US5015570A
Expired / Lapsed
US
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Molecular diagnosis of Alzheimer Disease
Assignee: Molecular Therapeutics Inc
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Filing: 1988-05-13
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Granted: 1991-05-14
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Expires: 2008-05-13
Abstract
Abstract A method for diagnosing Alzheimer Disease or a predisposition to develop Alzheimer Disease in an individual, by determining the presence of an alteration in the normal base sequence of the 24 base pairs appearing at the end of the APC coding sequence of the preAPC gene, or in the normal base sequence of the corresponding mRNA, in the DNA or RNA or such individual. The method detects the presence of a frameshift mutation in the preAPC gene postulated to result in the synthesis of the APC protein. Accumulation of APC protein in the brain is a phenomenon of Alzheimer Disease. A variety of nucleic acid hybridization techniques are applicable to the determination of an alteration in the preAPC gene sequence of interest.
Inventors
- 👤 George A. Scangos
- 👤 Peter M. M. Rae
- 👤 Axel J. Unterbeck
- 👤 Michael E. Kamarck
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 22:30
CPC Classifications
C; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6876; C12Q1/6883; C12Q1/6813; C12Q1/6827; C12Q2600/00; C12Q2600/156; Y; Y10; Y10S; Y10S436/00; Y10S436/811
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
67 words
A method for diagnosing Alzheimer Disease or a predisposition to develop Alzheimer Disease in an individual, comprising the step of determining the presence of an alteration in the normal DNA base sequence ' CAC TGT CGC TAT GAC AAC ACC GCC 3', or its normal complementary DNA or RNA sequences, in a sample of the DNA or RNA of such individual by hybridization with an aligonucleotide probe.
Claim 2
Independent Claim
67 words
A method for diagnosing Alzheimer Disease or a predisposition to develop Alzheimer Disease in an individual, comprising the step of determining the presence of an alteration in the normal DNA base sequence ' CAC TGT CGC TAT GAC AAC ACC GCC 3', or its normal complementary DNA or RNA sequences, in a sample of the DNA or RNA of such individual by hybridization with an aligonucleotide probe.
Claim 3
Dependent Claim
43 words
The method of claim 1 wherein such individual is presymptomatic for Alzheimer Disease and the presence of an alteration in said normal DNA base sequence, or in its complementary DNA or RNA sequences, indicates a risk that such individual will develop the disease.
Claim 4
Dependent Claim
77 words
The method of claim 1 wherein the presence of an alteration in said normal sequences is determined by obtaining sample DNA or RNA from said individual in single stranded form, hybridizing the single stranded sample DNA or RNA with an oligonucleotide probe comprising the DNA base sequence 5' CAC TGT CGC TAT GAC AAC ACC GCC 3' or its corresponding RNA base sequence, or their complementary DNA or RNA sequences, and analyzing resulting hybrids for imperfect homology.
Claim 5
Dependent Claim
46 words
The method of claim 3 wherein said oligonucleotide probe consists of less than 50 nucleotides and includes the 24 nucleotide DNA base sequence 5' CAC TGT CGC TAT GAC AAC ACC GCC 3', or its corresponding RNA base sequence, or their complementary DNA or RNA sequences.
Claim 6
Dependent Claim
16 words
The method of claim 4 wherein said oligonucleotide probe consists essentially of less than 30 nucleotides.
Claim 7
Dependent Claim
18 words
The method of claim 4 wherein said oligonucleotide probe consists essentially of only said 24 nucleotide base sequence.
Claim 8
Dependent Claim
33 words
The method of claim 3 wherein imperfect homology in said resulting hybrids is determined by exposing the hybrids to a single stranded specific nuclease and detecting the presence or absence of hybrid fragments.
Claim 9
Dependent Claim
84 words
The method of claim 1 wherein the presence of an alteration in said normal sequences is determined by obtaining sample DNA or RNA from said individual in single stranded form, hybridizing the single stranded sample DNA or RNA with an oligonucleotide probe having a base sequence of at least 10 nucleotides homologous with the DNA sequence of the preAPC gene having a mutation in said normal DNA base sequence or in its complementary DNA or RNA sequence, and analyzing resulting hybrids for perfect homology.
Claim 10
Dependent Claim
38 words
The method of claim 8 wherein said oligonucleotide probe consists essentially of up to 24 nucleotides corresponding to the base sequence of said mutated form of the normal DNA base sequence or its complementary DNA or RNA sequences.
Claim 11
Dependent Claim
11 words
The method of claim 1 wherein the sample is genomic DNA.
Claim 12
Dependent Claim
10 words
The method of claim 1 wherein the sample is mRNA.
Claim 13
Dependent Claim
56 words
An oligonucleotide probe for use in the diagnosis of Alzheimer Disease or a predisposition to develop Alzheimer Disease, consisting essentially of less than 50 nucleotides and including the 24 nucleotide DNA base sequence 5' CAC TGT CGC TAT GAC AAC ACC GCC 3' or its corresponding RNA base sequence, or their complementary DNA or RNA sequences.
Claim 14
Dependent Claim
56 words
An oligonucleotide probe for use in the diagnosis of Alzheimer Disease or a predisposition to develop Alzheimer Disease, consisting essentially of less than 50 nucleotides and including the 24 nucleotide DNA base sequence 5' CAC TGT CGC TAT GAC AAC ACC GCC 3' or its corresponding RNA base sequence, or their complementary DNA or RNA sequences.
Claim 15
Dependent Claim
12 words
The probe of claim 12 consisting essentially of less than 30 nucleotides.
Claim 16
Dependent Claim
14 words
The probe of claim 12 consisting essentially of only said 24 nucleotide base sequence.
Claim 17
Dependent Claim
10 words
The probe of claim 12 which additionally comprises a label.
Claim 18
Dependent Claim
21 words
The probe of claim 15 wherein said label is a radioactive isotope, a fluorescer, a chemiluminescer, or a specifically bindable ligand.
Claim 19
Dependent Claim
64 words
An oligonucleotide probe for use in the diagnosis of Alzheimer Disease or a predisposition to develop Alzheimer Disease, consisting essentially of at least 10 nucleotides whose base sequence is homologous with the DNA sequence of the preAPC gene having a mutation in the 24 nucleotide sequence 5' CAC TGT CGC TAT GAC AAC ACC GCC 3', or in its complementary DNA or RNA sequence.
Claim 20
Dependent Claim
64 words
An oligonucleotide probe for use in the diagnosis of Alzheimer Disease or a predisposition to develop Alzheimer Disease, consisting essentially of at least 10 nucleotides whose base sequence is homologous with the DNA sequence of the preAPC gene having a mutation in the 24 nucleotide sequence 5' CAC TGT CGC TAT GAC AAC ACC GCC 3', or in its complementary DNA or RNA sequence.
Claim 21
Dependent Claim
29 words
The probe of claim 17 consisting essentially of up to 24 nucleotides corresponding to the base sequence of said mutated DNA sequence or its complementary DNA or RNA sequences.
Claim 22
Dependent Claim
10 words
The probe of claim 17 which additionally comprises a label.
Claim 23
Dependent Claim
21 words
The probe of claim 19 wherein said label is a radioactive isotope, a fluorescer, a chemiluminescer, or a specifically bindable ligand.
References Cited (Backward Citations)
US4666829A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1994-05-13 | 1994-11-12 | 1995-05-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-05-13 | 1998-11-12 | 1999-05-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-05-13 | 2002-11-12 | 2003-05-14 | $7700.00 | Window Closed / Lapsed |