HRP20190756T1 - Cd3-vezujuće molekule sposobne za vezanje za humani i nehumani cd3 - Google Patents
Cd3-vezujuće molekule sposobne za vezanje za humani i nehumani cd3 Download PDFInfo
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- HRP20190756T1 HRP20190756T1 HRP20190756TT HRP20190756T HRP20190756T1 HR P20190756 T1 HRP20190756 T1 HR P20190756T1 HR P20190756T T HRP20190756T T HR P20190756TT HR P20190756 T HRP20190756 T HR P20190756T HR P20190756 T1 HRP20190756 T1 HR P20190756T1
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- binding
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- mab2
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Classifications
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- C03C2217/00—Coatings on glass
- C03C2217/40—Coatings comprising at least one inhomogeneous layer
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- C03C2217/46—Coatings comprising at least one inhomogeneous layer consisting of a dispersed phase in a continuous phase characterized by the dispersed phase
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Claims (19)
1. CD3-vezujuća molekula koja sadrži antigen-vezujući fragment antitijela, naznačen time što navedeni antigen-vezujući fragment sadrži CD3-specifičnu VL domenu antitijela i CD3-specifičnu VH domenu antitijela, pri čemu navedena CD3-specifična VL domena i navedena CD3-specifična VH domena formiraju antigen-vezujuću domenu sposobnu za imunospecifično vezanje za oba, epitop humanog CD3 i epitop CD3 nehumanog sisavca, gdje:
(I) navedena CD3-specifična VL domena je izabrana iz grupe koja se sastoji od h-mab2 VL-4 koji ima aminokiselinsku sekvencu SEQ ID NO:22, h-mab2 VL-6 koji ima aminokiselinsku sekvencu SEQ ID NO:26, h-mab2 VL-7 koji ima aminokiselinsku sekvencu SEQ ID NO:28, h-mab2 VL-8 koji ima aminokiselinsku sekvencu SEQ ID NO:30, h-mab2 VL-9 koji ima aminokiselinsku sekvencu SEQ ID NO:32 i h-mab2 VL-10 koji ima aminokiselinsku sekvencu SEQ ID NO:34, i
(II) navedenu CD3-specifičnu VH domenu je izabran iz grupe koja se sastoji od h-mab2 VH-1 koji ima aminokiselinsku sekvencu SEQ ID NO:36, h-mab2 VH-2 koji ima aminokiselinsku sekvencu SEQ ID NO:38, h-mab2 VH-3 koji ima aminokiselinsku sekvencu SEQ ID N0:40, h-mab2 VH-4 koji ima aminokiselinsku sekvencu SEQ ID NO:42, h-mab2 VH-5 koji ima aminokiselinsku sekvencu SEQ ID NO:44, h-mab2 VH-6 koji ima aminokiselinsku sekvencu SEQ ID NO:46, h-mab2 VH-7 koji ima aminokiselinsku sekvencu SEQ ID NO:48 i h-mab2 VH-8 koji ima aminokiselinsku sekvencu SEQ ID NO:50.
2. CD3-vezujuća molekula prema patentnom zahtjevu 1, naznačena time što navedena CD3-specifična VL domena je h-mab2 VL-6 koja ima aminokiselinsku sekvencu SEQ ID No:26.
3. CD3-vezujuća molekula prema bilo kojem od patentnih zahtjeva 1-2, naznačena time što navedena CD3-specifična VH domena je h-mab2 VH-8 koja ima aminokiselinsku sekvencu SEQ ID No:50, ili h-mab2 VH-4 koji ima aminokiselinsku sekvencu SEQ ID No:42.
4. CD3-vezujuća molekula prema bilo kojem od patentnih zahtjeva 1-3, naznačena time što je navedena molekula antitijelo.
5. CD3-vezujuće antitijelo prema patentnom zahtjevu 4, naznačeno time što navedeno antitijelo:
(A) nema Fc područje;
ili
(B) sadrži Fc područje koje:
(i) nema efektornu funkciju; ili
(ii) ima reduciranu efektornu funkciju; ili
(iii) pogoršava sposobnost Fc područja navedenog antitijela da se veže za Fc receptor;
pri čemu, navedeni nedostatak efektorske funkcije, navedena redukcija u efektorskoj funkciji i navedeno pogoršanje vezujuće aktivnosti je u odnosu na ono kod Fc receptora divljeg tipa.
6. CD3-vezujuća molekula prema bilo kojem od patentnih zahtjeva 1-3, naznačena time što navedena molekula je CD3-vezujuće diatijelo koje sadrži prvi polipeptidni lanac i drugi polipeptidni lanac, pri čemu su navedeni lanci kovalentno međusobno vezani, pri čemu:
(I) navedeni prvi polipeptidni lanac sadrži amino terminus i karboksi terminus i od N-terminusa do C-terminusa:
(i) domena (A) koja sadrži navedeni CD3-specifičnu VL domenu;
(ii) domena (B) koja sadrži vezujuće područje varijabilne domene teškog lanca drugog imunoglobulina (VH2); i
(iii) domena (C);
pri čemu se navedene domene (A) i (B) ne vežu međusobno tako da formiraju mjesto vezanja epitopa;
i
(II) navedeni drugi polipeptidni lanac sadrži amino terminus i karboksi terminus i od N-terminusa do C-terminusa:
(i) domena (D) koja sadrži vezujuće područje varijabilne domene lakog lanca navedenog drugog imunoglobulina (VL2);
(ii) domena (E) koja sadrži navedenu CD3-specifičnu VH domenu;
i
(iii) domena (F);
pri čemu navedene domene (D) i (E) se ne vežu međusobno tako da formiraju mjesto vezanja epitopa; i
pri čemu:
(1) navedene domene (A) i (E) se vežu tako da formiraju navedenu antigen-vezujuću domenu koja je sposobna za imunospecifično vezanje za oba, humani CD3 i za CD3 nehumanog sisavca;
(2) navedene domene (B) i (D) se vežu tako da formiraju vezujuće mjesto koje se imunospecifično veže za drugi epitop, pri čemu je navedeni drugi epitop različit od CD3 epitopa vezanog antigen-vezujućom domenom formiranom od navedene veze navedenih domena (A) i (E); i
(3) navedene domene (C) i (F) su kovalentno vezane međusobno.
7. CD3-vezujuća molekula prema patentom zahtjevu 6, naznačena time što navedeni drugi epitop nije epitop CD3.
8. CD3-vezujuća molekula prema patentnom zahtjevu 6, naznačena time što navedeni drugi epitop je epitop CD3 koji se razlikuje od CD3 epitopa vezanog antigen-vezujućom domenom formiranom od navedene veze navedenih domena (A) i (E).
9. CD3-vezujuća molekula prema bilo kojem od patentnih zahtjeva 1-8 koja je humanizirana.
10. CD3-vezujuća molekula prema bilo kojem od patentnih zahtjeva 1-3 ili 6-9 koja je sposobna za imunospecifično vezanje za CD3 i za fluorescein.
11. CD3-vezujuća molekula prema bilo kojem od patentnih zahtjeva 1-3 ili 6-9, koja je sposobna za imunospecifično vezanje za oba: (i) CD3 i (ii)(a) tumorski antigen, ili (ii)(b) antigen, receptor ili receptor ligand na staničnoj površini.
12. CD3-vezujuća molekula prema patentnom zahtjevu 11, naznačena time što navedena molekula je sposobna za imunospecifično vezanje za CD3 i za tumorski antigen eksprimiran na stanici tumora, pri čemu navedena stanica tumora je stanica tumora iz raka izabranog iz grupe koja se sastoji od: raka dojke, raka prostate, raka želudca, raka pluća, raka trbuha, raka debelog crijeva, rektalnog raka, raka gušterače, raka jetre, raka jajnika, raka oralne šupljine, faringealnog raka, raka jednjaka, raka grkljana, raka kosti, raka kože, melanoma, raka materice, testikularnog raka, raka mjehura, raka bubrega, raka mozga, glioblastoma, tiroiodnog raka, limfoma, mijeloma i leukemije.
13. CD3-vezujuća molekula prema patentnom zahtjevu 11, naznačena time što navedena molekula je sposobna za imunospecifično vezanje za CD3 i za antigen, receptor ili receptor ligand na staničnoj površini, pri čemu navedeni antigen, receptor ili receptor ligand na staničnoj površini je HER2/neu, B7-H3, CD20, PSMA, IGF-1R ili Ep-CAM.
14. CD3-vezujuća molekula prema patentnom zahtjevu 11, naznačena time što navedena molekula je sposobna za imunospecifično vezanje za CD3 i za antigen, receptor ili receptor ligand na staničnoj površini, pri čemu navedeni antigen, receptor ili receptor ligand na staničnoj površini je molekula uključena u vezu T stanice - B stanice, pri čemu je navedena molekula uključen u navedenu vezu T stanice - B stanice izabran iz grupe koja se sastoji od CD19, CD20, CD22, CD23, CD27, CD32B, CD38, CD40, CD79a, CD79b, CD80, CD86, LFA-I, LFA-3 i CFA-I.
15. CD3-vezujuće diatijelo prema bilo kojem od patentnih zahtjeva 6-14 naznačeno time što navedeno CD3-vezujuće diatijelo sadrži Fc domenu ili njegovu domenu.
16. Farmaceutska kompozicija koja sadrži CD3-vezujuću molekulu prema bilo kojem od patentnih zahtjeva 1-15, i farmaceutski prihvatljiv nosač, ekscipijens ili razblaživač.
17. CD3-vezujuća molekula prema bilo kojem od patentnih zahtjeva 1-15 ili farmaceutska kompozicija prema patentnom zahtjevu 16, za upotrebu u liječenju raka ili autoimune ili inflamatorne bolesti.
18. CD3-vezujuća molekula ili farmaceutska kompozicija za upotrebu prema patentnom zahtjevu 17, naznačena time što navedena autoimuna ili inflamatorna bolest je izabrana iz grupe koja se sastoji od: inzulin ovisnog dijabetesa tip I, reumatoidnog artritisa, sistemskog lupus eritematozisa, multiple skleroze, inflamatorne bolesti crijeva, mijastenije gravis, celijakije, Sjogrenovog sindroma, Gravesove bolesti, Crohnove bolesti, autoimunog hepatitisa, psorijaze, psorijatičkog artritisa, astme, alergijskog rinitisa, efekata transplantacije organa ili bolesti transplanta protiv domaćina (GVHD).
19. CD3-vezujuća molekula ili farmaceutska kompozicija za upotrebu prema patentnom zahtjevu 18, naznačena time što navedena autoimuna ili inflamatorna bolest je inzulin ovisan dijabetes tipa I.
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EP12790075.1A EP2714733B1 (en) | 2011-05-21 | 2012-05-16 | Cd3-binding molecules capable of binding to human and non-human cd3 |
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