HRP20110503T1 - MODIFICIRANE FUZIJE IZMEĐU TOPIVOG FGF RECEPTORA I Fc, S POBOLJŠANOM BIOLOŠKOM AKTIVNOŠĆU - Google Patents
MODIFICIRANE FUZIJE IZMEĐU TOPIVOG FGF RECEPTORA I Fc, S POBOLJŠANOM BIOLOŠKOM AKTIVNOŠĆU Download PDFInfo
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- HRP20110503T1 HRP20110503T1 HR20110503T HRP20110503T HRP20110503T1 HR P20110503 T1 HRP20110503 T1 HR P20110503T1 HR 20110503 T HR20110503 T HR 20110503T HR P20110503 T HRP20110503 T HR P20110503T HR P20110503 T1 HRP20110503 T1 HR P20110503T1
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- fgf receptor
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- 108091008794 FGF receptors Proteins 0.000 claims abstract 56
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 claims abstract 56
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Abstract
Modificirana fuzija između topivog FGF receptora i Fc, gdje je to fuzija između topivog fragmenta ili domene FGF receptora s Fc područjem imunoglobulina, naznačena time što prosječni broj jedinica sialinske kiseline po N-glikanu u FGF receptorskom ostatku je 0,9 ili veći. Patent sadrži još 38 patentnih zahtjeva.
Claims (39)
1. Modificirana fuzija između topivog FGF receptora i Fc, gdje je to fuzija između topivog fragmenta ili domene FGF receptora s Fc područjem imunoglobulina, naznačena time što prosječni broj jedinica sialinske kiseline po N-glikanu u FGF receptorskom ostatku je 0,9 ili veći.
2. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 1, naznačena time što prosječni broj jedinica sialinske kiseline po N-glikanu u FGF receptorskom ostatku je 1,2 ili veći.
3. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 1 ili 2, naznačena time što najviše 45% N-glikana u navedenom FGF receptorskom ostatku ne nosi sialilnu skupinu.
4. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačena time što je u najmanju ruku zauzeto 5. N-glikozilacijsko mjesto u FGF receptorskom ostatku.
5. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 4, naznačena time što je, uz to, zauzeto i 3., 4., 6. i 7. N-glikozilacijsko mjesto u FGF receptorskom ostatku.
6. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 5, naznačena time što je u najmanju zauzeto ruku 7 N-glikozilacijskih mjesta u FGF receptorskom ostatku.
7. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 6, naznačena time što su zauzeta sva N-glikozilacijska mjesta u FGF receptorskom ostatku.
8. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što vrijednost KD kod navedene fuzije za FGF2, prilikom mjerenja pomoću Biacore™, je između 1 i 5 nM.
9. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 8, naznačena time što vrijednost KD kod navedene fuzije za FGF2, prilikom mjerenja pomoću Biacore™, je otprilike 1,5 nM.
10. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što navedena fuzija posjeduje ADCC i/ili CDC aktivnost.
11. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što N-glikani u navedenoj fuziji su fukozilirani 60-100%.
12. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što navedena modificirana fuzija između topivog FGF receptora i Fc sadrži 3 manozna ostatka, u prosjeku 1,5 do 3,0 galaktoznih ostataka, u prosjeku 3,5 do 5 N-acetilglukozaminskih ostataka, te u prosjeku 0,6 do 1 fukozni ostatak po molekuli glikana.
13. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od patentnih zahtjeva 1 do 10, naznačena time što N-glikani u navedenoj fuziji su fukozilirani 0-60%.
14. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što FGF receptor se bira između FGF receptora 1 (FGFR1) i FGF receptora 2 (FGFR2).
15. Modificirani fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što FGF receptor se bira između izotipa IIIc FGF receptora 1 i izotipa IIIc FGF receptora 2.
16. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što topiva domena FGF receptora ima slijed kao što je iznijet u SEQ ID NO:4, ili slijed koji je u najmanju ruku 95% identičan sa SEQ ID NO:4.
17. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što Fc dio ima slijed kao što je iznijet u SEQ ID NO:6, ili slijed koji je u najmanju ruku 95% identičan sa SEQ ID NO:6.
18. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što navedena modificirana fuzija između topivog FGF receptora i Fc dodatno sadrži vezni slijed od najmanje 3 aminokiselinska ostatka.
19. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 18, naznačena time što vezni slijed je SAL (Ser-Ala-Leu).
20. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što modificirana fuzija između topivog FGF receptora i Fc ima polipeptidni slijed kao što je iznijet u SEQ ID NO:2, ili slijed koji je u najmanju ruku 95% identičan sa SEQ ID NO:2.
21. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačena time što modificirana fuzija između topivog FGF receptora i Fc dodatno sadrži signalni peptid sa SEQ ID:2
22. Stanica-domaćin, naznačena time što sadrži (i) nukleinsku kiselinu koja kodira modificiranu fuziju FGF receptora u skladu s bilo kojim od patentnih zahtjeva 1 do 21, (ii) nukleinsku kiselinu koja kodira α-1,4-galaktozil-transferazu i (iii) nukleinsku kiselinu koja kodira β-2,3-sialil-transferazu.
23. Stanica-domaćin u skladu s patentnim zahtjevom 22, naznačena time što navedena nukleinska kiselina koja kodira modificiranu fuziju FGF receptora sadrži nukleinskokiselinski slijed koji je u najmanju ruku 80 % identičan s nukleinskokiselinskim slijedom iz SEQ ID NO:1.
24. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od patentnih zahtjeva 1 do 21, naznačena time što je namijenjena da bude medikament.
25. Farmaceutski pripravak, naznačen time što sadrži modificiranu fuziju FGF receptora u skladu s bilo kojim od patentnih zahtjeva 1 do 21.
26. Farmaceutski pripravak u skladu s patentnim zahtjevom 25, naznačen time što navedeni pripravak sadrži dodatno terapijsko sredstvo.
27. Farmaceutski pripravak u skladu s patentnim zahtjevom 26, naznačen time što navedeno dodatno terapijsko sredstvo je antiangiogeno sredstvo ili kemoterapijsko sredstvo.
28. Farmaceutski pripravak u skladu s patentnim zahtjevom 27, naznačen time što navedeno antiangiogeno sredstvo je čimbenik tumorske nekroze, ili antagonist kiselog ili bazičnog čimbenika rasta fibroblasta (FGF), čimbenika rasta hepatocita (HGF), tkivnog čimbenika (TF), proteina C, proteina S, čimbenika rasta iz trombocita (PDGF) ili HER2 receptora.
29. Farmaceutski pripravak u skladu s patentnim zahtjevom 27, naznačen time što navedeno kemoterapijsko sredstvo se bira iz skupine koju čine antimikrotubularna sredstva, platinski koordinacijski kompleksi, alkilacijska sredstva, antibiotička sredstva, inhibitori topoizomeraze II, antimetaboliti, inhibitori topoizomeraze I, hormoni i hormonski analozi, inhibitori puteva prijenosa signala, inhibitori nereceptorske angiogene tirozin-kinaze, imunoterapijska sredstva, proapoptotska sredstva, te inhibitori signalizacije staničnog ciklusa.
30. Farmaceutski pripravak u skladu s patentnim zahtjevom 27, naznačen time što navedeno kemoterapijsko sredstvo se bira iz skupine koju čine Taxol i Taxotere.
31. Modificirana fuzija između topivog FGF receptora i Fc u skladu s bilo kojim od patentnih zahtjeva 1 do 21, naznačena time što je namijenjena liječenju raka.
32. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 31, naznačena time što je u kombinaciji s dodatnim terapijskim sredstvom.
33. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 32, naznačena time što navedeno dodatno terapijsko sredstvo je antiangiogeno sredstvo ili kemoterapijsko sredstvo.
34. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 33, naznačena time što navedeno antiangiogeno sredstvo je čimbenik tumorske nekroze, ili antagonist kiselog ili bazičnog čimbenika rasta fibroblasta (FGF), čimbenika rasta hepatocita (HGF), tkivnog čimbenika (TF), proteina C, proteina S, čimbenika rasta iz trombocita (PDGF) ili HER2 receptora.
35. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 33, naznačena time što navedeno kemoterapijsko sredstvo se bira iz skupine koju čine antimikrotubularna sredstva, platinski koordinacijski kompleksi, alkilacijska sredstva, antibiotička sredstva, inhibitori topoizomeraze II; antimetaboliti, inhibitori topoizomeraze I, hormoni i hormonski analozi, inhibitori puteva prijenosa signala, inhibitori nereceptorske angiogene tirozin-kinaze, imunoterapijska sredstva, proapoptotska sredstva, te inhibitori signalizacije staničnog ciklusa.
36. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 33, naznačena time što navedeno kemoterapijsko sredstvo se bira iz skupine koju čine Taxol i Taxotere.
37. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 31, naznačena time što se navedeni rak bira iz skupine koju čine karcinom, uključujući karcinom mokraćnog mjehura, dojke, debelog crijeva, glave i vrata, bubrega, uključujući karcinom bubrežnih stanica, jetra, pluća, jajnika, gušterače, želuca, vrata maternice, štitnjače i kože; uključujući karcinom pločastih stanica; krvotvorni tumori limfoidnog podrijetla, uključujući leukemiju, akutnu limfocitnu leukemiju, akutni limfoblastnu leukemiju, limfom B-stanica, limfom T-stanica, te Burkittov limfom; krvotvorni tumori mijeloidnog podrijetla, uključujući akutne i kronične mijelogene leukemije i promijelocitnu leukemiju; tumori mezenhimnog podrijetla, uključujući fibrosarkom i rabdomiosarkom; drugi tumori, uključujući melanom, seminom, tetratokarcinom, neuroblastom i gliom; tumori središnjeg i perifernog živčanog sustava, uključujući astrocitom, neuroblastom, gliom, te švanomi; tumori mezenhimnog podrijetla, uključujući fibrosarkom, rabdomiosarkome, te osteosarkom; te drugi tumori, uključujući melanom, pigmentnu kserodermu, keratoakantom, seminom, rak folikula štitnjače i teratokarcinom.
38. Modificirana fuzija između topivog FGF receptora i Fc u skladu s patentnim zahtjevom 37, naznačena time što se navedeni rak bira iz skupine koju čine melanom, leukemija, rak bubrega, rak debelog crijeva, rak jajnika, rak prostate, rak pluća, rak mokraćnog mjehura, rak dojke, te rak glave i vrata.
39. Postupak priprave modificirane fuzije između topivog FGF receptora i Fc u skladu s bilo kojim od patentnih zahtjeva 1 do 21, naznačen time što se sastoji u uzgoju stanice-domaćina u skladu s bilo kojim od patentnih zahtjeva 22 ili 23, te u prikupljanju izlučenog proteina.
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| EP07290042 | 2007-01-11 | ||
| PCT/IB2007/004354 WO2008065543A2 (en) | 2006-11-28 | 2007-11-28 | Modified soluble fgf receptor fc fusions with improved biological activity |
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2007
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- 2007-11-27 PE PE2007001663A patent/PE20081250A1/es not_active Application Discontinuation
- 2007-11-27 AR ARP070105241A patent/AR063975A1/es not_active Application Discontinuation
- 2007-11-28 PT PT07866627T patent/PT2092069E/pt unknown
- 2007-11-28 AT AT07866627T patent/ATE509106T1/de active
- 2007-11-28 KR KR1020097013421A patent/KR20090102769A/ko not_active Application Discontinuation
- 2007-11-28 MY MYPI20092137A patent/MY145914A/en unknown
- 2007-11-28 BR BRPI0719290-8A patent/BRPI0719290A2/pt not_active IP Right Cessation
- 2007-11-28 EA EA200970515A patent/EA018700B1/ru not_active IP Right Cessation
- 2007-11-28 AU AU2007326985A patent/AU2007326985C1/en not_active Ceased
- 2007-11-28 JP JP2009538805A patent/JP2010510801A/ja active Pending
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