CA2767919C - Procedes de preparation d'un glatiramere - Google Patents

Procedes de preparation d'un glatiramere Download PDF

Info

Publication number: CA2767919C
Authority: CA; Canada
Prior art keywords: mixture; solvent; protected; polypeptide; carboxyanhydride
Prior art date: 2004-10-29
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA2767919A

Other languages

English (en)

Other versions

CA2767919A1 (fr

Inventor

Anup Kumar Ray

Hiren Kumar V. Patel

Johannes Ludescher

Mariappan Anbazhagan

Mahendra R. Patel

Ingolf Macher

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sandoz AG

Original Assignee

Sandoz AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2004-10-29

Filing date

2005-10-27

Publication date

2013-10-08

2005-10-27 Application filed by Sandoz AG filed Critical Sandoz AG

2005-10-27 Priority claimed from CA2583589A external-priority patent/CA2583589C/fr

2006-05-11 Publication of CA2767919A1 publication Critical patent/CA2767919A1/fr

2013-10-08 Application granted granted Critical

2013-10-08 Publication of CA2767919C publication Critical patent/CA2767919C/fr

2025-10-27 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

108010072051 Glatiramer Acetate Proteins 0.000 title claims abstract description 164
238000000034 method Methods 0.000 title claims abstract description 72
YLOCGHYTXIINAI-XKUOMLDTSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 YLOCGHYTXIINAI-XKUOMLDTSA-N 0.000 title claims description 104
229940042385 glatiramer Drugs 0.000 title claims description 92
229920001184 polypeptide Polymers 0.000 claims abstract description 175
108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 175
102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 175
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims abstract description 72
FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 claims abstract description 59
229960003776 glatiramer acetate Drugs 0.000 claims abstract description 55
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 51
150000003839 salts Chemical class 0.000 claims abstract description 43
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims abstract description 37
229960003767 alanine Drugs 0.000 claims abstract description 37
229960004441 tyrosine Drugs 0.000 claims abstract description 37
QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims abstract description 34
QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims abstract description 34
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims abstract description 9
235000019766 L-Lysine Nutrition 0.000 claims abstract description 4
239000004472 Lysine Substances 0.000 claims abstract description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 152
239000000203 mixture Substances 0.000 claims description 143
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 95
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 72
239000002253 acid Substances 0.000 claims description 68
239000002904 solvent Substances 0.000 claims description 66
229930195714 L-glutamate Natural products 0.000 claims description 62
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 49
239000003513 alkali Substances 0.000 claims description 38
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims description 37
229910001854 alkali hydroxide Inorganic materials 0.000 claims description 36
239000000126 substance Substances 0.000 claims description 27
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 24
239000003880 polar aprotic solvent Substances 0.000 claims description 23
239000003999 initiator Substances 0.000 claims description 20
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 19
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
230000000379 polymerizing effect Effects 0.000 claims description 17
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 15
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 15
238000004519 manufacturing process Methods 0.000 claims description 14
WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 claims description 13
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
FJSKXQVRKZTKSI-UHFFFAOYSA-N 2,3-dimethylfuran Chemical compound CC=1C=COC=1C FJSKXQVRKZTKSI-UHFFFAOYSA-N 0.000 claims description 6
CWMOGYSHLXSGDW-UHFFFAOYSA-N 3,4-dichlorothiolane 1-oxide Chemical compound ClC1C(CS(=O)C1)Cl CWMOGYSHLXSGDW-UHFFFAOYSA-N 0.000 claims description 6
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
235000010216 calcium carbonate Nutrition 0.000 claims description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 3
239000000920 calcium hydroxide Substances 0.000 claims description 3
229910001861 calcium hydroxide Inorganic materials 0.000 claims description 3
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 3
239000000347 magnesium hydroxide Substances 0.000 claims description 3
229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 3
239000003586 protic polar solvent Substances 0.000 claims description 3
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims description 2
229910001863 barium hydroxide Inorganic materials 0.000 claims description 2
NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 claims description 2
229910000020 calcium bicarbonate Inorganic materials 0.000 claims description 2
229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
229910000032 lithium hydrogen carbonate Inorganic materials 0.000 claims description 2
HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 claims description 2
QWDJLDTYWNBUKE-UHFFFAOYSA-L magnesium bicarbonate Chemical compound [Mg+2].OC([O-])=O.OC([O-])=O QWDJLDTYWNBUKE-UHFFFAOYSA-L 0.000 claims description 2
235000014824 magnesium bicarbonate Nutrition 0.000 claims description 2
229910000022 magnesium bicarbonate Inorganic materials 0.000 claims description 2
239000002370 magnesium bicarbonate Substances 0.000 claims description 2
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 2
239000001095 magnesium carbonate Substances 0.000 claims description 2
229910000021 magnesium carbonate Inorganic materials 0.000 claims description 2
235000014380 magnesium carbonate Nutrition 0.000 claims description 2
235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
239000011736 potassium bicarbonate Substances 0.000 claims description 2
229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
235000011181 potassium carbonates Nutrition 0.000 claims description 2
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
229940086066 potassium hydrogencarbonate Drugs 0.000 claims description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
235000017550 sodium carbonate Nutrition 0.000 claims description 2
BGGHCRNCRWQABU-JTQLQIEISA-N (2s)-2-amino-5-oxo-5-phenylmethoxypentanoic acid Chemical compound OC(=O)[C@@H](N)CCC(=O)OCC1=CC=CC=C1 BGGHCRNCRWQABU-JTQLQIEISA-N 0.000 claims 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
239000011591 potassium Substances 0.000 claims 1
229910052700 potassium Inorganic materials 0.000 claims 1
229960003975 potassium Drugs 0.000 claims 1
239000000243 solution Substances 0.000 description 98
229960000583 acetic acid Drugs 0.000 description 50
235000011054 acetic acid Nutrition 0.000 description 45
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 42
239000007787 solid Substances 0.000 description 36
239000000047 product Substances 0.000 description 33
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 32
238000003756 stirring Methods 0.000 description 31
239000012528 membrane Substances 0.000 description 25
238000000502 dialysis Methods 0.000 description 22
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 19
239000007864 aqueous solution Substances 0.000 description 19
239000012458 free base Substances 0.000 description 18
229940038717 copaxone Drugs 0.000 description 17
239000000725 suspension Substances 0.000 description 15
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
229910021529 ammonia Inorganic materials 0.000 description 14
229940043279 diisopropylamine Drugs 0.000 description 14
238000011026 diafiltration Methods 0.000 description 13
239000012634 fragment Substances 0.000 description 13
125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 13
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 12
239000012071 phase Substances 0.000 description 12
239000000523 sample Substances 0.000 description 12
DQUHYEDEGRNAFO-QMMMGPOBSA-N (2s)-6-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CCCCN DQUHYEDEGRNAFO-QMMMGPOBSA-N 0.000 description 11
150000007513 acids Chemical class 0.000 description 10
230000015572 biosynthetic process Effects 0.000 description 10
238000010511 deprotection reaction Methods 0.000 description 10
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 10
238000002360 preparation method Methods 0.000 description 10
150000001412 amines Chemical class 0.000 description 9
238000003776 cleavage reaction Methods 0.000 description 9
238000009295 crossflow filtration Methods 0.000 description 9
WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 9
235000011167 hydrochloric acid Nutrition 0.000 description 9
229910000042 hydrogen bromide Inorganic materials 0.000 description 9
230000007017 scission Effects 0.000 description 9
238000006116 polymerization reaction Methods 0.000 description 8
239000000872 buffer Substances 0.000 description 7
239000001913 cellulose Substances 0.000 description 7
229920002678 cellulose Polymers 0.000 description 7
239000007788 liquid Substances 0.000 description 7
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 6
239000005695 Ammonium acetate Substances 0.000 description 6
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
229930195725 Mannitol Natural products 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
229940043376 ammonium acetate Drugs 0.000 description 6
235000019257 ammonium acetate Nutrition 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
239000000594 mannitol Substances 0.000 description 6
235000010355 mannitol Nutrition 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
238000000746 purification Methods 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
239000007858 starting material Substances 0.000 description 6
239000012362 glacial acetic acid Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
230000001363 autoimmune Effects 0.000 description 4
208000015114 central nervous system disease Diseases 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
201000010099 disease Diseases 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
239000003480 eluent Substances 0.000 description 4
238000004108 freeze drying Methods 0.000 description 4
230000002757 inflammatory effect Effects 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
159000000021 acetate salts Chemical class 0.000 description 3
235000004279 alanine Nutrition 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
238000013375 chromatographic separation Methods 0.000 description 3
229920001577 copolymer Polymers 0.000 description 3
238000002523 gelfiltration Methods 0.000 description 3
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 3
150000004678 hydrides Chemical class 0.000 description 3
229910000040 hydrogen fluoride Inorganic materials 0.000 description 3
229910052500 inorganic mineral Inorganic materials 0.000 description 3
229940098779 methanesulfonic acid Drugs 0.000 description 3
235000010755 mineral Nutrition 0.000 description 3
239000011707 mineral Substances 0.000 description 3
239000012429 reaction media Substances 0.000 description 3
238000012546 transfer Methods 0.000 description 3
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
238000005292 vacuum distillation Methods 0.000 description 3
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
241000694440 Colpidium aqueous Species 0.000 description 2
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
239000004677 Nylon Substances 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
239000008351 acetate buffer Substances 0.000 description 2
238000005903 acid hydrolysis reaction Methods 0.000 description 2
150000003973 alkyl amines Chemical class 0.000 description 2
239000008367 deionised water Substances 0.000 description 2
229910021641 deionized water Inorganic materials 0.000 description 2
WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 2
239000003814 drug Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
230000036571 hydration Effects 0.000 description 2
238000006703 hydration reaction Methods 0.000 description 2
239000005457 ice water Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
201000006417 multiple sclerosis Diseases 0.000 description 2
OBYVIBDTOCAXSN-UHFFFAOYSA-N n-butan-2-ylbutan-2-amine Chemical compound CCC(C)NC(C)CC OBYVIBDTOCAXSN-UHFFFAOYSA-N 0.000 description 2
229910000069 nitrogen hydride Inorganic materials 0.000 description 2
229920001778 nylon Polymers 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
238000005191 phase separation Methods 0.000 description 2
239000008363 phosphate buffer Substances 0.000 description 2
239000012488 sample solution Substances 0.000 description 2
238000000926 separation method Methods 0.000 description 2
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
KNCHTBNNSQSLRV-YFKPBYRVSA-N (2s)-6-amino-2-[(2,2,2-trifluoroacetyl)amino]hexanoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)C(F)(F)F KNCHTBNNSQSLRV-YFKPBYRVSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
229940124602 FDA-approved drug Drugs 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
239000002585 base Substances 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
238000002144 chemical decomposition reaction Methods 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000005227 gel permeation chromatography Methods 0.000 description 1
229960002989 glutamic acid Drugs 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000008176 lyophilized powder Substances 0.000 description 1
229960003646 lysine Drugs 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000010926 purge Methods 0.000 description 1
238000011084 recovery Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000009901 transfer hydrogenation reaction Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1

Landscapes

Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA2767919A 2004-10-29 2005-10-27 Procedes de preparation d'un glatiramere Expired - Fee Related CA2767919C (fr)

Applications Claiming Priority (9)

Application Number	Priority Date	Filing Date	Title
US62334604P	2004-10-29	2004-10-29
US60/623,346		2004-10-29
US65153505P	2005-02-09	2005-02-09
US65137205P	2005-02-09	2005-02-09
US60/651,535		2005-02-09
US60/651,372		2005-02-09
US72390105P	2005-10-05	2005-10-05
US60/723,901		2005-10-05
CA2583589A CA2583589C (fr)	2004-10-29	2005-10-27	Procedes de preparation d'un glatiramere

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2583589A Division CA2583589C (fr)	2004-10-29	2005-10-27	Procedes de preparation d'un glatiramere

Publications (2)

Publication Number	Publication Date
CA2767919A1 CA2767919A1 (fr)	2006-05-11
CA2767919C true CA2767919C (fr)	2013-10-08

Family

ID=45774355

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2767919A Expired - Fee Related CA2767919C (fr)	2004-10-29	2005-10-27	Procedes de preparation d'un glatiramere

Country Status (1)

Country	Link
CA (1)	CA2767919C (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2009129018A1 (fr)	2008-04-16	2009-10-22	Momenta Pharmaceuticals, Inc.	Analyse de compositions copolymères d'acides aminés

2005
- 2005-10-27 CA CA2767919A patent/CA2767919C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2767919A1 (fr)	2006-05-11

Legal Events

Date	Code	Title	Description
2012-02-13	EEER	Examination request
2017-12-09	MKLA	Lapsed	Effective date: 20171027

Publication	Publication Date	Title
CA2583589C (fr)	2012-04-24	Procedes de preparation d'un glatiramere
JP2008518930A5 (fr)	2012-01-12
US7138490B2 (en)	2006-11-21	Block copolymer reduced in impurity content, polymeric carrier, pharmaceutical preparations in polymeric form and process for the preparation of the same
AU2006211510B8 (en)	2011-04-21	Process for producing polypeptide mixtures using hydrogenolysis
US8212002B2 (en)	2012-07-03	Synthesis of glatiramer acetate
EP2414384B2 (fr)	2023-05-03	Régulation de compositions de copolymères
WO2004043995A2 (fr)	2004-05-27	Procede de preparation de polypeptide 1
CA2767919A1 (fr)	2006-05-11	Procedes de preparation d'un glatiramere
WO2011139752A2 (fr)	2011-11-10	Préparation de polypeptides et de leurs sels
GB2478837A (en)	2011-09-21	Preparation of glatiramer
WO2010104789A1 (fr)	2010-09-16	Procédé de production de copolymères aléatoires de polyamino acides
WO2012114167A1 (fr)	2012-08-30	Procédés de préparation de l'acétate de glatiramère