Monoclonal antibodies specific for PHF-tau, hybridomas secreting them, antigen recognition by these antibodies and their applications

摘要

PCT No. PCT/EP94/04146 Sec. 371 Date Jun. 20, 1996 Sec. 102(e) Date Jun. 20, 1996 PCT Filed Dec. 14, 1994 PCT Pub. No. WO95/17429 PCT Pub. Date Jun. 29, 1995Monoclonal antibody AT180 secreted by the hybridoma deposited at ECACC on Dec. 22, 1992 under No. 92122204, and monoclonal antibody AT270 secreted by the hybridoma deposited at ECACC on Jul. 7, 1993 under 93070774, each of which forms an immunological complex with a phosphorylated epitope of an antigen belonging to abnormally phosphorylated tau protein (PHF-tau) residing in the region spanning positions 143-254 with the following amino acid sequence: - 143 150 - NH2 - Lys Gly Ala Asp Gly Lys Thr Lys Ile - - 160 - Ala Thr Pro Arg Gly Ala Ala Pro Pro Gly - - 170 - Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile - - 180 - Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr - - 190 - Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser - - 200 - Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly - - 210 - Ser Pro Gly Thr Pro Gly Ser Arg Ser Arg - - 220 - Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg - - 230 - Glu Pro Lys Lys Val Ala Val Val Arg Thr - - 240 - Pro Pro Lys Ser Pro Ser Ser Ala Lys Ser - - 250 - Arg Leu Gln Thr Ala Pro Val Pro Met Pro - - Asp Leu Lys COOH - with each monoclonal antibody specifically detecting abnormally phosphorylated tau protein (PHF-tau) in cerebrospinal fluid (CSF).