DK3126381T3 - Claudin-6-specifikke immunoreceptorer og t-celleepitoper - Google Patents

Claudin-6-specifikke immunoreceptorer og t-celleepitoper Download PDF

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DK3126381T3
DK3126381T3 DK15712657.4T DK15712657T DK3126381T3 DK 3126381 T3 DK3126381 T3 DK 3126381T3 DK 15712657 T DK15712657 T DK 15712657T DK 3126381 T3 DK3126381 T3 DK 3126381T3
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cell
cells
cldn6
antigen
cell receptor
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DK3126381T4 (da
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Ugur Sahin
Özlem Türeci
Petra Simon
Ralf-Holger Voss
Andrea Breitkreuz
Kathleen Hobohm
Tana Omokoko
Holger Hoff
Karolina Anna Mroz
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Biontech Cell&Gene Therapies Gmbh
Tron Translationale Onkologie An Der Univ Der Johannes Gutenberg Univ Mainz Gemeinnuetzige Gmbh
Ganymed Pharmaceuticals Gmbh
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Claims (19)

1. Peptid, der omfatter en aminosyresekvens valgt fra gruppen bestående af SEQ ID NO: 3, 4 og 5, hvor peptidet er 100 eller færre, 50 eller færre, 20 eller færre eller 10 eller færre aminosyrer langt.
2. Peptid ifølge krav 1, der består af aminosyresekvensen valgt fra gruppen bestående af SEQ ID NO: 3, 4 og 5.
3. Nukleinsyre, der omfatter en nukleotidsekvens, der koder for peptidet ifølge krav 1 eller 2, hvor nukleinsyren fortrinsvis er en rekombinant nukleinsyre.
4. Celle, der omfatter nukleinsyren ifølge krav 3, fortrinsvis en celle, der repræsenterer peptidet ifølge krav 1 eller 2 eller et procesprodukt deraf.
5. T-cellereceptor, der specifikt binder til et peptid ifølge krav 1 eller 2, eventuelt i et kompleks med et MHC-molekyle, hvor T-cellereceptoren er valgt fra gruppen bestående af: (I) en T-cellereceptor, der omfatter: (i) en T-cellereceptors α-kæde, der omfatter alle tre CDR-sekvenseme af T-cellereceptorens a-kæde ifølge SEQ ID NO: x, og (ii) en T-cellereceptors β-kæde, der omfatter alle tre CDR-sekvenseme af en T-cellereceptors β-kæde ifølge SEQ ID NO: x+1; hvor x valgt fra gruppen bestående af 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 og 28 og (II) en T-cellereceptor, der omfatter: (i) en T-cellereceptors α-kæde, der omfatter T-cellereceptoren α-kædesekvens af SEQ ID NO: x, og (ii) en T-cellereceptors β-kæde, der omfatter T-cellereceptorens β-kædesekvens af SEQ ID NO: x+1; hvor x valgt fra gruppen bestående af 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 og 28.
6. Kunstig T-cellereceptor, der specifikt binder til claudin-6 (CLDN6), hvor den kunstige T-cellereceptor omfatter et bindingsdomæne for CLDN6, et transmembrandomæne og en T-cellesignaleringsdomæne, hvor bindingsdomænet for CLDN6 omfatter et variabelt område af en tungkæde af et immunoglobulin (VH) med en specificitet for CLDN6 (VH(CLDN6)) og et variabelt område af en letkæde af et immunoglobulin (VL) med en specificitet for CLDN6 (VL(CLDN6)), hvor bindingsdomænet for CLDN6 omfatter et VH(CLDN6), der omfatter en aminosyresekvens repræsenteret ved SEQ ID NO; 32 og et VL(CLDN6), der omfatter en aminosyresekvens repræsenteret ved SEQ ID NO: 33, 38 eller 39, hvor T-cellesignaleringsdomænet omfatter endodomænet af CD3-zeta, eventuelt i kombination med CD28.
7. Kunstig T-cellereceptor ifølge krav 6, hvor bindingsdomænet for CLDN6 omfatter et VH(CLDN6), der omfatter en aminosyresekvens repræsenteret ved SEQ ID NO: 32, og et VL(CLDN6), der omfatter en aminosyresekvens repræsenteret ved SEQ ID NO: 39.
8. Kunstig T-cellereceptor ifølge krav 6 eller 7, hvor bindingsdomænet for CLDN6 omfatter en aminosyresekvens repræsenteret ved SEQ ID NO: 40.
9. Kunstig T-cellereceptor ifølge et hvilket som helst af kravene 6 til 8, der omfatter et afstandsområde, der binder bindingsdomænet for CLDN6 til transmembrandomænet.
10. Kunstig T-cellereceptor ifølge et hvilket som helst af kravene 6 til 9, der omfatter strukturen: NH2 - signalpeptid - bindingsdomæne for CLDN6 - afstandsområde - transmembrandomæne - T-cellesignaleringsdomæne - COOH.
11. Kunstig T-cellereceptor ifølge et hvilket som helst af kravene 6 til 10, der omfatter aminosyresekvensen ifølge SEQ ID NO: 46.
12. Nukleinsyre, der omfatter en nukleotidsekvens, der koder for T-cellereceptoren ifølge krav 5, eller der koder for den kunstige T-cellereceptor ifølge et hvilket som helst af kravene 6 til 11.
13. Celle, der omfatter T-cellereceptoren ifølge krav 5, eller kunstig T-cellereceptor ifølge et hvilket som helst af kravene 6 til 11, og/eller der omfatter en nukleinsyre, der omfatter en nukleotidsekvens, der koder for T-cellereceptoren eller koder for den kunstige T-cellereceptor.
14. Fremgangsmåde til fremstilling af en immunreaktiv celle, der omfatter trinnet med transduktion af en T-celle med en nukleinsyre ifølge krav 12.
15. Farmaceutisk sammensætning, der omfatter en eller flere af: (i) peptidet ifølge krav 1 eller 2; (ii) nukleinsyren ifølge krav 3 eller 12; (iii) cellen ifølge krav 4 eller 13; (iv) T-cellereceptoren ifølge krav 5 og (v) den kunstige T-cellereceptor ifølge et hvilket som helst af kravene 6 til 11, der fortrinsvis endvidere omfatter en farmaceutisk acceptabel bærer.
16. Farmaceutisk sammensætning som defineret i krav 15 til anvendelse i terapi, fortrinsvis (a) til anvendelse i en fremgangsmåde til behandling eller forebyggelse af en cancersygdom eller (b) til anvendelse i en fremgangsmåde til induktion af et immunrespons hos et individ, hvilken fremgangsmåde omfatter administration til individet af den farmaceutiske sammensætning.
17. Fremgangsmåde ex vivo til stimulering, priming og/eller ekspansion af T-celler omfattende at bringe T-celler i kontakt med et/en eller flere af: peptid ifølge krav 1 eller 2, nukleinsyre ifølge krav 3 og/eller celle ifølge krav 4.
18. Peptid ifølge krav 1 eller 2, nukleinsyre ifølge krav 3 eller 12, celle ifølge krav 4 og 13, T-cellereceptor ifølge krav 5, eller kunstig T-cellereceptor ifølge et hvilket som helst af kravene 6 til 11, til anvendelse i en fremgangsmåde til eliminering af cancerceller hos et individ, der omfatter trinnet med tilvejebringelse til individet af en terapeutisk virksom mængde af peptidet, nukleinsyren, cellen, T-cellereceptoren eller den kunstige T-cellereceptor.
19. Fremgangsmåde til bestemmelse af et immunrespons hos et individ, omfattende bestemmelse af T-celler, der er reaktive med et peptid ifølge krav 1 eller 2 i en biologisk prøve isoleret fra individet.
DK15712657.4T 2014-04-01 2015-03-30 Claudin-6-specifikke immunoreceptorer og t-celleepitoper DK3126381T4 (da)

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EP2014000868 2014-04-01
EP2014072864 2014-10-24
PCT/EP2015/056899 WO2015150327A1 (en) 2014-04-01 2015-03-30 Claudin-6-specific immunoreceptors and t cell epitopes

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EP (3) EP3126381B2 (da)
JP (3) JP6726656B2 (da)
CN (3) CN106459165B (da)
AU (3) AU2015239683B2 (da)
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CA (1) CA2942459C (da)
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HR (1) HRP20190472T4 (da)
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