HUE035773T2 - Trivalens, humán légúti óriássejtes vírus (hrsv) elleni nanotestkonstrukciók légúti fertõzések megelõzésére és/vagy kezelésére - Google Patents
Trivalens, humán légúti óriássejtes vírus (hrsv) elleni nanotestkonstrukciók légúti fertõzések megelõzésére és/vagy kezelésére Download PDFInfo
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Claims (7)
- TRfVALENS. HUMÁN LÉGÚTI ÖRÍÁSSEJTES VÍRUS {HRSVj ELLENI NANOTEST·· UU ft JIRtó/V^ k MK.FUV.VSJ RV VS \ OO ktVVt íkt'RV Szabadat«» tgcny ponrok t t, a .sk<"\ pebpeps '>!, >«x R NON I \ ki ·. ttex 'ru<xx! 'Al\> Vk< ' M’Pk'ÍU''. kkxksxt'S'tc'tt (Aj trlvalens pollpeptid, amely a követkszkpeiipepbiOek köz«! választott: áj SEQ ;O NO: kikes 162--163 azérintl szekvenciák: b) pöiipépttóek, amelyck legföljebb 3, előnyősé» fögfötjobb 2<ai6eyössbbee legföljebb <·<·.>' ínnlnos-oban kölönbözrsk a SEQ ID NO: 142045 ée 16z- 165 ssförimS SEékvenkák bár«;«lyik6l:ól. fölföve, hogy :} a pobpepődbee tévő első ami«»$av-szeh vendît az t pozícióban aszparaginsavat ;Asp( D) Tartalmaz; és ti) a polipeptkl ugyanolyan vagy nagyobb ai'tföításssi kötődik a hRSV F fehérjéjéhez, trnnta 3, 2 vagy I ami* nosav-kölönbséget nom tartalmazó pollpepttó, áltól az affinitás felületi plazmonrezonancia eljárással mért, é$/vagy a pnlipeptid póföndájs azonos vagy stagasahb, sisal »potencia tnlfetztneüteltzácfös aasay-vetmcgba^ozotl,. cj.SBQ m NO: 77-29 és 158szerinti szekvenciák;, d) polipepiidek, amelyek legföljebb 3, előnyöse» legföljebb 2, előnyösebben legfeljebb egy aminosavban különbőznek.a. SEQ10 NO; 77-79 és 158 szeri«« szekvenciák bármelyikétől, Ibiiévé, hogy 1} .a .poíipeptldhen lévő «««rosse-sxekveaeliik I 63. pozíciójában glnta·««· (Gin, Q), « ?8. pozícióban lenni« (Leu, L), a iö, pnz&iófeá» at-ginln .(Árg, fö) ós/vagy a -85. pozícióban gíntaminsav (Óin. E) v<«:, ahol -a.· pozíciók a t ,,kr s.,n?e;.í xe et «xg s r,.x\,'«4. χ x) λ pe'sptptsd « 'xxx'han x.C'· r>j.x<'hb xVtxn,»’,\tt \exxK ,s «ΚΌ ; s.be ; «Ίχ<, «.mt a \ ? \rg' s ««; nosáv^kölónbségét nem tamimazó poiípeptid* 'ahol &s sifiosás fölüicti piazmonrczonanciá eljárással «föt« ávVagy a pekpeprd potcxcx»m <x«;:<« v,sg> «s sgncfö'k «föd a pmcEJv.e uxkvnentmkvx «·, ,χνκ \N .«cxixt:«<'/<'« Cj S.EQ ID NO: 1:59-161 szerint; szekvenciák; f) poiipeptidek amelyek legföljebb 3, előnyös«;: legmitebfe 2- deoj.öaebkm legföbebb egy ummmavhun kölönbőzsiek a S6Q 10 NO: 139-161 szerinti szekvenciák barmelytkernk íeitcvc, begy \> pepfö,k ' « « nexx- χ'\\„\r ' p<. 'X e<<\ n : p « « V1 « P' .. 1 asg; »' {.Arg, föl, a 20. pozimöba« lene«: (Lets, L) és a 108, pozmmb&n lenem th». 11 wn ahol a p-vk'mk « Kabar-seárpozás széria: megbátátözottak; és h: a «Ni««««« ngveneh«« tng> x,;e>eifö alttoha«.» befödik a bRS\ E föhcrje-ehce, mint« \ 2 usn;·. I ans« ií>>sav senkik eges «·,".{} GiSáföx;?« pnhpensífö ahol az aOklíás föioleti plaznx<«te?enancía e^arassal anas, es v<sg> s pf> tap«' x9. \a I 'i'b ko apó 'ns t,-;™« i'h s< sss > .x xi; e'-^atarozott; (0) írtvaíens· pPilpeptnl, ánföly 4 EesOtégiöbsii és 3 kenspleixensnsstas! íneghefös'ozö régióból (GI5R : áliö hátsóm aminosav-szekvenciát tartalmaz vagy abból áll, ahol, , ή ODRI s SPQ ID NCi: 98 szétOii sziskye««»?; «S - a CDR2 a SkQ 1D NO: KO szeri«« szekere«;: es - «CORS aSEQ10 NO; ki szeri«« ésrkv«r«ía, C tu' tk«s t 'b,'c ' , í X? s i «< iöl \ ' s ·,\S ; < ! ! \ !<X a> " < s ' ' ·. r 1 a i > sx -s η 1λ rev'.; « 1 csexs«.? aMl cso^rríNN \,tl?s.tvtt aj SEQ 10 NO: 66-76 szerinti szekvenciák b) amtrtosav-szek venuák, amelyek legfeljebb 3, előnyösen legfeljebb 2, előnyösebben legfeljebb egy ainl· η,ϋ,,οΡ m 1 éhmbo. IR k ? >1 Ο IV W ¢.0 'o..’eut',v'\e:n>'UA,\Ί teke"? hor,v I) az aminosav-szekvencia 105, poAciőjsbzn glntamín (Gin, 0) van, ahol a pozíctö Kababszámozássai ; ή cgis átáro £Óît, és •un i. •'îkwïi't <^\?nonei'sV ’K''s"î\ a kov\fe\ 4hkw 1 g m \ v \ A4' ? ami·· no&av’küiőnbséget nem tartalmazó poiipepùti, ahoi az affinitás felületi plazmonrezonaneia eljárással mért, èv'vagy a peiipeptkl potenciája azonos vagy magasabb, alsói s {xiseoela mikronewalizációs assay-vel meghatározóit. "•o · 3 'W '*>' S ' Ü S V·, , k d) attőrsösíiv-szekvetreíáií:, amelyek, legfeljebb 3, előnyőseit: legfeljebb 2, előnyösebben legfeljebb egy alni-nosyvbsit: külőftböisiek.aSÈQ tö’NÖ: 146-153 szerinti szekvenciák bármelyikétől, feliévé, hogy i) az atnlhosav-s^ekvencia 14. pozíciójába» prolin (Pro, ?}, s 1:9. pozfeiőban.arginin (Arg, fel, a 20, pozfcfe. ban lesel«: i'fees, L) ős a lös. pozícióban: leticin (Lett, L) van, aböl: tt,pozíciók a Kabat~számo»ás szerlor méghatáro* köttök; és II) a pollpepbd ugyanolyan vagy nagyobb ttidnstassni kötődik a hRSV F feltétjeiéhez, rmot a 3.
- 2 vagy 1 ans« I X o k V b \u ' tt rd η o ' h>\ pt, tu > ü mi U ! < o m mou , > >,u \ r pobpepíld potenciája azonos vagy magasabb. tőtől tt potencia mikroneotralizációs assay-vel megbatározott. 2 VI ognsoont s^m m, · oatcs- pobo'poP amsb taiR!'m.u„s a -4y· Η» \·3 V mt ,.ek\uiu,a vagy a SfeQ lD NO: 33 szerinti szekvenciából; áll, - tshrd az első glstantinsav aszpamginsavra lett cserélve, és ttotelybets adott esetben legalább egy, & SEQ10 NO·.?· 3 szerinti sZekvcnCiá löszét képező Vilii szekvenciában egy vagy több, « következők közöl: választott -antlnösav t tn s nt V t -ti ni \, tt!< ' V 5î\ V i <tt < t.v< h v ' t ·, ' ö, ,, \ A - \ ·. V pm· t . ArgiÓSGIo, GiniÖkLeo és Gly54Asp; vagy - antélybeo legalább egy, n ShQ ife feööő szerinti szekvencia részét képező VHU szekvenciában egy vagy több, a Κ',Κ·.ό1, 0' \ ' <"·, ' u'no'ts n tb'V Vb ut G -I'm V kV 1‘, W uö < 1' AlfeMSet, Gly78i,eu, Alak3Arg, AspSSölá, Arg lőSGln, ömlOSLen és Gly54Asp.
- 3. Az h vagy 2. Igétiypottt szermd írfeále&s: poiigepőfe amely ktrtahoazza a őEQ Ϊ13 NO: 33 szerinti szekvenciái: vagy a Si-3,) 113 NG 5-3 szerinti szekvenciából áll, amelyben legalább egyá SFQ ÍD NO;53 szerinti: szekvencia részét képező Vilit szekveneiábso a köveíkézŐ ásnlnOSavák ttsátáídótak: - VafeLeu, Alnbköo, GfetdAGly, Giy/hi.ea, AlaifeÁtg, AspkSGkt, ArgiöSGinés Gfeíiőktén; VrVki' Vt'Vt.! n \ gittig t vnió - GlyTSteUj Alaké Arg, Ásp§50iu és A|:gl03<3in' \ elei vn, M.íMPío, Vht4 k»i\, t )b"Pl en. Alaké At g VníVuín, Argit^Gh. CdeMSUn ,'s · fe, >4 Vp, - .AiakőArg, AspSSGlo, ArglOSGln, ÖlniősLeo és Giy.SéAsp; t. \ \ S s ", V t ,1 \ t X h <·. 1,1 V \ - GiySdAsp; - AfeidPro:, SerlVArg, Heá’ölfen és GlnlödLea; • Vei W>\ SuíWg, Ikfeől en, tálaio${ cm'! ,\l.tS< krg - AlsidPro, SerlkArg, ffe2öte«, öle 1 Ô-Sts» és AspbíGie; - AislAPro, SerlŐArg, ffe20ten, ölosOSkec és Argl OSGlít: - AiaidPro, SerlŐArg, Ue2öLeu, GinlOkLeit, Alaké Arg és AspSdGkt; - AlalAPro., SefiOArg,. fieSôLçig ölni OSfets, AiafSArg és ArgtöSOin; - AliiiApro, Sérl9Arg4 iieéöLea, Gin 108f.cn> Asp85öh.rés ArgsöSGIo; - AiaiAPro, 8erÍ9Arg> fl«26f,co, ölnlökfsn, Aí.a83Arg, AspkÓölt; és Arg fÛSGto» * GtolAsp; X < ! \ ' \ S! X \ >’ y \ U \ ’ X "> '' Ά ’"4.H ti \ ' t t'\ X süni A·' uNv' ^vR'uh, \t,fővén V Giolokl ct, ' Gto.l.Asp, Glyí-SLeu, AiaSâAfg, AspkSGÍa és Arg; OSGIn; - -GlulAsp, Vaöl.eu, AlítlAPrty Gto44Gly4 <Py7§l,e«, AiaöSArg, Asp85Glu> ArglöSGln, GlsW&Leu és GíySéAsp; ~ GtolAsp, .Aia83Arg,-AspbSGto, ArgiOSOln, GinlÖRLeu ásGIySPAsp; - OtolAsp, GiyvbLen, AialöArg, AspUSGin, ArgiiOGto és Giy54Asp; - GtolAsp és Gly54Asp; - GtolAsp, AiaxdPro, SeriOArg, IleaOLet; és. GírIOS-Lsu;. - G«1 Asp, AiaMPro. Ser SOArg. í|e20(.cu, GtoWSLeu és A-séJAtg; · GtolAsp, Aia-l4Pro, Sez'IPArg, iiefbbea, GlnliOLeu és A.sp85Gto> - GtolAsp, Aia-HPro, Scrl9Arg> Íle20ien> Clnl03f.s« és ArglOSGto; - GtolAsp, Ate-HPm, PerlNArg, Me30XxwQtoX$té». AíaíOArg és AspÖ5Glp; GtolAsp, AiaMPro. berlOArg. ItoeCü.ec, Gtolökfeu. Ala&sArg és AtglOSGlo; - GtolAsp, Aiaí4Pröj berlOArg,. Iie20k«n, Gtolöéfen, AspSSGto.és ÁrglOSGln; vagy » GtolAsp, AlaléPro, Serí 9Arg, liefOLen, Gtolöhfctg A!a83Arg, Aap85Gtoés ArglOSGin,
- 4, Az ló, igénypontok bármelyik® szerinti trivalens polipeptkf amely SFQ 143 NO; 77-79.., 143-145 és 158-165 szerint; szekvenciák bármelyikéi tanainsszza vagy abbéi áll.
- 5 ! bar λ ' -) x$<n\poH’o\ p<nnK\ViU w.» tnsakns ptospeptto t •ciíhnusia A'U ,'haus Un ttonvaa legalább a kővetkezők közöl választón bárom tnonovaiens aminosav-szekvenc-ta vagy tnonovaiens konstrukció és például égy vagy több linker összekapcsölásáósk lépéseit: ai Sb'Q IDNC. ;4í-A< wmn wl,sonnt,äto b) atninosav-szekvenciák, amelyek legfeljebb 3, előnyösen legfeljebb 2,. előnyösebben legfeljebb egy ami· nosavbép külön bözoek -a SEQ ID NO: 60-76 szerinti. szekvenciák bármely Ikétök leltévé, .hogy i) .az .amtooaav-szekvenfeia 105, poztoíójában -gtotamin főin. Qj van, ahol árpozíció KafeaMZámozással meghatározott; és il) a polipephd ugyanolyan vagy nagyobb affinitással kötődik a hRSV F fehérjéjéhez, mini a 3,2 vagy I ami-X X >x> · xi ' < < 15 ;r ; <i X Al ν' a X ? G vb n < X < i e ρ x > íx οοη* xi f;> Vsai \ x t \ χ poiipsplid polenélgía azonosvagy magasabb, ahol a potencia toiiNoaeitoPlizáeibs assay-vel :sv?gb;páföZötk ej SbQ ff) NO: 146-153 szerítoj szpkveneiáfc: áj mntoosMMzékvéífeiík, antelyck legfeljebb 3, előnyösen legfeljebb 2, előnyösebben legfeljebb egy afef nosavban különböznek a SEQ 113 NO: 146-Ί 53 -szerinti szekvenciák IsárnielylkétÓI, Ibiiévé, hogy il az amtuosav-szekvencia 14, poziesóíáhaa prolin (Pro, P), a 19. pozícióban argont; ; Ars. R), a 20. pozírf óban leucin (Leu, L) és a 108, pozícióban lent in (Let;, L) van, ahol a pozíciók a Kabat-számozás szerint tnegb&ié-rozoftak; és il) a poiipeptiíf ngyanniyan vagy ni&obh Nífeitossal kötődik a-hRSV F lébérjéjèhez, exinî a-3< 2 vagy |: ami- ss<:-st3v-ks.iksi?.bségeî nem tanaitnazó poiípsp5«K ahol az affinitás felőled plazmortrezonanela eljárással mért, és/vagy a pöiipoptíd potenciáit n»mo$ vágy -toagas&bbx áltól-a-polémia mikxoneutrailzáetős asssy-völ magbatározott, e) SEQ .119 NO; 138-141 és 154-157 szerinti szekvenciák; I) aminosav-szekveiteiák. amelyek legfeljebb 3, előnyösen legfeljebb 2, előnyösebben legfeljebb egy atni-nosavban.kölönböznek.a S.EQ 1D NO; 138-041 és 154-157 szerinti szekvenfffek bátspeiyikétöl, feltéve» högy i) az antinosav-szekvencia 1. pozíciójában aszparagtnsav íAsp. .0) va», aböl a pozíció a Kabaí-számozás szerint meghatározott; ős > í \ ' >1 -· ' 3 ax'- }'<'·> sbb 3 b'í S XV ' vRW > <p <t .. óit - ' >' 1 3 « nosavdctdőnbséget nem tartalmazd po.lipßpöd, sböl az affinitás felöieti pisizmoiiiózööáúffiá söéréssal méri, és/vagy a polipíípbO pöteoffiájs íkíöoös.vagymagmbb^ahoiapótettcta oitisfotrfftnt'alifetffiös assay-vel inegbalarozon,
- 6. Nuklelnsav vagy nakleottd-szekvencia, amely 1-4, igénypontok bármelyfee szerimi polipeptldet kódol.
- 7. űszda vagy .gazctoejt. amely M. igénypontok bármelyike. szerinti polipeptidel expresszai éfevagy áítrsly tartalmaz ö, igénypont szedni! ttukleinsavatvagy nnkleotid-szekvenclát, 8 \x.,'! !!\ . .-íf\h -4 !ί.?ίΛ<'0ί5Ρ\\ í'íüíiffA Λ<. S_'"f(í, p.'lít\‘pj\lffíf> igrt'tpo;! - Vi iipí S't'kk » savát vttgy nnkleotíti-szdkvenöi'át tartshttaz, 9, A 8, igénypont szffí'fctí készfenény, amely gyógyászati .készítmény. 10 ti>og>as.\t>i kes/nmcm, amUs I -I :gvospornok bam-eh -ke <.·<!fen pohpvptinet ps po-nicaabs bejuttatásra alkahnás hordozót IgnabW, H. Eljárás az 1-4. igénypontok bármelyike szerinti poiipepttd vagy a 3. vagy 0, igénypont szerinti készítmény ölösHipisáfa, amely eljárás t&nsltnttzza legalább- á következő Mpőséte: a) ő. igénypont szerinti nnkleinsav vagy nnkleon'd-szekveacia expresszálásat megfelelő gazdasejtben vagy gaz-összervözstbsn vagy más megfelelő expressziös módszerben. sa-' ' \fft\vtsp! ti za »<-t te gr,á<s»tt ív v.'Sx »Sx a»-X g» » t< mt-u ' kotofei' s.k lő’ót. amelyek között a gazda vagy gazdasejt expresszi! és/vagy előállít I -4. igéttypttn-c-k bármelyike szerinti polipeptldet vágy 8. vagy 9. igénypont szerinti készítményt. amit adott esetben a következő követ; b) az így előállítóit, 1-4, igénypontok bármelytké szerinti pob.pepíid izolálása és/vagy tisziitásá, Î2, Az 1-4. igénypontok bármelyike szerinti polípeptid és/vagy a §. vagy 9, igénypont szerinb készítmény a kővetkezők legalább egyikének megelőzésébe« és/vagy kezelésében tőrtéstö alkalmazásra: resplraiorikns betegség,. felső légúti fertőzés, alsó légúti fertőzés J>roaffbfelríísz, tfeíőgynlládás, diszpnoé» köhögés, zihálás és asztma. ti i \ 3\< <- t s t <. -n<. \ xí k< t> ä\ IX s; o tlt bx 1.1 t s * I» + >x >p» i X k >v ovlv \ s'inis pöbpffpiidét SáNáisttáz. Ï4. \ ' gxi!»3,> ', -Ί, 1 !'xi"3 X xp .X » 3,? x.3í<' , 3íx’x< >'i\ xt \í>\ >3 -C!x , <. ! x W \'?f? p< mhxiMx«. xio’e \ 4 tg 3\$\rU"k t'úunh ki'szumh Ό, jOpOik» I WÍo.a;
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