DK3105253T3 - Anti-Jagged1-antistoffer og fremgangsmåder til anvendelse - Google Patents

Anti-Jagged1-antistoffer og fremgangsmåder til anvendelse Download PDF

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DK3105253T3
DK3105253T3 DK15706124.3T DK15706124T DK3105253T3 DK 3105253 T3 DK3105253 T3 DK 3105253T3 DK 15706124 T DK15706124 T DK 15706124T DK 3105253 T3 DK3105253 T3 DK 3105253T3
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amino acid
antibody
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Yvonne Chinn
Julie Q Hang
Christian W Siebel
Yan Wu
Daniel Lafkas
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Hoffmann La Roche
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Claims (31)

1. Isoleret antistof, der binder sig til humant Jaggedl, hvor antistoffet omfatter en HVR-H1 omfattende aminosyresekvensen ifølge SEQ ID NO: 35 eller 78, en HVR-H2 omfattende aminosyresekvensen ifølge SEQ ID NO: 28 eller 36, en HVR-H3 omfattende aminosyresekvensen ifølge SEQ ID NO: 55 eller 59, hvor X er en hvilken som helst anden aminosyre end S eller H, en HVR-L1 omfattende aminosyresekvensen ifølge SEQ ID NO: 38, en HVR-L2 omfattende aminosyresekvensen ifølge SEQ ID NO: 39 og en HVR-L3 omfattende aminosyresekvensen ifølge SEQ ID NO: 16 eller 40.
2. Isoleret antistof ifølge krav 1, hvor antistoffet omfatter: a) HVR-H1 omfattende aminosyresekvensen ifølge SEQ ID NO: 78, HVR-H2 omfattende aminosyresekvensen ifølge SEQ ID NO: 36, HVR-H3 omfattende aminosyresekvensen ifølge SEQ ID NO: 55, HVR-L1 omfattende aminosyresekvensen ifølge SEQ ID NO: 38, HVR-L2 omfattende aminosyresekvensen ifølge SEQ ID NO: 39 og HVR-L3 omfattende aminosyresekvensen ifølge SEQ ID NO: 40; eller b) HVR-H1 omfattende aminosyresekvensen ifølge SEQ ID NO: 78, HVR-H2 omfattende aminosyresekvensen ifølge SEQ ID NO: 36, HVR-H3 omfattende aminosyresekvensen ifølge SEQ ID NO: 59, HVR-L1 omfattende aminosyresekvensen ifølge SEQ ID NO: 38, HVR-L2 omfattende aminosyresekvensen ifølge SEQ ID NO: 39 og HVR-L3 omfattende aminosyresekvensen ifølge SEQ ID NO: 16; eller c) HVR-H1 omfattende aminosyresekvensen ifølge SEQ ID NO: 78, HVR-H2 omfattende aminosyresekvensen ifølge SEQ ID NO: 28, HVR-H3 omfattende aminosyresekvensen ifølge SEQ ID NO: 59, HVR-L1 omfattende aminosyresekvensen ifølge SEQ ID NO: 38, HVR-L2 omfattende aminosyresekvensen ifølge SEQ ID NO: 39 og HVR-L3 omfattende aminosyresekvensen ifølge SEQ ID NO: 16.
3. Isoleret antistof ifølge et hvilket som helst af de foregående krav, hvor antistoffet omfatter: a) en VH-sekvens, der stemmer mindst 95 % overens med aminosyresekvensen ifølge SEQ ID NO: 54, og en VL-sekvens, der stemmer mindst 95 % overens med aminosyresekvensen ifølge SEQ ID NO: 34; eller b) en VH-sekvens, der stemmer mindst 95 % overens med aminosyresekvensen ifølge SEQ ID NO: 58, og en VL-sekvens, der stemmer mindst 95 % overens med aminosyresekvensen ifølge SEQ ID NO: 10; eller c) en VH-sekvens, der stemmer mindst 95 % overens med aminosyresekvensen ifølge SEQ ID NO: 62, og en VL-sekvens, der stemmer mindst 95 % overens med aminosyresekvensen ifølge SEQ ID NO: 26; eller d) en VH-sekvens ifølge SEQ ID NO: 54 og en VL-sekvens ifølge SEQ ID NO: 34; eller e) en VH-sekvens ifølge SEQ ID NO: 58 og en VL-sekvens ifølge SEQ ID NO: 10; eller f) en VH-sekvens ifølge SEQ ID NO: 62 og en VL-sekvens ifølge SEQ ID NO: 26.
4. Isoleret antistof ifølge krav 3, hvor antistoffet omfatter en VH-sekvens ifølge SEQ ID NO: 54 og en VL-sekvens ifølge SEQ ID NO: 34.
5. Isoleret antistof ifølge krav 4, hvor tungkæden omfatter aminosyresekvensen ifølge SEQ ID NO: 56 eller SEQ ID NO: 57, og letkæden omfatter aminosyresekvensen ifølge SEQ ID NO: 53.
6. Isoleret antistof ifølge et hvilket som helst af de foregående krav, hvor X er valgt blandt A, D, E, G, I, K, L, N, Q, R, T og V.
7. Isoleret antistof ifølge et hvilket som helst af de foregående krav, hvor X er T.
8. Isoleret antistof ifølge et hvilket som helst af de foregående krav, omfattende: a) HVR-H1 omfattende aminosyresekvensen ifølge SEQ ID NO: 78, HVR-H2 omfattende aminosyresekvensen ifølge SEQ ID NO: 36, HVR-H3 omfattende aminosyresekvensen ifølge SEQ ID NO: 37, HVR-L1 omfattende aminosyresekvensen ifølge SEQ ID NO: 38, HVR-L2 omfattende aminosyresekvensen ifølge SEQ ID NO: 39 og HVR-L3 omfattende aminosyresekvensen ifølge SEQ ID NO: 40; eller b) HVR-H1 omfattende aminosyresekvensen ifølge SEQ ID NO: 78, HVR-H2 omfattende aminosyresekvensen ifølge SEQ ID NO: 36, HVR-H3 omfattende aminosyresekvensen ifølge SEQ ID NO: 64, HVR-L1 omfattende aminosyresekvensen ifølge SEQ ID NO: 38, HVR-L2 omfattende aminosyresekvensen ifølge SEQ ID NO: 39 og HVR-L3 omfattende aminosyresekvensen ifølge SEQ ID NO: 16; eller c) HVR-H1 omfattende aminosyresekvensen ifølge SEQ ID NO: 78, HVR-H2 omfattende aminosyresekvensen ifølge SEQ ID NO: 28, HVR-H3 omfattende aminosyresekvensen ifølge SEQ ID NO: 64, HVR-L1 omfattende aminosyresekvensen ifølge SEQ ID NO: 38, HVR-L2 omfattende aminosyresekvensen ifølge SEQ ID NO: 39 og HVR-L3 omfattende aminosyresekvensen ifølge SEQ ID NO: 16; eller d) en VH-sekvens ifølge SEQ ID NO: 33 og en VL-sekvens ifølge SEQ ID NO: 34; eller e) en VH-sekvens ifølge SEQ ID NO: 65 og en VL-sekvens ifølge SEQ ID NO: 10; eller f) en VH-sekvens ifølge SEQ ID NO: 66 og en VL-sekvens ifølge SEQ ID NO: 26.
9. Isoleret antistof ifølge krav 8, hvor antistoffet omfatter en VH-sekvens ifølge SEQ ID NO: 33 og en VL-sekvens ifølge SEQ ID NO: 34.
10. Antistof ifølge et hvilket som helst af de foregående krav, der er et IgGl-antistof i fuld længde.
11. Antistof ifølge krav 10, hvor antistoffet i det væsentlige mangler en effektorfunktion.
12. Antistof ifølge krav 10 hvor tungkæden omfatter en N297G- eller N297A-mutation.
13. Isoleret antistof ifølge krav 8, hvor tungkæden omfatter aminosyresekvensen ifølge SEQ ID NO: 51, og letkæden omfatter aminosyresekvensen ifølge SEQ ID NO: 53.
14. Isoleret antistof ifølge krav 8, hvor tungkæden omfatter aminosyresekvensen ifølge SEQ ID NO: 52, og letkæden omfatter aminosyresekvensen ifølge SEQ ID NO: 53.
15. Antistof ifølge krav 8, hvor antistoffet omfatter: a) en tungkæde omfattende aminosyresekvensen ifølge SEQ ID NO: 69 og en letkæde omfattende aminosyresekvensen ifølge SEQ ID NO: 75; eller b) en tungkæde omfattende aminosyresekvensen ifølge SEQ ID NO: 70 og en letkæde omfattende aminosyresekvensen ifølge SEQ ID NO: 76; eller c) en tungkæde omfattende aminosyresekvensen ifølge SEQ ID NO: 79 og en letkæde omfattende aminosyresekvensen ifølge SEQ ID NO: 75; eller d) en tungkæde omfattende aminosyresekvensen ifølge SEQ ID NO: 80 og en letkæde omfattende aminosyresekvensen ifølge SEQ ID NO: 76.
16. Antistof ifølge et hvilket som helst af de foregående krav, hvor antistoffet er en antagonist for Jaggedl-medieret signalering.
17. Antistof ifølge et hvilket som helst af de foregående krav, hvor antistoffet ikke binder sig til humant Jagged2, og/eller hvor antistoffet ikke binder sig til humant DLL4, og/eller hvor antistoffet ikke binder sig til humant DLL1, og/eller hvor antistoffet ikke binder sig til murint Jagged2, murint DLL4 og/eller murint DLL1.
18. Isoleret nukleinsyre, der koder for antistoffet ifølge et hvilket som helst af de foregående krav.
19. Værtscelle, der omfatter den isolerede nukleinsyre ifølge krav 18.
20. Fremgangsmåde til fremstilling af et antistof, der omfatter dyrkning af værtscellen ifølge krav 19, således at antistoffet fremstilles.
21. Immunkonjugat, der omfatter antistoffet ifølge et hvilket som helst af kravene 1 til 17 og et cytotoksisk middel.
22. Farmaceutisk formulering, der omfattende antistoffet ifølge et hvilket som helst af kravene 1 til 17 og en farmaceutisk acceptabel bærer.
23. Antistof ifølge et hvilket som helst af kravene 1 til 17 eller immunkonjugat ifølge krav 21 til anvendelse som medikament.
24. Antistof ifølge et hvilket som helst af kravene 1 til 17 eller immunkonjugat ifølge krav 21 til anvendelse ved behandling afkræft.
25. Antistof ifølge et hvilket som helst af kravene 1 til 17 til anvendelse ved behandling af allergi, astma, autoimmun sygdom, sygdomme forbundet med bægercellemetaplasi (for eksempel i lungerne) og/eller overskydende slim.
26. Antistof til anvendelse ifølge krav 25 til anvendelse ved behandling en sygdom forbundet med bægercellemetaplasi.
27. Antistof til anvendelse ifølge krav 26 til anvendelse ved behandling af astma, cystisk fibrose, kronisk obstruktiv lungesygdom eller Barretts øsofagus.
28. Antistof til anvendelse ifølge krav 24, hvor kræften er udvalgt blandt brystkræft, lungekræft, hjernekræft, livmoderhalskræft, tyktarmskræft, leverkræft, galdegangskræft, bugspytkirtelkræft, hudkræft samt B-celle- og T-celle-maligniteter.
29. Isoleret antistof ifølge et hvilket som helst af kravene 1 til 17 konjugeret til en markør.
30. Isoleret antistof ifølge krav 29, hvor markøren er en positronemitter, fortrinsvis hvor positronemitteren er 89Zr.
31. Fremgangsmåde til påvisning af humant Jaggedl i en biologisk prøve, der omfatter at bringe den biologiske prøve i kontakt med antistoffet ifølge et hvilket som helst af kravene 1 til 17, 29 og 30 under betingelser, der tillader binding af antistoffet til et naturligt forekommende humant Jaggedl, og at påvise om et kompleks dannes mellem antistoffet og et naturligt forekommende humant Jaggedl i den biologiske prøve.
DK15706124.3T 2014-02-12 2015-02-11 Anti-Jagged1-antistoffer og fremgangsmåder til anvendelse DK3105253T3 (da)

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