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EP0155549A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

DNA encoding human tumor necrosis factor and human tumor necrosis factor polypeptide

Assignee: Sumitomo Pharma Co Ltd
•
Filing: 1985-02-26
•
Granted: —
•
Expires: 2005-02-26
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Abstract

Abstract A novel cloned DNA encoding a human tumor necrosis factor (TNF), a vector having said DNA inserted thereinto, a host transformed with said vector and a novel human TNF polypeptide, and processes for producing them.

Inventors

  • 👤 Masaaki Yamada
  • 👤 Yasuji Furutani
  • 👤 Mitsue Notake
  • 👤 Juniti Yamagishi

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-11-05 12:23
CPC Classifications
C; C12; C12N; C12N15/00; C07; C07K; C07K14/00; C07K14/435; C07K14/52; C07K14/525; C12N15/09; C12N15/63; C12N15/70; A; A61; A61K; A61K38/00; C07K2319/00; C07K2319/01; C07K2319/034; C07K2319/70; C07K2319/74; C07K2319/75

Claims Analysis

Total Claims: 92
Claim 1
Independent Claim 36 words
A DNA having or containing a base sequence corresponding to a human tumor necrosis factor polypeptide or its principal portion, or its allelic mutant polypeptide, or a base sequence resulting from modification of said base sequence.
Claim 2
Dependent Claim 36 words
A DNA having or containing a base sequence corresponding to a human tumor necrosis factor polypeptide or its principal portion, or its allelic mutant polypeptide, or a base sequence resulting from modification of said base sequence.
Claim 3
Dependent Claim 46 words
A DNA having a base sequence encoding a polypeptide containing the amino acid sequence of a human tumor necrosis factor or an active central portion thereof, or a mutant of said DNA resulting from mutation including allelic mutation or degeneration or partial modification of said DNA.
Claim 4
Dependent Claim 46 words
A DNA having a base sequence encoding a polypeptide containing the amino acid sequence of a human tumor necrosis factor or an active central portion thereof, or a mutant of said DNA resulting from mutation including allelic mutation or degeneration or partial modification of said DNA.
Claim 5
Dependent Claim 116 words
A DNA having or containing a base sequence corresponding to an amino acid sequence represented by the following formula [I] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A is a polypeptide of the formula [Ia] below in which one or more amino acids may be deleted or replaced by other amino acid(s), B is a peptide of the formula [Ib] below in which one to three amino acids may be deleted or replaced by other amino acid(s), X is a polypeptide, Y is Met, and m, n and p are 1 or 0; the formula [Ia] being as follows: and the formula [Ib] being as follows:
Claim 6
Dependent Claim 116 words
A DNA having or containing a base sequence corresponding to an amino acid sequence represented by the following formula [I] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A is a polypeptide of the formula [Ia] below in which one or more amino acids may be deleted or replaced by other amino acid(s), B is a peptide of the formula [Ib] below in which one to three amino acids may be deleted or replaced by other amino acid(s), X is a polypeptide, Y is Met, and m, n and p are 1 or 0; the formula [Ia] being as follows: and the formula [Ib] being as follows:
Claim 7
Dependent Claim 65 words
A DNA claimed in claim 3 having or containing a base sequence corresponding to an amino acid sequence represented by the following formula [I] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A, B, Y, m, n and p are the same as defined in claim 3, and X is a polypeptide of the formula [Ic]:
Claim 8
Dependent Claim 94 words
A DNA claimed in claim 3 having or containing a base sequence corresponding to an amino acid sequence represented by the following formula [I] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A is a polypeptide of the formula [Ia] shown in claim 3, B is a peptide of the formula [Ib] shown in claim 3, Y and p are the same as defined in claim 3, X is a polypeptide of the formula [Ic] shown in claim 4, and m and n are 1.
Claim 9
Dependent Claim 83 words
A DNA claimed in claim 3 having or containing a base sequence corresponding to an amino acid sequence represented by the following formula [I] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A is a polypeptide of the formula [Ia] shown in claim 3, B is a peptide of the formula [Ib] shown in claim 3, m is 1, n is 0, and Y and p are the same as defined in claim 3.
Claim 10
Dependent Claim 70 words
A DNA claimed in claim 3 having or containing a base sequence corresponding to an amino acid sequence represented by the following formula [I] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A is a polypeptide of the formula [Ia] shown in claim 3, n and m are 0, and Y and p are the same as defined in claim 3.
Claim 11
Dependent Claim 81 words
A DNA claimed in claim 3 having or containing a base sequence corresponding to an amino acid sequence represented by the following formula [1] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A is a polypeptide of the formula [Ia] in which one or more amino acids are deleted or replaced by other amino acid(s), m and n are 0, and Y and p are the same as defined in claim 3.
Claim 12
Dependent Claim 127 words
A DNA claimed in claim 3 having or containing a base sequence corresponding to an amino acid sequence represented by the following formula [I] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A is a polypeptide of the formula [Ia] in which Thr in the first position from the N-terminus, amino acids from the above Thr in the first position to Pro in the 6th position, amino acids from the above Thr in the first position to His in the 9th position, or amino acids from the above Thr in the first position to Ala in the 12th position are deleted, m and n are 0, and Y and p are the same as defined in claim 3.
Claim 13
Dependent Claim 87 words
A DNA claimed in claim 3 having or containing a base sequence corresponding to an amino acid sequence represented by the following formula [I) or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A is a polypeptide of the formula [Ia] in which Thr and His in the 66th and 67th positions from the N-terminus are replaced by His, Thr or Tyr, m and n are 0, and Y and p are the same as defined in claim 3.
Claim 14
Dependent Claim 51 words
ll. A DNA having at least a base sequence corresponding to an amino acid sequence represented by the following formula [Ia'] or an amino acid sequence of the following formula [Ia'] in which amino acid from Trp in the first position from N-terminus to Asp in the 27th position are deleted:
Claim 15
Dependent Claim 51 words
ll. A DNA having at least a base sequence corresponding to an amino acid sequence represented by the following formula [Ia'] or an amino acid sequence of the following formula [Ia'] in which amino acid from Trp in the first position from N-terminus to Asp in the 27th position are deleted:
Claim 16
Dependent Claim 119 words
A DNA having or containing a base sequence represented by the following formula [II] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A' is a base sequence of the formula [IIa] below in which one or more codons may be deleted or replaced by other codon(s), B' is a base sequence of the formula [IIb] below in which one to three codons may be deleted or replaced by other codon(s), X' is a base sequence of the formula [IIc] below, Y' is ATG, and m, n and p are 1 or 0; the formula [IIa] being as follows: the formula [IIb] being as follows: the formula [IIc] being as follows:
Claim 17
Dependent Claim 119 words
A DNA having or containing a base sequence represented by the following formula [II] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A' is a base sequence of the formula [IIa] below in which one or more codons may be deleted or replaced by other codon(s), B' is a base sequence of the formula [IIb] below in which one to three codons may be deleted or replaced by other codon(s), X' is a base sequence of the formula [IIc] below, Y' is ATG, and m, n and p are 1 or 0; the formula [IIa] being as follows: the formula [IIb] being as follows: the formula [IIc] being as follows:
Claim 18
Dependent Claim 79 words
A DNA claimed in claim 12 having or containing a base sequence represented by the following formula [II] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A' is a base sequence of the formula [IIa] shown in claim 12, B' is a base sequence of the formula [IIb] shown in claim 12, m and n are 1, and X', Y' and p are the same as defined in claim 12.
Claim 19
Dependent Claim 79 words
A DNA claimed in claim 12 having or containing a base sequence represented by the following formula [II] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A' is a base sequence of the formula [IIa] shown in claim 12, B' is a base sequence of the formula [IIb] shown in claim 12, m is 1, n is 0, and Y' and p are the same as defined in claim 12.
Claim 20
Dependent Claim 65 words
A DNA claimed in claim 12 having or containing a base sequence represented by the following formula [II] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A' is a base sequence of the formula [IIa] shown in claim 12, m and n are 0, and Y' and p are the same as defined in claim 12.
Claim 21
Dependent Claim 74 words
A DNA claimed in claim 12 having or containing a base sequence represented by the following formula [II] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A' is a base sequence of the formula [IIa] in which one or more codons are deleted or replaced by other codon(s), m and n are 0, and Y and p are the same as defined in claim 12.
Claim 22
Dependent Claim 121 words
A DNA claimed in claim 12 having or containing a base sequence represented by the following formula [II] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A' is a base sequence of the formula [IIa] in which ACC in the first codon from the 5 1- terminus, codons from the above ACC in the first codon to CCT in the 6th codon, codons from the above ACC in the first codon to CAT in the 9th codon, or codons from the above ACC in the first codon to GCA in the 12th codon are deleted, m and n are 0, and Y' and p are the same as defined in claim 12.
Claim 23
Dependent Claim 82 words
A DNA claimed in claim 12 having or containing a base sequence represented by the following formula [II] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A' is a base sequence of the formula [IIa] in which ACC and CAT in the 66th and 67th codons from the 5'-terminus are replaced by CAT, ACC or TAC, m and n are 0, and Y' and p are the same as defined in claim 12.
Claim 24
Dependent Claim 44 words
A DNA having at least a base sequence represented by the following formula [IIa'] or a base sequence of the formula [IIa'] in which codons from TGG in the first codon from the 5 1- terminus to GAC in the 27th codon are deleted:
Claim 25
Dependent Claim 44 words
A DNA having at least a base sequence represented by the following formula [IIa'] or a base sequence of the formula [IIa'] in which codons from TGG in the first codon from the 5 1- terminus to GAC in the 27th codon are deleted:
Claim 26
Dependent Claim 24 words
A DNA encoding a polypeptide of which activity is essetnially equivalent to that of a human tumor necrosis factor polypeptide or its principal portion.
Claim 27
Dependent Claim 24 words
A DNA encoding a polypeptide of which activity is essetnially equivalent to that of a human tumor necrosis factor polypeptide or its principal portion.
Claim 28
Dependent Claim 26 words
A DNA containing a base sequence which is different from but has high homology to a portion(s) of a base sequence encoding rabbit tumor necrosis factor.
Claim 29
Dependent Claim 26 words
A DNA containing a base sequence which is different from but has high homology to a portion(s) of a base sequence encoding rabbit tumor necrosis factor.
Claim 30
Dependent Claim 16 words
A vector into which the DNA of any one of claims 1 to 21 is inserted.
Claim 31
Dependent Claim 10 words
The vector of claim 22 which is an expression vector.
Claim 32
Dependent Claim 67 words
An expression vector of claim 23 which comprises a base sequence corresponding to an amino acid sequence represented by the following formula [I] wherein p is 1, and A, B, X, Y, m and n are the same as defined in claim 3, and having a termination codon at the 3'-terminus of said base sequence, wherein said base sequence is under the control of a transcriptional promoter.
Claim 33
Dependent Claim 18 words
An expression vector of claim 24 wherein the transcriptional promoter is a trp promoter or a tac promoter.
Claim 34
Dependent Claim 54 words
An expression vector of claim 24 wherein the base sequence corresponding to the amino acid sequence of formula [I] as defined in claim 24 having a termination codon at the 3'-terminus of said base sequence is connected in the correct translational reading frame to a second base sequence encoding a protein to be fused.
Claim 35
Dependent Claim 21 words
An expression vector of claim 26 wherein the second base sequence encoding a protein to be fused is a phoS gene.
Claim 36
Dependent Claim 11 words
A vector of claims 22-27 which can proliferate in Escherichia coli.
Claim 37
Dependent Claim 10 words
A vector of claim 28 which is Escherichia coli plasmid.
Claim 38
Dependent Claim 8 words
A vector of claim 29 which is pBR322.
Claim 39
Dependent Claim 9 words
A host transformed with a vector of claims 22-30.
Claim 40
Dependent Claim 8 words
A host of claim 31 which is microorganism.
Claim 41
Dependent Claim 9 words
A host of claim 32 which is Escherichia coli.
Claim 42
Dependent Claim 32 words
A polypeptide having or containing a human tumor necrosis factor polypeptide or its principal portion, a human tunor necrosis factor-like substance or its principal portion, or its chemically or enzymatically modified substance.
Claim 43
Dependent Claim 32 words
A polypeptide having or containing a human tumor necrosis factor polypeptide or its principal portion, a human tunor necrosis factor-like substance or its principal portion, or its chemically or enzymatically modified substance.
Claim 44
Dependent Claim 96 words
A polypeptide represented by the following formula [I] or its derivative or a salt thereof, wherein A is a polypeptide of the formula [Ia] below in which one or more amino acids may be deleted or replaced by other amino acid(s), B is a peptide of the formula [Ib] below in which one to three amino acids may be deleted or replaced by other amino acid(s), X is a polypeptide, Y is Met, and m, n and p are respectively 1 or 0; the formula [Ia] being as follows: and the formula [Ib] being as follows:
Claim 45
Dependent Claim 96 words
A polypeptide represented by the following formula [I] or its derivative or a salt thereof, wherein A is a polypeptide of the formula [Ia] below in which one or more amino acids may be deleted or replaced by other amino acid(s), B is a peptide of the formula [Ib] below in which one to three amino acids may be deleted or replaced by other amino acid(s), X is a polypeptide, Y is Met, and m, n and p are respectively 1 or 0; the formula [Ia] being as follows: and the formula [Ib] being as follows:
Claim 46
Dependent Claim 46 words
A polypeptide claimed in claim 35 represented by the following formula [I] or its derivative or a salt thereof, wherein A, B, Y, m, n and p are the same as defined in claim 35, and X is a polypeptide of the formula [Ic]being as follows:
Claim 47
Dependent Claim 66 words
A polypeptide claimed in claim 35 represented by the following formula [I] wherein A is a polypeptide of the formula [Ia] shown in claim 35, B is a peptide of the formula [Ib] shown in claim 35, X is a polypeptide of the formula [Ic] shown in claim 36, m and n are 1, and Y and p are the same as defined in claim 35.
Claim 48
Dependent Claim 55 words
A polypeptide claimed in claim 35 represented by the following formula [I] wherein A is a polypeptide of the formula [Ia] shown in claim 35, B is a peptide of the formula [Ib] shown in claim 35, m is 1, n is 0, and Y and p are the same as defined in claim 35.
Claim 49
Dependent Claim 42 words
A polypeptide claimed in claim 35 represented by the following formula [I] wherein A is a polypeptide of the formula [Ia] shown in claim 35, m and n are 0, and Y and p are the same as defined in claim 35.
Claim 50
Dependent Claim 46 words
A polypeptide claimed in claim 35 represented by the following formula [I] wherein A is a polypeptide of the formula [Ia] shown in claim 35, B is a peptide of the formula [Ib] shown in claim 35, m is 1, and n and p are 0.
Claim 51
Dependent Claim 31 words
A polypeptide claimed in claim 35 represented by the following formula [I] wherein A is a polypeptide of formula [Ia] shown in claim 35, and m, n and p are 0.
Claim 52
Dependent Claim 59 words
A polypeptide claimed in claim 35 represented by the following formula [I] or its derivative or its salt, wherein A is a polypeptide of the formula [Ia] in which one or more amino acids are deleted or replaced by other amino acid(s), m and n are 0, and Y and p are the same as defined in claim 35.
Claim 53
Dependent Claim 99 words
A polypeptide claimed in claim 35 represented by the following formula [IJ wherein A is a polypeptide of the formula [Ia] in which Thr in the first position from the N-terminus, amino acids from the above Thr in the first position to Pro in the 6th position, amino acids from the above Thr in the first position to His in the 9th position, or amino acids from the above Thr in the first position to Ala in the 12th position are deleted, m and n are 0, and Y and p are the same as defined in claim 35.
Claim 54
Dependent Claim 59 words
A polypeptide claimed in claim 35 represented by the following formula [I] wherein A is a polypeptide of the formula [Ia] in which Thr and His in the 66th and 67th positions from the N-terminus are replaced by His, Thr or Tyr, m and n are 0, and Y and p are the same as defined in claim 35.
Claim 55
Dependent Claim 43 words
A polypeptide containig at least a polypeptide represented by the following formula [Ia'] or a polypeptide of the formula [Ia l ] in which amino acid from Trp in the first position from the N-terminus to Asp in the 27th position are deleted:
Claim 56
Dependent Claim 43 words
A polypeptide containig at least a polypeptide represented by the following formula [Ia'] or a polypeptide of the formula [Ia l ] in which amino acid from Trp in the first position from the N-terminus to Asp in the 27th position are deleted:
Claim 57
Dependent Claim 21 words
A polypeptide of which activity is essentially equivalent to that of a human tumor necrosis factor polypeptide or its principal portion.
Claim 58
Dependent Claim 21 words
A polypeptide of which activity is essentially equivalent to that of a human tumor necrosis factor polypeptide or its principal portion.
Claim 59
Dependent Claim 22 words
A polypeptide containing a polypeptide which is different from, but has high homology to a portion(s) of a rabbit tumor necrosis factor.
Claim 60
Dependent Claim 22 words
A polypeptide containing a polypeptide which is different from, but has high homology to a portion(s) of a rabbit tumor necrosis factor.
Claim 61
Dependent Claim 20 words
A substance resulting from chemical or enzymatic modification of a polypeptide claimed in any one of claims 37 to 45:
Claim 62
Dependent Claim 17 words
A pharmaceutically acceptable salt of a poly- petide claimed in any one of claims 37 to 48.
Claim 63
Dependent Claim 17 words
An aggregate having a polypeptide claimed in any one of claims 37 to 49 as a subunit.
Claim 64
Dependent Claim 10 words
An aggregate claimed in claim 50 which is a trimer.
Claim 65
Dependent Claim 18 words
A trimer claimed in claim 51 which consists of a polypeptide claimed in claim 40 as a subunit.
Claim 66
Dependent Claim 19 words
A pharmaceutical composition of a substance claimed in any one of claims 34 to 52 as an active ingredient.
Claim 67
Dependent Claim 17 words
Use of any one of the substances claimed in claims 34 to 53 as an antitumor agent.
Claim 68
Dependent Claim 67 words
A process for production of a DNA having or containing a base sequence encoding a human tumor necrosis factor polypeptide, or a principal portion thereof, which comprises cultivating human macrophages together with inducer(s), separating a fraction containing a human tumor necrosis factor mRNA from the macrophages, preparing a cDNA library from the fraction, and cloning of cDNA encoding the human tumor necrosis factor or its principal portion.
Claim 69
Dependent Claim 67 words
A process for production of a DNA having or containing a base sequence encoding a human tumor necrosis factor polypeptide, or a principal portion thereof, which comprises cultivating human macrophages together with inducer(s), separating a fraction containing a human tumor necrosis factor mRNA from the macrophages, preparing a cDNA library from the fraction, and cloning of cDNA encoding the human tumor necrosis factor or its principal portion.
Claim 70
Dependent Claim 101 words
A process for producing a polypeptide having or containing a human tumor necrosis factor polypeptide or a principal portion thereof, which comprises cultivating human macrophages together with inducers, separating a fraction containing a human tumor necrosis factor mRNA from the macrophages, preparing a cDNA library from the fraction, cloning of cDNA encoding the human tumor necrosis factor or its principal portion, inserting the cloned cDNA into an expression vector, introducing the recombinant vector into a host to transform it, cultivating the transformant, and collecting the resulting polypeptide having or containing the human tumor necrosis factor polypeptide or a principal portion thereof.
Claim 71
Dependent Claim 101 words
A process for producing a polypeptide having or containing a human tumor necrosis factor polypeptide or a principal portion thereof, which comprises cultivating human macrophages together with inducers, separating a fraction containing a human tumor necrosis factor mRNA from the macrophages, preparing a cDNA library from the fraction, cloning of cDNA encoding the human tumor necrosis factor or its principal portion, inserting the cloned cDNA into an expression vector, introducing the recombinant vector into a host to transform it, cultivating the transformant, and collecting the resulting polypeptide having or containing the human tumor necrosis factor polypeptide or a principal portion thereof.
Claim 72
Dependent Claim 103 words
A process for producing a polypeptide having or containing a human tumor necrosis factor polypeptide or its principal portion, a human tumor necrosis factor-like substance or its principal portion, or its modified substance, which comprises inserting a DNA having or containing a base sequence encoding the human tumor necrosis factor polypeptide or its principal portion, or its modified base sequence into an expression vector, transforming a host with the recombinant vector, cultivating the host, and collecting the resulting polypeptide having or containing the human tumor necrosis factor polypeptide or a principal portion thereof from the host and then if desired, modifying the polypeptide.
Claim 73
Dependent Claim 103 words
A process for producing a polypeptide having or containing a human tumor necrosis factor polypeptide or its principal portion, a human tumor necrosis factor-like substance or its principal portion, or its modified substance, which comprises inserting a DNA having or containing a base sequence encoding the human tumor necrosis factor polypeptide or its principal portion, or its modified base sequence into an expression vector, transforming a host with the recombinant vector, cultivating the host, and collecting the resulting polypeptide having or containing the human tumor necrosis factor polypeptide or a principal portion thereof from the host and then if desired, modifying the polypeptide.
Claim 74
Dependent Claim 31 words
A process for producing or containing a DNA having a base sequence encoding a human tumor necrosis factor polypeptide or its principal portion, or a modified base sequence thereof, which comprises
Claim 75
Dependent Claim 31 words
A process for producing or containing a DNA having a base sequence encoding a human tumor necrosis factor polypeptide or its principal portion, or a modified base sequence thereof, which comprises
Claim 76
Dependent Claim 7 words
(1) cultivating human macrophages together with inducer(s),
Claim 77
Dependent Claim 7 words
(1) cultivating human macrophages together with inducer(s),
Claim 78
Dependent Claim 14 words
(2) separating a fraction containing a human tumor necrosis factor mRNA from the macrophages,
Claim 79
Dependent Claim 14 words
(2) separating a fraction containing a human tumor necrosis factor mRNA from the macrophages,
Claim 80
Dependent Claim 20 words
(3) preparing a single-stranded cDNA from the mRNA by using reverse transcriptase and then converting it to a double-stranded cDNA,
Claim 81
Dependent Claim 20 words
(3) preparing a single-stranded cDNA from the mRNA by using reverse transcriptase and then converting it to a double-stranded cDNA,
Claim 82
Dependent Claim 8 words
(4) inserting the double-stranded cDNA into a vector,
Claim 83
Dependent Claim 8 words
(4) inserting the double-stranded cDNA into a vector,
Claim 84
Dependent Claim 16 words
(5) introducing the recombinant vector into a host to transform it and construct a cDNA library,
Claim 85
Dependent Claim 16 words
(5) introducing the recombinant vector into a host to transform it and construct a cDNA library,
Claim 86
Dependent Claim 18 words
(6) cloning cDNA encoding the human tumor necrosis factor polypeptide or its principal portion from the library, and
Claim 87
Dependent Claim 18 words
(6) cloning cDNA encoding the human tumor necrosis factor polypeptide or its principal portion from the library, and
Claim 88
Dependent Claim 7 words
(7) as desired, modifying the cloned cDNA.
Claim 89
Dependent Claim 7 words
(7) as desired, modifying the cloned cDNA.
Claim 90
Dependent Claim 66 words
A process of claim 55 or 58 which is for the production of a DNA having or containing a base sequence corresponding to an amino acid sequence represented by the following formula [I] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A, B, X, Y, m, n and p are the same as defined in claim 3.
Claim 91
Dependent Claim 60 words
A process of claim 55 or 58 which is for the production of a DNA having or containing a base sequence represented by the following formula [II] or a base sequence having a termination codon at the 3'- terminus of said base sequence, wherein A', B', X', Y', m, n and p are the same as defined in claim 12.
Claim 92
Dependent Claim 45 words
A process of claim 56 or 57 which is for the production of a polypeptide represented by the following formula [I] or its derivative or a salt thereof, wherein A, B, X, Y, m, n and p are the same as defined in claim 35.

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