CA2398432C - Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides - Google Patents
Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides Download PDFInfo
- Publication number
- CA2398432C CA2398432C CA2398432A CA2398432A CA2398432C CA 2398432 C CA2398432 C CA 2398432C CA 2398432 A CA2398432 A CA 2398432A CA 2398432 A CA2398432 A CA 2398432A CA 2398432 C CA2398432 C CA 2398432C
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- CA
- Canada
- Prior art keywords
- nucleoside
- cpg dinucleotide
- oligonucleotide
- cpg
- dinucleotide
- 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.)
- Expired - Fee Related
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- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 287
- 239000002777 nucleoside Substances 0.000 title claims description 336
- 125000003835 nucleoside group Chemical group 0.000 title description 13
- 230000004048 modification Effects 0.000 title description 6
- 238000012986 modification Methods 0.000 title description 6
- 230000000638 stimulation Effects 0.000 title description 4
- 230000001404 mediated effect Effects 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 100
- 230000003308 immunostimulating effect Effects 0.000 claims abstract description 58
- 230000001965 increasing effect Effects 0.000 claims abstract description 21
- 230000028993 immune response Effects 0.000 claims abstract description 17
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 319
- 108091029430 CpG site Proteins 0.000 claims description 288
- 241000124008 Mammalia Species 0.000 claims description 22
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 19
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 19
- 239000002773 nucleotide Substances 0.000 claims description 13
- 125000003729 nucleotide group Chemical group 0.000 claims description 13
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims description 11
- 125000005600 alkyl phosphonate group Chemical group 0.000 claims description 10
- 235000000346 sugar Nutrition 0.000 claims description 8
- 150000008163 sugars Chemical class 0.000 claims description 6
- 230000001939 inductive effect Effects 0.000 claims description 5
- 230000002708 enhancing effect Effects 0.000 claims description 4
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- CTMZLDSMFCVUNX-VMIOUTBZSA-N cytidylyl-(3'->5')-guanosine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=C(C(N=C(N)N3)=O)N=C2)O)[C@@H](CO)O1 CTMZLDSMFCVUNX-VMIOUTBZSA-N 0.000 description 57
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- 230000024203 complement activation Effects 0.000 description 6
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- 125000003277 amino group Chemical group 0.000 description 5
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- -1 carbalkoxyl Chemical group 0.000 description 4
- 238000001516 cell proliferation assay Methods 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000002342 ribonucleoside Substances 0.000 description 4
- 210000004989 spleen cell Anatomy 0.000 description 4
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- 102000009016 Cholera Toxin Human genes 0.000 description 3
- 108010049048 Cholera Toxin Proteins 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000011284 combination treatment Methods 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000003292 diminished effect Effects 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 150000002972 pentoses Chemical class 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 2
- 150000008298 phosphoramidates Chemical class 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- JUDOLRSMWHVKGX-UHFFFAOYSA-N 1,1-dioxo-1$l^{6},2-benzodithiol-3-one Chemical compound C1=CC=C2C(=O)SS(=O)(=O)C2=C1 JUDOLRSMWHVKGX-UHFFFAOYSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
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- 108091007433 antigens Proteins 0.000 description 1
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- 210000003719 b-lymphocyte Anatomy 0.000 description 1
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- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 101150024925 cpg-7 gene Proteins 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical compound OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 125000000625 hexosyl group Chemical group 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000031942 natural killer cell mediated cytotoxicity Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 150000003291 riboses Chemical class 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
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
- C12N15/117—Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
-
- 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
- C12N2310/18—Type of nucleic acid acting by a non-sequence specific mechanism
-
- 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
-
- 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
- C12N2310/312—Phosphonates
- C12N2310/3125—Methylphosphonates
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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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
-
- 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
- C12N2310/319—Chemical structure of the backbone linked by 2'-5' linkages, i.e. having a free 3'-position
-
- 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
- C12N2310/32—Chemical structure of the sugar
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17856200P | 2000-01-26 | 2000-01-26 | |
| US60/178,562 | 2000-01-26 | ||
| PCT/US2001/002681 WO2001055370A2 (en) | 2000-01-26 | 2001-01-26 | MODULATION OF OLIGONUCLEOTIDE CpG-MEDIATED IMMUNE STIMULATION BY POSITIONAL MODIFICATION OF NUCLEOSIDES |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2398432A1 CA2398432A1 (en) | 2001-08-02 |
| CA2398432C true CA2398432C (en) | 2012-06-19 |
Family
ID=22653030
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2398432A Expired - Fee Related CA2398432C (en) | 2000-01-26 | 2001-01-26 | Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides |
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| EP (1) | EP1252307B1 (enExample) |
| JP (2) | JP4443810B2 (enExample) |
| AT (1) | ATE382690T1 (enExample) |
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| CA (1) | CA2398432C (enExample) |
| DE (1) | DE60132170T2 (enExample) |
| WO (1) | WO2001055370A2 (enExample) |
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| US7935675B1 (en) * | 1994-07-15 | 2011-05-03 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US20030022854A1 (en) | 1998-06-25 | 2003-01-30 | Dow Steven W. | Vaccines using nucleic acid-lipid complexes |
| US6949520B1 (en) | 1999-09-27 | 2005-09-27 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| AU9475001A (en) * | 2000-09-26 | 2002-04-08 | Hybridon Inc | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
| US7785610B2 (en) * | 2001-06-21 | 2010-08-31 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same—III |
| AU2002345847B2 (en) | 2001-06-21 | 2008-05-29 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same |
| JP4607452B2 (ja) | 2001-08-07 | 2011-01-05 | ダイナバックス テクノロジーズ コーポレイション | 免疫調節性組成物、製剤およびその使用方法 |
| US8834900B2 (en) | 2001-08-17 | 2014-09-16 | University Of Iowa Research Foundation | Combination motif immune stimulatory oligonucleotides with improved activity |
| US7276489B2 (en) * | 2002-10-24 | 2007-10-02 | Idera Pharmaceuticals, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5′ ends |
| CA2388049A1 (en) | 2002-05-30 | 2003-11-30 | Immunotech S.A. | Immunostimulatory oligonucleotides and uses thereof |
| AR040996A1 (es) | 2002-08-19 | 2005-04-27 | Coley Pharm Group Inc | Acidos nucleicos inmunoestimuladores |
| WO2004053104A2 (en) | 2002-12-11 | 2004-06-24 | Coley Pharmaceutical Group, Inc. | 5’ cpg nucleic acids and methods of use |
| PT1575977E (pt) | 2002-12-23 | 2009-12-15 | Dynavax Tech Corp | Oligonucleótidos de sequência imunoestimuladora e métodos de utilização dos mesmos |
| US8158768B2 (en) | 2002-12-23 | 2012-04-17 | Dynavax Technologies Corporation | Immunostimulatory sequence oligonucleotides and methods of using the same |
| CA2512484A1 (en) | 2003-01-16 | 2004-05-08 | Hybridon, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by utilizing modified immunostimulatory dinucleotides |
| US7354907B2 (en) | 2003-02-07 | 2008-04-08 | Idera Pharmaceuticals, Inc. | Short immunomodulatory oligonucleotides |
| ATE491463T1 (de) | 2003-02-20 | 2011-01-15 | Univ Connecticut Health Ct | Verfahren zur herstellung von alpha (2) makroglobulin-antigen-molekül-komplexen |
| JP2006528697A (ja) | 2003-05-16 | 2006-12-21 | イデラ ファーマシューティカルズ インコーポレイテッド | イムノマーを化学療法剤と組み合わせて用いる、癌の相乗的処置 |
| KR101126030B1 (ko) | 2003-07-15 | 2012-03-19 | 이데라 파마슈티칼즈, 인코포레이티드 | 사이토킨 및/또는 화학치료제 또는 방사선 치료와 연계하여면역자극 올리고누클레오티드 및/또는 이뮤노머 화합물을이용하여 면역계를 공동 상승 자극시키는 방법 |
| AU2004275876B2 (en) | 2003-09-25 | 2011-03-31 | Coley Pharmaceutical Gmbh | Nucleic acid-lipophilic conjugates |
| BRPI0416079A (pt) | 2003-10-30 | 2007-01-02 | Coley Pharm Gmbh | análogos de oligonucleotìdeos de classe c com uma potência imunoestimuladora aumentada |
| EP1699814A4 (en) | 2003-12-08 | 2009-01-14 | Hybridon Inc | MODULATION OF IMMUNOSTIMULATORY PROPERTIES OF COMPOUNDS FORMED FROM SMALL OLIGONUCLEOTIDES |
| JP2008501807A (ja) * | 2004-06-08 | 2008-01-24 | コーリー ファーマシューティカル ゲーエムベーハー | 抗原ならびに免疫活性化アゴニストおよび免疫活性化アンタゴニストのための担体基本骨格としての無塩基オリゴヌクレオチド |
| MY159370A (en) | 2004-10-20 | 2016-12-30 | Coley Pharm Group Inc | Semi-soft-class immunostimulatory oligonucleotides |
| AU2005313883B2 (en) * | 2004-12-09 | 2011-03-31 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inducing an immune response in a mammal and methods of avoiding an immune response to oligonucleotide agents such as short interfering RNAs |
| ES2542989T3 (es) | 2005-10-12 | 2015-08-13 | Idera Pharmaceuticals, Inc. | Compuestos oligonucleótidos inmuno reguladores (IRO) para modular la respuesta inmune basada en receptor semejante a Toll |
| US7470674B2 (en) | 2005-11-07 | 2008-12-30 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| US7776834B2 (en) * | 2005-11-07 | 2010-08-17 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| EP1942945B1 (en) | 2005-11-07 | 2011-10-19 | Idera Pharmaceuticals | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| MX2009003398A (es) | 2006-09-27 | 2009-08-12 | Coley Pharm Gmbh | Analogos de oligonucleotidos cpg que contienen analogos t hidrofobos con actividad inmunoestimuladora mejorada. |
| KR20110071108A (ko) * | 2008-10-06 | 2011-06-28 | 이데라 파마슈티칼즈, 인코포레이티드 | 고콜레스테롤혈증 및 고지혈증 및 이에 관련된 질병의 예방 및 치료에서 톨-유사 수용체의 저해제의 용도 |
| MX2011010050A (es) | 2009-03-25 | 2011-12-14 | Univ Texas | Composiciones para estimulación de resistencia inmune innata de mamiferos a patógenos. |
| US8486908B2 (en) | 2010-11-19 | 2013-07-16 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response |
| US10202615B2 (en) | 2010-12-10 | 2019-02-12 | Vanderbilt University | Mammalian genes involved in toxicity and infection |
| FR2975600B1 (fr) | 2011-05-24 | 2013-07-05 | Assist Publ Hopitaux De Paris | Agents pour le traitement de tumeurs |
| WO2016044839A2 (en) | 2014-09-19 | 2016-03-24 | The Board Of Regents Of The University Of Texas System | Compositions and methods for treating viral infections through stimulated innate immunity in combination with antiviral compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5149798A (en) | 1989-04-06 | 1992-09-22 | Worcester Foundation For Experimental Biology | Process for synthesizing oligonucleotides and their analogs adaptable to large scale syntheses |
| US5532130A (en) | 1993-07-20 | 1996-07-02 | Dyad Pharmaceutical Corporation | Methods and compositions for sequence-specific hybridization of RNA by 2'-5' oligonucleotides |
| US5801154A (en) * | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| US5886165A (en) * | 1996-09-24 | 1999-03-23 | Hybridon, Inc. | Mixed backbone antisense oligonucleotides containing 2'-5'-ribonucleotide- and 3'-5'-deoxyribonucleotides segments |
| US6426334B1 (en) * | 1997-04-30 | 2002-07-30 | Hybridon, Inc. | Oligonucleotide mediated specific cytokine induction and reduction of tumor growth in a mammal |
-
2001
- 2001-01-26 US US09/770,602 patent/US6815429B2/en not_active Expired - Fee Related
- 2001-01-26 CA CA2398432A patent/CA2398432C/en not_active Expired - Fee Related
- 2001-01-26 WO PCT/US2001/002681 patent/WO2001055370A2/en not_active Ceased
- 2001-01-26 AT AT01903365T patent/ATE382690T1/de not_active IP Right Cessation
- 2001-01-26 JP JP2001554399A patent/JP4443810B2/ja not_active Expired - Fee Related
- 2001-01-26 EP EP01903365A patent/EP1252307B1/en not_active Expired - Lifetime
- 2001-01-26 AU AU31193/01A patent/AU783687B2/en not_active Ceased
- 2001-01-26 DE DE60132170T patent/DE60132170T2/de not_active Expired - Lifetime
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2002
- 2002-12-09 US US10/314,647 patent/US7329648B2/en not_active Expired - Fee Related
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2009
- 2009-08-03 JP JP2009180403A patent/JP2009292829A/ja active Pending
Also Published As
| Publication number | Publication date |
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| EP1252307A2 (en) | 2002-10-30 |
| JP2003520811A (ja) | 2003-07-08 |
| JP4443810B2 (ja) | 2010-03-31 |
| WO2001055370A3 (en) | 2002-01-17 |
| US20030186912A1 (en) | 2003-10-02 |
| US6815429B2 (en) | 2004-11-09 |
| DE60132170T2 (de) | 2008-12-18 |
| WO2001055370A2 (en) | 2001-08-02 |
| DE60132170D1 (de) | 2008-02-14 |
| EP1252307B1 (en) | 2008-01-02 |
| US20020055475A1 (en) | 2002-05-09 |
| ATE382690T1 (de) | 2008-01-15 |
| AU3119301A (en) | 2001-08-07 |
| JP2009292829A (ja) | 2009-12-17 |
| CA2398432A1 (en) | 2001-08-02 |
| AU783687B2 (en) | 2005-11-24 |
| WO2001055370A9 (en) | 2002-10-17 |
| US7329648B2 (en) | 2008-02-12 |
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