JP2004519453A - ポリカチオン性化合物の用途 - Google Patents
ポリカチオン性化合物の用途 Download PDFInfo
- Publication number
- JP2004519453A JP2004519453A JP2002554134A JP2002554134A JP2004519453A JP 2004519453 A JP2004519453 A JP 2004519453A JP 2002554134 A JP2002554134 A JP 2002554134A JP 2002554134 A JP2002554134 A JP 2002554134A JP 2004519453 A JP2004519453 A JP 2004519453A
- Authority
- JP
- Japan
- Prior art keywords
- cpg
- poly
- arginine
- odn
- medicament
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 60
- 239000003814 drug Substances 0.000 claims abstract description 32
- 206010061218 Inflammation Diseases 0.000 claims abstract description 21
- 230000004054 inflammatory process Effects 0.000 claims abstract description 20
- 229920000724 poly(L-arginine) polymer Polymers 0.000 claims description 96
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 claims description 52
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 45
- 239000000427 antigen Substances 0.000 claims description 44
- 108091007433 antigens Proteins 0.000 claims description 44
- 102000036639 antigens Human genes 0.000 claims description 44
- 239000000203 mixture Substances 0.000 claims description 25
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 20
- 229960005486 vaccine Drugs 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 230000002163 immunogen Effects 0.000 claims description 7
- 125000000539 amino acid group Chemical group 0.000 claims description 6
- 244000052769 pathogen Species 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 229920001184 polypeptide Polymers 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 3
- 230000001363 autoimmune Effects 0.000 claims description 3
- 108010011110 polyarginine Proteins 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 229930010555 Inosine Natural products 0.000 claims description 2
- 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 claims description 2
- 108010039918 Polylysine Proteins 0.000 claims description 2
- 244000052616 bacterial pathogen Species 0.000 claims description 2
- 229960003786 inosine Drugs 0.000 claims description 2
- 108020004707 nucleic acids Proteins 0.000 claims description 2
- 102000039446 nucleic acids Human genes 0.000 claims description 2
- 150000007523 nucleic acids Chemical class 0.000 claims description 2
- 229920000656 polylysine Polymers 0.000 claims description 2
- 244000052613 viral pathogen Species 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 239000002158 endotoxin Substances 0.000 description 48
- 229920006008 lipopolysaccharide Polymers 0.000 description 47
- 241000699666 Mus <mouse, genus> Species 0.000 description 44
- 239000007924 injection Substances 0.000 description 44
- 238000002347 injection Methods 0.000 description 44
- 210000004443 dendritic cell Anatomy 0.000 description 41
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 40
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 40
- 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 38
- 102000004889 Interleukin-6 Human genes 0.000 description 33
- 108090001005 Interleukin-6 Proteins 0.000 description 33
- 238000004519 manufacturing process Methods 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 28
- 239000000126 substance Substances 0.000 description 28
- 102000004127 Cytokines Human genes 0.000 description 27
- 108090000695 Cytokines Proteins 0.000 description 27
- 230000009885 systemic effect Effects 0.000 description 25
- 230000000770 proinflammatory effect Effects 0.000 description 23
- 241000699670 Mus sp. Species 0.000 description 20
- 239000002609 medium Substances 0.000 description 20
- 239000006228 supernatant Substances 0.000 description 17
- 241000282414 Homo sapiens Species 0.000 description 16
- 238000000338 in vitro Methods 0.000 description 14
- 238000002965 ELISA Methods 0.000 description 13
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 108010007004 cathelin Proteins 0.000 description 11
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 10
- 238000009826 distribution Methods 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 10
- 238000006116 polymerization reaction Methods 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 9
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical compound OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 8
- 210000001185 bone marrow Anatomy 0.000 description 8
- JVJGCCBAOOWGEO-RUTPOYCXSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-4-amino-2-[[(2s,3s)-2-[[(2s,3s)-2-[[(2s)-2-azaniumyl-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-phenylpropanoyl]amino]-4-carboxylatobutanoyl]amino]-6-azaniumy Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=CC=C1 JVJGCCBAOOWGEO-RUTPOYCXSA-N 0.000 description 7
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 7
- 102100022297 Integrin alpha-X Human genes 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000002757 inflammatory effect Effects 0.000 description 7
- 230000017306 interleukin-6 production Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- 230000006433 tumor necrosis factor production Effects 0.000 description 7
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 6
- 239000007995 HEPES buffer Substances 0.000 description 6
- 238000011260 co-administration Methods 0.000 description 6
- 230000003308 immunostimulating effect Effects 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 210000001165 lymph node Anatomy 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 229920001917 Ficoll Polymers 0.000 description 4
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 4
- 102000043129 MHC class I family Human genes 0.000 description 4
- 108091054437 MHC class I family Proteins 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 125000002091 cationic group Chemical group 0.000 description 4
- 230000009918 complex formation Effects 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 210000003141 lower extremity Anatomy 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 239000003068 molecular probe Substances 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 238000001308 synthesis method Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 229920001661 Chitosan Polymers 0.000 description 3
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 3
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 102000043131 MHC class II family Human genes 0.000 description 3
- 108091054438 MHC class II family Proteins 0.000 description 3
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000002798 bone marrow cell Anatomy 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 210000000991 chicken egg Anatomy 0.000 description 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000012737 fresh medium Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000007108 local immune response Effects 0.000 description 3
- 230000005923 long-lasting effect Effects 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 210000003563 lymphoid tissue Anatomy 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 3
- 229920002851 polycationic polymer Polymers 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002255 vaccination Methods 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 108700042778 Antimicrobial Peptides Proteins 0.000 description 2
- 102000044503 Antimicrobial Peptides Human genes 0.000 description 2
- 102000000541 Defensins Human genes 0.000 description 2
- 108010002069 Defensins Proteins 0.000 description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- 101100453981 Rattus norvegicus Klk12 gene Proteins 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 108060001132 cathelicidin Proteins 0.000 description 2
- 102000014509 cathelicidin Human genes 0.000 description 2
- POIUWJQBRNEFGX-XAMSXPGMSA-N cathelicidin Chemical compound C([C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C)C1=CC=CC=C1 POIUWJQBRNEFGX-XAMSXPGMSA-N 0.000 description 2
- 229940000425 combination drug Drugs 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 229960001438 immunostimulant agent Drugs 0.000 description 2
- 239000003022 immunostimulating agent Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229920001308 poly(aminoacid) Polymers 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 210000005212 secondary lymphoid organ Anatomy 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 229940054269 sodium pyruvate Drugs 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- MEXAGTSTSPYCEP-NUBCRITNSA-N (2r)-2,6-diaminohexanoic acid;hydrobromide Chemical compound Br.NCCCC[C@@H](N)C(O)=O MEXAGTSTSPYCEP-NUBCRITNSA-N 0.000 description 1
- ZYECOAILUNWEAL-NUDFZHEQSA-N (4z)-4-[[2-methoxy-5-(phenylcarbamoyl)phenyl]hydrazinylidene]-n-(3-nitrophenyl)-3-oxonaphthalene-2-carboxamide Chemical compound COC1=CC=C(C(=O)NC=2C=CC=CC=2)C=C1N\N=C(C1=CC=CC=C1C=1)/C(=O)C=1C(=O)NC1=CC=CC([N+]([O-])=O)=C1 ZYECOAILUNWEAL-NUDFZHEQSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- 108700031308 Antennapedia Homeodomain Proteins 0.000 description 1
- 102000014133 Antimicrobial Cationic Peptides Human genes 0.000 description 1
- 108010050820 Antimicrobial Cationic Peptides Proteins 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241001647372 Chlamydia pneumoniae Species 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 206010009192 Circulatory collapse Diseases 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000011510 Elispot assay Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
- 101001002709 Homo sapiens Interleukin-4 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100180430 Mus musculus Klk1b4 gene Proteins 0.000 description 1
- 241000186366 Mycobacterium bovis Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 102100029251 Phagocytosis-stimulating peptide Human genes 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 108010084754 Tuftsin Proteins 0.000 description 1
- 241000607626 Vibrio cholerae Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 229940065181 bacillus anthracis Drugs 0.000 description 1
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 108010051081 dopachrome isomerase Proteins 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 102000046157 human CSF2 Human genes 0.000 description 1
- 102000055229 human IL4 Human genes 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- -1 pR60 Proteins 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 206010040560 shock Diseases 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000008718 systemic inflammatory response Effects 0.000 description 1
- JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 229940035670 tuftsin Drugs 0.000 description 1
- IESDGNYHXIOKRW-LEOABGAYSA-N tuftsin Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@H](CCCNC(N)=N)C(O)=O IESDGNYHXIOKRW-LEOABGAYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 229940118696 vibrio cholerae Drugs 0.000 description 1
Images
Classifications
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- 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
- A61K2039/55516—Proteins; Peptides
-
- 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
-
- 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
- A61K2039/55572—Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Virology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2001/000087 WO2001054720A1 (en) | 2000-01-28 | 2001-01-05 | Pharmaceutical composition for immunomodulation and preparation of vaccines comprising an antigen and an immunogenic oligodeoxynucleotide and a polycationic polymer as adjuvants |
| AT6702001 | 2001-04-25 | ||
| PCT/EP2002/000071 WO2002053185A2 (en) | 2001-01-05 | 2002-01-07 | Anti-inflammatory use of polycationic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004519453A true JP2004519453A (ja) | 2004-07-02 |
| JP2004519453A5 JP2004519453A5 (enExample) | 2005-12-22 |
Family
ID=25608381
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002554134A Pending JP2004519453A (ja) | 2001-01-05 | 2002-01-07 | ポリカチオン性化合物の用途 |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1347776A2 (enExample) |
| JP (1) | JP2004519453A (enExample) |
| WO (1) | WO2002053185A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007013613A1 (ja) | 2005-07-29 | 2007-02-01 | Suntory Limited | フコイダン又はフコイダン加水分解生成物と免疫賦活素材とを含む組成物 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1650012A (zh) | 2002-07-24 | 2005-08-03 | 英特塞尔股份公司 | 来自致病病毒的备选阅读框所编码的抗原 |
| EP1537418A2 (en) | 2002-09-13 | 2005-06-08 | Intercell AG | Method for isolating hepatitis c virus peptides |
| JP4676426B2 (ja) | 2003-03-24 | 2011-04-27 | インターツェル・アクチェンゲゼルシャフト | 改良型ワクチン |
| ES2351489T3 (es) * | 2003-03-24 | 2011-02-07 | Intercell Ag | Vacunas mejoradas. |
| CN102639142A (zh) | 2009-09-16 | 2012-08-15 | 杜克大学 | 内体Toll样受体活化的抑制 |
| US8765148B2 (en) | 2010-02-19 | 2014-07-01 | Valneva Austria Gmbh | 1C31 nanoparticles |
| US12447464B2 (en) | 2016-12-22 | 2025-10-21 | Duke University | Polycationic microfibers and methods of using the same |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1290141A (enExample) * | 1968-05-31 | 1972-09-20 | ||
| JPH09176038A (ja) * | 1995-09-18 | 1997-07-08 | Hisamitsu Pharmaceut Co Inc | 抗炎症性アンチセンス薬物 |
| RS50101B (sr) * | 1996-02-24 | 2009-01-22 | Boehringer Ingelheim International Gmbh., | Farmaceutski preparati za imunomodulaciju |
| NZ509101A (en) * | 1998-06-26 | 2003-07-25 | N | Pharmaceutical preparations for use in combatting or preventing surface infections caused by microorganisms |
| JP2000256196A (ja) * | 1999-03-05 | 2000-09-19 | Pias Arise Kk | 抗炎症,抗アレルギー剤 |
| DK1187629T3 (da) * | 1999-04-19 | 2005-01-17 | Glaxosmithkline Biolog Sa | Adjuvanssammensætning omfattende saponin og et immunostimulerende oligonucleotid |
| JP2001199903A (ja) * | 1999-11-09 | 2001-07-24 | Eizo Mori | 核酸含有複合体 |
| DE60100814T2 (de) * | 2000-06-08 | 2004-07-01 | Intercell Biomedizinische Forschungs- Und Entwicklungs Gmbh | Immunstimulierende oligodeoxynukleotide |
| AT410173B (de) * | 2000-06-08 | 2003-02-25 | Cistem Biotechnologies Gmbh | Antigene zusammensetzung |
-
2002
- 2002-01-07 EP EP02702238A patent/EP1347776A2/en not_active Withdrawn
- 2002-01-07 WO PCT/EP2002/000071 patent/WO2002053185A2/en not_active Ceased
- 2002-01-07 JP JP2002554134A patent/JP2004519453A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007013613A1 (ja) | 2005-07-29 | 2007-02-01 | Suntory Limited | フコイダン又はフコイダン加水分解生成物と免疫賦活素材とを含む組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002053185A3 (en) | 2002-10-31 |
| WO2002053185A2 (en) | 2002-07-11 |
| EP1347776A2 (en) | 2003-10-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU784403B2 (en) | Pharmaceutical composition for immunomodulation and preparation of vaccines comprising an antigen and an immunogenic oligodeoxynucleotide and a polycationic polymer as adjuvants | |
| RU2328305C2 (ru) | Вакцинная композиция | |
| JP5271471B2 (ja) | 免疫促進性オリゴデオキシヌクレオチド | |
| US20080025996A1 (en) | Methods and Compositions Comprising Polycationic Compounds | |
| AU2002212326A1 (en) | Vaccine composition comprising an antigen and a peptide having adjuvant properties | |
| JP2008222721A6 (ja) | ワクチン組成物 | |
| JP2004530428A (ja) | 免疫促進性オリゴデオキシ核酸分子 | |
| JP2004519453A (ja) | ポリカチオン性化合物の用途 | |
| JP2004519452A (ja) | ポリカチオン性化合物の用途 | |
| US20040081655A1 (en) | Methods and compositions comprising polycationic compounds | |
| AU2002235820A1 (en) | Anti-inflammatory use of polycationic compounds | |
| AU2002233302A1 (en) | Uses for polycationic compounds as vaccine adjuvants | |
| HK1055899B (en) | Vaccine composition comprising an antigen and a peptide having adjuvant properties |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20041228 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20041228 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080304 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080603 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080610 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080703 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080710 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080804 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080811 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080904 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20080904 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081224 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090323 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090330 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090423 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090501 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20091222 |