ES2550781T3 - Mimotopos de alfa-sinucleína y vacunas de los mismos para el tratamiento de los trastornos neurodegenerativos - Google Patents

Mimotopos de alfa-sinucleína y vacunas de los mismos para el tratamiento de los trastornos neurodegenerativos Download PDF

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ES2550781T3
ES2550781T3 ES09712380.6T ES09712380T ES2550781T3 ES 2550781 T3 ES2550781 T3 ES 2550781T3 ES 09712380 T ES09712380 T ES 09712380T ES 2550781 T3 ES2550781 T3 ES 2550781T3
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synuclein
alpha
treatment
mimotopes
vaccines
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Markus Mandler
Harald Weninger
Radmila Santic
Edith Kopinits
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Affiris AG
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Abstract

Por lo menos un compuesto que comprende un péptido que presenta la secuencia de aminoácidos seleccionada de entre el grupo que consiste en CDQPVLPD, CDMPVLPD, CDSPVLPD, CDQPVLPDN, CDMPVLPDN, CDSPVLPDN, CHDRPVTPD, CDRPVTPD, CDVPVLPD, CDTPVYPD, CDTPVIPD, CHDRPVTPDN, CDRPVTPDN, CDVPVLPDN, CDTPVYPDN, CDQPVLPDG, CDMPVLPDG, CDSPVLPDG, CDHPVHPDS, CDMPVSPDR, CDRPVYPDI, CDHPVTPDR, CDTPVLPDS, CDMPVTPDT, CDAPVTPDT, CDSPVVPDN, CDLPVTPDR, CDSPVHPDT, CDAPVRPDS, CDMPVWPDG, CDRPVQPDR, CYDRPVQPDR, CDMPVDADN, DQPVLPDC y DMPVLPDC, para la utilización para la prevención y/o el tratamiento de las sinucleinopatías.

Description

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E09712380
21-10-2015
determinaron con cada suero. Los títulos contra proteína alfa-sinucleína humana recombinante y beta-sinucleína humana recombinante se determinaron a partir del suero 3, respectivamente. Los sueros agrupados se sometieron a ensayo frente al epítopo de la alfa-sinucleína humana original (aa115-122). En general, se analizaron los sueros mediante la reacción contra péptidos acoplados a albúmina de suero bovino (ASB) y proteínas de longitud completa 5 recombinantes que se habían inmovilizado-sobre placas de ELISA. Se determinaron los títulos utilizando anticuerpos específicos anti-IgG de ratón. Ver los resultados detallados en las figuras 4 y 5.
2. Ensayos in situ de mimotopos
10 Los sueros seleccionados que inducían una reactividad cruzada contra a-sin también se sometieron a ensayo para la capacidad de detectar a-sin humano en secciones de cerebro de ratón in situ. Ver los resultados detallados en la figura 6.
3. Resultados 15
3.1. Identificación de un anticuerpo monoclonal (mAb) específico para alfa-sinucleína
La figura 1 ilustra la caracterización del anticuerpo monoclonal específico para alfa-sinucleína AFFiRiS3/9 (nombre interno: "A509", IgG1), derivado de la fusión AFFiRiS 3. 20
3.2. Cribado con mAb específico para alfa-sinucleína 3.2.1. Bibliotecas de expresión fágica Ph.D. 7 y 12
25 3.2.1.1. Cribado con anticuerpo monoclonal dirigido contra DMPVDPDN
Se identificaron 51 secuencias mediante el cribado de las bibliotecas de expresión fágica PhD7 y PhD12 en el presente cribado: la Tabla 1 resume los péptidos identificados y su capacidad de unión en comparación con la del epítopo original. 30 Tabla 1: unión de mimotopos de alfa-sinucleína al anticuerpo parental
Número interno de péptido
SEC ID nº Secuencia Capacidad de unión
p4456
2 CDQPVLPD 3
p4457
3 CDMPVLPD 3
p4458
4 CDSPVLPD 3
p4460
5 CDSPVWAE 1
p4461
6 CDTPVLAE 1
p4462
7 CDQPVLPDN 3
p4463
8 CDMPVLPDN 3
p4464
9 CDSPVLPDN 3
p4465
10 CDQPVTAEN 3
p4466
11 CDSPVWAEN 3
p4467
12 CDTPVLAEN 3
p4484
13 CHDRPVTPD 3
p4485
14 CDRPVTPD 3
p4486
15 CDNPVHPE 1
p4487
16 CDVPVLPD 3
p4488
17 CDTPVYPD 3
p4489
18 CDTPVIPD 3
p4490
19 CHDRPVTPDN 3
p4491
20 CDRPVTPDN 3
p4492
21 CDNPVHPEN 3
p4493
22 CDVPVLPDN 3
p4494
23 CDTPVYPDN 3
p4495
24 CDTPVIPDN 3
p4496
25 CDQPVLPDG 3
p4497
26 CDMPVLPDG 3
p4498
27 CDSPVLPDG 3
p4499
28 CDSPVWAEG 3
p4553
29 CDRPVAPEG 3
p4554
30 CDHPVHPDS 3
p4555
31 CDMPVSPDR 3
10
imagen9
imagen10

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  1. imagen1
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