PRODUCTS AND THEIR USE FOR THE DIAGNOSIS, PREVENTION AND/OR CARE OF HUMAN AND/OR ANIMAL PATHOLOGIES CHARACTERISED BY THE ANOMALOUS DEPOSITION OF B-AMYLOID AND/OR AMYLOID-LIKE SUBSTANCE IN HUMAN AND/OR ANIMAL ORGANS AND TISSUES, AND SCREENING METHOD FOR DETERMINING THE RISK OF SUCH PATHOLOGIES
1 Assignment
0 Petitions
Accused Products
Abstract
The patent refers to a screening method carried out on biological material isolated from human and/or animal organisms for determining the risk of human and/or animal pathologies expressing an anomalous deposition of β-amyloid and/or amyloid-like substance in human and/or animal organs and tissues, based on the investigation of the punctiform mutation Ala>Val in position 2 of the β-protein (corresponding to the Ala673Val mutation precursor of the β-protein containing 770 amino acids) in homozygosis or in heterozygosis. The patent provides for the possibility of: (1) creating unicellular or multicellular transgenic organisms expressing the Ala673Val mutation; (2) synthesising or producing peptides with such mutation and/or their derivatives and/or nucleic acids containing the same mutation; (3) using such products for studying the pathogenesis of the pathologies characterised by anomalous deposition of β-amyloid and/or amyloid substance and for the prevention, diagnosis and care of such diseases.
-
Citations
83 Claims
-
1-53. -53. (canceled)
-
54. A screening method for determining risk of pathologies characterised by anomalous deposition of β
- -amyloid and/or amyloid-like substance formed by any isoform of Aβ
, the method comprising screening for, in homozygous or heterozygous form, a Cytosine with a Thymidine at codon 673 of a sequence coding a human APP gene (D87675) (exons 16 and 17 of the APP gene are shown in SEQ ID NO
1), corresponding with nucleotide 2212 (c.2212C>
T transition) of an isoform of APP770 (SEQ ID NOS;
3,4) (NM—
000484.2), the mutation resulting in substitution of Alanine with Valine at the residue 673 of APP770 (SEQ ID NO
30), or at the analogous residue of other isoforms of APP (SEQ ID NOS;
32,34), which correspond to the position 2 of Aβ
(SEQ ID NOS;
36,
38). - View Dependent Claims (56, 57)
- -amyloid and/or amyloid-like substance formed by any isoform of Aβ
-
58. A construct comprising different isoforms of human APP or their fragments with Ala673Val mutation (SEQ ID NOS:
- 1, 3, 4, 7, 8, 11,
12) or other mutations at codon 673 of APP770 (SEQ ID NOS;
2, 5, 6, 9, 10, 13,
14) or their fragments (SEQ ID NOS;
15-20, 25-29), under control of any non-endogenous promoter. - View Dependent Claims (79, 80, 81)
- 1, 3, 4, 7, 8, 11,
-
59. A cell line transfected in a stable or transient manner with a construct comprising different isoforms of human APP or their fragments with Ala673Val mutation (SEQ ID NOS:
- 1, 3, 4, 7, 8, 11,
12) or other mutations at codon 673 of APP770 (SEQ ID NOS;
2, 5, 6, 9, 10, 13,
14) or their fragments (SEQ ID NOS;
15-20, 25-29), under control of any non-endogenous promoter.
- 1, 3, 4, 7, 8, 11,
- 60. A transgenic non-human mammal comprising, in heterozygous or homozygous form, a DNA sequence or its fragments which code for the different isoforms of human APP or their fragments containing an Ala673Val mutation or other mutations at codon 673 of APP770 or their fragments.
-
63. A transgenic non-human mammal rendered knock-out for endogenous APP, wherein the transgenic non-human mammal rendered knock-out carries a DNA sequence or its fragments which code for different isoforms of human APP or their fragments with Ala673Val (APP673v) mutation (SEQ ID NOS:
- 1, 4, 8, 12, 15-20) or other mutations at codon 673 of APP770 or their fragments (SEQ ID NOS;
2, 6, 10, 14, 15-20), in homozygous form (genotype APP673v/APP673v) or hemizygous form (genotype APP0/APP673v) or heterozygous form (genotype APP673A/APP673v). - View Dependent Claims (64, 65, 67, 83)
- 1, 4, 8, 12, 15-20) or other mutations at codon 673 of APP770 or their fragments (SEQ ID NOS;
-
68. A messenger RNA (mRNA) or fragments thereof containing a nucleotide sequence corresponding to positive-sense mRNA (SEQ ID NOS:
- 3, 7, 11, 25, 27,
29) or complementary negative-sense mRNA to DNA coding for the human APP with Ala673Val mutation or other mutations at codon 673 of APP770 (SEQ ID NOS;
5, 9, 13, 26, 28,
29). - View Dependent Claims (70)
- 3, 7, 11, 25, 27,
-
69. An RNA interference (RNAi) composition comprising a nucleotide sequence corresponding to DNA coding for the human APP with Ala673Val mutation or other mutations at codon 673 of APP770 (SEQ ID NOS:
- 5, 9, 13, 26, 28,
29). - View Dependent Claims (71)
- 5, 9, 13, 26, 28,
-
72. A non-immunogenic fragment of the human APP, including all the isoforms of Aβ
- or partial sequences thereof (SEQ ID NOS;
36-47, 54-55) including those truncated at the N-terminal and/or truncated or extended at the C-terminal, wherein the fragement includes Ala673Val mutation or other mutations at codon 673 of APP770 (SEQ ID NOS;
36-55). - View Dependent Claims (73, 74, 75, 76, 77, 78)
- or partial sequences thereof (SEQ ID NOS;
Specification