SI9210081B - Pneumococcal polysaccharide conjugate vaccine - Google Patents
Pneumococcal polysaccharide conjugate vaccine Download PDFInfo
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- SI9210081B SI9210081B SI9210081A SI9210081A SI9210081B SI 9210081 B SI9210081 B SI 9210081B SI 9210081 A SI9210081 A SI 9210081A SI 9210081 A SI9210081 A SI 9210081A SI 9210081 B SI9210081 B SI 9210081B
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- polysaccharide
- ompc
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- pneumococcal
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- 229920001282 polysaccharide Polymers 0.000 title claims abstract 32
- 239000005017 polysaccharide Substances 0.000 title claims abstract 32
- 150000004676 glycans Chemical class 0.000 title claims abstract 31
- 108010060123 Conjugate Vaccines Proteins 0.000 title abstract 2
- 229940031670 conjugate vaccine Drugs 0.000 title abstract 2
- 241000193998 Streptococcus pneumoniae Species 0.000 claims abstract 8
- 108090000623 proteins and genes Proteins 0.000 claims abstract 5
- 102000004169 proteins and genes Human genes 0.000 claims abstract 5
- 230000002163 immunogen Effects 0.000 claims abstract 4
- 238000000034 method Methods 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims abstract 3
- 229960005486 vaccine Drugs 0.000 claims abstract 3
- 244000052769 pathogen Species 0.000 claims abstract 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims 8
- 239000001488 sodium phosphate Substances 0.000 claims 8
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims 8
- 229940031000 streptococcus pneumoniae Drugs 0.000 claims 7
- 230000007062 hydrolysis Effects 0.000 claims 4
- 238000006460 hydrolysis reaction Methods 0.000 claims 4
- 230000021615 conjugation Effects 0.000 claims 3
- 238000005194 fractionation Methods 0.000 claims 3
- 238000000527 sonication Methods 0.000 claims 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- 238000010438 heat treatment Methods 0.000 claims 2
- 208000005252 hepatitis A Diseases 0.000 claims 2
- 239000012535 impurity Substances 0.000 claims 2
- 230000000269 nucleophilic effect Effects 0.000 claims 2
- 208000030507 AIDS Diseases 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 claims 1
- 241000606768 Haemophilus influenzae Species 0.000 claims 1
- 201000005505 Measles Diseases 0.000 claims 1
- 208000005647 Mumps Diseases 0.000 claims 1
- 241000588650 Neisseria meningitidis Species 0.000 claims 1
- 101710116435 Outer membrane protein Proteins 0.000 claims 1
- 201000005702 Pertussis Diseases 0.000 claims 1
- 241000194017 Streptococcus Species 0.000 claims 1
- 241001607520 Streptococcus pneumoniae 23F Species 0.000 claims 1
- 206010043376 Tetanus Diseases 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000001476 alcoholic effect Effects 0.000 claims 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical group [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 238000004458 analytical method Methods 0.000 claims 1
- 125000000129 anionic group Chemical group 0.000 claims 1
- 230000003497 anti-pneumococcal effect Effects 0.000 claims 1
- 239000000427 antigen Substances 0.000 claims 1
- 230000000890 antigenic effect Effects 0.000 claims 1
- 102000036639 antigens Human genes 0.000 claims 1
- 108091007433 antigens Proteins 0.000 claims 1
- 230000000903 blocking effect Effects 0.000 claims 1
- 125000002843 carboxylic acid group Chemical group 0.000 claims 1
- 238000004587 chromatography analysis Methods 0.000 claims 1
- 230000000295 complement effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 230000001268 conjugating effect Effects 0.000 claims 1
- 238000011109 contamination Methods 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- 206010013023 diphtheria Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 238000002270 exclusion chromatography Methods 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 claims 1
- 238000007306 functionalization reaction Methods 0.000 claims 1
- 229910052733 gallium Inorganic materials 0.000 claims 1
- 229940047650 haemophilus influenzae Drugs 0.000 claims 1
- 208000002672 hepatitis B Diseases 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 230000002519 immonomodulatory effect Effects 0.000 claims 1
- 230000003053 immunization Effects 0.000 claims 1
- 238000002649 immunization Methods 0.000 claims 1
- 230000000951 immunodiffusion Effects 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 208000010805 mumps infectious disease Diseases 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 230000001376 precipitating effect Effects 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 230000003252 repetitive effect Effects 0.000 claims 1
- 201000005404 rubella Diseases 0.000 claims 1
- 239000000523 sample Substances 0.000 claims 1
- 238000004513 sizing Methods 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 claims 1
- 230000036962 time dependent Effects 0.000 claims 1
- 238000000196 viscometry Methods 0.000 claims 1
- 230000028993 immune response Effects 0.000 abstract 3
- 230000001681 protective effect Effects 0.000 abstract 3
- 102000014914 Carrier Proteins Human genes 0.000 abstract 1
- 108010078791 Carrier Proteins Proteins 0.000 abstract 1
- 208000035109 Pneumococcal Infections Diseases 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 238000002255 vaccination Methods 0.000 abstract 1
Classifications
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- 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
- A61K39/095—Neisseria
-
- 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
- A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
- A61K39/092—Streptococcus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- 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
- A61K2039/6068—Other bacterial proteins, e.g. OMP
-
- 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
- A61K2039/62—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier
- A61K2039/627—Medicinal preparations containing antigens or antibodies characterised by the link between antigen and carrier characterised by the linker
-
- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Steroid Compounds (AREA)
Claims (9)
1 PATENTNI ZAHTEVKI 1. Konjugat, ki obsega imunogenski protein, kovalentno vezan na polisaharid, ki izvira iz enega ali več podtipov Streptococcusa 5 pneumoniae, pri čemer ima navedeni polisaharid povprečno manj kot okrog 1200 ponavljajočih se enot na molekulo, molsko maso med 1 x 101 2 in 1 x 106, polidisperznost med 1,0 in 1,4 in nivo kontaminacije s pnevmokoknim, za skupino specifičnim C-polisaharidom pod 3 % za tip specifičnega polisaharida. 10
2. Konjugat po zahtevku 1, označen s tem, da ima navedeni polisaharid indeks antigenosti med 0,7 in 1,1 in lastno viskoznost med 0,6 in 3,0 dL/g. 15
3. Konjugat po zahtevku 2, označen s tem, izvira navedeni polisaharid iz kateregakoli od podtipov Streptococcusa pneumoniae, izbranih izmed: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11 A, 20 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F in 33F. 1 Konjugat po zahtevku 3, 2 označen s tem, 2 da navedeni polisaharid izvira iz: 1) Streptococcus pneumoniae 6B, navedeni polisaharid pa ima: a) Mn med 3 x 105 in 6 x 105; 5 b) Kd (vrhunec) okoli 0,60 ± 0,05; c) Mw med 3 x 105 in 7 x 105; d) lastno viskoznost v 0,1 M natrijevem fosfatu, pH 7,2, med 1,0 in 2,0; in e) povprečno manj kot okoli 1000 ponavljajočih se enot na 10 molekulo; 2) Streptococcus pneumoniae 14, navedeni polisaharid pa ima: a) Mn med 3 x 105 in 8 x 105; b) Kd (vrhunec) okoli 0,60 ± 0,05; c) Mw med 4 x 105 in 1 x 106; in 15 d) lastno viskoznost v 0,1 M natrijevem fosfatu, pH 7,2, med 0,6 in 1,6; 3) Streptococcus pneumoniae 19F, navedeni polisaharid pa ima: a) Mn med 2 x 105 in 6 x 105; b) Kd (vrhunec) okoli 0,65 ± 0,05; 20 c) Mw med 2 x 105 in 6 x 105; d) lastno viskoznost v 0,1 M natrijevem fosfatu, pH 7,2, med 1,0 in 2,0; in 3 e) povprečno manj kot okoli 1000 ponavljajočih se enot na molekulo;
4) Streptococcus pneumoniae 23F, navedeni polisaharid pa ima: a) Mn med 2 x 105 in 6 x 105; 5 b) Kd (vrhunec) okoli 0,54 ± 0,05; c) Mw med 4 χ 105 in 8 x 105; d) lastno viskoznost v 0,1 M natrijevem fosfatu, pH 7,2, med 1,5 in 3,0; in e) povprečno manj kot okoli 1000 ponavljajočih se enot na 10 molekulo; 5) Streptococcus pneumoniae 4, navedeni polisaharid pa ima: a) Mn med 2 χ 105 in 4 χ 105; b) Kd (vrhunec) okoli 0,65 ± 0,05; c) Mw med 2 χ 105 in 5 x 105; 15 d) lastno viskoznost v 0,1 M natrijevem fosfatu, pH 7,2, med 1,0 in 3,0; in e) povprečno manj kot okoli 600 ponavljajočih se enot na molekulo; 6) Streptococcus pneumoniae 9V, navedeni polisaharid pa ima: 20 a) Mn med 3 χ 105 in 6 x 105; b) Kd (vrhunec) okoli 0,65 ± 0,05; c) Mw med 3 x 105 in 7 x 105; d) lastno viskoznost v 0,1 M natrijevem fosfatu, pH 7,2, med 1,0 in 2,0; in e) povprečno manj kot okoli 800 ponavljajočih se enot na molekulo; 7) Streptococcus pneumoniae 18C, pri navedeni polisaharid pa ima: a) MN med 2 x 105 in 6 x 105; b) Kd (vrhunec) okoli 0,65 ± 0,05; c) Mw med 2 x 105 in 6 x 105; d) lastno viskoznost v 0,1 M natrijevem fosfatu, pH 7,2, med 1,5 in 3,0; in e) povprečno manj kot okoli 700 ponavljajočih se enot na molekulo; ali mešanice katerihkoli od teh polisaharidov; pri čemer je navedeni polisaharid konjugiran na zunanji membranski proteinski kompleks (OMPC) Nisserie meningitidis b, ali MIEP podenoto le-tega.
5. Kovalentni konjugat po zahtevku 4, pri čemer so OMPC ali MIEP in Pn-Ps povezani preko vmesnika s formulo: PRO-N-COCHCH2CH2SCH2CONH(CH2)4 NHC-O-PnPs H AhC0CH3 0 za vezave preko polisaharidnih hidroksilov, ali
INH(CH2)4 NHjj-PnPs, 5 v primeru polisaharidov, ki nosijo skupine karboksilne kisline, kjer PRO predstavlja OMPC ali MIEP in Pn-Ps predstavlja pnevmokokni polisaharid ter ima konjugat masno razmerje Pn-Ps : OMPC ali Pn-Ps : MIEP med 0,05 in 0,5 in po hidrolizi in analizi amino kislin da razmerje 5 SCMHC/Lys med 0,01 in 0,15.
6. 10 15 Konjugat pnevmokoknega polisaharidno-imunogenega proteina, ki je proizveden s postopkom, v katerem: (a) kultiviramo pnevmokok in izoliramo surovi pnevmokokni polisaharid ali solubiliziramo prašek pnevmokoknega polisaharida; (b) očistimo in delno hidroliziramo polisaharid iz stopnje (a) do končne točke, določene vnaprej, da nastane polisaharid, dostopen za konjugiranje, ki nima več kot 30 %-nega zmanjšanja tipsko specifične antigenosti polisaharida v primerjavi s surovim polisaharidom iz stopnje (a); in (c) konjugiramo produkt iz stopnje (b) z imunogenim proteinom, pri čemer izberemo pnevmokok, gojen v stopnji (a), izmed enega ali več podtipov: 4, 6B, 9V, 14, 18C, 19F in 23F, pri čemer Pn-Ps ohrani svojo antigeno celovitost, izmerjeno z Ouchterlonyjevim preizkusom dvojne imunodifuzije ali preizkusom s časovno odvisno nefelometrijo ob uporabi tipsko specifičnega anti-Pn-Ps protitelesa, pri čemer je navedeni Pn-Ps pred konjugiranjem fizikalno strižno obdelan v Gaulinovi preši pri tlaku med okoli 13.8 MPa in 103 MPa 20 6 (2000 in 15000 PSI) ali hidroliziran s segrevanjem na 100° C 24 ur ali obdelan s soniciranjem do viskoznosti za 1 mg/ml raztopino v 0,9 M natrijevem kloridu ali končne točke (vrhunec) Kd, kot sledi za vsak navedeni podtip Pn-Ps: 5 Podtip Pn-Ps Ciljna končna viskoznost (mm2.s1) Ciljni končni Kd (vrhunec) Pn4-Ps 1,5-1,00 0,65 ± 0,05 Pn6B-Ps 1,3-1,00 0,60 ± 0,05 Pn9V-Ps 1,3-1,00 0,65 ± 0,05 Pn14-Ps 1,1 -0,95 0,60 ± 0,05 Pn18C-Ps 1,5-1,00 0,65 ± 0,05 Pn19F-Ps 1,3-1,00 0,65 ± 0,05 Pn23F-Ps 1,5-1,00 0,54 ± 0,05; čemur po izbiri sledi kromatografsko ali alkoholno frakcioniranje, da izberemo material, ki ima polidispenznost pod 1,4.
7. Postopek za izdelavo konjugata Pn-Ps-PRO, ki obsega 20 a) izolacijo surovega pnevmokoknega polisaharida, Pn-Ps; b) i-po izbiri čiščenje surovega Pn-Ps z ionsko izmenjevalno adsorpcijo nečistot; ii-delno hidrolizo ali mehansko strižno obdelavo surovega Pn-Ps; frakcioniranje delno hidroliziranega Pn-Ps po velikosti in čistosti; 7 d) derivatiziranje frakcioniranega Pn-Ps, ki izvira iz enega ali več pnevmokoknih podtipov v skladu s stopnjami (a)-(c), da se pokažejo dopolnjujoči se nukleofilni ali elektrofilni deli; e) izolacijo Neisseria meningitidis b OMPC ali MIEP; 5 f) funkcionalizacijo OMPC ali MIEP, da kaže reaktivne elektrofilne ali nukleofilne dele; g) konjugacijo polisaharida iz stopnje (d) s proteinom iz stopnje (f); h) blokado konjugata, da se odstranijo preostale funkcionalne skupine; i) izolacijo konjugatnega produkta, pri čemer stopnji (b) in (c) nadalje 10 obsegata: (b) 1-po izbiri adsorbiranje anionskih nečistoč na VVhatmanu DE52 pri pH raztopine okoli 5; 2-delno hidrolizo Pn-Ps v raztopini do končne viskoznosti, določene vnaprej tako, da se zmanjša vezava Pn-Ps na anti-pnevmokokno za tip is specifično protitelo za ne več kot 30% v primerjavi s surovim Pn-Ps, s 1. segrevanjem med 1 do 48 ur pri 50 do 150° C; ali 2. soniciranjem v razdobjih od 5 sekund do 5 minut v odvisnosti od nastavitve moči sonikacijske sonde, 20 čemur slede razdobja hlajenja in dodatne sonikacije; ali strižno obdelavo v Gaulinovi preši pri tlakih med 13,8 in 103 Mpa (med 2000 in 15000 PSI); in 3. 8 (c) frakcioniranje delno hidroliziranega Pn-Ps glede na velikost in čistost, pri čemer stopnja (c) obsega: Frakcioniranje hidroliziranega Pn-Ps in izbiranje frakcije, ki ima 5 molsko maso v območju med 1 χ 105 in 1 x 106, z i. - diferencialno topnostjo v alkoholu ob uporabi izopropanola pri koncentracijah, določenih vnaprej tako, da se obori Pn-Ps z želenim območjem velikosti, ali ii. - frakcioniranjem na koloni za tekočinsko velikostno io izključitveno kromatografijo, ki je sposobna, da vključi in frakcionira polisaharide v območju velikosti med 5 χ 104 in 1 x 106, pri čemer določimo končno točko hidrolize ali strižne obdelave z viskozimetrijo 1 mg/ml raztopine v 0,1 M natrijevem fosfatu, pH 7,2, is ali s kromatografijo za vsakega od navedenih polisaharidov v skladu s končno točko za ta podtip Pn-Ps: Podtip Pn-Ps Ciljna končna viskoznost Ciljni končni Kd (mm2.s1) (vrhunec) Pn4-Ps 1,5-1,00 0,65 ± 0,05 Pn6B-Ps 1,3-1,00 0,60 ± 0,05 Pn9V-Ps 1,3-1,00 0,65 ± 0,05 Pn14-Ps 1,1 -0,95 0,60 ± 0,05 Pn18C-Ps 1,5-1,00 0,65 ± 0,05 Pn19F-Ps 1,3-1,00 0,65 ± 0,05 Pn23F-Ps Ul I O o 0,54 ± 0,05 20 25 9
8. Uporaba konjugata po zahtevku 1 za proizvodnjo zdravila, ki je prilagojeno za imunizacijo zoper bolezenska stanja, do katerih pride zaradi pnevmokoknih patogenov.
9. Vakcinski pripravek, označen s tem, da obsega konjugat po zahtevku 1 in inerten nosilec in ki obsega po izbiri imunološko učinkovite količine adjuvanta ali imunomodularotornih spojin ali dodatnih imunogenov, pri čemer je navedeni inertni nosilec aluminijev hidroksid, aluminijev fosfat ali galun in pri čemer so navedeni dodatni imunogeni izbrani izmed ene ali več vakcin proti hepatitisu B, hepatitisu A, hepatitisu ne-A- ne-B, AIDS, difteriji-pertusisu-tetanusu, ošpicam, mumpsu, rdečkam, noricam, poliomielitisu in Haemophilus influenzae b, pri čemer obsega konjugat od enega do vseh konjugatov, izbranih izmed Pn4-Ps-OMPC, Pn6B-Ps-OMPC, Pn9V-Ps-OMPC, Pn14-Ps-OMPC, Pn18C-Ps-OMPC, Pn19F-Ps-OMPC, Pn23F-Ps-OMPC, Pn1-Ps-OMPC, Pn5-Ps-OMPC in Pn7F-Ps-OMPC. Za: MERCK &CO., INC. ZDA
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64657091A | 1991-01-28 | 1991-01-28 | |
| US80794291A | 1991-12-19 | 1991-12-19 | |
| YU8192A YU49068B (sh) | 1991-01-28 | 1992-01-27 | Postupak za izradu pneumokoknog polisaharidnog imunogenog proteinskog konjugata |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SI9210081A SI9210081A (en) | 1996-02-29 |
| SI9210081B true SI9210081B (en) | 2001-12-31 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI9210081A SI9210081B (en) | 1991-01-28 | 1992-01-27 | Pneumococcal polysaccharide conjugate vaccine |
Country Status (23)
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|---|---|
| US (1) | US5623057A (sl) |
| EP (1) | EP0497525B2 (sl) |
| JP (1) | JPH0794472B2 (sl) |
| KR (1) | KR100243958B1 (sl) |
| CN (1) | CN1080124C (sl) |
| AT (1) | ATE169825T1 (sl) |
| AU (1) | AU651656B2 (sl) |
| CA (1) | CA2059692C (sl) |
| CZ (1) | CZ283284B6 (sl) |
| DE (1) | DE69226668T3 (sl) |
| DK (1) | DK0497525T4 (sl) |
| ES (1) | ES2121820T5 (sl) |
| FI (1) | FI107370B (sl) |
| HU (1) | HU216101B (sl) |
| IE (1) | IE920244A1 (sl) |
| IL (5) | IL100716A (sl) |
| LV (1) | LV12309B (sl) |
| MX (1) | MX9200328A (sl) |
| NO (1) | NO304117B1 (sl) |
| NZ (1) | NZ241367A (sl) |
| SI (1) | SI9210081B (sl) |
| SK (1) | SK280659B6 (sl) |
| YU (1) | YU49068B (sl) |
Families Citing this family (135)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2059693C (en) * | 1991-01-28 | 2003-08-19 | Peter J. Kniskern | Polysaccharide antigens from streptococcus pneumoniae |
| US5445817A (en) * | 1992-08-21 | 1995-08-29 | The United States Of America As Represented By The Department Of Health And Human Services | Pertussis toxin used as a carrier protein with non-charged saccharides in conjugate vaccines |
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| US4707543A (en) * | 1985-09-17 | 1987-11-17 | The United States Of America As Represented By The Secretary Of The Army | Process for the preparation of detoxified polysaccharide-outer membrane protein complexes, and their use as antibacterial vaccines |
| US4727136A (en) * | 1985-10-01 | 1988-02-23 | Canadian Patents And Development Ltd. | Modified meningococcal group B polysaccharide for conjugate vaccine |
| ES2000034A6 (es) * | 1985-11-26 | 1987-10-01 | Schweiz Serum & Impfinst | Procedimiento para la preparacion de una vacuna viva contra paperas |
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| JP2754000B2 (ja) * | 1986-04-16 | 1998-05-20 | ザ ブリガム アンド ウィメンズ ホスピタル，インコーポレイテッド | 細菌抗原、抗体、ワクチン及びその製造方法 |
| NZ223009A (en) * | 1986-12-31 | 1990-06-26 | Nl Rivm Of Thoven | Oligosaccharides containing d-ribose d-ribitol and phosphate units mimicing haemophilus influenzae type b antigens |
| ATE105189T1 (de) * | 1988-04-19 | 1994-05-15 | American Cyanamid Co | Haemophilus influenzae typ b polysaccharidaussermembranprotein-konjugat als impfstoff. |
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-
1992
- 1992-01-20 CA CA002059692A patent/CA2059692C/en not_active Expired - Lifetime
- 1992-01-21 IL IL10071692A patent/IL100716A/en not_active IP Right Cessation
- 1992-01-21 IL IL11996192A patent/IL119961A/xx not_active IP Right Cessation
- 1992-01-21 IL IL11996292A patent/IL119962A/xx not_active IP Right Cessation
- 1992-01-22 NZ NZ241367A patent/NZ241367A/en not_active IP Right Cessation
- 1992-01-23 SK SK199-92A patent/SK280659B6/sk not_active IP Right Cessation
- 1992-01-23 CZ CS92199A patent/CZ283284B6/cs not_active IP Right Cessation
- 1992-01-24 AU AU10467/92A patent/AU651656B2/en not_active Expired
- 1992-01-27 DK DK92300655.5T patent/DK0497525T4/da active
- 1992-01-27 SI SI9210081A patent/SI9210081B/sl unknown
- 1992-01-27 IE IE024492A patent/IE920244A1/en unknown
- 1992-01-27 EP EP92300655A patent/EP0497525B2/en not_active Expired - Lifetime
- 1992-01-27 ES ES92300655T patent/ES2121820T5/es not_active Expired - Lifetime
- 1992-01-27 AT AT92300655T patent/ATE169825T1/de not_active IP Right Cessation
- 1992-01-27 YU YU8192A patent/YU49068B/sh unknown
- 1992-01-27 KR KR1019920001108A patent/KR100243958B1/ko not_active Expired - Lifetime
- 1992-01-27 CN CN92100700A patent/CN1080124C/zh not_active Expired - Lifetime
- 1992-01-27 DE DE69226668T patent/DE69226668T3/de not_active Expired - Lifetime
- 1992-01-27 NO NO920350A patent/NO304117B1/no not_active IP Right Cessation
- 1992-01-27 HU HUP9200252A patent/HU216101B/hu unknown
- 1992-01-27 MX MX9200328A patent/MX9200328A/es unknown
- 1992-01-27 FI FI920353A patent/FI107370B/fi active
- 1992-01-28 JP JP4012941A patent/JPH0794472B2/ja not_active Expired - Lifetime
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1994
- 1994-05-20 US US08/246,394 patent/US5623057A/en not_active Expired - Lifetime
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1997
- 1997-01-03 IL IL11996297A patent/IL119962A0/xx unknown
- 1997-01-03 IL IL11996197A patent/IL119961A0/xx unknown
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1999
- 1999-04-26 LV LVP-99-69A patent/LV12309B/en unknown
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Owner name: MERCK SHARP & DOHME CORP.; US Effective date: 20100330 |