HUE029692T2 - Emberi lambda variábilis régiókat és egér konstans régiókat tartalmazó könnyûláncot exprimáló egerek - Google Patents

Emberi lambda variábilis régiókat és egér konstans régiókat tartalmazó könnyûláncot exprimáló egerek Download PDF

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HUE029692T2
HUE029692T2 HUE11728508A HUE11728508A HUE029692T2 HU E029692 T2 HUE029692 T2 HU E029692T2 HU E11728508 A HUE11728508 A HU E11728508A HU E11728508 A HUE11728508 A HU E11728508A HU E029692 T2 HUE029692 T2 HU E029692T2
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mouse
gene
human
light chain
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Lynn Macdonald
Sean Stevens
Cagan Gurer
Andrew J Murphy
Karolina A Hosiawa
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Regeneron Pharma
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Claims (8)

  1. fWBËRI LAMBDA VARIÁBILIS RÉGIÓKAT ÉS EGÉR KONSTANS RÉGIÓKAT TARTALMAZÓ KŐNNYÖLÁNCOT iMUAfcâ LOEREK IBiABALMíPéRYPÖNTOK I. Ígér, amelyben megtalálható egy endogén A|pbga): kőanyiánöglié!, amely tartalmaz egy djraíéodéZéííen emberi lambda variábilis (hVA) és egy űjrarenctezetien emberi lam^a kapcsoló (hJA) génsasgmensi, ahol az egérben htögísiáihátó az ernlitslt endogén egér A fcénnyöiáéc alléi első VA-JA-CA génktöszterének .deiédéja és az errtllfóíi emberi VA és JA génszeg meneeket tartalmazó alléi második VA-JA-CA génkissztórében lévő V'AtöA génszegmensánek - részben: vagy egészben történő -belyéliésitésével, amelyek műtéti ötöm kapósotok aZénÉtalrnáaobik VA-JA-CA gsnkfeszfer egy édnígílen egér lambda konstans (CA) régiéjához, így az egér egy hVAí: HJA és egy egér CA génből származtatott kőonyűiáncet exprimât ahol az Enh 14, egér lambda 3* enhancer (Enh) és Enh 3,1 endogén enhancérék érintetlenek maradnak az. említett A Mnnytiiiho alielhen. 2; Az egér az 1-es igénypont szerint, ahol az ermogih A pmhdai könnyű lánc alléi több emberi VApttözegmenst taáaírtffcz. S. Az égét azoddigi igénypontok bármelyike ézerlnt, áhbPZisndögén A (lambda) könnyßläne all#: rendelkezik: a) legalább 12 újrareodexelien emberi νλ génszegmenssei; vagy b) i3~2S újrarendezetien emberi VAgénszegmenssel.
  2. 4. Az; egér a 3-as: igénypont szerint, ahol az, emberi VA génszegmahSék közé értendők a) a h:VA34,hVA4-3i hVA2-8,: hVAS-^ bVAö-lö, hVA2-ii és hVA342 szegmensek:: vagy :b) a hVA244, WÊM hÄll, IÄ18. hVA3-2l, hVA3-22, hVA2-23, hVAJ-25 és hVA3 27 szegmensek,
  3. 5, Az egér az Iteá igénypont szerint, aboi az endogén A (tömbös) Könnyétánc allé! égy újrarendezetlen JA génszegmenet törtölmaz, amely a hJAii:
  4. 6. Az egér az t-es igénypont szerint, ahol az endogén A (lambda) kőnnyőiánc alléi négy öjrarsndezetien embed JA génszegmenst tartalmaz,
  5. 7, Az egér s 0-os igénypont szerint. töheka négy ojrarendezeflen emberi JA génszepiéhé a JAI, JA2, JA3 és JA7,
    0, Az egér az l -ea lpnypom szerint; éhéi az endogén A (iambda) kenn y eláné aléíbél hiányzik egy endogén VA gánszegmens.
    3, Az egéf az 1-3, azMs és §-ss1pnypbntok bármelyike szerint; ahol az endogén töikappal ítönnyőíáns alléi törlődött 10 Az egér az 1-as igénypont szerint, ahol az endogén agár A könnyűiénc allé! tartaimezza: a) az emberi A konnyútönc iókusz egy folyamatos szekvenciáját, amely V'A3-i2 tÔi a VA3-t-lg törjed; fe) az emberi A könnyüíánc iókusz egy folyamatos smAveocíáját, amely VA3-29töi a VAS-IJg terjed; vagy e) egy az emberi A könnyüíánc fókusz folyamatos szekvenciáját, amely VA3-29-f$ VAd-l-lg terjed es egy az ember! A kdnnyfáoc fókusz folyamatos szekvenciáját, amely VA5-ő2-fól a VAI-40'lg terjed. II. izolált sejt, amely egy hVÁ, HJA és egy CA egér génből szármáztátok kônnyûtàneot ezprimál, ahol a sejt az eddigi fénypontok bármelyike szerint ei«gi!§ifört #gèÂsâ$roa2ifc isgy .abbéi kinyerhető, és aböl a sejtben magfóiáihaté agy újrarendezett emberi VA gèriszagmens és égy éjráréndázéit embed JA gènszegmens, es rendelkezik az említeti endogén egér A Mnnyíiiánc allét eisô és az említett embed VA Is áh. génszegmenseket töftöima^älli második VA-JA-CA génklaszfóróben lévő VA·JA génszogmensének - részben, vagy egészben történd - helyettesítésével, amelyek műtéti éten kapcsoltak az említett második VA-JA-CA gántöaszter egy éfiriieíien egér CA konstans régiéhoz, és ahol az Ünh 2.4, egér lambdas' enhancer (Enh) és IP 1,1 -^[|i)^iD»t:^.ÄÄ»ek maradnak az emliteff A konnyáiine akiiben.
  6. 12, Az izeiéit sejt a 11-es igénypont szerin t, ahol a bejt egy: B-limiocite. 13. izoÉt egèr embrionâlia őssejt (ES);, amelyben megtaiafóstö egy Pdögsn A (iambda) kébnyűiáhd: allét, amely tartalmaz egy ùjrareRdezsden®mberi VA és egy éjmtefufezetiea emberi JA génszegmpsi ahol: á sejtben megtáiáíható az emlitott endpgéb iiN/rÀ>· I ailÂt *<ί<ή# WX*, íX^í‘*!>. Λώι^Ι«ίϊ'>τ»ηΛηΛΪί «7 *mhívi .ίλ í>árt*7c5*ftmí:rn«ísítíSí aiiéf második VA-JA-CA génkíaszíerében tévé V<WA géhszegmensének - Észben, vagy egészben történő - helyettesítése, amelyek műtéti úton kapcsollak az említet? második VA-JA-CA génklaszísr egyérínteíien egér CA konstans régióhoz, ahol az Enh 2,4, egét iambda f enboneer (End! ás Enh 3:i endogén: énban-serok áriníeitönek maradnak az említett A könrtyöiénc aÉiben, 1:4,, Egér embrió, amply a :14as igénypont ^'ÉíbitrÉghstáríKí»»' őssejtet -taítsl^pza, vagy abbéi ileplÄ ki, vagy abbé! kinyerhető, ahol az egérenmriőbsn magfaiàihstèpgyendDgéh Atfemhde) könnyiláne alléi, amely tarfeimazegy öjtarendozellon emberi: VA és agy ujrárendezetien emberi JA géhszégmenst ahöl főiben megtalálható az omiífed áadogéh egér A könnydtáno síiéi első Va-JA~GA génkiasziéÉnek deíéoióm és az éneiéit emberi: VA és jAgénszegmaftöskititöriaimazó áiléi második VA-JA-CA génkiaszterében lévő VA-JA génszegmensének ·· részben, vagy egészben történő - helyettesítése, amelyek műtéti úton kapesőlíak az emiÄmisodik VAÉA-CA finkíasfeérégy érintötien eprCA konstans Églôhoz, és #hof azlnb 2:4 egér lambda 3'enhancer (Enh; ásinb 3,1 endogén ehhaneeÉk érintetlenek maradnakM említett Akónnyetáne aiíéiben. 15. A: l,2*e§ igénypont szerint meghatörozött SdímMta otyan bibridcma sÉl^îrehozâsàhoz, emely egy hVAihdA éségy egér GA génből szártnetot? KönnyűÉnect exprimai, ahol a hibridomp sejt az :14G igénypontok bármelyike szerint mepafemzott egérből származik vagy abból kinyerhető, ahöl a sejtben mégtaiáihaté sgy újrarendezett emberi VA gênszegméns és egy újrarendezett emberi JA génszagmens, és az emiiteíí andbgén egér A ktmnyíííáno allé! else VA-JA-CA gérikiaszteréneh delésíója és az említett çmben VA és JA génszegmensskef: tartaimaző -alléi második VA-JA-CA génkiaszterében::: iéyő VfeJA génszegmensének » részben, vagy egészben történő - helyettesítésével, «melyek műtéti élőn kapcsoltak az említett második VA-JA-GA génkSasztör egy éríntellen egér CA konstans ÉgjőhöZ, és ahol az inb |4, egér lambda :3‘ enhancer ;Sbh|és: Inb 3.1 endogén:enhancerek érintetlenek maradnak az emílleít A kcnnydlénc aiiélbéü,
  7. 16. Hibridémá sejt, amely egy hVA, hJA és egy CA egérgénbói szarn^aztatöltkánnyűlánédt exprimai, âbis hibridőma sett az 1-16 igénypcntak bármelyike szerint megbatározott egérből származik vagy abbéi kinyerhető, ahol a sejtben megtalálható egy újrarendezett embon VA gènszegmens és egy öjrarendézaít emberi JA génszegmens, ás az ül endogen egér A könnydlóno ili also VA-JA-CA genkiasztsmnak deléeíoja ás az emberi VA és JA gánszagmenseket tartalmazó síié! második VA-JA-CA génklászterében levő VA-JA génezegmensének * Észben, vagy egészben irténő * belyetfesifese, amelyek rnűíéti úton kapcsoltak az emSItöi második VA-JA-CA génkiasztsr egy érintötien egér CA konstans régióhoz, és abet az Enh 2.4, egér iambda 3' enhanesf {Enh} és Enh 3,1 endogén enhancerek érintettének maradnak az említett A konnyölánc aiíéiben.
  8. 17. Éödszer aolesiSétrehozasáraégéfben, antfey ferteimazzat a) egér kitételét egy antigénnek az 1-es ígénypont szehht; b) sz agár áiyi, az antigénre adott immunválasz kifejlődésén# iehétövó tóteiet;ás o) egy aniest leválasztását a (b) sz&amp;rinb egérből, amely kifejezetten m antigént ismeri fel, vagy egy aníifesttsyáiaszíássl a (b) szerinti egérből, amely tartalmaz egy immonógíohuíifl domóní, amply kifejezetten az antigént Isméd fel. vagy agy olyan nehézlánc és/vagy könnyűlánc variábilis domént kódoló nukfainsaVÉzékvencía azonoslfását a (h) szerinti egérben, amely kötÄ az gntíglnhéz, ahcliaz antitest egy h\% bJA és egy CA egir gfelhöi származtatott kénnyöiánco? tartalnmz,
HUE11728508A 2010-06-22 2011-06-22 Emberi lambda variábilis régiókat és egér konstans régiókat tartalmazó könnyûláncot exprimáló egerek HUE029692T2 (hu)

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