CA2512934A1 - Short immunomodulatory oligonucleotides - Google Patents
Short immunomodulatory oligonucleotides Download PDFInfo
- Publication number
- CA2512934A1 CA2512934A1 CA002512934A CA2512934A CA2512934A1 CA 2512934 A1 CA2512934 A1 CA 2512934A1 CA 002512934 A CA002512934 A CA 002512934A CA 2512934 A CA2512934 A CA 2512934A CA 2512934 A1 CA2512934 A1 CA 2512934A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- vertebrate
- nucleoside
- immunomer
- immunomers
- 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.)
- Abandoned
Links
- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 34
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 title abstract description 13
- 230000002519 immonomodulatory effect Effects 0.000 title description 2
- 241000699670 Mus sp. Species 0.000 claims description 16
- 239000002777 nucleoside Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 14
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 239000002773 nucleotide Substances 0.000 claims description 7
- 241000283690 Bos taurus Species 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- -1 N4-alkyl-cytosine Chemical compound 0.000 claims description 6
- 239000002215 arabinonucleoside Substances 0.000 claims description 6
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 6
- 229940104302 cytosine Drugs 0.000 claims description 6
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 6
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 6
- 125000003729 nucleotide group Chemical group 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 208000035657 Abasia Diseases 0.000 claims description 4
- 230000028993 immune response Effects 0.000 claims description 4
- 150000002972 pentoses Chemical class 0.000 claims description 4
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 claims description 3
- 241000251468 Actinopterygii Species 0.000 claims description 3
- 241000282472 Canis lupus familiaris Species 0.000 claims description 3
- 241000283086 Equidae Species 0.000 claims description 3
- 241000282326 Felis catus Species 0.000 claims description 3
- 241000282412 Homo Species 0.000 claims description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 3
- 241000700159 Rattus Species 0.000 claims description 3
- 241000282887 Suidae Species 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- MRWXACSTFXYYMV-FDDDBJFASA-N nebularine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC=C2N=C1 MRWXACSTFXYYMV-FDDDBJFASA-N 0.000 claims description 3
- 239000002212 purine nucleoside Substances 0.000 claims description 3
- 239000002718 pyrimidine nucleoside Substances 0.000 claims description 3
- NLLCDONDZDHLCI-UHFFFAOYSA-N 6-amino-5-hydroxy-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1O NLLCDONDZDHLCI-UHFFFAOYSA-N 0.000 claims description 2
- 239000013566 allergen Substances 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 229940088710 antibiotic agent Drugs 0.000 claims description 2
- 241000271566 Aves Species 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- 108010041986 DNA Vaccines Proteins 0.000 claims 1
- 229940021995 DNA vaccine Drugs 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 208000037883 airway inflammation Diseases 0.000 claims 1
- 208000026935 allergic disease Diseases 0.000 claims 1
- 230000007815 allergy Effects 0.000 claims 1
- 229940037003 alum Drugs 0.000 claims 1
- 239000000427 antigen Substances 0.000 claims 1
- 102000036639 antigens Human genes 0.000 claims 1
- 108091007433 antigens Proteins 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 229940044683 chemotherapy drug Drugs 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 244000052769 pathogen Species 0.000 claims 1
- 230000001717 pathogenic effect Effects 0.000 claims 1
- 229960005486 vaccine Drugs 0.000 claims 1
- 230000003308 immunostimulating effect Effects 0.000 abstract description 14
- 230000000638 stimulation Effects 0.000 abstract description 10
- 210000000987 immune system Anatomy 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 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 30
- 108020004414 DNA Proteins 0.000 description 20
- 238000004113 cell culture Methods 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 241000699666 Mus <mouse, genus> Species 0.000 description 16
- 210000004989 spleen cell Anatomy 0.000 description 16
- 102000004127 Cytokines Human genes 0.000 description 15
- 108090000695 Cytokines Proteins 0.000 description 15
- 230000006698 induction Effects 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 102000013462 Interleukin-12 Human genes 0.000 description 12
- 108010065805 Interleukin-12 Proteins 0.000 description 12
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 11
- 230000028327 secretion Effects 0.000 description 11
- 102000004889 Interleukin-6 Human genes 0.000 description 9
- 108090001005 Interleukin-6 Proteins 0.000 description 9
- 230000004913 activation Effects 0.000 description 9
- 239000002342 ribonucleoside Substances 0.000 description 9
- 210000002540 macrophage Anatomy 0.000 description 7
- 210000000952 spleen Anatomy 0.000 description 7
- 102000000743 Interleukin-5 Human genes 0.000 description 6
- 108010002616 Interleukin-5 Proteins 0.000 description 6
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 6
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 125000003835 nucleoside group Chemical group 0.000 description 5
- 241000894007 species Species 0.000 description 5
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 5
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 4
- 238000011725 BALB/c mouse Methods 0.000 description 4
- 238000011740 C57BL/6 mouse Methods 0.000 description 4
- 108010026206 Conalbumin Proteins 0.000 description 4
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical class 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 4
- 241000699660 Mus musculus Species 0.000 description 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- 150000008209 arabinosides Chemical class 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000011580 nude mouse model Methods 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 150000004713 phosphodiesters Chemical class 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 108091029430 CpG site Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 108091093037 Peptide nucleic acid Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 3
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 150000001480 arabinoses Chemical class 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- 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
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000239218 Limulus Species 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 206010041235 Snoring Diseases 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000008369 airway response Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000001369 canonical nucleoside group Chemical group 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000006166 lysate 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
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 108010041420 microbial alkaline proteinase inhibitor Proteins 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 108090000765 processed proteins & peptides Chemical group 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 102220223812 rs1060501208 Human genes 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008229 sterile water for irrigation Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- A61P37/08—Antiallergic agents
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Epidemiology (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 |
|---|---|---|---|
| US10/361,111 | 2003-02-07 | ||
| US10/361,111 US7354907B2 (en) | 2003-02-07 | 2003-02-07 | Short immunomodulatory oligonucleotides |
| PCT/US2004/000789 WO2004071468A2 (en) | 2003-02-07 | 2004-01-13 | Short immunomodulatory oligonucleotides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2512934A1 true CA2512934A1 (en) | 2004-08-26 |
Family
ID=32824138
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002512934A Abandoned CA2512934A1 (en) | 2003-02-07 | 2004-01-13 | Short immunomodulatory oligonucleotides |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US7354907B2 (https=) |
| EP (1) | EP1594432A4 (https=) |
| JP (1) | JP2007531510A (https=) |
| KR (1) | KR20050098302A (https=) |
| AU (1) | AU2004210625A1 (https=) |
| CA (1) | CA2512934A1 (https=) |
| MX (1) | MXPA05008360A (https=) |
| WO (1) | WO2004071468A2 (https=) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7785610B2 (en) * | 2001-06-21 | 2010-08-31 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same—III |
| EP2423335B1 (en) * | 2001-06-21 | 2014-05-14 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same |
| 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 |
| 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 |
| DE10328813B4 (de) * | 2003-06-20 | 2006-04-13 | Epigenomics Ag | Verfahren zur Untersuchung von Cytosin-Methylierungen in DNA-Sequenzen mittels triplexbildender Oligomere |
| JP4942646B2 (ja) * | 2004-06-15 | 2012-05-30 | 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 | 免疫賦活オリゴヌクレオチドマルチマー |
| US7498425B2 (en) * | 2004-06-15 | 2009-03-03 | Idera Pharmaceuticals, Inc. | Immunostimulatory oligonucleotide multimers |
| US7470674B2 (en) * | 2005-11-07 | 2008-12-30 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| US9096850B2 (en) * | 2009-08-24 | 2015-08-04 | Sirna Therapeutics, Inc. | Segmented micro RNA mimetics |
| JP6385957B2 (ja) * | 2013-01-08 | 2018-09-05 | 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Ｉｄｅｒａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | トール様受容体に基づく免疫応答を調節するための免疫調節オリゴヌクレオチド（ｉｒｏ）化合物 |
| EP3024936B1 (en) | 2013-07-25 | 2019-09-04 | Exicure, Inc. | Spherical nucleic acid-based constructs as immunostimulatory agents for prophylactic and therapeutic use |
| TR201908550T4 (tr) | 2014-06-04 | 2019-07-22 | Exicure Inc | Profilaktik veya terapötik uygulamalar için lipozomal sferik nükleik asitler tarafından immün modülatörlerin çok değerlikli teslimi. |
| US11213593B2 (en) | 2014-11-21 | 2022-01-04 | Northwestern University | Sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
| WO2018039629A2 (en) | 2016-08-25 | 2018-03-01 | Northwestern University | Micellar spherical nucleic acids from thermoresponsive, traceless templates |
| CN106754739A (zh) * | 2016-12-30 | 2017-05-31 | 天津三箭生物技术股份有限公司 | 小鼠抗人p53单克隆抗体及分泌该单克隆抗体的杂交瘤细胞株 |
| WO2018209270A1 (en) | 2017-05-11 | 2018-11-15 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (snas) |
| CN108178698A (zh) * | 2018-03-19 | 2018-06-19 | 联保作物科技有限公司 | 含嘧啶核苷类抗菌素和磷酸氢二钾的复配组合物、农业杀菌剂及其应用 |
| EP3950698A4 (en) * | 2019-03-28 | 2023-01-25 | Ajinomoto Co., Inc. | METHOD OF PREPARING AN OLIGONUCLEOTIDE WITH PHOSPHOROTHIOATE SITE |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5149797A (en) | 1990-02-15 | 1992-09-22 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of rna and production of encoded polypeptides |
| US6346614B1 (en) * | 1992-07-23 | 2002-02-12 | Hybridon, Inc. | Hybrid oligonucleotide phosphorothioates |
| US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US5968909A (en) * | 1995-08-04 | 1999-10-19 | Hybridon, Inc. | Method of modulating gene expression with reduced immunostimulatory response |
| US5856462A (en) * | 1996-09-10 | 1999-01-05 | Hybridon Incorporated | Oligonucleotides having modified CpG dinucleosides |
| US6426334B1 (en) * | 1997-04-30 | 2002-07-30 | Hybridon, Inc. | Oligonucleotide mediated specific cytokine induction and reduction of tumor growth in a mammal |
| EP2314693A3 (en) * | 1999-08-13 | 2012-11-28 | Idera Pharmaceuticals, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
| CA2398432C (en) * | 2000-01-26 | 2012-06-19 | Hybridon, Inc. | Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides |
| AU5736601A (en) * | 2000-05-01 | 2001-11-12 | Hybridon Inc | Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides |
| EP1399562A2 (en) * | 2000-07-19 | 2004-03-24 | PHARMACIA & UPJOHN COMPANY | Complete nucleotide sequence of staphylococcus aureus ribosomal protein gene, s20 and methods for the identification of antibacterial substances |
| AU2001294750C1 (en) | 2000-09-26 | 2008-09-18 | Idera Pharmaceuticals, Inc. | Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes |
| US7176296B2 (en) * | 2001-04-30 | 2007-02-13 | Idera Pharmaceuticals, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
| US7105495B2 (en) * | 2001-04-30 | 2006-09-12 | Idera Pharmaceuticals, Inc. | Modulation of oligonucleotide CpG-mediated immune stimulation by positional modification of nucleosides |
| US20030129605A1 (en) * | 2001-05-04 | 2003-07-10 | Dong Yu | Immunostimulatory activity of CpG oligonucleotides containing non-ionic methylphosophonate linkages |
| EP2423335B1 (en) * | 2001-06-21 | 2014-05-14 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same |
| WO2003035836A2 (en) * | 2001-10-24 | 2003-05-01 | Hybridon Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends |
| 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 |
| US7807803B2 (en) * | 2002-07-03 | 2010-10-05 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| EP1393745A1 (en) * | 2002-07-29 | 2004-03-03 | Hybridon, Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5'ends |
| 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 |
| MXPA05012421A (es) * | 2003-05-16 | 2006-02-22 | Hybridon Inc | Tratamiento sinergistico de cancer usando inmunomeros junto con agentes quimioterapeuticos. |
| MXPA05013658A (es) * | 2003-06-11 | 2006-03-02 | Hybridon Inc | Oligonucleotidos inmunomoduladores estabilizados. |
| MXPA06000619A (es) * | 2003-07-15 | 2006-04-11 | Hybridon Inc | Estimulacion sinergistica del sistema inmune usando oligonucleotidos inmunoestimuladores y/o compuestos inmunomeros en conjunto con citocinas y/o agentes quimioterapeuticos o terapia de radiacion. |
| AU2004275876B2 (en) * | 2003-09-25 | 2011-03-31 | Coley Pharmaceutical Gmbh | Nucleic acid-lipophilic conjugates |
| CA2549173A1 (en) * | 2003-12-08 | 2005-07-07 | Hybridon, Inc. | Modulation of immunostimulatory properties by small oligonucleotide-based compounds |
| JP2007523173A (ja) * | 2004-02-20 | 2007-08-16 | 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 | 修飾免疫調節オリゴヌクレオチドにより誘導された強力な粘膜免疫応答 |
| JP4942646B2 (ja) * | 2004-06-15 | 2012-05-30 | 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 | 免疫賦活オリゴヌクレオチドマルチマー |
| US7498425B2 (en) * | 2004-06-15 | 2009-03-03 | Idera Pharmaceuticals, Inc. | Immunostimulatory oligonucleotide multimers |
| WO2006011160A1 (en) * | 2004-06-28 | 2006-02-02 | Alembic Limited | Process for the preparation of azithromycin monohydrate isopropanol clathrate |
| EP1734583A1 (en) * | 2005-06-14 | 2006-12-20 | Photonis-DEP B.V. | Electron bombarded image sensor array device and its manufactoring method |
| US20070093439A1 (en) * | 2005-10-25 | 2007-04-26 | Idera Pharmaceuticals, Inc. | Short immunomodulatory oligonucleotides |
| MX2008006004A (es) * | 2005-11-07 | 2008-10-01 | Idera Pharmaceuticals Inc | Propiedades inmunoestimuladoras de compuestos a base de oligonucleotidos que comprenden dinucleotidos inmunoestimuladores modificados. |
| US7776834B2 (en) * | 2005-11-07 | 2010-08-17 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| US7470674B2 (en) * | 2005-11-07 | 2008-12-30 | Idera Pharmaceuticals, Inc. | Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides |
| MX2008008279A (es) * | 2005-12-20 | 2009-03-04 | Idera Pharmaceuticals Inc | Actividad inmunoestimuladora de oligonucleotidos inmunoestimuladores palindromicos que contienen diferentes longitudes de segmentos palindromicos. |
| MX2008008278A (es) | 2005-12-20 | 2008-10-01 | Idera Pharmaceuticals Inc | Agonistas sinteticos novedosos de receptores tipo toll que contienen modificaciones de dinucleotido cg. |
| PT2078080E (pt) * | 2006-09-27 | 2015-09-18 | Coley Pharm Gmbh | Análogos dos oligonucleotídeos cpg que contêm análogos t hidrofóbicos com atividade imunoestimulante potenciada |
| CN101610671A (zh) | 2006-12-12 | 2009-12-23 | 艾德拉药物股份有限公司 | 合成的tlr9激动剂 |
| KR20100053598A (ko) | 2007-08-01 | 2010-05-20 | 이데라 파마슈티칼즈, 인코포레이티드 | Ｔｌｒ９의 신규한 합성 효능제 |
-
2003
- 2003-02-07 US US10/361,111 patent/US7354907B2/en not_active Expired - Fee Related
-
2004
- 2004-01-13 CA CA002512934A patent/CA2512934A1/en not_active Abandoned
- 2004-01-13 MX MXPA05008360A patent/MXPA05008360A/es unknown
- 2004-01-13 EP EP04701751A patent/EP1594432A4/en not_active Withdrawn
- 2004-01-13 JP JP2006536535A patent/JP2007531510A/ja active Pending
- 2004-01-13 AU AU2004210625A patent/AU2004210625A1/en not_active Abandoned
- 2004-01-13 WO PCT/US2004/000789 patent/WO2004071468A2/en not_active Ceased
- 2004-01-13 KR KR1020057014457A patent/KR20050098302A/ko not_active Ceased
-
2007
- 2007-10-24 US US11/877,767 patent/US7851454B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004071468A2 (en) | 2004-08-26 |
| US7851454B2 (en) | 2010-12-14 |
| US20040156825A1 (en) | 2004-08-12 |
| WO2004071468A3 (en) | 2007-01-18 |
| US20090010938A1 (en) | 2009-01-08 |
| AU2004210625A1 (en) | 2004-08-26 |
| JP2007531510A (ja) | 2007-11-08 |
| EP1594432A4 (en) | 2008-08-06 |
| EP1594432A2 (en) | 2005-11-16 |
| MXPA05008360A (es) | 2005-11-04 |
| KR20050098302A (ko) | 2005-10-11 |
| US7354907B2 (en) | 2008-04-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7851454B2 (en) | Short immunomodulatory oligonucleotides | |
| JP5005878B2 (ja) | ５’末端の至適表示によるオリゴヌクレオチド化合物の免疫賦活性調節 | |
| AU2005257938B2 (en) | Immunostimulatory oligonucleotide multimers | |
| EP2343307B1 (en) | Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response | |
| JP4726997B2 (ja) | 修飾された免疫賦活性ジヌクレオチドを用いることによるオリゴヌクレオチドに基づく化合物の免疫賦活特性の調節 | |
| Bhagat et al. | CpG penta-and hexadeoxyribonucleotides as potent immunomodulatory agents | |
| US20070093439A1 (en) | Short immunomodulatory oligonucleotides | |
| WO2009154609A1 (en) | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response | |
| WO2009154610A1 (en) | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response | |
| WO2007050059A2 (en) | Short immunolomodulatory oligonucleotides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |