WO2001037893A1 - Method of covalent coupling - Google Patents
Method of covalent coupling Download PDFInfo
- Publication number
- WO2001037893A1 WO2001037893A1 PCT/SE2000/002198 SE0002198W WO0137893A1 WO 2001037893 A1 WO2001037893 A1 WO 2001037893A1 SE 0002198 W SE0002198 W SE 0002198W WO 0137893 A1 WO0137893 A1 WO 0137893A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- carried out
- heparin
- coupling
- alditol
- sodium
- Prior art date
Links
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
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/08—Polysaccharides
-
- 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
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0021—Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran
-
- 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
- C08B37/0069—Chondroitin-4-sulfate, i.e. chondroitin sulfate A; Dermatan sulfate, i.e. chondroitin sulfate B or beta-heparin; Chondroitin-6-sulfate, i.e. chondroitin sulfate C; Derivatives thereof
Definitions
- the present invention has for a mam object to provide a new method whereby the disadvantages of the prior art are eliminated or at least essentially reduced.
- a further object of the invention is to provide a process which involves "end-point" coupling to aminated substrates .
- a method of preparing conjugates by means of covalent coupling of a polysaccharide selected from heparin, heparin derivatives, at least partially deacetylated dermatan sulphate and dextran sulphate and a solid substance containing primary ammo groups is provided through the present invention.
- the method according to the invention is a method of heterogeneous character characterized by the following steps : a) reduction of the saccharide so that its terminal monosaccharide unit is converted to an alditol; b) pe ⁇ odate oxidation of the alditol formed m step a) to the formation of a terminal aldehyde group under cleavage of the monosaccharide unit between two vicinal groups selected from hydroxyl and ammo groups ; and c) reductive coupling of said alditol via the aldehyde group to the am o group of the solid substrate .
- the reduction m step a) above is suitably carried out with the reducing agent selected from borohydrates, catalytic reducing agents and Raney nickel . It is particularly preferred to carry out the reduction m step a) with a borohyd ⁇ de, especially sodium borohyd ⁇ de or potassium borohyd ⁇ de . With regard to the oxidation m step b) above it is suitably carried out with periodic acid or a sodium or potassium salt thereof.
- the reductive coupling in step c) above is suitably carried out with a cyanoborohydride , for example sodium cyanoborohydride or potassium cyanoborohydride.
- Particularly preferred polysaccharides are heparin and heparan sulphate.
- substrates aminated plas- tic objects for example having surface coatings of poly- ethylenimine or chitosan.
- Preferred surface coating is chitosan which in its capacity as a deacetylated chitin contains primary amino groups suited for the coupling techniques involved in the present invention.
- the invention also includes conjugates made by the method defined above.
- step b) involves the formation of a cyclic ester which is then cleaved and inter alia results in two aldehyde functions according to formula I below.
- the major part of the molecules in native heparin having a molecular weight of between about 7000 and about 25000 contains terminally the following sequence: - - 4 ) - ⁇ -D-GlcpNR- ( 1 - - 4 ) - ⁇ -D-GlcA,
- R is acetyl or -S0 3 H.
- the terminal group can be reduced to the alditol of formula III below, the pH-value suitably being maintained so high as not to lactonize the acid.
- the threo-glycol grouping is preferably oxidized and a compound of formula VI containing a terminal aldehyde group will be obtained.
- the reaction can possibly proceed further to the formation of an aldehyde function of C-atom 5.
- H-C-OH _ 10 H-C-O.
- H-C 0 ⁇ 10
- O H-C 0
- the coupling techniques according to the present invention constitute an essential contribution to the pos- sibility of immobilizing polysaccharides to aminated solid substrates while maintaining the original properties of the saccharide, for example biologic activity.
- the reduced heparin (2,9 g) is dissolved in 250 mL imidazol buffer, 40 mM, pH 6,5.
- Sodiumperiodate (640 mg) is also dissolved in 250 L imidazol buffer 40 mM, pH 6,5.
- the two solutions are mixed and are allowed to stand in a flask enclosed fo l at 0°C on ice under stirring for 5 minutes.
- 1 L glycerol is added for the purpose of destroying the excess periodate, and the solution is allowed to stand under stirring for 1 hour.
- the reaction mixture is then dialysed against 10 L distilled water for 18 hours and the heparin is finally freeze-dried.
- the yield of activated heparin (RO-heparin) is 2,4 g.
- Sodiumborohydride (225 mg) is dissolved in distilled water (150 mL) .
- the sodium salt of dextran sulphate (4 g, Pharmacia) is added and the reaction mixture is allowed to stand under stirring for 18 hours. After dialysis against 10 L distilled water for 18 hours the reduced dextran sulphate (heparinoide) is freeze-dried and the yield is 3,5 g.
- the reduced dextran sulphate (3,0 g) is dissolved in 250 mL imidazol buffer, 40 mM, pH 6,5.
- Sodiumperiodate (640 mg) is also dissolved in 250 mL imidazol buffer, 40 mM, pH 6,5.
- the RO-hepa ⁇ noide is coupled to an aminated poly- ethylene film prepared m accordance with Example 4, the coupling is carried out m the same manner as described m Example 6.
- the presence of dextran sulphate on the polyethylene film is visualized using an indicator, tolu- ldmblue, giving a lilac colour m the presence of sul- phated polysaccharide.
- the coupling yield is about 5 mg/cm 2 (determined using FTIR) .
- the invention is not restricted to the above embodiments and examples since the method is applicable to covalent coupling of all types of oligo and polysaccharides having a terminal reducing monosaccharide unit to all forms of substrates containing primary ammo groups .
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
- Materials For Medical Uses (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00980170A EP1231952A1 (en) | 1999-11-23 | 2000-11-09 | Method of covalent coupling |
JP2001539506A JP2003514957A (en) | 1999-11-23 | 2000-11-09 | Methods of covalent coupling |
AU17466/01A AU1746601A (en) | 1999-11-23 | 2000-11-09 | Method of covalent coupling |
US10/130,312 US6653457B1 (en) | 1999-11-23 | 2000-11-09 | Method of covalent coupling |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE9904241A SE515295C2 (en) | 1999-11-23 | 1999-11-23 | Process for the preparation of conjugates of a biologically active polysaccharide and a solid substrate, and such conjugates |
SE9904241-8 | 1999-11-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2001037893A1 true WO2001037893A1 (en) | 2001-05-31 |
Family
ID=20417829
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE2000/002198 WO2001037893A1 (en) | 1999-11-23 | 2000-11-09 | Method of covalent coupling |
Country Status (6)
Country | Link |
---|---|
US (1) | US6653457B1 (en) |
EP (1) | EP1231952A1 (en) |
JP (1) | JP2003514957A (en) |
AU (1) | AU1746601A (en) |
SE (1) | SE515295C2 (en) |
WO (1) | WO2001037893A1 (en) |
Cited By (5)
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DE10152407A1 (en) * | 2001-10-24 | 2003-05-08 | Aesculap Ag & Co Kg | Composition of at least two biocompatible chemically crosslinkable components |
WO2006071801A3 (en) * | 2004-12-27 | 2007-08-16 | Baxter Int | Polymer-von willebrand factor-conjugates |
US8053561B2 (en) | 2006-03-31 | 2011-11-08 | Baxter International Inc. | Pegylated factor VIII |
CN110041445A (en) * | 2019-05-17 | 2019-07-23 | 河南科技大学 | A method of by preparing neutral polysaccharide in Syringa pubescens |
US11020458B2 (en) | 2006-03-31 | 2021-06-01 | Takeda Pharmaceutical Company Limited | Factor VIII polymer conjugates |
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CN101370536A (en) | 2005-12-13 | 2009-02-18 | 埃克塞拉有限责任公司 | Method for extracorporeal removal of a pathogenic microbe, an inflammatory cell or an inflammatory protein from blood |
US8021677B2 (en) | 2006-05-12 | 2011-09-20 | Gore Enterprise Holdings, Inc. | Immobilized biologically active entities having a high degree of biological activity |
WO2008155683A1 (en) | 2007-06-18 | 2008-12-24 | Firmenich Sa | Malodor counteracting compositions and method for their use |
EP2167165B1 (en) * | 2007-06-18 | 2014-09-24 | ExThera Medical Corporation | Full length heparin for restoration of the condition of blood |
GB0816783D0 (en) | 2008-09-15 | 2008-10-22 | Carmeda Ab | Immobilised biological entities |
US8591932B2 (en) * | 2009-09-17 | 2013-11-26 | W. L. Gore & Associates, Inc. | Heparin entities and methods of use |
JP5925693B2 (en) | 2009-12-01 | 2016-05-25 | エクステラ・メディカル・コーポレーション | Method for removing cytokines from blood using surface-immobilized polysaccharides |
GB201004101D0 (en) | 2010-03-12 | 2010-04-28 | Carmeda Ab | Immobilised biological entities |
WO2012112724A1 (en) | 2011-02-15 | 2012-08-23 | Exthera Medical, Llc | Device and method for removal of blood-borne pathogens, toxins and inflammatory cytokines |
RU2625756C2 (en) | 2011-03-11 | 2017-07-18 | В.Л. Гор Энд Ассошиейтс, Инк. | Advanced immobilized biological objects |
EP2861273B1 (en) | 2012-06-13 | 2017-08-23 | ExThera Medical Corporation | Use of heparin and carbohydrates to treat cancer |
KR101702251B1 (en) * | 2012-11-29 | 2017-02-02 | 에스티팜 주식회사 | Bile acid oligomer conjugate for novel vesicular transport and use thereof |
US9272075B2 (en) | 2013-02-04 | 2016-03-01 | W.L. Gore & Associates, Inc. | Coating for substrate |
WO2014118382A1 (en) | 2013-02-04 | 2014-08-07 | W. L. Gore & Associates, Inc. | Coating for substrate |
CN110772677A (en) | 2013-06-24 | 2020-02-11 | 艾克塞拉医疗公司 | Blood filtration system comprising mannose coated substrate |
CN105705177B (en) | 2013-11-08 | 2019-10-22 | 艾克塞拉医疗公司 | Use the method for adsorbing medium diagnosis infectious diseases |
US11839698B2 (en) | 2014-03-13 | 2023-12-12 | W. L. Gore & Associates, Inc. | Drug composition and coating |
EP3134146A4 (en) | 2014-04-24 | 2018-01-10 | ExThera Medical Corporation | Method for removing bacteria from blood using high flow rate |
WO2016048901A1 (en) | 2014-09-22 | 2016-03-31 | Exthera Medical Corporation | Wearable hemoperfusion device |
EP3422943A4 (en) | 2016-03-02 | 2019-10-16 | ExThera Medical Corporation | Method for treating drug intoxication |
US11911551B2 (en) | 2016-03-02 | 2024-02-27 | Exthera Medical Corporation | Method for treating drug intoxication |
US20190275212A1 (en) | 2018-03-09 | 2019-09-12 | Carmeda Ab | Processes for immobilising biological entities |
WO2019170859A2 (en) | 2018-03-09 | 2019-09-12 | Carmeda Ab | Improvements to immobilising biological entities |
EP3860670A1 (en) | 2018-10-03 | 2021-08-11 | Carmeda AB | Immobilised biological entities |
KR20220009400A (en) | 2019-05-16 | 2022-01-24 | 엑스테라 메디컬 코퍼레이션 | Methods of Modulation of Endothelial Glycocalyx Structure |
Citations (9)
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---|---|---|---|---|
US4613665A (en) * | 1982-02-09 | 1986-09-23 | Olle Larm | Process for covalent coupling for the production of conjugates, and polysaccharide containing products thereby obtained |
WO1988000211A1 (en) * | 1986-07-07 | 1988-01-14 | Pharmacia Ab | A method for preparation of sulfated polysaccharides by treating the polysaccharide with a reducing agent before sulfation |
JPS63255299A (en) * | 1987-04-10 | 1988-10-21 | Snow Brand Milk Prod Co Ltd | Method for separating and purifying lactoferrin from milk |
WO1993024503A1 (en) * | 1992-06-01 | 1993-12-09 | The Biomembrane Institute | Sequential removal of monosaccharides from the reducing end of oligosaccharides and uses thereof |
US5529986A (en) * | 1991-09-26 | 1996-06-25 | Corline Systems Ab | Conjugate, its preparation and use and a substrate prepared with the conjugate |
US5679659A (en) * | 1995-08-22 | 1997-10-21 | Medtronic, Inc. | Method for making heparinized biomaterials |
US5728420A (en) * | 1996-08-09 | 1998-03-17 | Medtronic, Inc. | Oxidative method for attachment of glycoproteins to surfaces of medical devices |
WO1999033499A2 (en) * | 1997-12-31 | 1999-07-08 | Medtronic, Inc. | Attachment of biomolecules to medical device surfaces |
WO2000013718A1 (en) * | 1998-09-09 | 2000-03-16 | Norsk Hydro Asa | New process for preparing surface modification substances |
-
1999
- 1999-11-23 SE SE9904241A patent/SE515295C2/en not_active IP Right Cessation
-
2000
- 2000-11-09 EP EP00980170A patent/EP1231952A1/en not_active Withdrawn
- 2000-11-09 US US10/130,312 patent/US6653457B1/en not_active Expired - Lifetime
- 2000-11-09 WO PCT/SE2000/002198 patent/WO2001037893A1/en not_active Application Discontinuation
- 2000-11-09 AU AU17466/01A patent/AU1746601A/en not_active Abandoned
- 2000-11-09 JP JP2001539506A patent/JP2003514957A/en active Pending
Patent Citations (9)
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US4613665A (en) * | 1982-02-09 | 1986-09-23 | Olle Larm | Process for covalent coupling for the production of conjugates, and polysaccharide containing products thereby obtained |
WO1988000211A1 (en) * | 1986-07-07 | 1988-01-14 | Pharmacia Ab | A method for preparation of sulfated polysaccharides by treating the polysaccharide with a reducing agent before sulfation |
JPS63255299A (en) * | 1987-04-10 | 1988-10-21 | Snow Brand Milk Prod Co Ltd | Method for separating and purifying lactoferrin from milk |
US5529986A (en) * | 1991-09-26 | 1996-06-25 | Corline Systems Ab | Conjugate, its preparation and use and a substrate prepared with the conjugate |
WO1993024503A1 (en) * | 1992-06-01 | 1993-12-09 | The Biomembrane Institute | Sequential removal of monosaccharides from the reducing end of oligosaccharides and uses thereof |
US5679659A (en) * | 1995-08-22 | 1997-10-21 | Medtronic, Inc. | Method for making heparinized biomaterials |
US5728420A (en) * | 1996-08-09 | 1998-03-17 | Medtronic, Inc. | Oxidative method for attachment of glycoproteins to surfaces of medical devices |
WO1999033499A2 (en) * | 1997-12-31 | 1999-07-08 | Medtronic, Inc. | Attachment of biomolecules to medical device surfaces |
WO2000013718A1 (en) * | 1998-09-09 | 2000-03-16 | Norsk Hydro Asa | New process for preparing surface modification substances |
Non-Patent Citations (1)
Title |
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DATABASE WPI Week 8838, Derwent World Patents Index; AN 1988-342368, XP002909895 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10152407A1 (en) * | 2001-10-24 | 2003-05-08 | Aesculap Ag & Co Kg | Composition of at least two biocompatible chemically crosslinkable components |
WO2006071801A3 (en) * | 2004-12-27 | 2007-08-16 | Baxter Int | Polymer-von willebrand factor-conjugates |
US7884075B2 (en) | 2004-12-27 | 2011-02-08 | Baxter International Inc. | Polymer-factor VIII-von Willebrand factor-conjugates |
US8076463B2 (en) | 2004-12-27 | 2011-12-13 | Baxter International, Inc. | Polymer-von Willebrand factor-conjugates |
US8357779B2 (en) | 2004-12-27 | 2013-01-22 | Baxter International Inc. | Polymer-von Willebrand factor-conjugates |
US8835388B2 (en) | 2004-12-27 | 2014-09-16 | Baxter International Inc. | Polymer von Willebrand factor-conjugates |
US8053561B2 (en) | 2006-03-31 | 2011-11-08 | Baxter International Inc. | Pegylated factor VIII |
US11020458B2 (en) | 2006-03-31 | 2021-06-01 | Takeda Pharmaceutical Company Limited | Factor VIII polymer conjugates |
CN110041445A (en) * | 2019-05-17 | 2019-07-23 | 河南科技大学 | A method of by preparing neutral polysaccharide in Syringa pubescens |
Also Published As
Publication number | Publication date |
---|---|
SE515295C2 (en) | 2001-07-09 |
AU1746601A (en) | 2001-06-04 |
JP2003514957A (en) | 2003-04-22 |
SE9904241L (en) | 2001-05-24 |
EP1231952A1 (en) | 2002-08-21 |
SE9904241D0 (en) | 1999-11-23 |
US6653457B1 (en) | 2003-11-25 |
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