IMMUNOGENIC COMPOSITION

• US 20090252759A1
• Filed: 06/23/2006
• Published: 10/08/2009
• Est. Priority Date: 06/27/2005
• Status: Active Grant

• Current Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
• Original Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
• Inventors: Boutriau, Dominique `, Poolman, Jan, Denoel, Philippe, Capiau, Carine, Biemans, Ralph Leon, Duvivier, Pierre
• Granted Patent: US 9,931,397 B2
• Time in Patent Office: Days
• US Class Current: 424/197.110
• 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 relates to an immunogenic composition comprising at least 2 conjugates of N. meningitidis capsular saccharide and protein carrier, wherein said conjugates comprise at least 2 different N. meningitidis capsular saccharides selected from the group consisting of MenA, MenC, MenY and MenW, wherein at least one capsular saccharide is conjugated to a protein carrier with a saccharide:protein ratio (w/w) between 1:2-1:5, and wherein at least one different capsular saccharide is conjugated to a protein carrier with a saccharide:protein ratio (w/w) between 5:1-1:1.99.

Claims

1. An immunogenic composition comprising at least 2 conjugates of N. meningitidis capsular saccharide and protein carrier, wherein said conjugates comprise at least 2 different N. meningitidis capsular saccharides selected from the group consisting of MenA, MenC, MenY and MenW, wherein at least one capsular saccharide is conjugated to a protein carrier with a saccharide:

protein ratio (w/w) between 1;

2-1;

5, and wherein at least one different capsular saccharide is conjugated to a protein carrier with a saccharide;

protein ratio (w/w) between 5;

1-1;

1.99.

2. The immunogenic composition of claim 1, wherein MenA and/or MenC is/are conjugated to a protein carrier(s) with a saccharide:

protein ratio (w/w) between 1;

2-1;

5, and wherein one or more different capsular saccharides is/are conjugated to a protein carrier(s) with a saccharide;

protein ratio (w/w) between 5;

1-1;

1.99.

3. The immunogenic composition of claim 1, wherein MenW is present and the ratio of Men W saccharide to carrier protein is between 5:

1-1;

1.99, 2;

1-1;

1.99, 1.5;

1-1;

1.8, 1;

1-1;

1.7, 1;

1.2-1;

1.6, or 1;

1.4-1;

1.5 (w/w).

4. The immunogenic composition of claim 1, wherein MenY is present and the ratio of Men Y saccharide to carrier protein is between 5:

1-1;

1.99, 2;

1-1;

1.99, 1.5;

1-1;

1.9, 1;

1-1;

1.8, 1;

1.1-1;

1.6, or 1;

1.3-1;

1.4 (w/w).

5. The immunogenic composition of claim 1, wherein MenA is present and the ratio of Men A saccharide to carrier protein is between 1:

2-1;

5, 1;

2.4-1;

4, 1;

2.7-1;

3.5, or 1;

2.9-1;

3.1 (w/w).

6. The immunogenic composition of claim 1, wherein MenC is present and the ratio of Men C saccharide to carrier protein is between 5:

1-1;

1.99, 2;

1-1;

1.99, 1.5;

1-1;

1.8, 1.3;

1-1;

1.6, 1.2;

1-1;

1.4, or 1.1;

1-1;

1.2 (w/w).

7. The immunogenic composition of claim 1, wherein MenC is present and the ratio of Men C saccharide to carrier protein is between 1:

2-1;

5, 1;

2.5-1;

4.5, 1;

2.7-1;

4.3,1;

3-1;

4, or 1;

3.3-1;

3.5 (w/w).

8. The immunogenic composition of claim 1, wherein one or more capsular saccharides is/are conjugated through a linker to a carrier protein(s), and wherein one or more different capsular saccharides is/are directly conjugated to a carrier protein(s).

9. The immunogenic composition of claim 8, wherein one or more capsular saccharides is/are selected from a first group consisting of MenA and MenC which is/are conjugated through a linker to a carrier protein(s), and wherein one or more different capsular saccharides is/are selected from a second group consisting of MenC, MenY and MenW which is/are directly conjugated to a carrier protein(s).

14. The immunogenic composition of claim 1 wherein each N. meningitidis capsular saccharide is conjugated to a carrier protein independently selected from the group consisting of tetanus toxoid (TT), diphtheria toxoid (DT), CRM197, fragment C of TT and protein D.

15. The immunogenic composition of claim 14 wherein each N. meningitidis capsular saccharide is conjugated to the same carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT and protein D.

17. The immunogenic composition of claim 1 wherein each N. meningitidis capsular saccharide is separately conjugated to a separate carrier protein.

18. The immunogenic composition of claim 1 comprising two N. meningitidis capsular saccharide conjugates wherein each of the two capsular saccharides is separately, directly conjugated to a separate carrier protein.

19. The immunogenic composition of claim 18 wherein Men W and MenY, MenW and MenC, MenY and MenC, or MenW and MenC and MenY are directly conjugated to a carrier protein.

20. The immunogenic composition of claim 18 wherein two N. meningitidis saccharide conjugates are directly conjugated by CDAP chemistry.

21. The immunogenic composition of claim 1, comprising two N. meningitidis capsular saccharide conjugates wherein each of the two capsular saccharides is separately conjugated to the carrier protein via a linker.

33. The immunogenic composition of claim 1, wherein the average size of each N. meningitidis saccharide before conjugation is above 50 kDa.

47. The immunogenic composition of claim 1, further comprising a H. influenzae b capsular saccharide (Hib) conjugated to a carrier protein.

63. The immunogenic composition of claim 47 wherein the Hib conjugate is present in a lower dose than the dose of each of the at least two further bacterial saccharide conjugates.

75. The immunogenic composition of claim 1 comprising a N. meningitidis serogroup B outer membrane vesicle preparation or capsular saccharide.

76. A vaccine comprising the immunogenic composition of claim 1 and a pharmaceutically acceptable excipient.

77. 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, Haemophilus influenzae and Neisseria meningitidis, said kit comprising a first container comprising:

tetanus toxoid (TT),

diphtheria toxoid (DT), and

whole-cell or acellular pertussis components

and a second container comprising;

the immunogenic composition of claim 1.

78. A process for making the vaccine of claim 76 comprising the step of mixing the immunogenic composition of claim 1 with a pharmaceutically acceptable exipient.

79. A method of immunising a human host against disease caused by Neisseria meningitidis infection comprising administering to the host an immunoprotective dose of the immunogenic composition of claim 1.

80. A method of treating or preventing a disease caused by Neisseria meningitidis infection comprising administering to a patient in need thereof the immunogenic composition of claim 1.

10-13. -13. (canceled)

16. (canceled)

22-32. -32. (canceled)

34-46. -46. (canceled)

48-62. -62. (canceled)

64-74. -74. (canceled)

81. (canceled)

82. An immunogenic composition comprising at least 2 different saccharides conjugates, wherein each saccharide is conjugated to a carrier protein individually, wherein the carrier protein in each of the 2 conjugates is of the same type, wherein one or more saccharide(s) is/are conjugated to the carrier protein wherein the saccharide:

protein ratio (w/w) is between 1;

2-1;

5, and one or more different saccharides is/are conjugated to the carrier protein wherein the saccharide;

protein ratio (w/w) is between 5;

1-1;

1.99.

83. The immunogenic composition of claim 82, wherein one or more saccharide(s) is/are conjugated to the carrier protein via a first type of chemical group on the protein carrier, and wherein one or more saccharide(s) is/are conjugated to the carrier protein via a second type of chemical group on the protein carrier.

84. The immunogenic composition of claim 83, wherein the one or more saccharide(s) conjugated via the first type of chemical group on the protein carrier, is/are different to the one or more saccharide(s) conjugated via the second type of chemical group on the protein carrier.

85. An immunogenic composition of claim 84, wherein one or more saccharide(s) is/are conjugated to the carrier protein via a carboxyl group on the protein carrier, and one or more saccharide(s) is/are conjugated to the carrier protein via an amino group on the protein carrier.

86. An immunogenic composition of claim 83, wherein the first and second type of chemical group on the protein carrier are present on separate B- and/or T-cell epitopes on the carrier protein.

87. An immunogenic composition of claim 82, wherein the saccharides are selected from a group consisting of:

N. meningitidis serogroup A capsular saccharide (MenA), N. meningitidis serogroup C capsular saccharide (MenC), N. meningitidis serogroup Y capsular saccharide (MenY), N. meningitidis serogroup W capsular saccharide (MenW), Group B Streptococcus group I capsular saccharide, Group B Streptococcus group II capsular saccharide, Group B Streptococcus group III capsular saccharide, Group B Streptococcus group IV capsular saccharide, Group B Streptococcus group V capsular saccharide, Staphylococcus aureus type 5 capsular saccharide, Staphylococcus aureus type 8 capsular saccharide, Vi saccharide from Salmonella typhi, N. meningitidis LPS (such as L3 and/or L2), M. catarrhalis LPS, H. influenzae LPS, and from any of the capsular pneumococcal saccharides such as from serotype;

1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F or 33F.

88-116. -116. (canceled)