IMMUNOGENIC COMPOSITION
First Claim
1. An immunogenic composition comprising at least 2 different N. meningitidis capsular saccharides, wherein one or more is/are selected from a first group consisting of MenA, MenC, MenY and MenW which is/are conjugated through a linker to a carrier protein(s), and one or more different saccharides is/are selected from a second group consisting of MenA, MenC, MenY and MenW which is/are directly conjugated to a carrier protein(s).
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Abstract
The present application discloses an immunogenic composition comprising at least 2 different N. meningitidis capsular saccharides, wherein one or more is/are selected from a first group consisting of MenA, MenC, MenY and MenW which is/are conjugated to a protein carrier(s) wherein the saccharide:protein ratio (w/w) is between 1:2-1:5, and one or more different saccharides is/are selected from a second group consisting of MenA, MenC, MenY and MenW which is/are conjugated to a protein carrier(s) wherein the saccharide:protein ratio (w/w) is between 5:1-1:1.99.
104 Citations
106 Claims
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1. An immunogenic composition comprising at least 2 different N. meningitidis capsular saccharides, wherein one or more is/are selected from a first group consisting of MenA, MenC, MenY and MenW which is/are conjugated through a linker to a carrier protein(s), and one or more different saccharides is/are selected from a second group consisting of MenA, MenC, MenY and MenW which is/are directly conjugated to a carrier protein(s).
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 106)
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2. The immunogenic composition of claim 1 comprising at least 2 different N. meningitidis capsular saccharides, wherein one or more 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 one or more different saccharides is/are selected from a second group consisting of MenC, MenY and MenW which is/are directly conjugated to a carrier protein(s).
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3. The immunogenic composition of claim 2 comprising MenA capsular saccharide conjugated through a linker to a carrier protein, and MenC capsular saccharide directly conjugated to a carrier protein.
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4. The immunogenic composition of claim 2 comprising MenC capsular saccharide conjugated through a linker to a carrier protein, and MenY capsular saccharide directly conjugated to a carrier protein.
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5. The immunogenic composition of claim 2 comprising MenA and MenC capsular saccharides conjugated through a linker to a carrier protein(s), and MenY and Men W capsular saccharides directly conjugated to a carrier protein(s).
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6. The immunogenic composition of claim 2 comprising MenA capsular saccharide conjugated through a linker to a carrier protein, and MenC, MenY and Men W capsular saccharides directly conjugated to a carrier protein(s).
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7. The immunogenic composition of any preceding claim wherein each N. meningitidis capsular saccharide is conjugated to a carrier protein independently selected from the group consisting of TT, DT, CRM197, fragment C of TT and protein D.
-
8. The immunogenic composition of any preceding claim 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.
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9. The immunogenic composition of any preceding claim wherein each N. meningitidis capsular saccharide is conjugated to TT.
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10. The immunogenic composition of any preceding claim wherein each N. meningitidis capsular saccharide is separately conjugated to a separate carrier protein.
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11. The immunogenic composition of any preceding claim wherein each N. meningitidis capsular saccharide conjugate has a saccharide:
- carrier ratio of 1;
5-5;
1 or 1;
1-1;
4 (w/w).
- carrier ratio of 1;
-
12. The immunogenic composition of any preceding claim wherein at least one, two or three N. meningitidis capsular saccharide conjugate(s) is directly conjugated to a carrier protein.
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13. The immunogenic composition of claim 12 wherein Men W and/or MenY, MenW and/or MenC, MenY and/or MenC, or MenW and MenC and MenY are directly conjugated to a carrier protein.
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14. The immunogenic composition of claim 12 or 13 wherein at least one, two or three N. meningitidis saccharide conjugate(s) is directly conjugated by CDAP chemistry.
-
15. The immunogenic composition of any one of claims 12-14 wherein the ratio of Men W and/or Y saccharide to carrier protein is between 1:
- 0.5 and 1;
2 (w/w).
- 0.5 and 1;
-
16. The immunogenic composition of any one of claims 12-15 wherein the ratio of MenC saccharide to carrier protein is between 1:
- 0.5 and 1;
2 (w/w).
- 0.5 and 1;
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17. The immunogenic composition of any one of claims 1-16, wherein at least one, two or three N. meningitidis capsular saccharide(s) are conjugated to the carrier protein via a linker.
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18. The immunogenic composition of claim 17 wherein the linker is bifunctional.
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19. The immunogenic composition of claim 17 or 18 wherein the linker has two reactive amino groups.
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20. The immunogenic composition of claim 17 or 18 wherein the linker has two reactive carboxylic acid groups.
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21. The immunogenic composition of claim 17 or 18 wherein the linker has a reactive amino group at one end and a reactive carboxylic acid group at the other end.
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22. The immunogenic composition of claim 17-21 wherein the linker has between 4 and 12 carbon atoms.
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23. The immunogenic composition of claim 17 or 18 wherein the linker is ADH.
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24. The immunogenic composition of any one of claims 17-23 wherein the or each N. meningitidis capsular saccharide(s) conjugated via a linker are conjugated to the linker with CDAP chemistry.
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25. The immunogenic composition of claim 17-24 wherein the carrier protein is conjugated to the linker using carbodiimide chemistry, optionally using EDAC.
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26. The immunogenic composition of any one of claims 17-25 wherein the or each N. meningitidis capsular saccharide is conjugated to the linker before the carrier protein is conjugated to the linker.
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27. The immunogenic composition of any one of claims 17-26 wherein MenA is conjugated to a carrier protein via a linker.
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28. The immunogenic composition of claim 27 wherein the ratio of MenA saccharide to carrier protein is between 1:
- 2 and 1;
5 (w/w).
- 2 and 1;
-
29. The immunogenic composition of any one of claims 17-28 wherein MenC is conjugated to a carrier protein via a linker.
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30. The immunogenic composition of claim 34 wherein the ratio of MenC saccharide to carrier protein is between 1:
- 2 and 1;
5 (w/w).
- 2 and 1;
-
31. The immunogenic composition of any preceding claim comprising N. meningitidis capsular saccharides from at least two of serogroups A, C, W135 and Y conjugated to a carrier protein to produce a N. meningitidis capsular saccharide conjugate, wherein the average size of each N. meningitidis saccharide is above 50 kDa, 75 kDa, 100 kDa, 110 kDa, 120 kDa or 130 kDa.
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32. The immunogenic composition of claim 31, wherein each N. meningitidis saccharide is either a native polysaccharide or is sized by a factor of no more than x10.
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33. The immunogenic composition of claim 31 or 32 wherein each N. meningitidis capsular saccharide is a native polysaccharide.
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34. The immunogenic composition of claim 31 or 32, wherein at least one, two, three or four N. meningitidis capsular saccharide(s) is sized by microfluidization.
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35. The immunogenic composition of claim 31 or 32 wherein each N. meningitidis capsular saccharide is sized by a factor of no more than x10.
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36. The immunogenic composition of claim 31 or 32 wherein the N. meningitidis conjugates are made from a mixture of native polysaccharides and saccharides that are sized by a factor of no more than x10.
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37. The immunogenic composition of claim 36 wherein capsular saccharide from serogroup Y is sized by a factor of no more than x10.
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38. The immunogenic composition of claim 36 or 37 wherein capsular saccharides from serogroups A and C are native polysaccharides and saccharides from serogroups W135 and Y are sized by a factor of no more than x10.
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39. The immunogenic composition of claims 31-38 wherein the average size of each N. meningitidis capular saccharide is between 50 kDa and 300 KDa or 50 kDa and 200 kDa.
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40. The immunogenic composition of claims 31-39 comprising a MenA capsular saccharide having an average size of above 50 kDa, 75 kDa, 100 kDa or an average size of between 50-100 kDa or 55-90 KDa or 60-80 kDa.
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41. The immunogenic composition of claims 31-40 comprising a MenC capsular saccharide having an average size of above 50 kDa, 75 kDa, 100 kDa or between 100-200 kDa, 100-150 kDa, 80-120 kDa, 90-110 kDa, 150-200 kDa, 120-240 kDa, 140-220 kDa, 160-200 kDa or 190-200 kDa.
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42. The immunogenic composition of claims 31-41 comprising a MenY capsular saccharide, having an average size of above 50 kDa, 75 kDa, 100 kDa or between 60-190 kDa or 70-180 kDa or 80-170 kDa or 90-160 kDa or 100-150 kDa, 110-145 kDa or 120-140 kDa.
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43. The immunogenic composition of claims 31-42 comprising a MenW capsular saccharide having an average size of above 50 kDa, 75 kDa, 100 kDa or between 60-190 kDa or 70-180 kDa or 80-170 kDa or 90-160 kDa or 100-150 kDa, 140-180 kDa, 150-170 kDa or 110-140 kDa.
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44. The immunogenic composition of any preceding claim wherein the dose of each saccharide conjugate is between 2 and 20 μ
- g, 3 and 10 μ
g or 4 and 7 μ
g of saccharide.
- g, 3 and 10 μ
-
45. The immunogenic composition of any preceding claim further comprising a H. influenzae b capsular saccharide (Hib) conjugated to a carrier protein.
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46. The immunogenic composition of claim 45 wherein the H. influenzae b capsular saccharide is conjugated to a carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT and protein D.
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47. The immunogenic composition of claim 45 or 46, wherein the Hib saccharide is conjugated to the same carrier protein as for at least one, two, three or all of the N. meningitidis capsular saccharide conjugates.
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48. The immunogenic composition of claims 45-47, wherein the Hib saccharide is conjugated to TT.
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49. The immunogenic composition of claims 45-48 wherein the ratio of Hib to carrier protein in the Hib capsular saccharide conjugate is between 1:
- 5 and 5;
1 (w/w).
- 5 and 5;
-
50. The immunogenic composition of claim 49 wherein the ratio of Hib to carrier protein in the Hib capsular saccharide conjugate is between 1:
- 1 and 1;
4, 1;
2 and 1;
3.5 or around 1;
3 (w/w).
- 1 and 1;
-
51. The immunogenic composition of claims 45-50 wherein the Hib capsular saccharide is conjugated to the carrier protein via a linker.
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52. The immunogenic composition of claim 51 wherein the linker is bifunctional.
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53. The immunogenic composition of claim 51 or 52 wherein the linker has two reactive amino groups.
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54. The immunogenic composition of claim 51 or 52 wherein the linker has two reactive carboxylic acid groups.
-
55. The immunogenic composition of claim 51 or 52 wherein the linker has a reactive amino group at one end and a reactive carboxylic acid group at the other end.
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56. The immunogenic composition of any one of claims 51-55 wherein the linker has between 4 and 12 carbon atoms.
-
57. The immunogenic composition of claim 51 or 52 wherein the linker is ADH.
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58. The immunogenic composition of any one of claims 45-57 wherein the Hib saccharide is conjugated to the carrier protein or linker using CNBr or CDAP.
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59. The immunogenic composition of claim 51-58 wherein the carrier protein is conjugated to the Hib saccharide via the linker using a method comprising carbodiimide chemistry, optionally EDAC chemistry.
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60. The immunogenic composition of any one of claims 45-59 comprising a Hib saccharide conjugate and at least two further bacterial saccharide conjugates wherein the Hib conjugate is present in a lower dose than the mean dose of the at least two further bacterial saccharide conjugates.
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61. The immunogenic composition of claim 60 wherein the Hib conjugate is present in a lower dose than the dose of each of the at least two further bacterial saccharide conjugates.
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62. The immunogenic composition of claim 60 or 61 wherein the at least two further bacterial saccharide conjugates comprises N. meningitidis serogroup C capsular saccharide (MenC) conjugate.
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63. The immunogenic composition of any one of claims 60-62 wherein the at least two further bacterial saccharide conjugates comprises N. meningitidis serogroup Y capsular saccharide (MenY) conjugate.
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64. The immunogenic composition of any one of claims 60-63 wherein the at least two further bacterial saccharide conjugates comprises N. meningitidis serogroup A capsular saccharide (MenA) conjugate.
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65. The immunogenic composition of any one of claims 60-64 wherein the at least two further bacterial saccharide conjugates comprises N. meningitidis serogroup W135 capsular saccharide (MenW) conjugate.
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66. The immunogenic composition of any one of claims 60-65 wherein the at least two further bacterial saccharide conjugates comprise 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, 1A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F.
-
67. The immunogenic composition of any one of claims 60-66 wherein the at least two further bacterial saccharide conjugates comprise a S. typhi Vi capsular saccharide.
-
68. The immunogenic composition of any one of claims 60-67 wherein the dose of the Hib saccharide conjugate is between 0.1 and 9 μ
- g, 1 and 5 μ
g or 2 and 3 μ
g of saccharide.
- g, 1 and 5 μ
-
69. The immunogenic composition of any one of claims 60-68 wherein the dose of each of the at least two further saccharide conjugates is between 2 and 20 μ
- g, 3 and 10 μ
g or 4 and 7 μ
g of saccharide.
- g, 3 and 10 μ
-
70. The immunogenic composition of any one of claims 60-69 wherein the saccharide dose of the Hib saccharide conjugate is less than 90%, 75% or 60%, between 20% and 60% or around 50% of the mean saccharide dose of the at least two further saccharide conjugates.
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71. The immunogenic composition of any one of claims 60-70 wherein the saccharide dose of the Hib saccharide conjugate is less than 90%, 75% or 60% or is between 20-60% or is around 50% of the saccharide dose of each of the at least two further saccharide conjugates.
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72. The immunogenic composition of any one of claims 60-71 wherein the same carrier protein is used in the Hib conjugate and two or more of the at least two further bacterial saccharide conjugates.
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73. The immunogenic composition of any one of claims 1-72 comprising a N. meningitidis serogroup B outer membrane vesicle preparation or capsular saccharide.
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74. A vaccine comprising the immunogenic composition of any one of claims 1-73 and a pharmaceutically acceptable excipient.
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75. 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 wholecell or acellular pertussis components and a second container comprising: the immunogenic composition of any one of claims 1-73.
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76. A process for making the vaccine of claim 74 comprising the step of mixing the immunogenic composition of any one of claims 1-73 with a pharmaceutically acceptable exipient.
-
77. 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 or vaccine of claims 1-75.
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78. The immunogenic composition of claims 1-73 for use in the treatment or prevention of disease caused by Neisseria meningitidis infection.
-
79. The use of the immunogenic composition of any one of claims 1-73 in the manufacture of a medicament for the treatment or prevention of diseases caused by Neisseria meningitidis infection.
-
106. The immunogenic composition of claims 96-105, which is an immunogenic composition of claims 1-74.
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2. The immunogenic composition of claim 1 comprising at least 2 different N. meningitidis capsular saccharides, wherein one or more 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 one or more different saccharides is/are selected from a second group consisting of MenC, MenY and MenW which is/are directly conjugated to a carrier protein(s).
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80. An immunogenic composition comprising at least 2 different saccharides conjugated separately to the same type of carrier protein, 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 one or more saccharide(s) is/are conjugated to the carrier protein via a second type of chemical group on the protein carrier.
- View Dependent Claims (81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105)
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81. The immunogenic composition of claim 80, wherein the one or more saccharide(s) conjugated to the carrier protein via the first type of chemical group on the protein carrier, are different to the one or more saccharide(s) conjugated to the carrier protein via the second type of chemical group on the protein carrier.
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82. An immunogenic composition of claim 80 or 81 comprising at least 2 different saccharides conjugated separately to the same carrier protein, 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.
-
83. An immunogenic composition of claims 80-82, 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.
-
84. An immunogenic composition of claims 80-83, 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 11 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.
-
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 11 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;
-
85. The immunogenic composition of claims 80-84 wherein the carrier protein is selected from the group consisting of:
- TT, DT, CRM197, fragment C of TT and protein D.
-
86. The immunogenic composition of claims 80-84 wherein the carrier protein is TT.
-
87. An immunogenic composition of claims 80-86 comprising at least 2 different N. meningitidis capsular saccharides, wherein one or more is/are selected from a first group consisting of MenA and MenC which is/are conjugated to the carrier protein via the first type of chemical group on the protein carrier, and one or more different saccharides is/are selected from a second group consisting of MenC, MenY and MenW which is/are conjugated to the carrier protein via the second type of chemical group on the protein carrier.
-
88. An immunogenic composition of claim 87, wherein the first type of chemical group is a carboxyl group on the protein carrier, and the second type of chemical group is an amino group on the protein carrier.
-
89. The immunogenic composition of claims 87-88 comprising MenA conjugated via the first type of chemical group, and MenC conjugated via the second type of chemical group.
-
90. The immunogenic composition of claims 87-88 comprising MenC conjugated via the first type of chemical group, and MenY conjugated via the second type of chemical group.
-
91. The immunogenic composition of claims 87-88 comprising MenA conjugated via the first type of chemical group, and MenC, MenY and MenW conjugated via the second type of chemical group.
-
92. The immunogenic composition of claims 87-88 comprising MenA and MenC conjugated via the first type of chemical group, and MenY and MenW conjugated via the second type of chemical group.
-
93. The immunogenic composition of claims 87-92 further comprising a capsular saccharide from H. influenzae type b (Hib) conjugated to a carrier protein.
-
94. The immunogenic composition of claim 93, wherein Hib is conjugated to the same type of carrier protein as the N. meningitidis saccharides.
-
95. The immunogenic composition of claim 94, wherein Hib is conjugated to the carrier protein via either the first or second type of chemical group.
-
96. The immunogenic composition of claims 80-95, wherein the saccharides conjugated via the first type of chemical group do so through a linker, and the saccharides conjugated via the second type of chemical group do so directly, or wherein the saccharides conjugated via the second type of chemical group do so through a linker, and the saccharides conjugated via the first type of chemical group do so directly.
-
97. The immunogenic composition of claim 96 wherein the linker is bifunctional.
-
98. The immunogenic composition of claim 96 or 97, wherein the linker has between 4 and 12 carbon atoms.
-
99. The immunogenic composition of claims 96-98 wherein the linker has two reactive amino groups.
-
100. The immunogenic composition of claims 96-98 wherein the linker has two reactive carboxylic acid groups.
-
101. The immunogenic composition of claim claims 96-98 wherein the linker has a reactive amino group at one end and a reactive carboxylic acid group at the other end.
-
102. The immunogenic composition of claims 96-98 wherein the linker is ADH.
-
103. The immunogenic composition of claims 96-102, wherein the or each capsular saccharide(s) conjugated via a linker is conjugated to the linker with CDAP chemistry.
-
104. The immunogenic composition of claims 96-103, wherein the carrier protein is conjugated to the linker using carbodiimide chemistry, optionally using EDAC.
-
105. The immunogenic composition of claims 96-104, wherein the or each capsular saccharide is conjugated to the linker before the carrier protein is conjugated to the linker, or the linker is conjugated to the saccharide before it is conjugated to the carrier protein.
-
81. The immunogenic composition of claim 80, wherein the one or more saccharide(s) conjugated to the carrier protein via the first type of chemical group on the protein carrier, are different to the one or more saccharide(s) conjugated to the carrier protein via the second type of chemical group on the protein carrier.
Specification
- Resources
-
Current AssigneeGlaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
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Original AssigneeGlaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
-
InventorsPoolman, Jan, Denoel, Philippe, Capiau, Carine, Biemans, Ralph Leon, Duvivier, Pierre, Boutriau, Dominique
-
Granted Patent
-
Time in Patent OfficeDays
-
Field of Search
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US Class Current424/197.110
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CPC Class CodesA61K 2039/545 characterised by the dose, ...A61K 2039/55 characterised by the host/r...A61K 2039/575 humoral responseA61K 2039/6037 Bacterial toxins, e.g. diph...A61K 2039/62 characterised by the link b...A61K 2039/627 characterised by the linkerA61K 2039/70 Multivalent vaccineA61K 39/0017 Combination vaccines based ...A61K 39/0018 Combination vaccines based ...A61K 39/05 Actinobacteria, e.g. Actino...A61K 39/08 Clostridium, e.g. Clostridi...A61K 39/092 StreptococcusA61K 39/095 NeisseriaA61K 39/099 BordetellaA61K 39/102 Pasteurellales, e.g. Actino...A61K 39/116 Polyvalent bacterial antigensA61K 39/12 Viral antigensA61K 39/145 Orthomyxoviridae, e.g. infl...A61K 39/292 Serum hepatitis virus, hepa...A61K 39/385 Haptens or antigens, bound ...A61P 11/04 : for throat disordersA61P 11/14 : Antitussive agentsA61P 31/00 : Antiinfectives, i.e. antibi...A61P 31/04 : Antibacterial agentsA61P 31/12 : AntiviralsA61P 31/20 : for DNA virusesA61P 37/00 : Drugs for immunological or ...A61P 37/04 : ImmunostimulantsA61P 43/00 : Drugs for specific purposes...C07H 3/00 : Compounds containing only h...C12N 2730/10134 : Use of virus or viral compo...C12N 2760/16234 : Use of virus or viral compo...C12N 2760/16271 : Demonstrated in vivo effectC12N 2770/32634 : Use of virus or viral compo...C12N 7/00 : Viruses; Bacteriophages; Co...Y02A 50/30 : Against vector-borne diseas...