DK2640742T3 - Samling af antistofsekvenser og disses anvendelser - Google Patents

Samling af antistofsekvenser og disses anvendelser Download PDF

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DK2640742T3
DK2640742T3 DK11785411.7T DK11785411T DK2640742T3 DK 2640742 T3 DK2640742 T3 DK 2640742T3 DK 11785411 T DK11785411 T DK 11785411T DK 2640742 T3 DK2640742 T3 DK 2640742T3
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antibodies
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Yvonne Stark
Ingrid Schuster
Thomas Tiller
Stefanie Urlinger
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Morphosys Ag
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Claims (21)

1. Samling af syntetiske antistoffer eller funktionelle fragmenter deraf, hvor i det mindste 50% af antistoffeme eller funktionelle fragmenter omfatter variable tung kaede- og variable let kaede-par, hvor de strukturelle omrader af de naevnte variable tung kaede- og variable let kaede-par bestar af 25 eller Here kimbane-protein-sekvenser udvalgt blandt de variable tung kaede-par og variable let kaede-par udvisende sekven-serne saledes som defineret ifplge figurer 25-36: VH1-18 (SEQ ID NO: 204)/VKl-39 (SEQ ID NO: 236); VH1-18 (SEQ ID NO: 204)/VK3-15 (SEQ ID NO: 238); VH1-18 (SEQ ID NO: 204)/VK3-20 (SEQ ID NO: 239); VH1-46 (SEQ ID NO: 205)/VK3-15 (SEQ ID NO: 238); VH1-46 (SEQ ID NO: 205)/VLl-51 (SEQ ID NO: 252); VH1-46 (SEQ ID NO: 205)/VL3-21 (SEQ ID NO: 257); VH1-69*01 (SEQ ID NO: 206)/VLl-51 (SEQ ID NO: 252); VH3-07 (SEQ ID NO: 207)/VKl-12 (SEQ ID NO: 233); VH3-07 (SEQ ID NO: 207)/VKl-16 (SEQ ID NO: 234); VH3-07 (SEQ ID NO: 207)/VKl-27 (SEQ ID NO: 235); VH3-07 (SEQ ID NO: 207)/VKl-39 (SEQ ID NO: 236); VH3-07 (SEQ ID NO: 207)/VK3-15 (SEQ ID NO: 238); VH3-07 (SEQ ID NO: 207)/VLl-47 (SEQ ID NO: 251); VH3-07 (SEQ ID NO: 207)/VLl-51 (SEQ ID NO: 252); VH3-11 (SEQ ID NO: 208)/VKl-05 (SEQ ID NO: 230); VH3-11 (SEQ ID NO: 208)/VKl- 39 (SEQ ID NO: 236); VH3-11 (SEQ ID NO: 208)/VK3-15 (SEQ ID NO: 238); VH3-11 (SEQ ID NO: 208)/VLl-40 (SEQ ID NO: 2 50); VH3-11 (SEQ ID NO: 208)/VLl-47 (SEQ ID NO: 251); VH3-11 (SEQ ID NO: 208)NL1-51 (SEQ ID NO: 252); VH3-11 (SEQ ID NO: 208)/VL2-23 (SEQ ID NO: 255); VH3-15 (SEQ ID NO: 209)/VKl- 05 (SEQ ID NO: 230); VH3-15 (SEQ ID NO: 209)/VKl-06 (SEQ ID NO: 231); VH3- 15 (SEQ ID NO: 209)/VKl-12 (SEQ ID NO: 233); VH3-15 (SEQ ID NO: 209)/VKl- 16 (SEQ ID NO: 234); VH3-15 (SEQ ID NO: 209)/VKl-27 (SEQ ID NO: 235); VH3-15 (SEQ ID NO: 209)/VK3-ll (SEQ ID NO: 237); VH3-15 (SEQ ID NO: 209)/VLl- 40 (SEQ ID NO: 250); VH3-15 (SEQ ID NO: 209)/VLl-47 (SEQ ID NO: 251); VH3-15 (SEQ ID NO: 209)/VLl-51 (SEQ ID NO: 252); VH3-15 (SEQ ID NO: 209)/VL2- 14 (SEQ ID NO: 254); VH3-21 (SEQ ID NO: 210)/VK1-12 (SEQ ID NO: 233); VH3-21 (SEQ ID NO: 210)/VKl-27 (SEQ ID NO: 235); VH3-21 (SEQ ID NO: 210)/VL2-11 (SEQ ID NO: 253); VH3-23 (SEQ ID NO: 21Q/VK1-39 (SEQ ID NO: 236); VH3-23 (SEQ ID NO: 211)/VK3-15 (SEQ ID NO: 238); VH3-23 (SEQ ID NO: 21Q/VL2-23 (SEQ ID NO: 255); VH3-23 (SEQ ID NO: 211)/VL3-1 (SEQ ID NO: 256); VH3-30 (SEQ ID NO: 212)/VK3-20 (SEQ ID NO: 239); VH3-53 (SEQ ID NO: 213)/VK3- 15 (SEQ ID NO: 238); VH3-53 (SEQ ID NO: 213)/VL2-11 (SEQ ID NO: 253); VH3-74 (SEQ ID NO: 214)/VKl-05 (SEQ ID NO: 230); VH3-74 (SEQ ID NO: 214)/VK1- 06 (SEQ ID NO: 231); VH3-74 (SEQ ID NO: 214)/VK1-12 (SEQ ID NO: 2 33); VH3-74 (SEQ ID NO: 214)/VKl-27 (SEQ ID NO: 235); VH3-74 (SEQ ID NO: 214) /VK3-20 (SEQ ID NO: 239); VH3-74 (SEQ ID NO: 214)/VL1-51 (SEQ ID NO: 252); VH5-51 (SEQ ID NO: 215)/VKl-39 (SEQ ID NO: 236); VH5-51 (SEQ ID NO: 215) /VLl-40 (SEQ ID NO: 250); VH5-51 (SEQ ID NO: 215)/VL1-51 (SEQ ID NO: 252); VH6-1 (SEQ ID NO: 216)/VKl-09 (SEQ ID NO: 232); VH6-1 (SEQ ID NO: 216) /VK3-15 (SEQ ID NO: 238); VH6-1 (SEQ ID NO: 216)/VK3-20 (SEQ ID NO: 239) and VH6-1 (SEQ ID NO: 216)/VL1-51 (SEQ ID NO: 252).
2. Samling af syntetiske antistoffer eller funktionelle fragmenter deraf if0lge krav 1, hvor de strukturelle omrader af de variable tung kaede- og variable let kaede-par bestar af 30 eller Here kimbane-protein-sekvenser udvalgt blandt de variable tung kaede- og variable let kaede-par udvisende sekvenserne saledes som defineret if0lge figurer 25-36: VH1-18 (SEQ ID NO: 204)/VKl-39 (SEQ ID NO: 236); VH1-18 (SEQ ID NO: 204) /VK3-15 (SEQ ID NO: 238); VH1-18 (SEQ ID NO: 204)/VK3-20 (SEQ ID NO: 239); VH1-46 (SEQ ID NO: 205)/VK3-15 (SEQ ID NO: 238); VH1-46 (SEQ ID NO: 205) /VLl-51 (SEQ ID NO: 252); VH1-46 (SEQ ID NO: 205)/VL3-21 (SEQ ID NO: 257); VH1-69*01 (SEQ ID NO: 206)/VLl-51 (SEQ ID NO: 252); VH3-07 (SEQ ID NO: 207)/VKl-12 (SEQ ID NO: 233); VH3-07 (SEQ ID NO: 207)/VKl-16 (SEQ ID NO: 234); VH3-07 (SEQ ID NO: 207)/VKl-27 (SEQ ID NO: 235); VH3-07 (SEQ ID NO: 207)/VKl-39 (SEQ ID NO: 236); VH3-07 (SEQ ID NO: 207)/VK3-15 (SEQ ID NO: 238); VH3-07 (SEQ ID NO: 207)/VLl-47 (SEQ ID NO: 251); VH3-07 (SEQ ID NO: 207)/VLl-51 (SEQ ID NO: 252); VH3-11 (SEQ ID NO: 208)/VKl-05 (SEQ ID NO: 230); VH3-11 (SEQ ID NO: 208)/VKl-39 (SEQ ID NO: 236); VH3-11 (SEQ ID NO: 208)/VK3-15 (SEQ ID NO: 238); VH3-11 (SEQ ID NO: 208)/VLl-40 (SEQ ID NO: 250); VH3-11 (SEQ ID NO: 208)/VLl-47 (SEQ ID NO: 251); VH3-11 (SEQ ID NO: 208)/VLl-51 (SEQ ID NO: 252); VH3-11 (SEQ ID NO: 208)/VL2-23 (SEQ ID NO: 255); VH3-15 (SEQ ID NO: 209)/VKl-05 (SEQ ID NO: 230); VH3-15 (SEQ ID NO: 209)/VKl-06 (SEQ ID NO: 231); VH3-15 (SEQ ID NO: 209)/VKl-12 (SEQ ID NO: 233); VH3-15 (SEQ ID NO: 209)/VKl-16 (SEQ ID NO: 234); VH3-15 (SEQ ID NO: 209)/VKl-27 (SEQ ID NO: 235); VH3-15 (SEQ ID NO: 209)/VK3-ll (SEQ ID NO: 237); VH3-15 (SEQ ID NO: 209)/VLl-40 (SEQ ID NO: 250); VH3-15 (SEQ ID NO: 209)/VLl-47 (SEQ ID NO: 251); VH3-15 (SEQ ID NO: 209)/VLl-51 (SEQ ID NO: 252); VH3-15 (SEQ ID NO: 209)/VL2-14 (SEQ ID NO: 254); VH3-21 (SEQ ID NO: 210)/VK1-12 (SEQ ID NO: 233); VH3-21 (SEQ ID NO: 210)/VKl-27 (SEQ ID NO: 235); VH3-21 (SEQ ID NO: 210)/VL2-11 (SEQ ID NO: 253); VH3-23 (SEQ ID NO: 211)/VKl-39 (SEQ ID NO: 236); VH3-23 (SEQ ID NO: 211)/VK3-15 (SEQ ID NO: 238); VH3-23 (SEQ ID NO: 211)/VL2-23 (SEQ ID NO: 255); VH3-23 (SEQ ID NO: 211)/VL3-1 (SEQ ID NO: 256); VH3-30 (SEQ ID NO: 212)/VK3-20 (SEQ ID NO: 239); VH3-53 (SEQ ID NO: 213)/VK3-15 (SEQ ID NO: 238); VH3-53 (SEQ ID NO: 213)/VL2-11 (SEQ ID NO: 253); VH3-74 (SEQ ID NO: 214)/VKl-05 (SEQ ID NO: 230); VH3-74 (SEQ ID NO: 214)/VKl-06 (SEQ ID NO: 231); VH3-74 (SEQ ID NO: 214)/VK1-12 (SEQ ID NO: 233); VH3-74 (SEQ ID NO: 214)/VKl-27 (SEQ ID NO: 235); VH3-74 (SEQ ID NO: 214)/VK3-20 (SEQ ID NO: 239); VH3-74 (SEQ ID NO: 214)/VL1-51 (SEQ ID NO: 252); VH5-51 (SEQ ID NO: 215)/VKl-39 (SEQ ID NO: 236); VH5-51 (SEQ ID NO: 215)/VLl-40 (SEQ ID NO: 250); VH5-51 (SEQ ID NO: 215)/VL1-51 (SEQ ID NO: 252); VH6-1 (SEQ ID NO: 216)/VKl-09 (SFQ ID NO: 232); VH6-1 (SEQ ID NO: 216)/VK3-15 (SEQ ID NO: 238); VH6-1 (SEQ ID NO: 216)/VK3-20 (SEQ ID NO: 239) and VH6-1 (SEQ ID NO: 216)/VL1-51 (SEQ ID NO: 252).
3. Samling if0lge et hvilket som heist af de foregaende krav, hvor de strukturelle omrader af de variable tung kaede- og variable let kaede-par bestar af kimbane-protein-sekvenser udvalgt blandt de variable tung kaede- og variable let kaede-par udvisende sekvenserne saledes som defineret if0lge figurer 25-36: VH1-18 (SEQ ID NO: 204)/VK3-20 (SEQ ID NO: 239); VH1-46 (SEQ ID NO: 205)/VK3-15 (SEQ ID NO: 238); VH1-46 (SEQ ID NO: 205)/VLl-51 (SEQ ID NO: 252); VH1-69*01 (SEQ ID NO: 206)/VLl-51 (SEQ ID NO: 252); VH3-07 (SEQ ID NO: 207)/VKl-12 (SEQ ID NO: 233); VH3-07 (SEQ ID NO: 207)/VKl-27 (SEQ ID NO: 235); VH3-07 (SEQ ID NO: 207)/VK3-15 (SEQ ID NO: 238); VH3-07 (SEQ ID NO: 207)/VLl-47 (SEQ ID NO: 251); VH3-07 (SEQ ID NO: 207)/VLl-51 (SEQ ID NO: 252); VH3-11 (SEQ ID NO: 208)/VLl-40 (SEQ ID NO: 250); VH3-11 (SEQ ID NO: 208)/VLl-47 (SEQ ID NO: 251); VH3-11 (SEQ ID NO: 208)/VLl-51 (SEQ ID NO: 252); VH3-11 (SEQ ID NO: 208)/VL2-23 (SEQ ID NO: 255); VH3-15 (SEQ ID NO: 209)/VKl-05 (SEQ ID NO: 230); VH3-15 (SEQ ID NO: 209)/VKl-06 (SEQ ID NO: 231); VH3-15 (SEQ ID NO: 209)/VKl-12 (SEQ ID NO: 233); VH3-15 (SEQ ID NO: 209)/VKl-27 (SEQ ID NO: 235); VH3-15 (SEQ ID NO: 209)/VK3-ll (SEQ ID NO: 237); VH3-15 (SEQ ID NO: 209)/VLl-51 (SEQ ID NO: 252); VH3-21 (SEQ ID NO: 210)/VK1-12 (SEQ ID NO: 233); VH3-23 (SEQ ID NO: 21Q/VK1-39 (SEQ ID NO: 236); VH3-23 (SEQ ID NO: 21Q/VK3-15 (SEQ ID NO: 238); VH3-23 (SEQ ID NO: 211)/VL2-23 (SEQ ID NO: 255); VH3-23 (SEQ ID NO: 211)/VL3-1 (SEQ ID NO: 256); VH3-53 (SEQ ID NO: 213)/VK3-15 (SEQ ID NO: 238); VH3-53 (SEQ ID NO: 213)/VL2-11 (SEQ ID NO: 253); VH3-74 (SEQ ID NO: 214)/VKl-05 (SEQ ID NO: 230); VH3-74 (SEQ ID NO: 214)/VKl-06 (SEQ ID NO: 231); VH3-74 (SEQ ID NO: 214)/VK1-12 (SEQ ID NO: 233); VH3-74 (SEQ ID NO: 214)/VK3-20 (SEQ ID NO: 239); VH5-51 (SEQ ID NO: 215)/VKl-39 (SEQ ID NO: 236); VH5-51 (SEQ ID NO: 215)/VLl-40 (SEQ ID NO: 250); VH5-51 (SEQ ID NO: 215)/VL1-51 (SEQ ID NO: 252); VH6-1 (SEQ ID NO: 216)/VKl-09 (SEQ ID NO: 232); VH6-1 (SEQ ID NO: 216)/VK3-20 (SEQ ID NO: 239) and VH6-1 (SEQ ID NO: 216)/VL1-51 (SEQ ID NO: 252).
4. Samling af syntetiske antistoffer eller funktionelle fragmenter deraf if0lge krav 3, hvor de strukturelle omrader af de variable tung kaede- og variable let kaede-par bestar af kimbane-protein-sekvenser af de variable tung kaede- og variable let kaede-par udvi-sende sekvenseme saledes som defineret if0lge figurer 25-36: VH1-18 (SEQ ID NO: 204)/VK3-20 (SEQ ID NO: 239); VH1-46 (SEQ ID NO: 205)/VK3-15 (SEQ ID NO: 238); VH1-46 (SEQ ID NO: 205)/VLl-51 (SEQ ID NO: 252); VH1-69*01 (SEQ ID NO: 206)/VLl-51 (SEQ ID NO: 252); VH3-07 SEQ ID NO: 207)/VKl-12 (SEQ ID NO: 233); VH3-07 (SEQ ID NO: 207)/VKl-27 (SEQ ID NO: 235); H3 07 (SEQ ID NO: 207)/VK3-15 (SEQ ID NO: 238); VH3-07 (SEQ ID NO: 207)/VLl-47 (SEQ ID NO: 251); VH3-07 (SEQ ID NO: 207)/VLl-51 (SEQ ID NO: 252); VH3-11 (SEQ ID NO: 208)/VLl-40 (SEQ ID NO: 250); VH3-11 (SEQ ID NO: 208)/VLl-47 (SEQ ID NO: 251); VH3-11 (SEQ ID NO: 208)/VLl-51 (SEQ ID NO: 252); VH3-11 (SEQ ID NO: 208)/VL2-23 (SEQ ID NO: 255); VH3-15 (SEQ ID NO: 209)/VKl-05 SEQ ID NO: 230); VH3-15 (SEQ ID NO: 209)/VKl-06 (SEQ ID NO: 231); VH3-15 (SEQ ID NO: 209)/VKl-12 (SEQ ID NO: 233); VH3-15 (SEQ ID NO: 209)/VKl-27 (SEQ ID NO: 235); VH3-15 (SEQ ID NO: 209)/VK3-ll (SEQ ID NO: 237); VH3-15 (SEQ ID NO: 209)/VLl-51 (SEQ ID NO: 252); VH3-21 (SEQ ID NO: 210)/VK1-12 (SEQ ID NO: 233); VH3-23 (SEQ ID NO: 21Q/VK3-15 (SEQ ID NO: 238); VH3-53 (SEQ ID NO: 213)/VK3-15 (SEQ ID NO: 238); VH3-53 (SEQ ID NO: 213)/VL2-11 (SEQ ID NO: 253); VH3-74 (SEQ ID NO: 214)/VKl-05 (SEQ ID NO: 230); VH3-74 (SEQ ID NO: 214)/VKl-06 (SEQ ID NO: 231); VH3-74 (SEQ ID NO: 214)/VK1-12 (SEQ ID NO: 233); VH3-74 (SEQ ID NO: 214)/VK3-20 (SEQ ID NO: 239); VH5-51 (SEQ ID NO: 215)/VKl-39 (SEQ ID NO: 236); VH5-51 (SEQ ID NO: 215)/VLl-40 (SEQ ID NO: 250); VH5-51 (SEQ ID NO: 215)/VL1-51 (SEQ ID NO: 252); VH6-1 (SEQ ID NO: 216)/VKl-09 (SEQ ID NO: 232); VH6-1 (SEQ ID NO: 216)/VK3-20 (SEQ ID NO: 239) and VH6-1 (SEQ ID NO: 216)/VL1-51 (SEQ ID NO: 252).
5. Samling if0lge et hvilket som heist af de forudgaende krav, hvor de naevnte antistoffer eller funktionelle fragmenter deraf omfatter et eller Here komplementaritet- bestemmende omrader bestaende af kimbane-protein-sekvenser fra de respektive variable tung kaede- og variable let kaede-par.
6. Samling ifplge et hvilket som heist af de forudgaende krav, hvor de naevnte anti-stoffer eller funktionelle fragmenter deraf omfatter CDRl-omrader bestaende af kim-bane-protein-sekvenser fra de respektive variable tung kaede- og variable let kaede-par.
7. Samling ifplge et hvilket som heist af de forudgaende krav, hvor de naevnte anti-stoffer eller funktionelle fragmenter deraf omfatter CDR2-omrader bestaende af kim-bane-protein-sekvenser fra de respektive variable tung kaede- og variable let kaede-par.
8. Samling il'olge et hvilket som heist af de forudgaende krav, hvor de naevnte anti-stoffer eller funktionelle fragmenter deraf omfatter et eller Here komplementaritet-bestemmende omrader omfattende aminosyre-modifikationer, der fjerner potentielle steder med post-translatoriske modifikationer.
9. Samling il'olge krav 8, hvor de naevnte antistoffer eller funktionelle fragmenter deraf omfatter et eller Here tung kaede komplementaritet-bestemmende omrader omfattende de komplementaritet-bestemmende omrade-sekvenser fra de respektive tung kaeder an fort il'olge fig. 34-36.
10. Samling il'olge krav 9, hvor de naevnte antistoffer eller funktionelle fragmenter deraf omfatter HCDRl-omrader fra det respektive HCDRl-omrade an fort il'olge fig. 34.
11. Samling il'olge krav 9 eller 10, hvor de naevnte antistoffer eller funktionelle fragmenter deraf omfatter HCDR2-omrader fra det respektive HCDR2-omrade an fort ifplge fig. 35.
12. Samling il'olge et hvilket som heist af de forudgaende krav, hvor de naevnte antistoffer eller funktionelle fragmenter deraf omfatter et FR4-omrade udvalgt fra gruppen bestaende af JH4, JkI og .1 λ2/3 sekvenserne deraf er defineret il'olge fig. 40.
13. Samling il'olge et hvilket som heist af de forudgaende krav, hvor de naevnte antistoffer eller funktionelle fragmenter deraf omfatter et diversificeret HCDR3-omrade.
14. Samling if0lge et hvilket som heist af de forudgaende krav, hvor de naevnte anti-stoffer eller funktionelle fragmenter deraf omfatter et diversificeret LCDR3-omrade.
15. Samling if0lge et hvilket som heist af de forudgaende krav, hvor samlingen omfatter i det mindste 1 x 104 antistoffer eller funktionelle fragmenter deraf.
16. Samling if0lge et hvilket som heist af de forudgaende krav, hvor de naevnte antistoffer er udvalgt fra gruppeme bestaende af menneskelig IgGl, IgG2, IgG3, IgG4, IgA, IgE, IgM og IgD.
17. Samling if0lge et hvilket som heist af de forudgaende krav, hvor de naevnte funktionelle fragmenter af de naevnte antistoffer er udvalgt fra gruppen bestaende af Fab, F(ab’)2, Fab’, Fv og scFv.
18. Samling af nukleinsyrer, som koder en samling af antistoffer eller funktionelle fragmenter deraf ifplge et hvilket som heist af de forudgaende krav.
19. Vektor omfattende samlingen af nukleinsyrer if0lge krav 18.
20. Rekombinant vaertscelle omfattende nukleinsyrerne if0lge krav 18 eller vektoren ifplgekrav 19.
21. Fremgangsmade til identificering af et for et antigen specifikt antistof eller anti-stof-fragment omfattende: (a) etablering af beiwingskontakt for antigenet med en samling af antistoffer eller funktionelle fragmenter deraf ifplge krav 1, og (b) valg af et eller Here antistoffer eller antistof-fragmenter, som binder til det naevnte antigen.
DK11785411.7T 2010-11-19 2011-11-18 Samling af antistofsekvenser og disses anvendelser DK2640742T3 (da)

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PCT/EP2011/070473 WO2012066129A1 (en) 2010-11-19 2011-11-18 A collection and methods for its use

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