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EP0304013A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

A novel senile amyloid precursor protein and an antibody specific for the same

Assignee: Asahi Kasei Corp
•
Filing: 1988-08-16
•
Granted: —
•
Expires: 2008-08-16
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Abstract

Abstract A protein comprising a specific amino acid sequence including at least 55 amino acids and having a protease inhibiting activity is disclosed. Further, an antibody specific for the protein, a DNA coding for the protein, a complementary DNA to the DNA and RNA's corresponding to these DNA's, and human chromosomal DNA fragment coding for the protein are also disclosed. The protein, antibody, DNA RNA and human chromosomal DNA fragment of the present invention are useful for diagnosis of dysbolism in the central nervous system, including senile dementia Alzheimer's type.

Inventors

  • 👤 Nobuya Kitaguchi
  • 👤 Yasuyuki Takahashi
  • 👤 Yasuo Tokushima
  • 👤 Hirataka Itoh

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-11-09 16:19
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/68; G01N33/6893; G01N33/6896; C; C07; C07K; C07K14/00; C07K14/435; C07K14/46; C07K14/47; C07K14/4701; C07K14/4711; C07K14/81; C07K14/8107; C07K14/811; C07K14/8114; C07K16/00; C07K16/38; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6876; C12Q1/6883; C12Q2600/00; C12Q2600/158

Claims Analysis

Total Claims: 202
Claim 1
Independent Claim 15 words
A protein comprising an amino acid sequence repre­sented by the following formula (I): Val-Cys-Ser-Glu-Gln-Ala-Glu-Thr-Gly-Pro-Cys-­Arg-Ala-Met-Ile-Ser-Arg-Trp-Tyr-Phe-Asp-Val-­Thr-Glu-Gly-Lys-Cys-Ala-Pro-Phe-Phe-Tyr-Gly-­Gly-Cys-Gly-Gly-Asn-Arg-Asn-Asn-Phe-Asp-Thr-­Glu-Glu-Tyr-Cys-Met-Ala-Val-Cys-Gly-Ser-Ala      (I).
Claim 2
Dependent Claim 15 words
A protein comprising an amino acid sequence repre­sented by the following formula (I): Val-Cys-Ser-Glu-Gln-Ala-Glu-Thr-Gly-Pro-Cys-­Arg-Ala-Met-Ile-Ser-Arg-Trp-Tyr-Phe-Asp-Val-­Thr-Glu-Gly-Lys-Cys-Ala-Pro-Phe-Phe-Tyr-Gly-­Gly-Cys-Gly-Gly-Asn-Arg-Asn-Asn-Phe-Asp-Thr-­Glu-Glu-Tyr-Cys-Met-Ala-Val-Cys-Gly-Ser-Ala      (I).
Claim 3
Dependent Claim 34 words
A protein comprising an amino acid sequence represented by the following formula (II): Glu-(I)-Ile      (II) wherein (I) is a peptide having the same amino acid sequence as defined by formula (I) in claim 1.
Claim 4
Dependent Claim 87 words
A protein comprising an amino acid sequence represented by the following formula (III): X₁-(I)-X₂      (III) wherein (I) is a peptide having the same amino acid sequence as defined by formula (I) in claim 1, X₁ is a peptide having an amino acid sequence corresponding to the amino acid sequence of the 1st to 289th amino acids shown in Fig. 1(B), and X₂ is a peptide having an amino acid sequence corresponding to the amino acid sequence of the 345th to 751st amino acids shown in Fig. 1(B).
Claim 5
Dependent Claim 34 words
A protein comprising an amino acid sequence represented by the following formula (IV): Glu-(I)-Met-Ser-Gln-Ser-Leu-Leu-Lys-Thr-Thr-­Gln-Glu-Pro-Leu-Ala-Arg-Asp-Pro-Val-Lys-Leu      (IV) wherein (I) is a peptide having the same amino acid sequence as defined by formula (I) in claim 1.
Claim 6
Dependent Claim 87 words
A protein comprising an amino acid sequence represented by the following formula (V): X₃-(I)-X₄      (V) wherein (I) is a peptide having the same amino acid sequence as defined by formula (I) in claim 1, X₃ is a peptide having an amino acid sequence corresponding to the amino acid sequence of the 1st to 289th amino acids shown in Fig. 1(A), and X₄ is a peptide having an amino acid sequence corresponding to the amino acid sequence of the 345th to 770th amino acids shown in Fig. 1(A).
Claim 7
Dependent Claim 21 words
The protein according to any one of claims 1 to 5, which is a human brain senile plaque amyloid precursor protein.
Claim 8
Dependent Claim 17 words
The protein according to any one of claims 1 to 5, which has a protease inhibiting activity.
Claim 9
Dependent Claim 30 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence coding for a protein of claim 1 and a base sequence complementary thereto.
Claim 10
Dependent Claim 30 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence coding for a protein of claim 2 and a base sequence complementary thereto.
Claim 11
Dependent Claim 30 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence coding for a protein of claim 3 and a base sequence complementary thereto.
Claim 12
Dependent Claim 30 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence coding for a protein of claim 4 and a base sequence complementary thereto.
Claim 13
Dependent Claim 30 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence coding for a protein of claim 5 and a base sequence complementary thereto.
Claim 14
Dependent Claim 11 words
An RNA which corresponds to a DNA according to claim 8.
Claim 15
Dependent Claim 11 words
An RNA which corresponds to a DNA according to claim 9.
Claim 16
Dependent Claim 11 words
An RNA which corresponds to a DNA according to claim 10.
Claim 17
Dependent Claim 11 words
An RNA which corresponds to a DNA according to claim 11.
Claim 18
Dependent Claim 11 words
An RNA which corresponds to a DNA according to claim 12.
Claim 19
Dependent Claim 29 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula (VI): and a base sequence complementary thereto.
Claim 20
Dependent Claim 29 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula (VI): and a base sequence complementary thereto.
Claim 21
Dependent Claim 47 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence represented by formula (VII): G-(VI)-TT      (VII) wherein (VI) is a DNA having the same base sequence as defined by formula (VI) in claim 18, and a base sequence complementary thereto.
Claim 22
Dependent Claim 95 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula (VIII): Y₁-(VI)-Y₂      (VIII) wherein (VI) is a DNA having the same base sequence as defined by formula (VI) in claim 18, Y₁ is a DNA having a base sequence corres­ponding to the sequence of the 1st to 865th bases shown in Fig. 1(B), and Y₂ is a DNA having a base sequence corresponding to the base sequence of the 1034th to 2253rd bases shown in Fig. 1(B), and a base sequence complementary thereto.
Claim 23
Dependent Claim 72 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula (IX): (VI)-Y₃      (IX) wherein (VI) is a DNA having the same base sequence as defined by formula (VI) in claim 18, and Y₃ is a DNA having a base sequence represented by the following formula (X): TG TCCCAAAGTT TACTCAAGAC TACCCAGGAA CCTCTTGCCC GAGATCCTGT TAAAC      (X), and a base sequence complementary thereto.
Claim 24
Dependent Claim 63 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula (XI): G-(VI)-Y₃-TT      (XI) wherein (VI) is a DNA having the same base sequence as defined by formula (VI) in claim 18, and Y₃ has the same meaning as defined by formula (X) in claim 21, and a base sequence complementary thereto.
Claim 25
Dependent Claim 96 words
A DNA comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula (XII): Y₄-(VI)-Y₅      (XII): wherein (VI) is a DNA having the same base sequence as defined by formula (VI) in claim 18, Y₄ is a DNA having a base sequence corres­ponding to the base sequence of the 1st to 865th bases shown in Fig. 1(A), and Y₅ is a DNA having a base sequence corresponding to the base sequence of the 1034th to 2310th bases shown in Fig. 1(A), and a base sequence complementary thereto.
Claim 26
Dependent Claim 18 words
A human chromosomal DNA fragment comprising as an exon a base sequence represented by the following formula (VI):
Claim 27
Dependent Claim 18 words
A human chromosomal DNA fragment comprising as an exon a base sequence represented by the following formula (VI):
Claim 28
Dependent Claim 73 words
The human chromosomal DNA fragment according to claim 24, which further comprises at least a portion of a base sequence corresponding to the base sequence of the 1st to 85th bases shown in Fig. 5 and at least a portion of a base sequence corresponding to the base sequence of the 254th to 457th bases shown in Fig. 5, attached to said base sequence of formula (VI) at its 5′-end and 3′-end, respectively.
Claim 29
Dependent Claim 50 words
The human chromosomal DNA fragment according to claim 25, which further comprises a base sequence as shown in Fig. 6, and which has a molecular length of about 6.6 kb and a restriction endonuclease cleavage map as shown in (B) of Fig. 2 as a BamHI-BamHI insert in plasmid pAP246B.
Claim 30
Dependent Claim 45 words
The human chromosomal DNA fragment according to claim 25, which further comprises base sequences as shown in Figs. 6 and 7, respectively and which has a molecular length of about 37 kb and a restriction endonuclease cleavage map as shown in (A) of Fig. 2.
Claim 31
Dependent Claim 37 words
The human chromosomal DNA fragment according to any one of claims 24 to 27, which relates to expression of a portion of a human brain senile plaque amyloid precursor protein, said portion having a protease inhibiting activity.
Claim 32
Dependent Claim 26 words
A human chromosomal DNA fragment comprising as an exon a base sequence represented by the following formula (X): TG TCCCAAAGTT TACTCAAGAC TACCCAGGAA CCTCTTGCCC GAGATCCTGT TAAAC      (X).
Claim 33
Dependent Claim 26 words
A human chromosomal DNA fragment comprising as an exon a base sequence represented by the following formula (X): TG TCCCAAAGTT TACTCAAGAC TACCCAGGAA CCTCTTGCCC GAGATCCTGT TAAAC      (X).
Claim 34
Dependent Claim 73 words
The human chromosomal DNA fragment according to claim 29, which further comprises at least a portion of a base sequence corresponding to the base sequence of the 1st to 195th bases shown in Fig. 6 and at least a portion of a base sequence corresponding to the base sequence of the 253rd to 395th bases shown in Fig. 6, attached to said base sequence of formula (X) at its 5′-end and 3′-end, respec­tively.
Claim 35
Dependent Claim 37 words
The human chromosomal DNA fragment according to any one of claims 29 to 30, which relates to expression of a portion of a human brain senile plaque amyloid precursor protein, said portion having a protease inhibiting activity.
Claim 36
Dependent Claim 14 words
A human chromosomal DNA fragment comprising a base sequence as shown in Fig. 4.
Claim 37
Dependent Claim 14 words
A human chromosomal DNA fragment comprising a base sequence as shown in Fig. 4.
Claim 38
Dependent Claim 31 words
The human chromosomal DNA fragment according to claim 32, which has a molecular length of about 6.7 kb and a restriction endonuclease cleavage map as shown in (A) of Fig. 3.
Claim 39
Dependent Claim 37 words
The human chromosomal DNA fragment according to any one of claims 32 to 33, which relates to expression of a portion of a human brain senile plaque amyloid precursor protein, said portion having a protease inhibiting activity.
Claim 40
Dependent Claim 14 words
A human chromosomal DNA fragment comprising a base sequence as shown in Fig. 7.
Claim 41
Dependent Claim 14 words
A human chromosomal DNA fragment comprising a base sequence as shown in Fig. 7.
Claim 42
Dependent Claim 32 words
The human chromosomal DNA fragment according to claim 35, which relates to expression of a portion of a human brain senile plaque amyloid precursor protein, said portion having a protease inhibiting activity.
Claim 43
Dependent Claim 9 words
An RNA corresponding to a DNA of claim 18.
Claim 44
Dependent Claim 9 words
An RNA corresponding to a DNA of claim 19.
Claim 45
Dependent Claim 9 words
An RNA corresponding to a DNA of claim 20.
Claim 46
Dependent Claim 9 words
An RNA corresponding to a DNA of claim 21.
Claim 47
Dependent Claim 9 words
An RNA corresponding to a DNA of claim 22.
Claim 48
Dependent Claim 9 words
An RNA corresponding to a DNA of claim 23.
Claim 49
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 24.
Claim 50
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 25.
Claim 51
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 26.
Claim 52
Dependent Claim 13 words
An RNA corresponding to a human chromosomal DNA frag­ ment of claim 27.
Claim 53
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 28.
Claim 54
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 29.
Claim 55
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 30.
Claim 56
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 31.
Claim 57
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 32.
Claim 58
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 33.
Claim 59
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 34.
Claim 60
Dependent Claim 13 words
An RNA corresponding to a human chromosomal DNA frag­ ment of claim 35.
Claim 61
Dependent Claim 12 words
An RNA corresponding to a human chromosomal DNA frag­ment of claim 36.
Claim 62
Dependent Claim 34 words
A replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA coding for a protein comprising an amino acid sequence of formula (I) as defined in claim 1.
Claim 63
Dependent Claim 63 words
The replicable recombinant DNA according to claim 56, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA coding for said protein, constituting a reading frame so as to enable a fused peptide comprising said signal peptide and said protein to be produced by expression of said DNA's.
Claim 64
Dependent Claim 44 words
A transformant comprising a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA coding for a protein comprising an amino acid sequence of formula (I) as defined in claim 1.
Claim 65
Dependent Claim 34 words
A replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA coding for a protein comprising an amino acid sequence of formula (II) as defined in claim 2.
Claim 66
Dependent Claim 63 words
The replicable recombinant DNA according to claim 59, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA coding for said protein, constituting a reading frame so as to enable a fused peptide comprising said signal peptide and said protein to be produced by expression of said DNA's.
Claim 67
Dependent Claim 44 words
A transformant comprising a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA coding for a protein comprising an amino acid sequence of formula (II) as defined in claim 2.
Claim 68
Dependent Claim 34 words
A replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA coding for a protein comprising an amino acid sequence of formula (III) as defined in claim 3.
Claim 69
Dependent Claim 63 words
The replicable recombinant DNA according to claim 62, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA coding for said protein, constituting a reading frame so as to enable a fused peptide comprising said signal peptide and said protein to be produced by expression of said DNA's.
Claim 70
Dependent Claim 44 words
A transformant comprising a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA coding for a protein comprising an amino acid sequence of formula (III) as defined in claim 3.
Claim 71
Dependent Claim 34 words
A replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA coding for a protein comprising an amino acid sequence of formula (IV) as defined in claim 4.
Claim 72
Dependent Claim 63 words
The replicable recombinant DNA according to claim 65, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA coding for said protein, constituting a reading frame so as to enable a fused peptide comprising said signal peptide and said protein to be produced by expression of said DNA's.
Claim 73
Dependent Claim 44 words
A transformant comprising a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA coding for a protein comprising an amino acid sequence of formula (IV) as defined in claim 4.
Claim 74
Dependent Claim 34 words
A replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA coding for a protein comprising an amino acid sequence of formula (V) as defined in claim 5.
Claim 75
Dependent Claim 63 words
The replicable recombinant DNA according to claim 68, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA coding for said protein, constituting a reading frame so as to enable a fused peptide comprising said signal peptide and said protein to be produced by expression of said DNA's.
Claim 76
Dependent Claim 44 words
A transformant comprising a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA coding for a protein comprising an amino acid sequence of formula (V) as defined in claim 5.
Claim 77
Dependent Claim 28 words
A recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA compri­sing a base sequence of formula (VI) as defined in claim 18.
Claim 78
Dependent Claim 77 words
The replicable recombinant DNA according to claim 71, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA comprising a base sequence of formula (VI), constituting a reading frame so as to enable a fused peptide of said signal peptide and a peptide encoded by said DNA comprising the base sequence of formula (VI) to be produced by expression of said DNA's.
Claim 79
Dependent Claim 40 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA comprising a base sequence of formula (VI) as defined in claim 18.
Claim 80
Dependent Claim 28 words
A recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA compri­sing a base sequence of formula (VII) as defined in claim 19.
Claim 81
Dependent Claim 77 words
The replicable recombinant DNA according to claim 74, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA comprising a base sequence of formula (VII), constituting a reading frame so as to enable a fused peptide of said signal peptide and a peptide encoded by said DNA comprising the base sequence of formula (VII) to be produced by expression of said DNA's.
Claim 82
Dependent Claim 40 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA comprising a base sequence of formula (VII) as defined in claim 19.
Claim 83
Dependent Claim 28 words
A recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA compri­sing a base sequence of formula (VIII) as defined in claim 20.
Claim 84
Dependent Claim 77 words
The replicable recombinant DNA according to claim 77, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA comprising a base sequence of formula (VIII), constituting a reading frame so as to enable a fused peptide of said signal peptide and a peptide encoded by said DNA comprising the base sequence of formula (VIII) to be produced by expression of said DNA's.
Claim 85
Dependent Claim 40 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA comprising a base sequence of formula (VIII) as defined in claim 20.
Claim 86
Dependent Claim 28 words
A recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA compri­sing a base sequence of formula (IX) as defined in claim 21.
Claim 87
Dependent Claim 77 words
The replicable recombinant DNA according to claim 80, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA comprising a base sequence of formula (IX), constituting a reading frame so as to enable a fused peptide of said signal peptide and a peptide encoded by said DNA comprising the base sequence of formula (IX) to be produced by expression of said DNA's.
Claim 88
Dependent Claim 40 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA comprising a base sequence of formula (IX) as defined in claim 21.
Claim 89
Dependent Claim 28 words
A recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA compri­sing a base sequence of formula (XI) as defined in claim 22.
Claim 90
Dependent Claim 77 words
The replicable recombinant DNA according to claim 83, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA comprising a base sequence of formula (XI), constituting a reading frame so as to enable a fused peptide of said signal peptide and a peptide encoded by said DNA comprising the base sequence of formula (XI) to be produced by expression of said DNA's.
Claim 91
Dependent Claim 40 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA comprising a base sequence of formula (XI) as defined in claim 22.
Claim 92
Dependent Claim 28 words
A recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA compri­sing a base sequence of formula (XII) as defined in claim 23.
Claim 93
Dependent Claim 77 words
The replicable recombinant DNA according to claim 86, which further comprises a DNA coding for a signal peptide, said DNA coding for a signal peptide being ligated between said promoter and said DNA comprising a base sequence of formula (XII), constituting a reading frame so as to enable a fused peptide of said signal peptide and a peptide encoded by said DNA comprising the base sequence of formula (XII) to be produced by expression of said DNA's.
Claim 94
Dependent Claim 40 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA comprising a replicable expression vector and, ligated thereto, a promoter and a DNA comprising a base sequence of formula (XII) as defined in claim 23.
Claim 95
Dependent Claim 14 words
A replicable recombinant DNA comprising a replicable vector and a DNA of claim 18.
Claim 96
Dependent Claim 14 words
A replicable recombinant DNA comprising a replicable vector and a DNA of claim 19.
Claim 97
Dependent Claim 14 words
A replicable recombinant DNA comprising a replicable vector and a DNA of claim 20.
Claim 98
Dependent Claim 14 words
A replicable recombinant DNA comprising a replicable vector and a DNA of claim 21.
Claim 99
Dependent Claim 14 words
A replicable recombinant DNA comprising a replicable vector and a DNA of claim 22.
Claim 100
Dependent Claim 14 words
A replicable recombinant DNA comprising a replicable vector and a DNA of claim 23.
Claim 101
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 24.
Claim 102
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 25.
Claim 103
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 26.
Claim 104
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 27.
Claim 105
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 28.
Claim 106
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 29.
Claim 107
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 30.
Claim 108
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 31.
Claim 109
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 32.
Claim 110
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 33.
Claim 111
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 34.
Claim 112
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 35.
Claim 113
Dependent Claim 16 words
A replicable recombinant DNA comprising a replicable vector and a human chromosomal DNA of claim 36.
Claim 114
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 89.
Claim 115
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 90.
Claim 116
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 91.
Claim 117
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 92.
Claim 118
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 93.
Claim 119
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 94.
Claim 120
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 95.
Claim 121
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 96.
Claim 122
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 97.
Claim 123
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 98.
Claim 124
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 99.
Claim 125
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 100.
Claim 126
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 101.
Claim 127
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 102.
Claim 128
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 103.
Claim 129
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 104.
Claim 130
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 105.
Claim 131
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 106.
Claim 132
Dependent Claim 18 words
A transformant which comprises a microorganism or cell and, contained therein, a replicable recombinant DNA of claim 107.
Claim 133
Dependent Claim 5 words
Escherichia coli K-12 strain HB101(pGBP2).
Claim 134
Dependent Claim 5 words
Escherichia coli K-12 strain HB101(pGBP2).
Claim 135
Dependent Claim 5 words
Escherichia coli K-12 strain MC1061(pBB-3).
Claim 136
Dependent Claim 5 words
Escherichia coli K-12 strain MC1061(pBB-3).
Claim 137
Dependent Claim 5 words
Escherichia coli K-12 strain JM105(pAP246B).
Claim 138
Dependent Claim 5 words
Escherichia coli K-12 strain JM105(pAP246B).
Claim 139
Dependent Claim 5 words
Escherichia coli K-12 strain JM105(pGAP-K3).
Claim 140
Dependent Claim 5 words
Escherichia coli K-12 strain JM105(pGAP-K3).
Claim 141
Dependent Claim 21 words
An antibody specific for at least a portion of human brain senile plaque amyloid precursor protein having a protease inhibiting activity.
Claim 142
Dependent Claim 21 words
An antibody specific for at least a portion of human brain senile plaque amyloid precursor protein having a protease inhibiting activity.
Claim 143
Dependent Claim 22 words
The antibody according to claim 131, wherein said protein comprises an amino acid sequence of formula (I) as defined in claim 1.
Claim 144
Dependent Claim 22 words
The antibody according to claim 131, wherein said protein comprises an amino acid sequence of formula (II) as defined in claim 2.
Claim 145
Dependent Claim 22 words
The antibody according to claim 131, wherein said protein comprises an amino acid sequence of formula (III) as defined in claim 3.
Claim 146
Dependent Claim 22 words
The antibody according to claim 131, wherein said protein comprises an amino acid sequence of formula (IV) as defined in claim 4.
Claim 147
Dependent Claim 22 words
The antibody according to claim 131, wherein said protein comprises an amino acid sequence of formula (V) as defined in claim 5.
Claim 148
Dependent Claim 28 words
The antibody according to claim 131, wherein said portion comprises a sequence of at least five continuously sequenced amino acids in the amino acid sequence of said protein.
Claim 149
Dependent Claim 49 words
The antibody according to claim 137, wherein said portion comprises a sequence of at least five continuously sequenced amino acids in an amino acid sequence represented by the formula: Glu-Val-Val-Arg-(II)-Pro-Thr-Thr-Ala wherein (II) is a peptide having the same amino acid sequence as defined by formula (II) in claim 2.
Claim 150
Dependent Claim 49 words
The antibody according to claim 137, wherein said portion comprises a sequence of at least five continuously sequenced amino acids in an amino acid sequence represented by the formula: Glu-Val-Val-Arg-(IV)-Pro-Thr-Thr-Ala wherein (IV) is a peptide having the same amino acid sequence as defined by formula (IV) in claim 4.
Claim 151
Dependent Claim 15 words
The antibody according to any one of claims 131 to 139, which is an antiserum.
Claim 152
Dependent Claim 16 words
The antibody according to any one of claims 131 to 139, which is a polyclonal antibody.
Claim 153
Dependent Claim 16 words
The antibody according to any one of claims 131 to 139, which is a monoclonal antibody.
Claim 154
Dependent Claim 41 words
The antibody according to claim 142, which is a mono­clonal antibody produced by a cell line selected from the group consisting of a mouse hybrid cell line ADI1-7-5-2, a mouse hybrid cell line ADI1-4-6-1 and a mouse hybrid cell line ADI1-05-44-2.
Claim 155
Dependent Claim 30 words
A cell line which is capable of producing a monoclonal antibody specific for at least a portion of human brain senile plaque amyloid precursor protein having a protease inhibiting activity.
Claim 156
Dependent Claim 30 words
A cell line which is capable of producing a monoclonal antibody specific for at least a portion of human brain senile plaque amyloid precursor protein having a protease inhibiting activity.
Claim 157
Dependent Claim 15 words
The cell line according to claim 144, which is a mouse hybrid cell line ADI1-7-5-2.
Claim 158
Dependent Claim 15 words
The cell line according to claim 144, which is a mouse hybrid cell line ADI1-4-6-1.
Claim 159
Dependent Claim 15 words
The cell line according to claim 144, which is a mouse hybrid cell line ADI1-05-44-2.
Claim 160
Dependent Claim 34 words
A method for detecting at least a portion of human brain senile plaque amyloid precursor protein having a protease inhibiting activity, which comprises subjecting a sample to immunoassay using an antibody of claim 131.
Claim 161
Dependent Claim 22 words
The method according to claim 148, wherein said protein comprises an amino acid sequence of formula (I) as defined in claim 1.
Claim 162
Dependent Claim 22 words
The method according to claim 148, wherein said protein comprises an amino acid sequence of formula (II) as defined in claim 2.
Claim 163
Dependent Claim 22 words
The method according to claim 148, wherein said protein comprises an amino acid sequence of formula (III) as defined in claim 3.
Claim 164
Dependent Claim 22 words
The method according to claim 148, wherein said protein comprises an amino acid sequence of formula (IV) as defined in claim 4.
Claim 165
Dependent Claim 22 words
The method according to claim 148, wherein said protein comprises an amino acid sequence of formula (V) as defined in claim 5.
Claim 166
Dependent Claim 31 words
The method according to claim 148, wherein said immu­noassay is performed by a technique selected from the group consisting of a solid phase enzyme-linked immunosorbent assay, an immunoblotting and a radioimmunoassay.
Claim 167
Independent Claim 17 words
The method according to 148, wherein said sample is treated with a glycohydrolase before subjecting to immuno­assay.
Claim 168
Independent Claim 17 words
The method according to 148, wherein said sample is treated with a glycohydrolase before subjecting to immuno­assay.
Claim 169
Dependent Claim 59 words
A method for detecting a DNA of claim 18, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a DNA comprising at least a portion of a base sequence of formula (VI) as defined in claim 18, (ii) a complementary DNA to said DNA and (iii) RNA's corresponding thereto.
Claim 170
Dependent Claim 59 words
A method for detecting a DNA of claim 19, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a DNA comprising at least a portion of a base sequence of formula (VII) as defined in claim 19, (ii) a complementary DNA to said DNA and (iii) RNA's corresponding thereto.
Claim 171
Dependent Claim 59 words
A method for detecting a DNA of claim 20, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a DNA comprising at least a portion of a base sequence of formula (VIII) as defined in claim 20, (ii) a complementary DNA to said DNA and (iii) RNA's corresponding thereto.
Claim 172
Dependent Claim 59 words
A method for detecting a DNA of claim 21, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a DNA comprising at least a portion of a base sequence of formula (IX) as defined in claim 21, (ii) a complementary DNA to said DNA and (iii) RNA's corresponding thereto.
Claim 173
Dependent Claim 59 words
A method for detecting a DNA of claim 22, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a DNA comprising at least a portion of a base sequence of formula (XI) as defined in claim 22, (ii) a complementary DNA to said DNA and (iii) RNA's corresponding thereto.
Claim 174
Dependent Claim 59 words
A method for detecting a DNA of claim 23, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a DNA comprising at least a portion of a base sequence of formula (XII) as defined in claim 23, (ii) a complementary DNA to said DNA and (iii) RNA's corresponding thereto.
Claim 175
Dependent Claim 55 words
The method according to any one of claims 156 to 158, wherein said portion in DNA (i) is a sequence of at least twelve continuously sequenced bases in a base sequence of the formula: G GTGGTTCGAG-(VI)-TT CCTACAACA wherein (VI) is a DNA having the same base sequence as defined by formula (VI) in claim 18.
Claim 176
Dependent Claim 55 words
The method according to any one of claims 159 to 161, wherein said portion in DNA (i) is a sequence of at least twelve continuously sequenced bases in a base sequence of the formula: G GTGGTTCGAG-(IX)-TT CCTACAACA wherein (IX) is a DNA having the same base sequence as defined by formula (IX) in claim 21.
Claim 177
Independent Claim 32 words
The method according to any one of claims 156 to 161, wherein said hybridization is performed by a technique selected from the group consisting of a Southern blotting and a dot blotting.
Claim 178
Dependent Claim 61 words
A method for detecting an RNA corresponding to the DNA of claim 18, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a complementary DNA to a DNA comprising at least a portion of a base sequence of formula (VI) as defined in claim 18 and (ii) an RNA corresponding thereto.
Claim 179
Dependent Claim 61 words
A method for detecting an RNA corresponding to the DNA of claim 19, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a complementary DNA to a DNA comprising at least a portion of a base sequence of formula (VII) as defined in claim 19 and (ii) an RNA corresponding thereto.
Claim 180
Dependent Claim 61 words
A method for detecting an RNA corresponding to the DNA of claim 20, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a complementary DNA to a DNA comprising at least a portion of a base sequence of formula (VIII) as defined in claim 20 and (ii) an RNA corresponding thereto.
Claim 181
Dependent Claim 61 words
A method for detecting an RNA corresponding to the DNA of claim 21, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a complementary DNA to a DNA comprising at least a portion of a base sequence of formula (IX) as defined in claim 21 and (ii) an RNA corresponding thereto.
Claim 182
Dependent Claim 61 words
A method for detecting an RNA corresponding to the DNA of claim 22, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a complementary DNA to a DNA comprising at least a portion of a base sequence of formula (XI) as defined in claim 22 and (ii) an RNA corresponding thereto.
Claim 183
Dependent Claim 61 words
A method for detecting an RNA corresponding to the DNA of claim 23, which comprises subjecting a sample to assay by hybridization using a probe selected from the group consisting of (i) a complementary DNA to a DNA comprising at least a portion of a base sequence of formula (XII) as defined in claim 23 and (ii) an RNA corresponding thereto.
Claim 184
Dependent Claim 59 words
The method according to any one of claims 165 to 167, wherein said portion in DNA (i) is comprised of at least twelve continuously sequenced bases in a base sequence complementary to a base sequence of the formula: G GTGGTTCGAG-(VI)-TT CCTACAACA wherein (VI) is a DNA having the same base sequence as defined by formula (VI) in claim 18.
Claim 185
Dependent Claim 59 words
The method according to any one of claims 168 to 170, wherein said portion in DNA (i) is comprised of at least twelve continuously sequenced bases in a base sequence complementary to a base sequence of the formula: G GTGGTTCGAG-(IX)-TT CCTACAACA wherein (IX) is a DNA having the same base sequence as defined by formula (IX) in claim 21.
Claim 186
Independent Claim 31 words
The method according to any one of claims 165 to 170, wherein said hybridization is performed by a technique selected from the group consisting of a Northern blotting and dot blotting.
Claim 187
Dependent Claim 60 words
A method for detecting a human chromosomal DNA frag­ment relating to expression of a polypeptide having a protease inhibiting activity, said polypeptide being a portion of a human brain senile plaque amyloid precursor protein, which comprises subjecting a sample to assay by hybridization using as a probe at least a portion of a human chromosomal DNA fragment of claim 24.
Claim 188
Dependent Claim 27 words
The method according to claim 174, wherein said hy­bridization is performed by a technique selected from the group consisting of a Southern blotting and a dot blotting.
Claim 189
Dependent Claim 60 words
A method for detecting a human chromosomal DNA frag­ment relating to expression of a polypeptide having a protease inhibiting activity, said polypeptide being a portion of a human brain senile plaque amyloid precursor protein, which comprises subjecting a sample to assay by hybridization using as a probe at least a portion of a human chromosomal DNA fragment of claim 25.
Claim 190
Dependent Claim 27 words
The method according to claim 176, wherein said hy­bridization is performed by a technique selected from the group consisting of a Southern blotting and a dot blotting.
Claim 191
Dependent Claim 59 words
A method for detecting a human chromosomal DNA frag­ment relating to expression of a polypeptide having a protease inhibiting activity, said polypeptide being a portion of human brain senile plaque amyloid precursor protein, which comprising subjecting a sample to assay by hybridization using as a probe at least a portion of a human chromosomal DNA fragment of claim 26.
Claim 192
Dependent Claim 27 words
The method according to claim 178, wherein said hy­bridization is performed by a technique selected from the group consisting of a Southern blotting and a dot blotting.
Claim 193
Dependent Claim 60 words
A method for detecting a human chromosomal DNA frag­ment relating to expression of a polypeptide having a protease inhibiting activity, said polypeptide being a portion of a human brain senile plaque amyloid precursor protein, which comprising subjecting a sample to assay by hybridization using as a probe at least a portion of a human chromosomal DNA fragment of claim 27.
Claim 194
Dependent Claim 27 words
The method according to claim 180, wherein said hy­bridization is performed by a technique selected from the group consisting of a Southern blotting and a dot blotting.
Claim 195
Dependent Claim 60 words
A method for detecting a human chromosomal DNA frag­ment relating to expression of a polypeptide having a protease inhibiting a activity, polypeptide being a portion of a human brain senile plaque amyloid precursor protein, which comprising subjecting a sample to assay by hybridiza­tion using as a probe at least a portion of a human chromosomal DNA fragment of claim 29.
Claim 196
Dependent Claim 27 words
The method according to claim 182, wherein said hy­bridization is performed by a technique selected from the group consisting of a Southern blotting and a dot blotting.
Claim 197
Dependent Claim 60 words
A method for detecting a human chromosomal DNA frag­ment relating to expression of a polypeptide having a protease inhibiting activity, said polypeptide being a portion of a human brain senile plaque amyloid precursor protein, which comprises subjecting a sample to assay by hybridization using as a probe at least a portion of a human chromosomal DNA fragment of claim 30.
Claim 198
Dependent Claim 27 words
The method according to claim 184, wherein said hy­bridization is performed by a technique selected from the group consisting of a Southern blotting and a dot blotting.
Claim 199
Dependent Claim 60 words
A method for detecting a human chromosomal DNA frag­ment relating to expression of a polypeptide having a protease inhibiting activity, said polypeptide being a portion of a human brain senile plaque amyloid precursor protein, which comprises subjecting a sample to assay by hybridization using as a probe at least a portion of a human chromosomal DNA fragment of claim 32.
Claim 200
Dependent Claim 27 words
The method according to claim 186, wherein said hy­bridization is performed by a technique selected from the group consisting of a Southern blotting and a dot blotting.
Claim 201
Dependent Claim 60 words
A method for detecting a human chromosomal DNA frag­ment relating to expression of a polypeptide having a protease inhibiting activity, said polypeptide being a portion of a human brain senile plaque amyloid precursor protein, which comprises subjecting a sample to assay by hybridization using as a probe at least a portion of a human chromosomal DNA fragment of claim 35.
Claim 202
Dependent Claim 27 words
The method according to claim 188, wherein said hy­bridization is performed by a technique selected from the group consisting of a Southern blotting and a dot blotting.

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