DE69828330T2 - Aktiviertes Protein C Formulierungen - Google Patents
Aktiviertes Protein C Formulierungen Download PDFInfo
- Publication number
- DE69828330T2 DE69828330T2 DE69828330T DE69828330T DE69828330T2 DE 69828330 T2 DE69828330 T2 DE 69828330T2 DE 69828330 T DE69828330 T DE 69828330T DE 69828330 T DE69828330 T DE 69828330T DE 69828330 T2 DE69828330 T2 DE 69828330T2
- Authority
- DE
- Germany
- Prior art keywords
- formulation according
- formulation
- activated protein
- apc
- sucrose
- Prior art date
- 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 - Lifetime
Links
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- 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)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Vascular Medicine (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4525597P | 1997-04-28 | 1997-04-28 | |
| US45255P | 1997-04-28 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69828330D1 DE69828330D1 (de) | 2005-02-03 |
| DE69828330T2 true DE69828330T2 (de) | 2005-10-13 |
Family
ID=21936854
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69828330T Expired - Lifetime DE69828330T2 (de) | 1997-04-28 | 1998-04-28 | Aktiviertes Protein C Formulierungen |
Country Status (34)
| Country | Link |
|---|---|
| US (4) | US6162629A (OSRAM) |
| EP (2) | EP0875252B1 (OSRAM) |
| JP (2) | JP4383547B2 (OSRAM) |
| KR (2) | KR100564189B1 (OSRAM) |
| CN (2) | CN1227025C (OSRAM) |
| AR (2) | AR012010A1 (OSRAM) |
| AT (1) | ATE285788T1 (OSRAM) |
| AU (2) | AU743531B2 (OSRAM) |
| BR (2) | BR9809292A (OSRAM) |
| CA (2) | CA2287267C (OSRAM) |
| CO (2) | CO4940438A1 (OSRAM) |
| CZ (1) | CZ298429B6 (OSRAM) |
| DE (1) | DE69828330T2 (OSRAM) |
| DK (1) | DK0875252T3 (OSRAM) |
| EA (2) | EA004881B1 (OSRAM) |
| EG (1) | EG23685A (OSRAM) |
| ES (1) | ES2234072T3 (OSRAM) |
| HU (2) | HUP0003401A3 (OSRAM) |
| ID (2) | ID23172A (OSRAM) |
| IL (2) | IL132502A0 (OSRAM) |
| IN (2) | IN187157B (OSRAM) |
| MY (2) | MY118591A (OSRAM) |
| NO (2) | NO995134L (OSRAM) |
| NZ (2) | NZ500346A (OSRAM) |
| PE (2) | PE86299A1 (OSRAM) |
| PL (2) | PL195642B1 (OSRAM) |
| PT (1) | PT875252E (OSRAM) |
| SI (1) | SI0875252T1 (OSRAM) |
| SV (2) | SV1998000051A (OSRAM) |
| TR (2) | TR199902631T2 (OSRAM) |
| TW (2) | TWI242443B (OSRAM) |
| UA (2) | UA73071C2 (OSRAM) |
| WO (2) | WO1998048818A1 (OSRAM) |
| ZA (2) | ZA983497B (OSRAM) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA983497B (en) | 1997-04-28 | 1999-10-25 | Lilly Co Eli | Activated protein c formulations. |
| US6630137B1 (en) * | 1997-04-28 | 2003-10-07 | Eli Lilly And Company | Activated protein C formulations |
| HUP0001237A3 (en) * | 1997-10-20 | 2002-01-28 | Lilly Co Eli | Methods for treating vascular disorders |
| US6815533B1 (en) | 1998-07-31 | 2004-11-09 | Eli Lilly And Company | Cryogranulation of activated protein C |
| WO2000029014A1 (en) * | 1998-11-13 | 2000-05-25 | Eli Lilly And Company | Method of treating heparin-induced thrombocytopenia |
| DE69906568T2 (de) * | 1998-11-20 | 2004-02-12 | Eli Lilly And Co., Indianapolis | Behandlung von hämorrhagischem virusfieber mit protein c |
| WO2000030676A1 (en) * | 1998-11-23 | 2000-06-02 | Eli Lilly And Company | Method of treating sickle cell disease and thalassemia |
| ES2219094T3 (es) * | 1998-12-10 | 2004-11-16 | Eli Lilly And Company | Uso de proteina c para el tratamiento de la purpura trombocitopenica y el sindrome hemolitico uremico. |
| US6758938B1 (en) * | 1999-08-31 | 2004-07-06 | Micron Technology, Inc. | Delivery of dissolved ozone |
| 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 |
| EP1998266A3 (en) | 2001-02-19 | 2009-02-11 | Merck Patent GmbH | Method for identification of T-cell epitopes and use for preparing molecules with reduced immunogenicity |
| US7101982B2 (en) * | 2001-03-30 | 2006-09-05 | Immunex Corporation | Control of ph transitions during chromatography |
| EP1417055A4 (en) * | 2001-07-19 | 2007-09-26 | Dmi Biosciences Inc | USE OF COPPER CHELATORS TO PREVENT THE INACTIVATION OF PROTEIN C |
| US20030073636A1 (en) * | 2001-09-19 | 2003-04-17 | Oklahoma Medical Research Foundation | Method of treating diabetes |
| AU2002327649A1 (en) | 2001-09-19 | 2003-04-01 | Mcmaster University | Treatment of sepsis with tafi |
| DE10149030A1 (de) * | 2001-10-05 | 2003-04-10 | Viscum Ag | Stabile galenische gefriergetrocknete Arzneimittelzubereitung von rViscumin |
| KR20050036867A (ko) | 2001-10-15 | 2005-04-20 | 카이론 코포레이션 | 조직인자경로 억제제（ｔｆｐｉ）의 투여에 의한 중증폐렴의 치료 |
| BR0215216A (pt) | 2001-12-21 | 2004-11-16 | Novo Nordisk Healthcare Ag | Composição aquosa lìquida, método para preparar uma composição aquosa lìquida de um polipeptìdeo de fator vii, uso de uma composição aquosa lìquida, e, método para o tratamento de uma sìndrome de resposta ao fator vii |
| JP2005528351A (ja) * | 2002-03-08 | 2005-09-22 | イーライ・リリー・アンド・カンパニー | 活性化プロテインｃ製剤 |
| KR20050013148A (ko) | 2002-06-21 | 2005-02-02 | 노보 노르디스크 에이/에스 | 인자 ⅶ 폴리펩티드의 안정화된 고체 조성물 |
| CA2502378A1 (en) * | 2002-10-29 | 2004-05-13 | Alza Corporation | Stabilized, solid-state polypeptide particles |
| US20070142272A1 (en) * | 2003-01-24 | 2007-06-21 | Zlokovic Berislav V | Neuroprotective activity of activated protein c independent of its anticoagulant activity |
| US7897734B2 (en) | 2003-03-26 | 2011-03-01 | Novo Nordisk Healthcare Ag | Method for the production of proteins |
| WO2004112828A1 (en) * | 2003-06-25 | 2004-12-29 | Novo Nordisk Health Care Ag | Liquid composition of factor vii polypeptides |
| CA2560103A1 (en) * | 2004-03-17 | 2005-11-24 | Chiron Corporation | Treatment of severe community-acquired pneumonia by administration of tissue factor pathway inhibitor (tfpi) |
| JP2008507561A (ja) * | 2004-07-23 | 2008-03-13 | ザ ユニバーシティ オブ ロチェスター | 活性化プロテインｃによる、脳内のプラスミノゲン活性化因子の不都合な作用の阻害 |
| US20090148458A1 (en) * | 2005-06-23 | 2009-06-11 | The University Of British Columbia | Coagulation factor iii polymorphisms associated with prediction of subject outcome and response to therapy |
| ES2386972T3 (es) * | 2006-05-31 | 2012-09-10 | Genzyme Corporation | Uso de polisacáridos para la estimulación de la actividad enzimática |
| EP2041338A4 (en) * | 2006-06-09 | 2009-09-30 | Univ British Columbia | INTERFERON GAMMA POLYMORPHISMS AS INDICATORS OF RESULT IN SERIOUSLY SICK SUBJECTS |
| ATE512660T1 (de) * | 2007-03-05 | 2011-07-15 | Cadila Healthcare Ltd | Zusammensetzungen mit peg-interferon-alpha- konjugaten und raffinose als kryoschutzmittel |
| KR20100014674A (ko) | 2007-03-29 | 2010-02-10 | 아보트 러보러터리즈 | 결정성 항-사람 ｉｌ-12 항체 |
| NZ585702A (en) * | 2007-11-30 | 2013-08-30 | Abbott Lab | Protein formulations and methods of making same |
| US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
| WO2009089620A1 (en) * | 2008-01-15 | 2009-07-23 | The Universityof British Columbia | Protein c rs2069915 as a response predictor to survival and administration of activated protein c or protein c-like compound |
| AU2009319856A1 (en) * | 2008-11-28 | 2010-06-03 | Abbvie Inc. | Stable antibody compositions and methods for stabilizing same |
| WO2012068519A2 (en) | 2010-11-19 | 2012-05-24 | Sirius Genomics Inc. | Markers associated with response to activated protein c administration, and uses thereof |
| WO2012149197A2 (en) | 2011-04-27 | 2012-11-01 | Abbott Laboratories | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
| WO2013151727A1 (en) | 2012-04-03 | 2013-10-10 | Smith Medical Asd, Inc. | Heparin-bulking agent compositions and methods thereof |
| US9181572B2 (en) | 2012-04-20 | 2015-11-10 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
| US9150645B2 (en) | 2012-04-20 | 2015-10-06 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
| US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
| US9249182B2 (en) | 2012-05-24 | 2016-02-02 | Abbvie, Inc. | Purification of antibodies using hydrophobic interaction chromatography |
| IN2014DN11181A (OSRAM) | 2012-07-04 | 2015-10-02 | Univ Sydney | |
| US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
| AU2013309506A1 (en) | 2012-09-02 | 2015-03-12 | Abbvie Inc. | Methods to control protein heterogeneity |
| SG11201507230PA (en) | 2013-03-12 | 2015-10-29 | Abbvie Inc | Human antibodies that bind human tnf-alpha and methods of preparing the same |
| US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
| US8921526B2 (en) | 2013-03-14 | 2014-12-30 | Abbvie, Inc. | Mutated anti-TNFα antibodies and methods of their use |
| US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
| WO2015051293A2 (en) | 2013-10-04 | 2015-04-09 | Abbvie, Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
| US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
| US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
| US8946395B1 (en) | 2013-10-18 | 2015-02-03 | Abbvie Inc. | Purification of proteins using hydrophobic interaction chromatography |
| US20150139988A1 (en) | 2013-11-15 | 2015-05-21 | Abbvie, Inc. | Glycoengineered binding protein compositions |
| JP2017513944A (ja) | 2014-04-16 | 2017-06-01 | ジージー バイオテック エルエルシー | 異常な皮膚瘢痕化の治療 |
| AU2015246656B2 (en) | 2014-04-16 | 2020-06-18 | Zz Biotech Llc | Use of APC analogue for wound healing |
| US11058750B2 (en) | 2015-12-03 | 2021-07-13 | Mor Research Applications Ltd. | Compositions and methods for treatment of ocular diseases |
| US12343387B2 (en) * | 2016-06-01 | 2025-07-01 | Servier IP UK Limited | Formulations of polyalkylene oxide-asparaginase and methods of making and using the same |
| CN108159399B (zh) * | 2017-12-29 | 2020-07-24 | 华中科技大学同济医学院附属同济医院 | 一种凝血蛋白酶aPC在防治糖尿病心肌病药物中的应用 |
| WO2023119230A1 (en) | 2021-12-22 | 2023-06-29 | L'oreal | Coagulation pathway and nicotinamide-adenine dinucleotide pathway modulating compositions and methods of their use |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4775624A (en) * | 1985-02-08 | 1988-10-04 | Eli Lilly And Company | Vectors and compounds for expression of human protein C |
| US4849403A (en) * | 1985-05-29 | 1989-07-18 | Pentapharm Ag | Protein C activator, methods of preparation and use thereof |
| US5516650A (en) | 1985-06-27 | 1996-05-14 | Zymogenetics, Inc. | Production of activated protein C |
| AT399095B (de) * | 1986-03-27 | 1995-03-27 | Vukovich Thomas Dr | Verfahren zur auftrennung von proteinen mittels gradientenelution und vorrichtung zur durchführung des verfahrens |
| US5175087A (en) * | 1987-07-06 | 1992-12-29 | Biopool International, Inc. | Method of performing tissue plasminogen activator assay |
| CA1329760C (en) * | 1987-10-29 | 1994-05-24 | Ted C. K. Lee | Plasma and recombinant protein formulations in high ionic strength media |
| US4877608A (en) * | 1987-11-09 | 1989-10-31 | Rorer Pharmaceutical Corporation | Pharmaceutical plasma protein formulations in low ionic strength media |
| US4992373A (en) * | 1987-12-04 | 1991-02-12 | Eli Lilly And Company | Vectors and compounds for direct expression of activated human protein C |
| JP2739050B2 (ja) * | 1988-01-28 | 1998-04-08 | ヘキスト薬品工業株式会社 | 抗血液凝固剤 |
| JPH01226900A (ja) * | 1988-03-08 | 1989-09-11 | Green Cross Corp:The | プロテインｃの精製方法 |
| DE3823519A1 (de) * | 1988-07-12 | 1990-01-18 | Basf Ag | Verfahren zur reinigung von aktiviertem protein c |
| US4981952A (en) * | 1988-10-04 | 1991-01-01 | Eli Lilly And Company | Method for the purification of vitamin K-dependent proteins |
| US5093117A (en) * | 1989-01-24 | 1992-03-03 | Baxter International Inc. | Compositions and method for the treatment or prophylaxis of sepsis or septic shock |
| WO1991012320A1 (en) * | 1990-02-09 | 1991-08-22 | Zymogenetics, Inc. | Activated protein c with truncated light chain |
| IL97312A (en) * | 1990-02-23 | 1999-01-26 | Lilly Co Eli | A method of generating a polypeptide in an eukaryotic vector AND recombinant surrogate cell containing an enhanced transcriptional control unit based on the primary late adenovirus coefficient |
| US5040862A (en) | 1990-05-07 | 1991-08-20 | Corning Incorporated | Method of trimming optical power |
| AT402262B (de) * | 1991-06-20 | 1997-03-25 | Immuno Ag | Arzneimittel enthaltend aktiviertes protein c |
| US5413732A (en) * | 1991-08-19 | 1995-05-09 | Abaxis, Inc. | Reagent compositions for analytical testing |
| MY110664A (en) | 1992-05-21 | 1999-01-30 | Lilly Co Eli | Protein c derivatives |
| DE4234295A1 (de) * | 1992-10-12 | 1994-04-14 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| US5395923A (en) * | 1993-02-23 | 1995-03-07 | Haemacure-Biotech, Inc. | Process for the obtention of a biological adhesive made of concentrated coagulation factors by "salting-out" |
| JP2886061B2 (ja) * | 1993-10-29 | 1999-04-26 | 財団法人化学及血清療法研究所 | プロテインｃもしくは活性化プロテインｃの安定化方法及び安定化組成物 |
| JP3043558B2 (ja) * | 1993-10-29 | 2000-05-22 | 財団法人化学及血清療法研究所 | ヒト活性化プロテインｃ調製物及びその製法 |
| JPH07165605A (ja) * | 1993-12-16 | 1995-06-27 | Teijin Ltd | 活性化プロテインｃバイアル |
| NZ270271A (en) * | 1994-01-05 | 1996-07-26 | Lilly Co Eli | Minimizing protein c degradation |
| JPH08301786A (ja) * | 1995-05-11 | 1996-11-19 | Mochida Pharmaceut Co Ltd | 吸収性骨疾患予防・治療剤 |
| WO1997020043A1 (en) | 1995-11-30 | 1997-06-05 | Zymogenetics, Inc. | Protein c production in transgenic animals |
| ZA983497B (en) * | 1997-04-28 | 1999-10-25 | Lilly Co Eli | Activated protein c formulations. |
| HUP0001237A3 (en) | 1997-10-20 | 2002-01-28 | Lilly Co Eli | Methods for treating vascular disorders |
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1998
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- 1998-04-24 ID IDW991133A patent/ID22933A/id unknown
- 1998-04-24 PL PL98336889A patent/PL195090B1/pl not_active IP Right Cessation
- 1998-04-24 EA EA199900980A patent/EA002149B1/ru not_active IP Right Cessation
- 1998-04-24 TR TR1999/02529T patent/TR199902529T2/xx unknown
- 1998-04-24 KR KR1019997009835A patent/KR100564189B1/ko not_active Expired - Fee Related
- 1998-04-24 KR KR10-1999-7009933A patent/KR100450856B1/ko not_active Expired - Fee Related
- 1998-04-24 NZ NZ337828A patent/NZ337828A/en unknown
- 1998-04-26 EG EG45198A patent/EG23685A/xx active
- 1998-04-27 MY MYPI98001900A patent/MY118591A/en unknown
- 1998-04-27 SV SV1998000051A patent/SV1998000051A/es not_active Application Discontinuation
- 1998-04-27 SV SV1998000050A patent/SV1998000050A/es not_active Application Discontinuation
- 1998-04-27 IN IN752CA1998 patent/IN187157B/en unknown
- 1998-04-27 IN IN751CA1998 patent/IN183798B/en unknown
- 1998-04-27 MY MYPI98001899A patent/MY120984A/en unknown
- 1998-04-28 DE DE69828330T patent/DE69828330T2/de not_active Expired - Lifetime
- 1998-04-28 TW TW087106558A patent/TWI242443B/zh not_active IP Right Cessation
- 1998-04-28 DK DK98303311T patent/DK0875252T3/da active
- 1998-04-28 EP EP98303311A patent/EP0875252B1/en not_active Expired - Lifetime
- 1998-04-28 TW TW087106549A patent/TW585871B/zh not_active IP Right Cessation
- 1998-04-28 PT PT98303311T patent/PT875252E/pt unknown
- 1998-04-28 EP EP98303312A patent/EP0875563A3/en not_active Withdrawn
- 1998-04-28 SI SI9830752T patent/SI0875252T1/xx unknown
- 1998-04-28 ES ES98303311T patent/ES2234072T3/es not_active Expired - Lifetime
- 1998-04-28 AT AT98303311T patent/ATE285788T1/de not_active IP Right Cessation
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1999
- 1999-10-21 NO NO995134A patent/NO995134L/no not_active Application Discontinuation
- 1999-10-25 NO NO995198A patent/NO995198L/no not_active Application Discontinuation
-
2000
- 2000-09-14 US US09/662,232 patent/US6395270B1/en not_active Expired - Lifetime
- 2000-09-21 US US09/667,570 patent/US6436397B1/en not_active Expired - Lifetime
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