IL105456A - Vaccines of attenuated respiratory syncytial virus - Google Patents
Vaccines of attenuated respiratory syncytial virusInfo
- Publication number
- IL105456A IL105456A IL10545693A IL10545693A IL105456A IL 105456 A IL105456 A IL 105456A IL 10545693 A IL10545693 A IL 10545693A IL 10545693 A IL10545693 A IL 10545693A IL 105456 A IL105456 A IL 105456A
- Authority
- IL
- Israel
- Prior art keywords
- virus
- rsv
- attenuated
- respiratory syncytial
- cold
- Prior art date
Links
- 230000002238 attenuated effect Effects 0.000 title claims abstract description 133
- 229960005486 vaccine Drugs 0.000 title claims abstract description 69
- 241000725643 Respiratory syncytial virus Species 0.000 title claims abstract description 30
- 239000000203 mixture Substances 0.000 title claims abstract description 20
- 241000700605 Viruses Species 0.000 claims abstract description 293
- 230000035772 mutation Effects 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 30
- 210000000987 immune system Anatomy 0.000 claims abstract description 4
- 230000004936 stimulating effect Effects 0.000 claims abstract description 3
- 210000002345 respiratory system Anatomy 0.000 claims description 28
- 231100000350 mutagenesis Toxicity 0.000 claims description 17
- 238000002703 mutagenesis Methods 0.000 claims description 16
- 210000001989 nasopharynx Anatomy 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 10
- 230000028993 immune response Effects 0.000 claims description 9
- 239000002671 adjuvant Substances 0.000 claims description 4
- 239000000443 aerosol Substances 0.000 claims description 3
- 230000000241 respiratory effect Effects 0.000 claims description 3
- -1 droplet Substances 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 238000001212 derivatisation Methods 0.000 abstract description 3
- 230000010076 replication Effects 0.000 description 45
- 241001465754 Metazoa Species 0.000 description 27
- 241000282579 Pan Species 0.000 description 26
- 208000015181 infectious disease Diseases 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 22
- 210000003501 vero cell Anatomy 0.000 description 18
- 241000282412 Homo Species 0.000 description 17
- 230000007505 plaque formation Effects 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 15
- 230000002068 genetic effect Effects 0.000 description 14
- 208000036071 Rhinorrhea Diseases 0.000 description 13
- 206010039101 Rhinorrhoea Diseases 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 210000004072 lung Anatomy 0.000 description 12
- 241000282577 Pan troglodytes Species 0.000 description 11
- 238000004113 cell culture Methods 0.000 description 11
- 230000003053 immunization Effects 0.000 description 11
- 238000002649 immunization Methods 0.000 description 11
- 230000009385 viral infection Effects 0.000 description 11
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 230000003472 neutralizing effect Effects 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 230000001681 protective effect Effects 0.000 description 9
- 210000001944 turbinate Anatomy 0.000 description 9
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 8
- 229960002949 fluorouracil Drugs 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 7
- 239000002054 inoculum Substances 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 229940124679 RSV vaccine Drugs 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 230000003248 secreting effect Effects 0.000 description 6
- 241000283984 Rodentia Species 0.000 description 5
- 241000144282 Sigmodon Species 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 208000030500 lower respiratory tract disease Diseases 0.000 description 5
- 230000035945 sensitivity Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- 230000001018 virulence Effects 0.000 description 5
- 241000283690 Bos taurus Species 0.000 description 4
- 241000282693 Cercopithecidae Species 0.000 description 4
- 241000699660 Mus musculus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 206010046865 Vaccinia virus infection Diseases 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000005875 antibody response Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000011580 nude mouse model Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 210000003437 trachea Anatomy 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- 208000007089 vaccinia Diseases 0.000 description 4
- 206010006448 Bronchiolitis Diseases 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 206010035664 Pneumonia Diseases 0.000 description 3
- 241000144290 Sigmodon hispidus Species 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000120 cytopathologic effect Effects 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 210000003292 kidney cell Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 206010039083 rhinitis Diseases 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 239000005723 virus inoculator Substances 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- 208000031504 Asymptomatic Infections Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 208000018569 Respiratory Tract disease Diseases 0.000 description 2
- 102100021696 Syncytin-1 Human genes 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 239000002962 chemical mutagen Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000004264 monolayer culture Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229940031626 subunit vaccine Drugs 0.000 description 2
- 229940125575 vaccine candidate Drugs 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[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](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
- 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 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- WTLKTXIHIHFSGU-UHFFFAOYSA-N 2-nitrosoguanidine Chemical compound NC(N)=NN=O WTLKTXIHIHFSGU-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 1
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282552 Chlorocebus aethiops Species 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 101710121417 Envelope glycoprotein Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000711920 Human orthopneumovirus Species 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101000916271 Pan troglodytes Cardiotrophin-2 Proteins 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 208000035415 Reinfection Diseases 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229960002713 calcium chloride Drugs 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 229940031551 inactivated vaccine Drugs 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229960002816 potassium chloride Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011809 primate model Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 208000030925 respiratory syncytial virus infectious disease Diseases 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229960004249 sodium acetate Drugs 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000009120 supportive therapy Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/01—Preparation of mutants without inserting foreign genetic material therein; Screening processes therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
-
- 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
- A61K39/12—Viral antigens
-
- 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
- A61K39/12—Viral antigens
- A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- A61K2039/525—Virus
- A61K2039/5254—Virus 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/543—Mucosal route intranasal
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18534—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18561—Methods of inactivation or attenuation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Vertical, Hearth, Or Arc Furnaces (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87274692A | 1992-04-21 | 1992-04-21 | |
| US3994593A | 1993-04-09 | 1993-04-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL105456A0 IL105456A0 (en) | 1993-08-18 |
| IL105456A true IL105456A (en) | 1996-12-05 |
Family
ID=26716607
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL10545693A IL105456A (en) | 1992-04-21 | 1993-04-19 | Vaccines of attenuated respiratory syncytial virus |
Country Status (18)
| Country | Link |
|---|---|
| US (3) | US5922326A (fr) |
| EP (1) | EP0640128B1 (fr) |
| JP (1) | JP3883202B2 (fr) |
| KR (1) | KR100257171B1 (fr) |
| AT (1) | ATE181359T1 (fr) |
| AU (1) | AU683840B2 (fr) |
| CA (1) | CA2118509C (fr) |
| DE (1) | DE69325370T2 (fr) |
| DK (1) | DK0640128T3 (fr) |
| ES (1) | ES2132233T3 (fr) |
| GR (1) | GR3031208T3 (fr) |
| HU (1) | HU220189B (fr) |
| IL (1) | IL105456A (fr) |
| MX (1) | MX9302278A (fr) |
| NZ (1) | NZ252857A (fr) |
| RU (1) | RU2139729C1 (fr) |
| UA (1) | UA41315C2 (fr) |
| WO (1) | WO1993021310A1 (fr) |
Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9200117D0 (en) * | 1992-01-06 | 1992-02-26 | Connaught Lab | Production of recombinant chimeric proteins for vaccine use |
| TW275632B (fr) * | 1992-04-21 | 1996-05-11 | American Cyanamid Co | |
| US7083795B1 (en) | 1993-08-06 | 2006-08-01 | Sanofi Pasteur Limited | Inactivated respiratory syncytial viral vaccines |
| US7223410B1 (en) | 1994-08-05 | 2007-05-29 | Sanofi Pasteur Limited | Inactivated respiratory syncytial viral vaccines |
| US5789229A (en) * | 1994-09-30 | 1998-08-04 | Uab Research Foundation | Stranded RNA virus particles |
| US5716821A (en) * | 1994-09-30 | 1998-02-10 | Uab Research Foundation | Prevention and treatment of respiratory tract disease |
| US6083925A (en) | 1995-06-07 | 2000-07-04 | Connaught Laboratories Limited | Nucleic acid respiratory syncytial virus vaccines |
| US6019980A (en) * | 1995-06-07 | 2000-02-01 | Connaught Laboratories Limited | Nucleic acid respiratory syncytial virus vaccines |
| US6689367B1 (en) | 1995-09-27 | 2004-02-10 | The United States Of America As Represented By The Department Of Health And Human Services | Production of attenuated chimeric respiratory syncytial virus vaccines from cloned nucleotide sequences |
| US7485440B2 (en) | 1995-09-27 | 2009-02-03 | The United States Of America As Represented By The Department Of Health And Human Services | Production of attenuated respiratory syncytial virus vaccines involving modification of M2 ORF2 |
| WO1997012032A1 (fr) * | 1995-09-27 | 1997-04-03 | The Government Of The United States Of America, As Represented By The Department Of Health And Human Services | Production de virus syncytial respiratoire infectieux a partir de sequences de nucleotides clones |
| US7846455B2 (en) | 1996-07-15 | 2010-12-07 | The United States Of America As Represented By The Department Of Health And Human Services | Attenuated chimeric respiratory syncytial virus |
| US20050287540A1 (en) * | 1995-09-27 | 2005-12-29 | Murphy Brian R | Production of attenuated negative stranded RNA virus vaccines from cloned nucleotide sequences |
| EP0917592A4 (fr) * | 1996-04-04 | 2002-04-24 | Univ Michigan | Virus respiratoire syncytial attenue |
| US6077514A (en) * | 1996-04-04 | 2000-06-20 | The Regents Of The University Of Michigan | Attenuated respiratory syncytial virus |
| AU3431397A (en) * | 1996-07-12 | 1998-02-09 | Connaught Laboratories Limited | Two-step immunization procedure against the pyramyxoviridae family of viruses using attenuated viral strains and subunit protein preparation |
| ES2345643T3 (es) | 1996-07-15 | 2010-09-28 | The Government Of The Usa, As Represented By The Department Of Health And Human Services | Produccion de vacunas a base de virus respiratorio sincitial atenuado, a partir de secuencias nucleotidicas clonadas. |
| US6699476B1 (en) | 1996-07-15 | 2004-03-02 | Peter L. Collins | Production of recombinant respiratory syncytial viruses expressing immune modulatory molecules |
| CA2265554A1 (fr) * | 1996-09-27 | 1998-04-02 | American Cyanamid Company | Region promotrice 3' du genome et mutations du gene polymerase responsables de l'attenuation dans des virus de l'ordre appele mononegavirales |
| US7951383B2 (en) | 1997-05-23 | 2011-05-31 | The United States Of America As Represented By The Department Of Health And Human Services | Attenuated parainfluenza virus (PIV) vaccines |
| US7201907B1 (en) | 1997-05-23 | 2007-04-10 | The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Attenuated human-bovine chimeric parainfluenza virus(PIV) vaccines |
| US20030082209A1 (en) | 2000-07-05 | 2003-05-01 | Skiadopoulos Mario H. | Attenuated human-bovine chimeric parainfluenza virus (PIV) vaccines |
| US7632508B2 (en) | 1997-05-23 | 2009-12-15 | The United States Of America | Attenuated human-bovine chimeric parainfluenza virus (PIV) vaccines |
| US6410023B1 (en) | 1997-05-23 | 2002-06-25 | United States Of America | Recombinant parainfluenza virus vaccines attenuated by deletion or ablation of a non-essential gene |
| FR2764903A1 (fr) * | 1997-06-23 | 1998-12-24 | Pasteur Institut | Detection des infections par des paramyxovirus (virus respiratoire syncitial et virus parainfluenza) utilisant des polynucleotides codant de la proteine l |
| US20040005542A1 (en) | 2001-06-22 | 2004-01-08 | Krempl Christine D | Respiratory syncytial virus vaccines expressing protective antigens from promotor- proximal genes |
| US7662397B2 (en) | 1997-07-15 | 2010-02-16 | The United States Of America As Represented By The Department Of Health And Human Services | Respiratory syncytial virus vaccines expressing protective antigens from promoter-proximal genes |
| US6482414B1 (en) | 1998-08-13 | 2002-11-19 | The University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Cold-adapted equine influenza viruses |
| US6177082B1 (en) | 1998-08-13 | 2001-01-23 | The University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Cold-adapted equine influenza viruses |
| US6579528B1 (en) | 1998-08-13 | 2003-06-17 | The University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Cold-adapted equine influenza viruses |
| JP2002541785A (ja) | 1999-04-13 | 2002-12-10 | アメリカ合衆国 | クローン化ヌクレオチド配列からの弱毒化キメラ呼吸系発疹ウイルスワクチンの製造 |
| US7820182B2 (en) * | 1999-07-09 | 2010-10-26 | The United States Of America As Represented By The Department Of Health And Human Services | Production of attenuated, human-bovine chimeric respiratory syncytial viruses for use in immunogenic compositions |
| WO2001004335A2 (fr) * | 1999-07-09 | 2001-01-18 | The Government Of The United States Of America, As Represented By The Department Of Health And Humanservices | Production de vaccins a virus respiratoires syncitiaux chimeres humains-bovins attenues |
| AU2001249300B2 (en) | 2000-04-03 | 2006-02-16 | The University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Cold-adapted equine influenza viruses |
| WO2003028759A1 (fr) * | 2001-09-28 | 2003-04-10 | University Of South Florida | Vaccin a expression genique contre le rsv |
| CN103540613A (zh) * | 2002-04-26 | 2014-01-29 | 米迪缪尼有限公司 | 制备流感病毒的多质粒系统 |
| US7465456B2 (en) * | 2002-04-26 | 2008-12-16 | Medimmune, Llc | Multi plasmid system for the production of influenza virus |
| AU2003295339B2 (en) * | 2002-09-27 | 2009-03-26 | Medimmune, Llc | Functional mutations in respiratory syncytial virus |
| WO2004083397A2 (fr) * | 2003-03-18 | 2004-09-30 | Wyeth Holdings Corporation | Procede permettant d'accroitre les rendements de glycoproteines a surface vrs au moyen d'une souche de mutants du vrs |
| CA2520671C (fr) * | 2003-03-28 | 2014-03-18 | Medimmune Vaccines, Inc. | Compositions contenant un virus syncytial respiratoire de la souche 9320 du sous-groupe b, et procedes associes |
| CA2529647C (fr) | 2003-06-16 | 2013-08-13 | Medimmune Vaccines, Inc. | Hemagglutinine du virus de la grippe et variantes de la neuraminidase |
| BRPI0417672A (pt) * | 2003-12-17 | 2007-03-20 | Wyeth Corp | processos para produzir composições de vìrus estáveis em armazenamento, composições de vìrus e imunogênicas |
| WO2005062820A2 (fr) | 2003-12-23 | 2005-07-14 | Medimmune Vaccines, Inc | Systeme a plasmides multiples pour la production du virus de la grippe |
| CA2822895A1 (fr) | 2004-05-25 | 2005-12-08 | Medimmune, Llc | Variantes hemagglutinine et neuraminidase de la grippe |
| EP2441471B1 (fr) | 2005-03-08 | 2014-10-08 | MedImmune, LLC | Virus de la grippe réassortis |
| US7601356B2 (en) * | 2006-07-21 | 2009-10-13 | Medimmune, Llc | Methods and compositions for increasing replication capacity of an influenza virus |
| KR101586968B1 (ko) * | 2006-08-09 | 2016-01-20 | 메디뮨 엘엘씨 | 인플루엔자 헤마글루티닌 및 뉴라미니다제 변이체 |
| WO2008157583A1 (fr) * | 2007-06-18 | 2008-12-24 | Medimmune, Llc | Virus b de la grippe présentant des modifications du polypeptide de l'hémagglutinine |
| EP2069485A4 (fr) * | 2007-07-13 | 2011-05-25 | Medimmune Llc | Préparation de virus d'arn à brin négatif par électroporation |
| BRPI0915487A2 (pt) * | 2008-07-11 | 2017-06-27 | Medimmune Inc | hemaglutina de nfluenza e variantes de neuraminidase |
| AU2010213966B2 (en) | 2009-02-12 | 2015-01-22 | Medimmune, Llc | Influenza hemagglutinin and neuraminidase variants |
| GB201003630D0 (en) | 2010-03-04 | 2010-04-21 | Novartis Ag | Avian rotavirus |
| JP2015501141A (ja) | 2011-10-07 | 2015-01-15 | メディミューン，エルエルシー | インフルエンザヘマグルチニン変異体 |
| EP3875112A1 (fr) | 2012-04-13 | 2021-09-08 | The United States of America, as Represented By the Secretary, Department of Health and Human Services | Vaccin vivant atténué et génétiquement stable contre le virus respiratoire syncytial et sa production |
| KR20150127206A (ko) * | 2013-03-14 | 2015-11-16 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 나노입자-기재 조성물 |
| CA2906606A1 (fr) | 2013-03-14 | 2014-09-25 | Emory University | Rsv recombine avec des mutations silencieuses, vaccins, et procedes apparentes |
| BR112018008708A2 (pt) | 2015-10-29 | 2018-11-06 | Univ Emory | rsv quimérico, composições imunogênicas e métodos de uso |
| RU2746280C1 (ru) * | 2020-08-03 | 2021-04-12 | Федеральное государственное бюджетное научное учреждение "Федеральный исследовательский центр фундаментальной и трансляционной медицины" (ФИЦ ФТМ) | Штамм респираторно-синцитиального вируса RSV/Novosibirsk/66Hl/2018 для использования в диагностике респираторно-синцитиальной вирусной инфекции и исследования эффективности противовирусных препаратов in vitro |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4866034A (en) * | 1982-05-26 | 1989-09-12 | Ribi Immunochem Research Inc. | Refined detoxified endotoxin |
| US4800078A (en) * | 1987-05-28 | 1989-01-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Immunotherapeutic method of treating respiratory disease by intranasal administration of Igb |
| US5250298A (en) * | 1988-10-07 | 1993-10-05 | University Of Delaware | Live attenuated newcastle disease virus vaccines and preparation thereof |
-
1993
- 1993-04-19 IL IL10545693A patent/IL105456A/en not_active IP Right Cessation
- 1993-04-20 EP EP93912315A patent/EP0640128B1/fr not_active Expired - Lifetime
- 1993-04-20 ES ES93912315T patent/ES2132233T3/es not_active Expired - Lifetime
- 1993-04-20 UA UA94105948A patent/UA41315C2/uk unknown
- 1993-04-20 RU RU94045898A patent/RU2139729C1/ru not_active IP Right Cessation
- 1993-04-20 MX MX9302278A patent/MX9302278A/es not_active IP Right Cessation
- 1993-04-20 HU HU9403023A patent/HU220189B/hu not_active IP Right Cessation
- 1993-04-20 WO PCT/US1993/003670 patent/WO1993021310A1/fr active IP Right Grant
- 1993-04-20 DK DK93912315T patent/DK0640128T3/da active
- 1993-04-20 JP JP51866393A patent/JP3883202B2/ja not_active Expired - Fee Related
- 1993-04-20 CA CA002118509A patent/CA2118509C/fr not_active Expired - Fee Related
- 1993-04-20 KR KR1019940703740A patent/KR100257171B1/ko not_active IP Right Cessation
- 1993-04-20 NZ NZ252857A patent/NZ252857A/en not_active IP Right Cessation
- 1993-04-20 AT AT93912315T patent/ATE181359T1/de not_active IP Right Cessation
- 1993-04-20 AU AU42907/93A patent/AU683840B2/en not_active Ceased
- 1993-04-20 DE DE69325370T patent/DE69325370T2/de not_active Expired - Fee Related
-
1994
- 1994-10-21 US US08/327,263 patent/US5922326A/en not_active Expired - Lifetime
-
1995
- 1995-05-30 US US08/453,294 patent/US5882651A/en not_active Expired - Lifetime
- 1995-05-30 US US08/453,304 patent/US6284254B1/en not_active Expired - Lifetime
-
1999
- 1999-09-15 GR GR990402303T patent/GR3031208T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GR3031208T3 (en) | 1999-12-31 |
| EP0640128A1 (fr) | 1995-03-01 |
| DE69325370D1 (de) | 1999-07-22 |
| JPH07505891A (ja) | 1995-06-29 |
| KR100257171B1 (ko) | 2000-05-15 |
| CA2118509C (fr) | 2009-05-19 |
| IL105456A0 (en) | 1993-08-18 |
| NZ252857A (en) | 1997-06-24 |
| US5922326A (en) | 1999-07-13 |
| HUT69992A (en) | 1995-09-28 |
| ES2132233T3 (es) | 1999-08-16 |
| AU683840B2 (en) | 1997-11-27 |
| MX9302278A (es) | 1994-07-29 |
| DK0640128T3 (da) | 1999-11-22 |
| AU4290793A (en) | 1993-11-18 |
| WO1993021310A1 (fr) | 1993-10-28 |
| RU2139729C1 (ru) | 1999-10-20 |
| KR950701382A (ko) | 1995-03-23 |
| US6284254B1 (en) | 2001-09-04 |
| JP3883202B2 (ja) | 2007-02-21 |
| HU220189B (hu) | 2001-11-28 |
| HU9403023D0 (en) | 1994-12-28 |
| US5882651A (en) | 1999-03-16 |
| RU94045898A (ru) | 1996-09-20 |
| CA2118509A1 (fr) | 1993-10-28 |
| ATE181359T1 (de) | 1999-07-15 |
| EP0640128B1 (fr) | 1999-06-16 |
| UA41315C2 (uk) | 2001-09-17 |
| DE69325370T2 (de) | 1999-10-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0640128B1 (fr) | Compositions de vaccins a base de virus respiratoire syncytial attenue | |
| Stott et al. | Immune and histopathological responses in animals vaccinated with recombinant vaccinia viruses that express individual genes of human respiratory syncytial virus | |
| Crowe Jr et al. | A further attenuated derivative of a cold-passaged temperature-sensitive mutant of human respiratory syncytial virus retains immunogenicity and protective efficacy against wild-type challenge in seronegative chimpanzees | |
| Karron et al. | Evaluation of two live, cold-passaged, temperature-sensitive respiratory syncytial virus vaccines in chimpanzees and in human adults, infants, and children | |
| Byrd et al. | Animal models of respiratory syncytial virus infection | |
| Crowe Jr et al. | A comparison in chimpanzees of the immunogenicity and efficacy of live attenuated respiratory syncytial virus (RSV) temperature-sensitive mutant vaccines and vaccinia virus recombinants that express the surface glycoproteins of RSV | |
| CN100354425C (zh) | 减毒的人－牛嵌合呼吸道合胞病毒疫苗的生产 | |
| US3992522A (en) | Temperature-sensitive recombinant mutant viruses and a process for producing same | |
| US7150984B2 (en) | Attenuated human rotavirus vaccine | |
| US7169395B1 (en) | Multivalent immunogenic composition containing RSV subunit composition and influenza virus preparation | |
| EP0567100B1 (fr) | Mutant du virus syncytial respiratoire (RSV) et composition pharmaceutique contenant un tel mutant | |
| Prince et al. | Monophosphoryl lipid A adjuvant reverses a principal histologic parameter of formalin-inactivated respiratory syncytial virus vaccine-induced disease | |
| WO1998043668A9 (fr) | Virus syncytial respiratoire attenue | |
| Prince et al. | Respiratory syncytial virus infection in owl monkeys: viral shedding, immunological response, and associated illness caused by wild-type virus and two temperature-sensitive mutants | |
| Chanock et al. | Live viral vaccines for respiratory and enteric tract diseases | |
| Piazza et al. | Bovine respiratory syncytial virus protects cotton rats against human respiratory syncytial virus infection | |
| US7932074B1 (en) | Multivalent human-bovine rotavirus vaccine | |
| US7083795B1 (en) | Inactivated respiratory syncytial viral vaccines | |
| US7223410B1 (en) | Inactivated respiratory syncytial viral vaccines | |
| Hsu et al. | Isolation and characterization of a highly attenuated respiratory syncytial virus (RSV) vaccine candidate by mutagenesis of the incompletely attenuated RSV A2 ts-1 NG-1 mutant virus | |
| US12102671B2 (en) | Method of vaccination with an attenuated RSV vaccine formulation | |
| Norrby | Toward new viral vaccines for man | |
| Faverio et al. | Immunoprophylaxis of group B respiratory syncytial virus infection in cotton rats | |
| PL172087B1 (pl) | Szczepionka zawierajaca atenuowany wirus oddechowy (RS) PL PL PL | |
| Dolezalová et al. | Ability of temperature-sensitive mutants of the recombinant influenza S/N (H2N1) virus to induce immunity to parental (H0N1 and H2N2) viruses |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| HCA | Change of name of proprietor(s) after amalgamation | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |