JP3976742B2 - インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド - Google Patents
インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド Download PDFInfo
- Publication number
- JP3976742B2 JP3976742B2 JP2004053795A JP2004053795A JP3976742B2 JP 3976742 B2 JP3976742 B2 JP 3976742B2 JP 2004053795 A JP2004053795 A JP 2004053795A JP 2004053795 A JP2004053795 A JP 2004053795A JP 3976742 B2 JP3976742 B2 JP 3976742B2
- Authority
- JP
- Japan
- Prior art keywords
- ifn
- cpg dna
- activity
- sequence
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 108091034117 Oligonucleotide Proteins 0.000 title claims description 22
- 230000003308 immunostimulating effect Effects 0.000 title claims description 22
- 108010047761 Interferon-alpha Proteins 0.000 title description 58
- 102000006992 Interferon-alpha Human genes 0.000 title description 57
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 title description 5
- 239000000427 antigen Substances 0.000 claims description 52
- 108091007433 antigens Proteins 0.000 claims description 52
- 102000036639 antigens Human genes 0.000 claims description 52
- 239000003814 drug Substances 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000002955 immunomodulating agent Substances 0.000 claims description 5
- 230000002584 immunomodulator Effects 0.000 claims description 5
- 229940121354 immunomodulator Drugs 0.000 claims description 5
- CTMZLDSMFCVUNX-VMIOUTBZSA-N cytidylyl-(3'->5')-guanosine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=C(C(N=C(N)N3)=O)N=C2)O)[C@@H](CO)O1 CTMZLDSMFCVUNX-VMIOUTBZSA-N 0.000 description 139
- 108020004414 DNA Proteins 0.000 description 123
- 230000000694 effects Effects 0.000 description 61
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 54
- 239000002585 base Substances 0.000 description 37
- 210000000822 natural killer cell Anatomy 0.000 description 34
- 210000004027 cell Anatomy 0.000 description 28
- 230000001939 inductive effect Effects 0.000 description 25
- 238000004519 manufacturing process Methods 0.000 description 24
- 206010028980 Neoplasm Diseases 0.000 description 23
- 102100037850 Interferon gamma Human genes 0.000 description 20
- 108010074328 Interferon-gamma Proteins 0.000 description 20
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 20
- 238000007792 addition Methods 0.000 description 19
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 16
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 16
- 230000006698 induction Effects 0.000 description 15
- 108020004707 nucleic acids Proteins 0.000 description 15
- 102000039446 nucleic acids Human genes 0.000 description 15
- 150000007523 nucleic acids Chemical class 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 201000011510 cancer Diseases 0.000 description 14
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 description 14
- 102000004127 Cytokines Human genes 0.000 description 13
- 108090000695 Cytokines Proteins 0.000 description 13
- 102000013462 Interleukin-12 Human genes 0.000 description 12
- 108010065805 Interleukin-12 Proteins 0.000 description 12
- 230000004913 activation Effects 0.000 description 12
- 208000026935 allergic disease Diseases 0.000 description 11
- 230000011488 interferon-alpha production Effects 0.000 description 11
- 230000014509 gene expression Effects 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- 108091081548 Palindromic sequence Proteins 0.000 description 9
- 210000003719 b-lymphocyte Anatomy 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 210000000987 immune system Anatomy 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 9
- 230000009257 reactivity Effects 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 241000700605 Viruses Species 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 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 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 7
- 210000004443 dendritic cell Anatomy 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 208000035473 Communicable disease Diseases 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 239000013566 allergen Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000012228 culture supernatant Substances 0.000 description 6
- 230000036039 immunity Effects 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 230000002458 infectious effect Effects 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 108020000946 Bacterial DNA Proteins 0.000 description 5
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 5
- 241000233866 Fungi Species 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 206010020751 Hypersensitivity Diseases 0.000 description 5
- 230000006051 NK cell activation Effects 0.000 description 5
- 210000000612 antigen-presenting cell Anatomy 0.000 description 5
- -1 etc.) Proteins 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000031261 interleukin-10 production Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 241000251468 Actinopterygii Species 0.000 description 4
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 4
- 102000003814 Interleukin-10 Human genes 0.000 description 4
- 108090000174 Interleukin-10 Proteins 0.000 description 4
- 108090000978 Interleukin-4 Proteins 0.000 description 4
- 102000004388 Interleukin-4 Human genes 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 230000002708 enhancing effect Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 239000000693 micelle Substances 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000003844 B-cell-activation Effects 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- 241000286209 Phasianidae Species 0.000 description 3
- 241000288906 Primates Species 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 230000029662 T-helper 1 type immune response Effects 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 235000013330 chicken meat Nutrition 0.000 description 3
- 238000001246 colloidal dispersion Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 3
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000006177 thiolation reaction Methods 0.000 description 3
- 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 compound 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 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- 108020004491 Antisense DNA Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 108010069941 DNA receptor Proteins 0.000 description 2
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 229930186217 Glycolipid Natural products 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 108010032036 Interferon Regulatory Factor-7 Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 239000003816 antisense DNA Substances 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000003305 autocrine Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 230000019734 interleukin-12 production Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 244000000010 microbial pathogen Species 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 239000002088 nanocapsule Substances 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 239000012646 vaccine adjuvant Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- FVFVNNKYKYZTJU-UHFFFAOYSA-N 6-chloro-1,3,5-triazine-2,4-diamine Chemical group NC1=NC(N)=NC(Cl)=N1 FVFVNNKYKYZTJU-UHFFFAOYSA-N 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 108091029430 CpG site Proteins 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 208000004262 Food Hypersensitivity Diseases 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 1
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000002227 Interferon Type I Human genes 0.000 description 1
- 108010014726 Interferon Type I Proteins 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 102100038070 Interferon regulatory factor 7 Human genes 0.000 description 1
- 102100038251 Interferon regulatory factor 9 Human genes 0.000 description 1
- 101710157824 Interferon regulatory factor 9 Proteins 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 230000004163 JAK-STAT signaling pathway Effects 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 108010044012 STAT1 Transcription Factor Proteins 0.000 description 1
- 102000004265 STAT2 Transcription Factor Human genes 0.000 description 1
- 108010081691 STAT2 Transcription Factor Proteins 0.000 description 1
- 102100029904 Signal transducer and activator of transcription 1-alpha/beta Human genes 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 108010018242 Transcription Factor AP-1 Proteins 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 125000002843 carboxylic acid group Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000020932 food allergy Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000002434 immunopotentiative effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004053795A JP3976742B2 (ja) | 2004-02-27 | 2004-02-27 | インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド |
| PCT/JP2005/003693 WO2005083076A1 (ja) | 2004-02-27 | 2005-02-25 | インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド |
| US10/590,761 US7718623B2 (en) | 2004-02-27 | 2005-02-25 | Immunostimulatory oligonucleotide that induces interferon alpha |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2004053795A JP3976742B2 (ja) | 2004-02-27 | 2004-02-27 | インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005237328A JP2005237328A (ja) | 2005-09-08 |
| JP2005237328A5 JP2005237328A5 (enExample) | 2006-10-12 |
| JP3976742B2 true JP3976742B2 (ja) | 2007-09-19 |
Family
ID=34908763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004053795A Expired - Lifetime JP3976742B2 (ja) | 2004-02-27 | 2004-02-27 | インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US7718623B2 (enExample) |
| JP (1) | JP3976742B2 (enExample) |
| WO (1) | WO2005083076A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4817599B2 (ja) * | 2003-12-25 | 2011-11-16 | 独立行政法人科学技術振興機構 | 免疫活性増強剤とこれを用いた免疫活性の増強方法 |
| CA2653939C (en) | 2006-05-31 | 2013-01-22 | Toray Industries, Inc. | Immunostimulatory oligonucleotides and use thereof in pharmaceuticals |
| JP5280432B2 (ja) * | 2007-04-27 | 2013-09-04 | ヒュンジン ヤン | 比重の増加した細胞培養用支持体及びその製造方法 |
| WO2009069682A1 (ja) * | 2007-11-28 | 2009-06-04 | Toray Industries, Inc. | 肝炎の治療剤又は予防剤 |
| WO2009069447A1 (ja) * | 2007-11-28 | 2009-06-04 | Toray Industries, Inc. | インフルエンザワクチン用のアジュバント及びインフルエンザワクチン |
| WO2009069448A1 (ja) * | 2007-11-28 | 2009-06-04 | Toray Industries, Inc. | 日本脳炎ワクチン用のアジュバント及び日本脳炎ワクチン |
| ES2616051T3 (es) | 2008-12-02 | 2017-06-09 | Wave Life Sciences Japan, Inc. | Método para la síntesis de ácidos nucleicos modificados en el átomo de fósforo |
| CA2767253A1 (en) | 2009-07-06 | 2011-01-13 | Ontorii, Inc. | Novel nucleic acid prodrugs and methods of use thereof |
| EP2620428B1 (en) | 2010-09-24 | 2019-05-22 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| GB201021867D0 (en) * | 2010-12-23 | 2011-02-02 | Mologen Ag | Non-coding immunomodulatory DNA construct |
| JP5906019B2 (ja) * | 2011-03-31 | 2016-04-20 | 国立大学法人福井大学 | 免疫刺激ｇ９．１の抗結核ブースターワクチン創出への応用 |
| JP6128529B2 (ja) | 2011-07-19 | 2017-05-17 | ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． | 官能化核酸の合成のための方法 |
| BR112014016389A8 (pt) | 2012-01-16 | 2021-06-08 | Mckenna Elizabeth | composições e uso das mesmas para o tratamento de distúrbios e doenças hepáticas |
| US12268718B2 (en) | 2012-01-16 | 2025-04-08 | Labyrinth Holdings Llc | Control of cellular redox levels |
| AR091569A1 (es) * | 2012-06-28 | 2015-02-11 | Intervet Int Bv | Receptores de tipo toll |
| US9598458B2 (en) | 2012-07-13 | 2017-03-21 | Wave Life Sciences Japan, Inc. | Asymmetric auxiliary group |
| US9982257B2 (en) | 2012-07-13 | 2018-05-29 | Wave Life Sciences Ltd. | Chiral control |
| MX356830B (es) * | 2012-07-13 | 2018-06-15 | Shin Nippon Biomedical Laboratories Ltd | Adyuvante de acido nucleico quiral. |
| JP2015535829A (ja) * | 2012-09-21 | 2015-12-17 | マッケーナ、エリザベス | 天然に存在するＣｐＧオリゴヌクレオチド組成物およびその治療的適用 |
| US10144933B2 (en) | 2014-01-15 | 2018-12-04 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
| WO2015108046A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 抗アレルギー作用を有するキラル核酸アジュバンド及び抗アレルギー剤 |
| EP3095459A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having antitumor effect and antitumor agent |
| DK3094728T3 (da) | 2014-01-16 | 2022-05-16 | Wave Life Sciences Ltd | Kiralt design |
| LU92821B1 (en) | 2015-09-09 | 2017-03-20 | Mologen Ag | Combination comprising immunostimulatory oligonucleotides |
| GB2542425A (en) | 2015-09-21 | 2017-03-22 | Mologen Ag | Means for the treatment of HIV |
| WO2023049275A2 (en) * | 2021-09-23 | 2023-03-30 | Arnay Sciences, Llc | Cyclic structured oligonucleotides as therapeutic agents |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0468520A3 (en) * | 1990-07-27 | 1992-07-01 | Mitsui Toatsu Chemicals, Inc. | Immunostimulatory remedies containing palindromic dna sequences |
| DE69819150T3 (de) | 1997-06-06 | 2007-12-20 | Dynavax Technologies Corp., San Diego | Immunstimulierende oligonucleotide, zusammensetzungen davon, und verfahren zur verwendung davon |
| EP1067956B1 (en) | 1998-04-03 | 2007-03-14 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
| WO2001022990A2 (en) * | 1999-09-27 | 2001-04-05 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| US7585847B2 (en) * | 2000-02-03 | 2009-09-08 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
| WO2002002172A1 (en) * | 2000-06-30 | 2002-01-10 | Univ Jefferson | Dna palindrome - oligoguanylic acid compositions and uses thereof |
| US20030050268A1 (en) * | 2001-03-29 | 2003-03-13 | Krieg Arthur M. | Immunostimulatory nucleic acid for treatment of non-allergic inflammatory diseases |
| EP1450856B1 (en) | 2001-09-14 | 2009-11-11 | Cytos Biotechnology AG | Packaging of immunostimulatory cpg into virus-like particles: method of preparation and use |
| JP4360906B2 (ja) * | 2001-09-14 | 2009-11-11 | サイトス バイオテクノロジー アーゲー | ウィルス様粒子によって誘導される免疫応答を高めるための、抗原提示細胞のインビボでの活性化 |
| PL375306A1 (en) | 2002-06-20 | 2005-11-28 | Cytos Biotechnology Ag | Packaged virus-like particles for use as adjuvants: method of preparation and use |
-
2004
- 2004-02-27 JP JP2004053795A patent/JP3976742B2/ja not_active Expired - Lifetime
-
2005
- 2005-02-25 WO PCT/JP2005/003693 patent/WO2005083076A1/ja not_active Ceased
- 2005-02-25 US US10/590,761 patent/US7718623B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005083076A1 (ja) | 2005-09-09 |
| JP2005237328A (ja) | 2005-09-08 |
| US7718623B2 (en) | 2010-05-18 |
| US20070179101A1 (en) | 2007-08-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3976742B2 (ja) | インターフェロンアルファを誘導する免疫刺激オリゴヌクレオチド | |
| EP2901856B1 (en) | Immunostimulatory oligonucleotide multimers | |
| Krieg et al. | Mechanisms and therapeutic applications of immune stimulatory CpG DNA | |
| Shirota et al. | Recent progress concerning CpG DNA and its use as a vaccine adjuvant | |
| Hennessy et al. | Targeting Toll-like receptors: emerging therapeutics? | |
| Ashkar et al. | Toll-like receptor 9, CpG DNA and innate immunity | |
| JP2023093513A (ja) | 組み合わせワクチン装置および癌細胞を殺滅する方法 | |
| EP1511845B1 (en) | Immunostimulatory oligonucleotides and uses thereof | |
| JP2023015346A (ja) | 免疫療法のためのコア／シェル構造プラットホーム | |
| JP2008000001A (ja) | 免疫刺激オリゴヌクレオチドおよびその医薬用途 | |
| CN101460620B (zh) | 免疫刺激寡核苷酸及其药物用途 | |
| EP0855184A1 (en) | Pharmaceutical composition comprising a polynucleotide and an antigen especially for vaccination | |
| US7566702B2 (en) | Immunostimulatory oligonucleotide multimers | |
| EP3301179B1 (en) | Immunostimulating oligonucleotide complex | |
| JP2004530629A (ja) | 免疫刺激ｒｎａ／ｄｎａハイブリッド分子 | |
| DK2999787T3 (en) | COVALENT CLOSED, NON-Coding Immunomodulating DNA Construct | |
| KR20160055863A (ko) | 면역 부활 활성을 갖는 올리고뉴클레오티드 함유 복합체 및 그 용도 | |
| JP2012524793A (ja) | 免疫調節性生体分子を組み合わせて送達するためのヒドロゲル | |
| Chikh et al. | Synthetic methylated CpG ODNs are potent in vivo adjuvants when delivered in liposomal nanoparticles | |
| Wang et al. | CpG-independent synergistic induction of β-chemokines and a dendritic cell phenotype by orthophosphorothioate oligodeoxynucleotides and granulocyte-macrophage colony-stimulating factor in elutriated human primary monocytes | |
| JP7628274B2 (ja) | 免疫刺激オリゴヌクレオチド | |
| Payette et al. | Role of CpG motifs in immunostimulation and gene expression | |
| HK1211179B (en) | Immunostimulatory oligonucleotide multimers |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060829 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070213 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20070413 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20070522 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20070511 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20070619 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100629 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 3976742 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130629 Year of fee payment: 6 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313117 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313117 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |