IL135743A - Preparations and methods for the systemic administration of vaccines and cures - Google Patents
Preparations and methods for the systemic administration of vaccines and curesInfo
- Publication number
- IL135743A IL135743A IL13574398A IL13574398A IL135743A IL 135743 A IL135743 A IL 135743A IL 13574398 A IL13574398 A IL 13574398A IL 13574398 A IL13574398 A IL 13574398A IL 135743 A IL135743 A IL 135743A
- Authority
- IL
- Israel
- Prior art keywords
- botulinum toxin
- modified
- toxin
- modified botulinum
- rbont
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 21
- 229940124597 therapeutic agent Drugs 0.000 title claims description 15
- 229940126578 oral vaccine Drugs 0.000 title claims description 14
- 238000000034 method Methods 0.000 title claims description 13
- 239000000203 mixture Substances 0.000 title description 11
- 238000012385 systemic delivery Methods 0.000 title description 4
- 108030001720 Bontoxilysin Proteins 0.000 claims abstract description 88
- 229940053031 botulinum toxin Drugs 0.000 claims abstract description 75
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 15
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 15
- 241001465754 Metazoa Species 0.000 claims description 19
- 208000003508 Botulism Diseases 0.000 claims description 9
- 239000000427 antigen Substances 0.000 claims description 8
- 108091007433 antigens Proteins 0.000 claims description 8
- 102000036639 antigens Human genes 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 description 27
- 108700012359 toxins Proteins 0.000 description 27
- 102000004169 proteins and genes Human genes 0.000 description 26
- 239000003053 toxin Substances 0.000 description 26
- 231100000765 toxin Toxicity 0.000 description 26
- 229930186900 holotoxin Natural products 0.000 description 25
- 210000001035 gastrointestinal tract Anatomy 0.000 description 23
- 239000012634 fragment Substances 0.000 description 21
- 101000985023 Clostridium botulinum C phage Botulinum neurotoxin type C Proteins 0.000 description 20
- 210000002966 serum Anatomy 0.000 description 17
- 239000013612 plasmid Substances 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- 230000004572 zinc-binding Effects 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 229960005486 vaccine Drugs 0.000 description 13
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 9
- 238000007920 subcutaneous administration Methods 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- 210000001640 nerve ending Anatomy 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000013615 primer Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 230000001713 cholinergic effect Effects 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 239000002581 neurotoxin Substances 0.000 description 6
- 231100000618 neurotoxin Toxicity 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 101710138657 Neurotoxin Proteins 0.000 description 5
- 230000000890 antigenic effect Effects 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000001830 phrenic effect Effects 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 239000003656 tris buffered saline Substances 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 239000003155 DNA primer Substances 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 206010033799 Paralysis Diseases 0.000 description 4
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 4
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 4
- 206010043376 Tetanus Diseases 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 231100001103 botulinum neurotoxin Toxicity 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000012149 elution buffer Substances 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 238000003119 immunoblot Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 210000003568 synaptosome Anatomy 0.000 description 4
- 231100000820 toxicity test Toxicity 0.000 description 4
- 238000012384 transportation and delivery Methods 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- 241000193155 Clostridium botulinum Species 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 101710118538 Protease Proteins 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001378 electrochemiluminescence detection Methods 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 150000007523 nucleic acids Chemical group 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 229940023041 peptide vaccine Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 241001112695 Clostridiales Species 0.000 description 2
- 241000193449 Clostridium tetani Species 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102000004594 DNA Polymerase I Human genes 0.000 description 2
- 108010017826 DNA Polymerase I Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 240000008790 Musa x paradisiaca Species 0.000 description 2
- 235000018290 Musa x paradisiaca Nutrition 0.000 description 2
- 206010028347 Muscle twitching Diseases 0.000 description 2
- 206010029315 Neuromuscular blockade Diseases 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 201000005702 Pertussis Diseases 0.000 description 2
- 208000005374 Poisoning Diseases 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 2
- 206010037742 Rabies Diseases 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 244000061456 Solanum tuberosum Species 0.000 description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 description 2
- 108010055044 Tetanus Toxin Proteins 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 206010013023 diphtheria Diseases 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000000763 evoking effect Effects 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229940118376 tetanus toxin Drugs 0.000 description 2
- 229960000187 tissue plasminogen activator Drugs 0.000 description 2
- 231100000041 toxicology testing Toxicity 0.000 description 2
- 230000005945 translocation Effects 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
- 238000002255 vaccination Methods 0.000 description 2
- FMYBFLOWKQRBST-UHFFFAOYSA-N 2-[bis(carboxymethyl)amino]acetic acid;nickel Chemical compound [Ni].OC(=O)CN(CC(O)=O)CC(O)=O FMYBFLOWKQRBST-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108091028026 C-DNA Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241001647378 Chlamydia psittaci Species 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 241000186542 Clostridium baratii Species 0.000 description 1
- 241000193171 Clostridium butyricum Species 0.000 description 1
- 244000309714 Clostridium perfringens type C Species 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 208000000655 Distemper Diseases 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 208000000832 Equine Encephalomyelitis Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241001596967 Escherichia coli M15 Species 0.000 description 1
- 241000714165 Feline leukemia virus Species 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 206010016952 Food poisoning Diseases 0.000 description 1
- 208000019331 Foodborne disease Diseases 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
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- QIFOTGBMWFMXRC-UHFFFAOYSA-N Holotoxin A Natural products OC1C(OC)C(O)C(CO)OC1OC1C(O)C(OC2C(OCC(C2O)OC2C(C(O)C(OC3C(C(O)C(O)CO3)O)C(C)O2)O)OC2C(C3C(C=4C(C5(CC(=O)C6C5(C(OC6(CCCC(C)(C)O)C)=O)CC=4)C)CC3)(C)CC2)(C)C)OC(CO)C1O QIFOTGBMWFMXRC-UHFFFAOYSA-N 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 206010024238 Leptospirosis Diseases 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108091005461 Nucleic proteins Chemical group 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 108010035766 P-Selectin Proteins 0.000 description 1
- 102100023472 P-selectin Human genes 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 206010051497 Rhinotracheitis Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000003152 Yellow Fever Diseases 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000009056 active transport Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- -1 but not limited to Proteins 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 208000005098 feline infectious peritonitis Diseases 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- BIHNZKYXOTXXSP-GCBHNEMQSA-N holotoxin a Chemical compound O[C@@H]1[C@@H](OC)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](OC)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@@H](C)O3)O)[C@H](OC3C(C4[C@](C=5C([C@@]6(CC(=O)[C@H]7C6(C(O[C@]7(CCCC(C)=C)C)=O)CC=5)C)CC4)(C)CC3)(C)C)OC2)O)O[C@H](CO)[C@H]1O BIHNZKYXOTXXSP-GCBHNEMQSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 231100000580 in vitro toxicity testing Toxicity 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 210000003105 phrenic nerve Anatomy 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 235000008476 powdered milk Nutrition 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 231100000654 protein toxin Toxicity 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229940083575 sodium dodecyl sulfate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229960002766 tetanus vaccines Drugs 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 201000011423 wound botulism Diseases 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- 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
- 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
- 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
- A61K47/646—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 the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/542—Mucosal route oral/gastrointestinal
-
- 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
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/832—Drug, bio-affecting and body treating compositions involving bacterial toxin that has modified amino acid sequence
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/954,302 US6051239A (en) | 1997-10-20 | 1997-10-20 | Compositions and methods for systemic delivery of oral vaccines and therapeutic agents |
| PCT/US1998/021897 WO1999020306A1 (en) | 1997-10-20 | 1998-10-16 | Compositions and methods for systemic delivery of oral vaccines and therapeutic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL135743A0 IL135743A0 (en) | 2001-05-20 |
| IL135743A true IL135743A (en) | 2004-03-28 |
Family
ID=25495232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13574398A IL135743A (en) | 1997-10-20 | 1998-10-16 | Preparations and methods for the systemic administration of vaccines and cures |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6051239A (enExample) |
| EP (1) | EP1024827B1 (enExample) |
| JP (1) | JP2001522783A (enExample) |
| KR (1) | KR100594787B1 (enExample) |
| CN (1) | CN1246038C (enExample) |
| AT (1) | ATE355076T1 (enExample) |
| AU (1) | AU756475B2 (enExample) |
| BR (1) | BR9815255A (enExample) |
| CA (1) | CA2306995A1 (enExample) |
| DE (1) | DE69837209T2 (enExample) |
| EE (1) | EE200000536A (enExample) |
| HU (1) | HUP0101017A3 (enExample) |
| IL (1) | IL135743A (enExample) |
| NZ (1) | NZ504549A (enExample) |
| RU (1) | RU2227042C2 (enExample) |
| WO (1) | WO1999020306A1 (enExample) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7227010B2 (en) | 1993-09-21 | 2007-06-05 | United States Of America As Represented By The Secretary Of The Army | Recombinant light chains of botulinum neurotoxins and light chain fusion proteins for use in research and clinical therapy |
| US6967088B1 (en) * | 1995-03-16 | 2005-11-22 | Allergan, Inc. | Soluble recombinant botulinum toxin proteins |
| US8632785B2 (en) * | 2000-02-08 | 2014-01-21 | Allergan, Inc. | Clostridial toxin pharmaceutical composition containing a gelatin fragment |
| KR100753765B1 (ko) * | 2000-02-08 | 2007-08-31 | 알레간 인코포레이티드 | 보툴리눔 독소 약제학적 조성물 |
| US7780967B2 (en) * | 2000-02-08 | 2010-08-24 | Allergan, Inc. | Reduced toxicity Clostridial toxin pharmaceutical compositions |
| US20030118598A1 (en) * | 2000-02-08 | 2003-06-26 | Allergan, Inc. | Clostridial toxin pharmaceutical compositions |
| US20060269575A1 (en) * | 2000-02-08 | 2006-11-30 | Allergan, Inc. | Botulinum toxin pharmaceutical compositions formulated with recombinant albumin |
| US6903187B1 (en) * | 2000-07-21 | 2005-06-07 | Allergan, Inc. | Leucine-based motif and clostridial neurotoxins |
| AU2002228887B2 (en) * | 2000-11-06 | 2006-08-24 | United States Army Medical Research And Material Command | Recombinant light chains of botulinum neurotoxins and light chain fusion proteins for use in research and clinical therapy |
| US7273722B2 (en) * | 2000-11-29 | 2007-09-25 | Allergan, Inc. | Neurotoxins with enhanced target specificity |
| JP4707254B2 (ja) * | 2001-04-24 | 2011-06-22 | クミアイ化学工業株式会社 | 粒状組成物及びその製造方法 |
| US7691394B2 (en) * | 2002-05-28 | 2010-04-06 | Botulinum Toxin Research Associates, Inc. | High-potency botulinum toxin formulations |
| AU2003237346A1 (en) * | 2002-05-31 | 2003-12-19 | Thomas Jefferson University | Compositions and methods for transepithelial molecular transport |
| US20040086532A1 (en) * | 2002-11-05 | 2004-05-06 | Allergan, Inc., | Botulinum toxin formulations for oral administration |
| EP1629090B1 (en) * | 2002-11-06 | 2014-03-05 | iBio, Inc. | Expression of foreign sequences in plants using trans-activation system |
| US7491509B2 (en) | 2003-02-03 | 2009-02-17 | Fraunhofer Usa, Inc. | System for expression of genes in plants |
| US7683238B2 (en) * | 2002-11-12 | 2010-03-23 | iBio, Inc. and Fraunhofer USA, Inc. | Production of pharmaceutically active proteins in sprouted seedlings |
| US7692063B2 (en) * | 2002-11-12 | 2010-04-06 | Ibio, Inc. | Production of foreign nucleic acids and polypeptides in sprout systems |
| AU2003300666A1 (en) * | 2002-12-20 | 2004-07-29 | Botulinum Toxin Research Associates, Inc. | Pharmaceutical botulinum toxin compositions |
| US20040253274A1 (en) * | 2003-06-11 | 2004-12-16 | Allergan, Inc. | Use of a clostridial toxin to reduce appetite |
| US7172764B2 (en) * | 2003-11-17 | 2007-02-06 | Allergan, Inc. | Rescue agents for treating botulinum toxin intoxications |
| US20050129677A1 (en) * | 2003-12-10 | 2005-06-16 | Shengwen Li | Lipid rafts and clostridial toxins |
| AU2005216133A1 (en) * | 2004-02-20 | 2005-09-09 | Fraunhofer Usa, Inc. | Systems and methods for clonal expression in plants |
| US7306807B2 (en) | 2004-09-13 | 2007-12-11 | Wyeth | Hemorrhagic feline calicivirus, calicivirus vaccine and method for preventing calicivirus infection or disease |
| US7785606B2 (en) * | 2004-11-22 | 2010-08-31 | New York University | Genetically engineered clostridial genes, proteins encoded by the engineered genes, and uses thereof |
| JP4667507B2 (ja) | 2005-10-07 | 2011-04-13 | ファイザー・プロダクツ・インク | イヌインフルエンザを治療するワクチンおよび方法 |
| EP1931379B1 (en) | 2005-10-07 | 2013-05-29 | Health Protection Agency | Proteins with improved solubility and methods for producing and using same |
| US20080299149A1 (en) * | 2007-05-30 | 2008-12-04 | Wyeth | Raccoon Poxvirus Expressing Genes of Feline Antigens |
| US8445650B2 (en) * | 2007-09-25 | 2013-05-21 | Thomas Jefferson University | Mutant botulinum neurotoxin serotype A polypeptide and uses thereof |
| WO2010096134A1 (en) | 2008-12-04 | 2010-08-26 | Botulinum Toxin Research Associates, Inc. | Extended length botulinum toxin formulation for human or mammalian use |
| US9393291B2 (en) | 2012-04-12 | 2016-07-19 | Botulinum Toxin Research Associates, Inc. | Use of botulinum toxin for the treatment of cerebrovascular disease, renovascular and retinovascular circulatory beds |
| EP2948174B1 (en) | 2013-01-28 | 2019-09-11 | New York University | Treatment methods using atoxic neurotoxin derivatives |
| US9901627B2 (en) | 2014-07-18 | 2018-02-27 | Revance Therapeutics, Inc. | Topical ocular preparation of botulinum toxin for use in ocular surface disease |
| US11484580B2 (en) | 2014-07-18 | 2022-11-01 | Revance Therapeutics, Inc. | Topical ocular preparation of botulinum toxin for use in ocular surface disease |
| EP3230457B1 (en) | 2014-12-09 | 2021-06-30 | New York University | Clostridial neurotoxin fusion proteins, propeptide fusions, their expression, and use |
| BR112020012641A2 (pt) | 2017-12-20 | 2020-12-01 | Allergan, Inc. | polipeptídeos de domínio de ligação celular de toxina de botulinum e métodos de uso para rejuvenescimento da pele |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5919665A (en) * | 1989-10-31 | 1999-07-06 | Ophidian Pharmaceuticals, Inc. | Vaccine for clostridium botulinum neurotoxin |
| AU695623B2 (en) * | 1994-05-31 | 1998-08-20 | Allergan, Inc. | Modification of clostridial toxins for use as transport proteins |
| EP0796326A4 (en) * | 1994-10-24 | 2000-01-19 | Ophidian Pharm Inc | VACCINE AND ANTITOXIN FOR THE TREATMENT AND PREVENTION OF C. DIFFICILE DISEASE |
| WO1996040229A1 (en) * | 1995-06-07 | 1996-12-19 | Thomas Jefferson University | Vaccines synthesized by transgenic plants |
| WO1997032599A1 (en) * | 1996-03-08 | 1997-09-12 | The Regents Of The University Of California | Chemically-modified clostridiatoxin with improved properties |
-
1997
- 1997-10-20 US US08/954,302 patent/US6051239A/en not_active Expired - Fee Related
-
1998
- 1998-10-16 JP JP2000516701A patent/JP2001522783A/ja active Pending
- 1998-10-16 HU HU0101017A patent/HUP0101017A3/hu unknown
- 1998-10-16 DE DE69837209T patent/DE69837209T2/de not_active Expired - Fee Related
- 1998-10-16 AT AT98953617T patent/ATE355076T1/de not_active IP Right Cessation
- 1998-10-16 RU RU2000112547/15A patent/RU2227042C2/ru not_active IP Right Cessation
- 1998-10-16 EE EEP200000536A patent/EE200000536A/xx unknown
- 1998-10-16 AU AU10947/99A patent/AU756475B2/en not_active Ceased
- 1998-10-16 IL IL13574398A patent/IL135743A/en not_active IP Right Cessation
- 1998-10-16 BR BR9815255-6A patent/BR9815255A/pt not_active Application Discontinuation
- 1998-10-16 CA CA002306995A patent/CA2306995A1/en not_active Abandoned
- 1998-10-16 KR KR1020007004197A patent/KR100594787B1/ko not_active Expired - Fee Related
- 1998-10-16 CN CNB988112981A patent/CN1246038C/zh not_active Expired - Fee Related
- 1998-10-16 NZ NZ504549A patent/NZ504549A/xx unknown
- 1998-10-16 WO PCT/US1998/021897 patent/WO1999020306A1/en not_active Ceased
- 1998-10-16 EP EP98953617A patent/EP1024827B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE69837209T2 (de) | 2007-10-31 |
| HUP0101017A3 (en) | 2003-11-28 |
| HUP0101017A2 (hu) | 2001-07-30 |
| EP1024827B1 (en) | 2007-02-28 |
| CN1290174A (zh) | 2001-04-04 |
| WO1999020306A1 (en) | 1999-04-29 |
| BR9815255A (pt) | 2001-12-26 |
| DE69837209D1 (de) | 2007-04-12 |
| US6051239A (en) | 2000-04-18 |
| EP1024827A4 (en) | 2002-08-28 |
| EE200000536A (et) | 2002-04-15 |
| IL135743A0 (en) | 2001-05-20 |
| ATE355076T1 (de) | 2006-03-15 |
| EP1024827A1 (en) | 2000-08-09 |
| JP2001522783A (ja) | 2001-11-20 |
| AU756475B2 (en) | 2003-01-16 |
| CN1246038C (zh) | 2006-03-22 |
| RU2227042C2 (ru) | 2004-04-20 |
| CA2306995A1 (en) | 1999-04-29 |
| KR20010031236A (ko) | 2001-04-16 |
| NZ504549A (en) | 2002-12-20 |
| KR100594787B1 (ko) | 2006-07-03 |
| AU1094799A (en) | 1999-05-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1024827B1 (en) | Compositions and methods for systemic delivery of oral vaccines and therapeutic agents | |
| Kiyatkin et al. | Induction of an immune response by oral administration of recombinant botulinum toxin | |
| JP3927233B2 (ja) | 肺炎双球菌感染症に対する免疫化のための肺炎双球菌多糖−組み換えニューモリシン結合体ワクチン類 | |
| DE69332434T2 (de) | Clostridium perfringens Impfstoffe | |
| US8012479B2 (en) | Recombinant toxin fragments | |
| Pappenheimer Jr et al. | Diphtheria: Recent studies have clarified the molecular mechanisms involved in its pathogenesis. | |
| AU695623B2 (en) | Modification of clostridial toxins for use as transport proteins | |
| JP2714068B2 (ja) | 遺伝子操作による百日ぜきトキシンの無毒化 | |
| ES2277854T3 (es) | Neurotoxinas recombinantes activables. | |
| US7335361B2 (en) | Fusion antigen used as vaccine | |
| US6214602B1 (en) | Host cells for expression of clostridial toxins and proteins | |
| JP3578799B2 (ja) | ストレプトコッカス・スイス感染に対するワクチン | |
| NZ220027A (en) | Antigens or haptens coupled to escherichia coli outer membrane proteins for enhancement of immune response | |
| US6545126B1 (en) | Chimeric toxins | |
| CA2592627A1 (en) | Vaccine composition comprising a fibronectin binding protein or a fibronectin binding peptide | |
| JPH10234388A (ja) | 淋菌ｐｉタンパク質およびワクチンの製造 | |
| WO1998059053A1 (en) | Immonogenic fragments of toxin a of clostridium difficile | |
| KR20240031857A (ko) | Covid-19 백신을 임베딩하기 위한 파상풍 백신 플랫폼 | |
| EP0352250B1 (en) | Bordetella pertussis vaccine | |
| Mustafa et al. | Immunization of mice with the non-toxic HC50 domain of botulinum neurotoxin presented by rabies virus particles induces a strong immune response affording protection against high-dose botulinum neurotoxin challenge | |
| MXPA00003799A (en) | Compositions and methods for systemic delivery of oral vaccines and therapeutic agents | |
| CZ20001399A3 (cs) | Prostředky a způsoby pro systémové podání orálních vakcín a terapeutických činidel | |
| Shone et al. | Toxigenic clostridia | |
| WO2025257397A1 (en) | Live attenuated bordetella vaccines capable of producing and secreting heterologous antigens | |
| Joubert | Expression of the botulinum neurotoxin serotype D binding domain in Brevibacillus brevis and its evaluation as a candidate vaccine antigen in mice |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |