HUE034320T2 - Alfa-szinuklein csonkolt fragmensei lewy-testes betegségben - Google Patents
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- HUE034320T2 HUE034320T2 HUE04776059A HUE04776059A HUE034320T2 HU E034320 T2 HUE034320 T2 HU E034320T2 HU E04776059 A HUE04776059 A HU E04776059A HU E04776059 A HUE04776059 A HU E04776059A HU E034320 T2 HUE034320 T2 HU E034320T2
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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Claims (8)
- ttEM eSÛNKÛl^ FlMOMlMSEI LE W^krESTESrBLl'DCíSÉDBElk BzaMiaimb^ l< Jn vîtm êIjÉbs LBD: kezelésére alkalmazható Ikinsfcokkiíti aktivitási i|ÄÄtÖlÄgm amely Μ* taitMZKá a következők·",: ss ágens érimkezteterc L«wy4^ss' betegségben szenvedő betegekben jelenlévő alia-szinnkíein-íragmeipé|: amsly 8s*al jsllesnsalt, hogy benne intakt alfa-szmukléhi M egyseást követő: mhinosákja ék äs intakt alla-szisukMn C*temÉtáibsáröl lv2E egymást kővető sonnosav í|e|őeié|a yan. jőlesyéy: ss sife^szintíkiem-fragmens m*gr®|ééi|já arányának vagy ahol az ágenst: nem tmÄÜäaö kontrolihoz képest m- égPbhhkíŐ arányának: vágy météékének esökksnte azt. jelzi, hogy «s ágens; feli- ajmnakalógiai„aktivitással,
- 2. In vitro eljárás ágens LBD kezelésében alhaitnazható farmakológia! aktivitásának szkFióelésére, atneíy íartahnazsa: á köveíkeáókef: aiía-színukleln: sí<presszáió és az alfa-szinnkleint IVagmenssé iMdolgozo sóst árihíkezísteso az ágeassei, ahoi a Iktgtnens jelen van Lewy--ies<tes betegségben szenvedő betegekben es azzal jtOleffizéít, hogy ®a· -tetük! alfa-iszinukiein 100 egymást követő aminosavja és az intakt atfa-szíttukleln C-terniláiMsáfőiLD2S egymást kővető anmmsav deléciója van jelen; és a fragment, szinténekmmghmározásá a sejtben Séjib^^âptWÂÿà^»· ó^rfetö alapszinthez képesi; az alapszinthez képest a frágntens szintjének esőkkenése ázt jélzi. hely á&jágéatrHűi® Imseisglhen alk&k mázható farmakotőgiai aktlvhàs&al, ahol a sejt előnyösen embert sejt, előnyösebben nettrális sejt vags dopatníttetg sejt. 3. kijárás LBD kezelésére aíkuhnazható farmakológia! aktivitásai ágens szkrinelésére, amely tartalmazza a következőkét: entiSetiöl különböző, Lewy-iestes betegségben szenvedő betegekben jelenlévő alfa-«smüíeín-' 'fragmstïst etíptesazaiő: ttsäPszgstrikns állal éfsntleztetóáé az ágenssel, áhöl aiitagírtens $g$?]i jfcHésnzgtt, .bogy az intakt alta-szlnnkiein 100 egymást kővető ammosavja és az intakt alfa-színuklein C-tcrrmnáiisáröl i-25 egymást követő tmmmszv deléctőja van jelen; és a: fiegmens aggregéi! lórinál szinttének megaatárezása a franszgenikus állat agyában a fetgmgnssggregai! for?·· máinak összehgsmtlitható ttanszgetnkus áilathaii az ágens hiányában mérhető alapszintjöhöziképest. az alapszirhíiéz képea· a fragment, aggregált formái szintjenek csökkenése azt jelzi, hogy az ágasa brr az LBD; kezelésében afeimaz ható l&tn uko lógta i akti v hássa :, ahol a laaaszgentktjs állat előnyösen egér vagy Drosophila 4iv llljárás ágens LBD kezelésére alkalmazható farmakológiai aktivitásának szkrineléséré; amely tartalmazza a hövetkezbfe embertől különböző, »Ifa-szinukkittt espresszálő és az aífa-szim-kieim totgmenssá fei» áőlgozó transzgénikrts: állat érintkezletése az ágenssé 1, ahol a s ragmens je len van Lewy-testes lépégben szenvedő betegekben és azzal jeSiemzelt, hcmy gt inl&lf Plfit-sziitnklein I0U 4ψμ-Wall aifá-sziíuiklem C-termínáíisárói Î -25 egymást kővcíő amhmsav deléciója van jelen; és a Iragmests szintiének meghatározása neuráíis sejtben az ágens hiányában mért alapszinthez képest, .'azralaf.^t«jÍ^lépsL«::Éágm.óns szintjének csőkk«B*t,e azt jelzi, hogy az ágens bír az LBD kezelésére sikál- mazfetsté feííRsMiógiatl Ä*ki}. .5. llmszgenikts*. eÄÄ kûlfebôgë Ite előnyőse« egér -frsösz* gént: ismiimsi, sxueiy isttalmstz; Lswyőestes betegségben szenvedő betegekben jelenlévő alfa-sz«a«kieindragmensí: kódoló mikleinsav-szegmenshez mnkôdôképese«: kötött promőten, sdkd ag slfjksKlnukMa-kapaeaa «zXäl pl«8»*eit, bogy gg smaM a a« s, a !*·, a a <«0 v g>n <kx \ ^<?r> um »o wp e^ a? a ukt alte s, oak mr > turns takvaa' t > ν' mast kővető atninosav âelénlbjâ vanjelen, ahol a tragmens ¢: as ^ kh a ** u ar\a illában oa glosa < a/ tfUot attól hogy LBD legalább egy jellemzőié kifej fêkîjôn ben®% ahoi a pioneste? elöxtyösco PIK« F promener vagy alak a legalább agy jdletnző előnyösen snoforos íbnkeki károsodása vagy kognitív funkció károsodása. a, /?? vitro eljárás páciensben LBD jelenlétének vagy ama való fogékonyságnak & kimutatására, amely dinijének kirnatgtását e«r#sö^í«áltsib|yadék-mmífe!g stela frapaeas leien van Lesvydssíékbátépégbei'; szenvedő betegekben és azzal jelíetnpife hogy az inMét tdía-szmakleisv löt) egymást követő aôîmôsayjâ és az Intakt alfa^szinoklem üdermmálisázői K2S egymást követi aminosay deiédőja vsa jetM, a betegségtől mentes személyekben mérhető alapszinthez képest nagyobb szint LED jelen-kté; vagy arra való fogékonyságot jelez.
- 7. Ellenanyag, amely specifikusan kóiőáíkaiíá-sziníikkin ffagmenséhez anélkilh hogy specifikusan kö-tbdfté ä IIÖ :í£> ídtt í szettel szekvencia által meghatározott teljes tesszőságö aifeszmukléídhex. alibi a flagmens jelen van Lewy-testes betegségben szenvedő betegekben # azzal jellentzsík begy m- intakt alts-szundiéin IÖ0 egymást kővető aminosavja és az intakt sdía-szióuklem ódétmmál lséről Î-2S egytsssí: követő; ímnnosav deléemja van jelen, ahol az. ellenanyag előnyőseit embed vagy temanizált ellenanyag, élösyöséöhsn emberi Igü 1 ïzoîipus. vagy alfaszinukletn 20 ammosavnal rövidébe fetgrnense, sanely Inehtkái egy ilyen éllém anyagot:, ahol s ÍragTnsnv amely irtdokálja az ellettanyagot, tartalmazza a Lewytestés betegségben ázsmyédő jjeiégekben teleidé vő, csonkolt fragtaeas Cnemtmaílsát. 8, Λ ?. igénypont szettmi eüenantag LBD jeleniélének vagy arra vaii íbgékonysi^náktdiagnöszdzáiásá^ ban történő alkalmazásra. ahol az ellenanyag beadandó egy páciensnek, és a páciensben az ellenanyag kötődésének szintje meghatározandó, «bol a betegségiül memes személyekben lévő alapszinthez képest snttgasabb kbtcaesf iont LBÖjeienlue- vsg> erre vad foyókoa>,\apot vk sk A 7. igénypont sí.erinti ellenanyag vagy a 7, igénypont szerimi elletinayagot. indukáld, IzCt aíninös&vtiál tövidebb aifa-íiziíntklein fragntens. Lewy-testes betegség kezelésében vagy megelőzésében tö«éJ$'áikálpiaxásrs.
- 10. AHa-szintikiein fragmeese, amely jelen van Lmu -testes betegségben szenvedő betevőkben,, amely azzal JaHetszett, hogy az. Intakt aiüKSzinakidn iOO egytnást: kdvntő a-nixsosavin és az imnkt alts-szinukleln C-teminmiilíb! î*25 egymàÂve^aiRnpd» áéM#s van jÄ, Léivy-tés» bofôpégkozé]ésébén vagy meg-«lőzésében történő ttikaixoazám
- 11. AHa-szstiMklein iVagmease, amely jelen van Lewy.mstns betegaégiben szenve-iő betsígekben, anteiy azzal ieMematett, hogy az Ihtákí atià-ÂtnitkMt) 100 egymást kővéfő ámixtösayjá és az intakt allm-szimtklein É-töxnnoáhsárdl 1-23 egvoxast kővető aimnosay deiéeiói& vas jelén, a fhsgmens elleni eiienanyngokat Sartainsaző immsmválás^^kőitéi'iittiváossál köntbíxiáeiöban, sags amely hordozőnox kötőn, ezáltal fúziós í'dahjéi képez, ánol á hőrdöss^ a árágmexts elinni ellenanyagokat iaitaltostzir
- 12. Eljárd intakt «Ä békékben jelenlévő Mgmssst képző proieázra való szkrineleav, áltól a ihtgmess azzal jellemzett hogy as iatÄalf»"*zinukle|& iöö ofytnást kiveíi ámisösavja & «x î»tak? alià-stdanklem C-temÛMMsérél 1*2$ &$ymâsi |8u;-è amino$$? s következőket: a prnteâz inmhiso-rinak a?o«oÉI sx inhibitor érhifexfeisss a pioSsôïl: hirhhioasô sejtes «agf :sshX:síkfyoóM{ai, ahsi á pfoteáx kfeíáiiik as inhibitorhoz, os s proteâz télsz&badMss axÂibïteri^ii. l. 3; A12, igénypont széttöri eljárás« ah#az 1Ä1Ä ÂÂR«fc*pe^â4.t^ÿ IfÄi tdik-szoniMein 1 IS. és Kik poxidót közötti iegaïâhb S sortnoxávbol síié egymást kővető szegmeost tart&hmiz, előnyösen ahol s pepiid a HS, és 122> pozie-ók közötti legalább 5 strónosavbói átló egymást követé szegomnst tartalmaz. előnyösebben ahol az aorinösávak legalább egyike tratsricióa áliapötS máiég. 14: Az l-4>, 4, 12 és 13/igénypont ok banne^iip' :i^i: «ájátás,. #$?. 8® alik«s?döukÄ...:t8gm«ßS« ÁSÍT saoiáélbiikaipK,: II, Az j-4,, a, |s 12-14, Igloysoniok bitrinelyike «serimi ellátié, #oi az tahnazxa intakt alfa-szinukfeitt C-ternhnánxáröl 1 -23 nnymoox am ; nos a v oeiécsőját. 16, A/ t-4., 6. és 12*15. *gásyp»ni»k bármelyike szerinti eljárás, ahoi az a(fa*szíö»kls&5 rntgitiérsstí l-I If· vagy 12: Π. A? 1-4,, 6. ès i-X, ahol X jelentése i 30-139.
- 18. Az 1 -4„ 6. és 12-13. »g^pmotkÄ^fSte szerinti eljárás, ahol az aíriöszlrutkletn fegmense intakt alfá-szimtkiein, amely a C-terorinárison 23 aminosavvsi csonkolt. Í9. A 11. igénypont szerinti: aii-sziodkiolo-igpÄs vagyä :mj|ihp^ meg- ^tirözsít alfeato«zá^':4hől aznifö-szinokk-m tragmeose A53T mutációt hordoz,
- 20. A Ά igénypont szerinti efienanyag, a B, vagy 9. igénypont szertől:! slleoaoysg az: o« meghatározóit aikóteaxásra. A; ü , ysgy 19. igéi^m smktiéfm^tíkm^mmm 10. vagy 19, ígénypoot szerinti frogmens az ott omgh&tároxott alkalmazásra, ahol az aiia-sxinokiein fragmense tartalmazza intakt alla» szirmkloso: ClAertnirtálísáföi 1 -23 iälytöhos sminösáv doiéétOtst. m. A % vagy 20. igéitypht szerinti eíMányag, 4 I,, 9, és 2Ü.ígétiypont»k hátmelyike szerinti «Β«* Sö^ra*Ä^«W^«Ämazfcra, all - 1% vágy 20,ri|é«ypnnt szerint i aifk-szmukMtvtAtgmotrs vagy a :0., 19. vagy 2h,vlg|oypo:at szerinti tray mens az: Ott nmghaőiroxoit alkalmazásra, ahol az alfe-szimtkkún Sstgmense :4310 vagy 1-122, 23, A 7. vagy 30 igénypont szerinti cilenany&g, a 8.. 9. és 20.igénypontok bármelyik*::.szériát! ellen-suvsg az -öltmeghatározott alkalmazásra, a i 1 . 19, vagy 2o igém {tont szerinti alSa-szittukletiylriigtseos vagy a Kg J9 vagy 20. igénypont szerinti fragst a:· as az ott ínegh&táfítzött a ! κ a int ázásra, a no ; az álííbszltttAlem haameose l-X, ahol X jelentése 130-139. 24 A 7. igénypont saerimt elK-nanyagef 1 vagy 9, igénypont szertmt eiienanyagriiZ dt meglanárnantt aí.kitintazást-s, a 11. vagy 19. igénypont szerint! glik-xzimtkiein-fhtgotens vagy a 10. vagy 19. Igénypont szerinti tzgroens ax ott meghatározóit alkalmazásra, sáo! az mta-szinokiein h&gmense intakt aíia-sx9inklein; amely & C-temsmáNson 25 aminosttwoi csoiAölt
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| HUE04776059A HUE034320T2 (hu) | 2003-05-19 | 2004-05-19 | Alfa-szinuklein csonkolt fragmensei lewy-testes betegségben |
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| JP (2) | JP4820291B2 (hu) |
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| CY (2) | CY1119133T1 (hu) |
| DK (2) | DK2361928T3 (hu) |
| ES (2) | ES2640669T3 (hu) |
| HU (2) | HUE035044T2 (hu) |
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| PT (2) | PT1633189T (hu) |
| SI (2) | SI1633189T1 (hu) |
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- 2004-05-19 WO PCT/US2004/015836 patent/WO2005013889A2/en active Application Filing
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Also Published As
| Publication number | Publication date |
|---|---|
| JP4820291B2 (ja) | 2011-11-24 |
| EP1633189A4 (en) | 2006-07-19 |
| JP2011033633A (ja) | 2011-02-17 |
| CA2526900C (en) | 2015-11-24 |
| EP2361928B1 (en) | 2017-04-26 |
| CA2526900A1 (en) | 2005-02-17 |
| WO2005013889A2 (en) | 2005-02-17 |
| PT2361928T (pt) | 2017-07-21 |
| DK1633189T3 (en) | 2017-08-21 |
| PL2361928T3 (pl) | 2017-09-29 |
| SI1633189T1 (sl) | 2017-12-29 |
| DK2361928T3 (en) | 2017-07-03 |
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| CY1119556T1 (el) | 2018-03-07 |
| EP2361928A1 (en) | 2011-08-31 |
| ES2640669T3 (es) | 2017-11-03 |
| WO2005013889A9 (en) | 2005-06-02 |
| CY1119133T1 (el) | 2018-02-14 |
| EP1633189B1 (en) | 2017-07-05 |
| PT1633189T (pt) | 2017-10-04 |
| SI2361928T1 (sl) | 2017-07-31 |
| JP2007525464A (ja) | 2007-09-06 |
| HUE035044T2 (hu) | 2018-05-02 |
| US7306945B2 (en) | 2007-12-11 |
| PL1633189T3 (pl) | 2017-12-29 |
| EP1633189A2 (en) | 2006-03-15 |
| JP5766923B2 (ja) | 2015-08-19 |
| US20050198694A1 (en) | 2005-09-08 |
| ES2632216T3 (es) | 2017-09-11 |
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