HUE032090T2 - Az activin IIB receptor stabilizált variánsai - Google Patents

Az activin IIB receptor stabilizált variánsai Download PDF

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HUE032090T2
HUE032090T2 HUE09761055A HUE09761055A HUE032090T2 HU E032090 T2 HUE032090 T2 HU E032090T2 HU E09761055 A HUE09761055 A HU E09761055A HU E09761055 A HUE09761055 A HU E09761055A HU E032090 T2 HUE032090 T2 HU E032090T2
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seq
polypeptide
poz
substitution
ahol ahol
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Jeonghoon Sun
Lei-Ting Tony Tam
Mark Leo Michaels
Thomas C Boone
Rohini Deshpande
Yue-Sheng Li
Hq Han
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Amgen Inc
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Claims (5)

  1. ISM WLVK Η,ΗΓ.Λ ï rt MN JUSV L .JvfoláU fehérje., amely egy stabilizált aGivin ffB receptor poupepdóct tartalmaz* ahol a fc'oKm forge ροΐίρορόόίό » »oebh expound < davtn k ft fS|} orv oo HVp* d ,H«J\vvk , v<v\HUÍá,(U ιΐΊ i 12 rS - v tm 1 ' m \ S mutatjuk be fb| egy polipeplid, amely legalább 90%-os szekvencia-azonosságot mutat (a)~val, ahol a pohpeptid epv W-t vagy eg\ \ t tarínbrw,' a ? \zanm s/ckxenue 2<v,rt pozienoanak megfeleld pozícióban, és egy Tó tartalmaz a 2. számú szekvencia 44 es póznájának megfelelő pe/h.uoban. aboi a pohpeptal Kq*s ken kim <» mmartaünho . „ acte »n \ he,, vagy a GDT·· 11 -hez. és fp) polipeptldek, amelyek legalább 9$%-os s^vencm-azonosságot mutatnak la)-vul. ahol fe poUpepiid egs W-t vagy egy Yo tartalmaz a 2. számú szekvencia 28-as pozíciójának megfeleld pozícióban, és egy Tó tartalma*. :é '2, izihmoäzekycncla 44-esr pozíciójának megtetelö pozícióban, ahol a poiipeptkl képes kötődni a rmosztatmhoz, az activm Aá% vagy a GDP-1 Ghez,
  2. 2. Az 1. igénypont szerinti fehérje, ahol a poiipepód legalább egy heiemldg polipepüdhez mpcsolóclA:, 3. A 2. igénypont szerinti lehetje, ahol a heterológ polipeptid egy IgG Te dorne«, 4. Λ 2, igénypont szerinti fehérje, ahol a heleroiőg polipeplid egy linker szekvenciával vápádiódík a poHpepîùihez. A A 4. igénypont szerinti tehet je, ahol a linker sztkviniiÉ a 25. számú szekvencia-záz.lat, 27. számú szeks enda-\ áztat, 38, számú szekvencia-vázlat, 40, számú szék vendu-vázlat. 42, odmú szekvencia-vázlat. 44. számú szdkvencia-vázlat, 43, számú szekvencia-·vázlat, 46. számú szék-zenein-vázlat, 48, számú szekvencia-vázlat. 49, számú szekvencia-vázlat és 50. számú szekvenda-eázlat csoportban bemutatón szekvenciák közül választhatjuk ki. ú, Λ 3. igénypont szerinti lehérje, ahol a fehérje az alábbi cső port föl választó poli pepi idei .artaimaz; {a| egy polipéptid, amelynek a szekvenciáját a 8„ IC)., 16, lg 18. számú szekvencia-vázlaton mutálj ok. he ÇP) egy pohpeptid, amely legalább 90%-os szekvencia-azonosságot mutat tai-sai, ahol a pobpentu! ee\ W-t s xgv ec\ Y-t t muhmtz a 2 ,ιζ,ηη. -vedcm.; >. 28- o pvcavasuk vk o e.vtvíoo f G C', I-t tat.a n\o a * cn.i \ a i u< ' -4 5 m d megtelem pozícióban. ahol a polipeplid képes kötődni a mloszlaónhoz, az auhm A-hoz, vagy a GDI'-} t-he>\ és |c) pohpaptidek, amelyek legalább 95%-os szokvenctá^axonosságot mutatnak inyvah ahol a pohpeptid egy W-t vagy egy Y-t tartaíovaz a 2. számú szekvencia 28-as pozíciójúnak mvglmdo pozicu'han, cs ogy ló tartalmaz a 2 szama szvkveoma 44 e\ ptvnciótanak megfelelő pozícióban, ahol a pohpeptid képes kötődni a mioszfatinlmz, az acuvm A-hoz, vagy a GDf-1 iótéz. T« lóit kK t- I > V }» s',nn,i s ok vc» v »-vas’ » , \ m ' > \ *. · telked}::. B. (/obit tehene, amely egy stabilizált at. mm H B receptor poHpepùdet levAeiKuB; «a* te. car mvi .* xmKrn ;dm- pehpv l'ink.t * '- o\, κοζο - s>T'Uhvl v abs.nhaitul- ki (a) egy poltpepùd, »moly a 2. s/amû szekveneia-vádimm be rut itat ott .xsekveuciávm rendesek.. , ed V îcK'^ck kogy cm mmmvm.os k'ÈMttes \ a- e ? '-' 'eme szodooou Nb a- em love porte* zham » * net ammosmes he'venoMS v<m a ' s-verni rockseneia d es^vziemja-b&amp;n levő pozícióban, ahol a 2$-:ts pozícióban lesd hdyeUesiUN iohe? W '»gy >, <-'* a P***' mohán bvo-heiyôfeesii^ïi.l; (b) cm pohpeptid. umd\ a 2 szmitu vek sevens s'? d-vs er' n en u oaotu » *' Kí 5 s' rendelkezik, azzal az eltéi-éssel. hogy egy aminoàavas helyettesítés ven a 2. szama szeievencta zü· as pozleléfábaü levd pozícióban, és egy aminosavas helyettesük van a 2. .számú szesvetusa 44-es ptjzkléjába« levő pozleióham ahol a 28-as pozícióban levő helyettesítem lehel. V* vagy s. es a ;»t es pozícióban tévé helyettesbe*»B ; te) egy poiipephd, amely a 2. számú szekvencia 23-134-es amlnosavat aozóttí szekvenciával mm held Ά a/< al . élteievd, bogv egs umnoema» HelyctttemK van a 2 scmAi saóo'Ko „s ss pozidojában levő poz.ieii.lbnn, és egy amínosavas helyettesítés van a 2- izávm szekvencia 44-es oozidójában levő pozícióba«, ahol a 28-as pozícióban levő helyettesítes. lehet Y*: sagy N - «s a 44. es pozícióban levő helyettesítés 1 ; hl) oe\' rxdipeptich amely a 2. számú szekvencia 25-l34-cs aminosavar közötti szekvenciával crée \o<n . z ! '? d e'OsO hoe> e„^ u V'.’s \ Kettes tes van a ** » mmu s^edenu ,, u as pozíció iában lesé pozícióban, t-s egy tamnosavas helyettesítem van a a. számú szekvencia 44-cs y,n , m V },i\ leve* puítviob m. vl ni a 28 .u ,<v , v ?h n eső hcKdtosd',» tehet V\ v,p>v v. es a tt es pozícióban levő helyettesítés T; (e) egy pokpepttvi, amely legalább üö%-o$ szekvencia azonosságot mutat az (a) Hd> lantban sze-rop Ili szekvenciák bármelyikével. azzal az eltéréssel, bogy egy aminosavas helyettesítés van a z.. számú szekvenem 2h\í< poz**.iojdun levő pozícióban, e* vgs unnnosavus hdy enemies van a 2 szama szekwmcta 44-vs pooctoinbar. kno pozícióban, ohm a 28-as pozien-okm leve helyencsíte^ Mxt \\ x.^y k.esvt t-bcv póz Klóban levő helyem.ados I
  3. 9. Izolált mikleiasav molekula, amely a 8. igénypont sz.eriids pokpepudet sóón In poliouklcotklot tartalmaz. W< Izolált tmklditÄ Jlólélmlá, iatbely az alábbi csoportból választható poimukleotmoi tartalmaz; (al egy folnmkleotid, amely egx olyan pob.|Xfn*k't kod n. nndym s i vobcv <* ot a 3 c 12. és !4. s/mu'i szckveneia-vazlaam rautatmkbe {h; egy pohnukkond, amely vg> nl\,ai pohivpodet koi.nl. .r .. x 'egakbb ,'s v.c.. > cla-azonosságot mutat («}-γ»Ι, ahol a polipcptld egy W-t vagy egy V-t tartalmaz a 2. o',mm s.vkxukia 2e-as onzicuíjmak pv^ndelo p»> etóban > ' I f t,r ! no <s smnm szekveneta 4a es pozK'ioyan.*é mcgicleió ptizicmlun. ahol 4 poltperod keres ko tödíh a mioaztntinboz, az aeitvm Λ-hoz, vagy a (,Η.)Ι'- ! I -nez. és tgó egs po m* klc*u»d. an c v i'p < \ η n '' dot kodé t v ,g , b'á' *\ e»n ' dmazmtosságoi mutat 4a)-val, ahol a po II pepi ki egy W-f vagy egy Y-t tartalmaz a 2. számú szekv-oiKíia 2S-as pozleimánuk mcg-'delö pozkuóhatt. és égy I -l lurtnimaz a 2. számú szekvoncH): 44 es pozíciójának mc..;ck'ló on/.ciol .m. a!>ï? a j\v*>vppd \cpcs V*-litlni p tiloaztathúioz. áz attívm Λ-hoz, \ agy a GDI -11 -bűz. 11. \ h' sœnsiii ms\ ^ * s<ï\ rt o v \ t - «u « 0 «Ν'* * uk v > d k <^n» » · kb*.etkezo csoportból \álaszthnijak ki 3 , '« Π és Π s/amu szekvencia, satumra >.ace kompomon* terei.
  4. 12. V ptvViîsO!-'!. f'uk'e ' ! m,s\U <· d'O! > H > tuh.^OUw.tUM« î Z C '-iegakhh egy hcteiolèg khèrik ködeié pnimukleotidot. 13. A 12. Igénypont szériáit hülddnsav mojekglàg^i'ly a kdyeilpző csoportból válaszé káté polinukleutidoi tartalmaz; iá) i.fg> polinnkieotkl. amely egy olyan poljpepíidd kódok a melynek a szeavimeimát a S,. 10.. 16. es IS. »zárná szekvencia-vázlaton mueniuk be (b) egy polinukleottd, amely ogy olyarrpolipeptidet kódol, amely legalább 903»-os s?.ekven.< ; eis-iTzcmosságot mutat (anvak ahol a pnii pepiid egy W-í vagy egy Y-t tartalmai a 2- szama szekvencia 3$~as pozíciójának megfelelő po idd óban. és egy I 4 tartalmaz a 2. s/ámu szek-'.énein 44-es pozícióiénak meg felelő pozícióban. ahol a pohpepnd képes kötődni a miosztat inhoz, az uethm A-hoz\ vagy a (.sí >}-! hheu, és (e) egy poimukieotid. amely olyan pokpepudet kódok amely legalább 95%-o* s/eievcnei;*·· azonosságot mutat tuovak ahol a pofipeptid egy kV-i vagy «,g> V-t íaouinu, a , s/amú sielyenck pozíciójának megfelelő pozfdóban} és egy T-i tartalmaz a 2. ázáson szék-vendit 44-es pozíciójának megfelelő pozícióban, ahol a pofi pepiid képes kötődni a mmszUimhoz, az min m Vlm., \ag% a U1 >1 11 -hoz 14.. A 13 igénypont széttnlt ηοΜίπηνο mokkáin, ahol a pohnukleoud a'chsenciakti a következő csoportból vakíthatná, k'r Ύ, e., 15. (s 17. azàmù uckvenun, vagy ezek komplems. morei 15. Λ 10. Igénypont szerinti nukkinsav molekula, ahol a poliratkleotid működés szem* smt aKö ο V n vi sd »,\.to ην> ,κ íu v soze o.voti * d'oz kap», v.od \ lő. Egy rekomhináns vektor, amely a 10. igé«>fx>nt szerinti nukieinsav tsoÄpitisrtgii soazm 1?. Gazda ou ,mv s , ' e< n.enyp> r n< c*mu mkombma’'« 'ektort tat ta- rezz. Ifi. A Π. igénypont szerinti gazdasejt. ahol aga/.dasek egy emlős smi. !t. 1 Paras cgv u Y tRlÜ'l feherp e uaUítavira aaz.k jellemezte. bo.„> a " yem,p<au. -,,ν I dm< ne* uho > ,\orx> ok ΚΝζο,> lu*'os/uù, eme,·' um 0¾ nyék ok -os. ok . lobéi c represszióját, majd kinyerjük a tehénét.
  5. 20. Gyógyászati készítménye amely hatásos mennyiséget tartalmaz az l-b igénypontoké unj' \>o tnt dtcieho \ np s m^. uv *·&amp; v he n>' μ ~ ! 21. Λ 2u igeuypontv t m kevouvíg t ki.máz,«,* gyógyvérként 22. \ 2d. igéin pont wn no fc*u mevm izoms*a\.uVi' \ags .remhobkns rendéi lenesség kezelési eljárásában, amely amdelienesség leltet eulorbeteaseg, elldzás, biperglikómia ésrcsoníve.SE> lés. egy iben kezelésié O"^rtdá al -.n> un. 23.. /\ 22, igénypont szerinti készítmény alkalntazása, ahol az í/omsorvadás izomsorvadá-vos Utegseg ktásetkeznienye, amehet a következők közül választhatunk Li l/omsorvadas, amiouóílás laterális szklerózís. pangásos obstmktív tüdőbetegség, krónikus szívelégtelenség, rákos ksobezia, AIDS, veseelégteíenség, uréniiat reumás arthritis, életkorhoz kötődő szarkopénia, szervser' yadáh egrplts akgói szkdrámíh androgén megfosztás, égési sérülés, cukorbetegség, igomsurvadási bosszú ideig tartó ágyny-ugalom miatt, gerincvelő sérülés, s/o<>k. csonttörés, életkot vagy expozíció mi kro-grav i táci óva 1. 24. Λ 20, igénypont sz.erimi kéa/itnjény alkalmazása egy betegség kezelésében, amelyben ?iz neuem title v »> "sza 'd \ eu 'u ^ " 1 dr f.n ó.-r de\- -, ' z 2S. A »pompát \oo*'»»i xeU«« ? *»n***txAxiS'* xaox nkiatvhhu" »O'KJollorC' Og - âîimiy lohst CiiköTbofcgség, elMeás, Mjp^rgiiMim.m ososisisiyeaztës - vagy rák: teoMsérs szolgáik e!|é-sásban valé alkalmazássá: ahol az aeilsm iúlskpreAzIlödsk agy llyta kezelésre szerűié alanybásy ahol a vektor képes; egy syáctRÜB ptigepbcl expsxvsziéját szabályozós az aiaoybam lő, A készítmény 24. igénypont ..szerinti alkalnsazása, vagy a vektor "25 < igértypotri szeri sn ti: alkalnspaása^ahol a rák petefészek fák '2% M%: lAk igétsypppfek bármelyike szerinti lelökje alfealsóazása egy eyitáskasg uielynek ásljtt a zssmtetttes izotsigkuég: Mlvelése, vagy a zstrilMsitel szotllömeg zlirtblrieglieZ visaoíiyitptt ara-gyáuakrs giveliaSj ahol az elíáráy p&amp;mm ·· #%Ht· ieél: kie^î<ssl eljárása iemplàvak
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