PFEIFER, Andrea,MUHS, Andreas,PIHLGREN, Maria,ADOLFSSON, Oskar,VAN LEUVEN, Fred
申请号：
ES12769656
公开号：
ES2600915T3
申请日:
2012.10.05
申请国别(地区):
ES
年份:
2017
代理人:
摘要：
An antibody, or a functional fragment thereof, that specifically recognizes and binds a phosphoepitope in the mammalian Tau protein or a phosphoepitope in a fragment of the mammalian Tau protein, wherein said phosphoepitope has or is comprised in the sequence of amino acids VYKSPVVSGDTSPRHL (SEQ ID NO: 62) 5 (Tau aa 393-408 of SEQ ID NO: 67) comprising a phosphorylated Ser at position 396 (pS396) and at position 404 (pS404), wherein said antibody or antibody fragment has a soluble, oligomeric and insoluble phosphorylated Tau protein binding affinity with a dissociation constant in a range between 2 nM and 80 nM, and a rate of association constant in a range between 1.6 x 102 and 105 and can detect and / or modulate levels of soluble, oligomeric and insoluble phosphorylated Tau in vivo and wherein said antibody or fragment thereof comprises: a light chain variable region comprising a CDR1 with the amino acid sequence shown in SEQ ID NO: 106, a CDR2 with the amino acid sequence shown in SEQ ID NO: 107, and a CDR3 with the amino acid sequence shown in SEQ ID NO: 108 , and a heavy chain variable region comprising a CDR1 with the amino acid sequence shown in SEQ ID NO: 89, a CDR2 with the amino acid sequence shown in SEQ ID NO: 115, and a CDR3 with the amino acid sequence shown in SEQ ID NO: 91.Un anticuerpo, o un fragmento funcional del mismo, que reconoce y se une específicamente a un fosfoepítopo en la proteína Tau de mamífero o a un fosfoepítopo en un fragmento de la proteína Tau de mamífero, en donde dicho fosfoepítopo tiene o está comprendida en la secuencia de aminoácidos VYKSPVVSGDTSPRHL (SEQ ID NO: 62) 5 (Tau aa 393-408 de la SEQ ID NO: 67) que comprende un Ser fosforilado en la posición 396 (pS396) y en la posición 404 (pS404), en donde dicho anticuerpo o fragmento de anticuerpo tiene una afinidad de unión a la proteína Tau fosforilada soluble, oligomérica e insoluble con una constante de disociación en un intervalo de entre 2 nM y 80 nM, y una constante de vel
