CA2168409A1 - G cap-stabilized oligonucleotides - Google Patents

G cap-stabilized oligonucleotides

Info

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
Application number
CA002168409A
Other languages
French (fr)
Other versions
CA2168409C (en
Inventor
Anuschirwan Peyman
Eugen Uhlmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hoechst AG
Original Assignee
Hoechst AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Hoechst AG filed Critical Hoechst AG
Publication of CA2168409A1 publication Critical patent/CA2168409A1/en
Application granted granted Critical
Publication of CA2168409C publication Critical patent/CA2168409C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C12N15/1132—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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C12N15/1135—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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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.
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.
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.
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).
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.
CA2168409A 1995-01-31 1996-01-30 G cap-stabilized oligonucleotides Expired - Fee Related CA2168409C (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19502912.7 1995-01-31
DE19502912A DE19502912A1 (en) 1995-01-31 1995-01-31 G-Cap Stabilized Oligonucleotides

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
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)

* Cited by examiner, † Cited by third party
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
US6323185B1 (en) * 1993-04-23 2001-11-27 The United States Of America As Represented By The Department Of Health And Human Services Anti-viral guanosine-rich oligonucleotides and method of treating HIV
US6727230B1 (en) * 1994-03-25 2004-04-27 Coley Pharmaceutical Group, Inc. Immune stimulation by phosphorothioate oligonucleotide analogs
US20030026782A1 (en) * 1995-02-07 2003-02-06 Arthur M. Krieg Immunomodulatory oligonucleotides
US6207646B1 (en) 1994-07-15 2001-03-27 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
DE19502912A1 (en) * 1995-01-31 1996-08-01 Hoechst Ag G-Cap Stabilized Oligonucleotides
EP0910634A2 (en) * 1996-04-17 1999-04-28 Hoechst Marion Roussel Deutschland GmbH ANTISENSE INHIBITORS OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEgF/VPF) EXPRESSION
US9096636B2 (en) 1996-06-06 2015-08-04 Isis Pharmaceuticals, Inc. Chimeric oligomeric compounds and their use in gene modulation
US6776986B1 (en) 1996-06-06 2004-08-17 Novartis Ag Inhibition of HIV-1 replication by antisense RNA expression
US7812149B2 (en) 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
IL130192A0 (en) * 1996-12-27 2000-06-01 Icn Pharmaceuticals G-rich oligo aptamers and method of modulating an immune response
EP0917878A4 (en) * 1997-02-26 2004-05-19 Toray Industries Remedies for hepatitis
DE19750702A1 (en) * 1997-11-15 1999-05-27 Hoechst Marion Roussel De Gmbh Antisense oligonucleotides that bind to sequences encoding human tenascin for treating depigmentation, cancer, inflammation and cardiovascular disease
US20030022854A1 (en) 1998-06-25 2003-01-30 Dow Steven W. Vaccines using nucleic acid-lipid complexes
EP0979869A1 (en) * 1998-08-07 2000-02-16 Hoechst Marion Roussel Deutschland GmbH Short oligonucleotides for the inhibition of VEGF expression
EP0978561A1 (en) * 1998-08-07 2000-02-09 Hoechst Marion Roussel Deutschland GmbH Antisense oligonucleotides for the inhibition of VEGF expression
JP2002535015A (en) * 1999-01-29 2002-10-22 エイブイアイ バイオファーマ， インコーポレイテッド Non-invasive method for detecting target RNA
US7084125B2 (en) * 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
US20080318890A1 (en) * 1999-04-08 2008-12-25 Antisoma Research Limited Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin
JP2002541264A (en) 1999-04-08 2002-12-03 ユーエイビー・リサーチ・ファウンデーション Anti-proliferative activity of G-rich oligonucleotide and its use for binding to nucleolin
US20080318889A1 (en) * 1999-04-08 2008-12-25 Antisoma Research Limited Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin
US7960540B2 (en) * 1999-04-08 2011-06-14 Advanced Cancer Therapeutics, Llc Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin
US8114850B2 (en) * 1999-04-08 2012-02-14 Advanced Cancer Therapeutics, Llc Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin
DE19935303A1 (en) 1999-07-28 2001-02-08 Aventis Pharma Gmbh Oligonucleotides to inhibit the expression of human eg5
DE19935302A1 (en) * 1999-07-28 2001-02-08 Aventis Pharma Gmbh Conjugates and processes for their preparation and their use for the transport of molecules across biological membranes
US6949520B1 (en) * 1999-09-27 2005-09-27 Coley Pharmaceutical Group, Inc. Methods related to immunostimulatory nucleic acid-induced interferon
US7585847B2 (en) 2000-02-03 2009-09-08 Coley Pharmaceutical Group, Inc. Immunostimulatory nucleic acids for the treatment of asthma and allergy
WO2002022809A2 (en) * 2000-09-15 2002-03-21 Coley Pharmaceutical Gmbh PROCESS FOR HIGH THROUGHPUT SCREENING OF CpG-BASED IMMUNO-AGONIST/ANTAGONIST
EA200300473A1 (en) * 2000-10-16 2003-08-28 Неофарм, Инк. THERAPEUTIC COMPOSITION ON THE BASIS OF MITOXANTRON (OPTIONS) AND LIPID PREPARATION, THE METHOD OF ITS OBTAINING AND THE METHOD OF TREATING THE MAMMALISM DISEASE WITH ITS USE
ES2307568T3 (en) * 2000-12-08 2008-12-01 Coley Pharmaceutical Gmbh CPG TYPE NUCLEIC ACIDS AND SAME USE METHODS.
US6818787B2 (en) * 2001-06-11 2004-11-16 Xenoport, Inc. Prodrugs of GABA analogs, compositions and uses thereof
DE10226702A1 (en) * 2002-06-14 2004-09-09 Grünenthal GmbH Antisense oligonucleotides against PIM1
AR040996A1 (en) * 2002-08-19 2005-04-27 Coley Pharm Group Inc IMMUNE STIMULATING NUCLEIC ACIDS
CN1694959B (en) * 2002-09-13 2013-09-18 雷普利瑟公司 Non-sequence complementary antiviral oligonucleotides
US20050196382A1 (en) * 2002-09-13 2005-09-08 Replicor, Inc. Antiviral oligonucleotides targeting viral families
US20050282814A1 (en) * 2002-10-03 2005-12-22 Targegen, Inc. Vasculostatic agents and methods of use thereof
KR20110050745A (en) * 2002-10-03 2011-05-16 탈자진 인코포레이티드 Vasculostatic agents and methods of use thereof
CA2504929C (en) 2002-11-05 2014-07-22 Charles Allerson Compositions comprising alternating 2'-modified nucleosides for use in gene modulation
CA2504720C (en) 2002-11-05 2013-12-24 Isis Pharmaceuticals, Inc. Chimeric oligomeric compounds and their use in gene modulation
WO2004044141A2 (en) * 2002-11-05 2004-05-27 Isis Pharmaceuticals, Inc. Conjugated oligomeric compounds and their use in gene modulation
AU2003300919A1 (en) 2002-12-11 2004-06-30 Coley Pharmaceutical Gmbh 5' cpg nucleic acids and methods of use
US20040235770A1 (en) * 2003-04-02 2004-11-25 Coley Pharmaceutical Group, Ltd. Immunostimulatory nucleic acid oil-in-water formulations and related methods of use
CA2536139A1 (en) 2003-09-25 2005-04-07 Coley Pharmaceutical Group, Inc. Nucleic acid-lipophilic conjugates
US7480382B2 (en) * 2003-09-30 2009-01-20 Microsoft Corporation Image file container
US8569474B2 (en) 2004-03-09 2013-10-29 Isis Pharmaceuticals, Inc. Double stranded constructs comprising one or more short strands hybridized to a longer strand
CA2567574C (en) * 2004-04-08 2013-01-08 Targegen, Inc. Benzotriazine inhibitors of kinases
US8394947B2 (en) 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
EP1799656A4 (en) 2004-08-25 2009-09-02 Targegen Inc Heterocyclic compounds and methods of use
WO2006119619A1 (en) * 2005-05-06 2006-11-16 Replicor Inc. Oligonucleotides inhibiting cell proliferation
NZ563984A (en) * 2005-06-08 2011-11-25 Targegen Inc Methods and compositions for the treatment of ocular disorders
US8133900B2 (en) * 2005-11-01 2012-03-13 Targegen, Inc. Use of bi-aryl meta-pyrimidine inhibitors of kinases
KR101467723B1 (en) * 2005-11-01 2014-12-03 탈자진 인코포레이티드 Bi-aryl meta-pyrimidine inhibitors of kinases
US8604042B2 (en) * 2005-11-01 2013-12-10 Targegen, Inc. Bi-aryl meta-pyrimidine inhibitors of kinases
WO2007058323A1 (en) * 2005-11-17 2007-05-24 Napa Jenomics Co., Ltd. Method for production of nucleic acid homopolymer-bound functional nucleic acid medicine
JPWO2007058323A1 (en) * 2005-11-17 2009-05-07 Ｎａｐａ Ｊｅｎｏｍｉｃｓ 株式会社 Method for producing nucleic acid homopolymer-binding functional nucleic acid pharmaceutical
JP5713377B2 (en) 2005-12-28 2015-05-07 ザ スクリプス リサーチ インスティテュート Natural antisense and non-coding RNA transcripts as drug targets
US7691858B2 (en) * 2006-04-25 2010-04-06 Targegen, Inc. Kinase inhibitors and methods of use thereof
MX2009003398A (en) 2006-09-27 2009-08-12 Coley Pharm Gmbh Cpg oligonucleotide analogs containing hydrophobic t analogs with enhanced immunostimulatory activity.
US20090131351A1 (en) * 2007-11-16 2009-05-21 Antisoma Research Limited Methods, compositions, and kits for modulating tumor cell proliferation
CA2739464C (en) * 2008-10-03 2020-03-31 Opko Curna, Llc Treatment of apolipoprotein-a1 related diseases by inhibition of natural antisense transcript to apolipoprotein-a1
US8927511B2 (en) * 2008-12-04 2015-01-06 Curna, Inc. Treatment of vascular endothelial growth factor (VEGF) related diseases by inhibition of natural antisense transcript to VEGF
WO2010065787A2 (en) 2008-12-04 2010-06-10 Curna, Inc. Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene
CN102317458B (en) 2008-12-04 2018-01-02 库尔纳公司 Pass through treatment of the suppression of erythropoietin(EPO) (EPO) natural antisense transcript to EPO relevant diseases
JP5766126B2 (en) 2009-02-12 2015-08-19 クルナ・インコーポレーテッド Treatment of brain-derived neurotrophic factor (BDNF) -related diseases by suppression of natural antisense transcripts against BDNF
CN102482677B (en) 2009-03-16 2017-10-17 库尔纳公司 Nuclear factor (red blood cell derives 2) sample 2 (NRF2) relevant disease is treated by suppressing NRF2 natural antisense transcript
CN102549159B (en) 2009-03-17 2016-08-10 库尔纳公司 By suppressing to treat the disease that DLK1 is correlated with for the natural antisense transcript of δ sample 1 congener (DLK1)
ES2609655T3 (en) 2009-05-06 2017-04-21 Curna, Inc. Treatment of diseases related to tristetraproline (TTP) by inhibition of natural antisense transcript for TTP
WO2010129799A2 (en) 2009-05-06 2010-11-11 Curna, Inc. Treatment of lipid transport and metabolism gene related diseases by inhibition of natural antisense transcript to a lipid transport and metabolism gene
WO2010129861A2 (en) 2009-05-08 2010-11-11 Curna, Inc. Treatment of dystrophin family related diseases by inhibition of natural antisense transcript to dmd family
EP2432881B1 (en) 2009-05-18 2017-11-15 CuRNA, Inc. Treatment of reprogramming factor related diseases by inhibition of natural antisense transcript to a reprogramming factor
WO2010135695A2 (en) 2009-05-22 2010-11-25 Curna, Inc. TREATMENT OF TRANSCRIPTION FACTOR E3 (TFE3) and INSULIN RECEPTOR SUBSTRATE 2 (IRS2) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT TO TFE3
ES2618576T3 (en) 2009-05-28 2017-06-21 Curna, Inc. Treatment of diseases related to an antiviral gene by inhibiting a natural antisense transcript to an antiviral gene
JP6128846B2 (en) 2009-06-16 2017-05-17 クルナ・インコーポレーテッド Treatment of PON1 gene-related diseases by suppression of natural antisense transcripts against paraoxonase (PON1)
WO2010148050A2 (en) 2009-06-16 2010-12-23 Curna, Inc. Treatment of collagen gene related diseases by inhibition of natural antisense transcript to a collagen gene
WO2010151671A2 (en) 2009-06-24 2010-12-29 Curna, Inc. Treatment of tumor necrosis factor receptor 2 (tnfr2) related diseases by inhibition of natural antisense transcript to tnfr2
CA2765815A1 (en) 2009-06-26 2010-12-29 Opko Curna, Llc Treatment of down syndrome gene related diseases by inhibition of natural antisense transcript to a down syndrome gene
CA2768947C (en) 2009-07-24 2018-06-19 Opko Curna, Llc Treatment of sirtuin (sirt) related diseases by inhibition of natural antisense transcript to a sirtuin (sirt)
CA2769665A1 (en) 2009-08-05 2011-02-10 Opko Curna, Llc Treatment of insulin gene (ins) related diseases by inhibition of natural antisense transcript to an insulin gene (ins)
ES2599986T3 (en) 2009-08-11 2017-02-06 Curna, Inc. Treatment of adiponectin-related diseases (ADIPOQ) by inhibiting a natural antisense transcript of an adiponectin (ADIPOQ)
EP2982755B1 (en) 2009-08-21 2020-10-07 CuRNA, Inc. Treatment of 'c terminus of hsp70-interacting protein' (chip) related diseases by inhibition of natural antisense transcript to chip
KR101892760B1 (en) 2009-08-25 2018-08-28 큐알엔에이, 인크. Treatment of 'iq motif containing gtpase activating protein' (iqgap) related diseases by inhibition of natural antisense transcript to iqgap
CA2775111C (en) 2009-09-25 2019-12-31 Opko Curna, Llc Treatment of filaggrin (flg) related diseases by modulation of flg expression and activity
NO2513310T3 (en) 2009-12-16 2018-03-31
US9068183B2 (en) 2009-12-23 2015-06-30 Curna, Inc. Treatment of uncoupling protein 2 (UCP2) related diseases by inhibition of natural antisense transcript to UCP2
CN102869776B (en) 2009-12-23 2017-06-23 库尔纳公司 HGF relevant diseases are treated by suppressing the natural antisense transcript of HGF (HGF)
CA2785173A1 (en) 2009-12-29 2011-07-28 Curna, Inc. Treatment of nuclear respiratory factor 1 (nrf1) related diseases by inhibition of natural antisense transcript to nrf1
KR101853508B1 (en) 2009-12-29 2018-06-20 큐알엔에이, 인크. TREATMENT OF TUMOR PROTEIN 63 (p63) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT TO p63
ES2677044T3 (en) 2009-12-31 2018-07-27 Curna, Inc. Treatment of diseases related to insulin receptor substrate 2 (IRS2) by inhibition of natural antisense transcript for IRS2 and transcription factor E3 (TFE3)
US8946181B2 (en) 2010-01-04 2015-02-03 Curna, Inc. Treatment of interferon regulatory factor 8 (IRF8) related diseases by inhibition of natural antisense transcript to IRF8
RU2612161C2 (en) 2010-01-06 2017-03-02 Курна, Инк. Treatment of pancreatic developmental gene related diseases by inhibition of natural antisense transcript to pancreatic developmental gene
WO2011085347A2 (en) 2010-01-11 2011-07-14 Opko Curna, Llc Treatment of sex hormone binding globulin (shbg) related diseases by inhibition of natural antisense transcript to shbg
CN102782135A (en) 2010-01-25 2012-11-14 库尔纳公司 Treatment of RNase H1 related diseases by inhibition of natural antisense transcript to RNase H1
CA2790506A1 (en) 2010-02-22 2011-08-25 Curna, Inc. Treatment of pyrroline-5-carboxylate reductase 1 (pycr1) related diseases by inhibition of natural antisense transcript to pycr1
CN102869777B (en) 2010-04-02 2018-11-02 库尔纳公司 CSF3 relevant diseases are treated by inhibiting the natural antisense transcript of colony stimulating factor 3 (CSF3)
TWI644675B (en) 2010-04-09 2018-12-21 可娜公司 Treatment of fibroblast growth factor 21 (fgf21) related diseases by inhibition of natural antisense transcript to fgf21
WO2011133871A2 (en) * 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. 5'-end derivatives
CN107988228B (en) 2010-05-03 2022-01-25 库尔纳公司 Treatment of Sirtuin (SIRT) related diseases by inhibition of natural antisense transcript to Sirtuin (SIRT)
TWI531370B (en) 2010-05-14 2016-05-01 可娜公司 Treatment of par4 related diseases by inhibition of natural antisense transcript to par4
DK2576783T3 (en) 2010-05-26 2018-03-12 Curna Inc TREATMENT OF ATONAL HOMOLOGY 1- (ATOH1) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENCE TRANSCRIPTS AT ATOH1
DK2576784T3 (en) 2010-05-26 2018-02-26 Curna Inc TREATMENT OF METHIONIN SULPHOXIDE REDUCTASE A (MSRA) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENCE TRANSCRIPTION TO MSRA
CA2803882C (en) 2010-06-23 2022-10-18 Opko Curna, Llc Treatment of sodium channel, voltage-gated, alpha subunit (scna) related diseases by inhibition of natural antisense transcript to scna
NO2593547T3 (en) 2010-07-14 2018-04-14
RU2624048C2 (en) 2010-10-06 2017-06-30 Курна, Инк. Treatment of diseases associated with the sialidase 4 (neu4) gene, by gene neu4 natural antisense transcript inhibition
JP6049623B2 (en) 2010-10-22 2016-12-21 カッパーアールエヌエー，インコーポレイテッド Treatment of IDUA-related diseases by inhibition of natural antisense transcripts to α-L-iduronidase (IDUA)
AU2010363329A1 (en) 2010-11-07 2013-05-09 Targegen, Inc. Compositions and methods for treating myelofibrosis
US10000752B2 (en) 2010-11-18 2018-06-19 Curna, Inc. Antagonat compositions and methods of use
JP6071893B2 (en) 2010-11-23 2017-02-01 カッパーアールエヌエー，インコーポレイテッド Treatment of NANOG-related diseases by inhibition of natural antisense transcripts to NANOG
CN103620036B (en) 2011-06-09 2016-12-21 库尔纳公司 FXN relevant disease is treated by the natural antisense transcript of suppression Frataxin (FXN)
KR101991980B1 (en) 2011-09-06 2019-06-21 큐알엔에이, 인크. TREATMENT OF DISEASES RELATED TO ALPHA SUBUNITS OF SODIUM CHANNELS, VOLTAGE-GATED (SCNxA) WITH SMALL MOLECULES
EP2568289A3 (en) 2011-09-12 2013-04-03 International AIDS Vaccine Initiative Immunoselection of recombinant vesicular stomatitis virus expressing hiv-1 proteins by broadly neutralizing antibodies
US9402894B2 (en) 2011-10-27 2016-08-02 International Aids Vaccine Initiative Viral particles derived from an enveloped virus
ES2694592T3 (en) 2012-03-15 2018-12-21 Curna, Inc. Treatment of diseases related to brain-derived neurotrophic factor (BDNF) by inhibition of the natural antisense transcript of BDNF
US9347065B2 (en) 2012-03-29 2016-05-24 International Aids Vaccine Initiative Methods to improve vector expression and genetic stability
WO2015012060A1 (en) * 2013-07-23 2015-01-29 Ｎｅｃソリューションイノベータ株式会社 Sensor for target analysis, device for target analysis, and target analysis method using same
CN113797349A (en) * 2015-01-16 2021-12-17 希望之城 Cell penetrating antibodies
AU2016359629B2 (en) 2015-11-23 2023-03-09 Ranjan BATRA Tracking and manipulating cellular RNA via nuclear delivery of CRISPR/Cas9
JP7398279B2 (en) 2017-05-10 2023-12-14 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Targeted editing of cellular RNA by CRISPR/CAS9 nuclear delivery
WO2020214830A1 (en) * 2019-04-16 2020-10-22 The Regents Of The University Of California Protein translational control

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4514577A (en) 1982-10-15 1985-04-30 Ethyl Corporation Chemical process for preparing di-ortho benzyl phenols
US5514577A (en) * 1990-02-26 1996-05-07 Isis Pharmaceuticals, Inc. Oligonucleotide therapies for modulating the effects of herpes viruses
JPH07501314A (en) * 1991-05-10 1995-02-09 ハイブライドン　インコーポレイテッド 3'-end-capped oligonucleotide
JPH06508130A (en) * 1991-05-23 1994-09-14 テンプル　ユニバーシティ−オブ　ザ　コモンウェルス　システム　オブ　ハイヤー　エデュケーション Treatment of colorectal cancer with antisense oligonucleotides against the c-myb proto-oncogene
KR930016437A (en) * 1992-01-22 1993-08-26 귀틀라인, 슈미트 Oligonucleotide Analogues, Methods for Making and Uses thereof
AU678769B2 (en) * 1992-07-27 1997-06-12 Hybridon, Inc. Oligonucleotide alkylphosphonothioates
DE4321946A1 (en) * 1993-07-01 1995-01-12 Hoechst Ag Methylphosphonic acid esters, process for their preparation and their use
DE4408528A1 (en) * 1994-03-14 1995-09-28 Hoechst Ag Peptide oligonucleotide derivatives, their preparation and use
DE19502912A1 (en) * 1995-01-31 1996-08-01 Hoechst Ag G-Cap Stabilized Oligonucleotides

Also Published As

Publication number Publication date
AU4074795A (en) 1996-08-08
US6121434A (en) 2000-09-19
EP0726274A3 (en) 1998-01-07
AU711792B2 (en) 1999-10-21
US6013639A (en) 2000-01-11
ATE206715T1 (en) 2001-10-15
HK1012005A1 (en) 1999-07-23
US7229974B2 (en) 2007-06-12
JP4118348B2 (en) 2008-07-16
DK0726274T3 (en) 2002-02-04
CA2168409C (en) 2010-06-29
JPH08238093A (en) 1996-09-17
PT726274E (en) 2002-02-28
ES2165443T3 (en) 2002-03-16
DE19502912A1 (en) 1996-08-01
US20020151512A1 (en) 2002-10-17
EP0726274A2 (en) 1996-08-14
DE59607853D1 (en) 2001-11-15
EP0726274B1 (en) 2001-10-10

Similar Documents

Publication Publication Date Title
CA2168409A1 (en) G cap-stabilized oligonucleotides
AU696635B2 (en) Stabilized oligonucleotides and their use
CA2217780C (en) Polyether nucleic acids
NZ516839A (en) Oligonucleotides for inhibiting the expression of human mitotic kinesin related motor protein eg5
KR20010085347A (en) Short oligonucleotides for the inhibition of VEGF expression
US20050159375A1 (en) Novel oligonucleotides and related compounds
JP2018109015A (en) Tricyclic nucleosides and oligomeric compounds prepared therefrom
RU2010104618A (en) MOTIVES OF RNA SEQUENCE IN THE CONTEXT OF DEFINED INTERNUCLEOTIDE BINDS, INDUCING SPECIFIC IMMUNOMODULATING PROFILES
EP2976351B1 (en) Lipohillic oligonucleotide analogs
MXPA02009953A (en) Polyamide nucleic acid derivatives, agents and methods for producing them.
EP0978561A1 (en) Antisense oligonucleotides for the inhibition of VEGF expression
AU2001246536B2 (en) Polyamide nucleic acid derivatives, agents and methods for producing the same
US6017895A (en) Oligonucleotides possessing zwitterionic moieties
Yang et al. Synthesis and duplex stabilization of oligonucleotides consisting of isonucleosides
WO1994015620A1 (en) Novel oligonucleotides modified with non-nucleotide bridging groups
WO1997027206A1 (en) Oligonucleotide analogs
Meng Synthesis and binding of oligonucleotides containing 2'-modified sulfide-or sulfone-linked dimers
MXPA01000908A (en) Short oligonucleotides for the inhibition of vegf expression

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20160201