DK2374472T3 - Sammensætninger og fremgangsmåder til behandling af øjenforstyrrelser - Google Patents

Sammensætninger og fremgangsmåder til behandling af øjenforstyrrelser Download PDF

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DK2374472T3
DK2374472T3 DK11152204.1T DK11152204T DK2374472T3 DK 2374472 T3 DK2374472 T3 DK 2374472T3 DK 11152204 T DK11152204 T DK 11152204T DK 2374472 T3 DK2374472 T3 DK 2374472T3
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Claims (15)

1. Sammensætning, der omfatter mindst én inhibitor af plasmakallikrein, til anvendelse til behandling af en øjenforstyrrelse.
2. Sammensætning til anvendelse ifølge krav 1, hvor øjenforstyrrelsen er en forstyrrelse valgt fra gruppen, der består af: en ekssudativ og/eller inflammatorisk øjenforstyrrelse, en forstyrrelse forbundet med nedsat retinal karpermeabilitet og/eller -integritet, en forstyrrelse forbundet med retinal mikrokarruptur, der fører til fokale blødninger, en sygdom bag i øjet, en retinal sygdom, og en sygdom fortil i øjet.
3. Sammensætning til anvendelse ifølge krav 1 eller 2, hvor øjenforstyrrelsen er en forstyrrelse valgt fra gruppen, der består af: aldersrelateret makuladegeneration (ARMD), ekssudativ makuladegeneration, makulært ødem, aldersrelateret diskoid makuladegeneration, cystisk makulært ødem, palpebralt ødem, retinalt ødem, diabetisk retinopati, akut makulær neuroretinopati, central serøs chorioretinopati, chorioretinopati, choroidal neovaskularisering, neovaskulær makulopati, neovaskulært glaukom, obstruktive arterielle og venøse retinopatier (såsom retinal veneokklusion eller retinal arterieokklusion), central retinal veneokklusion, dissemineret intravaskulær koagulopati, retinal venegrenokklusion, hypertensive fundusforandringer, okulært iskæmisk syndrom, retinale arterielle mikroaneurismer, Coats sygdom, parafoveal telangiektasi, hemiretinal veneokklusion, papillophlebitis, central retinal arterieokklusion, retinal arteriegrenokklusion, karotidarteriesygdom (CAD), frosted branch angiitis, sejlcelleretinopati og andre hæmoglobinopatier, angioide strøg (streaks), diabetisk makulært ædem, øjenskade eller øjenoperation; retinal iskæmi eller degeneration fremkommet ved for eksempel skade, traume eller tumorer, uveitis, iritis, retinal vasculitis, endophthalmitis, panophthalmitis, metastatisk oftalmi, choroiditis, retinal pigment-epithelitis, conjunctivitis, cyclitis, scleritis, episcleritis, optisk neuritis, retrobulbær optisk neuritis, keratitis, blepharitis, ekssudativ retinaløsning, corneasår, konjunktivalt sår, kronisk nummular keratitis, Thygesons keratitis, progressivt Moorens sår, en inflammatorisk øjensygdom forårsaget af bakterie- eller virusinfektion, af en øjenoperation, af en fysisk skade på øjet, klinisk makulært ødem, angiografisk cystisk makulært ødem som følge af forskellige ætiologier, såsom diabetes, ekssudativ makuladegeneration, makulært ødem som følge af laserbehandling af retina, aldersrelateret makuladegeneration, retinopati ved præmaturitet, retinalt iskæmi og choroidal neovaskularisering, retinale sygdomme (diabetisk retinopati, diabetisk retinalt ødem, retinaløsning, senil makuladegeneration som følge af subretinal neovaskularisering, myopisk retinopati); inflammationssygdomme; uveitis i forbindelse med neoplasmer, såsom retinoblastom eller pseudogliom; neovaskularisering efter vitrektomi; vaskulære sygdomme (retinal iskæmi, choroidal vaskulær insufficiens, choroidal trombose, retinopatier som følge af karotidarterie-iskæmi); neovaskularisering af synsnerven, korneal neovaskularisering (som følge af inflammation, transplantation, udviklingshypoplasi i iris, korneale sygdomme eller opacifikationer med en ekssudativ eller inflammatorisk bestanddel, neovaskularisering som følge af penetrering af øjet eller kontusions-øjenskade; kronisk uveitis; anterior uveitis; inflammatoriske tilstande som følge af operationer, såsom LASIK, LASER, refraktionskirurgi, IOL-implantation; irreversibelt cornea-ødem som en komplikation ved kataraktoperation; ødem som følge af insult eller traume (fysisk, kemisk, farmakologisk); inflammation; conjunctivitis (såsom persistent allergisk, giant papillær, sæsonbetinget intermitterende allergisk, helårlig allergisk, toksisk, conjunctivitis forårsaget af infektion af bakterier, virus eller Chlamydia); keratoconjunctivitis (forårsrelateret, atopisk, sicca); iridocyclitis; iritis; scleritis; episcleritis; infektiøs keratitis; overfladisk punktformet keratitis; keratoconus; posterior polymorf dystrofi; Fuchs dystrofier (korneale eller endoteliale); afakisk og pseudofakisk bulløs keratopati; cornea-ødem; skleral sygdom; okulært cicatriciel pemfigoid; pars planitis; Posner Schlossmans syndrom; Behcets sygdom; Vogt-Koyanagi-Haradas syndrom; overfølsomhedsreaktioner; okulære overfladeforstyrrelser; konjunktivalt ødem; toxoplasmosis chorioretinitis; inflammatorisk pseudotumor i øjenhulen; kemose; konjunktival venekongestion; periorbital cellulitis; akut dacryocystitis; ikke-specifik vasculitis; sarkoidose; og cytomegalovirusinfektion.
4. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 3, hvor inhibitoren er en Kunitz-domænepolypeptidinhibitor.
5. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 4, hvor inhibitoren er et peptid, der omfatter aminosyresekvensen: Xaal Xaa2 Xaa3 Xaa4 Cys Xaa6 Xaa7 Xaa8 Xaa9 XaalO Xaall Gly Xaal3 Cys Xaal5 Xaal6 Xaal7 Xaal8 Xaal9 Xaa20 Xaa21 Xaa22 Xaa23 Xaa24 Xaa25 Xaa26 Xaa27 Xaa28 Xaa29 Cys Xaa31 Xaa32 Phe Xaa34 Xaa35 Gly Gly Cys Xaa39 Xaa40 Xaa41 Xaa42 Xaa43 Xaa44 Xaa45 Xaa46 Xaa47 Xaas48 Xaa49 Xaa50 Cys Xaa52 Xaa53 Xaa54 Cys Xaa56 Xaa57 Xaa58 (SEQ ID NO: 1), hvor Xaa'erne uafhængigt af hinanden er en hvilken som helst aminosyre.
6. Sammensætning til anvendelse ifølge krav 5, hvor et eller flere af følgende gælder: Xaal, Xaa2, Xaa3, Xaa4, Xaa56, Xaa57 eller Xaa58 uafhængigt af hinanden er en hvilken som helst aminosyre eller fraværende; XaalO er en aminosyre valgt fra gruppen, der består af Asp og Glu; Xaall er en aminosyre valgt fra gruppen, der består af Asp, Gly, Ser, Val, Asn, Ile, Ala og Thr; Xaal3 er en aminosyre valgt fra gruppen, der består af Arg, His, Pro, Asn, Ser, Thr, Ala, Gly, Lys og Gin; Xaal5 er en aminosyre valgt fra gruppen, der består af Arg, Lys, Ala, Ser, Gly, Met, Asn og Gin; Xaal6 er en aminosyre valgt fra gruppen, der består af Ala, Gly, Ser, Asp og Asn; Xaal7 er en aminosyre valgt fra gruppen, der består af Ala, Asn, Ser, Ile, Gly, Val, Gin og Thr; Xaal8 er en aminosyre valgt fra gruppen, der består af His, Leu, Gin og Ala; Xaal9 er en aminosyre valgt fra gruppen, der består af Pro, Gin, Leu, Asn og Ile; Xaa21 er en aminosyre valgt fra gruppen, der består af Trp, Phe, Tyr, His og Ile; Xaa22 er en aminosyre valgt fra gruppen, der består af Tyr og Phe ; Xaa23 er en aminosyre valgt fra gruppen, der består af Tyr og Phe ; Xaa31 er en aminosyre valgt fra gruppen, der består af Glu, Asp, Gin, Asn, Ser, Ala, Val, Leu, Ile og Thr; Xaa32 er en aminosyre valgt fra gruppen, der består af Glu, Gin, Asp Asn, Pro, Thr, Leu, Ser, Ala, Gly og Val; Xaa34 er en aminosyre valgt fra gruppen, der består af Thr, Ile, Ser, Val, Ala, Asn, Gly og Leu; Xaa35 er en aminosyre valgt fra gruppen, der består af Tyr, Trp og Phe; Xaa39 er en aminosyre valgt fra gruppen, der består af Glu, Gly, Ala, Ser og Asp; Xaa40 er en aminosyre valgt fra gruppen, der består af Gly og Ala; Xaa43 er en aminosyre valgt fra gruppen, der består af Asn og Gly; Xaa45 er en aminosyre valgt fra gruppen, der består af Phe og Tyr; Xaa6, Xaa7, Xaa8, Xaa9, Xaa20, Xaa24, Xaa25, Xaa26, Xaa27, Xaa28, Xaa29, Xaa41, Xaa42, Xaa44, Xaa46, Xaa47, Xaa48, Xaa49, Xaa50, Xaa52, Xaa53 og Xaa54 uafhængigt af hinanden er en hvilken som helst aminosyre.
7. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 6, hvor inhibitoren er et peptid valgt fra gruppen, der består af: Glu Ala Met His Ser Phe Gys Ala Phe Lys Ala Asp Asp Gly Pro Cys Arg Ala Ala His Pro Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly G!y Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:23> Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Arg Aia Ala His Pro Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Gys Glu Glu Phe Ile Tyr Gly Gly Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:2), Met His Ser Phe Cys Ala Phe Lys Ala Xaa10 Xaa11 Gly Xaat3 Cys Xaa15 Xaa16 Xaa17Xaa18Xaa13 Arg Xaa21 Phe Phe Asn Ile Phe Thr Arg Gin Cys Xaa31 Xaa32 Phe Xaa34 Xaa35 Gly Gly Cys Xaa39 Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp(SEQ ID NG:3), Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Lys Ala Asn His Leu Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Giy Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:4), Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Lys Ala Asn His Gin Arg Phe Phe Phe Asn De Phe Thr Arg Gin Cys Glu Glu Phe Thr Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Le« Glu Glu Cys Lys Lvs Met Cys Thr Arg Asp (SEQ ID N0:5), Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Lys Ala Asn His Gin Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Gin Phe Thr Tyr Gly Gly Cys Ala Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:6), Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Lys Ala Ser Leu Pro Arg Phe Phe Phe Asn le Phe Thr Arg Gin Cys Glu Glu Phe ile Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:7)t Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Lys Ala Asn His Gin Arg Phe Phe Phe Asn De Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:8), Met His Ser Phe Cys Åla Phe Lys Ala Asp Asp Gly His Cys Lys Gly Ala His Leu Arg Phe Phe Phe Asn De Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Gly Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:9), Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Arg Cys Lys Gly Ala His Leu Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe De Tyr Gly Gly Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO: 10), Met His Ser Phe Cys Ala Phe Lys Ala Asp Gly Gly Arg Cys Arg Gly Ala His Pro Arg Trp Phe Phe Asn De Phe Thr Arg Gin Cys Gin Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Len Glu Glu Cys Lys Lys Met Cys Thr Arg Asp(SEQ ID NO: 11), Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Arg Ala Ala His Pro Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Cys Gin Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO: 12), Met His Ser Phe Cys Ala Phe Lys Ala Asp Val Gly Arg Cys Arg Gly Ala His Pro Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Lea Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO: 13), Met His Ser Phe Cys Ala Phe Lys Ala Asp Val Gly Arg Cys Arg Gly Ala Gin Pro Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO: 14), Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Ser Cys Arg Ala Ala His Leu Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Åsn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Gys Thr Arg Asp (SEQ ID NO: 15), Met His Ser Phe Cys Ala Phe Lys Åla Glu Gly Gly Ser Cys Arg Ala Ala His Gin Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO: 16), Met His Ser Phe Cys Åla Phe Lys Ala Asp Asp Gly Pro Cys Arg Gly Ala His Leu Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO: 17), Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Arg Gly Ala Leu Pro Arg Trp Phe Phe Asn De Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NOTS), Met His Ser Phe Cys Ala Phe Lys Ala Asp Ser Gly Asn Cys Arg Gly Asn Leu Pro Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO: 19), Mel His Ser Phe Cys Ala Phe Lys Ala Asp Ser Gly Arg Cys Arg Gly Asn His Gin Arg Phe Phe Phe Asn ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:20), Met His Ser Phe Cys Ala Phe Lys Ala Asp Gly Gly Arg Cys Arg Ala Ile Gin Pro Arg Trp Phe Phe Asn De Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:21), Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Arg Cys Arg Gly Ala His Pro Arg Tip Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp {SEQ ID NO;22). Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala XaalO Xaal 1 Gly Xaal3 Cys XaalS Xaal6 Xaal7 XaalS Xaal? Arg Xaa21 Phe Phe Asn Ile Phe Thr Arg Gin Cys Xaa31 Xaa32 Phe Xaa34 Xaa35 Gly Gly Cys Xaa39 Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ IQ NO;24 b Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Lys Ala Asn His Leu Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Gla Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:25). Glu Ala Mel His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Lys Ala Asn His Gin Arg Phe Phe Phe Asm Ile Phe Thr Arg Gin Cys Glu Glu Phe Thr Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ IDNO:26), Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Lys Ala Asn His Gin Arg Phe Phe Phe Asn De Phe Thr Arg Gin Cys Glu Gin Phe Thr Tyr Gly Gly Cys Ala Gly Asn Gin Asn Arg Phe Glu Ser Len Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:27), Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Lys Ala Ser Leu Pro Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:28), Glu Aia Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Lys Ala Asn His Gin Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:29), Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Lys Gly Ala His Leu Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Gly Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ IDNO:30), Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Arg Cys Lys Gly Ala His Leu Arg Phe Phe Phe Asn De Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Gly Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glo Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ Π5 ΝΟ:31), Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Gly Gly Arg Cys Arg Gly Ala His Pro Arg Trp Phe Phe Asn De Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Len Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:32), Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Arg Ala Ala His Pro Arg Trp Phe Phe Asn De Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Lea Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ IDNO:33), Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Val Gly Arg Cys Arg Gly Ala His Pro Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:34), Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Val Gly Arg Cys Arg Gly Ala Gin Pro Arg Phe Phe Phe Asn De Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Åsa Gin Asn Arg Phe Glu Ser Leu Glu GI« Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID >10:35), Glu Ala Met His Ser Pie Cys Ala Phe Lys Ala Asp Asp Gly Ser Cys Arg Ala Ala His Leu Arg Tip Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ Ip NO»3S). Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Glu Gly Gly Ser Cys Arg Ala Ala His Glu Arg Trp Phe Phe Asn He Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:37), Glu Ala Mat His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Arg Gly Ala His Leu Arg Phe Phe Phe Asn 1te Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Giy Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Gys Lys Lys Met Cys Thr Arg Asp (SEQ I DN0:3S), Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly His Cys Arg Gly Ala Leu Pro Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Aig Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:39), Glu Ala Met His Ser Phe Cys Ala Phe Lys Aa Asp Ser Gly Asn Cys Arg Gly Asn Leu Pro Arg Phe Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID N O 40) Glu Ala Mel His Ser Phe Cys Ala 3he Lys Ala Asp Ser Gly Arg Cys Arg Gly Asn His Gin Arg Phe Phe ^hø Asr Te Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr A?ng Asp (SEQ ID NQ;41), Glu Ala Met His Ser Phe Cys Aa Phe Lys Ala Asp Gly Gly Arg Cys Arg Ala Ile Gin Pro Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO: -*2), and Glu Ala Met His Ser Phe Gys Ala Phe Lys Ala Asp Asp Gly Arg Gys Arg Gly Ala His Pro Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ser Tyr Gly Gly Cys Gly Gty Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Gys Lys Lys Met Cys Thr Arg Asp (SEQ ID N 0:43).
8. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 7, hvor inhibitoren er et peptid, der omfatter Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Arg Ala Ala His Pro Arg Trp Phe Phe Asn Ile Phe Thr Arg Gin Cys Glu Glu Phe Ile Tyr Gly Gly Cys Glu Gly Asn Gin Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO: 23) .
9. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 8, der omfatter en fysiologisk saltvandsopløsning.
10. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 9, hvor sammensætningen er udformet til administration i kombination med en anden terapi.
11. Sammensætning til anvendelse ifølge krav 10, hvor den anden terapi er udvalgt fra gruppen, der består af: fotodynamisk terapi, laserkirurgi, laserfotokoagulation, en biologisk behandling og en farmaceutisk behandling.
12. Sammensætning til anvendelse ifølge et hvilket som helst af kravene 1 til 11, hvor forstyrrelsen er ekssudativ retinopati, myofisk retinopati, makulært ødem, ekssudativ makuladegeneration, diabetisk retinopati eller retinal iskæmi, og sammensætningen omfatter et anti-angiogent middel.
13. Sammensætning til anvendelse ifølge krav 12, hvor det anti-angiogene middel blokerer aktiviteten af VEGF på endotelceller.
14. Sammensætning til anvendelse ifølge krav 1 til 13, hvor sammensætningen er til intravitreal injektion.
15. Sammensætning til anvendelse ifølge krav 14, hvor inhibitoren er til administration ved en koncentration på: mindre end 20 mg/ml, mindre end 7 mg/ml, mindre end 6 mg/ml, mindre end 5 mg/ml, mindre end 4 mg/ml, mindre end 3 mg/ml, mindre end 2 mg/ml eller mindre end 1 mg/ml, 5 gg/ml til 50 gg/ml, 35 gg/ml til 100 gg/ml, 100 gg/ml til 200 gg/ml, 200 gg/ml til 500 gg/ml, 500 gg/ml til 750 gg/ml eller 500 gg/ml til 1 mg/ml eller 21,2 gg/øje.
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EP1854477B9 (en) 2018-03-14
CY1121044T1 (el) 2019-12-11
EP1854477A3 (en) 2008-06-11
EP1854477A2 (en) 2007-11-14
EP2374472A3 (en) 2012-05-16
EP1854477B1 (en) 2016-08-03
CY1118767T1 (el) 2017-07-12
PL2374472T3 (pl) 2018-11-30
EP2374472A2 (en) 2011-10-12
EP2374472B1 (en) 2018-05-02
EP2374472B9 (en) 2019-06-12

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