ZA200403601B - Treatment of severe pneumonia by administration of tissue factor pathway inhibitor (TFPI) - Google Patents
Treatment of severe pneumonia by administration of tissue factor pathway inhibitor (TFPI) Download PDFInfo
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- ZA200403601B ZA200403601B ZA200403601A ZA200403601A ZA200403601B ZA 200403601 B ZA200403601 B ZA 200403601B ZA 200403601 A ZA200403601 A ZA 200403601A ZA 200403601 A ZA200403601 A ZA 200403601A ZA 200403601 B ZA200403601 B ZA 200403601B
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Classifications
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y10/00—Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
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- A—HUMAN NECESSITIES
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (1)
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| US32880601P | 2001-10-15 | 2001-10-15 |
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| EP (2) | EP1446138A4 (de) |
| JP (5) | JP2005506345A (de) |
| KR (2) | KR20050036867A (de) |
| CN (2) | CN1604790A (de) |
| AU (2) | AU2002365131B2 (de) |
| BR (2) | BR0213293A (de) |
| CA (2) | CA2463738A1 (de) |
| EA (2) | EA200400549A1 (de) |
| HU (2) | HUP0500472A2 (de) |
| IL (2) | IL161407A0 (de) |
| IS (2) | IS7224A (de) |
| MX (2) | MXPA04003547A (de) |
| NO (2) | NO20041996D0 (de) |
| PL (2) | PL374506A1 (de) |
| WO (2) | WO2003032904A2 (de) |
| ZA (2) | ZA200403601B (de) |
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| AU2002365131B2 (en) | 2001-10-15 | 2007-03-01 | Novartis Vaccines And Diagnostics, Inc. | Treatment of sepsis by low dose administration of tissue factor pathway inhibitor (TFPI) |
| ATE404176T1 (de) * | 2003-01-08 | 2008-08-15 | Novartis Vaccines & Diagnostic | Stabilisierte lyophilisierte zubereitungen mit gewebefaktor-inhibitor (tfpi) oder varianten des gewebefaktor-inhibitors |
| ATE516306T1 (de) * | 2003-08-13 | 2011-07-15 | Novartis Vaccines & Diagnostic | Verbessertes verfahren zur reinigung von tfpi und tfpi-analogen |
| CN101426520A (zh) * | 2004-03-17 | 2009-05-06 | 诺华疫苗和诊断公司 | 通过给予组织因子途径抑制剂（tfpi）治疗社区获得性重症肺炎 |
| CN101180074A (zh) * | 2005-04-15 | 2008-05-14 | 诺华疫苗和诊断公司 | 通过施用组织因子通路抑制剂(tfpi)治疗严重社区获得性肺炎 |
| US20090214506A1 (en) * | 2005-05-06 | 2009-08-27 | Novartis Ag | Use of TFPI to Treat Severe Bacterial Infections |
| AU2006246721B2 (en) | 2005-05-16 | 2012-12-13 | Abbvie Biotechnology Ltd | Use of TNF inhibitor for treatment of erosive polyarthritis |
| EP1906994B1 (de) * | 2005-06-24 | 2014-04-23 | Drugrecure ApS | Atemwegs-administration von aktiviertem protein c bei entzündungskrankheiten, die den atemtrakt betreffen |
| AU2006272653A1 (en) * | 2005-07-22 | 2007-02-01 | Novartis Ag | TFPI fragments as anti-microbial agents |
| US9624295B2 (en) | 2006-04-10 | 2017-04-18 | Abbvie Biotechnology Ltd. | Uses and compositions for treatment of psoriatic arthritis |
| WO2009014633A1 (en) * | 2007-07-20 | 2009-01-29 | Trustees Of The University Of Pennsylvania | Method of treating acute respiratory distress syndrome |
| WO2009129164A1 (en) * | 2008-04-15 | 2009-10-22 | Novartis Ag | Pharmaceutical combinations of tfpi-fragments and an antibiotic |
| UA112050C2 (uk) * | 2008-08-04 | 2016-07-25 | БАЄР ХЕЛСКЕР ЛЛСі | Терапевтична композиція, що містить моноклональне антитіло проти інгібітора шляху тканинного фактора (tfpi) |
| WO2012078968A2 (en) | 2010-12-10 | 2012-06-14 | Lifeline Scientific, Inc. | Machine perfusion with complement inhibitors |
| JP2014520873A (ja) | 2011-07-18 | 2014-08-25 | ザ ユニバーシティ オブ メルボルン | ｃ−Ｆｍｓアンタゴニストの使用 |
| CA2854882C (en) | 2011-11-15 | 2016-03-29 | Asahi Kasei Pharma Corporation | Medicament for therapeutic treatment and/or improvement of sepsis |
| MX2015014198A (es) | 2013-04-12 | 2015-12-11 | Morphosys Ag | Anticuerpos cuyo objetivo es m-csf. |
| US11908581B2 (en) | 2018-04-10 | 2024-02-20 | Hill-Rom Services, Inc. | Patient risk assessment based on data from multiple sources in a healthcare facility |
| US11504071B2 (en) | 2018-04-10 | 2022-11-22 | Hill-Rom Services, Inc. | Patient risk assessment based on data from multiple sources in a healthcare facility |
| WO2023142096A1 (en) * | 2022-01-30 | 2023-08-03 | Westlake University | Composition and method for preventing and/or treating clostridioides difficile infections caused by clade 2 strains |
Family Cites Families (76)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4399216A (en) * | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4603106A (en) * | 1982-02-22 | 1986-07-29 | The Rockefeller University | Lipoprotein lipase suppression by endotoxin-induced mediator (shock assay) |
| JPS5896026A (ja) * | 1981-10-30 | 1983-06-07 | Nippon Chemiphar Co Ltd | 新規ウロキナ−ゼ誘導体およびその製造法ならびにそれを含有する血栓溶解剤 |
| DE3219248A1 (de) | 1982-05-21 | 1983-11-24 | Solco Basel AG, Birsfelden | Verfahren zur gewinnung zellatmungsfoerdernder wirkstoffe aus kaelberblut |
| DE3380726D1 (en) * | 1982-06-24 | 1989-11-23 | Japan Chem Res | Long-acting composition |
| US4620948A (en) * | 1982-12-22 | 1986-11-04 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
| US4511502A (en) * | 1982-12-22 | 1985-04-16 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
| US4711845A (en) * | 1984-08-31 | 1987-12-08 | Cetus Corporation | Portable temperature-sensitive control cassette |
| US4569790A (en) * | 1984-03-28 | 1986-02-11 | Cetus Corporation | Process for recovering microbially produced interleukin-2 and purified recombinant interleukin-2 compositions |
| US4530787A (en) * | 1984-03-28 | 1985-07-23 | Cetus Corporation | Controlled oxidation of microbially produced cysteine-containing proteins |
| EP0179861A1 (de) | 1984-04-19 | 1986-05-07 | Agracetus | Verfahren und vektoren für die transformation von pflanzenzellen |
| US4572798A (en) * | 1984-12-06 | 1986-02-25 | Cetus Corporation | Method for promoting disulfide bond formation in recombinant proteins |
| US4847201A (en) * | 1985-02-05 | 1989-07-11 | Cetus Corporation | DNA encoding for CSF-1 and accompanying recombinant systems |
| US4683202A (en) * | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4683195A (en) * | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4748234A (en) * | 1985-06-26 | 1988-05-31 | Cetus Corporation | Process for recovering refractile bodies containing heterologous proteins from microbial hosts |
| US4766106A (en) * | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| CA1292686C (en) | 1986-10-27 | 1991-12-03 | Ze'ev Shaked | Pharmaceutical compositions of recombinant interleukin-2 and formulation process |
| CA1294215C (en) | 1986-10-27 | 1992-01-14 | Ze'ev Shaked | Pharmaceutical compositions of recombinant beta-interferon and formulation processes |
| US5110730A (en) * | 1987-03-31 | 1992-05-05 | The Scripps Research Institute | Human tissue factor related DNA segments |
| US5223427A (en) * | 1987-03-31 | 1993-06-29 | The Scripps Research Institute | Hybridomas producing monoclonal antibodies reactive with human tissue-factor glycoprotein heavy chain |
| US4929700A (en) * | 1987-04-16 | 1990-05-29 | Cetus Corporation | Production of purified, biologically active, bacterially produced recombinant human CSF-1 |
| US5106833A (en) * | 1987-07-23 | 1992-04-21 | Washington University | Coagulation inhibitors |
| US4966852A (en) * | 1987-07-23 | 1990-10-30 | Monsanto Company | DNA clone of human tissue factor inhibitor |
| IL87171A (en) | 1987-11-23 | 1995-08-31 | Monsanto Co | ANDC of human tissue factor inhibitor |
| US5219994A (en) * | 1988-11-08 | 1993-06-15 | W. Alton Jones Cell Science Center, Inc. | Inhibitor of tissue factor activity |
| DK412389D0 (da) | 1989-01-19 | 1989-01-19 | Novo Nordisk As | Fremgangsmaade til udvinding af oprenset epi protein fra en fermenteringsoploesning |
| DK408089D0 (da) | 1989-08-18 | 1989-08-18 | Novo Nordisk As | Proteiner |
| DK148890D0 (da) | 1990-06-19 | 1990-06-19 | Novo Nordisk As | Farmaceutisk praeparat |
| IE913004A1 (en) | 1990-08-27 | 1992-03-11 | Monsanto Co | Anticoagulant combination of laci and sulfated¹polysaccharides |
| US5506134A (en) | 1990-10-22 | 1996-04-09 | Corvas International, Inc. | Hypridoma and monoclonal antibody which inhibits blood coagulation tissue factor/factor VIIa complex |
| DK261490D0 (da) | 1990-10-31 | 1990-10-31 | Novo Nordisk As | New pharmaceutical compound |
| US5212091A (en) * | 1992-03-02 | 1993-05-18 | Monsanto Company | Method of producing tissue factor pathway inhibitor |
| US5276015A (en) | 1992-03-18 | 1994-01-04 | Washington University | Method of inhibiting microvascular thrombosis |
| USRE36476E (en) | 1992-03-18 | 1999-12-28 | Washington University | Method of inhibiting microvascular thrombosis |
| EP0643585B1 (de) * | 1992-06-01 | 1999-12-15 | Chiron Corporation | Zusammensetzungen enthaltend Lipoprotein-Associated-Coagulation-Inhibitor (LACI) zur Herstellung eines Medikaments zur Behandlung von akuten oder chronischen Enzündungen |
| US6063764A (en) * | 1992-06-01 | 2000-05-16 | Washington University & Chiron Corp. | Method for using lipoprotein associated coagulation inhibitor to treat sepsis |
| AU4408493A (en) | 1992-06-11 | 1994-01-04 | Washington University | Prophylaxis and treatment of sepsis and sepsis-associated coagulation disorders |
| US5589359A (en) * | 1994-08-05 | 1996-12-31 | Chiron Corporation | Chimeric proteins |
| JP3571378B2 (ja) * | 1994-09-30 | 2004-09-29 | 扶桑薬品工業株式会社 | 感染症診断用プローブ |
| JP3761914B2 (ja) * | 1994-11-17 | 2006-03-29 | 財団法人化学及血清療法研究所 | アンチトロンビンｉｉｉ及び組織因子凝固系インヒビター含有血栓症治療剤 |
| US5914316A (en) | 1994-12-16 | 1999-06-22 | Washington University | Method of inhibiting intimal hyperplasia |
| US5612363A (en) | 1995-06-02 | 1997-03-18 | Berlex Laboratories, Inc. | N,N-di(aryl) cyclic urea derivatives as anti-coagulants |
| US5885781A (en) | 1995-06-07 | 1999-03-23 | Chiron Corporation | Regulation of cytokine synthesis and release |
| PT1602667E (pt) | 1995-06-07 | 2007-07-13 | Searle Llc | Formulação aquosa que compreende tfpi e agentes de solubilização |
| US6242414B1 (en) | 1995-06-07 | 2001-06-05 | Chiron Corporation | Regulation of cytokine synthesis and release |
| US5888968A (en) | 1995-06-07 | 1999-03-30 | Chiron Corporation | TFPI formulation |
| US5902582A (en) | 1995-09-05 | 1999-05-11 | Chiron Corporation | Use of TFPI inhibitor for treatment of cancer |
| US5772629A (en) * | 1995-10-23 | 1998-06-30 | Localmed, Inc. | Localized intravascular delivery of TFPI for inhibition of restenosis in recanalized blood vessels |
| US5736364A (en) | 1995-12-04 | 1998-04-07 | Genentech, Inc. | Factor viia inhibitors |
| ATE254472T1 (de) | 1996-03-25 | 2003-12-15 | Chemo Sero Therapeut Res Inst | Hemmstoff für die gefässneubildung, der den gewebefaktor-inhibitor (tfpi) enthält |
| US5977057A (en) * | 1996-05-08 | 1999-11-02 | The University Of Vermont And State Agricultural College | Thrombosis prophylaxis for factor VLEIDEN carriers |
| CA2279345A1 (en) * | 1997-01-31 | 1998-08-06 | Human Genome Sciences, Inc. | Tissue factor pathway inhibitor-3 |
| US5981471A (en) | 1997-02-06 | 1999-11-09 | Entremed, Inc. | Compositions and methods for inhibiting cellular proliferation |
| EA002149B1 (ru) | 1997-04-28 | 2001-12-24 | Эли Лилли Энд Компани | Улучшенные способы приготовления активированного белка с |
| IL121191A0 (en) | 1997-06-29 | 1997-11-20 | Yeda Res & Dev | Synthetic peptides and pharmaceutical compositions comprising them |
| HUP0001237A3 (en) | 1997-10-20 | 2002-01-28 | Lilly Co Eli | Methods for treating vascular disorders |
| US6824997B1 (en) * | 1998-09-18 | 2004-11-30 | Binax, Inc. | Process and materials for the rapid detection of streptococcus pneumoniae employing purified antigen-specific antibodies |
| AU768075B2 (en) | 1998-10-22 | 2003-12-04 | Eli Lilly And Company | Methods for treating sepsis |
| EP1131091B1 (de) | 1998-11-20 | 2003-04-02 | Eli Lilly And Company | Behandlung von hämorrhagischem virusfieber mit protein c |
| AU4683299A (en) * | 1999-06-11 | 2001-01-02 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Detection of streptococcus pneumoniae and immunization against streptococcus pneumoniae infection |
| WO2000077246A2 (en) | 1999-06-14 | 2000-12-21 | Novo Nordisk A/S | A METHOD FOR IDENTIFYING A DRUG CANDIDATE HAVING AN INHIBITORY ACTION ON FVII-TF ACTIVITY, AND FVIIa/TF ACTIVITY INHIBITING COMPOUNDS |
| US6294648B1 (en) | 1999-07-20 | 2001-09-25 | Bayer Corporation | Protein having proteinase inhibitor activity |
| US6180607B1 (en) | 1999-08-05 | 2001-01-30 | Christopher Davies | Protein having proteinase inhibitor activity |
| BRPI0017437B8 (pt) | 1999-10-04 | 2021-05-25 | Chiron Corp | composição farmacêutica estabilizada contendo polipeptídeo il-2, método para aumentar estabilidade de interleucina-2 em uma composição farmacêutica, e uma forma seca da composição |
| EP1251868A1 (de) | 2000-01-06 | 2002-10-30 | Eli Lilly & Company | Kombinationstherapie zur behandlung entzündlicher und respiratorischer erkrankungen |
| EP1263943A1 (de) | 2000-02-11 | 2002-12-11 | Eli Lilly & Company | Protein c derivate |
| KR20020081330A (ko) | 2000-02-16 | 2002-10-26 | 노오쓰웨스턴 유니버시티 | 폴리펩토이드 폐 계면활성제 |
| DE10022092A1 (de) | 2000-05-08 | 2001-11-15 | Aventis Behring Gmbh | Stabilisiertes Protein-Präparat und Verfahren zu seiner Herstellung |
| US7015194B2 (en) | 2000-05-10 | 2006-03-21 | Novo Nordisk A/S | Pharmaceutical composition comprising factor VIIa and anti-TFPI |
| US6756208B2 (en) | 2001-02-28 | 2004-06-29 | John H. Griffin | Plasma glucosylceramide deficiency as risk factor for thrombosis and modulator of anticoagulant protein C |
| US6808927B2 (en) | 2001-04-04 | 2004-10-26 | American Diagnostica, Inc. | Method of preparation of stabilized thrombin-activatable fibrinolysis inhibitor (TAFI) and methods of use thereof |
| DE10132307A1 (de) | 2001-07-06 | 2003-01-30 | Aventis Behring Gmbh | Arzneizubereitung zur Inhalation von Antithrombin bei entzündlichen Lungenerkrankungen und ARDS |
| AU2002365131B2 (en) | 2001-10-15 | 2007-03-01 | Novartis Vaccines And Diagnostics, Inc. | Treatment of sepsis by low dose administration of tissue factor pathway inhibitor (TFPI) |
| US20020198138A1 (en) | 2002-06-07 | 2002-12-26 | Macias William Louis | Combination therapy for the treatment of inflammatory and respiratory diseases |
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2002
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2003
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2004
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