DK2657252T3 - Modificeret humant tumornekrosefaktor-receptor-1-polypeptid eller fragment deraf og fremgangsmåde til fremstilling deraf - Google Patents

Modificeret humant tumornekrosefaktor-receptor-1-polypeptid eller fragment deraf og fremgangsmåde til fremstilling deraf Download PDF

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DK2657252T3
DK2657252T3 DK11851725.9T DK11851725T DK2657252T3 DK 2657252 T3 DK2657252 T3 DK 2657252T3 DK 11851725 T DK11851725 T DK 11851725T DK 2657252 T3 DK2657252 T3 DK 2657252T3
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Sung Wuk Kim
Sung Soo Jun
Seung Kook Park
Song Young Kim
Eun Sun Kim
Jae Kap Jeong
Ha Na Kim
Yeon Jung Song
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Hanall Biopharma Co Ltd
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Claims (18)

1. Modificeret tumornekrosefaktor-receptor-l-polypeptid omfattende en aminosyresekvens valgt fra gruppen bestáende af: en aminosyresekvens omfattende en aminosyremodifikation valgt fra gruppen bestaende af L68V/S92I/H95F/R97P/H98A, L68V/S92M/H95F/R97P/H98A, L68V/S92H/H95F/R97P/H98A, L68V/S92I/H95F/R97P/H98G og L68V/S92M/H95F/R97P/H98G i en aminosyresekvens (TNFRI171) bestaende af aminosyrerne 41-211 af en aminosyresekvens af et vild-type tumornekrosefaktor-receptor-l-polypeptid vist med SEQ ID NO: 1; en aminosyresekvens omfattende en aminosyremodifikation valgt fra gruppen bestaende af L68V/S92I/H95F/R97P/H98A, L68V/S92M/H95F/R97P/H98A, L68V/S92H/H95F/R97P/H98A, L68V/S92I/H95F/R97P/H98G og L68V/S92M/H95F/R97P/H98G i en aminosyresekvens (TNFRI126) bestaende af aminosyrerne 41-166 af en aminosyresekvens af et vild-type tumornekrosefaktorreceptor-l-polypeptid vist med SEQ ID NO: 1; og en aminosyresekvens omfattende en aminosyremodifikation valgt fra gruppen bestaende af L68V/S92I/H95F/R97P/H98A, L68V/S92M/H95F/R97P/H98A, L68V/S92H/H95F/R97P/H98A, L68V/S92I/H95F/R97P/H98G og L68V/S92M/H95F/R97P/H98G i en aminosyresekvens (TNFRI105) bestaende af aminosyrerne 41-145 af en aminosyresekvens af et vild-type tumornekrosefaktorreceptor-l-polypeptid vist med SEQ ID NO: 1.
2. Modificeret tumornekrosefaktor-receptor-l-polypeptid ifolge krav 1, hvor aminosyresekvensen baseret pá aminosyresekvensen af TNFRI171 endvidere omfatter en modifikation af en aminosyregruppe ved position 161 eller 207; eller aminosyresekvensen baseret pá aminosyresekvensen af TNFRI126 endvidere omfatter en modifikation af en aminosyregruppe ved position 161.
3. Modificeret tumornekrosefaktor-receptor-l-polypeptid ifolge krav í, hvor aminosyregrupperne er modificeret pá en sádan máde at: K ved position 161 er substitueret med Q eller N; og D ved position 207 er substitueret med N.
4. Modificeret tumornekrosefaktor-receptor-l-polypeptid ifolge krav 1, hvor aminosyresekvensen baseret pá aminosyresekvensen ofTNFRI171 yderligere omfatter en substitution af E med P ved position 93; eller aminosyresekvensen baseret pá aminosyresekvensen of TNFRI126 yderligere omfatter en substitution af E med P ved position 93.
5. Modificeret tumornekrosefaktor-receptor-l-polypeptid ifplge krav 2, omfattende en aminosyremodifikation valgt fra gruppen bestáende af L68V/S92I/H95F/R97P/H98A/K161Q, L68V/S92I/H95F/R97P/H98A/K161N, L68V/S92I/H95F/R97P/H98A/D207N, L68V/S92M/H95F/R97P/H98A/K161Q, L68V/S92M/H95F/R97P/H98A/K161N, L68V/S92M/H95F/R97P/H98A/D207N, L68V/S92H/H95F/R97P/H98A/K161Q, L68V/S92H/H95F/R97P/H98A/K161N, L68V/S92H/H95F/R97P/H98A/D207N, L68V/S92I/H95F/R97P/H98G/K161Q, og L68V/S92M/H95F/R97P/H98G/K161N.
6. Modificeret tumornekrosefaktor-receptor-l-polypeptid ifolge krav 1, omfattende en aminosyresekvens valgt fra gruppen bestáende af SEQ ID NOS: 39, 44, 49, 54, 55, 61-72, 75, 78, 81, 82, og 86-98.
7. Polypeptidkompleks, omfattende to eller flere kopier af modificeret tumornekrosefaktor-receptor-l-polypeptid ifplge et hvilket som helst af kravene 1 til 6, hvilke kopier er kovalent bundet med hinanden.
8. Modificeret tumornekrosefaktor-receptor-l-polypeptid ifplge et hvilket som helst af kravene 1 til 6, yderligere omfattende en kemisk modifikation valgt fra gruppen bestáende af glycosylering, acylering, methylering, phosphorylering, hasylering, carbamylering, sulfation, prenylering, oxidation, guanidination, amidination, carbamylation, trinitrophenylering, nitrering, og PEGylering.
9. Modificeret tumornekrosefaktor-receptor-l-polypeptid, omfattende en aminosyresekvens omfattende en aminosyremodifikation af L68V/S92M/H95F/R97P/H98G/K161N ¡ en aminosyresekvens bestáende af aminosyrerne 41-211(TNFRI171) af en aminosyresekvens af et vild-type tumornekrosefaktorreceptor-l-polypeptid vist med SEQ ID NO: 1.
10. Gen omfattende en nukleotidsekvens der koder for et modificeret tumornekrosefaktor-receptor-l-polypeptid ifolge et hvilket som helst af kravene 1 til 6.
11. Genet ifplge krav 10, konstrueret pá basis af nukleotidsekvensen af SEQ ID NO: 5 med codonmodifikationer, hvilke codonmodifikationer er fremstillet sá at genet kan blive udtrykt ¡ E. coli.
12. En vektor der baerer genet ¡folge krav 10.
13. Celle, transformeret med vektoren ¡folge krav 12.
14. Cellen ifolge krav 13, hvor cellen er E. coli.
15. Farmaceutisk formulering, omfattende modificeret tumornekrosefaktor-receptor-l-polypeptidet ifolge et hvilket som helst af kravene 1 til 6.
16. Farmaceutisk sammensaetning til anvendelse i en fremgangsmáde til forebyggelse eller behandling af en TNF-medieret sygdom valgt fra gruppen bestáende af voksen-respiratorisk lidelsessyndrom, anoreksi, cáncer, kronisk traethedssyndrom, graft-versus-host afstodning, hyperalgesi, ¡nflammatorisk tarmsygdom, neuroinflammatorisk sygdom, ¡skaamisk/reperfusionsskade herunder cerebral ¡skaemi-, hjerneskade som folge af traume, epilepsi, haemorrhag eller slagtilfaelde, der hver kan fore til neurodegeneration, diabetes, multipel sclerose, ojensygdomme, smerte, pancreatitis, pulmonaar fibrose, rheumatoid arthritis, osteoarthritis, juvenil (rheumatoid) arthrltls, sero-negatlv polyarthritis, ankyloserende spondylitis, Reiter's syndrom og reaktiv arthritis, psoriatisk arthrltis, enteropatisk arthrltls, polymyosltls, dermatomyosltis, dermatosclerose, systemlsk sclerose, vasculltls, cerebral vasculltls, Sjogren's syndrom, rheumatoid feber, polychondrltls, polymyalgl rheumatlca, rheumatoid og storcellearterltls, septlsk chok, radloterapl-lnducerede blvlrknlnger, systemlsk lupus erythematosus, temporomandlbular ledsygdom, thyroldltls, og vaevstransplantatlon, omfattende modlflceret tumornekrosefaktor-receptor-1-polypeptld ¡folge et hvllket som helst af kravene 1 til 6.
17. Farmaceutlsk sammenssetnlng til anvendelse I en fremgangsmáde til forebyggelse eller behandllng af en TNF-medleret sygdom valgt fra gruppen bestáende af voksen-resplratorisk lidelse-syndrom, anoreksl, cáncer, kronisk traethedssyndrom, graft-versus-host afstpdnlng, hyperalgesl, ¡nflammatorlsk tarmsygdom, neurolnflammatorisk sygdom, iskaemi herunder cerebral iskaemi-/reperfuslonsskade, traume, epllepsl og haemorrhag, hver kausatlv af neurodegeneratlon, eller hjerneskade stammende fra spasme, diabetes, multlpel sclerose, ojensygdomme, smerte, pancreatitis, pulmonaer fibrose, rheumatoid arthrltls, osteoarthritis, juvenil (rheumatoid) arthrltls, sero-negatlv polyarthritis, ankyloserende spondylitis, Reiter's syndrom og reaktiv arthrltls, psoriatisk arthrltls, enteropatisk arthrltls, polymyosltls, dermatomyosltis, dermatosclerose, systemisk sclerose, vasculltis, cerebral vasculltis, Sjogren's syndrom, rheumatoid feber, polychondrltls, polymyalgl rheumatlca, rheumatoid og storcellearterltls, septlsk chok, radloterapl-lnducerede blvlrknlnger, systemlsk lupus erythematosus, temporomandlbular ledsygdom, thyroldltis, og vaevstransplantation, omfattende genet ¡folge krav 10 eller en vektor der bserer genet.
18. Fremgangsmáde til fremstllllng af det modlflcerede humane tumornekrose-faktor-receptor-l-polypeptld ¡folge et hvllket som helst af kravene 1 til 6, omfattende anvendelse af genet ifolge krav 10 eller en vektor der baerer genet.
DK11851725.9T 2010-12-23 2011-12-21 Modificeret humant tumornekrosefaktor-receptor-1-polypeptid eller fragment deraf og fremgangsmåde til fremstilling deraf DK2657252T3 (da)

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WO2012087017A2 (ko) 2012-06-28
CN103370334A (zh) 2013-10-23
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EP2657252A4 (en) 2015-02-25
US20120277142A1 (en) 2012-11-01
CN103370334B (zh) 2016-06-22
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KR101185310B1 (ko) 2012-09-21
US8754037B2 (en) 2014-06-17
ES2626418T3 (es) 2017-07-25
PL2657252T3 (pl) 2017-08-31
WO2012087017A3 (ko) 2012-08-16
JP5819439B2 (ja) 2015-11-24
JP2014501528A (ja) 2014-01-23

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