DK2361928T3 - Trunkerede fragmenter af alpha-synuklein i Lewy body-sygdom - Google Patents
Trunkerede fragmenter af alpha-synuklein i Lewy body-sygdom Download PDFInfo
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- DK2361928T3 DK2361928T3 DK10189868.2T DK10189868T DK2361928T3 DK 2361928 T3 DK2361928 T3 DK 2361928T3 DK 10189868 T DK10189868 T DK 10189868T DK 2361928 T3 DK2361928 T3 DK 2361928T3
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Claims (14)
1. Antistof der specifikt binder til et 1-122 eller 1-119 fragment af alpha-synuklein, uden specifikt at binde til alpha-synuklein i hele dens længde som defineret i SEQ ID No.l, eller et fragment der inducerer dette antistof hvor fragmentet der inducerer antistoffet har færre end 20 aminosyrer af alpha-synuklein og omfatter C-terminus af 1-122 eller 1-119 fragmentet af alpha-synuklein.
2. Antistof ifølge krav 1 der er et humant eller humaniseret antistof, fortrinsvis af human isotype-IgGl.
3. Antistof ifølge krav 1 eller krav 2, eller fragmentet der inducerer antistoffet ifølge krav 1, til anvendelse til behandling eller profylakse af Lewy body-sygdom.
4. Antistof ifølge krav 1 eller krav 2 til anvendelse til at diagnosticere tilstedeværelsen eller modtageligheden over for en LBD hvor antistoffet bliver indgivet til en patient og antistoffets bindingsniveau hos patienten bliver bestemt, hvor et højere niveau af binding i forhold til et basislinjeniveau hos personer der ikke er syge indikerer tilstedeværelse af eller modtagelighed over for LBD.
5. Fragment af alpha-synuklein med fuld længde som defineret i SEQ ID No.l, der er alpha-synuklein 1-122 eller 1-119.
6. Fragment ifølge krav 5, hvor fragmentet af alpha-synuklein bæreren mutation forbundet med arvelig Lewy Body-sygdom (LBD), eventuelt en A53T-mutation.
7. Fragment af alpha-synuklein som defineret i krav 5 eller krav 6 enten i kombination med en adjuvans der øger et immunrespons omfattende antistoffer til fragmentet, eller forbundet med en bærer der danner et fusionsprotein, hvor bæreren øger et immunrespons omfattende antistoffer til fragmentet.
8. In vitro fremgangsmåde til at screene for et middel med en farmakologisk aktivitet der er egnet til at behandle en LBD omfattende: at bringe midlet i kontakt med et fragment af alpha-synuklein som defineret i krav 5 eller krav 6; og at bestemme aggregationshastigheden eller -omfanget af fragmentet af alpha-synuklein, hvor en reduktion af aggregationshastigheden eller -omfanget i forhold til en kontrol uden midlet indikerer at midlet har den farmakologiske aktivitet.
9. In vitro fremgangsmåde til at screene et middel for en farmakologisk aktivitet der er egnet til at behandle en LBD, omfattende: at bringe en celle der udtrykker alpha-synuklein og bearbejder alpha-synuklein til et fragment som defineret i krav 5 eller krav 6 i kontakt med midlet; og at bestemme et niveau af fragmentet i cellen i forhold til et basislinjeniveau i den samme celletype i fravær af midlet, en reduktion af niveauet af fragmentet i forhold til basislinjen der indikerer at midlet har den farmakologiske aktivitet der er egnet til at behandle en LBD; hvor cellen fortrinsvis er en menneskecelle, mere fortrinsvis en neuronal celle eller en dopaminerg celle.
10. Fremgangsmåde til at screene for et middel med en farmakologisk aktivitet der er egnet til at behandle en LBD, omfattende at bringe et ikke-humant transgent dyr der udtrykker et fragment af alpha-synuklein som defineret i krav 5 eller krav 6 i kontakt med midlet; og at bestemme et niveau af aggregerede former af fragmentet i hjernen på det transgene dyr i forhold til et basislinjeniveau af aggregerede former af fragmentet hos et sammenligneligt transgent dyr ved fraværet af midlet, en reduktion af niveauet af de aggregerede former fragment i forhold til basislinjen der indikerer at midlet har en farmakologisk aktivitet der er egnet til at behandle en LBD, hvor det transgene dyr fortrinsvis er en mus eller en Drosophila.
11. Fremgangsmåde til at screene et middel for en farmakologisk aktivitet der er egnet til at behandle en LBD, omfattende at bringe et ikke-humant transgent dyr med et transgen der udtrykker alpha-synuklein og bearbejder alpha-synuklein til et fragment som defineret in krav 5 eller krav 6 i kontakt med midlet; og at bestemme et niveau af fragmentet i en neuronal celle i forhold til et basislinjeniveau i fraværet af midlet, en reduktion af niveauet af fragmenterne i forhold til basislinjen der indikerer at midlet har den farmakologiske aktivitet der er egnet til at behandle LBD.
12. Transgent ikke-humant dyr, fortrinsvis en mus eller Drosophila, med et genom omfattende et transgen omfattende: en promotor virksomt forbundet med et nukleinsyresegment der koder for et fragment af alpha-synuklein som defineret i et hvilket som helst af krav 5 eller krav 6, hvor ekspression af fragmentet hos det transgene dyr disponerer dyret til at udvikle mindst et kendetegn ved en LBD, hvor promotoren fortrinsvis er en PDGF-promotor, eller hvor det mindst ene kendetegn fortrinsvis er en svækkelse af bevægefunktion eller en svækkelse af kognitiv funktion.
13. In vitro fremgangsmåde til at detektere tilstedeværelse eller modtagelighed over for en LBD hos en patient, omfattende: at detektere et niveau af et fragment af alpha-synuklein som defineret i krav 5 eller krav 6 i en prøve af rygmarvsvæske, et niveau der er højere end et basislinjeniveau hos personer der ikke er syge indikerer tilstedeværelse af eller modtagelighed over for LBD.
14. Fremgangsmåde til at screene for en protease der spalter intakt alpha-synuklein for at danne et fragment som defineret i krav 5 eller krav 6 omfattende: at identificere en inhibitor af proteasen; at bringe inhibitoren i kontakt med et celle- eller vævsekstrakt indeholdende proteasen, hvorved proteasen binder til inhibitoren; og at frigøre proteasen fra inhibitoren, eventuelt hvor inhibitoren er et peptid af alpha-synuklein omfattende et tilstødende segment af mindst 5 rester af intakt alpha-synuklein mellem positioner 115 og 130, fortrinsvis hvor peptidet omfatter et tilstødende segment af mindst 5 rester mellem positioner 118 og 122, mere fortrinsvis hvor mindst en af resterne er en overgangstilstandsanalog.
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| TW200509968A (en) * | 2002-11-01 | 2005-03-16 | Elan Pharm Inc | Prevention and treatment of synucleinopathic disease |
| US9034337B2 (en) | 2003-10-31 | 2015-05-19 | Prothena Biosciences Limited | Treatment and delay of outset of synucleinopathic and amyloidogenic disease |
| US8506959B2 (en) | 2002-11-01 | 2013-08-13 | Neotope Biosciences Limited | Prevention and treatment of synucleinopathic and amyloidogenic disease |
| US8697082B2 (en) | 2002-11-01 | 2014-04-15 | Neotope Biosciences Limited | Prevention and treatment of synucleinopathic and amyloidogenic disease |
| US20080014194A1 (en) | 2003-10-31 | 2008-01-17 | Elan Pharmaceuticals, Inc. | Prevention and Treatment of Synucleinopathic and Amyloidogenic Disease |
| US7358331B2 (en) * | 2003-05-19 | 2008-04-15 | Elan Pharmaceuticals, Inc. | Truncated fragments of alpha-synuclein in Lewy body disease |
| JP4613824B2 (ja) * | 2003-10-30 | 2011-01-19 | 大正製薬株式会社 | トランスジェニック非ヒト哺乳動物 |
| WO2005047860A2 (en) | 2003-11-08 | 2005-05-26 | Elan Pharmaceuticals, Inc. | Antibodies to alpha-synuclein |
| MX2007001679A (es) | 2004-08-09 | 2007-05-23 | Elan Pharm Inc | Prevencion y tratamiento de la enfermedad sinucleinopatica y amiloidogenica. |
| US20070214509A1 (en) * | 2005-12-23 | 2007-09-13 | The Parkinson's Institute | Methods and systems for identifying compounds that modulate alpha-synuclein aggregation |
| US20090010894A1 (en) * | 2005-12-23 | 2009-01-08 | The Parkinson's Institute | Methods and systems for identifying compounds that modulate alpha-synuclein aggregation |
| LT3067066T (lt) | 2007-02-23 | 2019-06-25 | Prothena Biosciences Limited | Sinukleopatinių ir amiloidogeninių ligų prevencija ir gydymas |
| PL2118300T3 (pl) | 2007-02-23 | 2015-11-30 | Prothena Biosciences Ltd | Zapobieganie i leczenie synukleinopatii i amyloidozy |
| US8147833B2 (en) | 2007-02-23 | 2012-04-03 | Neotope Biosciences Limited | Prevention and treatment of synucleinopathic and amyloidogenic disease |
| AT506535B1 (de) | 2008-02-22 | 2010-04-15 | Affiris Forschungs & Entwicklungs Gmbh | Vaccine enthaltend alpha-synuclein-mimotope auf basis von peptiden |
| AU2009236583B2 (en) * | 2008-04-17 | 2015-07-16 | Declion Holdings Llc | Design and synthesis of directed sequence polymer compositions and antibodies thereof for the treatment of protein conformational disorders |
| DK2282758T3 (da) * | 2008-04-29 | 2019-02-25 | Bioarctic Ab | Antistoffer og vacciner til anvendelse i terapeutiske og diagnostiske fremgangsmåder for alpha-synuclein-relaterede lidelser |
| AT508638B1 (de) | 2009-08-21 | 2011-08-15 | Affiris Ag | Verwendung von peptiden und polypeptiden zur behandlung und/oder prävention von synukleinopathien |
| JP6006908B2 (ja) * | 2010-11-05 | 2016-10-12 | ブランダイス ユニバーシティＢｒａｎｄｅｉｓ Ｕｎｉｖｅｒｓｉｔｙ | Ｉｃｅ阻害化合物およびその使用 |
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| EP2659906A1 (en) | 2012-05-01 | 2013-11-06 | Affiris AG | Compositions |
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| US12156912B2 (en) | 2012-05-18 | 2024-12-03 | Board Of Regents Of The University Of Nebraska | Methods and compositions for inhibiting diseases of the central nervous system |
| JP2017501848A (ja) | 2013-11-19 | 2017-01-19 | プロセナ バイオサイエンシーズ リミテッド | 便秘症状からのレビー小体病の免疫療法のモニター |
| US9732148B2 (en) | 2014-10-16 | 2017-08-15 | Genentech, Inc. | Anti-α-synuclein antibodies and methods of use |
| GB201512203D0 (en) | 2015-07-13 | 2015-08-19 | Lundbeck & Co As H | Agents,uses and methods |
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2004
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- 2004-05-19 DK DK10189868.2T patent/DK2361928T3/da active
- 2004-05-19 ES ES04776059.0T patent/ES2640669T3/es not_active Expired - Lifetime
- 2004-05-19 PL PL10189868T patent/PL2361928T3/pl unknown
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- 2004-05-19 PT PT101898682T patent/PT2361928T/pt unknown
- 2004-05-19 HU HUE10189868A patent/HUE035044T2/en unknown
- 2004-05-19 HU HUE04776059A patent/HUE034320T2/en unknown
- 2004-05-19 PT PT47760590T patent/PT1633189T/pt unknown
- 2004-05-19 SI SI200432398A patent/SI2361928T1/sl unknown
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2017
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| ES2632216T3 (es) | 2017-09-11 |
| CA2526900C (en) | 2015-11-24 |
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| JP4820291B2 (ja) | 2011-11-24 |
| PL2361928T3 (pl) | 2017-09-29 |
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