CH649781A5 - Verfahren zur herstellung eines polyribosylribitolphosphats und einer dieses enthaltenden kombinationsvakzine. - Google Patents
Verfahren zur herstellung eines polyribosylribitolphosphats und einer dieses enthaltenden kombinationsvakzine. Download PDFInfo
- Publication number
- CH649781A5 CH649781A5 CH11125/78A CH1112578A CH649781A5 CH 649781 A5 CH649781 A5 CH 649781A5 CH 11125/78 A CH11125/78 A CH 11125/78A CH 1112578 A CH1112578 A CH 1112578A CH 649781 A5 CH649781 A5 CH 649781A5
- Authority
- CH
- Switzerland
- Prior art keywords
- prp
- bordetella pertussis
- haemophilus influenzae
- polyribosyl ribitol
- phosphate
- Prior art date
Links
- 229940001442 combination vaccine Drugs 0.000 title claims description 14
- VJDOAZKNBQCAGE-LMVFSUKVSA-N D-ribitol 5-phosphate Chemical compound OC[C@H](O)[C@H](O)[C@H](O)COP(O)(O)=O VJDOAZKNBQCAGE-LMVFSUKVSA-N 0.000 title claims description 13
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 238000000034 method Methods 0.000 claims description 31
- 241000588832 Bordetella pertussis Species 0.000 claims description 18
- 241000606768 Haemophilus influenzae Species 0.000 claims description 15
- 229940045808 haemophilus influenzae type b Drugs 0.000 claims description 14
- 239000000427 antigen Substances 0.000 claims description 12
- 102000036639 antigens Human genes 0.000 claims description 12
- 108091007433 antigens Proteins 0.000 claims description 12
- 241001465754 Metazoa Species 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 238000002955 isolation Methods 0.000 claims description 10
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 9
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 9
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 8
- 239000012153 distilled water Substances 0.000 claims description 8
- 239000012064 sodium phosphate buffer Substances 0.000 claims description 8
- 238000000855 fermentation Methods 0.000 claims description 7
- 230000004151 fermentation Effects 0.000 claims description 7
- 239000006228 supernatant Substances 0.000 claims description 7
- 238000000746 purification Methods 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 5
- 238000012869 ethanol precipitation Methods 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- 238000010828 elution Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 238000010668 complexation reaction Methods 0.000 claims 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 238000004458 analytical method Methods 0.000 claims 1
- 239000000872 buffer Substances 0.000 claims 1
- 238000004440 column chromatography Methods 0.000 claims 1
- 238000000502 dialysis Methods 0.000 claims 1
- CGMRCMMOCQYHAD-UHFFFAOYSA-J dicalcium hydroxide phosphate Chemical compound [OH-].[Ca++].[Ca++].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-J 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 239000011550 stock solution Substances 0.000 description 19
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 15
- 239000002953 phosphate buffered saline Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 201000005702 Pertussis Diseases 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 150000004676 glycans Chemical class 0.000 description 11
- 102000039446 nucleic acids Human genes 0.000 description 11
- 108020004707 nucleic acids Proteins 0.000 description 11
- 150000007523 nucleic acids Chemical class 0.000 description 11
- 229920001282 polysaccharide Polymers 0.000 description 11
- 239000005017 polysaccharide Substances 0.000 description 11
- 239000002158 endotoxin Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 229960005486 vaccine Drugs 0.000 description 8
- 239000012535 impurity Substances 0.000 description 6
- 108091005461 Nucleic proteins Proteins 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- 239000003463 adsorbent Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 150000002972 pentoses Chemical class 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000001488 sodium phosphate Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 230000005875 antibody response Effects 0.000 description 3
- 239000007621 bhi medium Substances 0.000 description 3
- 238000007865 diluting Methods 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 229910000397 disodium phosphate Inorganic materials 0.000 description 3
- 235000019800 disodium phosphate Nutrition 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- RYCLIXPGLDDLTM-UHFFFAOYSA-J tetrapotassium;phosphonato phosphate Chemical compound [K+].[K+].[K+].[K+].[O-]P([O-])(=O)OP([O-])([O-])=O RYCLIXPGLDDLTM-UHFFFAOYSA-J 0.000 description 3
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 3
- 229940033663 thimerosal Drugs 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229940025294 hemin Drugs 0.000 description 2
- BTIJJDXEELBZFS-QDUVMHSLSA-K hemin Chemical compound CC1=C(CCC(O)=O)C(C=C2C(CCC(O)=O)=C(C)\C(N2[Fe](Cl)N23)=C\4)=N\C1=C/C2=C(C)C(C=C)=C3\C=C/1C(C)=C(C=C)C/4=N\1 BTIJJDXEELBZFS-QDUVMHSLSA-K 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 229950006238 nadide Drugs 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- OIPPWFOQEKKFEE-UHFFFAOYSA-N orcinol Chemical compound CC1=CC(O)=CC(O)=C1 OIPPWFOQEKKFEE-UHFFFAOYSA-N 0.000 description 2
- 238000011218 seed culture Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- -1 Bio.Gel HTP Chemical compound 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 206010061190 Haemophilus infection Diseases 0.000 description 1
- 240000006024 Lactobacillus plantarum Species 0.000 description 1
- 241000239218 Limulus Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229920002274 Nalgene Polymers 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940052491 bordetella pertussis Drugs 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- RLGQACBPNDBWTB-UHFFFAOYSA-N cetyltrimethylammonium ion Chemical compound CCCCCCCCCCCCCCCC[N+](C)(C)C RLGQACBPNDBWTB-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 239000013530 defoamer Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 229940101270 nicotinamide adenine dinucleotide (nad) Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 229940066827 pertussis vaccine Drugs 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- MKWYFZFMAMBPQK-UHFFFAOYSA-J sodium feredetate Chemical compound [Na+].[Fe+3].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O MKWYFZFMAMBPQK-UHFFFAOYSA-J 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- 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
- A61K39/099—Bordetella
-
- 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
- A61K39/102—Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
-
- 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
- A61K2039/70—Multivalent vaccine
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Mycology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/846,466 US4196192A (en) | 1977-10-28 | 1977-10-28 | Combined Haemophilus influenzae type b and pertussis vaccine |
| US05/846,488 US4220717A (en) | 1977-12-22 | 1977-12-22 | Isolation and purification of polyribosyl ribitol phosphate from Haemophilus influenzae type b. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH649781A5 true CH649781A5 (de) | 1985-06-14 |
Family
ID=27126641
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH11125/78A CH649781A5 (de) | 1977-10-28 | 1978-10-27 | Verfahren zur herstellung eines polyribosylribitolphosphats und einer dieses enthaltenden kombinationsvakzine. |
Country Status (25)
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE889979A (fr) * | 1981-08-14 | 1982-02-15 | Smith Kline Rit | Procede de preparation de polysaccharides bacteriens capsulaires antigeniques purifies, produits obtenus et leur utilisation |
| CA1209036A (en) * | 1982-08-20 | 1986-08-05 | Joseph S.C. Kuo | Combined haemophilus influenzae and diphtheria, pertussis, tetanus vaccine |
| US4744982A (en) * | 1982-08-24 | 1988-05-17 | Hunter Kenneth W | Human monoclonal antibody reactive with polyribosylribitol phosphate |
| IL98715A0 (en) * | 1990-08-13 | 1992-07-15 | American Cyanamid Co | Filamentous hemaglutinin of bodetella pertussis as a carrier molecule for conjugate vaccines |
| WO1993004183A1 (en) * | 1991-08-16 | 1993-03-04 | Merck & Co., Inc. | Process for converting lipid-containing bacterial capsular polysaccharide into lipid-free polysaccharide |
| ATE176157T1 (de) * | 1992-10-27 | 1999-02-15 | American Cyanamid Co | Pädiatrische kombinationsvakzine mit verbesserter immunogenizität jeder vakzine komponente |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3395219A (en) * | 1964-12-11 | 1968-07-30 | Merck & Co Inc | Process for production of pertussis antigen |
| IL24946A (en) * | 1965-01-19 | 1969-05-28 | Merck & Co Inc | Process for preparing antibodies in cilus pertussis |
| US3465078A (en) * | 1965-10-21 | 1969-09-02 | Sydney Z Spiesel | Method of recovering antigens from bordetella pertussis cells |
| NL174267B (nl) * | 1969-05-20 | Roussel Uclaf | Verbetering van de werkwijze voor de bereiding van een somatisch antigeen volgens het nederlandse octrooischrift 169754 en werkwijze ter bereiding van een farmaceutisch preparaat. | |
| US3636192A (en) * | 1970-01-13 | 1972-01-18 | Us Army | Meningococcal polysaccharide vaccines |
| FR2253499B1 (enrdf_load_stackoverflow) * | 1973-12-10 | 1977-11-04 | Fabre Sa Pierre | |
| DE2461439C3 (de) * | 1974-12-24 | 1980-03-20 | Behringwerke Ag, 3550 Marburg | Verfahren zur Herstellung eines schützenden Antigens von Bordetella Pertussis sowie jenes enthaltendes Mittel |
| US3978209A (en) * | 1975-03-24 | 1976-08-31 | Merck & Co., Inc. | Endotoxin free meningococcus polysaccharides |
-
1978
- 1978-08-22 NZ NZ188211A patent/NZ188211A/en unknown
- 1978-08-25 IL IL55433A patent/IL55433A/xx unknown
- 1978-08-29 CA CA000310218A patent/CA1117866A/en not_active Expired
- 1978-08-30 AR AR273492A patent/AR218932A1/es active
- 1978-08-30 GR GR57127A patent/GR73991B/el unknown
- 1978-10-20 DE DE19782845745 patent/DE2845745A1/de active Granted
- 1978-10-24 IT IT51621/78A patent/IT1107570B/it active
- 1978-10-25 PH PH21738A patent/PH15882A/en unknown
- 1978-10-26 FI FI783269A patent/FI63674C/fi not_active IP Right Cessation
- 1978-10-26 AU AU41081/78A patent/AU520902B2/en not_active Expired
- 1978-10-26 FR FR7830517A patent/FR2407000B1/fr not_active Expired
- 1978-10-27 PL PL21054578A patent/PL210545A1/xx unknown
- 1978-10-27 DK DK479578A patent/DK154327C/da not_active IP Right Cessation
- 1978-10-27 SE SE7811192A patent/SE430753B/sv not_active IP Right Cessation
- 1978-10-27 GB GB7842230A patent/GB2007244B/en not_active Expired
- 1978-10-27 NL NL7810753A patent/NL7810753A/xx not_active Application Discontinuation
- 1978-10-27 YU YU02508/78A patent/YU250878A/xx unknown
- 1978-10-27 ES ES474611A patent/ES474611A1/es not_active Expired
- 1978-10-27 NO NO783635A patent/NO149611C/no unknown
- 1978-10-27 IE IE2146/78A patent/IE47474B1/en unknown
- 1978-10-27 CH CH11125/78A patent/CH649781A5/de not_active IP Right Cessation
- 1978-10-27 HU HU78AE546A patent/HU178166B/hu not_active IP Right Cessation
- 1978-10-27 BE BE191385A patent/BE871586A/xx not_active IP Right Cessation
- 1978-10-27 DD DD78208715A patent/DD140701A5/de unknown
- 1978-10-28 JP JP13310978A patent/JPS5480408A/ja active Granted
Also Published As
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