CA2168409A1 - G cap-stabilized oligonucleotides - Google Patents
G cap-stabilized oligonucleotidesInfo
- Publication number
- CA2168409A1 CA2168409A1 CA002168409A CA2168409A CA2168409A1 CA 2168409 A1 CA2168409 A1 CA 2168409A1 CA 002168409 A CA002168409 A CA 002168409A CA 2168409 A CA2168409 A CA 2168409A CA 2168409 A1 CA2168409 A1 CA 2168409A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- oligonucleotide
- uracil
- ribose
- particularly preferably
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1131—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
- C12N15/1132—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses against retroviridae, e.g. HIV
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1131—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
- C12N15/1133—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses against herpetoviridae, e.g. HSV
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- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1135—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1136—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against growth factors, growth regulators, cytokines, lymphokines or hormones
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/15—Nucleic acids forming more than 2 strands, e.g. TFOs
- C12N2310/151—Nucleic acids forming more than 2 strands, e.g. TFOs more than 3 strands, e.g. tetrads, H-DNA
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
Abstract
The invention relates to oligonucleotides of the formula 5'-(CAP)-(oligo)-(CAP)-3 where (Oligo) is a nucleotide sequence of from 10 to 40 nucleotides in length, and CAP is Gm, where m is an integer of from zero to ten, preferably of from two to six, particularly preferably of from three to five and very particularly preferably four, and where the two CAP's which are present in the molecule can be defined independently of each other and must be different in the case where m is zero at the 5' or 3' end and the end of the "Oligo" sequence is not formed by a guanine, to a process for their preparation, to pharmaceuticals con-taining the novel oligonucleotides, and to their use for preparing a pharmaceutical for treating diseases or for preparing a diagnostic agent.
Claims (16)
1.) An oligonucleotide of the formula 5'-(CAP)-(Oligo)-(CAP)-3' where (Oligo) is a nucleotide sequence of from 10 to 40 nucleotides in length, and CAP is Gm, where m is an integer of from zero to ten, preferably of from two to six, particularly preferably of from three to five and very particularly preferably four, and where the two CAP's which are present in the molecule can be defined independently of each other and must be different in the case where m is zero at the 5' or 3' end and the end of the "Oligo" sequence is not formed by a guanine.
2.) An oligonucleotide as claimed in claim 1, wherein the nucleotide sequence of the "(Oligo)" moiety originates from those regions of genes which are important for the transcription of DNA or the trans-lation of the corresponding mRNA.
3.) An oligonucleotide as claimed in claims 1 and 2, wherein (Oligo) is ACACCCAATTCTGAAAATGG (I), AGGTCCCTGTTCGGGCGCCA (II), GTCGACACCCAATTCTGAAAATGGATAA (III), GCTATGTCGACACCCAATTCTGAAA (IV), GTCGCTGTCTCCGCTTCTTCTTCCTG (V), GTCTCCGCTTCTTCTTCCTGCCATAGG (VI), GCGGGGCTCCATGGGGGTCG (VII), CAGCTGCAACCCAGC (VIII), GGCTGCTGGAGCGGGGCACAC (IX), AACGTTGAGGGGCAT (X), GTGCCGGGGTCTTCGGGC (XI), GGAGAACATCATGGTCGAAAG (XII), CCCGAGAACATCATGGTCGAAG (XIII), GGGGAAAGCCCGGCAAGGGG (XIV), CACCCGCCTTGGCCTCCCAC (XV), GGGACTCCGGCGCAGCGC (XVI), GGCAAACTTTCTTTTCCTCC (XVII), GGGAAGGAGGAGGATGAGG (XVIII), GGCAGTCATCCAGCTTCGGAG (XIX), GCAGTAAGCATCCATATC (XX), CCCCCACCACTTCCCCTCTC (XXI), CTCCCCCACCACTTCCCCTC (XXII), GCTGGGAGCCATAGCGAGG (XXIII), ACTGCTGCCTCTTGTCTCAGG (XXIV), CAATCAATGACTTCAAGAGTTC (XXV), GGTCCCTGTTCGGGCGCCA (XXVI), GTGCCGGGGTCTTCGGG (XXVII), GGAGGATGCTGAGGAGG (XXVIII), GGAGGATGCTGAGG (XXIX), CAGGAGGATGCTGAGGAGG (XXX), GGCTGCCATGGTCCC (XXXI), TCATGGTGTCCTTTGCAGCC (XXXII), TCATGGTGTCCTTTGCAG (XXXIII) or AAGTTCATGGTTTCGG (XXXIV).
4.) An oligonucleotide as claimed in claims 1 and 2, which has one of the sequences C*A*GGAGGAT*-GC*T*-GAGGA*G*G, preferably G*G*G*CAGGAGGAT*GC*T*
GAGGAGG*G*G*G and PY-G*G*G*GGAGGAT*GC*TGAGG*G*G*G, and particularly preferably G*G*G*GGAGGAT*GC*T*-GAGGAGG*G*G*G and G*G*G*GGAGGAT*GC*TGAGG*G*G*G.
GAGGAGG*G*G*G and PY-G*G*G*GGAGGAT*GC*TGAGG*G*G*G, and particularly preferably G*G*G*GGAGGAT*GC*T*-GAGGAGG*G*G*G and G*G*G*GGAGGAT*GC*TGAGG*G*G*G.
5.) An oligonucleotide as claimed in claims 1 to 3, which oligonucleotide is modified.
6.) An oligonucleotide as claimed in claim 5, wherein from 2 to 10 non-terminal pyrimidine nucleosides are modified.
7.) An oligonucleotide as claimed in claim 6, wherein the oligonucleotide is modified at the 5'-terminal and/or 3'-terminal nucleotide.
8.) An oligonucleotide as claimed in one of claims 5 to 7, wherein one or more groups of at least 1 to 4 nucleotides which are connected to each other is/
are not modified.
are not modified.
9.) An oligonucleotide as claimed in one of claims 5 to 8, wherein the modification is defined as (a) complete or partial replacement of the 3' and/
or 5' phosphoric diester bridges, and/or (b) complete or partial replacement of the 3' or 5' phosphoric diester bridges by "dephospho"
bridges, and/or (c) complete or partial replacement of the sugar phosphate backbone, and/or (d) complete or partial replacement of the .beta.-D-2'-deoxyribose units, and/or (e) complete or partial replacement of the natural nucleoside bases.
or 5' phosphoric diester bridges, and/or (b) complete or partial replacement of the 3' or 5' phosphoric diester bridges by "dephospho"
bridges, and/or (c) complete or partial replacement of the sugar phosphate backbone, and/or (d) complete or partial replacement of the .beta.-D-2'-deoxyribose units, and/or (e) complete or partial replacement of the natural nucleoside bases.
10.) An oligonucleotide as claimed in claim 9, wherein the modification is defined as (a) a phosphorothioate, phosphorodithioate, (NR1R2)-phosphoramidate, boranophosphate, phosphate-(C1-C21)-O-alkyl ester, phosphate-[(C6-C12)aryl-(C1-C21)-O-alkyl] ester, 2,2,2-trichlorodimethylethylphosphonate, (C1-C8)-alkylphosphonate or (C6-C12)-arylphosphonate bridge, preferably a phosphorothioate, phos-phorodithioate, (NR1R2)-phosphoramidate, phos-phate-O-methyl ester, phosphate-O-ethyl ester, phosphate-O-isopropyl ester, methylphosphonate or phenylphosphonate bridge, particularly preferably a phosphorothioate, phosphorodithio-ate or methylphosphonate bridge, and very particularly preferably a phosphorothioate bridge, where R1 and R2 are, independently of each other, hydrogen, or (C1-C18)-alkyl, (C6-C20)-aryl, (C6 C14)-aryl-(C1-C8)-alkyl or -(CH2)C-[NH(CH2)c]d-NR3R3, in which c is an integer of from 2 to 6, and d is an integer of from 0 to 6, and R3 are, independently of each other, hydrogen, (C1-C6)-alkyl or (C1-C4)-alkoxy-C1-C6-alkyl; prefer-ably, R1 and R2 are hydrogen, (C1-C8)-alkyl or methoxyethyl, particularly preferably hydrogen, (C1-C4)-alkyl or methoxyethyl, or R1 and R2, together with the nitrogen atom carrying them, form a 5-6-membered heterocyclic ring which can additionally contain a further hetero atom from the series O, S and N;
(b) formacetal, 3'-thioformacetal, methylhydroxyl-amine, oxime, methylenedimethylhydrazo, dimethylenesulfone or silyl groups, preferably formacetal and 3'-thioformacetals;
where, preferably, one, two or three phosphoric diester bridges are replaced at the 5' end and/or at the 3' end, preferably at the 5' end and at the 3' end, with it being preferable for the phosphoric diester bridges to be replaced at the pyrimidine positions;
(c) "morpholinonucleotiden-oligomer;
(d) .alpha.-D-2'-deoxyribose, L-2'-deoxyribose, 2'-F-2'-deoxyribose, 2'-O-(C1-C6)alkyl-ribose, 2'-O-(C2-C6)alkenyl-ribose, 2'-NH2-2'-deoxyribose, .beta.-D-xylofuranose, .alpha.-arabinofuranose, 2,4-di-deoxy-.beta.-D-erythrohexopyranose, or carbocyclic, open-chain or bicyclo sugar analogs, preferably as 2'-F-2'-deoxyribose, 2'-O-(C1-C6)alkyl-ribose, 2'-O-(C2-C6)alkenyl-ribose or 2'-NH2-2'-deoxyribose, particularly preferably as 2'-F-2'-deoxyribose, 2'-O-(C1-C4)alkyl-ribose, 2'-O-(C2-C4)alkenyl ribose or 2'-NH2-2'-deoxy-ribose, very particularly preferably as 2'-O-methyl-, 2'-O-allyl- or 2'-O-butyl-ribose, where, preferably, one, two or three ribose units are replaced at the 5' end and/or at the 3' end, preferably at the 5' end and at the 3' end, with the ribose units preferably being replaced at the pyrimidine positions;
(e) 5-(hydroxymethyl)uracil,5-aminouracil,pseudo-uracil, dihydrouracil, 5-(C1-C6)-alkyl-uracil, 5-(C2-C6)-alkenyl-uracil, 5-(C2-C6)-alkynyl-uracil, 5-(C1-C6)-alkyl-cytosine, 5-(C2-C6)-alkenyl-cytosine, 5-(C2-C6)-alkynyl-cytosine, 5-fluorouracil, 5-fluorocytosine, 5-chloro-uracil, 5-chlorocytosine, 5-bromouracil or 5-bromocytosine, preferably as 5-(C1-C6)-alkyl-uracil, 5-(C2-C6)-alkenyl-uracil, 5-(C2-C6)-alkynyl-uracil, 5-(C1-C6)-alkyl-cytosine, 5-(C2-C6)-alkenyl-cytosine, 5-(C2-C6)-alkynyl-cytosine, 5-fluorouracil, 5-fluorocytosine, 5-chlorouracil, 5-chlorocytosine, 5-bromouracil or 5-bromocytosine, particularly preferably as 5-(C3-C6)-alkyl-uracil, 5-(C2-C6)-alkenyl-uracil, 5-(C2-C6)-alkynyl-uracil, 5-(C1-C6)-alkyl-cytosine, 5-(C2-C6)-alkenyl-cytosine or 5-(C2-C6)-alkynyl-cytosine, very particularly preferably as 5-pentynylcytosine, 5-hexynyl-uracil or 5-hexynylcytosine, with the nucleoside bases not being replaced in the CAP regions, with preference being especially given to those of the abovementioned modifications included in groups a), b), c) and d), especially to those included in groups a) and d), and in particular to those included in group a).
(b) formacetal, 3'-thioformacetal, methylhydroxyl-amine, oxime, methylenedimethylhydrazo, dimethylenesulfone or silyl groups, preferably formacetal and 3'-thioformacetals;
where, preferably, one, two or three phosphoric diester bridges are replaced at the 5' end and/or at the 3' end, preferably at the 5' end and at the 3' end, with it being preferable for the phosphoric diester bridges to be replaced at the pyrimidine positions;
(c) "morpholinonucleotiden-oligomer;
(d) .alpha.-D-2'-deoxyribose, L-2'-deoxyribose, 2'-F-2'-deoxyribose, 2'-O-(C1-C6)alkyl-ribose, 2'-O-(C2-C6)alkenyl-ribose, 2'-NH2-2'-deoxyribose, .beta.-D-xylofuranose, .alpha.-arabinofuranose, 2,4-di-deoxy-.beta.-D-erythrohexopyranose, or carbocyclic, open-chain or bicyclo sugar analogs, preferably as 2'-F-2'-deoxyribose, 2'-O-(C1-C6)alkyl-ribose, 2'-O-(C2-C6)alkenyl-ribose or 2'-NH2-2'-deoxyribose, particularly preferably as 2'-F-2'-deoxyribose, 2'-O-(C1-C4)alkyl-ribose, 2'-O-(C2-C4)alkenyl ribose or 2'-NH2-2'-deoxy-ribose, very particularly preferably as 2'-O-methyl-, 2'-O-allyl- or 2'-O-butyl-ribose, where, preferably, one, two or three ribose units are replaced at the 5' end and/or at the 3' end, preferably at the 5' end and at the 3' end, with the ribose units preferably being replaced at the pyrimidine positions;
(e) 5-(hydroxymethyl)uracil,5-aminouracil,pseudo-uracil, dihydrouracil, 5-(C1-C6)-alkyl-uracil, 5-(C2-C6)-alkenyl-uracil, 5-(C2-C6)-alkynyl-uracil, 5-(C1-C6)-alkyl-cytosine, 5-(C2-C6)-alkenyl-cytosine, 5-(C2-C6)-alkynyl-cytosine, 5-fluorouracil, 5-fluorocytosine, 5-chloro-uracil, 5-chlorocytosine, 5-bromouracil or 5-bromocytosine, preferably as 5-(C1-C6)-alkyl-uracil, 5-(C2-C6)-alkenyl-uracil, 5-(C2-C6)-alkynyl-uracil, 5-(C1-C6)-alkyl-cytosine, 5-(C2-C6)-alkenyl-cytosine, 5-(C2-C6)-alkynyl-cytosine, 5-fluorouracil, 5-fluorocytosine, 5-chlorouracil, 5-chlorocytosine, 5-bromouracil or 5-bromocytosine, particularly preferably as 5-(C3-C6)-alkyl-uracil, 5-(C2-C6)-alkenyl-uracil, 5-(C2-C6)-alkynyl-uracil, 5-(C1-C6)-alkyl-cytosine, 5-(C2-C6)-alkenyl-cytosine or 5-(C2-C6)-alkynyl-cytosine, very particularly preferably as 5-pentynylcytosine, 5-hexynyl-uracil or 5-hexynylcytosine, with the nucleoside bases not being replaced in the CAP regions, with preference being especially given to those of the abovementioned modifications included in groups a), b), c) and d), especially to those included in groups a) and d), and in particular to those included in group a).
11.) An oligonucleotide as claimed in one of claims 1 to 10, which is linked, at the 5' end and/or the 3' end, to molecules selected from the group consisting of polylysine, intercalators, such as pyrene, acridine, phenazine and phenanthridine, fluorescent compounds, such as fluorescein, crosslinkers, such as psoralene and azidoproflavin, lipophilic mole-cules, such as (C12-C20)-alkyl, lipids, such as 1,2-dihexadecyl-rac-glycerol, steroids, such as choles-terol or testosterone, vitamins, such as vitamin E, and polyethylene glycol or oligoethylene glycol, (C12-C18)-alkyl-phosphate diesters or -O-CH2-CH(OH)-O-(C12-C18)-alkyl, preferably from lipophilic mole-cules, such as (C12-C20)-alkyl, and steroids, such as cholesterol or testosterone, polyethylene glycol or oligoethylene glycol, vitamin E, intercalators, such as pyrene, and (C14-C18)-alkyl-phosphate diesters and -O-CH2-CH(OH)-O-(C12-C16)-alkyl.
12.) An oligonucleotide as claimed in one of claims 1 to 11, which contains 3'-3' inversions and/or 5'-5' inversions at the 5' end and/or 3' end.
13.) A process for preparing an oligonucleotide as claimed in one of claims 1 to 12, which comprises synthesizing it chemically.
14.) A pharmaceutical, which contains one or more oligo-nucleotides as claimed in one of claims 1 to 12 and a physiologically acceptable excipient and also, where appropriate, suitable additives and/or auxili-ary substances.
15.) The use of an oligonucleotide as claimed in one of claims 1 to 12 for preparing a pharmaceutical for treating diseases which are caused by viruses, for treating cancer or restenosis, or for treating diseases which are influenced by integrins or cell-cell adhesion receptors or which are triggered by diffusible factors such as TNF-alpha.
16.) The use of an oligonucleotide as claimed in one of claims 1 to 12 for preparing a diagnoetic agent for diseases which are caused by viruses, for cancer or restenosie, or for diseases which are influenced by integrins or cell-cell adhesion receptors or are triggered by diffusible factors such as TNF-alpha.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19502912A DE19502912A1 (en) | 1995-01-31 | 1995-01-31 | G-Cap Stabilized Oligonucleotides |
DE19502912.7 | 1995-01-31 |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2168409A1 true CA2168409A1 (en) | 1996-08-01 |
CA2168409C CA2168409C (en) | 2010-06-29 |
Family
ID=7752688
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2168409A Expired - Fee Related CA2168409C (en) | 1995-01-31 | 1996-01-30 | G cap-stabilized oligonucleotides |
Country Status (11)
Country | Link |
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US (3) | US6013639A (en) |
EP (1) | EP0726274B1 (en) |
JP (1) | JP4118348B2 (en) |
AT (1) | ATE206715T1 (en) |
AU (1) | AU711792B2 (en) |
CA (1) | CA2168409C (en) |
DE (2) | DE19502912A1 (en) |
DK (1) | DK0726274T3 (en) |
ES (1) | ES2165443T3 (en) |
HK (1) | HK1012005A1 (en) |
PT (1) | PT726274E (en) |
Families Citing this family (118)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0642712U (en) * | 1992-11-16 | 1994-06-07 | 三笠産業株式会社 | Inner lid of container |
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-
1995
- 1995-01-31 DE DE19502912A patent/DE19502912A1/en not_active Withdrawn
- 1995-12-29 AU AU40747/95A patent/AU711792B2/en not_active Ceased
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1996
- 1996-01-25 DE DE59607853T patent/DE59607853D1/en not_active Expired - Lifetime
- 1996-01-25 EP EP96101018A patent/EP0726274B1/en not_active Expired - Lifetime
- 1996-01-25 PT PT96101018T patent/PT726274E/en unknown
- 1996-01-25 ES ES96101018T patent/ES2165443T3/en not_active Expired - Lifetime
- 1996-01-25 AT AT96101018T patent/ATE206715T1/en active
- 1996-01-25 DK DK96101018T patent/DK0726274T3/en active
- 1996-01-30 CA CA2168409A patent/CA2168409C/en not_active Expired - Fee Related
- 1996-01-31 US US08/594,452 patent/US6013639A/en not_active Expired - Fee Related
- 1996-01-31 JP JP01536396A patent/JP4118348B2/en not_active Expired - Fee Related
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1998
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1999
- 1999-02-26 US US09/258,408 patent/US6121434A/en not_active Expired - Lifetime
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ES2165443T3 (en) | 2002-03-16 |
DE59607853D1 (en) | 2001-11-15 |
EP0726274A3 (en) | 1998-01-07 |
DK0726274T3 (en) | 2002-02-04 |
US6013639A (en) | 2000-01-11 |
US20020151512A1 (en) | 2002-10-17 |
US7229974B2 (en) | 2007-06-12 |
AU711792B2 (en) | 1999-10-21 |
AU4074795A (en) | 1996-08-08 |
HK1012005A1 (en) | 1999-07-23 |
US6121434A (en) | 2000-09-19 |
PT726274E (en) | 2002-02-28 |
ATE206715T1 (en) | 2001-10-15 |
JP4118348B2 (en) | 2008-07-16 |
EP0726274A2 (en) | 1996-08-14 |
JPH08238093A (en) | 1996-09-17 |
CA2168409C (en) | 2010-06-29 |
DE19502912A1 (en) | 1996-08-01 |
EP0726274B1 (en) | 2001-10-10 |
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