ZA200600151B - Quil A fraction with low toxicity and use thereof - Google Patents
Quil A fraction with low toxicity and use thereof Download PDFInfo
- Publication number
- ZA200600151B ZA200600151B ZA200600151A ZA200600151A ZA200600151B ZA 200600151 B ZA200600151 B ZA 200600151B ZA 200600151 A ZA200600151 A ZA 200600151A ZA 200600151 A ZA200600151 A ZA 200600151A ZA 200600151 B ZA200600151 B ZA 200600151B
- Authority
- ZA
- South Africa
- Prior art keywords
- quil
- adjuvant
- fraction
- iscom
- composition
- Prior art date
Links
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 title claims description 67
- 231100000053 low toxicity Toxicity 0.000 title description 5
- 239000011159 matrix material Substances 0.000 claims description 150
- 239000002671 adjuvant Substances 0.000 claims description 94
- 239000000203 mixture Substances 0.000 claims description 83
- 239000002245 particle Substances 0.000 claims description 56
- 102000009016 Cholera Toxin Human genes 0.000 claims description 54
- 108010049048 Cholera Toxin Proteins 0.000 claims description 54
- 229940035032 monophosphoryl lipid a Drugs 0.000 claims description 53
- 210000003918 fraction a Anatomy 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 31
- 229930182490 saponin Natural products 0.000 claims description 26
- 150000007949 saponins Chemical class 0.000 claims description 26
- 235000017709 saponins Nutrition 0.000 claims description 26
- 239000000126 substance Substances 0.000 claims description 25
- 230000002519 immonomodulatory effect Effects 0.000 claims description 22
- 239000012634 fragment Substances 0.000 claims description 18
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 16
- 230000002195 synergetic effect Effects 0.000 claims description 15
- 230000028993 immune response Effects 0.000 claims description 14
- 235000009001 Quillaja saponaria Nutrition 0.000 claims description 13
- 210000002196 fr. b Anatomy 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- 241000588832 Bordetella pertussis Species 0.000 claims description 9
- 241001092142 Molina Species 0.000 claims description 9
- 239000003053 toxin Substances 0.000 claims description 9
- 231100000765 toxin Toxicity 0.000 claims description 9
- 108700012359 toxins Proteins 0.000 claims description 9
- 241001454523 Quillaja saponaria Species 0.000 claims description 8
- 210000000540 fraction c Anatomy 0.000 claims description 7
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- 230000002708 enhancing effect Effects 0.000 claims description 4
- 231100000699 Bacterial toxin Toxicity 0.000 claims description 3
- 108010039939 Cell Wall Skeleton Proteins 0.000 claims description 3
- 241000588724 Escherichia coli Species 0.000 claims description 3
- 108010002350 Interleukin-2 Proteins 0.000 claims description 3
- 108010028921 Lipopeptides Proteins 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 3
- 239000000688 bacterial toxin Substances 0.000 claims description 3
- 229920001400 block copolymer Polymers 0.000 claims description 3
- 210000004520 cell wall skeleton Anatomy 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000002955 immunomodulating agent Substances 0.000 claims description 3
- 229940121354 immunomodulator Drugs 0.000 claims description 3
- 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 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 241000894007 species Species 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 2
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims 2
- 241000699670 Mus sp. Species 0.000 description 79
- 108010058846 Ovalbumin Proteins 0.000 description 61
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- 229960000814 tetanus toxoid Drugs 0.000 description 57
- 230000004044 response Effects 0.000 description 50
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- 238000009472 formulation Methods 0.000 description 37
- 238000002649 immunization Methods 0.000 description 36
- 230000005875 antibody response Effects 0.000 description 34
- 239000000427 antigen Substances 0.000 description 33
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- 102000036639 antigens Human genes 0.000 description 33
- 229960005486 vaccine Drugs 0.000 description 31
- 230000000694 effects Effects 0.000 description 20
- 241000725643 Respiratory syncytial virus Species 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 17
- 238000002474 experimental method Methods 0.000 description 14
- 210000002966 serum Anatomy 0.000 description 13
- 210000004989 spleen cell Anatomy 0.000 description 13
- 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 12
- 238000002965 ELISA Methods 0.000 description 11
- 230000010261 cell growth Effects 0.000 description 11
- PIGTXFOGKFOFTO-FVFWYJKVSA-N (2S,3S,4S,5R,6R)-6-[[(3S,4S,4aR,6aR,6bS,8R,8aR,12aS,14aR,14bR)-8a-carboxy-4-formyl-8-hydroxy-4,6a,6b,11,11,14b-hexamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl]oxy]-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound O([C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)C[C@@H](O)[C@]1(CCC(C[C@H]14)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O PIGTXFOGKFOFTO-FVFWYJKVSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 10
- 238000007912 intraperitoneal administration Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 230000037452 priming Effects 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 230000003053 immunization Effects 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 238000007920 subcutaneous administration Methods 0.000 description 9
- 231100000331 toxic Toxicity 0.000 description 9
- 230000002588 toxic effect Effects 0.000 description 9
- 230000000240 adjuvant effect Effects 0.000 description 8
- 238000013401 experimental design Methods 0.000 description 8
- 244000052769 pathogen Species 0.000 description 8
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 8
- 229930006000 Sucrose Natural products 0.000 description 7
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 230000002163 immunogen Effects 0.000 description 7
- 239000005720 sucrose Substances 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 241001092473 Quillaja Species 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 230000009089 cytolysis Effects 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 230000000897 modulatory effect Effects 0.000 description 5
- 230000001717 pathogenic effect Effects 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 210000003501 vero cell Anatomy 0.000 description 5
- PIGTXFOGKFOFTO-PPEDVFHSSA-N CC1(C)CC[C@@]2([C@H](O)C[C@]3(C)C(=CC[C@@H]4[C@@]5(C)CCC(O[C@@H]6O[C@@H]([C@@H](O)[C@H](O)[C@H]6O)C(O)=O)[C@@](C)(C=O)[C@@H]5CC[C@@]34C)[C@@H]2C1)C(O)=O Chemical compound CC1(C)CC[C@@]2([C@H](O)C[C@]3(C)C(=CC[C@@H]4[C@@]5(C)CCC(O[C@@H]6O[C@@H]([C@@H](O)[C@H](O)[C@H]6O)C(O)=O)[C@@](C)(C=O)[C@@H]5CC[C@@]34C)[C@@H]2C1)C(O)=O PIGTXFOGKFOFTO-PPEDVFHSSA-N 0.000 description 4
- 206010043376 Tetanus Diseases 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 238000011785 NMRI mouse Methods 0.000 description 3
- 238000003349 alamar blue assay Methods 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000002101 lytic effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 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 2
- 229910018626 Al(OH) Inorganic materials 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 101710091045 Envelope protein Proteins 0.000 description 2
- 241000711920 Human orthopneumovirus Species 0.000 description 2
- 101710188315 Protein X Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 2
- 102100021696 Syncytin-1 Human genes 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 2
- 229940024545 aluminum hydroxide Drugs 0.000 description 2
- 244000309466 calf Species 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 150000002338 glycosides Chemical class 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011894 semi-preparative HPLC Methods 0.000 description 2
- 150000003432 sterols Chemical class 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 229940124873 Influenza virus vaccine Drugs 0.000 description 1
- 206010024769 Local reaction Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000219287 Saponaria Species 0.000 description 1
- 208000020967 Sever disease Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108010055044 Tetanus Toxin Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000008102 immune modulation Effects 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002766 immunoenhancing effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 229960003971 influenza vaccine Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 125000001446 muramyl group Chemical group N[C@@H](C=O)[C@@H](O[C@@H](C(=O)*)C)[C@H](O)[C@H](O)CO 0.000 description 1
- UMWKZHPREXJQGR-UHFFFAOYSA-N n-methyl-n-(2,3,4,5,6-pentahydroxyhexyl)decanamide Chemical compound CCCCCCCCCC(=O)N(C)CC(O)C(O)C(O)C(O)CO UMWKZHPREXJQGR-UHFFFAOYSA-N 0.000 description 1
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
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
- 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
- A61K2039/55577—Saponins; Quil A; QS21; ISCOMS
-
- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Compounds Of Unknown Constitution (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0301998A SE0301998D0 (sv) | 2003-07-07 | 2003-07-07 | Quil A fraction with low toxicity and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200600151B true ZA200600151B (en) | 2007-01-31 |
Family
ID=27731119
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200600151A ZA200600151B (en) | 2003-07-07 | 2006-01-06 | Quil A fraction with low toxicity and use thereof |
Country Status (15)
| Country | Link |
|---|---|
| US (8) | US8821881B2 (fr) |
| EP (1) | EP1648505B1 (fr) |
| JP (1) | JP4731475B2 (fr) |
| AT (1) | ATE442164T1 (fr) |
| AU (1) | AU2004254152B2 (fr) |
| BR (1) | BRPI0412444B8 (fr) |
| CA (1) | CA2529363C (fr) |
| DE (1) | DE602004023089D1 (fr) |
| DK (1) | DK1648505T3 (fr) |
| ES (1) | ES2331952T3 (fr) |
| NZ (1) | NZ544299A (fr) |
| PL (1) | PL1648505T3 (fr) |
| SE (1) | SE0301998D0 (fr) |
| WO (1) | WO2005002620A1 (fr) |
| ZA (1) | ZA200600151B (fr) |
Families Citing this family (101)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1104306E (pt) * | 1998-08-10 | 2006-05-31 | Antigenics Inc | Composicoes de cpg e adjuvantes de saponina e seus metodos |
| SE0202110D0 (sv) * | 2002-07-05 | 2002-07-05 | Isconova Ab | Iscom preparation and use thereof |
| SE0301998D0 (sv) | 2003-07-07 | 2003-07-07 | Isconova Ab | Quil A fraction with low toxicity and use thereof |
| US8007806B2 (en) | 2005-01-20 | 2011-08-30 | Isconova Ab | Vaccine composition comprising a fibronectin binding protein or a fibronectin binding peptide |
| EP1764369A1 (fr) * | 2005-09-16 | 2007-03-21 | Rhein Biotech Gesellschaft für neue biotechnologische Prozesse und Produkte mbH | Vaccins comprenant la protéine du noyau du HBV tronquée ainsi qu'un adjuvant à base de saponine |
| CN101448523A (zh) | 2006-03-24 | 2009-06-03 | 诺华疫苗和诊断有限两合公司 | 无需冷藏储存流感疫苗 |
| PT2054431E (pt) | 2006-06-09 | 2011-11-03 | Novartis Ag | Confórmeros de adesinas bacterianas |
| EP1902727A1 (fr) * | 2006-09-22 | 2008-03-26 | Rhein Biotech Gesellschaft für neue biotechnologische Prozesse und Produkte mbH | Vaccins comprenant la protéine du noyau du HBV tronquée ainsi qu'un adjuvant à base de saponine |
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| NL9002314A (nl) | 1990-10-23 | 1992-05-18 | Nederlanden Staat | Immunogene complexen, in het bijzonder iscoms. |
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- 2004-07-07 ES ES04749076T patent/ES2331952T3/es not_active Expired - Lifetime
- 2004-07-07 WO PCT/SE2004/001038 patent/WO2005002620A1/fr not_active Ceased
- 2004-07-07 JP JP2006518582A patent/JP4731475B2/ja not_active Expired - Lifetime
- 2004-07-07 AT AT04749076T patent/ATE442164T1/de not_active IP Right Cessation
- 2004-07-07 PL PL04749076T patent/PL1648505T3/pl unknown
- 2004-07-07 CA CA2529363A patent/CA2529363C/fr not_active Expired - Lifetime
- 2004-07-07 DE DE602004023089T patent/DE602004023089D1/de not_active Expired - Lifetime
- 2004-07-07 US US10/562,866 patent/US8821881B2/en active Active
- 2004-07-07 NZ NZ544299A patent/NZ544299A/en not_active IP Right Cessation
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2019
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| DK1648505T3 (da) | 2009-12-21 |
| PL1648505T3 (pl) | 2010-02-26 |
| ATE442164T1 (de) | 2009-09-15 |
| US20220241408A1 (en) | 2022-08-04 |
| US20160184427A1 (en) | 2016-06-30 |
| CA2529363A1 (fr) | 2005-01-13 |
| JP4731475B2 (ja) | 2011-07-27 |
| BRPI0412444B1 (pt) | 2016-06-14 |
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| SE0301998D0 (sv) | 2003-07-07 |
| EP1648505A1 (fr) | 2006-04-26 |
| BRPI0412444A (pt) | 2006-09-19 |
| ES2331952T3 (es) | 2010-01-21 |
| DE602004023089D1 (de) | 2009-10-22 |
| US20140335049A1 (en) | 2014-11-13 |
| WO2005002620A1 (fr) | 2005-01-13 |
| AU2004254152B2 (en) | 2009-10-29 |
| JP2007527386A (ja) | 2007-09-27 |
| US20060239963A1 (en) | 2006-10-26 |
| EP1648505B1 (fr) | 2009-09-09 |
| US20240024468A1 (en) | 2024-01-25 |
| NZ544299A (en) | 2009-03-31 |
| US20180369368A1 (en) | 2018-12-27 |
| CA2529363C (fr) | 2013-04-02 |
| BRPI0412444B8 (pt) | 2021-05-25 |
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