DK2118145T3 - Modified saccharides - Google Patents

Info

Publication number

DK2118145T3

DK2118145T3 DK08737594.5T DK08737594T DK2118145T3 DK 2118145 T3 DK2118145 T3 DK 2118145T3 DK 08737594 T DK08737594 T DK 08737594T DK 2118145 T3 DK2118145 T3 DK 2118145T3

Authority

DK

Denmark

Prior art keywords

saccharide

groups

group

modified

protein

Prior art date

2007-01-11

Links

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• 150000001720 carbohydrates Chemical class 0.000 title claims description 222
• 230000000903 blocking effect Effects 0.000 claims description 137
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 117
• 150000002482 oligosaccharides Chemical class 0.000 claims description 114
• 229920001542 oligosaccharide Polymers 0.000 claims description 108
• 108090000623 proteins and genes Proteins 0.000 claims description 103
• 102000004169 proteins and genes Human genes 0.000 claims description 98
• 239000000203 mixture Substances 0.000 claims description 91
• 108091007433 antigens Proteins 0.000 claims description 83
• 102000036639 antigens Human genes 0.000 claims description 83
• 150000004676 glycans Chemical class 0.000 claims description 77
• 239000000427 antigen Substances 0.000 claims description 76
• 229920001282 polysaccharide Polymers 0.000 claims description 74
• 239000005017 polysaccharide Substances 0.000 claims description 74
• 125000000217 alkyl group Chemical group 0.000 claims description 73
• 238000000034 method Methods 0.000 claims description 70
• 150000002772 monosaccharides Chemical group 0.000 claims description 65
• 229960005486 vaccine Drugs 0.000 claims description 65
• 239000002775 capsule Substances 0.000 claims description 32
• 230000008569 process Effects 0.000 claims description 28
• 241000894006 Bacteria Species 0.000 claims description 20
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 18
• 102000014914 Carrier Proteins Human genes 0.000 claims description 17
• 108010078791 Carrier Proteins Proteins 0.000 claims description 17
• 241000588650 Neisseria meningitidis Species 0.000 claims description 17
• 125000003277 amino group Chemical group 0.000 claims description 15
• 125000003172 aldehyde group Chemical group 0.000 claims description 14
• 238000006268 reductive amination reaction Methods 0.000 claims description 14
• 241000921898 Neisseria meningitidis serogroup A Species 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 12
• ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims description 11
• 229940079593 drug Drugs 0.000 claims description 10
• 229910052799 carbon Inorganic materials 0.000 claims description 9
• 201000010099 disease Diseases 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
• 229910052739 hydrogen Inorganic materials 0.000 claims description 7
• 231100000699 Bacterial toxin Toxicity 0.000 claims description 6
• 239000000688 bacterial toxin Substances 0.000 claims description 6
• 238000007248 oxidative elimination reaction Methods 0.000 claims description 6
• 108010053187 Diphtheria Toxin Proteins 0.000 claims description 5
• 102000016607 Diphtheria Toxin Human genes 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 239000003054 catalyst Substances 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• 229930182470 glycoside Natural products 0.000 claims description 3
• 239000012646 vaccine adjuvant Substances 0.000 claims description 3
• 229940124931 vaccine adjuvant Drugs 0.000 claims description 3
• 206010027202 Meningitis bacterial Diseases 0.000 claims description 2
• 201000009904 bacterial meningitis Diseases 0.000 claims description 2
• 238000006257 total synthesis reaction Methods 0.000 claims description 2
• 230000001268 conjugating effect Effects 0.000 claims 1
• 229910052711 selenium Inorganic materials 0.000 claims 1
• 229910052717 sulfur Inorganic materials 0.000 claims 1
• 235000018102 proteins Nutrition 0.000 description 89
• -1 5-hydroxypentyl Chemical group 0.000 description 68
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• PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 21
• PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 20
• 238000006460 hydrolysis reaction Methods 0.000 description 20
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 18
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• 150000001875 compounds Chemical class 0.000 description 16
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• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 14
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• YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• OVRNDRQMDRJTHS-OZRXBMAMSA-N N-acetyl-beta-D-mannosamine Chemical group CC(=O)N[C@@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-OZRXBMAMSA-N 0.000 description 12
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• TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 12
• 238000006467 substitution reaction Methods 0.000 description 12
• 239000004094 surface-active agent Substances 0.000 description 12
• BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 11
• 238000009472 formulation Methods 0.000 description 11
• 125000000623 heterocyclic group Chemical group 0.000 description 11
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 11
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• 239000012064 sodium phosphate buffer Substances 0.000 description 11
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• 108010031133 Transferrin-Binding Protein A Proteins 0.000 description 10
• 210000004027 cell Anatomy 0.000 description 10
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• 102000004196 processed proteins & peptides Human genes 0.000 description 10
• 239000001397 quillaja saponaria molina bark Substances 0.000 description 10
• STCOOQWBFONSKY-UHFFFAOYSA-N tributyl phosphate Chemical compound CCCCOP(=O)(OCCCC)OCCCC STCOOQWBFONSKY-UHFFFAOYSA-N 0.000 description 10
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• 108010031127 Transferrin-Binding Protein B Proteins 0.000 description 9
• 238000007385 chemical modification Methods 0.000 description 9
• 238000003860 storage Methods 0.000 description 9
• 241001212279 Neisseriales Species 0.000 description 8
• 108091034117 Oligonucleotide Proteins 0.000 description 8
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 8
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 8
• 229940001007 aluminium phosphate Drugs 0.000 description 8
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 8
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• 125000005647 linker group Chemical group 0.000 description 8
• 108020004707 nucleic acids Proteins 0.000 description 8
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• 108010060123 Conjugate Vaccines Proteins 0.000 description 7
• 241000699670 Mus sp. Species 0.000 description 7
• 101710116435 Outer membrane protein Proteins 0.000 description 7
• PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 7
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• DTCUHIUXNIRDBQ-UHFFFAOYSA-N 4,5-dihydroxypentyl carbamate Chemical compound C(N)(OCCCC(CO)O)=O DTCUHIUXNIRDBQ-UHFFFAOYSA-N 0.000 description 6
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
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• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 5
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