US2009155305A1PendingUtilityA1

Manufacture of Vaccines That Contain Both Hepatitis B Virus Surface Antigen and Surfactant

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Assignee: CONTORNI MARIOPriority: Nov 8, 2005Filed: Nov 7, 2006Published: Jun 18, 2009
Est. expiryNov 8, 2025(expired)· nominal 20-yr term from priority
Inventors:Mario Contorni
A61K 39/13A61K 39/05A61P 31/14A61K 39/099A61K 39/12C12N 2730/10122A61K 39/29A61K 39/102A61P 31/04A61K 39/39C07K 14/005A61K 2039/55505A61K 39/08A61P 31/16A61K 39/0017A61K 2039/70A61K 39/095A61P 31/12A61P 31/20A61K 39/292C12N 2730/10134A61K 2039/6037A61K 39/00Y02A50/30
67
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Claims

Abstract

When preparing HBsAg for use in a combination vaccine, it is known to add a non-ionic detergent after the HBsAg has been purified. Adding detergents after purification of HBsAg is not optimal, however, as it requires a separate processing step during manufacture. Thus the invention uses them during HBsAg purification.

Claims

exact text as granted — not AI-modified
1 . A process for preparing a combination vaccine, wherein the vaccine comprises: (i) a non-ionic surfactant, (ii) a hepatitis B virus (HBV) surface antigen, and (iii) an antigen from at least one non-HBV pathogen, and wherein the process comprises: (i) purifying the HBV surface antigen from recombinant yeast cells, wherein the purification includes a step in which the yeast cells are disrupted in the presence of the non-ionic surfactant, to give a purified HBsAg component; and (ii) combining the purified HBsAg component with at least one further antigen from a non-HBV pathogen, to give the combination vaccine. 
   
   
       2 . A process for preparing a combination vaccine, wherein the vaccine comprises: (i) a non-ionic surfactant, (ii) a hepatitis B virus (HBV) surface antigen (HBsAg), and (iii) an antigen from at least one non-HBV pathogen, and wherein the process comprises the step of combining a purified HBsAg with at least one further antigen from a non-HBV pathogen, to give the combination vaccine, wherein the HBsAg was prepared by a process in which recombinant HBsAg-expressing yeast cells were disrupted in the presence of the non-ionic surfactant. 
   
   
       3 . An immunogenic composition comprising (i) a non-ionic surfactant, (ii) a hepatitis B virus (HBV) surface antigen, and (iii) an antigen from at least one non-HBV pathogen, wherein the HBV surface antigen was prepared by a process in which recombinant HBsAg-expressing yeast cells were disrupted in the presence of the non-ionic surfactant. 
   
   
       4 . The process of  claim 1 , wherein the non-ionic surfactant includes poly(oxyethene) residues. 
   
   
       5 . The process of  claim 4 , wherein the non-ionic surfactant is a polyoxyethylene sorbitan ester. 
   
   
       6 . The process of  claim 5 , wherein the non-ionic surfactant is polysorbate 20. 
   
   
       7 . The process of  claim 1 , wherein the non-ionic surfactant is present in the final product at ≦30 μg/ml. 
   
   
       8 . The process of  claim 1 , wherein the non-ionic surfactant is present in the final product at ≦50 μg for every 100 μg of HBsAg. 
   
   
       9 . The process of  claim 1 , wherein: (i) the at least one non-HBV pathogens includes  C. diphtheriae  and  C. tetani ; (ii) the antigens from these two pathogens are a diphtheria toxoid and a tetanus toxoid; and (iii) the diphtheria and tetanus toxoids are initially present in admixed form that is substantially free from polysorbate 20. 
   
   
       10 . The process of claim J_, wherein the HBV surface antigen is non-glycosylated. 
   
   
       11 . The process of  claim 1 , wherein the HBV surface antigen is in the form of particles including a lipid matrix comprising phospholipids. 
   
   
       12 . The process of  claim 1 , wherein the HBV surface antigen is from HBV subtype adw2. 
   
   
       13 . The process of  claim 1 , wherein the HBV surface antigen is present in the final composition at about 10 μg per dose. 
   
   
       14 . The process of  claim 1 , wherein the vaccine includes a Hib conjugate, a meningococcal conjugate, and/or a pneumococcal conjugate. 
   
   
       15 . The process of  claim 1 , wherein the vaccine is selected from: a 3-valent HBsAg, D, T composition; a 4-valent HBsAg, D, T, Pw composition; a 5-valent HBsAg, D, T, Pw, Hib composition; a 7-valent HBsAg, D, T, Pw, Hib, MenA, MenC composition; a 8-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenW135 composition; a 8-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenY composition; a 9-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenW135, MenY composition; a 4-valent HBsAg, D, T, Pa composition; a 5-valent HBsAg, D, T, Pa, Hib composition; a 5-valent HBsAg, D, T, Pa, poliovirus composition; a 6-valent HBsAg, D, T, Pa, poliovirus, Hib composition; a 7-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenA composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenY composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenW135 composition; a 10-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenA, MenW135, MenY composition; a 2-valent HBsAg, Hib composition; and a 2-valent HBsAg, hepatitis A virus composition. 
   
   
       16 . The composition of  claim 3 , wherein the vaccine includes an aluminium phosphate adjuvant and/or an aluminium hydroxide adjuvant. 
   
   
       17 . The composition of  claim 3 , wherein the vaccine includes both aluminium phosphate and aluminium hydroxide adjuvants. 
   
   
       18 . The composition of  claim 16 , wherein the concentration Al 3+  in the vaccine is ≦5 mg/ml. 
   
   
       19 . The process of  claim 1 , wherein the process comprises adding a pre-mixed D-T component. 
   
   
       20 . The process of  claim 1 , wherein the process comprises adding a pre-mixed D-T-Pw component. 
   
   
       21 . The process of  claim 20 , wherein the pre-mixed D-T-Pw component includes both aluminium phosphate and aluminium hydroxide adjuvants. 
   
   
       22 . (canceled) 
   
   
       23 . A kit for preparing a pentavalent composition, wherein: the pentavalent composition comprises HBsAg, D, T, Pw and a Hib-T conjugate antigens; the D and T antigens are adsorbed to an aluminium hydroxide adjuvant; the HBsAg and Hib-T are adsorbed to an aluminium phosphate adjuvant; the HBsAg, D, T and Pw components are in aqueous form in a first container; the Hib-T is in lyophilised form in combination with lactose in a second container; and the HBsAg was prepared by a process in which recombinant HBsAg-expressing yeast cells were disrupted in the presence of the non-ionic surfactant. 
   
   
       24 . A kit for preparing a heptavalent composition, wherein: the heptavalent composition comprises HBsAg, D, T, Pw, a Hib-T conjugate, a MenA conjugate and a MenC conjugate; the HBsAg, D, T and Pw components are in aqueous form in a first container; the three conjugates are lyophilised form in a second container; the first container also includes both aluminium hydroxide and aluminium phosphate adjuvants, wherein the D and T antigens are adsorbed to aluminium hydroxide and HBsAg is adsorbed to aluminium phosphate; and the HBsAg was prepared by a process in which recombinant HBsAg-expressing yeast cells were disrupted in the presence of the non-ionic surfactant. 
   
   
       25 . The kit of  claim 24 , wherein the first container additionally includes thimerosal. 
   
   
       26 . The process of  claim 2 , wherein the non-ionic surfactant includes poly(oxyethene) residues. 
   
   
       27 . The composition of  claim 3 , wherein the non-ionic surfactant includes poly(oxyethene) residues. 
   
   
       28 . The process of  claim 26 , wherein the non-ionic surfactant is a polyoxyethylene sorbitan ester. 
   
   
       29 . The composition of  claim 27 , wherein the non-ionic surfactant is a polyoxyethylene sorbitan ester. 
   
   
       30 . The process of  claim 28 , wherein the non-ionic surfactant is polysorbate 20. 
   
   
       31 . The composition of  claim 29 , wherein the non-ionic surfactant is polysorbate 20. 
   
   
       32 . The process of  claim 2 , wherein the non-ionic surfactant is present in the final product at ≦30 μg/ml. 
   
   
       33 . The composition of  claim 3 , wherein the non-ionic surfactant is present in the final product at ≦30 μg/ml. 
   
   
       34 . The process of  claim 2 , wherein the non-ionic surfactant is present in the final product at ≦50 μg for every 100 μg of HBsAg. 
   
   
       35 . The composition of  claim 3 , wherein the non-ionic surfactant is present in the final product at ≦50 μg for every 100 μg of HBsAg. 
   
   
       36 . The process of  claim 2 , wherein: (i) the at least one non-HBV pathogens includes  C. diphtheriae  and  C. tetani ; (ii) the antigens from these two pathogens are a diphtheria toxoid and a tetanus toxoid; and (iii) the diphtheria and tetanus toxoids are initially present in admixed form that is substantially free from polysorbate 20. 
   
   
       37 . The process of  claim 2 , wherein the HBV surface antigen is non-glycosylated. 
   
   
       38 . The composition of  claim 3 , wherein the HBV surface antigen is non-glycosylated. 
   
   
       39 . The process of  claim 2 , wherein the HBV surface antigen is in the form of particles including a lipid matrix comprising phospholipids. 
   
   
       40 . The composition of  claim 3 , wherein the HBV surface antigen is in the form of particles including a lipid matrix comprising phospholipids. 
   
   
       41 . The process of  claim 2 , wherein the HBV surface antigen is from HBV subtype adw2. 
   
   
       42 . The composition of  claim 3 , wherein the HBV surface antigen is from HBV subtype adw2. 
   
   
       43 . The process of  claim 2 , wherein the HBV surface antigen is present in the final composition at about 10 μg per dose. 
   
   
       44 . The composition of  claim 3 , wherein the HBV surface antigen is present in the final composition at about 10 μg per dose. 
   
   
       45 . The process of  claim 2 , wherein the vaccine includes a Hib conjugate, a meningococcal conjugate, and/or a pneumococcal conjugate. 
   
   
       46 . The composition of  claim 3 , wherein the vaccine includes a Hib conjugate, a meningococcal conjugate, and/or a pneumococcal conjugate. 
   
   
       47 . The process of  claim 2 , wherein the vaccine is selected from: a 3-valent HBsAg, D, T composition; a 4-valent HBsAg, D, T, Pw composition; a 5-valent HBsAg, D, T, Pw, Hib composition; a 7-valent HBsAg, D, T, Pw, Hib, MenA, MenC composition; a 8-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenW135 composition; a 8-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenY composition; a 9-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenW135, MenY composition; a 4-valent HBsAg, D, T, Pa composition; a 5-valent HBsAg, D, T, Pa, Hib composition; a 5-valent HBsAg, D, T, Pa, poliovirus composition; a 6-valent HBsAg, D, T, Pa, poliovirus, Hib composition; a 7-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenA composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenY composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenW135 composition; a 10-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenA, MenW135, MenY composition; a 2-valent HBsAg, Hib composition; and a 2-valent HBsAg, hepatitis A virus composition. 
   
   
       48 . The composition of  claim 3 , wherein the vaccine is selected from: a 3-valent HBsAg, D, T composition; a 4-valent HBsAg, D, T, Pw composition; a 5-valent HBsAg, D, T, Pw, Hib composition; a 7-valent HBsAg, D, T, Pw, Hib, MenA, MenC composition; a 8-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenW135 composition; a 8-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenY composition; a 9-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenW135, MenY composition; a 4-valent HBsAg, D, T, Pa composition; a 5-valent HBsAg, D, T, Pa, Hib composition; a 5-valent HBsAg, D, T, Pa, poliovirus composition; a 6-valent HBsAg, D, T, Pa, poliovirus, Hib composition; a 7-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenA composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenY composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenW135 composition; a 10-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenA, MenW135, MenY composition; a 2-valent HBsAg, Hib composition; and a 2-valent HBsAg, hepatitis A virus composition. 
   
   
       49 . The composition of  claim 48 , wherein the vaccine includes an aluminium phosphate adjuvant and/or an aluminium hydroxide adjuvant. 
   
   
       50 . The composition of  claim 48 , wherein the vaccine includes both aluminium phosphate and aluminium hydroxide adjuvants. 
   
   
       51 . The composition of  claim 17 , wherein the concentration Al 3+  in the vaccine is ≦5 mg/ml. 
   
   
       52 . The composition of  claim 49 , wherein the concentration Al 3+  in the vaccine is ≦5 mg/ml. 
   
   
       53 . The composition of  claim 50 , wherein the concentration Al 3+  in the vaccine is ≦5 mg/ml. 
   
   
       54 . The process of  claim 2 , wherein the process comprises adding a pre-mixed D-T component. 
   
   
       55 . The process of  claim 2 , wherein the process comprises adding a pre-mixed D-T-Pw component. 
   
   
       56 . The process of  claim 55 , wherein the pre-mixed D-T-Pw component includes both aluminium phosphate and aluminium hydroxide adjuvants.

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