Patent EP0284105A2 successfully refreshed from Google Patents.
EP0284105A2
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Human manganese superoxide dismutase and methods of treatment
Assignee: Savient Pharmaceuticals Inc
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Filing: 1988-03-25
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Granted: —
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Expires: 2008-03-25
Abstract
Abstract A double-stranded cDNA molecule which includes DNA encoding human manganese superoxide dismutase has been created. The sequence of one strand of a double-stranded DNA molecule which encodes human manganese superoxide dismutase has been discovered. Such molecules may be introduced in prokaryotic, e.g., bacterial, or eucaryotic, e.g., yeast or mammalian, cells and the resulting cells cultured or grown under suitable conditions so as to produce human manganese superoxide dismutase, human manganese superoxide dismutase analogs or human manganese superoxide dismutase mutants which may then be recovered. By this invention, human manganese superoxide dismutase gene fragments from various plasmids may be ligated to yield a complete genomic human manganese superoxide dismutase gene fragment. Human manganese superoxide dismutase, analogs, or mutants may be used to catalyze the reduction of superoxide radicals, reduce reperfusion injury, prolong the survival time of isolated organs, or treat inflammations. The invention also concerns a method of producing enzymatically active human manganese superoxide dismutase compounds in a bacterial cell which contains and is capable of expressing a DNA sequence encoding the superoxide dismutase compound by maintaining the bac terial cell under suitable conditions and in a suitable production medium. The production medium is supplemented with an amount of Mn⁺⁺ so that the concentration of Mn⁺⁺ in the medium is greater than about 2 ppm. Genomic manganese superoxide dismutase DNA should also be capable of expression in eucaryotic cells under suitable conditions. This invention also concerns a method of recovering purified enzymatically active manganese superoxide dismutase, analogs or mutants from bacterial cells. It should also be possible to recover manganese SOD from genomic manganese superoxide dismutase DNA expressed in eucaryotic cells using similar methods. The invention further concerns uses of the human manganese superoxide dismutase, human manganese superoxide dismutase analogs or human manganese superoxide dismutase mutants, various new analogs, compositions of the compounds and methods of treating various disorders using these compositions.
Inventors
- 👤 Jacob R. Hartman
- 👤 Yaffa Beck
- 👤 Abraham Nimrod
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-08 05:00
CPC Classifications
C; C12; C12N; C12N9/00; C12N9/0004; C12N9/0089; A; A61; A61K; A61K38/00; A61K38/16; A61K38/43; A61K38/44; A61K38/446; A61P; A61P11/00; A61P19/00; A61P19/02; A61P29/00
Claims Analysis
Total Claims: 50
Claim 1
Independent Claim
57 words
A method of treating a subject suffering from a disorder associated with the generation of oxygen free radicals in quantities sufficient to cause undesirable symptoms which comprises administering to the subject an amount of human manganese superoxide dismutase, a human manganese superoxide dismutase analog or a human manganese superoxide dismutase mutant effective to alleviate the undesirable symptoms.
Claim 2
Independent Claim
57 words
A method of treating a subject suffering from a disorder associated with the generation of oxygen free radicals in quantities sufficient to cause undesirable symptoms which comprises administering to the subject an amount of human manganese superoxide dismutase, a human manganese superoxide dismutase analog or a human manganese superoxide dismutase mutant effective to alleviate the undesirable symptoms.
Claim 3
Dependent Claim
11 words
A method of claim 1, wherein the undesirable symptoms comprise inflammation.
Claim 4
Dependent Claim
11 words
A method of claim 2, wherein the inflammation is synovial inflammation.
Claim 5
Dependent Claim
25 words
A method of claim 3, wherein the human manganese superoxide dismutase, human manganese superoxide dismutase analog, or human manganese superoxide dismutase mutant is administered intraarticularly.
Claim 6
Dependent Claim
32 words
A method of claim 4, wherein the amount of human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant is between about 1 and about 200 mg/joint.
Claim 7
Dependent Claim
16 words
A method of claim 1, wherein the disorder is arthritis and the undesirable symptoms comprise inflammation.
Claim 8
Dependent Claim
25 words
A method of claim 6, wherein the human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant is administered daily.
Claim 9
Dependent Claim
37 words
A method of claim 7, wherein the amount of human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant is between about 1 and about 100 mg/kilogram body weight of the subject.
Claim 10
Dependent Claim
37 words
A method of claim 8, wherein the amount of human manganese superoxide dimustase, human manganese superoxide dimustase analog or human manganese superoxide dimustase mutant is between about 3 and about 50 mg/kilogram body weight of the subject.
Claim 11
Dependent Claim
24 words
A method of claim 6, wherein the human superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant is administered subcutaneously.
Claim 12
Dependent Claim
24 words
A method of claim 6, wherein the human superoxide dismutase, human manganese superoxide dismutase analog or human manganese supeoxide dismutase mutant is administered intravenously.
Claim 13
Dependent Claim
12 words
A method of claim 1, wherein the undesirable symptoms comprise lung fibrosis.
Claim 14
Dependent Claim
25 words
A method of claim 12, wherein the human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant is administered daily.
Claim 15
Dependent Claim
39 words
A method according to claim 13, wherein the amount of human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manga nese superoxide dismutase mutant is between about 1 and about 100 mg/kilogram body weight of the subject.
Claim 16
Dependent Claim
37 words
A method of claim 14, wherein the amount of human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant is between about 3 and about 50 mg/kilogram body weight of the subject.
Claim 17
Dependent Claim
14 words
A method of claim 12, wherein the fibrosis is induced by an anti-neoplastic agent.
Claim 18
Dependent Claim
12 words
A method of claim 12, wherein the fibrosis is induced by radiation.
Claim 19
Dependent Claim
11 words
A method of claim 16, wherein the anti-neoplastic agent is bleomycin.
Claim 20
Dependent Claim
25 words
A method of claim 12, wherein the human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant is administered subcutaneously.
Claim 21
Dependent Claim
25 words
A method of claim 12, wherein the human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant is administered intravenously.
Claim 22
Dependent Claim
25 words
A method of claim 12, wherein the human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant is administered intratracheally.
Claim 23
Dependent Claim
32 words
A double-stranded DNA molecule which encodes human manganese superoxide dismutase or a human manga nese superoxide dismutase analog and the coding strand of which has the nucleotide sequence shown in Figure 6.
Claim 24
Dependent Claim
32 words
A double-stranded DNA molecule which encodes human manganese superoxide dismutase or a human manga nese superoxide dismutase analog and the coding strand of which has the nucleotide sequence shown in Figure 6.
Claim 25
Dependent Claim
37 words
A double-stranded DNA molecule which encodes a human manganese superoxide dismutase mutant and the coding strand of which has a nucleotide sequence which varies from the nucleotide sequence shown in Figure 6 by one or more nucleotides.
Claim 26
Dependent Claim
37 words
A double-stranded DNA molecule which encodes a human manganese superoxide dismutase mutant and the coding strand of which has a nucleotide sequence which varies from the nucleotide sequence shown in Figure 6 by one or more nucleotides.
Claim 27
Dependent Claim
13 words
A cloning vehicle which comprises the DNA molecule of claim 22 or 23.
Claim 28
Dependent Claim
15 words
A cloning vehicle containing a fragment of the DNA molecule of claim 22 or 23.
Claim 29
Dependent Claim
19 words
A plasmid of claim 25, designated pMSG11-1 and deposited in Escherichia coli strain MC1061 under ATCC Accession No. 67363.
Claim 30
Dependent Claim
17 words
A plasmid of claim 25, designated pMSG4 and deposited in strain MC1061 under ATCC Accession No. 67364.
Claim 31
Dependent Claim
19 words
A plasmid of claim 25, designated pMSG-1b and deposited in Escherichia coli strain MC1061 under ATCC Accession No. 67365.
Claim 32
Dependent Claim
17 words
A eucaryotic cell in culture in which the DNA sequence of claim 22 or 23 is expressed.
Claim 33
Dependent Claim
13 words
A eucaryotic cell transformed with the cloning vehicle of claim 22 or 23.
Claim 34
Dependent Claim
14 words
A eucaryotic cell of claim 29 wherein the DNA is present in multiple copies.
Claim 35
Dependent Claim
33 words
A eucaryotic cell of claim 29, wherein the expression of the DNA is regulated by the regulatory elements associated with the noncoding DNA region of human manganese superoxide dismutase shown in Figure 6.
Claim 36
Dependent Claim
6 words
A mammalian cell of claim 29.
Claim 37
Dependent Claim
7 words
A human HeLa cell of claim 33.
Claim 38
Dependent Claim
7 words
A mouse L cell of claim 29.
Claim 39
Dependent Claim
69 words
A method for producing human manganese superoxide dismutase, human manganese superoxide dismutase analog, or human manganese superoxide dismutase mutant which comprises growing the eucaryotic cell of claim 29 under suitable conditions permitting production of the human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant and recovering the resulting human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant.
Claim 40
Dependent Claim
22 words
Human manganese superoxide dismutase, human manganese superoxide dismutase analog, or human manganese superoxide dismutase mutant produced by the method of claim 36.
Claim 41
Dependent Claim
41 words
A pharmaceutical composition comprising an amount of human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant effective to alleviate the undesirable symptoms associated with the generation of oxygen free radicals and a pharmaceutically acceptable carrier.
Claim 42
Dependent Claim
41 words
A pharmaceutical composition comprising an amount of human manganese superoxide dismutase, human manganese superoxide dismutase analog or human manganese superoxide dismutase mutant effective to alleviate the undesirable symptoms associated with the generation of oxygen free radicals and a pharmaceutically acceptable carrier.
Claim 43
Dependent Claim
34 words
A human manganese superoxide dismutase analog in which at least one of the human manganese superoxide dismutase polypeptides differs from naturally-occurring human manganese superoxide dismutase polypeptide by the absence of lysine at the N-terminus.
Claim 44
Dependent Claim
34 words
A human manganese superoxide dismutase analog in which at least one of the human manganese superoxide dismutase polypeptides differs from naturally-occurring human manganese superoxide dismutase polypeptide by the absence of lysine at the N-terminus.
Claim 45
Dependent Claim
37 words
A human manganese superoxide dismutase analog in which at least one of the human manganese superoxide dismutase polypeptides differs from naturally-occurring human manganese superoxide dismutase polypeptide by the absence of both lysine and histidine at the N-terminus.
Claim 46
Dependent Claim
37 words
A human manganese superoxide dismutase analog in which at least one of the human manganese superoxide dismutase polypeptides differs from naturally-occurring human manganese superoxide dismutase polypeptide by the absence of both lysine and histidine at the N-terminus.
Claim 47
Dependent Claim
31 words
A pharmaceutical composition comprising an amount of the analog of claim 39 effective to alleviate the undesirable symptoms associated with the generation of oxygen free radicals and a pharmaceutically acceptable carrier.
Claim 48
Dependent Claim
31 words
A pharmaceutical composition comprising an amount of the analog of claim 40 effective to alleviate the undesirable symptoms associated with the generation of oxygen free radicals and a pharmaceutically acceptable carrier.
Claim 49
Dependent Claim
45 words
A method of treating a subject suffering from a disorder associated with the generation of oxygen free radicals in quantities sufficient to cause undesirable symptoms which comprises administering to the subject an amount of the analog of claim 39 effective to alleviate the undesirable symptoms.
Claim 50
Dependent Claim
46 words
A method of treating a subject suffering from a disorder associated with the generation of oxygen free radicals in quantities sufficient to cause undesirable symptoms which comprises administering to the subject an effective amount of the analog of claim 40 effective to alleviate the undesirable symptoms.
References Cited (Backward Citations)
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