20151130T1 HR P20151130 T1 HRP20151130 T1 HR P20151130T1 HR P20151130T T HRP20151130T T HR P20151130TT HR P20151130 T HRP20151130 T HR P20151130T HR P20151130 T1 HRP20151130 T1 HR P20151130T1
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caspase
domain
ligand
fusion protein
receptor
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HRP20151130TT
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Yuanyuan Chu
Ralf KĂĽhn
Wolfgang Wurst
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Helmholtz Zentrum MĂĽnchen Deutsches Forschungszentrum fĂĽr Gesundheit und Umwelt (GmbH)
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    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6472Cysteine endopeptidases (3.4.22)
    • C12N9/6475Interleukin 1-beta convertase-like enzymes (3.4.22.10; 3.4.22.36; 3.4.22.63)
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P35/00Antineoplastic agents
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    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/72Receptors; Cell surface antigens; Cell surface determinants for hormones
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/72Receptors; Cell surface antigens; Cell surface determinants for hormones
    • C07K14/721Steroid/thyroid hormone superfamily, e.g. GR, EcR, androgen receptor, oestrogen receptor
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide

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Claims (17)

1. Fuzijski protein koji obuhvaća (a) domenu kaspaze koja može inducirati apoptozu i (b) domenu koja kao ligand veže nuklearni hormonski receptor, pri čemu se domena koja kao ligand veže nuklearni hormonski receptor aktivira nakon vezanja liganda za domenu koja kao ligand veže nuklearni receptor.
2. Fuzijski protein prema zahtjevu 1, a) gdje nakon što se ligand izloži domeni koja kao ligand veže nuklearni hormonski receptor, fuzijski protein može inducirati apoptozu u stanici, poželjno eukariotskoj stanici, koja eksprimira fuzijski protein; i/ili b) gdje domena kaspaze jest kaspaza, izabrana iz grupe koja obuhvaća Kaspazu-2, Kaspazu-3, Kaspazu-6, Kaspazu-7, Kaspazu-8, Kaspazu-9, Kaspazu-10, Kaspazu-12, najpoželjnije Kaspazu-8 ili Kaspazu-9 i/ili; c) gdje se nuklearni hormonski receptor izabire iz grupe koja obuhvaća Estrogenski receptor, progesteronski receptor, glukokortikoidni receptor, androgeni receptor i/ili d) gdje je domena koja kao ligand veže nuklearni hormonski receptor vezana za N-kraj ili C-kraj domene kaspaze, poželjno gdje je domena koja kao ligand veže nuklearni hormonski receptor vezana za C-kraj domene kaspaze; i/ili e) gdje je domena koja kao ligand veže nuklearni hormonski receptor vezana izravno za domenu kaspaze.
3. Fuzijski protein prema zahtjevu 2, a) gdje je kaspaza od sisavaca, kaspaza od glodavaca ili humana kaspaza, izabrana iz grupe koja obuhvaća Kaspazu-2, Kaspazu-3, Kaspazu-6, Kaspazu-7, Kaspazu-8, Kaspazu-9, Kaspazu-10, Kaspazu-12, najpoželjnije Kaspazu-8 ili Kaspazu-9; i/ili b) gdje domena kaspaze obuhvaća ili se sastoji od aminokiselinske sekvence SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 67 ili SEQ ID NO: 68.
4. Fuzijski protein prema zahtjevu 2, a) gdje nuklearni hormonski receptor jest Estrogenski receptor, i/ili b) gdje receptor jest nuklearni hormonski receptor od sisavca ili humani, izabran iz grupe koja obuhvaća Estrogenski receptor, progesteronski receptor, glukokortikoidni receptor, androgeni receptor i mutant ER(T2) Estrogenskog receptora definirano u SEQ ID NO: 80.
5. Fuzijski protein prema zahtjevu 1 ili 4, gdje domena koja kao ligand veže nuklearni hormonski receptor jest vezana za domenu kaspaze preko poveznice (linker), poželjno a) gdje se linker sastoji od 1 do 100 aminokiselinskih ostataka, posebno se u biti sastoji od neutralnih aminokiselina; i/ili b) gdje linker obuhvaća dio nuklearnog hormonskog receptora D i F sekvenca domene koje su bočne domeni koja veže ligand.
6. Fuzijski protein prema bilo kojem od zahtjeva 1 do 5 koji obuhvaća aminokiselinsku sekvencu, izabranu iz grupe koja obuhvaća SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 29, SEQ ID NO: 32 ili SEQ ID NO: 37.
7. Nukleinska kiselina koja kodira fuzijski protein prema bilo kojem od zahtjeva 1 do 6.
8. Vektor koji obuhvaća nukleinsku kiselinu prema zahtjevu 7.
9. Stanica koja obuhvaća nukleinsku kiselinu prema zahtjevu 7 i/ili vektor prema zahtjevu 8.
10. Postupak proizvodnje fuzijskog proteina prema bilo kojem od zahtjeva 1 do 6 koji obuhvaća - uzgoj kulture stanica prema zahtjevu 9 pod uvjetima koji su pogodni za proizvodnju fuzijskog proteina.
11. Ne-humani transgenični organizam, poželjno ne-humani transgenični sisavac ili riba zebrica, koji sadrži nukleinsku kiselinu prema zahtjevu 7 ili vektor prema zahtjevu 8.
12. Uporaba fuzijskog proteina prema bilo kojem od zahtjeva 1 do 6 za ligandom-posredovanu indukciju apoptoze stanice, poželjno eukariotske stanice, još poželjnije stanice sisavca ili stanice ribe zebrice, posebno humane stanice, gdje uporaba ne uključuje terapijski i/ili dijagnostički postupak.
13. Uporaba prema zahtjevu 12 za ispitivanje funkcije stanica, tkiva i/ili organa, posebno za ispitivanje funkcije stanica u različitim stupnjevima razvoja ili kao model bolesti.
14. In vitro postupak za indukciju apoptoze stanice koja eksprimira fuzijski protein prema bilo kojem od zahtjeva 1 do 6, postupak obuhvaća - dovođenje u doticaj stanične domene koja kao ligand veže nuklearni hormonski receptor s ligandom koji može inducrati apoptozu stanice.
15. In vitro postupak za identifikaciju liganda za domenu koja kao ligand veže nuklearni hormonski receptor ili njegove funkcionalno aktivne varijante, postupak obuhvaća - dovođenje u doticaj stanične domene koja kao ligand veže nuklearni hormonski receptor prema zahtjevu 9 sa supstancom; i - identifikacija supstance kao liganda, ovisno o sposobnosti indukcije apoptoze stanice.
16. Fuzijski protein prema bilo kojem od zahtjeva 1 do 6, nukleinska kiselina prema zahtjevu 7, vektor prema zahtjevu 8 i/ili stanica prema zahtjevu 9 za uporabu kao lijek.
17. Fuzijski protein prema bilo kojem od zahtjeva 1 do 6, nukleinska kiselina prema zahtjevu 7, vektor prema zahtjevu 8 i/ili stanica prema zahtjevu 9 za uporabu u liječenju bolesti gdje je potrebno pojačati apoptozu, posebno za liječenje raka ili kod ili nakon transplantacije, posebno kao sigurnosni mehanizam.
HRP20151130TT 2007-06-21 2015-10-26 Fuzijski protein koji sadrži domenu kaspaze i vezujuä†u domenu nuklearnog hormonskog receptora te uz njega vezani postupci i uporabe HRP20151130T1 (hr)

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Application Number Priority Date Filing Date Title
EP07012138A EP2006376A1 (en) 2007-06-21 2007-06-21 Fusion protein comprising a caspase domain and a nuclear hormone receptor binding domain and methods and uses thereof
PCT/EP2008/005013 WO2008155133A2 (en) 2007-06-21 2008-06-20 Fusion protein comprising a caspase domain and a nuclear hormone receptor binding domain and methods and uses thereof
EP08784530.1A EP2173869B1 (en) 2007-06-21 2008-06-20 Fusion protein comprising a caspase domain and a nuclear hormone receptor binding domain and methods and uses thereof

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HUE025829T2 (en) 2016-04-28
US20110023137A1 (en) 2011-01-27
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US8530168B2 (en) 2013-09-10
EP2173869A2 (en) 2010-04-14
WO2008155133A2 (en) 2008-12-24
EP2006376A1 (en) 2008-12-24
DK2173869T3 (en) 2015-11-16
WO2008155133A3 (en) 2009-04-02
ES2553170T3 (es) 2015-12-04
PT2173869E (pt) 2015-11-23

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