DK2361924T3 - Fremgangsmåde til fremstillingen af blandinger af trifluoracetyl-glatirameracetat under anvendelse af oprenset hydrogenbromid - Google Patents
Fremgangsmåde til fremstillingen af blandinger af trifluoracetyl-glatirameracetat under anvendelse af oprenset hydrogenbromid Download PDFInfo
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- DK2361924T3 DK2361924T3 DK10194363.7T DK10194363T DK2361924T3 DK 2361924 T3 DK2361924 T3 DK 2361924T3 DK 10194363 T DK10194363 T DK 10194363T DK 2361924 T3 DK2361924 T3 DK 2361924T3
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- mixture
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- acetic acid
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- glatiramer acetate
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- 238000000034 method Methods 0.000 title claims abstract description 53
- 230000008569 process Effects 0.000 title claims abstract description 43
- 229960003776 glatiramer acetate Drugs 0.000 title claims description 122
- 108010072051 Glatiramer Acetate Proteins 0.000 title claims description 121
- -1 trifluoroacetyl glatiramer acetate Chemical compound 0.000 title claims description 22
- 238000002360 preparation method Methods 0.000 title claims description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 title description 77
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- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 33
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- 125000003798 L-tyrosyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4713—Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Rehabilitation Therapy (AREA)
- Transplantation (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Claims (32)
1.1 en fremgangsmåde til at opnå en blanding af trifluoracetyl-glatirameracetat, hvor blandingen har en ønsket gennemsnitsmolekylvægt og hvor under fremgangsmåden en batch af en blanding af polypeptider, der hver består af alanin, γ-benzylglutamat, tyrosin og trifluoracetyllysin afbeskyttes med en opløsning af hydrogenbromid i eddikesyre, forbedringen omfattende anvendelse afen opløsning af hydrogenbromid i eddikesyre, hvilken opløsning omfatter mindre end 0,1% frit brom.
2. Fremgangsmåden ifølge krav 1, hvor forbedringen yderligere omfatter anvendelse af en opløsning af hydrogenbromid i eddikesyre der omfatter mindre end 500 ppm metalionurenheder.
3. I en fremgangsmåde til at opnå en blanding af trifluoracetyl-glatirameracetat, hvor blandingen har en ønsket gennemsnitsmolekylvægt og hvor under fremgangsmåden en batch af en blanding af polypeptider, der hver består af alanin, y-benzylglutamat, tyrosin og trifluoracetyllysin afbeskyttes med en opløsning af hydrogenbromid i eddikesyre, forbedringen omfattende anvendelse afen opløsning af hydrogenbromid i eddikesyre, hvilken opløsning omfatter mindre end 500 ppm metalionurenheder.
4. Fremgangsmåde til fremstilling afen blanding af trifluoracetyl-glatirameracetat, hvor blandingen har en ønsket gennemsnitsmolekylvægt omfattende afbeskyttelse af en blanding af polypeptider hver bestående af alanin, y-benzylglutamat, tyrosin og trifluoracetyllysin med en opløsning af hydrogenbromid i eddikesyre, hvilken opløsning omfatter mindre end 0,5% frit brom og mindre end 500 ppm metalionurenheder.
5. Fremgangsmåde til at opnå et farmaceutisk præparat indeholdende en blanding af glatirameracetat, og hvor blandingen har en ønsket gennemsnitsmolekylvægt, der omfatter at a) polymerisere N-carboxyanhydriderne af tyrosin, alanin, γ-benzylglutamat og N-trifluoracetyllysin til at danne en blanding af beskyttede polypeptider; b) afbeskytte de beskyttede polypeptider med en opløsning af hydrogenbromid i eddikesyre, hvilken opløsning omfatter mindre end 0,5% frit brom og mindre end 1000 ppm metalionurenheder, til at danne en blanding af trifluoracetylpolypeptider; c) omsætte blandingen af trifluoracetylpolypeptider med vandigt piperidin til at danne en opløsning af vandig blanding af polypeptider, der hver består af alanin, glutaminsyre, tyrosin og lysin; og d) oprense blandingen af polypeptider.
6. Fremgangsmåde til fremstilling af glatirameracetat omfattende trinnene at: a) polymerisere N-carboxyanhydriderne af tyrosin, alanin, γ-benzylglutamat og N-trifluoracetyllysin til at danne beskyttet glatirameracetat; b) afbeskytte beskyttet glatirameracetat med en opløsning af hydrogenbromid i eddikesyre, hvilken opløsning omfatter mindre end 0,5% frit brom og mindre end 1000 ppm metalionurenheder, til at danne trifluoracetyl-glatirameracetat; c) omsætte triflu o racetyl-glatirameracetat med vandig piperidin for at danne en opløsning af glatirameracetat; og d) oprense glatirameracetatet.
7. Fremgangsmåden ifølge et hvilket som helst af kravene 1-6, hvor opløsningen af hydrogenbromid i eddikesyre omfatter mindre end 0,05% frit brom, fortrinsvis mindre end 0,01% frit brom, mere fortrinsvis mindre end 0,001% frit brom, endnu mere fortrinsvis opløsningen af hydrogenbromid i eddikesyre er bromfri.
8. Fremgangsmåden ifølge krav 7, hvor opløsningen af hydrogenbromid i eddikesyre omfatter mindre end 100 ppm metalionurenheder.
9. Fremgangsmåden ifølge krav 8, hvor opløsningen af hydrogenbromid i eddikesyre omfatter mindre end 30 ppm metalionurenheder.
10. Fremgangsmåden ifølge krav 9, hvor opløsningen af hydrogenbromid i eddikesyre omfatter mindre end 20 ppm metalionurenheder.
11. Fremgangsmåden ifølge krav 10, hvor opløsningen af hydrogenbromid i eddikesyre omfatter mindre end 10 ppm metalionurenheder.
12. Fremgangsmåden ifølge krav 11, hvor opløsningen af hydrogenbromid i eddikesyre er fri for metalionurenheder.
13. Fremgangsmåden ifølge et hvilket som helst af kravene 1-12, hvor farven af opløsningen af hydrogenbromid i eddikesyre er mindre end 2000 APHA.
14. Fremgangsmåden ifølge krav 13, hvor farven af opløsningen af hydrogenbromid i eddikesyre er mindre end 1000 APHA.
15. Fremgangsmåden ifølge krav 14, hvor farven af opløsningen af hydrogenbromid i eddikesyre er mindre end 700 APHA.
16. Fremgangsmåden ifølge krav 15, hvor farven af opløsningen af hydrogenbromid i eddikesyre er mindre end 500 APHA.
17. Fremgangsmåden ifølge et hvilket som helst af kravene 1-16, hvor hydrogenbromidet i eddikesyreopløsningen fremstilles i en ikke-metallisk reaktor.
18. Fremgangsmåden ifølge et hvilket som helst af kravene 1-17, hvor hydrogenbromidet i eddikesyreopløsningen fremstilles i en glas-belagt eller Teflon- belagt reaktor.
19. Blanding af trifluoracetyl-glatirameracetat, hvor blandingen haren ønsket gennemsnitsmolekylvægt, ikke over 0,1% bromeret tyrosin og mindre end 1000 ppm metalionurenheder.
20. Blanding af g latira me racetat hvor blandingen har en ønsket molekylvægt og mindre end 1000 ppm metalionurenheder.
21. Blandingen ifølge et hvilket som helst kravene 19-20, hvor blandingen omfatter mindre end 500 ppm metalionurenheder.
22. Blandingen ifølge krav 21, hvor blandingen omfatter mindre end 100 ppm metalionurenheder.
23. Blandingen ifølge krav 22, hvor blandingen omfatter mindre end 30 ppm metalionurenheder.
24. Blandingen ifølge krav 23, hvor blandingen omfatter mindre end 20 ppm metalionurenheder.
25. Blandingen ifølge krav 24, hvor blandingen omfatter mindre end 10 ppm metalionurenheder.
26. Blandingen ifølge krav 25, hvor blandingen er fri for metalionurenheder.
27. Blandingen ifølge et hvilket som helst kravene 19-26, hvor farven af blandingen er mindre end 1000 APHA, fortrinsvis mindre end 700 APHA.
28. Blandingen ifølge krav 28, hvor farven af blandingen er mindre end 500 APHA.
29. Fremgangsmåde til fremstilling af et farmaceutisk præparat indeholdende en blanding af glatirameracetat, hvor blandingen har en forudbestemt procentandel af bromeret tyrosin der er acceptabel til inklusion i et farmaceutisk præparat, der omfatter opnåelse af en batch af glatirameracetat; måle procentandelen af bromeret tyrosin af batchen ved en fremgangsmåde omfattende a) hydrdolysere batchen for at opnå et hydrolysat; b) eluere hydrolysatet gennem en kromatografisk søjle; c) måle niveauet af bromtyrosin i hydrolysatet; d) fremstille prøveopløsninger af aminosyrekomponetnerne fra batchen og af bromtyrosin; e) eluere prøveopløsningerne gennem søjlen fra trin b); og f) beregne procentandelen af bromeret tyrosin i batchen; og inkludere i det farmaceutiske præparat en batch kun hvis dets procentandel af bromeret tyrosin måles til mindre end 0,3%.
30. Trifluoracetyl-glatirameracetat fremstillet ved fremgangsmåden ifølge et hvilket som helst af kravene 1-4 eller 7-18.
31. Glatirameracetat fremstillet ved fremgangsmåden ifølge et hvilket som helst af kravene 5-18.
32. Anvendelse af blandingen af trifluoracetyl glatirameracetat ifølge et hvilket som helst af kravene 19 eller 21-28 eller trifluoracetyl glatirameracetatet ifølge krav 30 i fremstillingen af glatirameracetat.
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| US60884304P | 2004-09-09 | 2004-09-09 | |
| EP10150124A EP2177528B1 (en) | 2004-09-09 | 2005-09-09 | Process for the preparation of mixtures of trifluoroacetyl glatiramer acetate using purified hydrobromic acid |
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| DK05791236.2T DK1799703T3 (da) | 2004-09-09 | 2005-09-09 | Fremgangsmåde til fremstilling af blandinger af polypeptider ved hjælp af oprenset hydrogenbromid |
| DK10150124.5T DK2177528T3 (da) | 2004-09-09 | 2005-09-09 | Fremgangsmåde til fremstilling af blandinger af trifluoracetylglatirameracetat ved anvendelse af oprenset hydrogenbromid |
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| DK10150124.5T DK2177528T3 (da) | 2004-09-09 | 2005-09-09 | Fremgangsmåde til fremstilling af blandinger af trifluoracetylglatirameracetat ved anvendelse af oprenset hydrogenbromid |
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| WO2006083608A1 (en) * | 2005-02-02 | 2006-08-10 | Teva Pharmaceutical Industries, Ltd. | Process for producing polypeptide mixtures using hydrogenolysis |
| CA2606194A1 (en) * | 2005-04-25 | 2006-11-02 | Yeda Research And Development Company | Markers associated with the therapeutic efficacy of glatiramer acetate |
| WO2007072865A1 (ja) | 2005-12-22 | 2007-06-28 | Pioneer Corporation | 施設情報配信装置、通信端末、施設情報配信方法、情報出力方法、プログラム、および記録媒体 |
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