WO2019198096A1 - Composition de vaccin méningococcique tétravalente et son procédé de préparation - Google Patents

Composition de vaccin méningococcique tétravalente et son procédé de préparation Download PDF

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Publication number
WO2019198096A1
WO2019198096A1 PCT/IN2019/050286 IN2019050286W WO2019198096A1 WO 2019198096 A1 WO2019198096 A1 WO 2019198096A1 IN 2019050286 W IN2019050286 W IN 2019050286W WO 2019198096 A1 WO2019198096 A1 WO 2019198096A1
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formulation
polysaccharide
serogroup
conjugates
tetravalent
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PCT/IN2019/050286
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Davinder Gill
Sandeep Sharma
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Msd Wellcome Trust Hilleman Laboratories Pvt. Ltd.
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Publication of WO2019198096A1 publication Critical patent/WO2019198096A1/fr

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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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/646—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
    • 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
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • 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]
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions

Definitions

  • the present invention relates to novel polysaccharide - protein conjugate vaccine composition. More particularly, the present invention relates to a tetravalent conjugate vaccine formulation of Neisseria meningitidis serogroup A, C, Y, W capsular polysaccharides (Men A, C, Y, W) conjugated to non-toxic mutant of diphtheria toxin called cross reacting material (CRM197) as carrier protein along with pharmaceutically acceptable components/excipients.
  • the tetravalent conjugate vaccine of the present invention is a fully liquid or lyophilized or liquid-lyo formulation with or without adjuvant.
  • Vaccine manufacture and composition is complex and tightly regulated to ensure safety of the individuals and to maximize efficacy and stability. All vaccines contain an active component which generates the protective immune response. The vaccines also contain pharmaceutically acceptable additional components to enhance the stability of formulation and/or immunogenicity for strong protective immune response.
  • the World Health Organization recommends that countries with a moderate or high rate of disease or with frequent outbreaks of a vaccine preventable disease should routinely vaccinate. In countries with a low risk of disease, they recommend that high risk groups should be immunized.
  • Meningococcal disease is an acute, potentially severe illness caused by the bacterium Neisseria meningitidis.
  • N. meningitidis (Meningococcus) is an aerobic gram-negative bacterium that has been serologically classified mainly into 13 serogroups A, B, C, D, 29E, PL I, K, L, W135, X, Y and Z.
  • the grouping system is based on the capsular polysaccharides of the organisms.
  • N. meningitidis is transmitted by aerosol or direct contact with respiratory secretions of patients or healthy human carriers.
  • the endemic disease occurs primarily in children and adolescents, with highest attack rates in infants aged 3- 12 months, whereas in epidemics older children and young adults may be more involved.
  • the rapid progression of meningococcal disease frequently results in death within 1-2 days after onset, the N. meningitidis infections can be prevented by vaccination.
  • Immunization is the only rational approach to control the meningitis disease.
  • the most effective vaccines for N. meningitidis are polysaccharide-protein conjugate vaccines which are formed by the covalent attachment of activated protein to active polysaccharide.
  • Polysaccharide undergoes some chemical modification which is known as“activation” process prior to attachment to a carrier protein because most of the native polysaccharides cannot be chemically efficiently linked to a carrier protein without activation.
  • Serogroup A has been the most common cause of epidemic disease in sub-Saharan Africa.
  • Serogroups B and C are responsible for the majority of cases in developed— countries, with the remaining cases being caused by serogroups W135 (or simply W) and Y.
  • Serogroup C cases have been observed recently in sub-Saharan Africa where the serogroup was not so prevalent historically.
  • a tetravalent meningococcal ACYW polysaccharide- protein conjugate vaccine could offer a good coverage against meningococcal disease due to most prevalent serogroups except B for which a conjugate vaccine is remote possibility due to structural similarity of MenB capsular polysaccharide with the molecules found in human neuronal cells.
  • various monovalent or multivalent vaccines including serogroup A, C, Y and W polysaccharide conjugates are licensed for sale in market.
  • the existing state of art discloses vaccines for the prevention of various serogroups including A. meningitidis sero group A, B, C, W and Y such as the US patent application no. PCT/EP2006/006188 teaches an immunogenic composition comprising meningococcal capsular polysaccharide from at least one of the groups A, C, W and Y conjugated to a carrier protein.
  • the available multivalent meningococcal conjugate vaccines are of higher cost and have complex formulations.
  • meningococcal conjugate vaccine which has higher homogeneity, higher immunogenicity, lower cost and is simple to formulate and administer.
  • the main object of present invention is to provide a novel polysaccharide - protein conjugate vaccine composition.
  • Yet another object of the present invention is to provide novel polysaccharide - protein conjugate vaccine composition in a fully liquid or lyophilized or liquid-lyo vaccine formulation.
  • Yet another object of the present invention is to provide novel polysaccharide - protein conjugate vaccine composition wherein said composition is capable of being used in production of a tetravalent meningococcal ACYW-CRM197 combination vaccine containing serogroup ACYW polysaccharides each conjugated to non-toxic mutant of diphtheria toxin called cross reacting material (CRM197) as carrier protein.
  • CCM197 cross reacting material
  • Yet another object of the present invention is to provide a novel vaccine formulation of polysaccharide - protein conjugate vaccine composition comprising of polysaccharide - protein conjugates along with pharmaceutically acceptable components/ excipients.
  • Yet another object of the present invention is to provide a novel vaccine formulation of polysaccharide - protein conjugate vaccine composition comprising of tetravalent meningococcal ACYW-CRM197 polysaccharide - protein conjugates along with pharmaceutically acceptable components/excipients .
  • Yet another object of the present invention is to provide novel polysaccharide - protein conjugate vaccine composition with or without adjuvant.
  • Yet another object of the present invention is to provide the optimum dosage of each of the conjugates in the vaccine composition and formulation.
  • Yet another object of the present invention is to provide a tetravalent vaccine formulation which is stable at high temperatures and shows high immunogenicity and antigenicity.
  • the present invention provides a novel polysaccharide - protein conjugate vaccine composition and formulation thereof. More particularly, the present invention relates to a conjugate vaccine formulation comprising of polysaccharide - protein conjugates produced using conjugation chemistry.
  • the conjugation chemistry used includes known cyanylation chemistry.
  • the formulation of present invention is capable of being used in production of tetravalent meningococcal combination vaccines.
  • the polysaccharides used for preparing conjugates of the present invention are obtained through optimized fermentation process.
  • the novel vaccine formulation of polysaccharide - protein conjugate vaccine composition comprises of polysaccharide - protein conjugates along with pharmaceutically acceptable components/excipients. All the conjugates in vaccine composition and formulation have same carrier protein.
  • the novel polysaccharide - protein conjugate vaccine formulation of present invention comprises of four polysaccharide-protein conjugates.
  • the polysaccharide is selected from gram negative bacteria, belonging to Neisseria meningitidis capsular serogroup A, C, Y and W polysaccharides.
  • CRM197 is used as the carrier protein in preparing all the conjugates.
  • the capsular polysaccharide is degraded to smaller sizes suitable for conjugation with carrier protein to obtain conjugates with high antigenicity and high immunogenicity.
  • the capsular polysaccharide is degraded in the size range of average mol. weight from 20kDa to 250kDa preferably of average 20kDa, 50kDa, lOOkDa and 200kDa when tested for molecular weight estimation using Pullulan standards on HPLC PWXL4000 and 5000 columns in series.
  • the polysaccharides are activated but carrier protein may or may not be activated before conjugation.
  • the individual conjugates are obtained with linker or without any linker.
  • the size degraded capsular polysaccharide (sized capsular polysaccharide) is conjugated with carrier protein.
  • the formulation contains the conjugates prepared by optimized cyanylation chemistry for each of serogroup A, C, Y and W polysaccharides.
  • the monovalent bulk conjugates are purified by gel filtration chromatography or salt precipitation method and stored in suitable buffered saline.
  • the pharmaceutically acceptable excipients can be buffer, preservative, stabilizer, surfactant, either alone or in combination with or without adjuvant.
  • the formulation of present invention is liquid or lyophilized or liquid-lyo formulation with mono- or multi-dose regimen with or without a preservative.
  • the formulation of present invention is preferably a wholly liquid formulation.
  • the present invention also provides the optimum dosage of each of the conjugates in the vaccine composition and formulation.
  • the present invention provides a novel polysaccharide - protein conjugate vaccine composition and formulation thereof. More particularly, the present invention relates to a conjugate vaccine composition comprising of polysaccharide - protein conjugates produced using conjugation chemistry.
  • the conjugation chemistry used is known cyanylation chemistry.
  • the composition of present invention is capable of being used in production of an adjuvanted or non- adjuvanted tetravalent combination vaccine.
  • the vaccine formulation is a fully liquid or lyophilized or liquid-lyo formulation.
  • the novel vaccine formulation of present invention comprises of polysaccharide - protein conjugates along with pharmaceutically acceptable components/excipients. All the conjugates in vaccine composition and formulation have same carrier protein.
  • the present invention provides a tetravalent vaccine formulation.
  • the novel polysaccharide - protein conjugate vaccine composition and formulation of present invention comprises of four individual polysaccharide- protein conjugates.
  • the polysaccharide is selected from gram negative bacteria Neisseria meningitidis serogroup A, C, Y and W capsular polysaccharides.
  • the carrier protein used for preparing all the conjugates is CRM 197.
  • the capsular polysaccharide is degraded to smaller sizes suitable for conjugation with carrier protein to obtain conjugates with high antigenicity, high immunogenicity and high stability.
  • the capsular polysaccharide is degraded in the size range of average Molecular weight from 20kDa to 250kDa, preferably 50, 100 and 200kDa when tested for molecular weight using Pullulan standards on HPLC PWXL4000 and 5000 columns in series.
  • the polysaccharide is activated but carrier protein may or may not be activated before conjugation.
  • the conjugates are produced with or without linker arm between polysaccharide and protein moieties.
  • the conjugates with the linker arm are produced by attaching the linker to the carrier protein.
  • the conjugates are purified by salt precipitation or by Gel filtration chromatography.
  • the monovalent bulk conjugates are stored in phosphate buffered saline for MenC, Y and W-CRM197 conjugates and in MES buffer for MenA-CRMl97 conjugate.
  • the novel multivalent polysaccharide-protein conjugate vaccine formulation of the present invention comprises of meningococcal serogroups A, C, Y, W polysaccharides each individually conjugated to CRM 197 (Men ACYW- CRM197) wherein serogroup A, C, Y and W polysaccharides are conjugated using optimized cyanylation chemistry.
  • Each said conjugate has the carrier protein to polysaccharide ratio between 0.25-1.1.
  • the novel multivalent polysaccharide-protein conjugate vaccine formulation of the present invention comprises of meningococcal serogroups A, C, Y, W polysaccharides each individually conjugated to CRM 197 (Men ACYW- CRM197) mixed with one or more buffer and one or more pharmaceutically acceptable excipients with or without adjuvant.
  • the tetravalent polysaccharide-protein conjugate vaccine formulation is preferably a wholly liquid tetravalent conjugate vaccine comprises of meningococcal serogroups A, C, Y, W polysaccharides each individually conjugated to CRM 197 (Men ACYW-CRM197) mixed with one or more buffer and one or more pharmaceutically acceptable excipients with or without adjuvant.
  • the osmolality of formulation ranges between 240-330 mOsmol/Kg.
  • the pharmaceutically acceptable excipients can be buffer, preservative, stabilizer, surfactant, either alone or in combination with or without any adjuvant.
  • the stabilizers may be selected from sucrose, lactose, arabinose, maltose or a combination thereof.
  • the formulation of present invention is a liquid or lyophilized or liquid-lyo combination formulation with mono- or multi-dose regimen with or without a preservative.
  • novel tetravalent liquid polysaccharide- protein conjugate vaccine formulation of the present invention comprises of
  • novel tetravalent liquid polysaccharide-protein conjugate vaccine formulation of the present invention comprises of
  • the ingredients are mixed by stirring at room temperature for 0.5-2 hours and followed by filling in vials and storage at 2-8°C.
  • Buffer 10-25 mM Phosphate buffered saline (pH 7.0 +
  • Another embodiment of the liquid formulation without adjuvant providing desired osmolality, high stability and desired immunogenicity comprises of
  • Another embodiment of the lyophilized formulation without adjuvant providing desired osmolality, high stability and desired immunogenicity comprises of
  • the MenACYW-CRMl97 conjugates are lyophilized with one or more of the stabilizers including Sucrose, Maltose or Lactose and the lyophilized ingredients are mixed with buffer components stored in another vial before use.
  • the vials containing lyophilized components and diluent buffer are stored at 2-8°C.
  • liquid formulation with adjuvant providing desired osmolality, high stability and desired immunogenicity comprises of Ingredient Quantity/ Concentration
  • the ingredients are mixed by stirring at room temperature for 0.5-2 hours
  • the formulations of the present invention without adjuvant have been tested for osmolality, stability and immunogenicity.
  • the formulations have been exposed to high temperatures of 25+2 °C for 6 months to check the rise in the free polysaccharide content.
  • the free polysaccharide content in the vaccine formulation has been separated by deoxycholate (DOC) precipitation and filtration method and estimated by High performance anion exchange chromatography with pulsed amperometric detector (HPAEC-PAD) method.
  • DOC deoxycholate
  • HPAEC-PAD High performance anion exchange chromatography with pulsed amperometric detector
  • the formulation is stable at high temperatures. Considering 40% free PS as the maximum target, the formulation shows stability at the high temperature of 25 ⁇ 2°C for at least 5 months and at 5 ⁇ 3°C for at least 6 months in ongoing stability studies.
  • the formulation of the present invention is preferably in liquid form.
  • the present invention also provides the optimum dosage of each of the conjugates in the vaccine composition and formulation.
  • the optimum dose is 5-10 pg of serogroup A polysaccharide and 5 pg of serogroup C, Y and W polysaccharide per human dose with or without adjuvant.
  • Example 1 Preparation of different tetra valent Meningococcal liquid formulations to establish the product stability in the presence of different excipients and buffers:
  • Meningococcal ACYW-CRM197 formulations have been 5 prepared by mixing the antigen with the buffers like PBS buffer and Histidine or a combination thereof.
  • the formulations have been prepared as per the Table 1 below:
  • Table 1 Matrix for the formulation of liquid tetravalent Meningococcal 0 ACYW-CRM197 conjugate vaccine prepared with PS of average size 110 kDa.
  • Example 2 Preparation of different tetravalent Meningococcal ACYW- CRM197 liquid formulations with different bulk conjugate characteristics:
  • the tetravalent Meningococcal formulations have been prepared with or without any adjuvant and different characteristics of monovalent bulk conjugates. All the formulations have been prepared in PBS. The following matrix has been used to prepare the different formulations: 0 Table 3: Matrix for the preparation of liquid tetravalent meningococcal ACYW-CRM197 conjugate vaccine formulations
  • Example 3 Stability of tetravalent Meningococcal ACYW-CRM liquid formulations at Accelerated and Real-Time conditions:
  • Samples have been stored for a period of 6 months under accelerated conditions tested on monthly interval and for 3 years at real time storage conditions tested at quarterly intervals in first year and 6 monthly in 2 nd and 3 rd year (Study ongoing, data available till 6 months). Samples have been withdrawn as per standard plan and analyzed for the best stability indicating parameter of free PS % content over time.
  • mice Groups of 10-12 female mice (6-9 weeks old) have been immunized at 2 week interval with novel liquid non-adjuvanted or adjuvanted tetravalent meningococcal ACYW-CRM197 conjugate vaccine F-A to F-K and a vehicle control without bulk conjugates and a licensed Men ACYW conjugate vaccine as positive control. All immunizations have been performed by administering of vaccine via subcutaneous route in mice. Each mouse has been immunized with formulation equivalent to 1-2 pg polysaccharide per serogroup. Serogroup specific anti-meningococcal functional antibody titers by serum bactericidal assay in sera collected post 2 and 3 dose.
  • Example 5 Serum Bactericidal Assay (SBA) for the serogroup specific functional antibody titration
  • N. meningitidis serogroup specific bacterial stock has been grown overnight on sheep blood agar plate at 37°C with 5% C0 2 . Isolated colonies have been picked and incubated on the surface of another sheep blood agar plate at 37°C with 5% C0 2 . The bacterial growth from second plate have been resuspended in optimized SBA buffer for respective serogroup to achieve 250-1000 colony forming units per 10 pl. Quality control (QC) sera and test sera samples have been heat inactivated for 30 min at 56 °C. In micro well plate, 20 m ⁇ of serial two fold dilutions of test serum has been mixed with 10 m ⁇ of bacteria at the working dilution and 10 m ⁇ of baby rabbit complement (Pel-Freez).

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Abstract

La présente invention concerne une nouvelle composition de vaccin conjugué polysaccharide-protéine et une formulation obtenue par un procédé de fermentation optimisé. La formulation est une formulation tétravalente liquide ou lyophilisée ou les deux à la fois de polysaccharides de la capsule des sérogroupes A, C, Y et W de Neisseria meningitidis (Men A, C, Y, W), chaque desdits polysaccharides étant conjugué séparément à un mutant non toxique de la toxine diphtérique appelée protéine porteuse (CRM197) de matière de réaction croisée afin d'obtenir des conjugués Men A, C, Y, W – CRM197, associés à un ou plusieurs tampons et avec ou sans adjuvant, ainsi qu'à des composants/excipients pharmaceutiquement acceptables.
PCT/IN2019/050286 2018-04-11 2019-04-08 Composition de vaccin méningococcique tétravalente et son procédé de préparation WO2019198096A1 (fr)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002058737A2 (fr) * 2001-01-23 2002-08-01 Aventis Pasteur Vaccin meningococcique polyvalent prrepare avec un conjugue de polysaccharide et de proteine
WO2003009869A1 (fr) * 2001-07-26 2003-02-06 Chiron Srl. Vaccins comprenant des adjuvants aluminium et histidine
WO2006075170A1 (fr) * 2005-01-14 2006-07-20 Novartis Vaccines And Diagnostics Srl Vaccination a base de conjugues antimeningocciques
WO2007000342A2 (fr) * 2005-06-27 2007-01-04 Glaxosmithkline Biologicals S.A. Composition immunogène
WO2013114268A1 (fr) * 2012-01-30 2013-08-08 Serum Institute Of India Ltd. Composition immunogène
WO2015181834A2 (fr) * 2014-05-24 2015-12-03 Biological E Limited Nouveau vaccin conjugué méningococcique semi-synthétique
WO2019003238A1 (fr) * 2017-06-27 2019-01-03 Msd Wellcome Trust Hilleman Laboratories Pvt. Ltd. Nouvelle composition vaccinale multivalente à base de conjugués polysaccharide – protéine et formulation de cette dernière

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002058737A2 (fr) * 2001-01-23 2002-08-01 Aventis Pasteur Vaccin meningococcique polyvalent prrepare avec un conjugue de polysaccharide et de proteine
WO2003009869A1 (fr) * 2001-07-26 2003-02-06 Chiron Srl. Vaccins comprenant des adjuvants aluminium et histidine
WO2006075170A1 (fr) * 2005-01-14 2006-07-20 Novartis Vaccines And Diagnostics Srl Vaccination a base de conjugues antimeningocciques
WO2007000342A2 (fr) * 2005-06-27 2007-01-04 Glaxosmithkline Biologicals S.A. Composition immunogène
WO2013114268A1 (fr) * 2012-01-30 2013-08-08 Serum Institute Of India Ltd. Composition immunogène
WO2015181834A2 (fr) * 2014-05-24 2015-12-03 Biological E Limited Nouveau vaccin conjugué méningococcique semi-synthétique
WO2019003238A1 (fr) * 2017-06-27 2019-01-03 Msd Wellcome Trust Hilleman Laboratories Pvt. Ltd. Nouvelle composition vaccinale multivalente à base de conjugués polysaccharide – protéine et formulation de cette dernière

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