UA72194C2 - Method of treatment for patients with acquired hypercoagulable state or acquired protein c deficiency - Google Patents
Method of treatment for patients with acquired hypercoagulable state or acquired protein c deficiency Download PDFInfo
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- UA72194C2 UA72194C2 UA2000042259A UA2000042259A UA72194C2 UA 72194 C2 UA72194 C2 UA 72194C2 UA 2000042259 A UA2000042259 A UA 2000042259A UA 2000042259 A UA2000042259 A UA 2000042259A UA 72194 C2 UA72194 C2 UA 72194C2
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Classifications
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- 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)
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- C12Y—ENZYMES
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Landscapes
- Health & Medical Sciences (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6254997P | 1997-10-20 | 1997-10-20 | |
| US6476597P | 1997-11-07 | 1997-11-07 | |
| PCT/US1998/021723 WO1999020293A1 (fr) | 1997-10-20 | 1998-10-14 | Methodes de traitement d'etats d'hypercoagulabilite ou de carence acquise en proteine c |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA72194C2 true UA72194C2 (en) | 2005-02-15 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2000042259A UA72194C2 (en) | 1997-10-20 | 1998-10-14 | Method of treatment for patients with acquired hypercoagulable state or acquired protein c deficiency |
Country Status (28)
| Country | Link |
|---|---|
| US (7) | US6037322A (fr) |
| EP (2) | EP1449537A3 (fr) |
| JP (2) | JP3805981B2 (fr) |
| KR (1) | KR100798174B1 (fr) |
| CN (1) | CN1276726A (fr) |
| AT (1) | ATE292979T1 (fr) |
| AU (1) | AU748417B2 (fr) |
| BR (1) | BR9812965A (fr) |
| CA (1) | CA2306983A1 (fr) |
| DE (1) | DE69829721T2 (fr) |
| DK (1) | DK0913156T3 (fr) |
| EA (1) | EA002496B1 (fr) |
| ES (1) | ES2239382T3 (fr) |
| HK (1) | HK1020529A1 (fr) |
| HU (2) | HUP0001237A3 (fr) |
| ID (1) | ID24901A (fr) |
| IL (2) | IL135712A0 (fr) |
| MY (1) | MY117655A (fr) |
| NO (1) | NO20002005L (fr) |
| NZ (1) | NZ504026A (fr) |
| PL (1) | PL200515B1 (fr) |
| PT (1) | PT913156E (fr) |
| SI (1) | SI0913156T1 (fr) |
| TR (1) | TR200001059T2 (fr) |
| TW (1) | TWI225404B (fr) |
| UA (1) | UA72194C2 (fr) |
| WO (1) | WO1999020293A1 (fr) |
| ZA (1) | ZA989385B (fr) |
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| EA002149B1 (ru) | 1997-04-28 | 2001-12-24 | Эли Лилли Энд Компани | Улучшенные способы приготовления активированного белка с |
| 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 |
| US20040202645A1 (en) * | 2003-04-08 | 2004-10-14 | Khan Nisar Ahmed | Administration of gene-regulatory peptides |
| US7175679B2 (en) * | 2001-03-29 | 2007-02-13 | Biotempt B.V. | Oligopeptide treatment of NF-κB mediated inflammation |
| US8680059B2 (en) | 1998-05-20 | 2014-03-25 | Biotempt B.V. | Oligopeptide acetate and formulations thereof |
| US20050227925A1 (en) * | 2004-04-08 | 2005-10-13 | Robbert Benner | Compositions capable of reducing elevated blood urea concentration |
| US6921751B1 (en) * | 1998-05-20 | 2005-07-26 | Erasmus Universiteit Rotterdam | Immunoregulator |
| EP1138692A1 (fr) * | 2000-03-29 | 2001-10-04 | Erasmus Universiteit Rotterdam | Fragments de gonadotrophine chorionique humaine comme immunorégulateurs |
| US20030220258A1 (en) | 2001-12-21 | 2003-11-27 | Robbert Benner | Treatment of ischemic events |
| US6844315B2 (en) * | 1998-05-20 | 2005-01-18 | Erasmus Universiteit Rotterdam | Immunoregulator |
| US6287516B1 (en) | 1998-07-10 | 2001-09-11 | Immunocept, L.L.C. | Hemofiltration systems, methods, and devices used to treat inflammatory mediator related disease |
| US20040199099A1 (en) * | 1998-07-10 | 2004-10-07 | Matson James R | Hemofiltration systems, methods and devices used to treat inflammatory mediator related disease |
| EP1124573A1 (fr) | 1998-10-22 | 2001-08-22 | Eli Lilly And Company | Methodes de traitement de la septicemie |
| EP1128842B1 (fr) * | 1998-11-13 | 2006-03-15 | Eli Lilly And Company | Utilisation de la proteine c pour la preparation d'un medicament pour le traitement de la thrombopenie immunitaire de l'heparine |
| DK1133314T3 (da) * | 1998-11-23 | 2003-04-14 | Lilly Co Eli | Protein C til behandling af seglcellesygdom og thalassæmi |
| AU2001238034A1 (en) | 2000-02-04 | 2001-08-14 | The Scripps Research Institute | Neuroprotective, antithrombotic and anti-inflammatory uses of activated protein c (apc) |
| US6736972B1 (en) | 2000-03-24 | 2004-05-18 | Immunocept, L.L.C. | Method and system for providing therapeutic agents with hemofiltration for reducing inflammatory mediator related diseases |
| US8535258B2 (en) * | 2000-03-24 | 2013-09-17 | Immunocept, L.L.C. | Hemofiltration methods for treatment of diseases in a mammal |
| US7291122B2 (en) * | 2000-03-24 | 2007-11-06 | Immunocept, L.L.C. | Hemofiltration methods for treatment of diseases in a mammal |
| US7204981B2 (en) * | 2000-03-28 | 2007-04-17 | Eli Lilly And Company | Methods of treating diseases with activated protein C |
| WO2001072328A2 (fr) * | 2000-03-28 | 2001-10-04 | Eli Lilly And Company | Methodes de traitement de maladies a l'aide de la proteine c activee |
| USRE43279E1 (en) | 2000-03-29 | 2012-03-27 | Biotemp B.V. | Compositions capable of reducing elevated blood urea concentration |
| US7358330B2 (en) | 2001-03-29 | 2008-04-15 | Biotempt B.V. | Immunoregulatory compositions |
| US20050037430A1 (en) * | 2000-03-29 | 2005-02-17 | Biotempt B.V. | Methods and uses for protein breakdown products |
| US7576174B2 (en) * | 2000-03-29 | 2009-08-18 | Biotempt B.V. | Compositions capable of reducing elevated blood urea concentration |
| EP1300418A1 (fr) | 2001-10-04 | 2003-04-09 | Erasmus Universiteit Rotterdam | Régulation génétique par des oligopeptides |
| US8597516B2 (en) * | 2000-05-16 | 2013-12-03 | Immunocept, L.L.C. | Methods and systems for colloid exchange therapy |
| US6787040B2 (en) * | 2000-05-16 | 2004-09-07 | Immunocept, L.L.C. | Method and system for colloid exchange therapy |
| AU2001262939A1 (en) * | 2000-05-24 | 2001-12-03 | Eli Lilly And Company | Formulations and use of activated protein c and protein c zymogen for treating hypercoagulable states |
| WO2002024215A2 (fr) * | 2000-09-18 | 2002-03-28 | Eli Lilly And Company | Procedes d'utilisation de proteine c activee en vue de reduire la duree d'une hospitalisation dans une service de soins intensifs et des depenses entrainees |
| ES2309167T3 (es) | 2001-02-19 | 2008-12-16 | Merck Patent Gmbh | Metodo para identificar epitotes de celulas t y metodo para preparar moleculas con inmunogenicidad reducida. |
| US20040198652A1 (en) * | 2001-04-24 | 2004-10-07 | Carter J. Paul | Methods and compositions for preventing and treating septic shock and endotoxemia |
| ATE550073T1 (de) | 2001-06-13 | 2012-04-15 | Univ Sydney | Protein c für die wundheilung |
| JP2004535461A (ja) * | 2001-07-19 | 2004-11-25 | ディーエムアイ バイオサイエンシズ インコーポレイテッド | プロテインｃの不活性化を抑制するための銅キレート剤の使用 |
| US20030220259A1 (en) * | 2001-12-21 | 2003-11-27 | Robbert Benner | Treatment of neurological disorders |
| KR20040040489A (ko) | 2001-10-15 | 2004-05-12 | 카이론 코포레이션 | 조직 인자 경로 억제제（ｔｆｐｉ）의 저용량 투여에 의한패혈증의 치료 |
| US7501391B2 (en) * | 2001-12-21 | 2009-03-10 | Biotempt B.V. | Treatment of transplant survival |
| US20030220257A1 (en) * | 2001-12-21 | 2003-11-27 | Robbert Benner | Treatment of trauma |
| US20030220261A1 (en) * | 2001-12-21 | 2003-11-27 | Khan Nisar Ahmed | Treatment of iatrogenic disease |
| US20080318871A1 (en) * | 2001-12-21 | 2008-12-25 | Khan Nisar A | Treatment of neurological disorders |
| US7786084B2 (en) | 2001-12-21 | 2010-08-31 | Biotempt B.V. | Treatment of burns |
| US20030220260A1 (en) * | 2001-12-21 | 2003-11-27 | Khan Nisar Ahmed | Peptide compositions |
| US7560433B2 (en) * | 2001-12-21 | 2009-07-14 | Biotempt B.V. | Treatment of multiple sclerosis (MS) |
| US20030224995A1 (en) * | 2001-12-21 | 2003-12-04 | Khan Nisar Ahmed | Treatment of burns |
| US20040013661A1 (en) * | 2001-12-21 | 2004-01-22 | Gert Wensvoort | Stratification |
| EP1485121A4 (fr) * | 2002-03-08 | 2007-11-07 | Lilly Co Eli | Formulations de proteines c activees |
| TW200407335A (en) * | 2002-07-22 | 2004-05-16 | Chugai Pharmaceutical Co Ltd | Non-neutralizing antibody to inhibit the inactivation of activated protein C |
| WO2004014315A2 (fr) * | 2002-08-13 | 2004-02-19 | Arbios Systems, Inc. | Therapie d'echange de plasma selectif |
| WO2004056309A2 (fr) | 2002-12-05 | 2004-07-08 | Socratech L.L.C. | Activite neuroprotectrice de la proteine c activee independante de son activite anticoagulante |
| WO2004065418A1 (fr) * | 2003-01-20 | 2004-08-05 | Chugai Seiyaku Kabushiki Kaisha | Anticorps de neutralisation anti-pci |
| US20070142272A1 (en) * | 2003-01-24 | 2007-06-21 | Zlokovic Berislav V | Neuroprotective activity of activated protein c independent of its anticoagulant activity |
| US7517529B2 (en) * | 2003-04-08 | 2009-04-14 | Biotempt B.V. | Treatment of type I diabetes |
| EP1628530B8 (fr) | 2003-05-15 | 2012-08-01 | Genentech, Inc. | Procedes et compositions pour la prevention et le traitement de la sepsie |
| US9192657B2 (en) | 2003-07-08 | 2015-11-24 | The Scripps Research Institute | Activated protein C variants with normal cytoprotective activity but reduced anticoagulant activity |
| US7498305B2 (en) * | 2003-07-08 | 2009-03-03 | The Scripps Research Institute | Activated protein C variants with normal cytoprotective activity but reduced anticoagulant activity |
| US20090227669A1 (en) * | 2004-01-23 | 2009-09-10 | The University Of Toledo | Compositions and Methods for Perioperative Bladder Instillation |
| SG150552A1 (en) * | 2004-03-17 | 2009-03-30 | Chiron Corp | Treatment of severe community-acquired pneumonia by administration of tissue factor pathway inhibitor (tfpi) |
| WO2005111231A2 (fr) * | 2004-05-11 | 2005-11-24 | Heptest Laboratories, Inc. | Compositions, kit et procede en une etape permettant de surveiller des composes possedant des activites d'antifacteur xa et/ou d'antifacteur iia |
| WO2006014839A2 (fr) * | 2004-07-23 | 2006-02-09 | The University Of Rochester | La proteine c activee inhibe les effets secondaires de l'activateur de plasminogene dans le cerveau |
| US9107917B2 (en) * | 2005-05-13 | 2015-08-18 | The Feinstein Institute For Medical Research | Treatment of sepsis and inflammation with alpha2A adrenergic antagonists |
| ZA200800251B (en) * | 2005-06-24 | 2009-04-29 | Drugrecure Aps | Airway administration of tissue factor pathway inhibitor in inflammatory conditions affecting the respiratory track |
| AU2006266609C1 (en) | 2005-07-05 | 2011-10-27 | Biotempt B.V. | Treatment of tumors |
| EP1864692A1 (fr) * | 2006-06-07 | 2007-12-12 | Biotempt B.V. | Utilisation de peptides pour la protection contre les radiolésions |
| US7785857B2 (en) * | 2006-08-31 | 2010-08-31 | Saint Louis University | Protein C variant |
| GR1005700B (el) * | 2006-09-01 | 2007-10-22 | (40%) ����� �������� | Τροπος αντιμετωπισης της 1ης φασης του εγκαυματοσσε μη σηπτικους ασθενεις με συνεχη ενδοφλεβια χορηγηση ενεργοποιημενης πρωτεινης-c για 48 ωρες με στοχο τη μειωση της τελικης εγκαυματικης βλαβης καιαυξηση της ταχυτητας επουλωσης κατα τα πρωτα επτα μετεγκαυματικα 24ωρα |
| CA2668187A1 (fr) * | 2006-10-31 | 2008-06-19 | The Scripps Research Institute | Schema posologique de proteine c activee et de ses variants presentant une activite anticoagulante reduite |
| RU2445365C1 (ru) * | 2010-11-03 | 2012-03-20 | Общество с ограниченной ответственностью "Инновационный Центр "Новые Технологии и Материалы" (ООО "ИЦ Новтехмат") | Штамм гибридных культивируемых клеток mus musculus - продуцент моноклональных антител, специфичных к протеину с человека (варианты) |
| RU2490722C1 (ru) * | 2012-04-24 | 2013-08-20 | Федеральное государственное бюджетное учреждение науки Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук (ИХБФМ СО РАН) | Способ восстановления кровотока в регионе тромбированной вены в эксперименте |
| CN104394883B (zh) | 2012-07-04 | 2017-05-31 | 悉尼大学 | 炎性皮肤病症的治疗 |
| CA2946028C (fr) | 2014-04-16 | 2022-10-11 | Zz Biotech Llc | Traitement de cicatrices cutanees anormales |
| JP7277484B2 (ja) | 2018-06-15 | 2023-05-19 | エービー サンドビック マテリアルズ テクノロジー | 二相ステンレス鋼ストリップおよびそれを製造するための方法 |
Family Cites Families (17)
| 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 |
| US5516650A (en) * | 1985-06-27 | 1996-05-14 | Zymogenetics, Inc. | Production of activated protein C |
| US5084274A (en) * | 1987-11-17 | 1992-01-28 | Scripps Clinic And Research Foundation | Inhibition of arterial thrombotic occlusion or thromboembolism |
| US4992373A (en) * | 1987-12-04 | 1991-02-12 | Eli Lilly And Company | Vectors and compounds for direct expression of activated human protein C |
| US5009889A (en) * | 1987-12-31 | 1991-04-23 | Oklahoma Medical Research Foundation | Treatment of dysfunctional vascular endothelium using activated protein C |
| GB8819607D0 (en) * | 1988-08-17 | 1988-09-21 | Wellcome Found | Novel combination |
| US4981952A (en) * | 1988-10-04 | 1991-01-01 | Eli Lilly And Company | Method for the purification of vitamin K-dependent proteins |
| US5254532A (en) * | 1989-06-26 | 1993-10-19 | Immuno Aktiengesellschaft Fur Chemisch-Medizinische Produkte | Preparation for treating and preventing thromboses and thromboembolic complications, use of such a preparation and a method of producing the same |
| 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 |
| AT402262B (de) * | 1991-06-20 | 1997-03-25 | Immuno Ag | Arzneimittel enthaltend aktiviertes protein c |
| MY110664A (en) * | 1992-05-21 | 1999-01-30 | Lilly Co Eli | Protein c derivatives |
| JP3434326B2 (ja) * | 1992-08-25 | 2003-08-04 | 財団法人化学及血清療法研究所 | 成人呼吸窮迫症候群（ａｒｄｓ）予防、治療剤 |
| JP2825739B2 (ja) * | 1993-09-20 | 1998-11-18 | 帝人株式会社 | 急性肝不全治療剤 |
| JP3802104B2 (ja) * | 1995-05-31 | 2006-07-26 | 財団法人化学及血清療法研究所 | 脊髄損傷に伴う神経障害の予防・治療剤 |
| WO1997020043A1 (fr) * | 1995-11-30 | 1997-06-05 | Zymogenetics, Inc. | Production de proteine c chez des animaux transgeniques |
| EA002149B1 (ru) * | 1997-04-28 | 2001-12-24 | Эли Лилли Энд Компани | Улучшенные способы приготовления активированного белка с |
| HUP0001237A3 (en) * | 1997-10-20 | 2002-01-28 | Lilly Co Eli | Methods for treating vascular disorders |
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- 1998-10-14 UA UA2000042259A patent/UA72194C2/uk unknown
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- 1998-10-14 JP JP2000516690A patent/JP3805981B2/ja not_active Expired - Fee Related
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- 1998-10-14 WO PCT/US1998/021723 patent/WO1999020293A1/fr not_active Application Discontinuation
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- 1998-10-15 EP EP04005955A patent/EP1449537A3/fr not_active Withdrawn
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