TR201908291T4 - Şifrelenmiş bir tümör antijeninin ekspresyonunun arttırılmasına yönelik bir histon sap-ilmiği ve bir poli(a) sekansı veya bir poliadenilasyon sinyali içeren veya bunun için kodlama yapan nükleik asit. - Google Patents

Şifrelenmiş bir tümör antijeninin ekspresyonunun arttırılmasına yönelik bir histon sap-ilmiği ve bir poli(a) sekansı veya bir poliadenilasyon sinyali içeren veya bunun için kodlama yapan nükleik asit. Download PDF

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Publication number
TR201908291T4
TR201908291T4 TR2019/08291T TR201908291T TR201908291T4 TR 201908291 T4 TR201908291 T4 TR 201908291T4 TR 2019/08291 T TR2019/08291 T TR 2019/08291T TR 201908291 T TR201908291 T TR 201908291T TR 201908291 T4 TR201908291 T4 TR 201908291T4
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sequence
stem
nucleotide
loop
complementary
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TR2019/08291T
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Thess Andreas
Schlake Thomas
Probst Jochen
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Curevac Ag
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    • C12N2830/50—Vector systems having a special element relevant for transcription regulating RNA stability, not being an intron, e.g. poly A signal

Abstract

Mevcut buluş, bir tümör antijeni veya bunun bir fragmanını, varyantını veya türevini içeren en az bir peptidi veya proteini şifreleyen bir kodlama bölgesi, en az bir histon sap-ilmiği ve bir poli(A) sekansı veya bir poliadenilasyon sinyali içeren veya bunlar için kodlama yapan bir nükleik asit sekansı ile ilgilidir. Ek olarak mevcut buluş, nükleik asidin, adı geçen şifrelenmiş peptidin veya proteinin ekspresyonunu arttırmak amacıyla kullanılmasını sunar. Bu ayrıca bunun, farmasötik bir kompozisyonun, özellikle bir aşının hazırlanmasında, örn. kanserin veya tümör hastalıklarının tedavisinde kullanılmaya yönelik kullanımını açıklar. Mevcut buluş ayrıca bir tümör antijeni veya bunun bir fragmanını, varyantını veya türevini içeren bir peptidin veya proteinin ekspresyonunun, bir histon sap-ilmiği ve bir poli(A) sekansı veya bir poliadenilasyon sinyali içeren veya bunlar için kodlama yapan nükleik asit kullanılarak arttırılmasına yönelik bir yöntem tarif eder.

Claims (2)

ISTEMLER
1. Asagidakileri içeren kit veya parça kiti: A) bir kodlama bölgesi içeren veya bunun için kodlaina yapan bir nükleik asit, burada kodlaina bölgesi, NY-ESO-l tümör antijenini veya bunun bir fragmanini içeren en az bir peptidi veya proteini sifreler; B) bir kodlama bölgesi içeren veya bunun için kodlama yapan bir nükleik asit, burada kodlama bölgesi, 5T4 tümör antijenini veya bunun bir fragmanini içeren en az bir peptidi veya proteini sifreler; C) bir kodlama bölgesi içeren veya bunun için kodlama yapan bir nükleik asit, burada kodlama bölgesi, surViVin tümör anti jenini veya bunun bir fragmanini içeren en az bir peptidi veya proteini sifreler; D) bir kodlama bölgesi içeren veya bunun için kodlama yapan bir nükleik asit, burada kodlama bölgesi, MAGE-Cl tümör antijenini veya bunun bir fragmanini içeren en az bir peptidi veya proteini sifreler; ve E) bir kodlama bölgesi içeren veya bunun için kodlama yapan bir nükleik asit, burada kodlama bölgesi, MAGE-CZ tümör antijenini veya bunun bir fragmanini içeren en az bir peptidi veya proteini sifreler, burada NY-ESO-l, 5T4, surVivin, MAGE-Cl veya MAGE-C2 fragmani, en az alti amiiio asit artigi uzunlugundadir; burada her nükleik asit A, B, C, D veya E - 5' 'ten 3' 'e dogrultuda - asagidakileri içerir veya bunlar için kodlama yapar a) kodlama bölgesi, b) en az bir histon sap-ilmigi ve e) bir poli(A) sekansi; a) kodlama bölgesi, b) bir poli(A) sekansi, ve c) en az bir histon sap-ilmigi; burada i) veya ii)'deki en az bir histon sap-ilmigi, asagidaki formül (1) veya (II) arasindan seçilir: formül (I) (sap sinirlama elemanlari olmayan sap-ilmik sekansi): sap 1 ilmik sap2 formül (II) (sap sinirlama elemanlari ile sap-ilmik sekansi): Ni- 5 [No ch1 3] INiu(Un)Nii 4] [N: ;CNMJ Ni i› sapl sapl ilmik sap2 sap2 sap] veya sap2 sinirlama elemanlari N 1-6, 1 ila 6, tercihen 2 ila 6, daha fazla tercihen 2 ila 5, hatta daha fazla tercihen 3 ila 5, en fazla tercihen 4 ila 5 veya 5 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; sapl [N0_2GN3_5], sap2 elemani ile geri komplementer veya kismen geri komplementerdir ve 5 ila 7 nükleotitlik ardisik bir sekanstir, burada N0_2, 0 ila 2, tercihen 0 ila 1, daha fazla tercihen l N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindaii seçilir; burada N3_5, 3 ila 5, tercihen 4 ila 5, daha fazla tercihen 4 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir ve burada G, guaiiosin veya bunun bir analogudur ve sap2'de bunun komplementer nükleotidi sitidinin guanosin ile degistirilmesi kosuluyla istege bagli olarak bir sitidin veya bunun bir analogu ile degistirilebilir; ilmik sekansi [N0_4(U/T)N0_4], sapl ve sap2 elemanlari arasinda bulunur ve 3 ila 5 nükleotitlik, daha fazla tercihen 4 nükleotitlik ardisik bir sekanstir; buradaki her N0_4 birbirinden bagimsiz olarak 0 ila 4, tercihen 1 ila 3, daha fazla tercihen 1 ila 2 N'lik ardisik bir sekanstir, buradaki her N birbirindeii bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; ve burada U/T, üridini ya da istege bagli olarak tiinidini temsil eder; sap2 [N3_5CN0_2], sap] elemani ile geri komplementer veya kismen geri komplementerdir ve 5 ila 7 nükleotitlik ardisik bir sekanstir, burada N3_5, 3 ila 5, tercihen 4 ila 5, daha fazla tercihen 4 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit aiialogu arasindaii seçilir; burada Nm, 0 ila 2, tercihen 0 ila 1, daha fazla tercihen l N'lik ardisik bir sekanstir, buradaki her N birbiriiiden bagimsiz olarak A, U, T, G veya C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; ve burada C, sitidin veya bunun bir analogudur ve sapl'de bunun komplementer nükleotidi guanosinin sitidin ile degistirilmesi kosuluyla istege bagli olarak bir guanosin veya bunun bir analogu ile degistirilebilir; sapl ve sap2, birbirleri ile baz eslesmesi yaparak bir geri komplementer sekans olusturabilir, burada baz eslesmesi, sapl ve sap2 arasinda meydana gelebilir, veya bir kismen geri komplementer sekans olusturabilir, burada sapl ve sap2zwamndaekmklnrbazegemnemineydmuigdebün;ve burada en az bir histon sap-ilmigi, sap-ilmik baglanma proteinine (SLBP) baglanir; ve burada her nükleik asit A, B, C, D veya E ayrica en az 10 sitidin nükleotit içeren bir poli(C) sekansi içerir veya bunun için kodlama MAGELZ, mammaglobin A, MART-l/melan-A, MART-2, MART-
2/m, matris proteini 22, MClR, M-CSF, MEl/m, mezotelin, MG50/PXDN, MMPl 1, MN/CA IX anti jeni, MRP-3, MUC-l, MUC- 2, MUM-l/m, MUM-Z/m, MUM-3/m, iniyosin sinifi I/m, NA88-A, N-asetilglukozaminiltransferaz-V, Neo-PAP, Neo-PAP/m, NFYC/m, NGEP, NMP22, NPM/ALK, N-Ras/m, NSE, OAl, OFA-iLRP, OGT, OGT/in, OS-9, OS-9/m, osteokalsin, oste0p0ntin, p15, p190 minör bcr-abl, p53, p53/1n, PAGE-4, PAI-l, PAI-Z, PAP, PART-l, PATE, PDEF, Pim-l-Kinaz, Pin-l, Pml/PARalpha, POTE, PRAME, PRDXS/m, prostein, proteinaz-3, PSA, PSCA, PSGR, PSM, PSMA, PTPRK/m, RAGE-l, RBAFÖOO/m, RHAMM/CD168, RUI, RUZ, S- 100, SAGE, SART-l, SART-Z, SART-3, SCC, SIRTZ/m, Spl7, SSX- l, SSX-Z/HOM-MEL-40, SSX-4, STAMP-l, STEAP-l, surviVin-ZB, SYT-SSX-l, SYT-SSX-Z, TA-90, TAG-72, TARP, TEL-AMLI, TGFbeta, TGFbetaRII, TGM-4, TPI/in, TRAG-3, TRG, TRP-l, TRP- 2/6b, TRP/INTZ, TRP-p8, tirosinaz, UPA, VEGFRI, VEGFR-Z/FLK- 1, WT] ve bir lenfoid kan hücresinin immünoglobulin idiyotipi veya bir lenfoid kan hücresinin bir T hücresi reseptörü idiyotipi, veya adi geçern tümör anti jeninin bir fragmani, burada fragman, en az alti amino asit artiklik bir uzunluga sahiptir. proteinini sifrelemez, burada raportör protein, marker veya seçim proteini, NY-ESO-l, 5T4, surViVin, MAGE-Cl, MAGE-C2 veya istem 2 veya 3'e göre tanimlanan bir tümör anti jeni degildir. 50 ila yaklasik 250 adenosin nükleotitlik bir sekans, en fazla tercihen yaklasik 60 ila yaklasik 250 adenosin nükleotitlik bir sekans içerir. C) bir kodlama bölgesi içeren veya bunun için kodlama yapan bir nükleik asit, burada kodlama bölgesi, surViVin tümör anti jenini veya bunun bir fragmanini içeren en az bir peptidi veya proteini sifreler; D) bir kodlama bölgesi içeren veya bunun için kodlama yapan bir nükleik asit, burada kodlama bölgesi, MAGE-Cl tümör antijenini veya bunun bir fragmanini içeren en az bir peptidi veya proteini sifreler; ve E) bir kodlama bölgesi içeren veya bunun için kodlama yapan bir nükleik asit, burada kodlama bölgesi, MAGE-C2 tümör antijenini veya bunun bir fragmanini içeren en az bir peptidi veya proteini sifreler, burada NY-ESO-l, 5T4, survivin, MAGE-Cl veya MAGE-C2 fragmani, en az alti amino asit artigi uzunluguiidadir; burada her nükleik asit A, B, C, D veya E - 5' 'ten 3' 'e dogrultuda - asagidakileri içerir veya bunlar için kodlama yapar a) kodlama bölgesi, b) en az bir histon sap-ilmigi ve e) bir poli(A) sekansi; a) kodlama bölgesi, b) bir poli(A) sekansi, ve c) en az bir histon sap-ilmigi; burada i) veya ii)'deki en az bir histon sap-ilmigi, asagidaki formül (1) veya (II) arasindan seçilir: formül (I) (sap sinirlama elemanlari olmayan sap-ilmik sekansi): sap] ilmik sap2 formül (II) (sap sinirlama elemanlari ile sap-ilmik sekansi): NislNMGNi-sjl LNtliiiLJ/rlNÜji [Ni-sCNu.2I Ni-e sap] sap] ilinik sap2 sap2 sap] veya sap2 sinirlama elemanlari Nm,, ] ila 6, tercihen 2 ila 6, daha fazla tercihen 2 ila 5, hatta daha fazla tercihen 3 ila 5, en fazla tercihen 4 ila 5 veya 5 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; sap] [N0_2GN3_5], sap2 elemani ile geri komplementer veya kismen geri komplementerdir ve 5 ila 7 nükleotitlik ardisik bir sekanstir; burada Nm, 0 ila 2, tercihen 0 ila 1, daha fazla tercihen 1 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; burada N3_5, 3 ila 5, tercihen 4 ila 5, daha fazla tercihen 4 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir ve burada G, guanosin veya bunun bir analogudur ve sap2'de bunun komplementer nükleotidi sitidinin guanosin ile degistirilmesi kosuluyla istege bagli olarak bir sitidin veya bunun bir analogu ile degistirilebilir; ilmik sekansi [N0_4(U/T)N0_4], sapl ve sap2 elemanlari arasinda bulunur ve 3 ila 5 nükleotitlik, daha fazla tercihen 4 nükleotitlik ardisik bir sekanstir; buradaki her N04 birbirinden bagimsiz olarak 0 ila 4, tercihen 1 ila 3, daha fazla tercihen 1 ila 2 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; ve burada U/T, üridini ya da istege bagli olarak timidini temsil eder; sap2 [N3_5CN0_2], sap] elemani ile geri komplementer veya kisinen geri komplementerdir ve 5 ila 7 nükleotitlik ardisik bir sekanstir; burada N3_5, 3 ila 5, tercihen 4 ila 5, daha fazla tercihen 4 N'lik ardisik bir sekanstir, buradaki her N birbiriiiden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; burada Nm, 0 ila 2, tercihen 0 ila 1, daha fazla tercihen l N'lik ardisik bir sekanstir, buradaki her N birbirinden bagiinsiz olarak A, U, T, G veya C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; ve burada C, sitidin veya bunun bir analogudur ve sapl'de bunun komplementer nükleotidi guanosinin sitidin ile degistirilmesi kosuluyla istege bagli olarak bir guanosin veya bunun bir analogu ile degistirilebilir; sapl ve sap2, birbirleri ile baz eslesmesi yaparak bir geri komplementer sekans olusturabilir, burada baz eslesmesi, sapl ve sap2 arasinda meydana gelebilir, veya bir kismen geri komplementer sekans olusturabilir, burada sap] ve sap2 arasinda eksik bir haz eslesmesi meydana gelebilir; ve burada en az bir histon sap-ilmigi, sap-ilmik baglanma proteinine (SLBP) baglanir. burada her nükleik asit A, B, C, D veya E - 5' 'ten 3' 'e dogrultuda - asagidakileri içerir veya bunlar için kodlama yapar a) kodlama bölgesi, b) en az bir histon sap-ilinigi ve o) bir poli(A) sekaiisi; a) kodlama bölgesi, b) bir poli(A) sekansi, ve c) en az bir histon sap-ilmigi; burada i) veya ii)'deki en az bir histon sap-ilmigi, asagidaki formül (1) veya (II) arasindan seçilir: formu] (I) (sap sinirlama elemanlari olniayan sap-ilniik sekansi): sap] ilmik sap2 formül (II) (sap sinirlama elemanlari ile sap-ilmik sekansi): Ni-6 [NO ZGN]-îl [NOHÄU/TINQU [N3.5CNQ.2] Nu. sap] sap] ilmik sap2 sap2 sapl veya sap2 sinirlama elemanlari N1_6, 1 ila 6, tercihen 2 ila 6, daha fazla tercihen 2 ila 5, hatta daha fazla tercihen 3 ila 5, en fazla tercihen 4 ila 5 veya 5 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; sapl [N0_2GN3_5], sap2 eleinani ile geri komplementer veya kismen geri komplementerdir ve 5 ila 7 nükleotitlik ardisik bir sekanstir, burada N04, 0 ila 2, tercihen 0 ila 1, daha fazla tercihen 1 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; burada N3_5, 3 ila 5, tercihen 4 ila 5, daha fazla tercihen 4 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir ve burada G, guanosin veya bunun bir analogudur ve sap2'de bunun komplementer nükleotidi sitidinin guanosin ile degistirilmesi kosuluyla istege bagli olarak bir sitidin veya bunun bir analogu ile degistirilebilir; ilmik sekansi [N0_4(U/T)N0_4], sapl ve sap2 elemanlari arasinda bulunur ve 3 ila 5 nükleotitlik, daha fazla tercihen 4 nükleotitlik ardisik bir sekanstir; buradaki her N0_4 birbirinden bagimsiz olarak 0 ila 4, tercihen 1 ila 3, daha fazla tercihen 1 ila 2 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; ve burada U/T, üridini ya da istege bagli olarak tiinidini temsil eder; sap2 [N3_5CN0_2], sapl elemani ile geri komplementer veya kismen geri komplementerdir ve 5 ila 7 nükleotitlik ardisik bir sekanstir; burada N3_5, 3 ila 5, tercihen 4 ila 5, daha fazla tercihen 4 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G ve C arasindan seçilen bir nükleotit ya da bunun bir nükleotit aiialogu arasindan seçilir; burada N0_2, 0 ila 2, tercihen 0 ila 1, daha fazla tercihen 1 N'lik ardisik bir sekanstir, buradaki her N birbirinden bagimsiz olarak A, U, T, G veya C arasindan seçilen bir nükleotit ya da bunun bir nükleotit analogu arasindan seçilir; ve burada C, sitidin veya bunun bir analogudur ve sapl'de bunun komplementer nükleotidi guanosinin sitidin ile degistirilmesi kosuluyla istege bagli olarak bir guanosin veya bunun bir analogu ile degistirilebilir; sapl ve sap2, birbirleri ile baz eslesinesi yaparak bir geri komplementer sekans olusturabilir, burada baz eslesmesi, sapl ve sap2 arasinda ineydana gelebilir, veya bir kismen geri komplementer sekans olusturabilir, burada sap] ve sap2 arasinda eksik bir baz eslesmesi meydana gelebilir; ve burada en az bir histon sap-ilmigi, sap-ilmik baglanma proteinine (SLBP) baglanir. ilgilidir. Kardiyovasküler hastaliklardan ve enfeksiyöz hastaliklardan ayri olarak tümörlerin ve kaiiser hastaliklarinin meydana gelmesi, modern toplumda en sik ölüm nedenlerinden biridir ve birçok durumda terapi ve takip eden rehabilitasyon önlemleri baglaminda önemli maliyetler ile baglantilidir. Tümörlerin ve kanser hastaliklarinin tedavisi büyük ölçüde örnegin meydana gelen tümörün tipine, tedavi edilecek hastanin yasina, kanser hücrelerinin hastadaki dagilimina, vb. baglidir. Günümüzde kanser terapisi geleneksel sekilde invazif operasyonlara ek olarak radyasyon terapisi veya kemoterapi kullanilarak gerçeklestirilir. Bununla birlikte bu geleneksel terapiler tipik olarak immün sisteme olagan disi stres getirir ve bazi durumlarda ancak sinirli dereceye kadar kullanilabilir. Ek olarak bu geleneksel terapilerin büyük kisini, immün sistemin yenilenmesine izin verinek için tedaviler arasinda uzun araliklar gerektirir.
TR2019/08291T 2012-02-15 2013-02-15 Şifrelenmiş bir tümör antijeninin ekspresyonunun arttırılmasına yönelik bir histon sap-ilmiği ve bir poli(a) sekansı veya bir poliadenilasyon sinyali içeren veya bunun için kodlama yapan nükleik asit. TR201908291T4 (tr)

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