Antibody binding a linear epitope of human p53 and diagnostic applications thereof
AssigneeDiadem S.r.l.
InventorsMaurizio Memo, Daniela Letizia Uberti
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Abstract
The invention relates to an anti-human p53 antibody suitable for specifically binding a linear epitope which is exposed only in a conformationally altered isoform of the characteristic p53 protein of patients with Alzheimer's disease or prone to develop Alzheimer's disease or cognitive impairment during ageing. Methods and diagnostic and prognostic kits are also described.
Claims19
A method of identifying in a subject the presence of Alzheimer's disease which is sporadic Alzheimer's disease (SAD) or familial Alzheimer's disease (FAD) comprising the steps of
- (i) contacting a biological sample of said subject with
- a) an antibody specific for an altered isoform of human p53 protein, said antibody comprising a heavy chain variable region comprising complementary determining region (CDR) 1 (SEQ ID NO:8), CDR2 (SEQ ID NO:
- 9) and CDR3 (SEQ ID NO:
- 10) and a light chain variable region comprising CDR1 (SEQ ID NO:11), CDR2 (SEQ ID NO:
- 12) and CDR3 (SEQ ID NO:
- 13) and
- b) an antibody specific for a wild type conformation of human p53 protein,
- wherein said contacting is performed under conditions which permit formation of an immunocomplex between said antibody and said human p53 protein isoform;
- (ii) quantifying the amount of immunocomplex formed between said altered isoform of human p53 protein and said antibody specific for said altered isoform;
- (iii) quantifying the amount of immunocomplex formed between a wild type isoform of human p53 protein and an antibody specific for said wild type human p53 protein isoform
- (iv) determining a ratio of said amount of quantified immunocomplex of (ii) and said amount of quantified immunocomplex of (iii) in said sample,
- wherein a ratio greater than 1 indicates the presence of sporadic (SAD) or familial (FAD) Alzheimer's disease in said subject.
A method of identifying Alzheimer's Disease (AD) in a subject, comprising
- (i) contacting a biological sample of said subject with an antibody specific for an altered isoform of human p53 protein, said antibody comprising a heavy chain variable region comprising complementary determining region (CDR) 1 (SEQ ID NO:8), CDR2 (SEQ ID NO:
- 9) and CDR3 (SEQ ID NO:
- 10) and a light chain variable region comprising CDR1 (SEQ ID NO:11), CDR2 (SEQ ID NO:
- 12) and CDR3 (SEQ ID NO:
- 13);
- (ii) quantifying the amount of an immunocomplex formed between said altered isoform of human p53 protein and said antibody,
- wherein the presence of a higher amount of said immunocomplex when compared with the amount of said immunocomplex found in a dementia-free control patient identifies Alzheimer's disease in said subject.
A method of detecting an isoform of human p53 protein in a biological sample of a human subject, said isoform being conformationally altered with respect to the wild-type human p53 protein, the method comprising the steps of:
- a. contacting the sample with an anti-human p53 antibody comprising a heavy chain variable region comprising CDR1 (SEQ ID NO:8), CDR2 (SEQ ID NO:
- 9) and CDR3 (SEQ ID NO:
- 10) and a light chain variable region comprising CDR1 (SEQ ID NO:11), CDR2 (SEQ ID NO:
- 12) and CDR3 (SEQ ID NO:
- 13), and
- b. detecting formation of an immunocomplex between human p53 protein and said antibody in said sample, wherein said formation of said immunocomplex indicates the presence of said isoform in said sample.
Dependencies are inferred from the claim text.