KR20150133770A - 톡소이드, 조성물 및 관련 방법 - Google Patents
톡소이드, 조성물 및 관련 방법 Download PDFInfo
- Publication number
- KR20150133770A KR20150133770A KR1020157029566A KR20157029566A KR20150133770A KR 20150133770 A KR20150133770 A KR 20150133770A KR 1020157029566 A KR1020157029566 A KR 1020157029566A KR 20157029566 A KR20157029566 A KR 20157029566A KR 20150133770 A KR20150133770 A KR 20150133770A
- Authority
- KR
- South Korea
- Prior art keywords
- toxoid
- formaldehyde
- toxin
- purified
- composition
- 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.)
- Withdrawn
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 138
- 238000000034 method Methods 0.000 title claims abstract description 83
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 421
- 229960005486 vaccine Drugs 0.000 claims abstract description 45
- 101710084578 Short neurotoxin 1 Proteins 0.000 claims description 64
- 101710182532 Toxin a Proteins 0.000 claims description 64
- 101710182223 Toxin B Proteins 0.000 claims description 61
- 241000193163 Clostridioides difficile Species 0.000 claims description 45
- 230000008569 process Effects 0.000 claims description 27
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 21
- 238000011534 incubation Methods 0.000 claims description 20
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- 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 claims description 11
- 229930006000 Sucrose Natural products 0.000 claims description 11
- 239000005720 sucrose Substances 0.000 claims description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 229910019142 PO4 Inorganic materials 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 6
- 239000010452 phosphate Substances 0.000 claims description 6
- 239000007853 buffer solution Substances 0.000 claims description 5
- 239000004471 Glycine Substances 0.000 claims description 4
- 230000002163 immunogen Effects 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
- 235000000346 sugar Nutrition 0.000 claims description 3
- 150000005846 sugar alcohols Chemical class 0.000 claims description 2
- 239000003053 toxin Substances 0.000 abstract description 75
- 231100000765 toxin Toxicity 0.000 abstract description 75
- 108700012359 toxins Proteins 0.000 abstract description 75
- 230000009849 deactivation Effects 0.000 abstract description 5
- 230000000415 inactivating effect Effects 0.000 abstract description 5
- 231100000065 noncytotoxic Toxicity 0.000 abstract description 3
- 230000002020 noncytotoxic effect Effects 0.000 abstract description 3
- 231100001102 clostridial toxin Toxicity 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 37
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 34
- 238000002965 ELISA Methods 0.000 description 23
- 239000007983 Tris buffer Substances 0.000 description 23
- 238000003556 assay Methods 0.000 description 20
- 231100000135 cytotoxicity Toxicity 0.000 description 20
- 230000003013 cytotoxicity Effects 0.000 description 20
- 239000000872 buffer Substances 0.000 description 19
- 241000699800 Cricetinae Species 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 18
- 239000003814 drug Substances 0.000 description 18
- 238000002784 cytotoxicity assay Methods 0.000 description 16
- 231100000263 cytotoxicity test Toxicity 0.000 description 16
- 208000015181 infectious disease Diseases 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 229940079593 drug Drugs 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 235000002639 sodium chloride Nutrition 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 238000005571 anion exchange chromatography Methods 0.000 description 10
- 239000003085 diluting agent Substances 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 230000001900 immune effect Effects 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 238000003860 storage Methods 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 239000002671 adjuvant Substances 0.000 description 8
- 230000001147 anti-toxic effect Effects 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 7
- 238000000502 dialysis Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 230000005847 immunogenicity Effects 0.000 description 7
- 239000008363 phosphate buffer Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 241001460678 Napo <wasp> Species 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 241000193403 Clostridium Species 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000002779 inactivation Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000004448 titration Methods 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 4
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 4
- 235000011130 ammonium sulphate Nutrition 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 4
- 238000000099 in vitro assay Methods 0.000 description 4
- 238000005462 in vivo assay Methods 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- 208000034628 Celiac artery compression syndrome Diseases 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- -1 about 0.001% Chemical compound 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 238000005349 anion exchange Methods 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000009295 crossflow filtration Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000000569 multi-angle light scattering Methods 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- 229960002920 sorbitol Drugs 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- 241000648967 Clostridioides difficile ATCC 43255 Species 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000008098 formaldehyde solution Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000009145 protein modification Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011218 seed culture Methods 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010003011 Appendicitis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 239000012619 Butyl Sepharose® Substances 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- UFUVLHLTWXBHGZ-MGZQPHGTSA-N [(2r,3r,4s,5r,6r)-6-[(1s,2s)-2-chloro-1-[[(2s,4r)-1-methyl-4-propylpyrrolidine-2-carbonyl]amino]propyl]-4,5-dihydroxy-2-methylsulfanyloxan-3-yl] dihydrogen phosphate Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](OP(O)(O)=O)[C@@H](SC)O1 UFUVLHLTWXBHGZ-MGZQPHGTSA-N 0.000 description 1
- PTTGRYBBCYZPSL-UHFFFAOYSA-H [Al+3].[Al+3].OOP([O-])([O-])=O.OOP([O-])([O-])=O.OOP([O-])([O-])=O Chemical compound [Al+3].[Al+3].OOP([O-])([O-])=O.OOP([O-])([O-])=O.OOP([O-])([O-])=O PTTGRYBBCYZPSL-UHFFFAOYSA-H 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- BBWBEZAMXFGUGK-UHFFFAOYSA-N bis(dodecylsulfanyl)-methylarsane Chemical compound CCCCCCCCCCCCS[As](C)SCCCCCCCCCCCC BBWBEZAMXFGUGK-UHFFFAOYSA-N 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 229960002227 clindamycin Drugs 0.000 description 1
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 description 1
- 229960002291 clindamycin phosphate Drugs 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000011118 depth filtration Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical compound CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 239000012537 formulation buffer Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 229940031551 inactivated vaccine Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 239000011654 magnesium acetate Substances 0.000 description 1
- 235000011285 magnesium acetate Nutrition 0.000 description 1
- 229940069446 magnesium acetate Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000011147 magnesium chloride Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 238000003525 physicochemical assay Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000013139 quantization Methods 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000012421 spiking Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004580 weight loss Effects 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
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/522—Bacterial cells; Fungal cells; Protozoal cells avirulent or attenuated
-
- 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
- A61K2039/55505—Inorganic adjuvants
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361790423P | 2013-03-15 | 2013-03-15 | |
| US61/790,423 | 2013-03-15 | ||
| PCT/US2014/029035 WO2014144567A2 (en) | 2013-03-15 | 2014-03-14 | Toxoid, compositions and related methods |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20150133770A true KR20150133770A (ko) | 2015-11-30 |
Family
ID=50489430
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020157029566A Withdrawn KR20150133770A (ko) | 2013-03-15 | 2014-03-14 | 톡소이드, 조성물 및 관련 방법 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US20160045586A1 (https=) |
| EP (1) | EP2968507A2 (https=) |
| JP (1) | JP2016516721A (https=) |
| KR (1) | KR20150133770A (https=) |
| CN (1) | CN105338997A (https=) |
| AR (1) | AR095669A1 (https=) |
| AU (1) | AU2014228956A1 (https=) |
| BR (1) | BR112015023332A2 (https=) |
| CA (1) | CA2907154A1 (https=) |
| HK (1) | HK1213800A1 (https=) |
| SG (1) | SG11201507608PA (https=) |
| TW (1) | TWI624474B (https=) |
| WO (1) | WO2014144567A2 (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR086199A1 (es) | 2011-04-22 | 2013-11-27 | Wyeth Llc | Composiciones relacionadas con una toxina de clostridium difficile mutante y sus metodos |
| BR122016023101B1 (pt) * | 2012-10-21 | 2022-03-22 | Pfizer Inc | Polipeptídeo, composição imunogênica que o compreende, bem como célula recombinante derivada de clostridium difficile |
| JP6691477B2 (ja) * | 2013-06-14 | 2020-04-28 | サノフィ パストゥール インコーポレイテッド | クロストリジウム・ディフィシル（ｃ．ｄｉｆｆｉｃｉｌｅ）に対して免疫する組成物及び方法 |
| BR112017024443A2 (pt) * | 2015-05-15 | 2018-10-23 | Sanofi Pasteur Inc | métodos para imunização contra clostridium difficile |
| US11154605B2 (en) | 2017-06-09 | 2021-10-26 | Hipra Scientific, S.L.U. | Vaccine comprising Clostridium toxoids |
| US10096313B1 (en) * | 2017-09-20 | 2018-10-09 | Bose Corporation | Parallel active noise reduction (ANR) and hear-through signal flow paths in acoustic devices |
| EP4168032A2 (en) | 2020-06-19 | 2023-04-26 | Pfizer Inc. | Immunogenic compositions against clostridioides (clostridium) difficile and methods thereof |
| JP2024546686A (ja) * | 2021-12-06 | 2024-12-26 | ラトガース，ザ ステート ユニバーシティ オブ ニュー ジャージー | 癌を治療するための組成物及び方法 |
| CN120615016A (zh) | 2023-02-02 | 2025-09-09 | 葛兰素史克生物有限公司 | 免疫原性组合物 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6967088B1 (en) * | 1995-03-16 | 2005-11-22 | Allergan, Inc. | Soluble recombinant botulinum toxin proteins |
| US5610023A (en) * | 1995-03-31 | 1997-03-11 | Lee Laboratories, Inc. | Method of purification of clostridium difficile toxin A and production of mono-specific antibodies |
| EP2305293A3 (en) * | 1997-10-20 | 2013-11-06 | Sanofi Pasteur Biologics Co. | Immunization against Clostridium difficile disease |
| US6969520B2 (en) * | 1997-10-20 | 2005-11-29 | Acambis Inc. | Active immunization against clostridium difficile disease |
| US6669520B2 (en) | 2001-09-19 | 2003-12-30 | United Microelectronics Corp. | Method of fabricating an LC panel |
| MX2010001054A (es) | 2007-07-26 | 2010-04-21 | Sanofi Pasteur Ltd | Composiciones adyuvantes antigenicas y metodos. |
| HUE037932T2 (hu) | 2007-09-14 | 2018-09-28 | Sanofi Pasteur Biologics Llc | Clostridium difficile A és B toxoidjait tartalmazó gyógyászati kompozíciók |
| GB201011968D0 (en) * | 2010-07-16 | 2010-09-01 | Secr Defence | Toxoiding method |
-
2014
- 2014-03-14 KR KR1020157029566A patent/KR20150133770A/ko not_active Withdrawn
- 2014-03-14 US US14/776,145 patent/US20160045586A1/en not_active Abandoned
- 2014-03-14 EP EP14717950.1A patent/EP2968507A2/en not_active Withdrawn
- 2014-03-14 CN CN201480021368.4A patent/CN105338997A/zh active Pending
- 2014-03-14 BR BR112015023332A patent/BR112015023332A2/pt not_active IP Right Cessation
- 2014-03-14 HK HK16101854.5A patent/HK1213800A1/zh unknown
- 2014-03-14 SG SG11201507608PA patent/SG11201507608PA/en unknown
- 2014-03-14 JP JP2016502966A patent/JP2016516721A/ja active Pending
- 2014-03-14 AU AU2014228956A patent/AU2014228956A1/en not_active Abandoned
- 2014-03-14 WO PCT/US2014/029035 patent/WO2014144567A2/en not_active Ceased
- 2014-03-14 CA CA2907154A patent/CA2907154A1/en not_active Abandoned
- 2014-03-17 TW TW103110044A patent/TWI624474B/zh not_active IP Right Cessation
- 2014-03-18 AR ARP140101275A patent/AR095669A1/es unknown
-
2017
- 2017-10-02 US US15/722,029 patent/US20180028637A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20180028637A1 (en) | 2018-02-01 |
| SG11201507608PA (en) | 2015-10-29 |
| JP2016516721A (ja) | 2016-06-09 |
| US20160045586A1 (en) | 2016-02-18 |
| CA2907154A1 (en) | 2014-09-18 |
| WO2014144567A2 (en) | 2014-09-18 |
| AR095669A1 (es) | 2015-11-04 |
| WO2014144567A3 (en) | 2014-12-04 |
| TW201514197A (zh) | 2015-04-16 |
| AU2014228956A1 (en) | 2015-10-08 |
| CN105338997A (zh) | 2016-02-17 |
| HK1213800A1 (zh) | 2016-07-15 |
| BR112015023332A2 (pt) | 2017-08-22 |
| TWI624474B (zh) | 2018-05-21 |
| EP2968507A2 (en) | 2016-01-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20150133770A (ko) | 톡소이드, 조성물 및 관련 방법 | |
| US9724402B2 (en) | Neisseria meningitidis composition and methods thereof | |
| AU2011201804B2 (en) | Active immunization against clostridium difficile disease | |
| JP3280675B2 (ja) | 多価ｄｔｐポリオワクチン | |
| US11472850B2 (en) | Neisseria meningitidis composition and methods thereof | |
| KR20180054629A (ko) | 장외 병원성 e. 콜리에 대한 면역 보호를 위한 방법 및 조성물 | |
| CN102238960B (zh) | 制造疫苗的方法 | |
| KR20150133771A (ko) | 톡소이드, 조성물 및 관련 방법 | |
| US20180110849A1 (en) | Methods for immunizing against clostridium difficile | |
| CN110251667A (zh) | 一种免疫组合制剂及其制备方法和应用 | |
| NZ731330B2 (en) | Neisseria meningitidis compositions and methods thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20151014 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |