DK2762489T3 - GLYCOSYLED POLYPEPTIDE AND PHARMACEUTICAL COMPOSITION CONTAINING SAME - Google Patents

Info

Publication number

DK2762489T3

DK2762489T3 DK12836998.0T DK12836998T DK2762489T3 DK 2762489 T3 DK2762489 T3 DK 2762489T3 DK 12836998 T DK12836998 T DK 12836998T DK 2762489 T3 DK2762489 T3 DK 2762489T3

Authority

DK

Denmark

Prior art keywords

leu

polypeptide

fmoc

binding

asn

Prior art date

2011-10-01

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• 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 410
• 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 344
• 229920001184 polypeptide Polymers 0.000 title claims abstract description 343
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 35
• 108090000467 Interferon-beta Proteins 0.000 claims abstract description 145
• 102000003996 Interferon-beta Human genes 0.000 claims abstract description 121
• 229960001388 interferon-beta Drugs 0.000 claims abstract description 121
• 238000000034 method Methods 0.000 claims abstract description 95
• 230000000694 effects Effects 0.000 claims abstract description 37
• 235000000346 sugar Nutrition 0.000 claims description 295
• 150000001413 amino acids Chemical class 0.000 claims description 194
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 114
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 99
• 238000004519 manufacturing process Methods 0.000 claims description 91
• 125000006239 protecting group Chemical group 0.000 claims description 54
• 239000000126 substance Substances 0.000 claims description 47
• 239000000203 mixture Substances 0.000 claims description 31
• 238000003786 synthesis reaction Methods 0.000 claims description 31
• SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 claims description 29
• SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 claims description 29
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
• 201000010099 disease Diseases 0.000 claims description 18
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 238000002360 preparation method Methods 0.000 claims description 7
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 6
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
• 150000003839 salts Chemical class 0.000 claims description 5
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• 206010008909 Chronic Hepatitis Diseases 0.000 claims description 4
• 208000006154 Chronic hepatitis C Diseases 0.000 claims description 4
• 206010016654 Fibrosis Diseases 0.000 claims description 4
• 208000005176 Hepatitis C Diseases 0.000 claims description 4
• 206010019755 Hepatitis chronic active Diseases 0.000 claims description 4
• 208000000172 Medulloblastoma Diseases 0.000 claims description 4
• 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 claims description 4
• 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 claims description 4
• 125000004849 alkoxymethyl group Chemical group 0.000 claims description 4
• 230000007882 cirrhosis Effects 0.000 claims description 4
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 4
• 208000010710 hepatitis C virus infection Diseases 0.000 claims description 4
• 201000006417 multiple sclerosis Diseases 0.000 claims description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
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• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 57
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• 239000013076 target substance Substances 0.000 description 42
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• QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 40
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 40
• 238000010511 deprotection reaction Methods 0.000 description 40
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 38
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• 235000018417 cysteine Nutrition 0.000 description 34
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• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 33
• PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 32
• XXMFJKNOJSDQBM-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;hydrate Chemical compound [OH3+].[O-]C(=O)C(F)(F)F XXMFJKNOJSDQBM-UHFFFAOYSA-N 0.000 description 31
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 31
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 31
• 125000003277 amino group Chemical group 0.000 description 31
• 238000010438 heat treatment Methods 0.000 description 31
• 210000004899 c-terminal region Anatomy 0.000 description 30
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• PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 29
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