IMMUNOGENIC COMPOSITION

• US 20150044253A1
• Filed: 10/28/2014
• Published: 02/12/2015
• Est. Priority Date: 06/27/2005
• Status: Active Grant

• Current Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
• Original Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
• Inventors: BIEMANS, Ralph Leon, BOUTRIAU, Dominique, CAPIAU, Carine, DENOEL, Philippe, DUVIVIER, Pierre, POOLMAN, Jan
• Granted Patent: US 9,358,279 B2
• Time in Patent Office: Days
• US Class Current: 424/194.1
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61K 2039/575 humoral response
• CPC Class Codes: A61K 2039/6037 Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
• CPC Class Codes: A61K 2039/62 characterised by the link between antigen and carrier
• CPC Class Codes: A61K 2039/627 characterised by the linker
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/0017 Combination vaccines based on whole cell diphtheria-tetanus-pertussis
• CPC Class Codes: A61K 39/0018 Combination vaccines based on acellular diphtheria-tetanus-pertussis
• CPC Class Codes: A61K 39/05 Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella, Corynebacterium; Propionibacterium Mycobacterium A61K39/04
• CPC Class Codes: A61K 39/08 Clostridium, e.g. Clostridium tetani
• CPC Class Codes: A61K 39/092 Streptococcus
• CPC Class Codes: A61K 39/095 Neisseria
• CPC Class Codes: A61K 39/099 Bordetella
• CPC Class Codes: A61K 39/102 Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
• CPC Class Codes: A61K 39/116 Polyvalent bacterial antigens
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• CPC Class Codes: A61P 11/04 : for throat disorders
• CPC Class Codes: A61P 11/14 : Antitussive agents
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 3/00 : Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms preparation by hydrolysis of di-or polysaccharides C13; separation or purification of sucrose, glucose, fructose, lactose or maltose C13
• CPC Class Codes: C12N 2730/10134 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/16234 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/16271 : Demonstrated in vivo effect
• CPC Class Codes: C12N 2770/32634 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present application discloses an immunogenic composition comprising a Hib saccharide conjugate, at least one additional bacterial, for example N. meningitidis, saccharide conjugate(s), and a further antigen selected from the group consisting of whole cell pertussis and hepatitis B surface antigen, wherein the saccharide dose of the Hib saccharide conjugate is less than 5 μg.

Claims

1. An immunogenic composition comprising a Hib saccharide conjugate, at least one additional bacterial, for example N. meningitidis, saccharide conjugate(s), and a further antigen selected from the group consisting of whole cell pertussis and hepatitis B surface antigen, wherein the saccharide dose of the Hib saccharide conjugate is less than 5 μ

g.

2. The immunogenic composition of claim 1 wherein the saccharide dose of the or each of the at least one additional bacterial, for example N. meningitidis, saccharide conjugate(s) is less than 6 μ

g.

3. The immunogenic composition of claim 1 or 2 wherein the at least one additional bacterial saccharide conjugate(s) comprises a N. meningitidis capsular saccharide derived from a strain selected from the group consisting of serogroups A, B, C, W135 and Y.

4. The immunogenic composition of claim 3 comprising N. meningitidis serogroup C capsular saccharide (MenC).

5. The immunogenic composition of claim 3 or 4 comprising N. meningitidis serogroup A capsular saccharide (MenA).

6. The immunogenic composition of any one of claims 3-5 comprising N. meningitidis serogroup Y capsular saccharide (MenY).

7. The immunogenic composition of any one of claims 3-6 comprising N. meningitidis serogroup W135 capsular saccharide (MenW).

8. The immunogenic composition of any preceding claim comprising DT, TT, Pw and HepB.

9. The immunogenic composition of any preceding claim comprising a N. meningitidis serogroup B outer membrane vesicle preparation.

10. The immunogenic composition of any preceding claim comprising a S. pneumoniae capsular saccharide derived from a strain selected from the group consisting of serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F.

11. The immunogenic composition of any preceding claim comprising a S. typhi Vi capsular saccharide.

12. The immunogenic composition of any preceding claim wherein the same carrier protein is used in the Hib conjugate and the or each of the at least one N. meningitidis saccharide conjugate(s).

13. The immunogenic composition of any preceding claim wherein the Hib saccharide is conjugated to a carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT, protein D, OMPC and pneumolysin.

14. The immunogenic composition of any preceding claim wherein the or each of the at least one N. meningitidis saccharide(s) are conjugated to a carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT, protein D, OMPC and pneumolysin.

15. The immunogenic composition of any preceding claim wherein the ratio of Hib to carrier protein in the Hib saccharide conjugate is between 1:

5 and 5;

1, 1;

1 and 1;

4, 1;

2 and 1;

3.5 or around 1;

3 (w/w).

16. The immunogenic composition of any preceding claim wherein the the Hib saccharide is conjugated to the carrier protein via a linker.

17. The immunogenic composition of claim 16 wherein the linker is bifunctional.

18. The immunogenic composition of claim 17 wherein the linker has two reactive amino groups.

19. The immunogenic composition of claim 17 wherein the linker has two reactive carboxylic acid groups.

20. The immunogenic composition of claim 16 wherein the linker has a reactive amino group at one end and a reactive carboxylic acid group at the other end.

21. The immunogenic composition of any one of claims 16-20 wherein the linker has between 4 and 12 carbon atoms.

22. The immunogenic composition of claim 16 or 17 wherein the linker is ADH.

23. The immunogenic composition of any one of claims 1-22 wherein the Hib saccharide is conjugated to the carrier protein or linker using CNBr or CDAP.

24. The immunogenic composition of any preceding claim wherein the carrier protein is conjugated to the Hib saccharide or linker using carbodiimide chemistry, optionally EDAC chemistry.

25. The immunogenic composition of any preceding claim wherein the or each of the N. meningitidis saccharide conjugate(s) has a saccharide:

carrier ratio of 1;

5-5;

1 or 1;

1-1;

4(w/w).

26. The immunogenic composition of any preceding claim wherein at least one of the N. meningitidis saccharides is directly conjugated to a carrier protein.

27. The immunogenic composition of claim 26 wherein the at least one N. meningitidis saccharide is Men W and/or MenY, MenW and/or MenC, MenY and/or MenC, or MenW and MenC and MenY.

28. The immunogenic composition of claim 26 or 27 wherein the at least one N. meningitidis saccharide is directly conjugated by CDAP chemistry.

29. The immunogenic composition of any one of claims 26-28 wherein the ratio of Men W and/or Y saccharide to carrier protein is between 1:

0.5 and 1;

2.

30. The immunogenic composition of any one of claims 26-29 wherein the ratio of MenC saccharide to carrier protein is between 1:

0.5 and 1;

2.

31. The immunogenic composition of any preceding claim wherein one or more of the N. meningitidis saccharides is conjugated to the carrier protein via a linker.

32. The immunogenic composition of claim 31 wherein the linker is bifunctional.

33. The immunogenic composition of claim 32 wherein the linker has two reactive amino groups.

34. The immunogenic composition of claim 32 wherein the linker has two reactive carboxylic acid groups.

35. The immunogenic composition of claim 32 wherein the linker has a reactive amino group at one end and a reactive carboxylic acid group at the other end.

36. The immunogenic composition of claim 31-35 wherein the linker has between 4 and 12 carbon atoms.

37. The immunogenic composition of claim 31 or 32 wherein the linker is ADH.

38. The immunogenic composition of any one of claims 31-37 wherein the or each one or more of the N. meningitidis saccharides is conjugated to the linker with CDAP chemistry.

39. The immunogenic composition of claim 31-38 wherein the carrier protein is conjugated to the linker using carbodiimide chemistry, optionally using EDAC.

40. The immunogenic composition of any one of claims 31-39 wherein the or each N. meningitidis saccharide(s) is conjugated to the linker before the carrier protein is conjugated to the linker.

41. The immunogenic composition of any one of claims 31-40 wherein MenA is conjugated to a carrier protein via a linker.

42. The immunogenic composition of claim 41 wherein the ratio of MenA saccharide to carrier protein is between 1:

2 and 1;

5.

43. The immunogenic composition of any one of claims 31-42 wherein MenC is conjugated to a carrier protein via a linker.

44. The immunogenic composition of claim 43 wherein the ratio of MenC saccharide to carrier protein is between 1:

2 and 1;

5.

45. The immunogenic composition of any preceding claim, wherein the MenA saccharide, where present, has a molecular weight of above 50 kDa, 75 kDa, 100 kDa or an average size of between 50-100 kDa, 55-90 KDa or 60-80 kDa.

46. The immunogenic composition of any preceding claim wherein the MenC saccharide, where present, has a molecular weight of above 50 kDa, 75 kDa, 100 kDa or an average size of between 100-200 kDa, 100-150 kDa or 150-200 kDa.

47. The immunogenic composition of any preceding claim wherein the MenY saccharide, where present, has a molecular weight of above 50 kDa, 75 kDa, 100 kDa or an average size of between 60-190 kDa, 70-180 kDa, 80-170 kDa, 90-160 kDa, 100-150 kDa or 110-140 kDa.

48. The immunogenic composition of any preceding claim wherein the MenW saccharide, where present, has a molecular weight of above 50 kDa, 75 kDa, 100 kDa or an average size of between 60-190 kDa, 70-180 kDa, 80-170 kDa, 90-160 kDa, 100-150 kDa or 110-140 kDa.

49. The immunogenic composition of any preceding claim wherein MenC, where present is at least partially O-acetylated such that at least 30% of the repeat units are O-acetylated at at least one position.

50. The immunogenic composition of any preceding claim wherein MenY, where present is at least partially O-acetylated such that at least 20% of the repeat units are O-acetylated at at least one position.

51. The immunogenic composition of any preceding claim wherein MenW, where present is at least partially O-acetylated such that at least 30% of the repeat units are O-acetylated at at least one position.

52. The immunogenic composition of any preceding claim wherein MenA, where present is at least partially O-acetylated such that at least 50% of the repeat units are O-acetylated at at least one position.

53. The immunogenic composition of any preceding claim wherein the hib saccharide conjugate and the at least one N. meningitidis saccharide conjugate(s) are not adsorbed to aluminium salts.

54. The immunogenic composition of any preceding claim which is unadjuvanted.

55. The immunogenic composition of any preceding claim which is buffered at between pH 7.0 and 8.0.

56. A vaccine comprising the immunogenic composition of any one of claims 1-55 and a pharmaceutically acceptable excipient.

57. A vaccine kit for concomitant or sequential administration comprising two multi-valent immunogenic compositions for conferring protection in a host against disease caused by Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae, and Haemophilus influenzae, said kit comprising a first container comprising:

tetanus toxoid (TT), and

diphtheria toxoid (DT), and

whole cell pertussis components, and/or hepatitis B surface antigen;

and a second container comprising an immunogenic composition comprising the immunogenic composition of any one of claims 1-55.

58. The vaccine kit of claim 57 wherein the first container further comprises hepatitis B surface antigen adsorbed on aluminium phosphate.

59. The vaccine kit of claim 57 or 58 wherein the first or second container further comprises inactivated polio virus (IPV).

60. A process for making the immunogenic composition of any one of claims 1-55 comprising the step of mixing a Hib saccharide conjugate with at least one additional bacterial saccharide conjugate(s) and a further antigen selected from the group consisting of whole cell pertussis amd hepatitis B surface antigen to form a composition wherein the saccharide dose of the Hib saccharide conjugate is less than 5 μ

g and the saccharide dose of the or each of the at least one additional bacterial saccharide conjugate(s) is less than 6 μ

g.

61. A method of immunising a human host against meningitis comprising administering to the host an immunoprotective dose of the immunogenic composition, vaccine or kit of any one of claims 1-59.

62. A method of immunising a human host against disease caused by Haemophilus influenzae comprising administering to the host an immunoprotective dose of the immunogenic composition, vaccine or kit of any one of claims 1-59.

63. A method of immunising a human host against disease caused by Neisseria meningitidis comprising administering to the host an immunoprotective dose of the immunogenic composition, vaccine or kit of any one of claims 1-59.

64. The immunogenic composition, vaccine or kit of any one of claims 1-59 for use in the treatment or prevention of meningitis.

65. The immunogenic composition, vaccine or kit of any one of claims 1-59 for use in the treatment or prevention of disease caused by Haemophilus influenzae.

66. The immunogenic composition, vaccine or kit of any one of claims 1-59 for use in the treatment or prevention of disease caused by Neisseria meningitidis.

67. The use of the immunogenic composition, vaccine or kit of any one of claims 1-59 in the manufacture of a medicament for the treatment or prevention of meningitis.

68. The use of the immunogenic composition, vaccine or kit of any one of claims 1-59 in the manufacture of a medicament for the treatment or prevention of disease caused by Haemophilus influenzae.

69. The use of the immunogenic composition, vaccine or kit of any one of claims 1-59 in the manufacture of a medicament for the treatment or prevention of diseases caused by Neisseria meningitidis.