CA2562756C - Methods for controlling angiogenesis and cell proliferation using a desulphatohirudin - Google Patents
Methods for controlling angiogenesis and cell proliferation using a desulphatohirudin Download PDFInfo
- Publication number
- CA2562756C CA2562756C CA2562756A CA2562756A CA2562756C CA 2562756 C CA2562756 C CA 2562756C CA 2562756 A CA2562756 A CA 2562756A CA 2562756 A CA2562756 A CA 2562756A CA 2562756 C CA2562756 C CA 2562756C
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- Prior art keywords
- desulphatohirudin
- administration
- angiogenesis
- glu
- medicament
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- Expired - Lifetime
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Classifications
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- 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
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
- A61K38/58—Protease inhibitors from animals; from humans from leeches, e.g. hirudin, eglin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (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)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US56174104P | 2004-04-12 | 2004-04-12 | |
| US60/561,741 | 2004-04-12 | ||
| PCT/US2005/011549 WO2005099749A2 (en) | 2004-04-12 | 2005-04-05 | Methods for controlling angiogenesis and cell proliferation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2562756A1 CA2562756A1 (en) | 2005-10-27 |
| CA2562756C true CA2562756C (en) | 2011-08-23 |
Family
ID=35150501
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2562756A Expired - Lifetime CA2562756C (en) | 2004-04-12 | 2005-04-05 | Methods for controlling angiogenesis and cell proliferation using a desulphatohirudin |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US7795205B2 (enExample) |
| EP (1) | EP1753291A4 (enExample) |
| JP (1) | JP2007532646A (enExample) |
| AU (1) | AU2005232625B2 (enExample) |
| BR (1) | BRPI0509876A (enExample) |
| CA (1) | CA2562756C (enExample) |
| IL (1) | IL178578A (enExample) |
| MY (1) | MY146091A (enExample) |
| NZ (1) | NZ551146A (enExample) |
| SG (1) | SG160323A1 (enExample) |
| TW (1) | TWI362941B (enExample) |
| WO (1) | WO2005099749A2 (enExample) |
| ZA (1) | ZA200609219B (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7795205B2 (en) * | 2004-04-12 | 2010-09-14 | Canyon Pharmaceuticals, Inc. | Methods for effecting regression of tumor mass and size in a metastasized pancreatic tumor |
| WO2006045503A1 (en) | 2004-10-19 | 2006-05-04 | Lonza Ag | Method for solid phase peptide synthesis |
| US20100239627A1 (en) * | 2009-03-20 | 2010-09-23 | Wilson Kurt Whitekettle | Quarternary ammonium salts delivery systems |
| US20100239630A1 (en) * | 2009-03-20 | 2010-09-23 | Wilson Kurt Whitekettle | Phosphonium salts delivery systems |
| US20100239626A1 (en) * | 2009-03-20 | 2010-09-23 | Wilson Kurt Whitekettle | Propanediol delivery systems |
| US20100239651A1 (en) * | 2009-03-20 | 2010-09-23 | Wilson Kurt Whitekettle | Nitrilopropionamide delivery systems |
| US20100239650A1 (en) * | 2009-03-20 | 2010-09-23 | Wilson Kurt Whitekettle | Isothiazolin biodelivery systems |
| US7803762B1 (en) | 2009-08-20 | 2010-09-28 | The Medicines Company | Ready-to-use bivalirudin compositions |
| US7985733B1 (en) | 2010-01-06 | 2011-07-26 | The Medicines Company | Buffer-based method for preparing bivalirudin drug product |
| CN104906037A (zh) * | 2015-06-23 | 2015-09-16 | 广西复鑫益生物科技有限公司平南分公司 | 一种重组水蛭素滴眼液及其制备方法 |
| CN110404060A (zh) * | 2018-04-28 | 2019-11-05 | 复旦大学 | 凝血酶抑制剂在制备抗肿瘤侵袭转移药物中的用途 |
Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU178398B (en) | 1979-06-12 | 1982-04-28 | Gyogyszerkutato Intezet | Process for producing new agmatine derivatives of activity against haemagglutination |
| DE3586333T2 (de) | 1984-03-27 | 1992-12-10 | Transgene Sa | Expressionsvektoren fuer hirudin, transformierte zellen und verfahren zur herstellung von hirudin. |
| DE3438296A1 (de) | 1984-04-18 | 1985-11-07 | Hoechst Ag, 6230 Frankfurt | Neue polypeptide mit blutgerinnungshemmender wirkung, verfahren zu deren herstellung bzw. gewinnung, deren verwendung und diese enthaltende mittel |
| ATE64956T1 (de) | 1984-06-14 | 1991-07-15 | Ciba Geigy Ag | Verfahren zur herstellung von thrombininhibitoren. |
| DE3445532A1 (de) | 1984-12-13 | 1986-06-19 | Plantorgan Werk Heinrich G.E. Christensen, KG, 2903 Bad Zwischenahn | Hirudin-pa, desulfatohirudine-pa, verfahren zur herstellung und pharmazeutische mittel, die diese wirkstoffe enthalten |
| HU192646B (en) | 1984-12-21 | 1987-06-29 | Gyogyszerkutato Intezet | Process for preparing new n-alkyl-peptide aldehydes |
| CA1341029C (en) | 1985-02-04 | 2000-06-20 | Michael Kolb | Peptidase inhibitors |
| DE3738541A1 (de) | 1987-11-13 | 1989-05-24 | Hoechst Ag | Verfahren zur isolierung und reinigung von hirudin |
| FR2593518B1 (fr) | 1985-05-02 | 1989-09-08 | Transgene Sa | Vecteurs d'expression et de secretion de l'hirudine par les levures transformees |
| MY101203A (en) | 1985-12-12 | 1991-08-17 | Ucp Gen Pharma Ag | Production of thrombin iinhibitors. |
| MC1834A1 (fr) | 1986-07-10 | 1988-06-03 | Transgene Sa | Bloc fonctionnel d'adn et plasmide codant pour l'hirudine,levure transformee,procede de preparation de l'hirudine,hirudine obtenue et son utilisation |
| US5352664A (en) | 1986-10-31 | 1994-10-04 | Board Of Regents, The University Of Texas System | Thrombin derived polypeptides; compositions and methods for use |
| US5187157A (en) | 1987-06-05 | 1993-02-16 | Du Pont Merck Pharmaceutical Company | Peptide boronic acid inhibitors of trypsin-like proteases |
| AU604925B2 (en) | 1988-02-23 | 1991-01-03 | Schering Aktiengesellschaft | A hirudin derivative |
| AU614121B2 (en) | 1988-05-04 | 1991-08-22 | Novartis Ag | Improvements in the production of polypeptides |
| GB8817161D0 (en) | 1988-07-19 | 1988-08-24 | Ciba Geigy Ag | Modified proteins |
| GB8817160D0 (en) | 1988-07-19 | 1988-08-24 | Ciba Geigy Ag | Novel proteins |
| EP0362002B1 (en) | 1988-09-01 | 1995-07-26 | Merrell Dow Pharmaceuticals Inc. | HIV protease inhibitors |
| JPH04500802A (ja) * | 1988-09-29 | 1992-02-13 | バイオジェン インコーポレイテッド | ヒルジンペプチド |
| ZA897514B (en) | 1988-10-07 | 1990-06-27 | Merrell Dow Pharma | Novel peptidase inhibitors |
| FR2645175B1 (fr) | 1989-03-31 | 1994-02-18 | Transgene Sa | Souche de saccharomyces cerevisiaeproductrice d'une proteine heterologue et procede de preparation de ladite proteine heterologue par fermentation de ladite souche |
| US5096092A (en) * | 1990-03-13 | 1992-03-17 | Mmm, Ltd. | Food dispensing apparatus utilizing inflatable bladder |
| TW201303B (enExample) | 1990-07-05 | 1993-03-01 | Hoffmann La Roche | |
| ATE140929T1 (de) | 1990-11-08 | 1996-08-15 | Japan Energy Corp | Hirudinmutante, deren herstellung, antikoagulans, sekretorischer vektor, durch besagten vektor transformierter mikroorganismus und herstellung eines produkts durch besagten mikroorganismus |
| DE4041185A1 (de) * | 1990-12-21 | 1992-06-25 | Knoll Ag | Verwendung von hirudin und dessen muteinen zur kombinationsbehandlung von tumoren |
| AU659432B2 (en) | 1991-03-08 | 1995-05-18 | Novartis Ag | A method for the inhibition or prevention of tumor cell metastasis with hirudin |
| CA2075154A1 (en) | 1991-08-06 | 1993-02-07 | Neelakantan Balasubramanian | Peptide aldehydes as antithrombotic agents |
| SE9102462D0 (sv) | 1991-08-28 | 1991-08-28 | Astra Ab | New isosteric peptides |
| CZ333492A3 (en) | 1991-11-12 | 1993-09-15 | Lilly Co Eli | Dipeptide of l-azetidine-2-carboxylic acids and l-argininaldehyde, process of its preparation and pharmaceutical preparation in which said dipeptide is comprised |
| SE9103612D0 (sv) | 1991-12-04 | 1991-12-04 | Astra Ab | New peptide derivatives |
| EP0629212B1 (en) | 1992-03-04 | 1997-10-08 | Gyogyszerkutato Intezet Kft. | New anticoagulant peptide derivatives and pharmaceutical compositions containing the same as well as a process for the preparation thereof |
| TW223629B (enExample) | 1992-03-06 | 1994-05-11 | Hoffmann La Roche | |
| ATE196927T1 (de) | 1992-09-04 | 2000-10-15 | Novartis Ag | Verfahren zur herstellung von proteaseinhibitoren |
| AU675981B2 (en) | 1992-12-02 | 1997-02-27 | Bristol-Myers Squibb Company | Guanidinyl-substituted heterocyclic thrombin inhibitors |
| GB9303275D0 (en) | 1993-02-18 | 1993-04-07 | Ciba Geigy Ag | Pharmaceutical compositions |
| SE9301916D0 (sv) | 1993-06-03 | 1993-06-03 | Ab Astra | New peptides derivatives |
| DE4321444A1 (de) | 1993-06-28 | 1995-01-05 | Bernd Prof Dr Clement | Pharmazeutische Zubereitung |
| EP0648780A1 (en) | 1993-08-26 | 1995-04-19 | Bristol-Myers Squibb Company | Heterocyclic thrombin inhibitors |
| TW394760B (en) | 1993-09-07 | 2000-06-21 | Hoffmann La Roche | Novel Carboxamides, process for their preparation and pharmaceutical composition containing the same |
| GB9401448D0 (en) | 1994-01-26 | 1994-03-23 | Ciba Geigy Ag | Stable dry powders |
| GB9401447D0 (en) | 1994-01-26 | 1994-03-23 | Ciba Geigy Ag | Pharmaceutical compositions |
| CA2140598C (en) | 1994-01-27 | 2010-03-09 | Masahiro Ohshima | Prolineamide derivatives |
| IL112795A (en) | 1994-03-04 | 2001-01-28 | Astrazeneca Ab | Peptide derivatives as antithrombic agents their preparation and pharmaceutical compositions containing them |
| US5561146A (en) | 1994-06-10 | 1996-10-01 | Bristol-Myers Squibb Company | Modified guanidino and amidino thrombin inhibitors |
| DE4421052A1 (de) | 1994-06-17 | 1995-12-21 | Basf Ag | Neue Thrombininhibitoren, ihre Herstellung und Verwendung |
| US5843925A (en) | 1994-12-13 | 1998-12-01 | American Cyanamid Company | Methods for inhibiting angiogenesis, proliferation of endothelial or tumor cells and tumor growth |
| EP0873356A1 (de) | 1995-02-17 | 1998-10-28 | Basf Aktiengesellschaft | Neue dipeptidische amidine als thrombin-inhibitoren |
| SE9600216D0 (sv) | 1996-01-18 | 1996-01-18 | Hans Arne Hansson | Styrning av läkningsprocesser |
| PL329851A1 (en) | 1996-05-01 | 1999-04-12 | Lilly Co Eli | Treatment of diseases associated with vegf |
| US6573256B2 (en) | 1996-12-30 | 2003-06-03 | Bone Care International, Inc. | Method of inhibiting angiogenesis using active vitamin D analogues |
| US6537585B1 (en) * | 1999-03-26 | 2003-03-25 | Guilford Pharmaceuticals, Inc. | Methods and compositions for treating solid tumors |
| DE10033195A1 (de) | 2000-07-07 | 2002-03-21 | Aventis Pharma Gmbh | Bifunktionale Fusionsproteine aus Hirudin und TAP |
| US6696483B2 (en) | 2000-10-03 | 2004-02-24 | Oncopharmaceutical, Inc. | Inhibitors of angiogenesis and tumor growth for local and systemic administration |
| US6476068B1 (en) * | 2001-12-06 | 2002-11-05 | Pharmacia Italia, S.P.A. | Platinum derivative pharmaceutical formulations |
| US7795205B2 (en) * | 2004-04-12 | 2010-09-14 | Canyon Pharmaceuticals, Inc. | Methods for effecting regression of tumor mass and size in a metastasized pancreatic tumor |
-
2005
- 2005-04-04 US US11/099,370 patent/US7795205B2/en not_active Expired - Lifetime
- 2005-04-05 JP JP2007508384A patent/JP2007532646A/ja active Pending
- 2005-04-05 EP EP05763698A patent/EP1753291A4/en not_active Withdrawn
- 2005-04-05 NZ NZ551146A patent/NZ551146A/en not_active IP Right Cessation
- 2005-04-05 AU AU2005232625A patent/AU2005232625B2/en not_active Ceased
- 2005-04-05 BR BRPI0509876-9A patent/BRPI0509876A/pt not_active IP Right Cessation
- 2005-04-05 CA CA2562756A patent/CA2562756C/en not_active Expired - Lifetime
- 2005-04-05 SG SG200907751-2A patent/SG160323A1/en unknown
- 2005-04-05 WO PCT/US2005/011549 patent/WO2005099749A2/en not_active Ceased
- 2005-04-11 TW TW094111335A patent/TWI362941B/zh not_active IP Right Cessation
- 2005-04-11 MY MYPI20051599A patent/MY146091A/en unknown
-
2006
- 2006-10-15 IL IL178578A patent/IL178578A/en not_active IP Right Cessation
- 2006-11-06 ZA ZA2006/09219A patent/ZA200609219B/en unknown
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2009
- 2009-05-19 US US12/468,700 patent/US20090269422A1/en not_active Abandoned
-
2010
- 2010-09-13 US US12/880,981 patent/US20110224150A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| IL178578A (en) | 2013-06-27 |
| US20110224150A1 (en) | 2011-09-15 |
| WO2005099749A2 (en) | 2005-10-27 |
| AU2005232625B2 (en) | 2011-07-28 |
| SG160323A1 (en) | 2010-04-29 |
| EP1753291A4 (en) | 2009-08-12 |
| NZ551146A (en) | 2009-04-30 |
| CA2562756A1 (en) | 2005-10-27 |
| TWI362941B (en) | 2012-05-01 |
| IL178578A0 (en) | 2007-02-11 |
| US7795205B2 (en) | 2010-09-14 |
| ZA200609219B (en) | 2012-02-29 |
| US20050233966A1 (en) | 2005-10-20 |
| JP2007532646A (ja) | 2007-11-15 |
| US20090269422A1 (en) | 2009-10-29 |
| TW200538466A (en) | 2005-12-01 |
| BRPI0509876A (pt) | 2007-10-16 |
| EP1753291A2 (en) | 2007-02-21 |
| AU2005232625A1 (en) | 2005-10-27 |
| WO2005099749A3 (en) | 2006-08-03 |
| MY146091A (en) | 2012-06-29 |
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