NO320157B1 - Fremgangsmate for a minimalisere nedbrytning av aktivert protein C, samt stabilt farmasoytisk preparat omfattende aktivert protein C og vandig opplosning av dette. - Google Patents
Fremgangsmate for a minimalisere nedbrytning av aktivert protein C, samt stabilt farmasoytisk preparat omfattende aktivert protein C og vandig opplosning av dette. Download PDFInfo
- Publication number
- NO320157B1 NO320157B1 NO19950018A NO950018A NO320157B1 NO 320157 B1 NO320157 B1 NO 320157B1 NO 19950018 A NO19950018 A NO 19950018A NO 950018 A NO950018 A NO 950018A NO 320157 B1 NO320157 B1 NO 320157B1
- Authority
- NO
- Norway
- Prior art keywords
- activated protein
- apc
- protein
- solution
- activity
- Prior art date
Links
- 101800004937 Protein C Proteins 0.000 title claims abstract description 50
- 101800001700 Saposin-D Proteins 0.000 title claims abstract description 50
- 229960000856 protein c Drugs 0.000 title claims abstract description 50
- 238000000034 method Methods 0.000 title claims abstract description 24
- 102100036546 Salivary acidic proline-rich phosphoprotein 1/2 Human genes 0.000 title claims abstract 9
- 230000015556 catabolic process Effects 0.000 title claims description 6
- 239000007864 aqueous solution Substances 0.000 title claims description 4
- 238000006731 degradation reaction Methods 0.000 title claims description 3
- 230000008569 process Effects 0.000 title description 2
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 36
- 239000000243 solution Substances 0.000 claims description 22
- 239000011780 sodium chloride Substances 0.000 claims description 18
- 239000000872 buffer Substances 0.000 claims description 12
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 8
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical group CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 claims description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- 239000001509 sodium citrate Substances 0.000 claims description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 19
- 238000012545 processing Methods 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 abstract description 3
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- 238000009472 formulation Methods 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 3
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- 238000011084 recovery Methods 0.000 abstract 1
- 102000017975 Protein C Human genes 0.000 description 41
- 230000003024 amidolytic effect Effects 0.000 description 16
- 101500025568 Homo sapiens Saposin-D Proteins 0.000 description 15
- 229940100689 human protein c Drugs 0.000 description 15
- 239000007983 Tris buffer Substances 0.000 description 14
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 14
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- 238000001994 activation Methods 0.000 description 7
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- 102000010911 Enzyme Precursors Human genes 0.000 description 5
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- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
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- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 108010000499 Thromboplastin Proteins 0.000 description 3
- 102000002262 Thromboplastin Human genes 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
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- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
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- MKWKNSIESPFAQN-UHFFFAOYSA-N N-cyclohexyl-2-aminoethanesulfonic acid Chemical compound OS(=O)(=O)CCNC1CCCCC1 MKWKNSIESPFAQN-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
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- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 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
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4866—Protein C (3.4.21.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6464—Protein C (3.4.21.69)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21069—Protein C activated (3.4.21.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17783294A | 1994-01-05 | 1994-01-05 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO950018D0 NO950018D0 (no) | 1995-01-03 |
| NO950018L NO950018L (no) | 1995-07-06 |
| NO320157B1 true NO320157B1 (no) | 2005-11-07 |
Family
ID=22650141
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19950018A NO320157B1 (no) | 1994-01-05 | 1995-01-03 | Fremgangsmate for a minimalisere nedbrytning av aktivert protein C, samt stabilt farmasoytisk preparat omfattende aktivert protein C og vandig opplosning av dette. |
| NO2006006C NO2006006I1 (no) | 1994-01-05 | 2006-05-02 | Aktivert protein C |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO2006006C NO2006006I1 (no) | 1994-01-05 | 2006-05-02 | Aktivert protein C |
Country Status (29)
| Country | Link |
|---|---|
| EP (2) | EP1087011A3 (uk) |
| JP (1) | JP3778588B2 (uk) |
| KR (1) | KR950032287A (uk) |
| CN (1) | CN1109891A (uk) |
| AT (1) | ATE201045T1 (uk) |
| AU (1) | AU1003195A (uk) |
| BR (1) | BR9500017A (uk) |
| CA (1) | CA2139468C (uk) |
| CO (1) | CO4600680A1 (uk) |
| CZ (1) | CZ1395A3 (uk) |
| DE (2) | DE10299053I2 (uk) |
| DK (1) | DK0662513T3 (uk) |
| ES (1) | ES2156190T3 (uk) |
| FI (1) | FI115635B (uk) |
| GR (1) | GR3036277T3 (uk) |
| HU (1) | HUT70465A (uk) |
| IL (1) | IL112236A (uk) |
| LU (2) | LU90993I2 (uk) |
| NL (1) | NL300108I2 (uk) |
| NO (2) | NO320157B1 (uk) |
| NZ (1) | NZ270271A (uk) |
| PE (1) | PE43995A1 (uk) |
| PL (1) | PL180703B1 (uk) |
| PT (1) | PT662513E (uk) |
| RU (1) | RU2167936C2 (uk) |
| SI (1) | SI0662513T1 (uk) |
| UA (1) | UA39178C2 (uk) |
| YU (1) | YU295A (uk) |
| ZA (1) | ZA9514B (uk) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1557463A1 (en) * | 1997-04-28 | 2005-07-27 | Eli Lilly & Company | Improved methods for processing activated protein C |
| US6630137B1 (en) | 1997-04-28 | 2003-10-07 | Eli Lilly And Company | Activated protein C formulations |
| UA55448C2 (uk) * | 1997-04-28 | 2003-04-15 | Елі Ліллі Енд Компані | Стійка ліофілізована лікарська форма з активованим білком с (варіанти) та виріб, який її містить |
| US7204981B2 (en) | 2000-03-28 | 2007-04-17 | Eli Lilly And Company | Methods of treating diseases with activated protein C |
| CA2410567A1 (en) | 2000-05-24 | 2001-11-29 | Eli Lilly And Company | Formulations and use of activated protein c and protein c zymogen for treating hypercoagulable states |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT402262B (de) * | 1991-06-20 | 1997-03-25 | Immuno Ag | Arzneimittel enthaltend aktiviertes protein c |
-
1994
- 1994-12-22 NZ NZ270271A patent/NZ270271A/xx unknown
-
1995
- 1995-01-03 AU AU10031/95A patent/AU1003195A/en not_active Abandoned
- 1995-01-03 NO NO19950018A patent/NO320157B1/no not_active IP Right Cessation
- 1995-01-03 CO CO95000126A patent/CO4600680A1/es unknown
- 1995-01-03 KR KR1019950000002A patent/KR950032287A/ko active IP Right Grant
- 1995-01-03 CZ CZ9513A patent/CZ1395A3/cs unknown
- 1995-01-03 ZA ZA9514A patent/ZA9514B/xx unknown
- 1995-01-03 IL IL11223695A patent/IL112236A/xx not_active IP Right Cessation
- 1995-01-03 PL PL95306671A patent/PL180703B1/pl unknown
- 1995-01-03 CA CA002139468A patent/CA2139468C/en not_active Expired - Fee Related
- 1995-01-03 PE PE1995258411A patent/PE43995A1/es not_active Application Discontinuation
- 1995-01-04 EP EP00203385A patent/EP1087011A3/en not_active Withdrawn
- 1995-01-04 SI SI9530503T patent/SI0662513T1/xx unknown
- 1995-01-04 EP EP95300042A patent/EP0662513B1/en not_active Expired - Lifetime
- 1995-01-04 FI FI950044A patent/FI115635B/fi not_active IP Right Cessation
- 1995-01-04 PT PT95300042T patent/PT662513E/pt unknown
- 1995-01-04 ES ES95300042T patent/ES2156190T3/es not_active Expired - Lifetime
- 1995-01-04 DE DE2002199053 patent/DE10299053I2/de active Active
- 1995-01-04 RU RU95100178/13A patent/RU2167936C2/ru active
- 1995-01-04 DK DK95300042T patent/DK0662513T3/da active
- 1995-01-04 JP JP00008695A patent/JP3778588B2/ja not_active Expired - Fee Related
- 1995-01-04 AT AT95300042T patent/ATE201045T1/de active
- 1995-01-04 CN CN95101130A patent/CN1109891A/zh active Pending
- 1995-01-04 HU HU9500021A patent/HUT70465A/hu unknown
- 1995-01-04 BR BR9500017A patent/BR9500017A/pt not_active IP Right Cessation
- 1995-01-04 YU YU295A patent/YU295A/sh unknown
- 1995-01-04 UA UA95018011A patent/UA39178C2/uk unknown
- 1995-01-04 DE DE69520844T patent/DE69520844T2/de not_active Expired - Lifetime
-
2001
- 2001-07-24 GR GR20010401126T patent/GR3036277T3/el unknown
-
2002
- 2002-12-03 NL NL300108C patent/NL300108I2/nl unknown
- 2002-12-18 LU LU90993C patent/LU90993I2/fr unknown
- 2002-12-18 LU LU90992C patent/LU90992I2/fr unknown
-
2006
- 2006-05-02 NO NO2006006C patent/NO2006006I1/no unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| SPCF | Filing of supplementary protection certificate |
Free format text: PRODUCT NAME: XIGRIS (DROTRECOGIN ALFA); NAT. REG. NO/DATE: EU102225001 20020913; FIRST ERG. NO/DATE: EU , 5590801 20020627 Spc suppl protection certif: 2006006 Filing date: 20060502 |
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| MM1K | Lapsed by not paying the annual fees |