JP2001513776A - LPS関連障害の処置における非メチル化CpGジヌクレオチドを含む核酸の使用 - Google Patents
LPS関連障害の処置における非メチル化CpGジヌクレオチドを含む核酸の使用Info
- Publication number
- JP2001513776A JP2001513776A JP53781098A JP53781098A JP2001513776A JP 2001513776 A JP2001513776 A JP 2001513776A JP 53781098 A JP53781098 A JP 53781098A JP 53781098 A JP53781098 A JP 53781098A JP 2001513776 A JP2001513776 A JP 2001513776A
- Authority
- JP
- Japan
- Prior art keywords
- nucleic acid
- cpg
- acid sequence
- bases
- lps
- 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.)
- Ceased
Links
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 68
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 43
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 43
- 238000011282 treatment Methods 0.000 title description 13
- 238000000034 method Methods 0.000 claims abstract description 73
- 239000002158 endotoxin Substances 0.000 claims abstract description 53
- 229920006008 lipopolysaccharide Polymers 0.000 claims abstract description 19
- 102000004127 Cytokines Human genes 0.000 claims description 43
- 108090000695 Cytokines Proteins 0.000 claims description 43
- 108010065805 Interleukin-12 Proteins 0.000 claims description 31
- 102000013462 Interleukin-12 Human genes 0.000 claims description 31
- 239000002773 nucleotide Substances 0.000 claims description 28
- 125000003729 nucleotide group Chemical group 0.000 claims description 28
- 108010074328 Interferon-gamma Proteins 0.000 claims description 24
- 108090000174 Interleukin-10 Proteins 0.000 claims description 24
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 23
- 102000003814 Interleukin-10 Human genes 0.000 claims description 22
- 230000028709 inflammatory response Effects 0.000 claims description 21
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 17
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 15
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 15
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims description 14
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 14
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 14
- 230000007423 decrease Effects 0.000 claims description 13
- 101710151803 Mitochondrial intermediate peptidase 2 Proteins 0.000 claims description 10
- 230000001154 acute effect Effects 0.000 claims description 10
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 10
- 239000013638 trimer Substances 0.000 claims description 10
- 229940104230 thymidine Drugs 0.000 claims description 8
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims description 7
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims description 7
- 229940104302 cytosine Drugs 0.000 claims description 7
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 6
- 229930024421 Adenine Natural products 0.000 claims description 6
- 229960000643 adenine Drugs 0.000 claims description 6
- 102000008070 Interferon-gamma Human genes 0.000 claims description 5
- 229960003130 interferon gamma Drugs 0.000 claims description 5
- 229940113082 thymine Drugs 0.000 claims description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical group C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 230000004075 alteration Effects 0.000 claims 2
- 230000004044 response Effects 0.000 abstract description 29
- 230000028993 immune response Effects 0.000 abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 11
- 208000019693 Lung disease Diseases 0.000 abstract description 6
- 230000001900 immune effect Effects 0.000 abstract description 4
- CTMZLDSMFCVUNX-VMIOUTBZSA-N cytidylyl-(3'->5')-guanosine Chemical class 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 131
- 108091034117 Oligonucleotide Proteins 0.000 description 99
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 description 92
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 61
- 101500027983 Rattus norvegicus Octadecaneuropeptide Proteins 0.000 description 60
- 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 description 53
- 210000004027 cell Anatomy 0.000 description 45
- 210000004072 lung Anatomy 0.000 description 42
- 230000000694 effects Effects 0.000 description 35
- 241000699670 Mus sp. Species 0.000 description 29
- 235000013601 eggs Nutrition 0.000 description 29
- 229940117681 interleukin-12 Drugs 0.000 description 29
- 108020004414 DNA Proteins 0.000 description 22
- 241000699666 Mus <mouse, genus> Species 0.000 description 20
- 102100037850 Interferon gamma Human genes 0.000 description 19
- 210000003719 b-lymphocyte Anatomy 0.000 description 19
- 230000004913 activation Effects 0.000 description 16
- 238000002474 experimental method Methods 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 15
- 238000003556 assay Methods 0.000 description 13
- 210000001616 monocyte Anatomy 0.000 description 13
- 108090001005 Interleukin-6 Proteins 0.000 description 12
- 102000004889 Interleukin-6 Human genes 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 11
- 241000588724 Escherichia coli Species 0.000 description 11
- 208000006673 asthma Diseases 0.000 description 11
- 210000003622 mature neutrocyte Anatomy 0.000 description 11
- 208000035475 disorder Diseases 0.000 description 10
- 210000000822 natural killer cell Anatomy 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 9
- 210000004969 inflammatory cell Anatomy 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 230000028327 secretion Effects 0.000 description 9
- 102000004388 Interleukin-4 Human genes 0.000 description 8
- 108090000978 Interleukin-4 Proteins 0.000 description 8
- 239000000427 antigen Substances 0.000 description 8
- 102000036639 antigens Human genes 0.000 description 8
- 108091007433 antigens Proteins 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 210000003979 eosinophil Anatomy 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 210000000440 neutrophil Anatomy 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 230000004199 lung function Effects 0.000 description 7
- 208000023504 respiratory system disease Diseases 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000004936 stimulating effect Effects 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 230000000692 anti-sense effect Effects 0.000 description 6
- 230000004663 cell proliferation Effects 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 229940028885 interleukin-4 Drugs 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 230000011987 methylation Effects 0.000 description 6
- 238000007069 methylation reaction Methods 0.000 description 6
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 5
- 101710163270 Nuclease Proteins 0.000 description 5
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 5
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 5
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 4
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 241000242680 Schistosoma mansoni Species 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000019734 interleukin-12 production Effects 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000002101 lytic effect Effects 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000002685 pulmonary effect Effects 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 230000008718 systemic inflammatory response Effects 0.000 description 4
- -1 Acetyl- Chemical group 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 108091029430 CpG site Proteins 0.000 description 3
- 208000037487 Endotoxemia Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 208000032456 Hemorrhagic Shock Diseases 0.000 description 3
- 108010093965 Polymyxin B Proteins 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 102000006382 Ribonucleases Human genes 0.000 description 3
- 108010083644 Ribonucleases Proteins 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- 206010049771 Shock haemorrhagic Diseases 0.000 description 3
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- KDWFDOFTPHDNJL-TUBOTVQJSA-N odn-2006 Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=S)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=S)O[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(S)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C(N=C(N)C=C2)=O)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=O)OC[C@@H]2[C@H](C[C@@H](O2)N2C(NC(=O)C(C)=C2)=O)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C(N=C(N)C=C2)=O)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C3=C(C(NC(N)=N3)=O)N=C2)O)N2C(N=C(N)C=C2)=O)O)[C@@H](O)C1 KDWFDOFTPHDNJL-TUBOTVQJSA-N 0.000 description 3
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 3
- 230000001991 pathophysiological effect Effects 0.000 description 3
- 229920000024 polymyxin B Polymers 0.000 description 3
- 229960005266 polymyxin b Drugs 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001541 thymus gland Anatomy 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 2
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical group CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108020000946 Bacterial DNA Proteins 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108010042407 Endonucleases Proteins 0.000 description 2
- 102000004533 Endonucleases Human genes 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- 229920001917 Ficoll Polymers 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 102000000646 Interleukin-3 Human genes 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 208000038016 acute inflammation Diseases 0.000 description 2
- 230000006022 acute inflammation Effects 0.000 description 2
- 206010069351 acute lung injury Diseases 0.000 description 2
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000020411 cell activation Effects 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000012869 ethanol precipitation Methods 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 230000000622 irritating effect Effects 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 201000002364 leukopenia Diseases 0.000 description 2
- 231100001022 leukopenia Toxicity 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000002297 mitogenic effect Effects 0.000 description 2
- 239000006199 nebulizer Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- 150000003904 phospholipids Chemical group 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000009325 pulmonary function Effects 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 230000029069 type 2 immune response Effects 0.000 description 2
- 229940045145 uridine Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 108020004463 18S ribosomal RNA Proteins 0.000 description 1
- 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 1
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010060921 Abdominal abscess Diseases 0.000 description 1
- 101710099705 Anti-lipopolysaccharide factor Proteins 0.000 description 1
- 241001043246 Athyma Species 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 201000001178 Bacterial Pneumonia Diseases 0.000 description 1
- 231100000699 Bacterial toxin Toxicity 0.000 description 1
- 229920002799 BoPET Polymers 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 241001529572 Chaceon affinis Species 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000030933 DNA methylation on cytosine Effects 0.000 description 1
- 108010063593 DNA modification methylase SssI Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 241000698776 Duma Species 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010059028 Gastrointestinal ischaemia Diseases 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 241000519695 Ilex integra Species 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 102000004560 Interleukin-12 Receptors Human genes 0.000 description 1
- 108010017515 Interleukin-12 Receptors Proteins 0.000 description 1
- 102000014158 Interleukin-12 Subunit p40 Human genes 0.000 description 1
- 108010011429 Interleukin-12 Subunit p40 Proteins 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 102000010631 Kininogens Human genes 0.000 description 1
- 108010077861 Kininogens Proteins 0.000 description 1
- 241000239218 Limulus Species 0.000 description 1
- 206010025102 Lung infiltration Diseases 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 101000981253 Mus musculus GPI-linked NAD(P)(+)-arginine ADP-ribosyltransferase 1 Proteins 0.000 description 1
- 101001044384 Mus musculus Interferon gamma Proteins 0.000 description 1
- 239000005041 Mylar™ Substances 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 208000006816 Neonatal Sepsis Diseases 0.000 description 1
- 206010073310 Occupational exposures Diseases 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 102000002278 Ribosomal Proteins Human genes 0.000 description 1
- 108010000605 Ribosomal Proteins Proteins 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- 241000242678 Schistosoma Species 0.000 description 1
- 206010053879 Sepsis syndrome Diseases 0.000 description 1
- 241001611093 Stimula Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000607598 Vibrio Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000009692 acute damage Effects 0.000 description 1
- 208000012871 acute dyspnea Diseases 0.000 description 1
- 230000010398 acute inflammatory response Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000005600 alkyl phosphonate group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 210000004423 amoeboid cell Anatomy 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 208000002352 blister Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 101150075908 cpg-4 gene Proteins 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 229940096118 ella Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000010855 food raising agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 208000027096 gram-negative bacterial infections Diseases 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 206010024378 leukocytosis Diseases 0.000 description 1
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000004579 marble Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000002433 mononuclear leukocyte Anatomy 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 231100000675 occupational exposure Toxicity 0.000 description 1
- 208000014055 occupational lung disease Diseases 0.000 description 1
- DHYWDEXXBWTTEH-UHFFFAOYSA-N odn 2007 Chemical compound O=C1NC(=O)C(C)=CN1C1OC(COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(O)=O)C(O)C1 DHYWDEXXBWTTEH-UHFFFAOYSA-N 0.000 description 1
- 230000001662 opsonic effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000027317 positive regulation of immune response Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000001533 respiratory mucosa Anatomy 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 210000004708 ribosome subunit Anatomy 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 208000026775 severe diarrhea Diseases 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- 230000000476 thermogenic effect Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- OOLLAFOLCSJHRE-ZHAKMVSLSA-N ulipristal acetate Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(OC(C)=O)C(C)=O)[C@]2(C)C1 OOLLAFOLCSJHRE-ZHAKMVSLSA-N 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000000277 virosome Substances 0.000 description 1
- 239000002023 wood Substances 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.気流の急性減少を有するまたは有する危険のある被験体を処置する方法で あって、 少なくとも1つの非メチル化CpGを含む核酸配列の治療的有効量を、気流の急 性減少を有するかまたは有する危険のある被験体に投与する工程であって、ここ で、該核酸が、少なくとも以下の式を含み、 5'N1X1CGX2N23'(配列番号1) ここで、少なくとも1つのヌクレオチドが、連続するCpGを分離し;X1が、アデ ニン、グアニン、またはチミジンであり;X2が、シトシンまたはチミンであり; Nが、任意のヌクレオチドであり、そしてN1+N2が、約2〜26塩基である、工程 、 を包含する、方法。 2.前記核酸配列が、8〜30塩基長である、請求項1に記載の方法。 3.前記被験体がヒトである、請求項1に記載の方法。 4.前記気流の急性減少が、リポ多糖(LPS)曝露から生じる、請求項1に記 載の方法。 5.前記気流の急性減少が、エンドトキシン曝露から生じる、請求項1に記載 の方法。 6.N1およびN2が、CCGGクアドマーまたは1つより多くのCGGトリマーを含み ;そして前記核酸配列が、約8〜30塩基長である、請求項5に記載の方法。 7.前記核酸配列が、配列番号2である、請求項5に記載の方法。 8.請求項1に記載の方法であって、前記核酸配列が以下の式を有し: 5'N1X1X2CGX3X4N23'(配列番号3) ここで、少なくとも1つのヌクレオチドが、連続するCpGを分離し;X1X2が、GpT 、GpG、GpA、ApT、およびApAからなる群より選択され;X3X4が、TpTまたはCpTか らなる群より選択され;Nが、任意のヌクレオチドであり、そしてN1+N2が、約 0〜26塩基である、方法。 9.N1およびN2が、CCGGクアドマーまたは1つより多くのCCGもしくはCGGトリ マーを含み;そして前記核酸配列が、約8〜30塩基長である、請求項8に記載の 方法。 10.リポ多糖(LPS)を吸入したかまたは吸入した危険のある被験体におい て炎症応答を阻害する方法であって、 少なくとも1つの非メチル化CpGを含む核酸配列の炎症応答を阻害するために 有効な量を、リポ多糖(LPS)を吸入したまたは吸入した危険のある被験体に投 与する工程であって、ここで、該核酸が、少なくとも以下の式を含み、 5'N1X1CGX2N23'(配列番号1) ここで、少なくとも1つのヌクレオチドが、連続するCpGを分離し;X1が、アデ ニン、グアニン、またはチミジンであり;X2が、シトシンまたはチミンであり; Nが、任意のヌクレオチドであり、そしてN1+N2が、約2〜26塩基である、工程 、 を包含する、方法。 11.前記核酸配列が、8〜30塩基長である、請求項10に記載の方法。 12.前記被験体がヒトである、請求項10に記載の方法。 13.前記被験体がLPSを吸入した、請求項10に記載の方法。 14.N1およびN2が、CCGGクアドマーまたは1つより多くのCGGトリマーを含 み;そして前記核酸配列が、約8〜30塩基長である、請求項13に記載の方法。 15.前記核酸配列が、配列番号2である、請求項13に記載の方法。 16.請求項10に記載の方法であって、前記核酸配列が以下の式を有し: 5'N1X1X2CGX3X4N23'(配列番号3) ここで、少なくとも1つのヌクレオチドが、連続するCpGを分離し;X1X2が、GpT 、GpG、GpA、ApT、およびApAからなる群より選択され;X3X4が、TpTまたはCpTか らなる群より選択され;Nが、任意のヌクレオチドであり、そしてN1+N2が、約 0〜26塩基である、方法。 17.N1およびN2が、CCGGクアドマーまたは1つより多くのCCGもしくはCGGト リマーを含み;そして前記核酸配列が、約8〜30塩基長である、請求項16に記 載の方法。 18.リポ多糖(LPS)を吸入したまたは吸入した危険のある被験体において サイトカインのレベルを改変する方法であって、 少なくとも1つの非メチル化CpGを含む核酸配列の治療的有効量を、被験体に 投与する工程であって、ここで、該核酸が、少なくとも以下の式を含み、 5'N1X1CGX2N23'(配列番号1) ここで、少なくとも1つのヌクレオチドが、連続するCpGを分離し;X1が、アデ ニン、グアニン、またはチミジンであり;X2が、シトシンまたはチミンであり; Nが、任意のヌクレオチドであり、そしてN1+N2が、約2〜26塩基である、工程 、 を包含する、方法。 19.前記核酸配列が、約8〜30塩基長である、請求項18に記載の方法。 20.前記被験体がヒトである、請求項18に記載の方法。 21.前記被験体がLPSを吸入した、請求項18に記載の方法。 22.請求項18に記載の方法であって、前記核酸配列が以下の式を有し: 5'N1X1CGX2N23'(配列番号1) ここで、少なくとも1つのヌクレオチドが、連続するCpGを分離し;X1が、アデ ニン、グアニン、またはチミジンであり;X2が、シトシンまたはチミンであり; Nが、任意のヌクレオチドであり、そしてN1+N2が、約0〜26塩基である、方法 。 23.N1およびN2が、CCGGクアドマーまたは1つより多くのCGGトリマーを含 まず;そして前記核酸配列が、約8〜30塩基長である、請求項22に記載の方法 。 24.請求項18に記載の方法であって、前記核酸配列が以下の式を有し: 5'N1X1X2CGX3X4N23'(配列番号3) ここで、少なくとも1つのヌクレオチドが、連続するCpGを分離し;X1X2が、GpT 、GpG、GpA、ApT、およびApAからなる群より選択され;X3X4が、TpTまたはCpTか らなる群より選択され;Nが、任意のヌクレオチドであり、そしてN1+N2が、約 0〜26塩基長である、 方法。 25.N1およびN2が、CCGGクアドマーまたは1つより多くのCCGトリマーもし くはCGGトリマーを含み;そして前記核酸配列が、約8〜30塩基長である、請求 項24に記載の方法。 26.前記改変が、前記サイトカインのレベルの減少である、請求項18に記 載の方法。 27.前記改変が、前記サイトカインのレベルの増加であり、そして該サイト カインが、MIP-2、IL-10、およびIL-12からなる群より選択される、請求項18 に記載の方法。 28.前記サイトカインが、TNF-α、MIP-2、IL-10、IL-12、およびインター フェロン-γからなる群より選択される、請求項18に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3940597P | 1997-02-28 | 1997-02-28 | |
US60/039,405 | 1997-02-28 | ||
PCT/US1998/003678 WO1998037919A1 (en) | 1997-02-28 | 1998-02-25 | USE OF NUCLEIC ACIDS CONTAINING UNMETHYLATED CpG DINUCLEOTIDE IN THE TREATMENT OF LPS-ASSOCIATED DISORDERS |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2001513776A true JP2001513776A (ja) | 2001-09-04 |
JP2001513776A5 JP2001513776A5 (ja) | 2005-10-06 |
Family
ID=21905269
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP53781098A Ceased JP2001513776A (ja) | 1997-02-28 | 1998-02-25 | LPS関連障害の処置における非メチル化CpGジヌクレオチドを含む核酸の使用 |
Country Status (6)
Country | Link |
---|---|
US (1) | US6214806B1 (ja) |
EP (1) | EP1039935A4 (ja) |
JP (1) | JP2001513776A (ja) |
AU (1) | AU738513B2 (ja) |
CA (1) | CA2281838A1 (ja) |
WO (1) | WO1998037919A1 (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002500159A (ja) * | 1997-09-05 | 2002-01-08 | 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 | 抗原刺激顆粒球媒介炎症を予防または軽減するための免疫刺激オリゴヌクレオチドの使用 |
JP2005502338A (ja) * | 2001-08-17 | 2005-01-27 | コーリー ファーマシューティカル グループ,インコーポレイテッド | 改善した活性を有する組み合わせモチーフ免疫刺激オリゴヌクレオチド |
JP2006508693A (ja) * | 2002-08-19 | 2006-03-16 | コーリー ファーマシューティカル グループ,インコーポレイテッド | 免疫刺激性核酸 |
US7858589B2 (en) * | 1998-08-10 | 2010-12-28 | Antigenics Inc. | Compositions of CpG and saponin adjuvants and uses thereof |
Families Citing this family (327)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7189834B2 (en) * | 1993-05-11 | 2007-03-13 | Marshall William E | Oligoribonucleotides alert the immune system of animals to the imminence of microbial infection |
US5849719A (en) * | 1993-08-26 | 1998-12-15 | The Regents Of The University Of California | Method for treating allergic lung disease |
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 |
US7935675B1 (en) | 1994-07-15 | 2011-05-03 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
US6429199B1 (en) | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
WO1997025429A1 (en) | 1996-01-04 | 1997-07-17 | Rican Limited | Helicobacter pylori bacterioferritin |
US20030078223A1 (en) * | 1996-01-30 | 2003-04-24 | Eyal Raz | Compositions and methods for modulating an immune response |
ATE292980T1 (de) * | 1996-10-11 | 2005-04-15 | Univ California | Immunostimulierende oligonucleotidekonjugate |
EP0855184A1 (en) * | 1997-01-23 | 1998-07-29 | Grayson B. Dr. Lipford | Pharmaceutical composition comprising a polynucleotide and an antigen especially for vaccination |
JP2001513776A (ja) | 1997-02-28 | 2001-09-04 | ユニバーシティ オブ アイオワ リサーチ ファウンデーション | LPS関連障害の処置における非メチル化CpGジヌクレオチドを含む核酸の使用 |
US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
US6426334B1 (en) | 1997-04-30 | 2002-07-30 | Hybridon, Inc. | Oligonucleotide mediated specific cytokine induction and reduction of tumor growth in a mammal |
ATE370740T1 (de) | 1997-05-20 | 2007-09-15 | Ottawa Health Research Inst | Verfahren zur herstellung von nukleinsäurekonstrukten |
CA2291483C (en) | 1997-06-06 | 2012-09-18 | Dynavax Technologies Corporation | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
US6589940B1 (en) | 1997-06-06 | 2003-07-08 | Dynavax Technologies Corporation | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
US20040006034A1 (en) * | 1998-06-05 | 2004-01-08 | Eyal Raz | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
US7138384B1 (en) | 1997-08-29 | 2006-11-21 | The Regents Of The University Of California | Modulators of DNA cytosine-5 methyltransferase and methods for use thereof |
GB9727262D0 (en) * | 1997-12-24 | 1998-02-25 | Smithkline Beecham Biolog | Vaccine |
ES2284247T3 (es) * | 1998-04-03 | 2007-11-01 | University Of Iowa Research Foundation | Metodos y productos para estimular el sistema inmunitario usando oligonucleotidos y citoquinas inmunoterapeuticos. |
JP2002514397A (ja) * | 1998-05-14 | 2002-05-21 | コーリー ファーマシューティカル ゲーエムベーハー | CpGオリゴヌクレオチドを用いる造血調節の方法 |
CA2330916C (en) | 1998-05-19 | 2011-04-05 | Research Development Foundation | Triterpene compositions and methods for use thereof |
ES2272069T3 (es) | 1998-05-22 | 2007-04-16 | Ottawa Health Research Institute | Metodos y productos para inducir inmunidad en mucosas. |
US6562798B1 (en) | 1998-06-05 | 2003-05-13 | Dynavax Technologies Corp. | Immunostimulatory oligonucleotides with modified bases and methods of use thereof |
US20030022854A1 (en) | 1998-06-25 | 2003-01-30 | Dow Steven W. | Vaccines using nucleic acid-lipid complexes |
US6693086B1 (en) * | 1998-06-25 | 2004-02-17 | National Jewish Medical And Research Center | Systemic immune activation method using nucleic acid-lipid complexes |
EP1113818B1 (en) * | 1998-09-18 | 2006-05-17 | Dynavax Technologies Corporation | METHODS OF TREATING IgE-ASSOCIATED DISORDERS AND COMPOSITIONS FOR USE THEREIN |
NZ513935A (en) | 1999-02-17 | 2004-02-27 | Csl Ltd | Immunogenic complexes and methods relating thereto |
ES2228454T3 (es) | 1999-02-26 | 2005-04-16 | Chiron S.R.L. | Mejora de la actividad bacteriana de antigenos de neisseria con oligonucleotidos que contienen motivos cg. |
CA2689696C (en) | 1999-02-26 | 2013-08-06 | Novartis Vaccines And Diagnostics, Inc. | Microemulsions with adsorbed macromolecules and microparticles |
US6977245B2 (en) | 1999-04-12 | 2005-12-20 | The United States Of America As Represented By The Department Of Health And Human Services | Oligodeoxynucleotide and its use to induce an immune response |
AU4343700A (en) | 1999-04-12 | 2000-11-14 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Oligodeoxynucleotide and its use to induce an immune response |
US6558670B1 (en) | 1999-04-19 | 2003-05-06 | Smithkline Beechman Biologicals S.A. | Vaccine adjuvants |
GB9908885D0 (en) * | 1999-04-19 | 1999-06-16 | Smithkline Beecham Biolog | Vccine |
AU764969B2 (en) * | 1999-04-19 | 2003-09-04 | Smithkline Beecham Biologicals (Sa) | Vaccines |
CA2376634A1 (en) * | 1999-06-08 | 2000-12-14 | Aventis Pasteur | Immunostimulant oligonucleotide |
FR2797263B1 (fr) * | 1999-08-06 | 2003-09-19 | Pasteur Merieux Serums Vacc | Oligonucleotide immunostimulant |
GB9915204D0 (en) * | 1999-06-29 | 1999-09-01 | Smithkline Beecham Biolog | Vaccine |
DE60023300T2 (de) * | 1999-06-29 | 2006-07-06 | Glaxosmithkline Biologicals S.A. | Verwendung von cpg als adjuvans für hivimpstoff |
US6514948B1 (en) * | 1999-07-02 | 2003-02-04 | The Regents Of The University Of California | Method for enhancing an immune response |
US7479285B1 (en) | 1999-08-19 | 2009-01-20 | Dynavax Technologies Corporation | Methods of modulating an immune response using immunostimulatory sequences and compositions for use therein |
MXPA02003108A (es) * | 1999-09-25 | 2003-10-14 | Univ Iowa Res Found | Acidos nucleicos inmunoestimuladores. |
US6949520B1 (en) * | 1999-09-27 | 2005-09-27 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
US7223398B1 (en) | 1999-11-15 | 2007-05-29 | Dynavax Technologies Corporation | Immunomodulatory compositions containing an immunostimulatory sequence linked to antigen and methods of use thereof |
JP2003527352A (ja) * | 2000-01-13 | 2003-09-16 | アンティジェニクス インコーポレーテッド | Cpgおよびサポニンの自然免疫刺激化合物、ならびにそれらの方法 |
ATE378348T1 (de) | 2000-01-14 | 2007-11-15 | Us Health | Oligodeoxynukleotide und ihre verwendung zur induktion einer immunreaktion |
EP1253947A4 (en) * | 2000-01-31 | 2005-01-05 | Univ California | IMMUNOMODULATED POLYNUCLEOTIDES FOR THE TREATMENT OF INFECTIONS BY INTRA-CELLULAR DISEASES |
US7585847B2 (en) * | 2000-02-03 | 2009-09-08 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
US20030130217A1 (en) * | 2000-02-23 | 2003-07-10 | Eyal Raz | Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation |
IL151345A0 (en) | 2000-02-23 | 2003-04-10 | Univ California | Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation |
US20040131628A1 (en) * | 2000-03-08 | 2004-07-08 | Bratzler Robert L. | Nucleic acids for the treatment of disorders associated with microorganisms |
US7157437B2 (en) | 2000-03-10 | 2007-01-02 | Dynavax Technologies Corporation | Methods of ameliorating symptoms of herpes infection using immunomodulatory polynucleotide sequences |
US7129222B2 (en) * | 2000-03-10 | 2006-10-31 | Dynavax Technologies Corporation | Immunomodulatory formulations and methods for use thereof |
US20010046967A1 (en) | 2000-03-10 | 2001-11-29 | Gary Van Nest | Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide |
US20020098199A1 (en) | 2000-03-10 | 2002-07-25 | Gary Van Nest | Methods of suppressing hepatitis virus infection using immunomodulatory polynucleotide sequences |
US20030129251A1 (en) | 2000-03-10 | 2003-07-10 | Gary Van Nest | Biodegradable immunomodulatory formulations and methods for use thereof |
PT1296714E (pt) | 2000-06-22 | 2009-10-15 | Coley Pharm Gmbh | Combinação de cpg e anticorpos dirigidos contra cd19, cd20, cd22 ou cd40 para o tratamento ou prevenção do cancro |
WO2002002172A1 (en) * | 2000-06-30 | 2002-01-10 | Univ Jefferson | Dna palindrome - oligoguanylic acid compositions and uses thereof |
KR100917101B1 (ko) * | 2000-08-04 | 2009-09-15 | 도요 보세키 가부시키가이샤 | 플렉시블 금속적층체 및 그 제조방법 |
EP1366077B1 (en) | 2000-09-15 | 2011-05-25 | Coley Pharmaceutical GmbH | PROCESS FOR HIGH THROUGHPUT SCREENING OF CpG-BASED IMMUNO-AGONIST/ANTAGONIST |
EP2189473A3 (en) | 2000-10-27 | 2010-08-11 | Novartis Vaccines and Diagnostics S.r.l. | Nucleic and proteins from streptococcus groups A & B |
ES2307568T3 (es) * | 2000-12-08 | 2008-12-01 | Coley Pharmaceutical Gmbh | Acidos nucleicos de tipo cpg y metodos de uso de los mismos. |
AU2002231336B2 (en) * | 2000-12-27 | 2007-06-28 | Surefire Medical, Inc. D/B/A Trisalus Life Sciences | Immunomodulatory polynucleotides and methods of using the same |
US20030050268A1 (en) * | 2001-03-29 | 2003-03-13 | Krieg Arthur M. | Immunostimulatory nucleic acid for treatment of non-allergic inflammatory diseases |
ES2288555T3 (es) | 2001-05-21 | 2008-01-16 | Intercell Ag | Moleculas de oligodesoxinucleotidos inmunoestimuladores. |
US6818787B2 (en) * | 2001-06-11 | 2004-11-16 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
GB0115176D0 (en) | 2001-06-20 | 2001-08-15 | Chiron Spa | Capular polysaccharide solubilisation and combination vaccines |
ES2487645T3 (es) * | 2001-06-21 | 2014-08-22 | Dynavax Technologies Corporation | Compuestos inmunomoduladores quiméricos y métodos de uso de los mismos |
US7785610B2 (en) * | 2001-06-21 | 2010-08-31 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same—III |
CZ20033515A3 (cs) * | 2001-06-29 | 2005-01-12 | Chiron Corporation | Kompozice vakcíny HCV E1E2 |
GB0118249D0 (en) | 2001-07-26 | 2001-09-19 | Chiron Spa | Histidine vaccines |
US7666674B2 (en) | 2001-07-27 | 2010-02-23 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of sterically stabilized cationic liposomes to efficiently deliver CPG oligonucleotides in vivo |
GB0121591D0 (en) | 2001-09-06 | 2001-10-24 | Chiron Spa | Hybrid and tandem expression of neisserial proteins |
AU2002318944A1 (en) * | 2001-08-01 | 2003-02-17 | Coley Pharmaceutical Gmbh | Methods and compositions relating to plasmacytoid dendritic cells |
US20030133988A1 (en) * | 2001-08-07 | 2003-07-17 | Fearon Karen L. | Immunomodulatory compositions, formulations, and methods for use thereof |
WO2003020884A2 (en) * | 2001-08-14 | 2003-03-13 | The Government Of The United States Of America As Represented By The Secretary Of Health And Human Services | Method for rapid generation of mature dendritic cells |
AU2002331720B2 (en) | 2001-08-24 | 2007-10-11 | Johns Hopkins University | Proaerolysin containing protease activation sequences and methods of use for treatment of prostate cancer |
WO2003022296A1 (en) * | 2001-09-07 | 2003-03-20 | The Trustees Of Boston University | Method and composition for treating immune complex associated disorders |
WO2003024481A2 (en) | 2001-09-14 | 2003-03-27 | Cytos Biotechnology Ag | Packaging of immunostimulatory substances into virus-like particles: method of preparation and use |
WO2003027313A2 (en) | 2001-09-24 | 2003-04-03 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | SUPPRESSORS OF CpG OLIGONUCLEOTIDES AND METHODS OF USE |
US20030119774A1 (en) * | 2001-09-25 | 2003-06-26 | Marianna Foldvari | Compositions and methods for stimulating an immune response |
AR045702A1 (es) | 2001-10-03 | 2005-11-09 | Chiron Corp | Composiciones de adyuvantes. |
CA2461315A1 (en) * | 2001-10-05 | 2003-04-17 | Coley Pharmaceutical Gmbh | Toll-like receptor 3 signaling agonists and antagonists |
WO2003094836A2 (en) * | 2001-10-12 | 2003-11-20 | University Of Iowa Research Foundation | Methods and products for enhancing immune responses using imidazoquinoline compounds |
US8466116B2 (en) | 2001-12-20 | 2013-06-18 | The Unites States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of CpG oligodeoxynucleotides to induce epithelial cell growth |
AU2002366710A1 (en) | 2001-12-20 | 2003-07-09 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of | USE OF CpG OLIGODEOXYNUCLEOTIDES TO INDUCE ANGIOGENESIS |
AU2003215316A1 (en) | 2002-02-20 | 2003-09-09 | Chiron Corporation | Microparticles with adsorbed polypeptide-containing molecules |
EP2368431A1 (en) | 2002-04-04 | 2011-09-28 | Coley Pharmaceutical GmbH | Immunostimulatory G,U-containing oligoribonucleotides |
KR100456681B1 (ko) * | 2002-05-22 | 2004-11-10 | 주식회사 대웅 | 박테리아의 염색체 dna 파쇄물과 비독성리포폴리사카라이드를 포함하는 면역강화 및 조절 조성물 |
CA2388049A1 (en) | 2002-05-30 | 2003-11-30 | Immunotech S.A. | Immunostimulatory oligonucleotides and uses thereof |
AU2003243409A1 (en) * | 2002-06-05 | 2003-12-22 | Coley Pharmaceutical Group, Inc. | Method for treating autoimmune or inflammatory diseases with combinations of inhibitory oligonucleotides and small molecule antagonists of immunostimulatory cpg nucleic acids |
US20040053880A1 (en) * | 2002-07-03 | 2004-03-18 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
US7807803B2 (en) * | 2002-07-03 | 2010-10-05 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
US7605138B2 (en) * | 2002-07-03 | 2009-10-20 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
US7576066B2 (en) * | 2002-07-03 | 2009-08-18 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
US7569553B2 (en) * | 2002-07-03 | 2009-08-04 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
AU2003255969A1 (en) * | 2002-07-17 | 2004-02-02 | Coley Pharmaceutical Gmbh | Use of cpg nucleic acids in prion-disease |
JP2005533855A (ja) | 2002-07-24 | 2005-11-10 | インターツェル・アクチェンゲゼルシャフト | 病原性ウイルスからの別のリーディングフレームによりコードされる抗原 |
AU2003263963A1 (en) | 2002-08-01 | 2004-02-23 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of | Method of treating inflammatory arthropathies with suppressors of cpg oligonucleotides |
GB0220194D0 (en) | 2002-08-30 | 2002-10-09 | Chiron Spa | Improved vesicles |
JP2006504687A (ja) | 2002-09-13 | 2006-02-09 | インターツェル・アクチェンゲゼルシャフト | C型肝炎ウイルスペプチドの単離方法 |
US8263091B2 (en) * | 2002-09-18 | 2012-09-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating and preventing infections in immunocompromised subjects with immunostimulatory CpG oligonucleotides |
US8043622B2 (en) | 2002-10-08 | 2011-10-25 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides |
MXPA05004588A (es) | 2002-10-29 | 2005-12-14 | Coley Pharmaceutical Group Ltd | Metodos y productos relacionados con el tratamiento y prevencion de infeccion de virus de hepatitis c. |
JP4976653B2 (ja) * | 2002-11-01 | 2012-07-18 | ザ ガバメント オブ ザ ユナイテッド ステイツ オブ アメリカ アズ リプレゼンティッド バイ ザ セクレタリー オブ ザ デパートメント オブ ヘルス アンド ヒューマン サービシス | 免疫刺激性CpGオリゴヌクレオチドを用いてバイオテロ病原体による感染症を予防する方法 |
WO2004041183A2 (en) * | 2002-11-01 | 2004-05-21 | The Regents Of The University Of California | Methods of treating pulmonary fibrotic disorders |
DK2279746T3 (da) | 2002-11-15 | 2013-11-25 | Novartis Vaccines & Diagnostic | Overfladeproteiner i neisseria meningitidis |
US8039443B2 (en) * | 2002-11-21 | 2011-10-18 | Archemix Corporation | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
US10100316B2 (en) * | 2002-11-21 | 2018-10-16 | Archemix Llc | Aptamers comprising CPG motifs |
US8853376B2 (en) | 2002-11-21 | 2014-10-07 | Archemix Llc | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
US20050124565A1 (en) * | 2002-11-21 | 2005-06-09 | Diener John L. | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
GB0227346D0 (en) | 2002-11-22 | 2002-12-31 | Chiron Spa | 741 |
WO2004052293A2 (en) * | 2002-12-11 | 2004-06-24 | Hawaii Biotech, Inc. | Recombinant vaccine against flavivirus infection |
AU2003300919A1 (en) | 2002-12-11 | 2004-06-30 | Coley Pharmaceutical Gmbh | 5' cpg nucleic acids and methods of use |
SI1575977T1 (sl) | 2002-12-23 | 2010-01-29 | Dynavax Tech Corp | Imunostimulirni sekvenčni polinukleotidi in postopki za njihovo uporabo |
US8158768B2 (en) | 2002-12-23 | 2012-04-17 | Dynavax Technologies Corporation | Immunostimulatory sequence oligonucleotides and methods of using the same |
WO2004060396A2 (en) | 2002-12-27 | 2004-07-22 | Chiron Corporation | Immunogenic compositions containing phospholpid |
ES2562456T3 (es) | 2003-03-24 | 2016-03-04 | Valneva Austria Gmbh | Uso de un adyuvante que induce una respuesta inmune Th1 para mejorar las respuestas inmunes |
CA2521050A1 (en) * | 2003-04-02 | 2004-10-14 | Coley Pharmaceutical Group, Ltd. | Immunostimulatory nucleic acid oil-in-water formulations and related methods of use |
JP2007525177A (ja) | 2003-04-21 | 2007-09-06 | アーケミックス コーポレイション | 血小板由来増殖因子に対する安定化アプタマーおよび腫瘍治療剤としてのそれらの使用 |
AU2004238139B2 (en) * | 2003-05-15 | 2009-12-03 | Mitsui Dm Sugar Co.,Ltd. | Immunostimulating Agents |
EP1633778B1 (en) | 2003-06-05 | 2013-09-11 | GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Poly-gamma-glutamic acid conjugates for eliciting immune responses directed against bacilli |
JP2007524615A (ja) * | 2003-06-20 | 2007-08-30 | コーリー ファーマシューティカル ゲーエムベーハー | 低分子トール様レセプター(tlr)アンタゴニスト |
US20060035242A1 (en) | 2004-08-13 | 2006-02-16 | Michelitsch Melissa D | Prion-specific peptide reagents |
EP1663316A2 (en) * | 2003-09-25 | 2006-06-07 | Coley Pharmaceutical Group, Inc. | Nucleic acid lipophilic conjugates |
UA88457C2 (ru) * | 2003-10-30 | 2009-10-26 | Коли Фармасьютикал Гмбх | Иммуностимулирующая нуклеиновая кислота с улучшенной иммуностимулирующей эффективностью |
US20050239733A1 (en) * | 2003-10-31 | 2005-10-27 | Coley Pharmaceutical Gmbh | Sequence requirements for inhibitory oligonucleotides |
US20050100983A1 (en) * | 2003-11-06 | 2005-05-12 | Coley Pharmaceutical Gmbh | Cell-free methods for identifying compounds that affect toll-like receptor 9 (TLR9) signaling |
WO2005072290A2 (en) * | 2004-01-23 | 2005-08-11 | Joslin Diabetes Center | Methods of treating, reducing, or preventing autoimmune conditions |
AU2005230938A1 (en) | 2004-02-19 | 2005-10-20 | Coley Pharmaceutical Gmbh | Immunostimulatory viral RNA oligonucleotides |
AU2005220910A1 (en) * | 2004-03-05 | 2005-09-22 | Archemix Corp. | Aptamers to the human IL-12 cytokine family and their use as autoimmune disease therapeutics |
US20060193821A1 (en) * | 2004-03-05 | 2006-08-31 | Diener John L | Aptamers to the human IL-12 cytokine family and their use as autoimmune disease therapeutics |
TWI235440B (en) * | 2004-03-31 | 2005-07-01 | Advanced Semiconductor Eng | Method for making leadless semiconductor package |
US7579450B2 (en) * | 2004-04-26 | 2009-08-25 | Archemix Corp. | Nucleic acid ligands specific to immunoglobulin E and their use as atopic disease therapeutics |
CN1989439B (zh) * | 2004-05-06 | 2010-12-29 | 美国政府健康及人类服务部 | 治疗葡萄膜炎的方法以及组合物 |
EP2484374A1 (en) | 2004-07-18 | 2012-08-08 | CSL Limited | Immuno stimulating complex and oligonucleotide formulations for inducing enhanced interferon-gamma responses |
ES2344739T3 (es) | 2004-09-24 | 2010-09-06 | Intercell Ag | Proteina capsidial vp1 modificada del parvovirus b19. |
US8846051B2 (en) | 2004-10-08 | 2014-09-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention | Modulation of replicative fitness by deoptimization of synonymous codons |
MY159370A (en) * | 2004-10-20 | 2016-12-30 | Coley Pharm Group Inc | Semi-soft-class immunostimulatory oligonucleotides |
EP1807107B1 (en) | 2004-11-02 | 2011-09-07 | Archemix Corp. | Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics |
US9809824B2 (en) | 2004-12-13 | 2017-11-07 | The United States Of America, Represented By The Secretary, Department Of Health And Human Services | CpG oligonucleotide prodrugs, compositions thereof and associated therapeutic methods |
EP2682126B1 (en) | 2005-01-27 | 2016-11-23 | Children's Hospital & Research Center at Oakland | GNA1870-based vesicle vaccines for broad spectrum protection against diseases caused by Neisseria meningitidis |
JP2008531018A (ja) * | 2005-02-24 | 2008-08-14 | コーリー ファーマシューティカル グループ,インコーポレイテッド | 免疫刺激性オリゴヌクレオチド |
BRPI0610449A2 (pt) * | 2005-04-08 | 2012-01-10 | Coley Pharm Group Inc | métodos para tratar asma exarcebada por doença infecciosa |
US20060241076A1 (en) * | 2005-04-26 | 2006-10-26 | Coley Pharmaceutical Gmbh | Modified oligoribonucleotide analogs with enhanced immunostimulatory activity |
JP5220594B2 (ja) | 2005-06-14 | 2013-06-26 | プロトクス セラピューティックス インコーポレイティッド | ポア形成修飾タンパク質を用いて良性前立腺肥大症を治療または予防する方法 |
KR20080025181A (ko) | 2005-06-30 | 2008-03-19 | 아케믹스 코포레이션 | 완전 2'-변형된 핵산 전사체를 생성하기 위한 물질 및 방법 |
US8101385B2 (en) | 2005-06-30 | 2012-01-24 | Archemix Corp. | Materials and methods for the generation of transcripts comprising modified nucleotides |
SI2269622T1 (sl) | 2005-07-01 | 2014-05-30 | Index Pharmaceuticals Ab | CpG OLIGONUKLEOTIDI, KI SE UPORABLJAJO ZA IZBOLJĹ ANJE STEROIDNE AKTIVNOSTI PRI STEROIDNO ODVISNIH BOLNIKIH |
ATE439135T1 (de) * | 2005-07-01 | 2009-08-15 | Index Pharmaceuticals Ab | Modulierung der reaktion auf steroide |
EA200800268A1 (ru) * | 2005-07-07 | 2008-06-30 | Коли Фармасьютикал Груп, Инк. | КОМБИНИРОВАННАЯ ТЕРАПИЯ АНТИТЕЛОМ ПРОТИВ CTLA-4 И СОДЕРЖАЩИМ CpG-МОТИВ СИНТЕТИЧЕСКИМ ОЛИГОДЕЗОКСИНУКЛЕОТИДОМ ДЛЯ ЛЕЧЕНИЯ ЗЛОКАЧЕСТВЕННОЙ ОПУХОЛИ |
US20080206276A1 (en) | 2005-07-08 | 2008-08-28 | Michael Otto | Targeting Poly-Gamma-Glutamic Acid to Treat Staphylococcus Epidermidis and Related Infections |
KR20080048067A (ko) * | 2005-09-16 | 2008-05-30 | 콜리 파마슈티칼 게엠베하 | 포스포디에스테르 주쇄를 갖는 면역자극성 단일가닥리보핵산 |
CN101321868A (zh) * | 2005-09-16 | 2008-12-10 | 科利制药公司 | 通过核苷酸修饰调节短干扰核糖核酸(siRNA)的免疫刺激特性 |
US20070081972A1 (en) * | 2005-09-30 | 2007-04-12 | The University Of Iowa Research Foundation | Polymer-based delivery system for immunotherapy of cancer |
CA2625969A1 (en) * | 2005-10-28 | 2007-05-03 | Index Pharmaceuticals Ab | Composition and method for the prevention, treatment and/or alleviation of an inflammatory disease |
CA2630738C (en) | 2005-11-25 | 2013-09-03 | Coley Pharmaceutical Gmbh | Immunostimulatory oligoribonucleotides |
EP1973608A1 (en) | 2005-12-14 | 2008-10-01 | Cytos Biotechnology AG | Immunostimulatory nucleic acid packaged particles for the treatment of hypersensitivity |
EP1991678B2 (en) * | 2006-02-15 | 2020-07-15 | Rechtsanwalt Thomas Beck | Compositions and methods for oligonucleotide formulations |
EP2397854B1 (en) | 2006-03-14 | 2014-06-04 | Oregon Health and Science University | Methods for detecting a mycobacterium tuberculosis infection |
US20100016250A1 (en) | 2006-04-14 | 2010-01-21 | Kyowa Hakko Kirin Co., Ltd. | Toll-like receptor 9 agonists |
US20070243290A1 (en) * | 2006-04-18 | 2007-10-18 | Melody Thompson | Method of tailoring infant formulas to individual nutritional needs prior to use |
CA2655108C (en) | 2006-06-12 | 2019-05-07 | Cytos Biotechnology Ag | Processes for packaging oligonucleotides into virus-like particles of rna bacteriophages |
KR101251707B1 (ko) * | 2006-09-27 | 2013-04-11 | 콜리 파마슈티칼 게엠베하 | 면역 자극 활성이 증강된 소수성 T 유사체를 함유하는 CpG 올리고뉴클레오티드 유사체 |
KR20090058584A (ko) * | 2006-10-26 | 2009-06-09 | 콜리 파마슈티칼 게엠베하 | 올리고리보뉴클레오티드 및 그의 용도 |
DK2444806T3 (da) | 2006-11-01 | 2014-07-21 | Ventana Med Syst Inc | Haptener, haptenkonjugater, sammensætninger deraf og fremgangsmåde til deres fremstilling og anvendelse |
US20090142362A1 (en) * | 2006-11-06 | 2009-06-04 | Avant Immunotherapeutics, Inc. | Peptide-based vaccine compositions to endogenous cholesteryl ester transfer protein (CETP) |
DK2918598T3 (en) | 2007-02-28 | 2019-04-29 | The Govt Of U S A As Represented By The Secretary Of The Dept Of Health And Human Services | Brachyury polypeptides and methods of use |
CA2699190A1 (en) | 2007-04-19 | 2009-10-30 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Use of toll-like receptor-9 agonists, toll-like receptor-4 antagonists, and/or nuclear oligomerization domain-2 agonists for the treatment or prevention of toll-like receptor-4-associated disorders |
US8518903B2 (en) | 2007-04-19 | 2013-08-27 | University of Pittsburgh—of the Commonwealth System of Higher Education | Use of toll-like receptor-9 agonists |
US8320302B2 (en) | 2007-04-20 | 2012-11-27 | Elster Electricity, Llc | Over the air microcontroller flash memory updates |
AU2008252577A1 (en) | 2007-05-17 | 2008-11-27 | Coley Pharmaceutical Gmbh | Class A oligonucleotides with immunostimulatory potency |
HUE025645T2 (hu) * | 2007-05-18 | 2016-04-28 | Adiutide Pharmaceuticals Gmbh | Immunstimuláló hatású foszfát-módosított oligonukleotid analógok |
DK2167963T3 (da) | 2007-05-23 | 2019-06-24 | Ventana Med Syst Inc | Polymerbærere til immunhistokemi og in situ-hybridisering |
JP2010527633A (ja) * | 2007-05-25 | 2010-08-19 | セントコア・オーソ・バイオテツク・インコーポレーテツド | Toll様受容体3モジュレーター及びその使用 |
CN101820908A (zh) | 2007-10-09 | 2010-09-01 | 科利制药公司 | 包含改性糖部分的免疫刺激寡核苷酸类似物 |
CA2703519C (en) | 2007-11-09 | 2017-04-18 | The Salk Institute For Biological Studies | Use of tam receptor inhibitors as immunoenhancers and tam activators as immunosuppressors |
US8815253B2 (en) | 2007-12-07 | 2014-08-26 | Novartis Ag | Compositions for inducing immune responses |
US9511131B2 (en) | 2008-03-10 | 2016-12-06 | Children's Hospital & Research Center Oakland | Chimeric factor H binding proteins (fHBP) containing a heterologous B domain and methods of use |
WO2009143292A2 (en) | 2008-05-21 | 2009-11-26 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating pneumoconiosis with oligodeoxynucleotides |
WO2009149013A2 (en) | 2008-06-05 | 2009-12-10 | Ventana Medical Systems, Inc. | Compositions comprising nanomaterials and method for using such compositions for histochemical processes |
ES2728949T3 (es) | 2008-06-27 | 2019-10-29 | Zoetis Services Llc | Composiciones adyuvantes novedosas |
EP2385371B1 (en) | 2008-09-22 | 2014-10-22 | Oregon Health and Science University | Methods for detecting a mycobacterium tuberculosis infection |
CA2737352C (en) | 2008-10-16 | 2017-06-27 | University Of Saskatchewan | Combination adjuvant formulation |
KR101644221B1 (ko) | 2008-12-09 | 2016-07-29 | 화이자 백신스 엘엘씨 | IgE CH3 펩티드 백신 |
US8664183B2 (en) | 2009-02-27 | 2014-03-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | SPANX-B polypeptides and their use |
MX2011010050A (es) | 2009-03-25 | 2011-12-14 | Univ Texas | Composiciones para estimulación de resistencia inmune innata de mamiferos a patógenos. |
RU2536248C2 (ru) | 2009-04-30 | 2014-12-20 | Коули Фармасьютикал Груп, Инк. | Пневмококковая вакцина и ее применения |
EP2435092A2 (en) | 2009-05-27 | 2012-04-04 | Selecta Biosciences, Inc. | Nanocarriers possessing components with different rates of release |
NZ598356A (en) | 2009-07-30 | 2014-06-27 | Pfizer Vaccines Llc | Antigenic tau peptides and uses thereof |
US8598327B2 (en) | 2009-08-18 | 2013-12-03 | Baxter International Inc. | Aptamers to tissue factor pathway inhibitor and their use as bleeding disorder therapeutics |
US8252913B2 (en) * | 2009-08-18 | 2012-08-28 | Baxter International Inc. | Aptamers to tissue factor pathway inhibitor and their use as bleeding disorder therapeutics |
WO2011026111A1 (en) | 2009-08-31 | 2011-03-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Oral delivery of a vaccine to the large intestine to induce mucosal immunity |
MX2012002639A (es) | 2009-09-03 | 2012-03-14 | Pfizer Vaccines Llc | Vacuna de pcsk9. |
CN102782138A (zh) | 2009-10-07 | 2012-11-14 | Uvic工业合伙公司 | 包含热敏性转基因的疫苗 |
WO2011047340A1 (en) | 2009-10-16 | 2011-04-21 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Insertion of foreign genes in rubella virus and their stable expression in a live, attenuated viral vaccine |
EP3263124A1 (en) | 2009-11-20 | 2018-01-03 | Oregon Health&Science University | Methods for producing an immune response to tuberculosis |
CN107412754A (zh) | 2009-12-22 | 2017-12-01 | 塞尔德克斯医疗公司 | 疫苗组合物 |
WO2011112599A2 (en) | 2010-03-12 | 2011-09-15 | The United States Of America, As Represented By The Secretary. Department Of Health & Human Services | Immunogenic pote peptides and methods of use |
EP3327028B1 (en) | 2010-03-30 | 2022-03-16 | Children's Hospital & Research Center at Oakland | Factor h binding proteins (fhbp) with altered properties and methods of use thereof |
ES2788198T3 (es) | 2010-05-14 | 2020-10-20 | Univ Oregon Health & Science | Vectores de CMVH y CMVRh recombinantes que codifican un antígeno heterólogo aislado del virus de la hepatitis B y usos de los mismos |
ES2661978T3 (es) | 2010-05-26 | 2018-04-04 | Selecta Biosciences, Inc. | Vacunas multivalentes de nanovehículos sintéticos |
EP2576613A1 (en) | 2010-06-07 | 2013-04-10 | Pfizer Inc. | Her-2 peptides and vaccines |
EP2942061A3 (en) | 2010-06-07 | 2016-01-13 | Pfizer Vaccines LLC | Ige ch3 peptide vaccine |
US8883171B2 (en) | 2010-09-14 | 2014-11-11 | University of Pittsburgh—of the Commonwealth System of Higher Education | Computationally optimized broadly reactive antigens for influenza |
US10668092B2 (en) | 2010-09-24 | 2020-06-02 | The John Hopkins University | Compositions and methods for treatment of inflammatory disorders |
US9072760B2 (en) | 2010-09-24 | 2015-07-07 | University of Pittsburgh—of the Commonwealth System of Higher Education | TLR4 inhibitors for the treatment of human infectious and inflammatory disorders |
EA201390660A1 (ru) | 2010-11-05 | 2013-11-29 | Селекта Байосайенсиз, Инк. | Модифицированные никотиновые соединения и связанные способы |
WO2012088425A2 (en) | 2010-12-22 | 2012-06-28 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Gap junction-enhancing agents for treatment of necrotizing enterocolitis and inflammatory bowel disease |
CA2827160A1 (en) | 2011-02-11 | 2012-08-16 | Baxter Healthcare S.A. | Aptamers to tissue factor pathway inhibitor and their use as bleeding disorder therapeutics |
EP2680883B1 (en) | 2011-03-02 | 2018-09-05 | Pfizer Inc | Pcsk9 vaccine |
WO2012142480A1 (en) * | 2011-04-14 | 2012-10-18 | Beth Israel Deaconess Medical Center, Inc. | Chimeric rna oligonucleotides and uses thereof |
FR2975600B1 (fr) | 2011-05-24 | 2013-07-05 | Assist Publ Hopitaux De Paris | Agents pour le traitement de tumeurs |
CN109912602A (zh) | 2011-06-01 | 2019-06-21 | 贾纳斯生物治疗有限公司 | 新型免疫系统调节剂 |
ES2583877T3 (es) | 2011-06-01 | 2016-09-22 | Janus Biotherapeutics, Inc. | Moduladores novedosos del sistema inmunitario |
JP6113155B2 (ja) | 2011-06-20 | 2017-04-12 | ユニバーシティ オブ ピッツバーグ − オブ ザ コモンウェルス システム オブ ハイヤー エデュケイション | 計算で最適化した広い反応性を示すh1n1インフルエンザの抗原 |
CN109172819A (zh) | 2011-07-29 | 2019-01-11 | 西莱克塔生物科技公司 | 产生体液和细胞毒性t淋巴细胞(ctl)免疫应答的合成纳米载体 |
WO2013039792A1 (en) | 2011-09-12 | 2013-03-21 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Immunogens based on an hiv-1 gp120 v1v2 epitope |
US20140234360A1 (en) | 2011-09-30 | 2014-08-21 | The United States of America, as represented by the Secretary, Dept.of Health and Human Services | Influenza vaccine |
IN2014KN00948A (ja) | 2011-10-04 | 2015-08-21 | Janus Biotherapeutics Inc | |
AU2012326079B2 (en) | 2011-10-20 | 2017-01-12 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Dengue virus E-glycoprotein polypeptides containing mutations that eliminate immunodominant cross-reactive epitopes |
EP2804613A4 (en) | 2012-01-16 | 2015-12-09 | Elizabeth Mckenna | COMPOSITIONS AND METHODS FOR TREATING DISEASES AND HEPATIC DISORDERS |
US20140086849A1 (en) | 2012-09-21 | 2014-03-27 | Elizabeth McKenna | Naturally-Occurring CpG Oligonucleotide Compositions and Therapeutic Applications Thereof |
WO2013119683A1 (en) | 2012-02-07 | 2013-08-15 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Computationally optimized broadly reactive antigens for h3n2, h2n2, and b influenza viruses |
CA2863949C (en) | 2012-02-13 | 2021-06-29 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Computationally optimized broadly reactive antigens for human and avian h5n1 influenza |
US9421250B2 (en) | 2012-03-23 | 2016-08-23 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pathogenic phlebovirus isolates and compositions and methods of use |
RU2737765C2 (ru) | 2012-05-04 | 2020-12-02 | Пфайзер Инк. | Простатоассоциированные антигены и иммунотерапевтические схемы на основе вакцин |
WO2013177291A1 (en) | 2012-05-23 | 2013-11-28 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Salmonella typhi ty21a expressing yersinia pestis f1-v fusion protein and uses thereof |
CN104428008B (zh) | 2012-05-24 | 2020-10-09 | 美国政府(由卫生和人类服务部的部长所代表) | 多价脑膜炎球菌缀合物及制备缀合物的方法 |
US9687542B2 (en) | 2012-06-19 | 2017-06-27 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Rift valley fever virus replicon particles and use thereof |
WO2014043518A1 (en) | 2012-09-14 | 2014-03-20 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Brachyury protein, non-poxvirus non-yeast vectors encoding brachyury protein, and their use |
WO2014052453A1 (en) * | 2012-09-25 | 2014-04-03 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Oral therapy of necrotizing enterocolitis |
CA2909721A1 (en) | 2013-04-19 | 2014-10-23 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Lone star virus |
CN112999344A (zh) | 2013-05-15 | 2021-06-22 | 阿尔伯达大学董事会 | E1e2 hcv疫苗及使用方法 |
WO2015042369A2 (en) | 2013-09-19 | 2015-03-26 | Zoetis Llc | Oil-based adjuvants |
WO2015048785A2 (en) | 2013-09-30 | 2015-04-02 | Los Alamos National Security, Llc | Mosaic conserved region hiv immunogenic polypeptides |
BR112016008806A2 (pt) | 2013-11-01 | 2017-10-03 | Pfizer | Vetores para expressão de antígenos associados à próstata |
JP6758185B2 (ja) | 2013-12-13 | 2020-09-23 | ザ ユナイテッド ステイツ オブ アメリカ, アズ リプレゼンテッド バイ ザ セクレタリー, デパートメント オブ ヘルス アンド ヒューマン サービシーズ | マルチエピトープtarpペプチドワクチンおよびその使用 |
US11160855B2 (en) | 2014-01-21 | 2021-11-02 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
WO2015110940A2 (en) | 2014-01-21 | 2015-07-30 | Pfizer Inc. | Streptococcus pneumoniae capsular polysaccharides and conjugates thereof |
AU2015208821B2 (en) | 2014-01-21 | 2017-11-02 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
SI3583947T1 (sl) | 2014-01-21 | 2024-01-31 | Pfizer Inc. | Kapsularni polisaharidi streptococcus pneumoniae in njihovi konjugati |
WO2015123291A1 (en) | 2014-02-11 | 2015-08-20 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Pcsk9 vaccine and methods of using the same |
US20170121373A1 (en) | 2014-05-30 | 2017-05-04 | Sanofi Pasteur Inc. | Expression and conformational analysis of engineered influenza hemagglutinin |
ES2725948T3 (es) | 2014-06-04 | 2019-09-30 | Exicure Inc | Suministro multivalente de inmunomoduladores mediante ácidos nucleicos esféricos liposomales para aplicaciones profilácticas o terapéuticas |
CN107108629A (zh) | 2014-08-22 | 2017-08-29 | 贾纳斯生物治疗有限公司 | 新颖的n2, n4, n7, 6‑四取代的蝶啶‑2,4,7‑三胺和2, 4, 6, 7‑四取代的蝶啶化合物及其合成和使用方法 |
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 |
PL3244917T3 (pl) | 2015-01-15 | 2023-07-17 | Pfizer Inc. | Kompozycje immunogenne do zastosowania w szczepionkach przeciwko pneumokokom |
PL3244920T3 (pl) | 2015-01-16 | 2023-09-25 | Zoetis Services Llc | Szczepionka przeciw pryszczycy |
CA3014427A1 (en) | 2015-02-13 | 2016-08-18 | Icahn School Of Medicine At Mount Sinai | Rna containing compositions and methods of their use |
WO2016196846A2 (en) | 2015-06-02 | 2016-12-08 | Sanofi Pasteur Inc. | Engineered influenza antigenic polypeptides and immunogenic compositions thereof |
ES2895148T3 (es) | 2015-06-10 | 2022-02-17 | Us Health | Procesos para la producción y purificación de composiciones que contienen ácidos nucleicos |
KR102225282B1 (ko) | 2015-07-21 | 2021-03-10 | 화이자 인코포레이티드 | 접합된 캡슐형 사카라이드 항원을 포함하는 면역원성 조성물, 그를 포함하는 키트 및 그의 용도 |
WO2017062246A1 (en) | 2015-10-05 | 2017-04-13 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Human rota virus g9p[6] strain and use as a vaccine |
US11266726B2 (en) | 2015-10-30 | 2022-03-08 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Compositions and methods for the treatment of HER2-expressing solid tumors |
WO2017085586A1 (en) | 2015-11-20 | 2017-05-26 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
TWI709647B (zh) | 2016-01-19 | 2020-11-11 | 美商輝瑞股份有限公司 | 癌症疫苗 |
WO2017189448A1 (en) | 2016-04-25 | 2017-11-02 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Bivalent immunogenic conjugate for malaria and typhoid |
AU2017261360A1 (en) | 2016-05-06 | 2018-11-29 | Exicure Operating Company | Liposomal Spherical Nucleic Acid (SNA) constructs presenting Antisense Oligonucleotides (ASO) for specific knockdown of interleukin 17 receptor MRNA |
WO2017201390A1 (en) | 2016-05-19 | 2017-11-23 | The Regents Of The University Of Michigan | Novel adjuvant compositions |
US10844097B2 (en) | 2016-06-02 | 2020-11-24 | Sanofi Pasteur Inc. | Engineered influenza antigenic polypeptides and immunogenic compositions thereof |
BR112018075078A2 (pt) | 2016-06-03 | 2019-03-06 | Sanofi Pasteur Inc. | modificação de polipeptídeos da hemaglutinina do influenza manipulados |
WO2017218339A1 (en) | 2016-06-13 | 2017-12-21 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Nucleic acids encoding zika virus-like particles and their use in zika virus vaccines and diagnostic assays |
CA3030154A1 (en) | 2016-07-08 | 2018-01-11 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric dengue/zika viruses live-attenuated zika virus vaccines |
WO2018009603A1 (en) | 2016-07-08 | 2018-01-11 | The United State of America, as represented by the Secretary, Department of Health and Human Service | Chimeric west nile/zika viruses and methods of use |
CA3031797A1 (en) | 2016-08-05 | 2018-02-08 | Sanofi Pasteur, Inc. | Multivalent pneumococcal polysaccharide-protein conjugate composition |
SG11201900794PA (en) | 2016-08-05 | 2019-02-27 | Sanofi Pasteur Inc | Multivalent pneumococcal polysaccharide-protein conjugate composition |
US10172933B2 (en) | 2016-10-31 | 2019-01-08 | The United States Of America, As Represented By The Secretary Of Agriculture | Mosaic vaccines for serotype a foot-and-mouth disease virus |
HRP20220573T1 (hr) | 2017-01-20 | 2022-06-10 | Pfizer Inc. | Imunogeni pripravci, namijenjeni upotrebi u pneumokoknim cjepivima |
WO2018201090A1 (en) | 2017-04-28 | 2018-11-01 | Exicure, Inc. | Synthesis of spherical nucleic acids using lipophilic moieties |
WO2019018744A1 (en) | 2017-07-21 | 2019-01-24 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | IMMUNOGENIC COMPOSITIONS OF NEISSERIA MENINGITIDIS |
EP3703745B1 (en) | 2017-11-04 | 2024-04-10 | Nevada Research & Innovation Corporation | Immunogenic conjugates and methods of use thereof |
US11116830B2 (en) | 2017-12-18 | 2021-09-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Bacterial polysaccharide-conjugated carrier proteins and use thereof |
US11224648B2 (en) | 2017-12-19 | 2022-01-18 | Massachusetts Institute Of Technology | Antigen-adjuvant coupling reagents and methods of use |
EP3743107A1 (en) | 2018-01-22 | 2020-12-02 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Broadly protective inactivated influenza virus vaccine |
US11633471B2 (en) | 2018-03-06 | 2023-04-25 | Unm Rainforest Innovations | Compositions and methods for reducing serum triglycerides |
WO2019191257A1 (en) | 2018-03-28 | 2019-10-03 | Sanofi Pasteur Inc. | Methods of generating broadly protective vaccine compositions comprising hemagglutinin |
KR20210018206A (ko) | 2018-04-03 | 2021-02-17 | 사노피 | 항원성 호흡기 세포융합 바이러스 폴리펩타이드 |
EP3773708A2 (en) | 2018-04-03 | 2021-02-17 | Sanofi | Antigenic epstein barr virus polypeptides |
CN112512564A (zh) | 2018-04-03 | 2021-03-16 | 赛诺菲 | 铁蛋白蛋白 |
CN112584858A (zh) | 2018-04-03 | 2021-03-30 | 赛诺菲 | 抗原性ospa多肽 |
EP3773703A1 (en) | 2018-04-03 | 2021-02-17 | Sanofi | Antigenic influenza-ferritin polypeptides |
US11260119B2 (en) | 2018-08-24 | 2022-03-01 | Pfizer Inc. | Escherichia coli compositions and methods thereof |
KR20210124205A (ko) | 2018-12-04 | 2021-10-14 | 더 락커펠러 유니버시티 | Hiv 백신 면역원 |
EP3894547A1 (en) | 2018-12-12 | 2021-10-20 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Recombinant mumps virus vaccine expressing genotype g fusion and hemagglutinin-neuraminidase proteins |
EP3893926A1 (en) | 2018-12-12 | 2021-10-20 | Pfizer Inc. | Immunogenic multiple hetero-antigen polysaccharide-protein conjugates and uses thereof |
US20220023410A1 (en) | 2018-12-14 | 2022-01-27 | University Of Georgia Research Foundation, Inc. | Crimean-congo hemorrhagic fever virus replicon particles and use thereof |
WO2020205986A1 (en) | 2019-04-02 | 2020-10-08 | Sanofi | Antigenic multimeric respiratory syncytial virus polypeptides |
US20220184199A1 (en) | 2019-04-10 | 2022-06-16 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens, kits comprising the same and uses thereof |
MX2022005252A (es) | 2019-11-01 | 2022-06-08 | Pfizer | Composiciones de escherichia coli y metodos de las mismas. |
WO2021127271A1 (en) | 2019-12-17 | 2021-06-24 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Live attenuated leishmania parasite vaccines with enhanced safety characteristics |
MX2022010350A (es) | 2020-02-23 | 2022-09-19 | Pfizer | Composiciones de esquerichia coli y sus metodos. |
JP2023515829A (ja) | 2020-02-28 | 2023-04-14 | サノフィ パスツール インコーポレイテッド | 小児対象のための高用量インフルエンザワクチン |
US11213482B1 (en) | 2020-03-05 | 2022-01-04 | University of Pittsburgh—Of the Commonwealth System of Higher Educat | SARS-CoV-2 subunit vaccine and microneedle array delivery system |
JP2023546615A (ja) | 2020-10-27 | 2023-11-06 | ファイザー・インク | 大腸菌組成物およびその方法 |
AU2021373358A1 (en) | 2020-11-04 | 2023-06-01 | Pfizer Inc. | Immunogenic compositions for use in pneumococcal vaccines |
CA3200968A1 (en) | 2020-11-10 | 2022-05-19 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
US20220202923A1 (en) | 2020-12-23 | 2022-06-30 | Pfizer Inc. | E. coli fimh mutants and uses thereof |
WO2022147373A1 (en) | 2020-12-31 | 2022-07-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Antibody-guided pcsk9-mimicking immunogens lacking 9-residue sequence overlap with human proteins |
CN117425668A (zh) | 2021-03-16 | 2024-01-19 | 国立大学法人大阪大学 | SARS-CoV-2病毒特异性滤泡辅助性T细胞Tfh |
EP4310171A1 (en) | 2021-03-16 | 2024-01-24 | Osaka University | Novel medical technique using follicular t-cells |
WO2022249106A2 (en) | 2021-05-28 | 2022-12-01 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
US20220387576A1 (en) | 2021-05-28 | 2022-12-08 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
WO2023288263A1 (en) | 2021-07-16 | 2023-01-19 | The Board Of Trustees Of The University Of Illinois | Universal vaccine for influenza virus based on tetrameric m2 protein incorporated into nanodiscs |
EP4384534A1 (en) | 2021-08-11 | 2024-06-19 | Sanofi Pasteur, Inc. | Truncated influenza neuraminidase and methods of using the same |
WO2023059857A1 (en) | 2021-10-08 | 2023-04-13 | Sanofi Pasteur Inc. | Multivalent influenza vaccines |
AR127585A1 (es) | 2021-11-05 | 2024-02-07 | Sanofi Sa | Vacuna de arn de virus sincicial respiratorio |
CA3237139A1 (en) | 2021-11-05 | 2023-05-11 | Sanofi | Hybrid multivalent influenza vaccines comprising hemagglutinin and neuraminidase and methods of using the same |
CA3237134A1 (en) | 2021-11-05 | 2023-05-11 | Timothy ALEFANTIS | Multivalent influenza vaccines comprising recombinant hemagglutinin and neuraminidase and methods of using the same |
CA3239417A1 (en) | 2021-11-30 | 2023-06-08 | Yvonne CHAN | Human metapneumovirus vaccines |
CA3239461A1 (en) | 2021-11-30 | 2023-06-08 | Yvonne CHAN | Human metapneumovirus viral vector-based vaccines |
WO2023111262A1 (en) | 2021-12-17 | 2023-06-22 | Sanofi | Lyme disease rna vaccine |
WO2023135515A1 (en) | 2022-01-13 | 2023-07-20 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
WO2023144206A1 (en) | 2022-01-27 | 2023-08-03 | Sanofi Pasteur | Modified vero cells and methods of using the same for virus production |
WO2023161817A1 (en) | 2022-02-25 | 2023-08-31 | Pfizer Inc. | Methods for incorporating azido groups in bacterial capsular polysaccharides |
WO2023177577A1 (en) | 2022-03-14 | 2023-09-21 | Sanofi Pasteur Inc. | Machine-learning techniques in protein design for vaccine generation |
TW202408567A (zh) | 2022-05-06 | 2024-03-01 | 法商賽諾菲公司 | 用於核酸疫苗之訊息序列 |
WO2023218322A1 (en) | 2022-05-11 | 2023-11-16 | Pfizer Inc. | Process for producing of vaccine formulations with preservatives |
WO2024094881A1 (en) | 2022-11-04 | 2024-05-10 | Sanofi | Respiratory syncytial virus rna vaccination |
WO2024110827A1 (en) | 2022-11-21 | 2024-05-30 | Pfizer Inc. | Methods for preparing conjugated capsular saccharide antigens and uses thereof |
US20240181028A1 (en) | 2022-11-22 | 2024-06-06 | Pfizer Inc. | Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof |
WO2024116096A1 (en) | 2022-12-01 | 2024-06-06 | Pfizer Inc. | Pneumococcal conjugate vaccine formulations |
WO2024121380A1 (en) | 2022-12-08 | 2024-06-13 | Pierre Fabre Medicament | Vaccinal composition and adjuvant |
WO2024127215A2 (en) | 2022-12-13 | 2024-06-20 | Pfizer Inc. | Immunogenic compositions and methods for eliciting an immune response against clostridioides (clostridium) difficile |
WO2024133515A1 (en) | 2022-12-20 | 2024-06-27 | Sanofi | Rhinovirus mrna vaccine |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3906092A (en) | 1971-11-26 | 1975-09-16 | Merck & Co Inc | Stimulation of antibody response |
US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
DE3280400D1 (de) | 1981-10-23 | 1992-06-04 | Molecular Biosystems Inc | Oligonukleotides heilmittel und dessen herstellungsverfahren. |
CA1339596C (en) | 1987-08-07 | 1997-12-23 | New England Medical Center Hospitals, Inc. | Viral expression inhibitors |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US5786189A (en) | 1989-11-29 | 1998-07-28 | Smithkline Beecham Biologicals (S.A.) | Vaccine |
US5514577A (en) | 1990-02-26 | 1996-05-07 | Isis Pharmaceuticals, Inc. | Oligonucleotide therapies for modulating the effects of herpes viruses |
US5248670A (en) | 1990-02-26 | 1993-09-28 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides for inhibiting herpesviruses |
EP0468520A3 (en) | 1990-07-27 | 1992-07-01 | Mitsui Toatsu Chemicals, Inc. | Immunostimulatory remedies containing palindromic dna sequences |
AU649717B2 (en) | 1990-08-16 | 1994-06-02 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating the effects of cytomegalovirus infections |
JPH06509704A (ja) | 1991-04-18 | 1994-11-02 | ザ ソールク インスチチュート フォア バイオロジカル スタディズ | 特定dna配列に選択的に結合する蛋白質に対する偽構築体として有用なオリゴデオキシヌクレオチドおよびオリゴヌクレオチド |
EP0587749A4 (en) | 1991-05-31 | 1995-08-30 | Genta Inc | Compositions and delivery systems for transdermal administration of neutral oligomers |
AU4685593A (en) * | 1992-07-17 | 1994-02-14 | Aprogenex, Inc. | Enriching and identyfying fetal cells in maternal blood for in situ hybridization |
US5585479A (en) | 1992-07-24 | 1996-12-17 | The United States Of America As Represented By The Secretary Of The Navy | Antisense oligonucleotides directed against human ELAM-I RNA |
WO1995005853A1 (en) | 1993-08-26 | 1995-03-02 | The Regents Of The University Of California | Method, compositions and devices for administration of naked polynucleotides which encode biologically active peptides |
US5849719A (en) | 1993-08-26 | 1998-12-15 | The Regents Of The University Of California | Method for treating allergic lung disease |
US5830877A (en) | 1993-08-26 | 1998-11-03 | The Regents Of The University Of California | Method, compositions and devices for administration of naked polynucleotides which encode antigens and immunostimulatory |
US5679647A (en) | 1993-08-26 | 1997-10-21 | The Regents Of The University Of California | Methods and devices for immunizing a host against tumor-associated antigens through administration of naked polynucleotides which encode tumor-associated antigenic peptides |
US5804566A (en) | 1993-08-26 | 1998-09-08 | The Regents Of The University Of California | Methods and devices for immunizing a host through administration of naked polynucleotides with encode allergenic peptides |
WO1995026204A1 (en) | 1994-03-25 | 1995-10-05 | Isis Pharmaceuticals, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
WO1996002555A1 (en) | 1994-07-15 | 1996-02-01 | The University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
JPH10502820A (ja) * | 1994-07-18 | 1998-03-17 | ユニバーシティ・オブ・ノース・カロライナ・アット・チャペル・ヒル | 腫瘍増殖、浸潤および転移を阻害するためのオリゴヌクレオシド化合物および方法 |
US6004813A (en) | 1995-05-11 | 1999-12-21 | Applied Research Systems Ars Holding N.V. | Il-6 activity inhibitor |
US5994315A (en) * | 1995-06-07 | 1999-11-30 | East Carolina University | Low adenosine agent, composition, kit and method for treatment of airway disease |
ATE437943T1 (de) | 1996-01-30 | 2009-08-15 | Univ California | Expressionsvektoren, die eine antigen-spezifische immunantwort induzieren, und methoden für ihre verwendung. |
JP2001513776A (ja) | 1997-02-28 | 2001-09-04 | ユニバーシティ オブ アイオワ リサーチ ファウンデーション | LPS関連障害の処置における非メチル化CpGジヌクレオチドを含む核酸の使用 |
AU8018298A (en) | 1997-06-05 | 1998-12-21 | Imperial Chemical Industries | Method for the preparation of carbamates |
CA2291483C (en) | 1997-06-06 | 2012-09-18 | Dynavax Technologies Corporation | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
-
1998
- 1998-02-25 JP JP53781098A patent/JP2001513776A/ja not_active Ceased
- 1998-02-25 WO PCT/US1998/003678 patent/WO1998037919A1/en active IP Right Grant
- 1998-02-25 US US09/030,701 patent/US6214806B1/en not_active Expired - Fee Related
- 1998-02-25 AU AU66674/98A patent/AU738513B2/en not_active Ceased
- 1998-02-25 EP EP98908714A patent/EP1039935A4/en not_active Withdrawn
- 1998-02-25 CA CA002281838A patent/CA2281838A1/en not_active Abandoned
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002500159A (ja) * | 1997-09-05 | 2002-01-08 | 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 | 抗原刺激顆粒球媒介炎症を予防または軽減するための免疫刺激オリゴヌクレオチドの使用 |
JP4663113B2 (ja) * | 1997-09-05 | 2011-03-30 | 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 | 抗原刺激顆粒球媒介炎症を予防または軽減するための免疫刺激オリゴヌクレオチドの使用 |
US7858589B2 (en) * | 1998-08-10 | 2010-12-28 | Antigenics Inc. | Compositions of CpG and saponin adjuvants and uses thereof |
JP2005502338A (ja) * | 2001-08-17 | 2005-01-27 | コーリー ファーマシューティカル グループ,インコーポレイテッド | 改善した活性を有する組み合わせモチーフ免疫刺激オリゴヌクレオチド |
JP2006508693A (ja) * | 2002-08-19 | 2006-03-16 | コーリー ファーマシューティカル グループ,インコーポレイテッド | 免疫刺激性核酸 |
Also Published As
Publication number | Publication date |
---|---|
AU6667498A (en) | 1998-09-18 |
US6214806B1 (en) | 2001-04-10 |
EP1039935A4 (en) | 2005-04-27 |
CA2281838A1 (en) | 1998-09-03 |
AU738513B2 (en) | 2001-09-20 |
EP1039935A1 (en) | 2000-10-04 |
WO1998037919A1 (en) | 1998-09-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2001513776A (ja) | LPS関連障害の処置における非メチル化CpGジヌクレオチドを含む核酸の使用 | |
JP4663113B2 (ja) | 抗原刺激顆粒球媒介炎症を予防または軽減するための免疫刺激オリゴヌクレオチドの使用 | |
EP1511845B1 (en) | Immunostimulatory oligonucleotides and uses thereof | |
EP2901856B1 (en) | Immunostimulatory oligonucleotide multimers | |
Schwartz et al. | CpG motifs in bacterial DNA cause inflammation in the lower respiratory tract. | |
JP5074392B2 (ja) | 免疫促進方法 | |
Deng et al. | CpG oligodeoxynucleotides stimulate protective innate immunity against pulmonary Klebsiella infection | |
JP4976653B2 (ja) | 免疫刺激性CpGオリゴヌクレオチドを用いてバイオテロ病原体による感染症を予防する方法 | |
EP2034015B1 (en) | Immunostimulatory oligonucleotide and pharmaceutical application thereof | |
EP1904077B1 (en) | Modulating responsiveness to steroids | |
US20060094680A1 (en) | Immunostimulatory oligonucleotide multimers | |
MX2007012488A (es) | Metodos para el tratamiento de asma exacerbado por enfermedad infecciosa. | |
JP2003527352A (ja) | Cpgおよびサポニンの自然免疫刺激化合物、ならびにそれらの方法 | |
JP2001503267A (ja) | 免疫刺激性核酸分子 | |
JP2009132737A (ja) | 刺激性免疫応答用の核酸組成物 | |
US8043622B2 (en) | Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides | |
CA2452909A1 (en) | Immunostimulatory oligodeoxynucleotides | |
Bhagat et al. | CpG penta-and hexadeoxyribonucleotides as potent immunomodulatory agents | |
BR112015016420B1 (pt) | Composto de oligonucleotídeo imunorregulatório, composição farmacêutica e uso do composto iro ou da composição farmacêutica | |
JP2009513629A (ja) | 炎症性疾患を予防、処置、および/または緩和する組成物および方法 | |
Tong et al. | Differential expression of cytokine genes and iNOS induced by nonviable nontypeable Haemophilus influenzae or its LOS mutants during acute otitis media in the rat | |
Yordanov et al. | Candida albicans double-stranded DNA can participate in the host defense against disseminated candidiasis | |
Alam et al. | In Vivo Role of p38 Mitogen-Activated Protein Kinase in Mediating the Anti-inflammatory Effects of CpG... | |
CA2487904A1 (en) | Immunostimulatory oligonucleotides and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050224 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050224 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081209 |
|
A313 | Final decision of rejection without a dissenting response from the applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A313 Effective date: 20090420 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090602 |