SI20008B - Improved meningococcal polysaccharide conjugate vaccine - Google Patents
Improved meningococcal polysaccharide conjugate vaccine Download PDFInfo
- Publication number
- SI20008B SI20008B SI9110243A SI9110243A SI20008B SI 20008 B SI20008 B SI 20008B SI 9110243 A SI9110243 A SI 9110243A SI 9110243 A SI9110243 A SI 9110243A SI 20008 B SI20008 B SI 20008B
- Authority
- SI
- Slovenia
- Prior art keywords
- group
- butanoyl
- polysaccharide
- pentanoyl
- modified polysaccharide
- Prior art date
Links
- 229920001282 polysaccharide Polymers 0.000 title claims abstract 19
- 239000005017 polysaccharide Substances 0.000 title claims abstract 19
- 150000004676 glycans Chemical class 0.000 title claims abstract 18
- 108010060123 Conjugate Vaccines Proteins 0.000 title 1
- 229940031670 conjugate vaccine Drugs 0.000 title 1
- 125000003047 N-acetyl group Chemical group 0.000 claims abstract 6
- 108090000623 proteins and genes Proteins 0.000 claims abstract 4
- 102000004169 proteins and genes Human genes 0.000 claims abstract 4
- 229960000814 tetanus toxoid Drugs 0.000 claims abstract 2
- -1 n-butanoyl Chemical group 0.000 claims 28
- 125000002252 acyl group Chemical group 0.000 claims 7
- 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 claims 4
- 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 claims 4
- 229960005486 vaccine Drugs 0.000 claims 4
- 241000588650 Neisseria meningitidis Species 0.000 claims 3
- 241000588724 Escherichia coli Species 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 108010074605 gamma-Globulins Proteins 0.000 claims 2
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims 2
- 108010077805 Bacterial Proteins Proteins 0.000 claims 1
- 108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 claims 1
- 201000009906 Meningitis Diseases 0.000 claims 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [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
- 230000000890 antigenic effect Effects 0.000 claims 1
- BUACSMWVFUNQET-UHFFFAOYSA-H dialuminum;trisulfate;hydrate Chemical compound O.[Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O BUACSMWVFUNQET-UHFFFAOYSA-H 0.000 claims 1
- 229960003983 diphtheria toxoid Drugs 0.000 claims 1
- 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 230000003053 immunization Effects 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 claims 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims 1
- 229960004889 salicylic acid Drugs 0.000 claims 1
- 230000028327 secretion Effects 0.000 claims 1
- 241000617590 Escherichia coli K1 Species 0.000 abstract 2
- 241000588677 Neisseria meningitidis serogroup B Species 0.000 abstract 1
- 230000021615 conjugation Effects 0.000 abstract 1
- 230000006698 induction Effects 0.000 abstract 1
- 208000015181 infectious disease Diseases 0.000 abstract 1
- 230000001681 protective effect Effects 0.000 abstract 1
- 125000005629 sialic acid group Chemical group 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
- C07K16/1228—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K16/1232—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia from Escherichia (G)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/025—Enterobacteriales, e.g. Enterobacter
- A61K39/0258—Escherichia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
- C07K16/1217—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Neisseriaceae (F)
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Claims (16)
- Λ IZBOLJŠANO MENINGOKOKALNO POLISAHARIDNO KONJUGIRANO CEPIVO PATENTNI ZAHTEVKI 1. Modificirani polisaharid skupine B Neisseria Meningitidis, značilen po tem, da ima ostanek sialinske kisline N-acetilnih skupin naravnega polisaharida nadomeščene s C4-C8-acilnimi skupinami, kjer ima modificirani polisaharid povprečno molekulsko maso v obsegu 10.000 do 50.000 Daltonov.
- 2. Modificirani polisaharid KI iz ovojnice E. coli, značilen po tem, da ima ostanek sialinske kisline iz N-acetilnih skupin naravnega polisaharida nadomeščene s C4-C8 acilnimi skupinami, kjer ima modificirani polisaharid povprečno molekulsko maso v obsegu 10.000 do 50.000 Daltonov.
- 3. Modificiran polisaharid po zahtevku 1 , značilen po tem, da je C4-C8 acilna skupina izbrana iz skupine, ki jo sestavljajo n-butanoil, izobutanoil, n-pentanoil, n-heksanoil, n-heptanoil in n-oktanoil.
- 4.Modificirani polisaharid po zahtevku 3, značilen po tem, da je acilna skupina izbrana iz skupine, ki jo sestavljajo n-butanoil, izo-butanoil, n-pentanoil in n- heksanoil. 2 ^ · Modificiran polisaharid po zahtevku 2 , značilen po tem, da je C4-C8 skupina izbrana iz skupine, ki jo sestavljajo n-butanoil, izo-butanoil, n-pentanoil, n-heksanoil, n-heptanoil in n-oktanoil.
- 6.Modificirani polisaharid po zahtevku 5, značilen po tem, da je acilna skupina izbrana iz skupine, ki jo sestavljajo n-butanoil, izo-butanoil, n-pentanoil in n-heksanoil. 1 - Polisaharid po zahtevku 1, značilen po tem, da je od 90% do 100% ostanka slatinske kisline N-acetilnih skupin nadomeščeno s C^-Cg-acilnimi skupinami.
- 8. Polisaharid po zahtevku 2, značilen po tem, da je od 90% do 100% ostanka sialinske kisline N-acetilnih skupin nadomeščeno s C4-Ce-acilnimi skupinami.
- 9. Antigenski konjugat, značilen po tem, da obsega modificirano skupino polisaharida B Neisseria meningitidis, ki ima ostanek sialinske kisline N-acetilne skupine nadomeščen z N-C^-Cg-acilno skupino, konjugiran na imunološko primeren protein, kjer ima modificirani polisaharid povprečno molekulsko maso v obsegu 10.000 do 50.000 Daltonov.
- 10. Konjugat po zahtevku 9, značilen po tem, da je acilna skupina izbrana iz skupine, ki jo sestavljajo n-butanoil, izo-butanoil, n-pentanoil, izo-pentanoil, neo-pentanoil, heksanoil, heptanoil in oktanoil.
- 11. Konjugat po zahtevku 10, značilen po tem, da je acilna skupina izbrana iz skupine, ki jo sestavljajo n-butanoil, izo-butanoil, n-pentanoil in heksanoil. 3
- 12. Konjugat po zahtevku 9, značilen po tem, da je protein izbran iz skupine, ki jo sestavljajo tetanusni toksoid, difteria toksoid, navzkrižno reaktivni material (CRM) in bakterijski proteinski nosilec.
- 13. Konjugat po zahtevku 9, značilen po tem, da sta protein in polisaharid povezana kovalentno z vezjo -CH2-NH-protein.
- 14. Konjugat po zahtevku 12, značilen po tem, da je CRM CRM197.
- 15. Cepivo, značilno po tem, da obsega konjugat po zahtevku 9 in farmacevtsko sprejemljiv injekcijski nosilec.
- 16. Cepivo po zahtevku 15, značilno po tem, da nadalje obsega tudi fiziološko sprejemljiv adjuvant.
- 17. Cepivo po zahtevku 16, značilno po tem, da je omenjeni adjuvant izbran iz skupine, ki jo sestavljajo aluminijev hidroksid, aluminijev fosfat in aluminijev sulfat.
- 18. Gama globulinska frakcija, značilna po tem, da je sposobna pasivno zaščititi proti meningitisu, ki ga povzroča skupina B N. meningitidis in E. coli KI, omenjeno frakcijo pa pridobivamo z imunizacijo sesalcev s cepivom, po zahtevku 17, nakar sledi izločaje gama globulina iz omenjenega sesalca.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US44819589A | 1989-12-14 | 1989-12-14 | |
| YU24391A YU24391A (sh) | 1989-12-14 | 1990-12-14 | Poboljšana meningokokna polisaharid kon-jugovana vakcina |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SI20008A SI20008A (sl) | 2000-02-29 |
| SI20008B true SI20008B (en) | 2001-02-28 |
Family
ID=23779371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI9110243A SI20008B (en) | 1989-12-14 | 1990-12-14 | Improved meningococcal polysaccharide conjugate vaccine |
Country Status (30)
| Country | Link |
|---|---|
| US (3) | US5576002A (sl) |
| EP (1) | EP0504202B1 (sl) |
| JP (1) | JP2637845B2 (sl) |
| KR (1) | KR0158436B1 (sl) |
| CN (4) | CN1049223C (sl) |
| AR (1) | AR243934A1 (sl) |
| AT (1) | ATE121947T1 (sl) |
| AU (1) | AU641715B2 (sl) |
| BR (1) | BR9007917A (sl) |
| CA (1) | CA2071811C (sl) |
| CZ (1) | CZ283530B6 (sl) |
| DE (1) | DE69019164T2 (sl) |
| DK (1) | DK0504202T3 (sl) |
| ES (1) | ES2071288T3 (sl) |
| FI (2) | FI104539B (sl) |
| HR (1) | HRP920872A2 (sl) |
| HU (2) | HU9201966D0 (sl) |
| IE (1) | IE68414B1 (sl) |
| IL (1) | IL96676A (sl) |
| IN (1) | IN171747B (sl) |
| NO (2) | NO305275B1 (sl) |
| NZ (1) | NZ236471A (sl) |
| PH (1) | PH30305A (sl) |
| PL (2) | PL166659B1 (sl) |
| RO (1) | RO111416B1 (sl) |
| RU (1) | RU2105568C1 (sl) |
| SI (1) | SI20008B (sl) |
| WO (1) | WO1991008772A1 (sl) |
| YU (1) | YU24391A (sl) |
| ZA (1) | ZA9010065B (sl) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5648241A (en) * | 1989-09-15 | 1997-07-15 | The General Hospital Corporation | Conjugate vaccine against group B streptococcus |
| AU641715B2 (en) * | 1989-12-14 | 1993-09-30 | National Research Council Of Canada | Improved meningococcal polysaccharide conjugate vaccine |
| ES2160601T3 (es) * | 1992-09-24 | 2001-11-16 | Brigham & Womens Hospital | Vacunas de conjugado de polisacaridos de estreptococos del grupo b tipo ii y tipo v-proteina. |
| US5439808A (en) * | 1993-07-23 | 1995-08-08 | North American Vaccine, Inc. | Method for the high level expression, purification and refolding of the outer membrane group B porin proteins from Neisseria meningitidis |
| US6153406A (en) * | 1993-07-23 | 2000-11-28 | North American Vaccine, Inc. | Method for the high level expression, purification and refolding of the outer membrane protein P2 from Haemophilus influenzae type B |
| US5700787A (en) * | 1994-09-02 | 1997-12-23 | Brigham & Women's Hospital, Inc. | Capsular polysaccharide immunomodulator |
| US5679654A (en) * | 1994-09-02 | 1997-10-21 | Brigham & Women's Hospital, Inc. | Capsular polysaccharide immunomodulator |
| US5747287A (en) * | 1995-04-28 | 1998-05-05 | North American Vaccine, Inc. | Method for the high level expression, purification and refolding of the outer membrane group B porin proteins from Neisseria meningitidis |
| EP1090642B8 (en) * | 1995-06-07 | 2010-08-11 | GlaxoSmithKline Biologicals s.a. | Vaccines comprising a polysaccharide antigen-carrier protein conjugate and free carrier protein |
| US5811102A (en) | 1995-06-07 | 1998-09-22 | National Research Council Of Canada | Modified meningococcal polysaccharide conjugate vaccines |
| US6284884B1 (en) | 1995-06-07 | 2001-09-04 | North American Vaccine, Inc. | Antigenic group B streptococcus type II and type III polysaccharide fragments having a 2,5-anhydro-D-mannose terminal structure and conjugate vaccine thereof |
| ZA97248B (en) * | 1996-01-18 | 1997-07-18 | Rohm & Haas | Method for identifying and quantifying polymers utilizing immunoassay techniques |
| ATE252602T1 (de) | 1996-08-27 | 2003-11-15 | Chiron Corp | Meningokokkus b-epitop ausbildende monoklonale antikoerper und deren verwendung zur herstellung von impfstoffzusammenstellungen |
| ATE208629T1 (de) | 1996-08-27 | 2001-11-15 | Chiron Corp | Neisseria meningitidis serogruppe b glykokonjugate und verfahren zu deren verwendung |
| US6426074B1 (en) * | 1997-03-19 | 2002-07-30 | The Brigham And Women's Hospital Inc. | Group B Streptococcus vaccine |
| EP0994723A1 (en) | 1997-06-24 | 2000-04-26 | Chiron Corporation | Methods of immunizing adults using anti-meningococcal vaccine compositions |
| PT1630168E (pt) | 1997-08-27 | 2011-07-20 | Novartis Vaccines & Diagnostic | Compostos miméticos moleculares de péptidos de meningococos do serogrupo b |
| ES2611464T3 (es) | 1997-12-23 | 2017-05-09 | Pfizer Ireland Pharmaceuticals | Polisacárido capsular bacteriano para su uso como vacuna o para su unión a proteínas en vacunas de conjugados |
| NZ509986A (en) * | 1998-08-19 | 2003-10-31 | Baxter Healthcare S | Immunogenic beta-propionamido-linked polysaccharide and oligosaccharide protein conjugates as vaccines |
| US6436653B1 (en) | 1998-12-15 | 2002-08-20 | Exiqon A/S | Method for introduction of reporter groups into bacterial lipopolysaccharide-derived carbohydrates and the subsequent coupling of such derivatives onto solid surfaces |
| US7083777B1 (en) * | 1999-04-02 | 2006-08-01 | The Brigham And Women's Hospital, Inc. | Immunomodulating polymers |
| US6518037B2 (en) * | 1999-11-12 | 2003-02-11 | University Of Iowa Research Foundation | Two-component system that controls bacterial membrane synthesis |
| GB9928196D0 (en) * | 1999-11-29 | 2000-01-26 | Chiron Spa | Combinations of B, C and other antigens |
| SV2003000753A (es) | 2000-12-05 | 2003-06-16 | Brigham & Womens Hospital | Uso de polisacaridos zwitterionicos para la especifica modulacion del progreso inmunologico |
| RU2322451C2 (ru) | 2001-04-17 | 2008-04-20 | Новартис Вэксинс Энд Диагностикс, Инк. | Молекулярные миметики эпитопов менингококка в, которые вызывают выработку функционально активных антител |
| GB0115176D0 (en) * | 2001-06-20 | 2001-08-15 | Chiron Spa | Capular polysaccharide solubilisation and combination vaccines |
| GB0121591D0 (en) * | 2001-09-06 | 2001-10-24 | Chiron Spa | Hybrid and tandem expression of neisserial proteins |
| AR045702A1 (es) | 2001-10-03 | 2005-11-09 | Chiron Corp | Composiciones de adyuvantes. |
| DK1490409T3 (da) * | 2002-03-26 | 2009-03-23 | Novartis Vaccines & Diagnostic | Modificerede saccharider med forbedret stabilitet i vand |
| WO2004089407A2 (en) * | 2003-03-31 | 2004-10-21 | The Brigham And Women's Hospital, Inc. | Zwitterionic immunomodulators for the treatment of asthma and allergy |
| US7731967B2 (en) | 2003-04-30 | 2010-06-08 | Novartis Vaccines And Diagnostics, Inc. | Compositions for inducing immune responses |
| JP4566194B2 (ja) | 2003-08-12 | 2010-10-20 | リポクセン テクノロジーズ リミテッド | タンパク質の誘導体化及び結合のためのシアル酸誘導体 |
| WO2006002402A2 (en) | 2004-06-23 | 2006-01-05 | Children's Hospital & Research Center At Oakland | Polysaccharide derivatives and uses in induction of an immune response |
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| US11491181B2 (en) | 2016-07-15 | 2022-11-08 | President And Fellows Of Harvard College | Glycolipid compositions and methods of use |
| PE20191107A1 (es) * | 2017-01-31 | 2019-08-26 | Pfizer | Composiciones de neisseria meningitidis y metodos respectivos |
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| US4695624A (en) * | 1984-05-10 | 1987-09-22 | Merck & Co., Inc. | Covalently-modified polyanionic bacterial polysaccharides, stable covalent conjugates of such polysaccharides and immunogenic proteins with bigeneric spacers, and methods of preparing such polysaccharides and conjugates and of confirming covalency |
| US4727136A (en) * | 1985-10-01 | 1988-02-23 | Canadian Patents And Development Ltd. | Modified meningococcal group B polysaccharide for conjugate vaccine |
| AU641715B2 (en) * | 1989-12-14 | 1993-09-30 | National Research Council Of Canada | Improved meningococcal polysaccharide conjugate vaccine |
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1990
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1992
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1993
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1994
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1995
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