DK1753783T3 - Anti-cd3-antistoffer og fremgangsmåder til anvendelse deraf - Google Patents
Anti-cd3-antistoffer og fremgangsmåder til anvendelse deraf Download PDFInfo
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- DK1753783T3 DK1753783T3 DK05761845.6T DK05761845T DK1753783T3 DK 1753783 T3 DK1753783 T3 DK 1753783T3 DK 05761845 T DK05761845 T DK 05761845T DK 1753783 T3 DK1753783 T3 DK 1753783T3
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Claims (21)
1. Isoleret, fuldstændigt humant monoklonalt CD3-antistof eller fragment deraf, omfattende en tung-kæde aminosyresekvens omfattende tre komplementaritetsbestemmende områder (CDRs) og en let-kæde aminosyresekvens omfattende tre CDRs, hvor de tre tung-kæde CDRs og de tre let-kæde CDRs er udvalgt fra: a. et variabel-tung-kæde CDR1 (VH CDR1) omfattende aminosyresekvensen GYGMH (SEQ ID NR:27), et variabel-tung-kæde CDR2 (VH CDR2) omfattende aminosyresekvensen VIWYDGSKKYYVDSVKG (SEQ ID NR:28), et variabel-tung-kæde CDR3 (VH CDR3) omfattende aminosyresekvensen QMGYWHFDL (SEQ ID NR:29), et variabel-let-kæde CDR1 (VL CDR1) omfattende aminosyresekvensen RASQSVSSYLA (SEQ ID NR:30), et variabel-let-kæde CDR2 (VL CDR2) omfattende aminosyresekvensen DASNRAT (SEQ ID NR:31) og et variabel-let-kæde CDR3 (VL CDR3) omfattende aminosyresekvensen QQRSNWPPLT (SEQ ID NR:32); b. et VH CDR1 omfattende aminosyresekvensen SYGMH (SEQ ID NR:33), et VH CDR2 omfattende aminosyresekvensen IIWYDGSKKNYADSVKG (SEQ ID NR:34), et VH CDR3 omfattende aminosyresekvensen GTGYNWFDP (SEQ ID NR:35), et VL CDR1 omfattende aminosyresekvensen (SEQ ID NR:36), RASQGISSALA (SEQ ID NR:39) eller WASQGISSYLA (SEQ ID NR:43), et VL CDR2 omfattende aminosyresekvensen GASSRAT (SEQ ID NR:37), YASSLQS (SEQ ID NR:40) eller DASSLGS (SEQ ID NR:42), og et VL CDR3 omfattende aminosyresekvensen QQYGSSPIT (SEQ ID NR:38) eller QQYYSTLT (SEQ ID NR:41); og c. et VH CDR1 omfattende aminosyren SYGMH (SEQ ID NR:33); a VH CDR2 omfattende aminosyresekvensen AIWYNGRKQDYADSVKG (SEQ ID NR:44); og et VH CDR3 omfattende aminosyresekvensen GTGYNWFDP (SEQ ID NR:35); et VL CDR1 omfattende aminosyresekvensen RASQSVSSYLA (SEQ ID NR:30) eller RASQGISSALA (SEQ ID NR:39); et VL CDR2 omfattende aminosyresekvensen DASNRAT (SEQ ID NR:31) eller DASSLES (SEQ ID NR:46); og et VL CDR3 omfattende aminosyresekvensen QQRSNWPWT (SEQ ID NR:45) eller QQFNSYPIT (SEQ ID NR:47); hvor antistoffet indeholder mindst en første mutation i den tunge kæde ved position 234 og en anden mutation ved position 235, og hvor den første mutation resulterer i en alaninrest ved position 234, og den anden mutation resulterer i en glutaminsyrerest ved position 235.
2. Antistof ifølge krav 1 eller fragment deraf, der inhiberer binding af det monoklonale murine anti-human-antistof OKT3 til en T-lymfocyt.
3. Antistof ifølge krav 1 eller fragment deraf, der binder en epitop, som helt eller delvist indbefatter aminosyresekvensen EMGGITQTPYKVSISGT (SEQ ID NR:67).
4. Antistof ifølge krav 1 eller fragment deraf, omfattende et VH CDR1 omfattende aminosyresekvensen af GYGMH (SEQ ID NR:27); et VH CDR2 omfattende aminosyresekvensen af VIWYDGSKKYYVDSVKG (SEQ ID NR:28); et VH CDR3 omfattende aminosyresekvensen af QMGYWHFDL (SEQ ID NR:29); et VL CDR1 omfattende aminosyresekvensen af RASQSVSSYLA (SEQ ID NR:30); et VL CDR2 omfattende aminosyresekvensen af DASNRAT (SEQ ID NR:31); og et VL CDR3 omfattende aminosyresekvensen af QQRSNWPPLT (SEQ ID NR:32), og hvor antistoffet endvidere omfatter en variabel tung-kæde omfattende aminosyresekvensen af SEQ ID NR: 2 og en variabel let-kæde omfattende aminosyresekvensen af SEQ ID NR: 4.
5. Antistof ifølge krav 1 eller fragment deraf, omfattende en tung-kæde med tre CDRs, omfattende et VH CDR1 omfattende aminosyresekvensen af GYGMH (SEQ ID NR:27); et VH CDR2 omfattende aminosyresekvensen af VIWYDGSKKYYVDSVKG (SEQ ID NR:28); et VH CDR3 omfattende aminosyresekvensen af QMGYWHFDL (SEQ ID NR:29) og en let-kæde med tre CDRs, omfattende et VL CDR1 omfattende aminosyresekvensen af RASQSVSSYLA (SEQ ID NR:30); et VL CDR2 omfattende aminosyresekvensen af DASNRAT (SEQ ID NR:31); og et VL CDR3 omfattende aminosyresekvensen af QQRSNWPPLT (SEQ ID NR:32), og hvor antistoffet endvidere omfatter en variabel tung-kæde omfattende aminosyresekvensen af SEQ ID NR:6 og en variabel let-kæde omfattende aminosyresekvensen af SEQ ID NR: 8.
6. Antistof ifølge krav 1 eller fragment deraf, der har en tung-kæde med tre CDRs, omfattende et VH CDR1 omfattende aminosyresekvensen SYGMH (SEQ ID NR:33); et VH CDR2 omfattende aminosyresekvensen af IIWYDGSKKNYADSVKG (SEQ ID NR:34); et VH CDR3 omfattende aminosyresekvensen af GTGYNWFDP (SEQ ID NR:35); og en let-kæde med tre CDRs omfattende et VL CDR1 omfattende aminosyresekvensen af RASQSVSSSYLA (SEQ ID NR:36); RASQGISSALA (SEQ ID NR:39); eller WASQGISSYLA (SEQ ID NR:43); et VL CDR2 omfattende aminosyresekvensen af GASSRAT (SEQ ID NR:37), YASSLQS (SEQ ID NR:40) eller DASSLGS (SEQ ID NR:42); og et VL CDR3 omfattende aminosyresekvensen af QQYGSSPIT (SEQ ID NR:38) eller QQYYSTLT (SEQ ID NR:41), og hvor antistoffet endvidere omfatter en variabel tungkæde omfattende aminosyresekvensen af SEQ ID NR: 10 og en variabel letkæde omfattende aminosyresekvensen af SEQ ID NR: 16, 17, 18, 19 eller 20.
7. Antistof ifølge krav 1 eller fragment deraf, der har en tung-kæde med tre CDRs, omfattende et VH CDR1 omfattende aminosyresekvensen SYGMH (SEQ ID NR:33); et VH CDR2 omfattende aminosyresekvensen af AIWYNGRKQDYADSVKG (SEQ ID NR:44); et VH CDR3 omfattende aminosyresekvensen af GTGYNWFDP (SEQ ID NR:35); og en let-kæde med tre CDRs, omfattende et VL CDR1 omfattende aminosyresekvensen af RASQSVSSYLA (SEQ ID NR:30) eller RASQGISSALA (SEQ ID NR:39); et VL CDR2 omfattende aminosyresekvensen af DASNRAT (SEQ ID NR:31) eller DASSLES (SEQ ID NR:46); og et VL CDR3 omfattende aminosyresekvensen af QQRSNWPWT (SEQ ID NR:45) eller QQFNSYPIT (SEQ ID NR:47), og hvor antistoffet omfatter et tung-kæde variabelt område omfattende aminosyresekvensen af SEQ ID NR: 22 og et let-kæde variabelt område omfattende aminosyresekvensen af SEQ ID NR: 25 eller 26.
8. Antistof ifølge krav 1 eller fragment deraf, omfattende et framework 2-område (FWR2) omfattende aminosyresekvensen WVRQAPGKGLEWV (SEQ ID NR:73).
9. Antistof ifølge krav 1 eller fragment deraf, omfattende et framework 3- område (FRW3) omfattende aminosyresekvensen RFTISRDNSKNTLYLQMNSLRAEDTAVYYCA (SEQ ID NR:74).
10. Antistof ifølge krav 1 eller fragment deraf, omfattende et variabelt område beliggende C-terminal til CDR3-området, hvor det variable område omfatter aminosyresekvensen VTVSS (SEQ ID NR:64) ved en position, der er C-terminal til CDR3-området.
11. Antistof ifølge krav 10 eller fragment deraf, omfattende et variabelt område beliggende C-terminal til CDR3-området, hvor det variable område omfatter aminosyresekvensen GTLVTVSS (SEQ ID NR:65) ved en position, der er C-terminal til CDR3-området.
12. Antistof ifølge krav 10 eller fragment deraf, omfattende et variabelt område beliggende C-terminal til CDR3-området, hvor det variable område omfatter aminosyresekvensen WGRGTLVTVSS (SEQ ID NR:66) ved en position, der er C-terminal til CDR3-området.
13. Farmaceutisk sammensætning omfattende et antistof eller et fragment deraf ifølge et hvilket som helst af krav 1 til 12.
14. Antistof eller fragment deraf ifølge et hvilket som helst af de foregående krav til anvendelse som medikament.
15. Anvendelse af antistoffet eller fragmentet deraf ifølge et hvilket som helst af krav 1 til 12 til fremstilling af et medikament til behandling eller forebyggelse af et med en immunrelateret sygdom associeret symptom eller et symptom, der er relateret til afstødelse associeret med organtransplantation.
16. Anvendelse ifølge krav 15, hvor individet yderligere indgives et andet middel.
17. Anvendelse ifølge krav 15, hvor den immunrelaterede sygdom er udvalgt fra en autoimmunsygdom og en inflammatorisk lidelse.
18. Isoleret nukleinsyremolekyle, der koder for et antistof eller et fragment deraf ifølge et hvilket som helst af krav 1 til 12.
19. Vektor, omfattende nukleinsyremolekylet ifølge krav 18.
20. Værtscelle, omfattende vektoren ifølge krav 19.
21. Fremgangsmåde til fremstilling af antistoffet or fragmentet deraf ifølge et hvilket som helst af krav 1 til 12, omfattende trinnene dyrkning af værtscellen ifølge krav 20 under betingelser, der er egnede til produktion af antistoffet.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US57648304P | 2004-06-03 | 2004-06-03 | |
US60915304P | 2004-09-10 | 2004-09-10 | |
PCT/US2005/019922 WO2005118635A2 (en) | 2004-06-03 | 2005-06-03 | Anti-cd3 antibodies and methods of use thereof |
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Publication Number | Publication Date |
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DK1753783T3 true DK1753783T3 (da) | 2014-11-17 |
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Application Number | Title | Priority Date | Filing Date |
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DK05761845.6T DK1753783T3 (da) | 2004-06-03 | 2005-06-03 | Anti-cd3-antistoffer og fremgangsmåder til anvendelse deraf |
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Country | Link |
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US (5) | US7728114B2 (da) |
EP (1) | EP1753783B1 (da) |
JP (5) | JP5139800B2 (da) |
KR (1) | KR101266716B1 (da) |
AU (1) | AU2005250499B2 (da) |
BR (1) | BRPI0511782B8 (da) |
CA (1) | CA2569509C (da) |
DK (1) | DK1753783T3 (da) |
EA (1) | EA010350B1 (da) |
ES (1) | ES2526343T3 (da) |
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