NO321705B1 - Vaksiner med modifiserte meningokokk/polysakkarid-konjugater - Google Patents
Vaksiner med modifiserte meningokokk/polysakkarid-konjugater Download PDFInfo
- Publication number
- NO321705B1 NO321705B1 NO19975547A NO975547A NO321705B1 NO 321705 B1 NO321705 B1 NO 321705B1 NO 19975547 A NO19975547 A NO 19975547A NO 975547 A NO975547 A NO 975547A NO 321705 B1 NO321705 B1 NO 321705B1
- Authority
- NO
- Norway
- Prior art keywords
- polysaccharide
- protein
- conjugate molecule
- group
- meningococcal
- Prior art date
Links
- 229920001282 polysaccharide Polymers 0.000 title claims description 88
- 239000005017 polysaccharide Substances 0.000 title claims description 88
- 150000004676 glycans Chemical class 0.000 title claims description 85
- 229960005486 vaccine Drugs 0.000 title claims description 40
- 102000004169 proteins and genes Human genes 0.000 claims description 43
- 108090000623 proteins and genes Proteins 0.000 claims description 42
- 241000588650 Neisseria meningitidis Species 0.000 claims description 15
- 241000894006 Bacteria Species 0.000 claims description 13
- 150000004804 polysaccharides Polymers 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 229960000814 tetanus toxoid Drugs 0.000 claims description 8
- 101710116435 Outer membrane protein Proteins 0.000 claims description 7
- 210000002966 serum Anatomy 0.000 claims description 6
- 241000588653 Neisseria Species 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 239000012634 fragment Substances 0.000 claims description 5
- 230000003053 immunization Effects 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000003047 N-acetyl group Chemical group 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 241000617590 Escherichia coli K1 Species 0.000 claims description 3
- 229960003983 diphtheria toxoid Drugs 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- 108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 2
- 235000018102 proteins Nutrition 0.000 claims 14
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- 125000000217 alkyl group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 description 19
- 241000699670 Mus sp. Species 0.000 description 14
- 239000002671 adjuvant Substances 0.000 description 12
- 230000000844 anti-bacterial effect Effects 0.000 description 12
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- 238000010790 dilution Methods 0.000 description 8
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- -1 stearyl tyrosine Chemical compound 0.000 description 7
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- 241000588724 Escherichia coli Species 0.000 description 6
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- 230000005847 immunogenicity Effects 0.000 description 6
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- 108010078791 Carrier Proteins Proteins 0.000 description 5
- 239000012981 Hank's balanced salt solution Substances 0.000 description 5
- 201000009906 Meningitis Diseases 0.000 description 5
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000021615 conjugation Effects 0.000 description 5
- 230000009260 cross reactivity Effects 0.000 description 5
- 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 5
- 239000012153 distilled water Substances 0.000 description 5
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- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
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- 238000006243 chemical reaction Methods 0.000 description 4
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- 125000005629 sialic acid group Chemical group 0.000 description 4
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- 229940037003 alum Drugs 0.000 description 3
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
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- 210000001519 tissue Anatomy 0.000 description 3
- 108010077805 Bacterial Proteins Proteins 0.000 description 2
- 108010060123 Conjugate Vaccines Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000588677 Neisseria meningitidis serogroup B Species 0.000 description 2
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 2
- 125000003172 aldehyde group Chemical group 0.000 description 2
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
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- 230000001580 bacterial effect Effects 0.000 description 2
- 238000012754 cardiac puncture Methods 0.000 description 2
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- 230000001332 colony forming effect Effects 0.000 description 2
- 238000004737 colorimetric analysis Methods 0.000 description 2
- 229940031670 conjugate vaccine Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 108010074605 gamma-Globulins Proteins 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000006058 immune tolerance Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000009851 immunogenic response Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010027202 Meningitis bacterial Diseases 0.000 description 1
- 206010027249 Meningitis meningococcal Diseases 0.000 description 1
- 201000010924 Meningococcal meningitis Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 102000011830 Neural cell adhesion Human genes 0.000 description 1
- 108050002172 Neural cell adhesion Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 201000009904 bacterial meningitis Diseases 0.000 description 1
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- 229940045808 haemophilus influenzae type b Drugs 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
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- 238000010348 incorporation Methods 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- 238000000053 physical method Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/08—Clostridium, e.g. Clostridium tetani
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/095—Neisseria
-
- 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
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- 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
- 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
- Y10S424/831—Drug, bio-affecting and body treating compositions involving capsular polysaccharide of bacterium, e.g. polyribosyl ribitol phosphate
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/484,569 US5811102A (en) | 1995-06-07 | 1995-06-07 | Modified meningococcal polysaccharide conjugate vaccines |
| PCT/CA1996/000379 WO1996040239A1 (en) | 1995-06-07 | 1996-06-07 | Modified meningococcal polysaccharide conjugate vaccines |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO975547D0 NO975547D0 (no) | 1997-12-02 |
| NO975547L NO975547L (no) | 1998-02-09 |
| NO321705B1 true NO321705B1 (no) | 2006-06-26 |
Family
ID=23924694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19975547A NO321705B1 (no) | 1995-06-07 | 1997-12-02 | Vaksiner med modifiserte meningokokk/polysakkarid-konjugater |
Country Status (18)
| Country | Link |
|---|---|
| US (4) | US5811102A (de) |
| EP (1) | EP0831898B1 (de) |
| JP (2) | JP4171068B2 (de) |
| KR (1) | KR100452475B1 (de) |
| CN (1) | CN1163270C (de) |
| AT (1) | ATE238064T1 (de) |
| AU (1) | AU706053B2 (de) |
| BR (1) | BR9609229A (de) |
| CA (1) | CA2223567C (de) |
| CZ (1) | CZ391497A3 (de) |
| DE (1) | DE69627652T2 (de) |
| ES (1) | ES2196153T3 (de) |
| HU (1) | HU224972B1 (de) |
| IL (3) | IL147121A (de) |
| NO (1) | NO321705B1 (de) |
| PL (1) | PL184125B1 (de) |
| WO (1) | WO1996040239A1 (de) |
| ZA (1) | ZA964823B (de) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7655699B1 (en) | 1992-04-22 | 2010-02-02 | Eisai Inc. | Compounds having selective activity for retinoid X receptors, and means for modulation of processes mediated by retinoid X receptors |
| US20030157129A1 (en) * | 1995-06-23 | 2003-08-21 | Smithkline Beecham Biologicals S.A. | Vaccine comprising a polysaccharide antigen - carrier protein conjugate and free carrier protein |
| WO1998008543A1 (en) * | 1996-08-27 | 1998-03-05 | Chiron Corporation | Neisseria meningitidis serogroup b glycoconjugates and methods of using the same |
| US6048527A (en) * | 1996-08-27 | 2000-04-11 | Chiron Corporation | Antibodies that define unique Meningococcal B epitopes and vaccine compositions |
| US6299881B1 (en) * | 1997-03-24 | 2001-10-09 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | Uronium salts for activating hydroxyls, carboxyls, and polysaccharides, and conjugate vaccines, immunogens, and other useful immunological reagents produced using uronium salts |
| EP3118225A1 (de) * | 1997-12-23 | 2017-01-18 | Pfizer Ireland Pharmaceuticals | Verfahren zur extraktion und isolierung von bakteriellen kapsulären polysacchariden zur verwendung als vakzinen oder als mit proteinen verknüpften konjugatvakzinen |
| ATE446107T1 (de) * | 1998-08-19 | 2009-11-15 | Baxter Healthcare Sa | Immunogenes beta-propionamido-gebundenes polysaccharid-protein konjugat geeignet als impfstoff und hergestellt bei verwendung von n- acryloyliertem polysaccharid |
| US6585973B1 (en) | 1998-10-29 | 2003-07-01 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | Method for preparing solid phase conjugated vaccine |
| CA2279134A1 (en) * | 1999-07-29 | 2001-01-29 | Tianmin Liu | Novel strategy for carbohydrate-based therapeutic vaccines |
| US20040009195A1 (en) * | 2000-07-28 | 2004-01-15 | Jennings Harold J | Modified sialic acid vaccines |
| GB0024200D0 (en) * | 2000-10-03 | 2000-11-15 | Smithkline Beecham Sa | Component vaccine |
| KR100947751B1 (ko) * | 2001-01-23 | 2010-03-18 | 아벤티스 파스퇴르 | 다가 수막구균 폴리사카라이드-단백질 접합체 백신 |
| US7534444B2 (en) * | 2001-04-17 | 2009-05-19 | Novattis Vaccines And Diagnostics, Inc. | Molecular mimetics of meningococcal B epitopes which elicit functionally active antibodies |
| GB0115176D0 (en) | 2001-06-20 | 2001-08-15 | Chiron Spa | Capular polysaccharide solubilisation and combination vaccines |
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| US10828361B2 (en) * | 2006-03-22 | 2020-11-10 | Glaxosmithkline Biologicals Sa | Regimens for immunisation with meningococcal conjugates |
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| US4057685A (en) * | 1972-02-02 | 1977-11-08 | Abbott Laboratories | Chemically modified endotoxin immunizing agent |
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| US4673574A (en) * | 1981-08-31 | 1987-06-16 | Anderson Porter W | Immunogenic conjugates |
| US4902506A (en) * | 1983-07-05 | 1990-02-20 | The University Of Rochester | Immunogenic conjugates |
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| US4496538A (en) * | 1982-07-06 | 1985-01-29 | Connaught Laboratories, Inc. | Haemophilus influenzae b polysaccharide-diphtheria toxoid conjugate vaccine |
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| US4601903A (en) | 1985-05-01 | 1986-07-22 | The United States Of America As Represented By The Department Of Health And Human Services | Vaccine against Neisseria meningitidis Group B serotype 2 invasive disease |
| US4727136A (en) * | 1985-10-01 | 1988-02-23 | Canadian Patents And Development Ltd. | Modified meningococcal group B polysaccharide for conjugate vaccine |
| US5034516A (en) * | 1987-08-04 | 1991-07-23 | University Of Ottawa | Synthetic antigens of sialic acid and derivatives thereof |
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-
1995
- 1995-06-07 US US08/484,569 patent/US5811102A/en not_active Expired - Fee Related
-
1996
- 1996-06-07 HU HU9802664A patent/HU224972B1/hu not_active IP Right Cessation
- 1996-06-07 WO PCT/CA1996/000379 patent/WO1996040239A1/en not_active Application Discontinuation
- 1996-06-07 EP EP96917303A patent/EP0831898B1/de not_active Expired - Lifetime
- 1996-06-07 CZ CZ973914A patent/CZ391497A3/cs unknown
- 1996-06-07 PL PL96323862A patent/PL184125B1/pl not_active IP Right Cessation
- 1996-06-07 AT AT96917303T patent/ATE238064T1/de not_active IP Right Cessation
- 1996-06-07 AU AU59937/96A patent/AU706053B2/en not_active Ceased
- 1996-06-07 IL IL147121A patent/IL147121A/en not_active IP Right Cessation
- 1996-06-07 BR BR9609229A patent/BR9609229A/pt unknown
- 1996-06-07 CN CNB961945826A patent/CN1163270C/zh not_active Expired - Fee Related
- 1996-06-07 ES ES96917303T patent/ES2196153T3/es not_active Expired - Lifetime
- 1996-06-07 JP JP50004397A patent/JP4171068B2/ja not_active Expired - Fee Related
- 1996-06-07 IL IL11860496A patent/IL118604A0/xx not_active IP Right Cessation
- 1996-06-07 ZA ZA964823A patent/ZA964823B/xx unknown
- 1996-06-07 KR KR1019970709190A patent/KR100452475B1/ko not_active IP Right Cessation
- 1996-06-07 CA CA002223567A patent/CA2223567C/en not_active Expired - Lifetime
- 1996-06-07 DE DE69627652T patent/DE69627652T2/de not_active Expired - Fee Related
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1997
- 1997-12-02 NO NO19975547A patent/NO321705B1/no not_active IP Right Cessation
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1998
- 1998-02-11 US US09/022,155 patent/US5969130A/en not_active Expired - Fee Related
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1999
- 1999-07-20 US US09/357,491 patent/US6350449B1/en not_active Expired - Fee Related
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2001
- 2001-07-20 US US09/910,568 patent/US6596283B2/en not_active Expired - Fee Related
- 2001-12-16 IL IL14712101A patent/IL147121A0/xx unknown
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