HRP20110187T1 - Multispecifične deimunizirane tvari koje vežu cd3 - Google Patents

Multispecifične deimunizirane tvari koje vežu cd3 Download PDF

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HRP20110187T1
HRP20110187T1 HR20110187T HRP20110187T HRP20110187T1 HR P20110187 T1 HRP20110187 T1 HR P20110187T1 HR 20110187 T HR20110187 T HR 20110187T HR P20110187 T HRP20110187 T HR P20110187T HR P20110187 T1 HRP20110187 T1 HR P20110187T1
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specific binding
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binding construct
acid sequence
construct
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Hofmeister Robert
Kohleisen Birgit
Lenkkeri-Sch�tz Ulla
Itin Christian
B�uerle Patrick
J. Carr Francis
A. Hamilton Anita
Williams Stephen
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Micromet Ag
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Abstract

Citotoksički aktivan specifičan vezujući konstrukt za CD3 koji sadrži prvu domenu koja se specifično veže za ljudski CD3 i drugu vezujuću domenu na bazi Ig-a, pri čemu je prva domena deimunizirana i sadrži CDR-H1 regiju sa sekvencom aminokiselina kako je prikazano u SEQ ID NO: 88, CDR-H2 regiju sa sekvencom aminokiselina kako je prikazano u SEQ ID NO: 90 ili 92 i CDR-H3 regiju sa sekvencom aminokiselina kako je prikazano u SEQ ID NO.: 96, 108,119, 120, 121, 122, 123, 124, 125, 126 ili 127; ipri čemu prva domena dalje sadrži u svom okviru H1 sekvencu VKK i gdje prijelazna sekvenca između okvira H1 i CDRH1 regije obuhvaća sekvencu Ala-Ser-Gly-Tyr-Thr-Phe (ASGYTF; SEQ ID NO.: 233). Patent sadrži još 31 patentni zahtjev.

Claims (32)

1. Citotoksički aktivan specifičan vezujući konstrukt za CD3 koji sadrži prvu domenu koja se specifično veže za ljudski CD3 i drugu vezujuću domenu na bazi Ig-a, pri čemu je prva domena deimunizirana i sadrži CDR-H1 regiju sa sekvencom aminokiselina kako je prikazano u SEQ ID NO: 88, CDR-H2 regiju sa sekvencom aminokiselina kako je prikazano u SEQ ID NO: 90 ili 92 i CDR-H3 regiju sa sekvencom aminokiselina kako je prikazano u SEQ ID NO.: 96, 108,119, 120, 121, 122, 123, 124, 125, 126 ili 127; i pri čemu prva domena dalje sadrži u svom okviru H1 sekvencu VKK i gdje prijelazna sekvenca između okvira H1 i CDRH1 regije obuhvaća sekvencu Ala-Ser-Gly-Tyr-Thr-Phe (ASGYTF; SEQ ID NO.: 233).
2. Citotoksički aktivan specifičan vezujući konstrukt za CD3 prema zahtjevu 1, naznačen time što dalje sadrži u prvoj domeni okvir H3 koji obuhvaća sekvencu Met-Glu-Leu-Ser (MELS; SEQ ID NO.: 234).
3. Citotoksički aktivan specifičan vezujući konstrukt za CD3 prema zahtjevu 1 ili 2, naznačen time što dalje sadrži u prvoj domeni okvir H3 koji obuhvaća sekvencu Ile-Thr-Thr-Asp-Lys (ITTDK; SEQ ID NO.: 235).
4. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 3, naznačen time što prva domena koja se specifično veže za ljudski CD3 sadrži okvir H1 kako je prikazano u SEQ ID NO.: 152 ili 153.
5. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 4, naznačen time što prva domena koja se specifično veže za ljudski CD3 sadrži okvir H2 kako je prikazano u SEQ ID NO.: 156 ili 157.
6. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 5, naznačen time što prva domena koja se specifično veže za ljudski CD3 sadrži okvir H3 kako je prikazano u SEQ ID NO.: 160 ili 161.
7. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 6, naznačen time što prva domena koja se specifično veže za ljudski CD3 sadrži okvir H4 kako je prikazano u SEQ ID NO.: 164 ili 165.
8. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 7, naznačen time što konstrukt sadrži VH-regiju kako je prikazano u SEQ ID NO.:74 ili 76.
9. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 8, naznačen time što konstrukt sadrži CDR-L1 kako je prikazano u SEQ ID NO.: 98 ili 100.
10. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 9, naznačen time što konstrukt sadrži CDR-L2 kako je prikazano u SEQ ID NO.:102.
11. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 10, naznačen time što konstrukt sadrži CDR-L3 kako je prikazano u SEQ ID NO.:104.
12. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 11, naznačen time što sadrži VL regiju u svom CD3-specifičnom dijelu, pri čemu je ta VL regija izabrana iz skupine koja obuhvaća SEQ ID NO.: 78, SEQ ID NO.: 80, SEQ ID NO.: 82 i SEQ ID NO.: 112.
13. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 12, naznačen time što je druga domena na bazi Ig-a scFv.
14. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 13, naznačen time što druga domena na bazi Ig-a i/ili (a) vezna linker-regija(regije) jest/su humanizirane i/ili deimunizirane.
15. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 14, naznačen time što druga domena na bazi Ig-a sadrži mjesto interakcije s antigenom, specifično za molekulu na staničnoj površini.
16. Specifičan vezujući konstrukt za CD3 prema zahtjevu 15, naznačen time što je molekula stanične površine biljeg specifičan za tumor.
17. Specifičan vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 16, naznačen time što druga domena na bazi Ig-a sadrži mjesto interakcije s antigenom, specifično za EpCAM.
18. Specifičan vezujući konstrukt za CD3 prema zahtjevu 17, naznačen time što on sam sadrži sekvencu aminokiselina izabranu iz skupine (a) sekvence aminokiselina kako je prikazano u bilo kojoj od SEQ ID NO.: 31, 33, 35, 37, 39, 49, 55, 58, 61, 63, 65, 67, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323 i 325; (b) sekvence aminokiselina koju kodira sekvenca nukleinske kiseline kako je prikazano u bilo kojoj od SEQ ID NO.: 30, 32, 34, 36, 38, 48, 54, 57, 60, 62, 64, 66, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322 i 324; i (c) sekvence aminokiselina koju kodira sekvenca nukleinske kiseline koja je degenerirana kao rezultat genskog koda nukleotidne sekvence (b); (d) i sekvence aminokiselina koju kodira sekvenca nukleinske kiseline koja hibridizira s komplementarnim lancem sekvence nukleinske kiseline kako je određeni pod (b) pod strogim uvjetima hibridizacije.
19. Sekvenca nukleinske kiseline koja kodira specifični vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 18.
20. Vektor koji sadrži sekvencu nukleinske kiseline prema zahtjevu 19.
21. Vektor prema zahtjevu 20, naznačen time što dalje sadrži sekvencu nukleinske kiseline koja je regulatorna sekvenca operativno povezana sa spomenutom sekvencom nukleinske kiseline prema zahtjevu 19.
22. Vektor prema zahtjevu 20 ili 21, naznačen time što je vektor ekspresijski vektor.
23. Domaćin transformiran ili transficiran vektorom prema bilo kojem od zahtjeva 20 do 22.
24. Postupak proizvodnje specifičnog vezujućeg konstrukta za CD3 prema bilo kojem od zahtjeva 1 do 18, taj postupak obuhvaća uzgoj kulture domaćina prema zahtjevu 23 pod uvjetima koji omogućavaju ekspresiju polipeptidnog konstrukta i izoliranje dobivenog polipeptidnog konstrukta iz kulture.
25. Smjesa koja sadrži specifični vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 18 ili proizveden prema postupku iz zahtjeva 24, molekulu nukleinske kiseline prema zahtjevu 19, vektor prema bilo kojem od zahtjeva 20 do 22 ili domaćina prema zahtjevu 23 i, po izboru, proteinski spoj koji može izazvati aktivaciju signala za stanice imunog odgovora.
26. Smjesa prema zahtjevu 25, naznačena time što je to farmaceutska smjesa koja dalje sadrži, po izboru, odgovarajuće oblike nosača, stabilizatora i/ili pomoćnih tvari.
27. Smjesa prema zahtjevu 25, naznačena time što je to dijagnostička smjesa koja dalje sadrži, po izboru, sredstva i načine otkrivanja.
28. Uporaba specifičnog vezujućeg konstrukta za CD3 prema bilo kojem od zahtjeva 1 do 18 ili kako je proizveden prema postupku iz zahtjeva 24; molekule nukleinske kiseline prema zahtjevu 19; vektora prema bilo kojem od zahtjeva 20 do 22; ili domaćina prema zahtjevu 23, za pripremu farmaceutske smjese za prevenciju, liječenje ili poboljšanje proliferativne bolesti, tumora, upalnih bolesti, imunološkog poremećaja, autoimune bolesti, zarazne bolesti, virusne bolesti, alergijskih reakcija, parazitskih reakcija, bolesti presadak-protiv-domaćina ili bolesti domaćin-protiv-presatka.
29. Uporaba prema zahtjevu 28, naznačena time što se farmaceutska smjesa daje istodobno, ili ne istodobno, s proteinskim spojem koji može izazvati aktivaciju signala za stanice imunog odgovora.
30. Farmaceutska smjesa, naznačena time što sadrži specifični vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 18 ili kako je proizveden prema postupku iz zahtjeva 24; molekulu nukleinske kiseline prema zahtjevu 19; vektor prema bilo kojem od zahtjeva 20 do 22; ili domaćina prema zahtjevu 23, za uporabu za prevenciju, liječenje ili poboljšanje proliferativne bolesti, tumora, upalnih bolesti, imunološkog poremećaja, autoimune bolesti, zarazne bolesti, virusne bolesti, alergijskih reakcija, parazitskih reakcija, bolesti presadak-protiv-domaćina ili bolesti domaćin-protiv-presatka
31. Farmaceutska smjesa prema zahtjevu 30, naznačena time što se ona daje istodobno, ili ne istodobno, s proteinskim spojem koji može izazvati aktivaciju signala za stanice imunog odgovora.
32. Set koji sadrži specifični vezujući konstrukt za CD3 prema bilo kojem od zahtjeva 1 do 18 ili kako je proizveden prema postupku iz zahtjeva 24; molekulu nukleinske kiseline prema zahtjevu 19; vektor prema bilo kojem od zahtjeva 20 do 22; ili domaćina prema zahtjevu 23
HR20110187T 2003-10-16 2011-03-14 Multispecifične deimunizirane tvari koje vežu cd3 HRP20110187T1 (hr)

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Application Number Priority Date Filing Date Title
EP03023581 2003-10-16
PCT/EP2004/011646 WO2005040220A1 (en) 2003-10-16 2004-10-15 Multispecific deimmunized cd3-binders

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