HUE033825T2 - A béta-amiloid fehérje protofibrillum formájára specifikus ellenanyagok - Google Patents
A béta-amiloid fehérje protofibrillum formájára specifikus ellenanyagok Download PDFInfo
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Claims (15)
- A béta-antiloki fehérje prfeöfíhrlliim femaifára specifikus ellenanyagok SZÄBÄÄill IGÉNYPONTOK 1. izolált monoklonálts ellenanyag, amely specifikusan MfeÄhafMsa lep, és fel színi plaz-mö® SPMnciásía! mfeye legállbb 10^ Mfe iffinie; nsnai az Ap pepiM egy protoibrillorn IfeMfeanak ^IkôÂmîàciés.^itopjàhfsÇt^xol. a protofiWlinm ggippot egy .AjNprfeofibrilIum izmának égy exponált régiója képviseli, amely aj.f számé sz#y@íKlía-vikÍTOn bemutatott ammosay szekvenciái |an#naz-za, tanahuaz továbbá egy yáaÉÉbüts :kö»nyö...:pÄ,;::siEsäy egy CDK.Î régiói taftáímaz, amint ází a ti. aÄÄ iitoeneiäAigliiön ^ééjak'bé, taititeaz ep^ ;GO!k2 régiói, amint azt. a 24 számé vázlaton mutatjuk be., és tartalmaz egy COM régiói, amint azt s 15. számé szekvencia-vázlatraimirtaijuk be, miamÄfartalmaz ep yaálbllis nehéz láncot, amely egy CDR! régiót tartalmaz, amiét azt a aóészá-· mó pekypKíia--vázÍatori matatjuk be, tartalmaz egy CDR2 régiót, amint azt a 21, számé saekvenéia'-vázlaton mt:áa|iik be, és tmfámaz égy CÖR3 régiót amint azt a 22. számé be.
- 2. Azi: 1, igénypont szerinti izolált rmmoklonálfe ellenanyag, amelyben az exponált régió taríalnrazzaimll a ·4< számé szekveneia-vazlatou bemutatott amínosav szekvenciát
- 3. Az. 1. vagy 2 igénypont szerinti monoklonális ellenanyag, amelyet a PTÁ-8S3Ö ATCC letéti számonhozzátérhetö hibrklómávai állítunk elő.
- 4. AzT, vagy 2. igénypont szerinti monoklonális éllenáíiyág, amely tartalmaz még; egy variábilis kötmyll láncot, amely az 5. szánté sz$kyeneia--vlzfálöm szekvenciát tartalmazza, valamint tartalmaz egy variábilis nehéz láncot,. amply a % számé szekvencia-vázlaton bemutatott arninosav szekvenciát tartalmazza.
- 5. Az 1-4. Igénypontok bármelyike szerinti inmnóMénáis: ellenanyag, ahol azóéllM-anyag egy humanizált monoklonális ellenanyag’.
- 6. Az 1-*» z.em pontok mume.vtko vountf monok onabs cllenumag alto· ar v kv anyag égy humán nlnnokionális éllenanyág. f. Ijjáris egv, az 1-6. igénypontok bármelyike szerinti monoklonális ellenanyag eliálll-fására^ azzal jellemezve, hogy a követkézé lépéseket tartalmazza: faj egy nem-humán emlőst Irnmnnizálnnk a ó-amiold pepii fii>teftbriîluâï:ÂihâijâYâil;;. (h j ;á Szóban iötgó: emlős B-sej tjei· kinyerj ük, (e) a kinyeri Betekből hibridőmikai lésáiÉ, Mm mëhmfèfgè biferidörnlk eilen* anyagokat termelnek, és (di) olyan liífeáiémákat szelektálunk, amelyek tpeelfkusan a bitammllolö pepid proíoibriltan áef^öB kötődő Ânânpgokaï teonelnefc, mifeö^bén ®inj?nâiis affinitást matai* oak a béta-armkid papid monomer vagy dimer tormájához. S Eljárás béia-amilosd pepiid protofibril ium tormája mennyiségi meghatározására egy szövet* vagy folyadék-mintában, azzal jellemezve, hogy a kóvmkéző lépéseket tartalmazza: (a) egy alanyból kinyerjük a szövet* vagy folyadék-mintát; (b> a szövet- vagy folyadék-mintái érintkezésbe hozzuk az 1-6. igénypontok bármelyike szerinti ntönoklonáiis eMensoyaggal, vagy annak egy speeidkus fíngmenséveg amely specifikusan kötődik a béta-amioid peptld pfotefíbeHbím formájához, miközben mimmaiis affinitást mutat a hétámnuloid pepid alacsony molekulasúlya formáihoz; és (e) a béíámtnllöid pepiid pmtofíhrihum termáját mennyiségileg meglmtfezzok a mlniá* ban.
- 9. Készlet a béla-amiloid peptkl protofbrillmn formájának kimutatására, miközben nagyobb affinitást műtét a béta-amilóid pepiid ptofotibrrllum formájához, mint a héla-anoloid pop* id alacsony moiékntasdiyd formáihoz, azzal jellemezve, hogy a következő kontpönensekéi tárták mázzá: (a) Az foö. Igénypontok bármelyike szerinti mönoklonália ellenanyag, vagy annak fugmense, amely in virmkipm speeilllólsah kitddnt a béta-ámílold pepid prötotlbrílluin formájm Pák égy ismétlődé: konformációs epitofpooz, miközben mínimiiís afopstiat mutai a hétá-ámlóid pepiid alacsony molekulasdlyu tormáihoz; és (h) reagens, amely közvetlenül: vagy közvetve kötődik a szóban forgó ellenanyaghoz vagy fragmenséhez, tfo Gyógyászati kesznmem, amely tartalmaz p) egy monoklendis ellenamagot, vágy annak az áfo, igénypontok bármelyike szerinti variábilis régió íYagmensép amely specifikusán kői-osönbátiffiá lép m AjS-amiloid protofibnllum formájává!, ás (n> egy gyögyászátiái elfogadható jpídozöt,: Ahol a szöban fosgé ppeelilmAíosöpbsilst «. mëbmi forgó eiienanpg variábilis régiója Ikagmeusének a protoibrilláns AB formához való affinitásának és a többi formához váló affinitásának az aránya nagyobb, mint körülbelül 2, IL Ä i 1. igénypont szerinti gyógyászati készítmény, amelyben az ellenanyag egy mono-klonábs ellenanyag. !2. A 10. tgénypónt szerinti gyógyászati készítmény, a ? igénypont szerint* eljárás, vagy ai. igéhypott készlet, áhöl az ellenanyagot a PT&-8&30 ÄCC letéti száígon iozzáfebetö hihridómáva! illiltjuk elő 13. A ! I igénypont szem.iti gyógyászati készítmény, amelyben a monoklonal is ellenanyag egy humámzalt monoklönális elféöanyag, vagy egy humán monokJonális ellenanyag.
- 14. Egy. a ΡΤΛ-8830 ATCC letéti számon hozzáférhető hibridóma. II Izolált nykleinsav molekula, amely az 1-6. Igénypontok bármelyike szerimi: elén-anyagot kódolta, ahol a. vartaiijg nehézjáne irapMMsS Z számú szekvencia-vázlaton bemutatott atpthoaav szekvenciát tartalmazza. ti, liláit hiklÄilr amely az 1-6 igénypontok bfendyíke szerinti éUm* a»pgPi.lÄ|^ 'áhöl'»: nuktüh» mólékéla. a S. mámé. szekvencia-vázlaton bemutatott nuMeotü azekvenéldttatlaimazza:, ÍZ. Expressziét; vektor az I-6. igénypontok bármelyike szerinti ellenanyag expresszálá-Sához égy rékórnbinlbs: gazdassltben, ahol a szóban forgó expressziés vektor a 15. vagy 1.6. igény-porit szerinti nokleinsav molekulát tartalmazza. Ifi. lenyésziétí: pzdasejt, amely az bfo. Igénypontok bármelyike szerinti ellenanyagot expresszáija, ahol a szóban forgó gazdasdí a 1.1-igénypont szetlni ezpeaszios vektort tartalmazza.
- 19. Izolált nukieinsav molekula, amely m 1-1. Igénypontok birméiylke szerinti ellett-anyagot kódop, ahol a variábilis könnyű line i-afmgns az 5. szánté latoit amino sav szekvenciát tartalmazza.
- 20. Izolált nukleiusav molekula, amely m i~ó. igénypontok bármelyike szerinti: éilon-anyagot kódolja, ahol a rsukiomvn molekula a 6. számú szekvencia-vázlaton bemutatott nukleoiid Székvéticiár tartalmazza,
- 21. Ixpressziós vektor az l-Ó. igénypontok bármelyike szerinti ellenanyag: exprésszálásahoz, egy rekcmbinans gazctejíben*. iáiban forgó expresszms vektora Sil vagy 20 igénypont szerinti nukletnsav molekulát tartalmazza, 22 Terű, észten gazdasep, amely az 1-6 igénypontok bármelyike \aenntí elírnámago* expr#äpllja.s :alioi a szóban forgó gaz|||ejt a 21. igénypont szerinti expresszios vefeiortlaftalmazzäv
- 23. Az 1-6. igénypontok bármelyike szerinti moaoklonálís ellenanyag, vagy annak variábilis régió íragmense, egy olyan áilappt:teiiés4fem:IMíÉÍ.ii»ÍÍatra. amelyet béta-annioid szál tartóitok lerakódása jellemez.
- 24. Egy, az 1-6 igénypontok bármelyike szariptimonókkatalis ellenanyag, vagy annak egy antigén-kötő fragmente gyogylszatiíag hatásos nmnnylségénék basznliata az Alzheimer kór teliépésebez és progressziójához kapcsolódó béta-amiioM tartók lerakódás kezelésében és/vágy megelőzésében történő használatra,
- 25, Az igénypontok bármelyike szerlotl rnonofclonáHs ellenanyag, vagy annak egy andgénAőtó fiegomnse, az Alzheimer kór kezelésében történő Msználaira.
- 26. Az l-ó. igénypontok. bármelyike szerinti monoklonálís ellenanyag, vagy annak egy antlgéB~kötő üagmensk a bétá-amiloid szil tarlóitok képződésének és lerakódásénak megakadályozásában történő alkalmazáshoz.
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SE0401601D0 (sv) | 2004-06-21 | 2004-06-21 | Bioarctic Neuroscience Ab | Protofibril specific antibodies and uses thereof |
DE602007011415D1 (de) | 2006-03-23 | 2011-02-03 | Bioartic Neuroscience Ab | Verbesserte protofibrilselektive antikörper und deren verwendung |
IL199534A (en) | 2007-01-05 | 2013-01-31 | Univ Zuerich | An isolated human antibody capable of detecting a neoepitope in a disease-related protein, a polynucleotide encoding an antibody, a vector containing the polynucleotide, a host cell containing the polynucleotide or vector, a preparation containing the antibody and related methods and uses. |
AU2008203703C1 (en) * | 2007-01-05 | 2014-04-03 | University Of Zurich | Method of providing disease-specific binding molecules and targets |
WO2009065054A2 (en) | 2007-11-16 | 2009-05-22 | The Rockefeller University | Antibodies specific for the protofibril form of beta-amyloid protein |
CA2746778C (en) | 2008-12-19 | 2019-04-23 | University Of Zurich | Human anti-alpha-synuclein autoantibodies |
FR2945538B1 (fr) | 2009-05-12 | 2014-12-26 | Sanofi Aventis | Anticorps humanises specifiques de la forme protofibrillaire du peptide beta-amyloide. |
WO2011001366A1 (en) * | 2009-06-29 | 2011-01-06 | Bioartic Neuroscience Ab | N-terminal truncated amyloid beta protofibrils/ oligomers for use in therapeutic and diagnostic methods for alzheimer's disease |
US10266585B2 (en) | 2009-08-28 | 2019-04-23 | The Board Of Regents Of The Univerity Of Texas System | Methods of treating brain injury |
US8486940B2 (en) | 2009-09-11 | 2013-07-16 | Probiodrug Ag | Inhibitors |
EP2595644B1 (en) | 2010-07-23 | 2016-03-30 | Gwangju Institute of Science and Technology | Amyloid-beta clearance |
EP2627357B1 (en) | 2010-10-15 | 2017-05-03 | The Board of Regents of The University of Texas System | Antibodies that bind amyloid oligomers |
AR085302A1 (es) | 2011-02-24 | 2013-09-18 | Sanofi Sa | Metodo de produccion de anticuerpos sialilados |
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