CZ303030B6 - Deriváty cástecne desulfatovaných glykosaminoglykanu s antiangiogenním úcinkem a postrádajících antikoagulacní úcinky - Google Patents
Deriváty cástecne desulfatovaných glykosaminoglykanu s antiangiogenním úcinkem a postrádajících antikoagulacní úcinky Download PDFInfo
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- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 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 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000002294 steroidal antiinflammatory agent Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
- 229960005314 suramin Drugs 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000004862 vasculogenesis Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0075—Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
-
- 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
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/727—Heparin; Heparan
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- 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
- A61P9/08—Vasodilators for multiple indications
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Polymers & Plastics (AREA)
- Diabetes (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Ophthalmology & Optometry (AREA)
- Toxicology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2000RM000041A IT1316986B1 (it) | 2000-01-25 | 2000-01-25 | Derivati glicosamminoglicani parzialmente desolfatati nonanticoagulanti ad attivita' antiangiogenica. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ20022308A3 CZ20022308A3 (cs) | 2003-01-15 |
| CZ303030B6 true CZ303030B6 (cs) | 2012-03-07 |
Family
ID=11454382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20022308A CZ303030B6 (cs) | 2000-01-25 | 2001-01-24 | Deriváty cástecne desulfatovaných glykosaminoglykanu s antiangiogenním úcinkem a postrádajících antikoagulacní úcinky |
Country Status (21)
| Country | Link |
|---|---|
| US (4) | US20030013682A1 (https=) |
| EP (1) | EP1268558B1 (https=) |
| JP (1) | JP5371167B2 (https=) |
| KR (1) | KR100812406B1 (https=) |
| CN (1) | CN100540570C (https=) |
| AT (1) | ATE348115T1 (https=) |
| AU (1) | AU782632B2 (https=) |
| BR (1) | BR0107696A (https=) |
| CA (1) | CA2397964C (https=) |
| CY (1) | CY1108001T1 (https=) |
| CZ (1) | CZ303030B6 (https=) |
| DE (1) | DE60125154T2 (https=) |
| DK (1) | DK1268558T3 (https=) |
| ES (1) | ES2277911T3 (https=) |
| HU (1) | HU229509B1 (https=) |
| IT (1) | IT1316986B1 (https=) |
| MX (1) | MXPA02007195A (https=) |
| PL (1) | PL209479B1 (https=) |
| PT (1) | PT1268558E (https=) |
| SK (1) | SK287566B6 (https=) |
| WO (1) | WO2001055221A1 (https=) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1316986B1 (it) | 2000-01-25 | 2003-05-26 | Sigma Tau Ind Farmaceuti | Derivati glicosamminoglicani parzialmente desolfatati nonanticoagulanti ad attivita' antiangiogenica. |
| US7781416B2 (en) | 2000-01-25 | 2010-08-24 | Sigma-Tau Research Switzerland S.A. | Derivatives of partially desulphated glycosaminoglycans as heparanase inhibitors, endowed with antiangiogenic activity and devoid of anticoagulating effect |
| AU2008202261B2 (en) * | 2001-09-12 | 2011-07-28 | Leadiant Biosciences S.A. | Derivatives of partially desulphated glycosaminoglycans as heparanase inhibitors, endowed with antiangiogenic activity and devoid of anticoagulating effect |
| SK288335B6 (sk) * | 2001-09-12 | 2016-02-02 | Sigma-Tau Research Switzerland S.A. | Čiastočne alebo úplne N-desulfatovaný, N-reacetylovaný heparín, spôsob jeho prípravy, jeho použitie na prípravu liečiva s inhibičným účinkom na heparanázu, s antiangiogénnym a protizápalovým účinkom a farmaceutický prostriedok s jeho obsahom |
| WO2005095463A1 (en) | 2004-03-26 | 2005-10-13 | Glycogenesys, Inc. | Modified pectins, compositions and methods related thereto |
| WO2009007224A1 (en) * | 2007-07-10 | 2009-01-15 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Low molecular weight heparin derivatives having neuroprotective activity |
| US8592393B2 (en) | 2007-11-02 | 2013-11-26 | Momenta Pharmaceuticals, Inc. | Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization |
| US8569262B2 (en) | 2007-11-02 | 2013-10-29 | Momenta Pharmaceuticals, Inc. | Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization |
| ES2567079T3 (es) | 2007-11-02 | 2016-04-19 | Momenta Pharmaceuticals, Inc. | Composiciones de polisacáridos que no son anticoagulantes |
| EP2207811B1 (en) * | 2007-11-02 | 2017-01-04 | Momenta Pharmaceuticals, Inc. | Non-anticoagulant polysaccharide compositions |
| BR112012026542A2 (pt) | 2010-04-16 | 2016-07-12 | Momenta Pharmaceuticals Inc | abordagem seletiva de tecido |
| US8431826B2 (en) | 2010-05-14 | 2013-04-30 | James Robert Howard | Capacitive power and ground plane structure utilizing fractal elements for the reduction of radiated emissions |
| CA2795868A1 (en) | 2010-06-17 | 2011-12-22 | Momenta Pharmaceuticals, Inc. | Methods and compositions for modulating hair growth |
| WO2013095215A1 (en) | 2011-12-19 | 2013-06-27 | Dilaforette Ab | Low anticoagulant heparins |
| CN104144950B (zh) | 2011-12-19 | 2017-09-05 | 迪乐方有限责任公司 | 含有重复的二糖单元的非抗凝的葡糖胺聚糖及其医药用途 |
| AU2012363033B2 (en) | 2011-12-28 | 2016-06-02 | Galectin Therapeutics, Inc. | Composition of novel carbohydrate drug for treatment of human diseases |
| ES2848538T3 (es) | 2012-06-06 | 2021-08-10 | Galectin Therapeutics Inc | Composiciones de galacto-ramnogalacturonato para el tratamiento de enfermedades asociadas con elevada óxido nítrico sintasa inducible |
| US9507912B2 (en) | 2012-08-31 | 2016-11-29 | Nuvectra Corporation | Method and system of simulating a pulse generator on a clinician programmer |
| DK2900061T3 (da) | 2012-09-17 | 2020-03-02 | Galectin Therapeutics Inc | Fremgangsmåde til forstærkning af specifikke immunterapier ved cancerbehandling |
| US8828971B2 (en) | 2012-10-10 | 2014-09-09 | Galectin Therapeutics, Inc. | Galactose-pronged carbohydrate compounds for the treatment of diabetic nephropathy and associated disorders |
| US9339515B2 (en) | 2013-02-20 | 2016-05-17 | Galectin Therapeutics, Inc. | Method for treatment of pulmonary fibrosis |
| JP6132302B2 (ja) * | 2013-05-28 | 2017-05-24 | リーディアント・バイオサイエンシーズ・ソシエタ・アノニマＬｅａｄｉａｎｔ Ｂｉｏｓｃｉｅｎｃｅｓ Ｓ．Ａ． | 抗血管新生活性を有し、抗凝血効果を有さない、ヘパラナーゼ阻害剤としての部分的に脱硫酸化されたグリコサミノグリカンの誘導体 |
| JP2016520613A (ja) | 2013-05-28 | 2016-07-14 | モメンタ ファーマシューティカルズ インコーポレイテッド | 薬学的組成物 |
| ITLO20130005A1 (it) | 2013-10-31 | 2015-05-01 | He E Biochimiche G Ronzonr S R | Derivati di glucosamminoglicani n-desolfatati e loro uso come farmaci |
| ITLO20130006A1 (it) | 2013-11-06 | 2015-05-07 | He E Biochimiche G Ronzoni S R | Derivati carbossilati di glucosamminoglicani e loro uso come farmaci |
| CN103724458B (zh) * | 2014-01-17 | 2016-03-30 | 福州大学 | 含n-非取代葡萄糖胺肝素六糖的制备及其纯化 |
| BR112017018869A2 (pt) | 2015-03-06 | 2018-04-17 | Leadiant Biosciences S.A | roneparstat e roneparstat para o uso, kit de partes e kit de partes para o uso, composição farmacêutica, método para tratar um mamífero e método para inibição, tratamento, e/ou prevenção de mieloma múltiplo, mieloma de células plasmáticas, mieloma recorrente, refratário ou recidivante em um sujeito |
| JP2016014148A (ja) * | 2015-09-10 | 2016-01-28 | シグマ−タウ・リサーチ・スウィッツァーランド・ソシエテ・アノニム | 抗血管新生活性を有し、抗凝血効果を有さない、ヘパラナーゼ阻害剤としての部分的に脱硫酸化されたグリコサミノグリカンの誘導体 |
| CN107177015A (zh) * | 2016-03-11 | 2017-09-19 | 梁颖 | 一种重乙酰化肝素修饰物及其制备方法和应用 |
| US11787783B2 (en) | 2016-12-13 | 2023-10-17 | Beta Therapeutics Pty Ltd | Heparanase inhibitors and use thereof |
| WO2018107200A1 (en) | 2016-12-13 | 2018-06-21 | Beta Therapeutics Pty Ltd | Heparanase inhibitors and use thereof |
| CN108424474B (zh) * | 2017-02-15 | 2023-07-25 | 清华大学 | 去抗凝肝素衍生物及其用于炎症性肠病的治疗 |
| WO2019149179A1 (zh) * | 2018-02-02 | 2019-08-08 | 深圳市海普瑞药业集团股份有限公司 | 糖胺聚糖衍生物及其制备方法和用途 |
| EP3705126A1 (en) | 2019-03-05 | 2020-09-09 | Leadiant Biosciences S.p.A. | Roneparstat for the treatment of amyloidosis |
| CN114901702B (zh) * | 2019-12-27 | 2024-01-09 | 深圳市海普瑞药业集团股份有限公司 | 一种糖胺聚糖衍生物及其应用 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4500519A (en) * | 1978-11-06 | 1985-02-19 | Choay S.A. | Mucopolysaccharides having biological properties, preparation and method of use |
| WO1988001280A1 (en) * | 1986-08-21 | 1988-02-25 | Board Of Regents, The University Of Texas System | Glycosaminoglycan derivatives and their use as inhibitors of tumor invasiveness or metastatic profusion |
| US5668118A (en) * | 1992-07-24 | 1997-09-16 | Cavalier Pharmaceuticals | Method of synthesis of 2-O-desulfated Heparin and use thereof for inhibition of elastase and Cathepspin G |
| US5808021A (en) * | 1992-12-22 | 1998-09-15 | Glycomed Incorporated | Method for controlling O-desulfation of heparin |
| WO1999027976A1 (en) * | 1997-11-28 | 1999-06-10 | Baxter Biotech Technology S.A.R.L. | Non thrombogenic polymers with compatibility with organic fluids and tissues |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5262403A (en) | 1986-03-10 | 1993-11-16 | Board Of Regents, The University Of Texas System | Glycosaminoglycan derivatives and their use as inhibitors of tumor invasiveness of metastatic profusion-II |
| IL79255A0 (en) | 1986-06-26 | 1986-09-30 | Hadassah Med Org | Composition for metastasis prevention |
| FR2614026B1 (fr) * | 1987-04-16 | 1992-04-17 | Sanofi Sa | Heparines de bas poids moleculaire, a structure reguliere, leur preparation et leurs applications biologiques |
| US5280016A (en) * | 1991-03-29 | 1994-01-18 | Glycomed Incorporated | Non-anticoagulant heparin derivatives |
| JPH05157344A (ja) * | 1991-12-09 | 1993-06-22 | Mitsubishi Heavy Ind Ltd | 空気調和機の吹出口 |
| JPH0512822A (ja) | 1991-12-16 | 1993-01-22 | Seiko Epson Corp | カートリツジ |
| JPH06157344A (ja) * | 1992-02-07 | 1994-06-03 | Childrens Medical Center Corp:The | 血管新生阻害のための医薬製剤及び血管新生阻害方法 |
| US5296471A (en) | 1992-12-22 | 1994-03-22 | Glycomed Incorporated | Method for controlling o-desulfation of heparin and compositions produced thereby |
| IT1264709B1 (it) | 1993-07-12 | 1996-10-04 | Italfarmaco Spa | Derivati eparinici ad attivita' antimetastatica |
| US5583121A (en) * | 1994-01-12 | 1996-12-10 | Michigan State University | Non-anticoagulant chemically modified heparinoids for treating hypovolemic shock and related shock syndromes |
| AU2435795A (en) * | 1994-05-06 | 1995-11-29 | Glycomed Incorporated | O-desulfated heparin derivatives, methods of making and uses thereof |
| IL114951A (en) * | 1995-08-15 | 1999-08-17 | Hadasit Med Res Service | Quinazolinone-containing pharmaceutical compositions for prevention of neovascularization |
| US5854221A (en) * | 1996-12-12 | 1998-12-29 | The Children's Medical Center Corporation | Endothelial cell proliferation inhibitor and method of use |
| ATE203534T1 (de) * | 1996-01-15 | 2001-08-15 | Janssen Pharmaceutica Nv | Angiogenesis hemmende pyridazinamine |
| JP4051099B2 (ja) * | 1997-01-31 | 2008-02-20 | 生化学工業株式会社 | 低分子化ヘパリン、その製造法及び医薬組成物 |
| IT1296998B1 (it) * | 1997-12-19 | 1999-08-03 | Derivati Organici Lab | Composizione costituita da frazioni di eparina avente caratteristiche riproducibili con peso molecolare medio di 5200 d |
| IT1316986B1 (it) | 2000-01-25 | 2003-05-26 | Sigma Tau Ind Farmaceuti | Derivati glicosamminoglicani parzialmente desolfatati nonanticoagulanti ad attivita' antiangiogenica. |
| US7781416B2 (en) * | 2000-01-25 | 2010-08-24 | Sigma-Tau Research Switzerland S.A. | Derivatives of partially desulphated glycosaminoglycans as heparanase inhibitors, endowed with antiangiogenic activity and devoid of anticoagulating effect |
-
2000
- 2000-01-25 IT IT2000RM000041A patent/IT1316986B1/it active
-
2001
- 2001-01-24 KR KR1020027009395A patent/KR100812406B1/ko not_active Expired - Fee Related
- 2001-01-24 HU HU0204196A patent/HU229509B1/hu not_active IP Right Cessation
- 2001-01-24 CZ CZ20022308A patent/CZ303030B6/cs not_active IP Right Cessation
- 2001-01-24 SK SK1067-2002A patent/SK287566B6/sk not_active IP Right Cessation
- 2001-01-24 MX MXPA02007195A patent/MXPA02007195A/es active IP Right Grant
- 2001-01-24 PT PT01906098T patent/PT1268558E/pt unknown
- 2001-01-24 US US10/182,185 patent/US20030013682A1/en not_active Abandoned
- 2001-01-24 AU AU34064/01A patent/AU782632B2/en not_active Ceased
- 2001-01-24 WO PCT/IT2001/000034 patent/WO2001055221A1/en not_active Ceased
- 2001-01-24 DK DK01906098T patent/DK1268558T3/da active
- 2001-01-24 JP JP2001561068A patent/JP5371167B2/ja not_active Expired - Fee Related
- 2001-01-24 EP EP01906098A patent/EP1268558B1/en not_active Expired - Lifetime
- 2001-01-24 ES ES01906098T patent/ES2277911T3/es not_active Expired - Lifetime
- 2001-01-24 AT AT01906098T patent/ATE348115T1/de active
- 2001-01-24 CA CA2397964A patent/CA2397964C/en not_active Expired - Fee Related
- 2001-01-24 PL PL357209A patent/PL209479B1/pl unknown
- 2001-01-24 CN CNB018040942A patent/CN100540570C/zh not_active Expired - Fee Related
- 2001-01-24 DE DE60125154T patent/DE60125154T2/de not_active Expired - Lifetime
- 2001-01-24 BR BR0107696-5A patent/BR0107696A/pt not_active IP Right Cessation
-
2004
- 2004-10-19 US US10/967,255 patent/US20050107331A1/en not_active Abandoned
-
2005
- 2005-01-04 US US11/028,512 patent/US7790700B2/en not_active Expired - Fee Related
-
2007
- 2007-02-01 CY CY20071100140T patent/CY1108001T1/el unknown
-
2010
- 2010-08-05 US US12/851,166 patent/US8222231B2/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4500519A (en) * | 1978-11-06 | 1985-02-19 | Choay S.A. | Mucopolysaccharides having biological properties, preparation and method of use |
| WO1988001280A1 (en) * | 1986-08-21 | 1988-02-25 | Board Of Regents, The University Of Texas System | Glycosaminoglycan derivatives and their use as inhibitors of tumor invasiveness or metastatic profusion |
| US5668118A (en) * | 1992-07-24 | 1997-09-16 | Cavalier Pharmaceuticals | Method of synthesis of 2-O-desulfated Heparin and use thereof for inhibition of elastase and Cathepspin G |
| US5912237A (en) * | 1992-07-24 | 1999-06-15 | Carolinas Healthcare System | Method of synthesis of desulfated heparin and use thereof for inhibition of elastase and cathespin |
| US5808021A (en) * | 1992-12-22 | 1998-09-15 | Glycomed Incorporated | Method for controlling O-desulfation of heparin |
| WO1999027976A1 (en) * | 1997-11-28 | 1999-06-10 | Baxter Biotech Technology S.A.R.L. | Non thrombogenic polymers with compatibility with organic fluids and tissues |
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| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20160124 |