US4879226A
Expired / Lapsed
US
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Novel human physiologically active polypeptide
Assignee: Asahi Kasei Corp
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Filing: 1984-04-06
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Granted: 1989-11-07
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Expires: 2004-04-06
Abstract
Abstract A human physiologically active polypeptide, human Tumor Necrosis Factor (human TNF), comprising a specific amino acid sequence of 155 amino acid residues. The base sequence of the DNA coding for the human TNF has been determined using rabbit TNF cDNA. The human TNF can be advantageously produced on a large scale by recombinant DNA technique. The human TNF of the present invention has been found to be excellent in inducing necrosis of tumors with no toxic effect upon the normal tissues of the living body.
Inventors
- 👤 Robert B. Wallace
- 👤 Hirataka Itoh
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 10:46
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/11; C07; C07K; C07K14/00; C07K14/435; C07K14/52; C07K14/525; A; A61; A61P; A61P31/00; A61P31/12; A61P35/00; C12P; C12P21/00; C12P21/02; A61K; A61K38/00; Y; Y10; Y10S; Y10S435/00; Y10S435/8215; Y10S435/948; Y10S530/00; Y10S530/827; Y10S530/828
Claims Analysis
Total Claims: 54
Claim 1
Independent Claim
118 words
An isolated physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the following formula: ##STR1## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor.
Claim 2
Dependent Claim
118 words
An isolated physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the following formula: ##STR1## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor.
Claim 3
Dependent Claim
122 words
A composition of matter consisting essentially of a physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the formula: ##STR2## wherein Gln stands for glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor.
Claim 4
Dependent Claim
122 words
A composition of matter consisting essentially of a physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the formula: ##STR2## wherein Gln stands for glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor.
Claim 5
Dependent Claim
147 words
A composition of matter comprising an effective anti-tumor amount of a physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the formula: ##STR3## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor, wherein said human polypeptide or variant thereof is derived from a microorganism or cell transformed with a gene for said polypeptide.
Claim 6
Dependent Claim
147 words
A composition of matter comprising an effective anti-tumor amount of a physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the formula: ##STR3## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor, wherein said human polypeptide or variant thereof is derived from a microorganism or cell transformed with a gene for said polypeptide.
Claim 7
Dependent Claim
19 words
The composition of claim 3, which is prepared by cultivating said microorganism, recovering said polypeptide and purifying said polypeptide.
Claim 8
Dependent Claim
20 words
The composition of claim 4, wherein said polypeptide consists of an amino acid sequence represented by the following formula: ##STR4##
Claim 9
Independent Claim
219 words
A method for producing a physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the following formula: ##STR5## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue or a variant of said polypeptide having all of the activity of human tumor necrosis factor which comprises: (a) ligating a deoxyribonucleic acid comprising a base sequence coding for said physiologically active polypeptide to a replicable expression vehicle to obtain a replicable recombinant DNA comprising said deoxyribonucleic acid and said replicable expression vehicle; (b) transforming cells of a microorganism or cell culture with said replicable recombinant DNA to form transformants; (c) selecting said transformants from parent cells of the microorganism or cell culture; (d) incubating said transformants, causing said transformants to express said deoxyribonucleic acid and produce a physiologically active human polypeptide; and (e) isolating said human physiologically active polypeptide from the incubated transformants.
Claim 10
Independent Claim
219 words
A method for producing a physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the following formula: ##STR5## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue or a variant of said polypeptide having all of the activity of human tumor necrosis factor which comprises: (a) ligating a deoxyribonucleic acid comprising a base sequence coding for said physiologically active polypeptide to a replicable expression vehicle to obtain a replicable recombinant DNA comprising said deoxyribonucleic acid and said replicable expression vehicle; (b) transforming cells of a microorganism or cell culture with said replicable recombinant DNA to form transformants; (c) selecting said transformants from parent cells of the microorganism or cell culture; (d) incubating said transformants, causing said transformants to express said deoxyribonucleic acid and produce a physiologically active human polypeptide; and (e) isolating said human physiologically active polypeptide from the incubated transformants.
Claim 11
Dependent Claim
14 words
The method of claim 6, further comprising the step of purifying the isolated polypeptide.
Claim 12
Dependent Claim
144 words
An isolated deoxyribonucleic acid capable of coding for a human tumor necrosis factor polypeptide having tumor necrosis factor activity comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula and a base sequence complementary to said base sequence: ##STR6## wherein A stands for a deoxyadenylic acid residue, G a deoxyguanylic acid residue, C a deoxycytidylic acid residue and T a thymidylic acid residue and wherein the left end and right end of said formula represent the 5'-hydroxyl group side and 3'-hydroxyl group side, respectively, or comprising a base sequence which is obtained by substituting at least one base of said base sequence in accordance with the degeneracy of the Genetic Code, or a base sequence which codes for a variant of said human polypeptide having all of the activity of human tumor necrosis factor.
Claim 13
Dependent Claim
144 words
An isolated deoxyribonucleic acid capable of coding for a human tumor necrosis factor polypeptide having tumor necrosis factor activity comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula and a base sequence complementary to said base sequence: ##STR6## wherein A stands for a deoxyadenylic acid residue, G a deoxyguanylic acid residue, C a deoxycytidylic acid residue and T a thymidylic acid residue and wherein the left end and right end of said formula represent the 5'-hydroxyl group side and 3'-hydroxyl group side, respectively, or comprising a base sequence which is obtained by substituting at least one base of said base sequence in accordance with the degeneracy of the Genetic Code, or a base sequence which codes for a variant of said human polypeptide having all of the activity of human tumor necrosis factor.
Claim 14
Dependent Claim
153 words
A replicable recombinant DNA which comprises a replicable expression vehicle and a deoxyribonucleic acid capable of coding for a human tumor necrosis factor polypeptide having tumor necrosis factor activity comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula and a base sequence complementary to said base sequence: ##STR7## wherein A stands for deoxyadenylic acid residue, G a deoxyguanylic acid residue, C a deoxycytidylic acid residue and T a thymidylic acid residue and wherein the left end and right end of said formula represent the 5'-hydroxyl group side and 3'-hydroxyl group side, respectively, or comprising a base sequence which is obtained by substituting at least one base of said base sequence in accordance with the degeneracy of the Genetic Code, or a base sequence which codes for a variant of said human polypeptide having all of the activity of human tumor necrosis factor.
Claim 15
Dependent Claim
153 words
A replicable recombinant DNA which comprises a replicable expression vehicle and a deoxyribonucleic acid capable of coding for a human tumor necrosis factor polypeptide having tumor necrosis factor activity comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula and a base sequence complementary to said base sequence: ##STR7## wherein A stands for deoxyadenylic acid residue, G a deoxyguanylic acid residue, C a deoxycytidylic acid residue and T a thymidylic acid residue and wherein the left end and right end of said formula represent the 5'-hydroxyl group side and 3'-hydroxyl group side, respectively, or comprising a base sequence which is obtained by substituting at least one base of said base sequence in accordance with the degeneracy of the Genetic Code, or a base sequence which codes for a variant of said human polypeptide having all of the activity of human tumor necrosis factor.
Claim 16
Dependent Claim
161 words
A microorganism or cell culture transformed with a replicable recombinant DNA which comprises a replicable expression vehicle and a deoxyribonucleic acid capable of coding for a human tumor necrosis factor polypeptide having tumor necrosis factor activity comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula and a base sequence complementary to said base sequence: ##STR8## wherein A stands for a deoxyadenylic acid residue, G a deoxyguanylic acid residue, C a deoxycytidylic acid residue and T a thymidylic acid residue and wherein the left end and right end of said formula represent the 5'-hydroxyl group side and 3'-hydroxyl group side, respectively, or comprising a base sequence which is obtained by substituting at least one base of said base sequence in accordance with the degeneracy of the Genetic Code, or a base sequence which codes for a variant of said human polypeptide having all of the activity of human tumor necrosis factor.
Claim 17
Dependent Claim
161 words
A microorganism or cell culture transformed with a replicable recombinant DNA which comprises a replicable expression vehicle and a deoxyribonucleic acid capable of coding for a human tumor necrosis factor polypeptide having tumor necrosis factor activity comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula and a base sequence complementary to said base sequence: ##STR8## wherein A stands for a deoxyadenylic acid residue, G a deoxyguanylic acid residue, C a deoxycytidylic acid residue and T a thymidylic acid residue and wherein the left end and right end of said formula represent the 5'-hydroxyl group side and 3'-hydroxyl group side, respectively, or comprising a base sequence which is obtained by substituting at least one base of said base sequence in accordance with the degeneracy of the Genetic Code, or a base sequence which codes for a variant of said human polypeptide having all of the activity of human tumor necrosis factor.
Claim 18
Dependent Claim
158 words
A microorganism transformed with a replicable recombinant DNA which comprises a replicable expression vehicle and a deoxyribonucleic acid capable of coding for a human tumor necrosis factor polypeptide having tumor necrosis factor activity comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula and a base sequence complementary to said base sequence: ##STR9## wherein A stands for a deoxyadenylic acid residue, G a deoxyguanylic acid residue, C a deoxycytidylic acid residue and T a thymidylic acid residue and wherein the left end and right end of said formula represent the 5'-hydroxyl group side and 3'-hydroxyl group side, respectively, or comprising a base sequence which is obtained by substituting at least one base of said base sequence in accordance with the degeneracy of the Genetic Code or a base sequence which codes for a variant of said human polypeptide having all of the activity of human tumor necrosis factor.
Claim 19
Dependent Claim
158 words
A microorganism transformed with a replicable recombinant DNA which comprises a replicable expression vehicle and a deoxyribonucleic acid capable of coding for a human tumor necrosis factor polypeptide having tumor necrosis factor activity comprising at least one base sequence selected from the group consisting of a base sequence represented by the following formula and a base sequence complementary to said base sequence: ##STR9## wherein A stands for a deoxyadenylic acid residue, G a deoxyguanylic acid residue, C a deoxycytidylic acid residue and T a thymidylic acid residue and wherein the left end and right end of said formula represent the 5'-hydroxyl group side and 3'-hydroxyl group side, respectively, or comprising a base sequence which is obtained by substituting at least one base of said base sequence in accordance with the degeneracy of the Genetic Code or a base sequence which codes for a variant of said human polypeptide having all of the activity of human tumor necrosis factor.
Claim 20
Dependent Claim
12 words
The transformed microorganism of claim 11, wherein said microorganism is a bacterium.
Claim 21
Dependent Claim
12 words
The transformed microorganism of claim 12, wherein said bacterium is Escherichia coli.
Claim 22
Dependent Claim
109 words
The transformed microorganism of claim 11, which is capable of producing a human tumor necrosis factor polypeptide consisting of an amino acid sequence of the formula: ##STR10## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue.
Claim 23
Dependent Claim
14 words
The transformed microorganism of claim 13, wherein said Escherichia coli is Escherichia coli K-12.
Claim 24
Dependent Claim
20 words
The transformed microorganism of claim 11, wherein said microorganism is a bacterium and said replicable expression vehicle is a plasmid.
Claim 25
Dependent Claim
12 words
The transformed microorganism of claim 16, wherein said bacterium is Escherichia coli.
Claim 26
Dependent Claim
138 words
A pharmaceutical composition comprising: an effective anti-tumor or anti-viral amount of a physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the following formula: ##STR11## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor; and at least one pharmaceutically acceptable carrier, diluent or excipient.
Claim 27
Dependent Claim
138 words
A pharmaceutical composition comprising: an effective anti-tumor or anti-viral amount of a physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the following formula: ##STR11## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor; and at least one pharmaceutically acceptable carrier, diluent or excipient.
Claim 28
Dependent Claim
20 words
The pharmaceutical composition of claim 18, wherein said polypeptide comprises an amino acid sequence represented by the following formula: ##STR12##
Claim 29
Dependent Claim
21 words
The pharmaceutical composition of claim 19, wherein said polypeptide consists of an amino acid sequence represented by the following formula: ##STR13##
Claim 30
Dependent Claim
13 words
The pharmaceutical composition of claim 19, which is a pharmaceutically acceptable, injectable solution.
Claim 31
Dependent Claim
13 words
The pharmaceutical composition of claim 20, which is a pharmaceutically acceptable, injectable solution.
Claim 32
Dependent Claim
13 words
The pharmaceutical composition of claim 20, which is a pharmaceutically acceptable, injectable solution.
Claim 33
Independent Claim
134 words
A method for treating tumors which comprises administering to a host an effective anti-tumor amount of a purified physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the following formula: ##STR14## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor.
Claim 34
Independent Claim
134 words
A method for treating tumors which comprises administering to a host an effective anti-tumor amount of a purified physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the following formula: ##STR14## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor.
Claim 35
Dependent Claim
19 words
The method of claim 24, wherein said polypeptide comprises an amino acid sequence represented by the following formula: ##STR15##
Claim 36
Dependent Claim
20 words
The method of claim 24, wherein said polypeptide consists of an amino acid sequence represented by the following formula: ##STR16##
Claim 37
Dependent Claim
20 words
The method of claim 24, wherein said polypeptide is administered by injecting a pharmaceutically acceptable, injectable solution of said polypeptide.
Claim 38
Dependent Claim
154 words
A process for preparing a polypeptide having human tumor necrosis factor activity which comprises: cultivating a microorganism or cell culture transformed with a deoxyribonucleic acid comprising a base sequence capable of coding for a physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the following formula: ##STR17## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor; and recovering said polypeptide.
Claim 39
Dependent Claim
154 words
A process for preparing a polypeptide having human tumor necrosis factor activity which comprises: cultivating a microorganism or cell culture transformed with a deoxyribonucleic acid comprising a base sequence capable of coding for a physiologically active human tumor necrosis factor polypeptide comprising an amino acid sequence represented by the following formula: ##STR17## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue, or a variant of said polypeptide having all of the activity of human tumor necrosis factor; and recovering said polypeptide.
Claim 40
Dependent Claim
111 words
The process of claim 28, wherein said base sequence comprises at least one base sequence selected from the group consisting of a base sequence represented by the following formula and a base sequence complementary to said base sequence: ##STR18## wherein A stands for a deoxyadenylic acid residue, G a deoxyguanylic acid residue, C a deoxycytidylic acid residue and T a thymidylic acid residue and wherein the left end and right end of said formula represent the 5'-hydroxyl group side and 3'-hydroxyl group side, respectively, or comprising a base sequence which is obtained by substituting at least one base of said base sequence in accordance with the degeneracy of the Genetic Code.
Claim 41
Dependent Claim
36 words
The process of claim 28, which comprises cultivating a microorganism transformed with a plasmid containing said base sequence in a culture medium, recovering said polypeptide from said microorganism or said culture medium and purifying said polypeptide.
Claim 42
Dependent Claim
11 words
The process of claim 30, wherein said microorganism is a bacterium.
Claim 43
Dependent Claim
11 words
The process of claim 31, wherein said bacterium is Escherichia coli.
Claim 44
Dependent Claim
13 words
The process of claim 32, wherein said Escherichia coli is Escherichia coli K-12.
Claim 45
Dependent Claim
8 words
The microorganism E. coli k-12 strain JM83 (pHGE).
Claim 46
Dependent Claim
8 words
The microorganism E. coli k-12 strain JM83 (pHGE).
Claim 47
Dependent Claim
3 words
The plasmid pHGE.
Claim 48
Dependent Claim
3 words
The plasmid pHGE.
Claim 49
Dependent Claim
108 words
Isolated human genomic DNA which upon expression results in a human tumor necrosis factor polypeptide having an amino acid sequence represented by the following formula: ##STR19## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue.
Claim 50
Dependent Claim
108 words
Isolated human genomic DNA which upon expression results in a human tumor necrosis factor polypeptide having an amino acid sequence represented by the following formula: ##STR19## wherein Gln stands for a glutamine residue, Asp an aspartic acid residue, Pro a proline residue, Tyr a tyrosine residue, Val a valine residue, Lys a lysine residue, Glu a glutamic acid residue, Ala an alanine residue, Asn an asparagine residue, Leu a leucine residue, Phe a phenylalanine residue, Gly a glycine residue, His a histidine residue, Ser a serine residue, Thr a threonine residue, Ile an isoleucine residue, Trp a tryptophan residue, Arg an arginine residue, and Cys a cysteine residue.
Claim 51
Dependent Claim
18 words
A replicable recombinant DNA which comprises: a replicable vector; and the isolated human genomic DNA of claim 36.
Claim 52
Dependent Claim
11 words
The replicable recombinant DNA of claim 37, which is a plasmid.
Claim 53
Dependent Claim
11 words
A microorganism transformed with the replicable recombinant DNA of claim 38.
Claim 54
Dependent Claim
9 words
The microorganism of claim 39, which is E. coli.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-11-06 | 1993-05-08 | 1993-11-07 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-11-06 | 1997-05-08 | 1997-11-07 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-11-06 | 2001-05-08 | 2001-11-07 | $7700.00 | Window Closed / Lapsed |