DK2691421T3 - Antistoffer mod nyreforbundet antigen 1 og antigenbindende fragmenter deraf - Google Patents
Antistoffer mod nyreforbundet antigen 1 og antigenbindende fragmenter deraf Download PDFInfo
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- DK2691421T3 DK2691421T3 DK12765926.6T DK12765926T DK2691421T3 DK 2691421 T3 DK2691421 T3 DK 2691421T3 DK 12765926 T DK12765926 T DK 12765926T DK 2691421 T3 DK2691421 T3 DK 2691421T3
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Claims (19)
1. Antistof eller antigenbindende fragment deraf, der binder til nyreforbundet antigen 1 (KAAG1) , hvilket antistof omfatter en variabel region af tung kæde, der har: a. en CDRHl-sekvens, der omfatter SEQ ID NO: 5 eller er som vist i SEQ ID NO: 5, b. en CDRH2-sekvens, der omfatter SEQ ID NO: 6 eller er som vist i SEQ ID NO: 6, og c. en CDRH3-sekvens, der omfatter SEQ ID NO: 7 eller er som vist i SEQ ID NO: 7; og en variabel region af let kæde, der har d. en CDRLl-sekvens, der omfatter SEQ ID NO: 8 eller er som vist i SEQ ID NO: 8, e. en CDRL2-sekvens, der omfatter SEQ ID NO: 9 eller er som vist i SEQ ID NO: 9, og f. en CDRL3-sekvens, der omfatter SEQ ID NO: 10 eller er som vist i SEQ ID NO: 10.
2. Antistof eller antigenbindende fragment deraf ifølge krav 1, hvor den variable region af tung kæde er som vist i SEQ ID NO: 35, SEQ ID NO: 36 eller SEQ ID NO: 37, og/eller hvor den variable region af let kæde er som vist i SEQ ID NO: 30, SEQ ID NO: 31 eller SEQ ID NO: 32.
3. Antistof eller antigenbindende fragment deraf ifølge krav 1, hvor den variable region af tung kæde er som vist i SEQ ID NO: 41, SEQ ID NO: 38, SEQ ID NO: 39 eller SEQ ID NO: 40, og/eller hvor den variable region af let kæde er som vist i SEQ ID NO: 33 eller SEQ ID NO: 34.
4. Antistof eller antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 3, hvor antistoffet omfatter den tunge kæde som vist i SEQ ID NO: 49, SEQ ID NO: 46, SEQ ID NO: 47 eller SEQ ID NO: 48, og/eller den lette kæde som vist i SEQ ID NO: 43 eller SEQ ID NO: 44.
5. Antistof eller antigenbindende fragment deraf ifølge krav 1 eller 3, hvor antistoffet eller det antigenbindende fragment deraf omfatter: a. den variable region af tung kæde som vist i SEQ ID NO: 41 og den variable region af let kæde som vist i SEQ ID NO: 33; b. den tunge kæde som vist i SEQ ID NO: 4 9 og den lette kæde som vist i SEQ ID NO: 43; c. den variable region af tung kæde som vist i SEQ ID NO: 38 og den variable region af let kæde som vist i SEQ ID NO: 33; d. den tunge kæde som vist i SEQ ID NO: 4 6 og den lette kæde som vist i SEQ ID NO: 43; e. den variable region af tung kæde som vist i SEQ ID NO: 39 og den variable region af let kæde som vist i SEQ ID NO: 33; f. den tunge kæde som vist i SEQ ID NO: 47 og den lette kæde som vist i SEQ ID NO: 43; g. den variable region af tung kæde som vist i SEQ ID NO: 40 og den variable region af let kæde som vist i SEQ ID NO: 33; h. den tunge kæde som vist i SEQ ID NO: 48 og den lette kæde som vist i SEQ ID NO: 43; i. den variable region af tung kæde som vist i SEQ ID NO: 41 og den variable region af let kæde som vist i SEQ ID NO: 34; j. den tunge kæde som vist i SEQ ID NO: 4 9 og den lette kæde som vist i SEQ ID NO: 44; k. den variable region af tung kæde som vist i SEQ ID NO: 38 og den variable region af let kæde som vist i SEQ ID NO: 34; l. den tunge kæde som vist i SEQ ID NO: 4 6 og den lette kæde som vist i SEQ ID NO: 44; m. den variable region af tung kæde som vist i SEQ ID NO: 39 og den variable region af let kæde som vist i SEQ ID NO: 34; n. den tunge kæde som vist i SEQ ID NO: 47 og den lette kæde som vist i SEQ ID NO: 44; o. den variable region af tung kæde som vist i SEQ ID NO: 40 og den variable region af let kæde som vist i SEQ ID NO: 34; p. den tunge kæde som vist i SEQ ID NO: 48 og den lette kæde som vist i SEQ ID NO: 44; q. den variable region af tung kæde som vist i SEQ ID NO: 2 og den variable region af let kæde som vist i SEQ ID NO: 4; eller r. den tunge kæde som vist i SEQ ID NO: 45 og den lette kæde som vist i SEQ ID NO: 42.
6. Antistof eller antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 5, hvor antistoffet eller det antigenbindende fragment deraf er konjugeret med en terapeutisk del, et cytotoksisk middel eller med en påviselig del.
7. Antistof eller antigenbindende fragment deraf ifølge krav 6, hvor det cytotoksiske middel omfatter et auristatin.
8. Antistof eller antigenbindende fragment deraf ifølge krav 7, hvor auristatin omfatter monomethylauristatin E eller monomethylauristatin F.
9. Nukleinsyre, der koder for (i) en variabel region af let kæde og en variabel region af tung kæde af antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 5; eller (ii) en let kæde og en tung kæde af antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 5.
10. Vektor, der omfatter nukleinsyren ifølge krav 9.
11. Isoleret celle, der omfatter (i) nukleinsyren ifølge krav 9; (ii) en vektor, der omfatter et nukleinsyremolekyle, der koder for en variabel region af let kæde og en variabel region af tung kæde af antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravne 1 til 5; (iii) en vektor, der omfatter et nukleinsyremolekyle, der koder for en variabel region af let kæde af antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 5, og en vektor, der omfatter et nukleinsyremolekyle, der koder for en variabel region af tung kæde af antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 5; (iv) en vektor, der omfatter et nukleinsyremolekyle, der koder for en let kæde og en tung kæde af antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravne 1 til 5; (v) en vektor, der omfatter et nukleinsyremolekyle, der koder for en let kæde af antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 5, og en vektor, der omfatter et nukleinsyremolekyle, der koder for en tung kæde af antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 5; eller (vi) antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 8.
12. Farmaceutisk sammensætning, der omfatter antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 8 og et farmaceutisk acceptabelt bæremateriale.
13. Ex vivo-anvendelse af et antistof eller et antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 8 til påvisning af en tumor eller til diagnosticering af cancer, hvor tumoren eller canceren omfatter celler, der udtrykker KAAGl eller en KAAGl-variant.
14. Antistof eller antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 8 til anvendelse til in vivo-påvisning af en tumor eller til in vivo-diagnosticering af cancer, hvor tumoren eller canceren omfatter celler, der udtrykker KAAGl eller en KAAGl-variant.
15. Antistof eller antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 8 til anvendelse til behandling af cancer, der omfatter celler, der udtrykker KAAGl eller en KAAGl-variant.
16. Anvendelse af antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 8 til in vitro-påvisning af celler, der udtrykker KAAGl eller en KAAGl-variant.
17. Anvendelse ifølge krav 13 eller antistof eller antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 8 til anvendelse ifølge krav 14 eller krav 15, hvor canceren er udvalgt fra gruppen, der består af ovariecancer, hudcancer, nyrecancer, colorektal cancer, sarkom, leukæmi, hjernecancer, thyreoideacancer, brystcancer, prostatacancer, øsofageal cancer, blærecancer, lungecancer, hoved- og halscancer, metastatisk ovariecancer, metastatisk hudcancer, metastatisk nyrecancer, metastatisk colorektal cancer, metastatisk sarkom, metastatisk leukæmi, metastatisk hjernecancer, metastatisk thyreoideacancer, metastatisk brystcancer, metastatisk prostatacancer, metastatisk øsofageal cancer, metastatisk blærecancer, metastatisk lungecancer og metastatisk hoved- og halscancer.
18. Kit, der omfatter antistoffet eller det antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1 til 8.
19. Fremgangsmåde til fremstilling af et antistof ifølge et hvilket som helst af kravene 1 til 5, hvilken fremgangsmåde omfatter ekspression af et polypeptid eller RNA fra nukleotidsekvensen, der er i stand til at kode for lette og tunge immunoglobulinkæder af antistoffet i et værtscellesystem.
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