CA2331274A1 - Hybrid protein for inhibiting the degranulation of mastocytes and the use thereof - Google Patents
Hybrid protein for inhibiting the degranulation of mastocytes and the use thereof Download PDFInfo
- Publication number
- CA2331274A1 CA2331274A1 CA002331274A CA2331274A CA2331274A1 CA 2331274 A1 CA2331274 A1 CA 2331274A1 CA 002331274 A CA002331274 A CA 002331274A CA 2331274 A CA2331274 A CA 2331274A CA 2331274 A1 CA2331274 A1 CA 2331274A1
- Authority
- CA
- Canada
- Prior art keywords
- mastocytes
- protein
- protease
- basophils
- fragment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 102000004169 proteins and genes Human genes 0.000 title claims abstract 22
- 108090000623 proteins and genes Proteins 0.000 title claims abstract 22
- 210000003630 histaminocyte Anatomy 0.000 title claims abstract 13
- 230000002401 inhibitory effect Effects 0.000 title claims 2
- 210000003651 basophil Anatomy 0.000 claims abstract 10
- 108091005804 Peptidases Proteins 0.000 claims abstract 9
- 239000004365 Protease Substances 0.000 claims abstract 9
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract 9
- 239000012634 fragment Substances 0.000 claims 6
- 108010055044 Tetanus Toxin Proteins 0.000 claims 4
- 229940118376 tetanus toxin Drugs 0.000 claims 4
- 108030001720 Bontoxilysin Proteins 0.000 claims 3
- 241000193155 Clostridium botulinum Species 0.000 claims 3
- 229940053031 botulinum toxin Drugs 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 230000028327 secretion Effects 0.000 claims 3
- 239000003053 toxin Substances 0.000 claims 3
- 231100000765 toxin Toxicity 0.000 claims 3
- 108700012359 toxins Proteins 0.000 claims 3
- 108010002231 IgA-specific serine endopeptidase Proteins 0.000 claims 2
- 102000009438 IgE Receptors Human genes 0.000 claims 2
- 108010073816 IgE Receptors Proteins 0.000 claims 2
- 241000588652 Neisseria gonorrhoeae Species 0.000 claims 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims 1
- 102000004257 Potassium Channel Human genes 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 claims 1
- 108010077372 mast cell degranulating peptide Proteins 0.000 claims 1
- QMBRLNFAEHGOLY-UHFFFAOYSA-N mcd peptide Chemical compound N1C(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)C(C)CC)CSSCC(C(=O)NCC(=O)NC(CCCCN)C(=O)NC(CC(N)=O)C(N)=O)NC(=O)C(C(C)CC)NC(=O)C(CCCCN)NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(C(C)CC)NC(=O)C(CC2N=CN=C2)NC(=O)C2CCCN2C(=O)C(CCCCN)NC(=O)C(C(C)CC)NC(=O)C(C(C)C)NC2=O)CSSCC1C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC2CC1C=NC=N1 QMBRLNFAEHGOLY-UHFFFAOYSA-N 0.000 claims 1
- 108020001213 potassium channel Proteins 0.000 claims 1
- 230000003248 secreting effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against Fc-receptors, e.g. CD16, CD32, CD64
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Saccharide Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Fire-Extinguishing Compositions (AREA)
Abstract
The invention relates to a hybrid protein comprising or comprised of (i) a known protein which binds to mastocytes and/or basophils in a known manner and/or is absorbed thereby, and of (ii) a protease which splits one or more proteins of the secretory apparatus of the mastocytes and/or basophils.
Claims (6)
1. Hybrid protein comprising or consisting of (i) a protein known per se, said protein binding to mastocytes and/or basophils and/or being taken up by these cells in a manner known per se, (ii) a protease known per se, said protease cleaving one or several proteins of the secretion apparatus of the mastocytes and/or basophils.
2. Hybrid protein comprising or consisting of (i) a protein binding to mastocytes and/or basophils and/or being taken up by these cells, wherein the protein (i) is selected from the group consisting of:
IgE;
IgE fragment, in particular IgE Fc fragment;
antibody against IgE receptor of mastocytes and/or basophils; fragment of the antibody against IgE receptor of mastocytes and/or basophils, in particular Fab fragment; antibody against mastocyte-specific potassium channel; and inactive but binding MCD peptide; and (ii) a protease, in particular a protease known per se, cleaving one or several proteins of the secretion apparatus of the mastocytes and/or basophils.
IgE;
IgE fragment, in particular IgE Fc fragment;
antibody against IgE receptor of mastocytes and/or basophils; fragment of the antibody against IgE receptor of mastocytes and/or basophils, in particular Fab fragment; antibody against mastocyte-specific potassium channel; and inactive but binding MCD peptide; and (ii) a protease, in particular a protease known per se, cleaving one or several proteins of the secretion apparatus of the mastocytes and/or basophils.
3. Hybrid protein comprising or consisting of (i) a protein, in particular a protein known per se, said protein binding to mastocytes and/or basophils and/or being taken up by these cells, in particular in a manner known per se;
and (ii) a protease, said protease cleaving one or several proteins of the secretion apparatus of the mastocytes and/or basophils, wherein the protease (ii) is selected from the group consisting of:
light chain of a Clostridium botulinum toxin, in particular the toxins of type A, B, C1, D, E, F, and G;
catalytically active fragment of the light chain of a Clostridium botulinum toxin, in particular a toxin of type A, B, C1, D, E, F, and G;
light chain of the tetanus toxin (TeNT);
catalytically active fragment of the light chain of the tetanus toxin;
IgA protease of Neisseria gonorrhoeae; and catalytic domain of the IgA protease of Neisseria gonorrhoeae.
and (ii) a protease, said protease cleaving one or several proteins of the secretion apparatus of the mastocytes and/or basophils, wherein the protease (ii) is selected from the group consisting of:
light chain of a Clostridium botulinum toxin, in particular the toxins of type A, B, C1, D, E, F, and G;
catalytically active fragment of the light chain of a Clostridium botulinum toxin, in particular a toxin of type A, B, C1, D, E, F, and G;
light chain of the tetanus toxin (TeNT);
catalytically active fragment of the light chain of the tetanus toxin;
IgA protease of Neisseria gonorrhoeae; and catalytic domain of the IgA protease of Neisseria gonorrhoeae.
4. Hybrid protein of claim 2 or 3, characterized in that the protein (i) is selected from the group according to claim 2 and the protease (ii) is selected from the group according to claim 3.
5. The hybrid protein of claim 4, characterized in that the N-terminal portion of the heavy chain of the respective toxin (H N fragment) or a fragment thereof may be part of the hybrid protein, in addition to the light chain of a Clostridium botulinum toxin or of the tetanus toxin.
6. Use of a hybrid protein of any of claims 1 to 5 for inhibiting the degranulation of mastocytes.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19821285.2 | 1998-05-13 | ||
| DE19821285 | 1998-05-13 | ||
| PCT/EP1999/003272 WO1999058571A2 (en) | 1998-05-13 | 1999-05-12 | Hybrid protein for inhibiting the degranulation of mastocytes and the use thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2331274A1 true CA2331274A1 (en) | 1999-11-18 |
| CA2331274C CA2331274C (en) | 2010-04-06 |
Family
ID=7867540
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2331274A Expired - Fee Related CA2331274C (en) | 1998-05-13 | 1999-05-12 | Hybrid protein for inhibiting the degranulation of mastocytes and the use thereof |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP1084146B1 (en) |
| JP (1) | JP4549533B2 (en) |
| KR (1) | KR100580541B1 (en) |
| CN (1) | CN1241945C (en) |
| AT (1) | ATE227739T1 (en) |
| AU (1) | AU755513B2 (en) |
| BR (1) | BR9910359A (en) |
| CA (1) | CA2331274C (en) |
| CU (1) | CU22997A3 (en) |
| CZ (1) | CZ294376B6 (en) |
| DE (1) | DE59903410D1 (en) |
| DK (1) | DK1084146T3 (en) |
| ES (1) | ES2187200T3 (en) |
| HK (1) | HK1036994A1 (en) |
| HU (1) | HUP0103601A3 (en) |
| IL (2) | IL139478A0 (en) |
| MX (1) | MXPA00011148A (en) |
| NO (1) | NO328361B1 (en) |
| PL (1) | PL201879B1 (en) |
| PT (1) | PT1084146E (en) |
| RU (1) | RU2214420C2 (en) |
| WO (1) | WO1999058571A2 (en) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9721189D0 (en) | 1997-10-08 | 1997-12-03 | Speywood Lab The Limited | Analgesic conjugates |
| GB9818548D0 (en) | 1998-08-25 | 1998-10-21 | Microbiological Res Authority | Treatment of mucas hypersecretion |
| US20040071736A1 (en) | 1998-08-25 | 2004-04-15 | Health Protection Agency | Methods and compounds for the treatment of mucus hypersecretion |
| US20080038274A1 (en) | 1999-09-23 | 2008-02-14 | Foster Keith A | Inhibition of secretion from non-neuronal cells |
| GB9922554D0 (en) * | 1999-09-23 | 1999-11-24 | Microbiological Res Authority | Inhibition of secretion from non-neuronal cells |
| CA2413301A1 (en) * | 2000-06-28 | 2002-01-03 | Ira Sanders | Methods for using tetanus toxin for benificial purposes in animals (mammals) |
| GB0321344D0 (en) * | 2003-09-11 | 2003-10-15 | Health Prot Agency | Re-targeted toxin conjugates |
| GB0426394D0 (en) | 2004-12-01 | 2005-01-05 | Health Prot Agency | Fusion proteins |
| KR100845278B1 (en) * | 2006-08-04 | 2008-07-09 | 포항공과대학교 산학협력단 | Peptide for activating mast cell and immunomodulator comprising the same |
| EP2719392B1 (en) | 2008-06-12 | 2019-07-24 | Ipsen Bioinnovation Limited | Fusion proteins for use in the treatment of acromegaly |
| JP5799397B2 (en) | 2008-06-12 | 2015-10-28 | イプセン・バイオイノベーション・リミテッドＩｐｓｅｎ Ｂｉｏｉｎｎｏｖａｔｉｏｎ Ｌｉｍｉｔｅｄ | Cancer suppression |
| RU2525194C2 (en) * | 2008-07-31 | 2014-08-10 | Тотал Маркетинг Сёрвисез | Constructions and methods for production and secretion of cell wall-cleaving enzymes |
| GB0820970D0 (en) | 2008-11-17 | 2008-12-24 | Syntaxin Ltd | Suppression of cancer |
| CN102241774B (en) * | 2010-05-27 | 2014-05-14 | 四川大学 | Recombinant IgE-Fc-anti EGFR single chain variable fragment fusion protein, its preparation method and its application |
| GB201108108D0 (en) | 2011-05-16 | 2011-06-29 | Syntaxin Ltd | Therapeutic fusion proteins |
| US20140056870A1 (en) | 2012-08-27 | 2014-02-27 | Allergan, Inc. | Fusion proteins |
| GB201312317D0 (en) | 2013-07-09 | 2013-08-21 | Syntaxin Ltd | Cationic neurotoxins |
| EP3242884B1 (en) | 2015-01-09 | 2021-02-24 | Ipsen Bioinnovation Limited | Cationic neurotoxins |
| GB201517450D0 (en) | 2015-10-02 | 2015-11-18 | Ipsen Biopharm Ltd | Method |
| EP3263710A1 (en) | 2016-07-01 | 2018-01-03 | Ipsen Biopharm Limited | Production of activated clostridial neurotoxins |
| GB201815817D0 (en) | 2018-09-28 | 2018-11-14 | Ispen Biopharm Ltd | Clostridial neurotoxins comprising and exogenous activation loop |
| GB201900621D0 (en) | 2019-01-16 | 2019-03-06 | Ipsen Biopharm Ltd | Labelled polypeptides |
| GB201914034D0 (en) | 2019-09-30 | 2019-11-13 | Ipsen Biopharm Ltd | Treatment of neurological disorders |
| GB202100566D0 (en) | 2021-01-15 | 2021-03-03 | Ipsen Biopharm Ltd | Treatment of brain damage |
| GB202104294D0 (en) | 2021-03-26 | 2021-05-12 | Ipsen Biopharm Ltd | Clostridial neurotoxins comprising an exogenous activation loop |
| AU2021438810A1 (en) | 2021-03-30 | 2023-09-21 | Ipsen Biopharm Limited | Catalytically inactive clostridial neurotoxins for the treatment of pain & inflammatory disorders |
| AU2022247196A1 (en) | 2021-03-30 | 2023-10-05 | Ipsen Biopharm Limited | Treatment of pain & inflammatory disorders |
| GB202116795D0 (en) | 2021-11-22 | 2022-01-05 | Ipsen Biopharm Ltd | Treatment of visceral pain |
| PL244930B1 (en) | 2021-12-08 | 2024-04-02 | Gdanski Univ Medyczny | Use of 2-methoxyestradiol in the treatment of mastocytosis |
| GB202214229D0 (en) | 2022-09-28 | 2022-11-09 | Ipsen Biopharm Ltd | Clostridial neurotoxins comprising an activating endosomal protease cleavage site |
| GB202214232D0 (en) | 2022-09-28 | 2022-11-09 | Ispen Biopharm Ltd | Clostridial neurotoxins comprising an activating exogenous protease cleavage site |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9305735D0 (en) * | 1993-03-19 | 1993-05-05 | North John R | Novel agent for controlling cell activity |
| IL116436A (en) * | 1995-12-18 | 2006-12-31 | Yissum Res Dev Co | Fc?Á-PE CHIMERIC PROTEIN FOR TARGETED TREATMENT OF ALLERGY RESPONSES AND |
-
1999
- 1999-05-12 WO PCT/EP1999/003272 patent/WO1999058571A2/en active IP Right Grant
- 1999-05-12 BR BR9910359-1A patent/BR9910359A/en not_active Application Discontinuation
- 1999-05-12 CN CNB998060615A patent/CN1241945C/en not_active Expired - Fee Related
- 1999-05-12 PT PT99950347T patent/PT1084146E/en unknown
- 1999-05-12 EP EP99950347A patent/EP1084146B1/en not_active Expired - Lifetime
- 1999-05-12 HU HU0103601A patent/HUP0103601A3/en unknown
- 1999-05-12 CA CA2331274A patent/CA2331274C/en not_active Expired - Fee Related
- 1999-05-12 AU AU42605/99A patent/AU755513B2/en not_active Ceased
- 1999-05-12 ES ES99950347T patent/ES2187200T3/en not_active Expired - Lifetime
- 1999-05-12 DK DK99950347T patent/DK1084146T3/en active
- 1999-05-12 DE DE59903410T patent/DE59903410D1/en not_active Expired - Lifetime
- 1999-05-12 PL PL344752A patent/PL201879B1/en not_active IP Right Cessation
- 1999-05-12 AT AT99950347T patent/ATE227739T1/en active
- 1999-05-12 IL IL13947899A patent/IL139478A0/en active IP Right Grant
- 1999-05-12 CZ CZ20004161A patent/CZ294376B6/en not_active IP Right Cessation
- 1999-05-12 RU RU2000131217/04A patent/RU2214420C2/en not_active IP Right Cessation
- 1999-05-12 KR KR1020007011584A patent/KR100580541B1/en not_active IP Right Cessation
- 1999-05-12 JP JP2000548373A patent/JP4549533B2/en not_active Expired - Fee Related
- 1999-05-12 MX MXPA00011148A patent/MXPA00011148A/en not_active IP Right Cessation
-
2000
- 2000-10-30 CU CU20000234A patent/CU22997A3/en not_active IP Right Cessation
- 2000-11-05 IL IL139478A patent/IL139478A/en not_active IP Right Cessation
- 2000-11-08 NO NO20005637A patent/NO328361B1/en not_active IP Right Cessation
-
2001
- 2001-09-21 HK HK01106685A patent/HK1036994A1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2331274C (en) | 2010-04-06 |
| DE59903410D1 (en) | 2002-12-19 |
| RU2214420C2 (en) | 2003-10-20 |
| EP1084146B1 (en) | 2002-11-13 |
| AU755513B2 (en) | 2002-12-12 |
| KR20010042825A (en) | 2001-05-25 |
| NO328361B1 (en) | 2010-02-01 |
| EP1084146A2 (en) | 2001-03-21 |
| BR9910359A (en) | 2001-01-09 |
| CZ294376B6 (en) | 2004-12-15 |
| CN1300295A (en) | 2001-06-20 |
| ATE227739T1 (en) | 2002-11-15 |
| IL139478A (en) | 2008-06-05 |
| WO1999058571A3 (en) | 2000-02-03 |
| WO1999058571A2 (en) | 1999-11-18 |
| CU22997A3 (en) | 2004-10-12 |
| PT1084146E (en) | 2003-02-28 |
| NO20005637D0 (en) | 2000-11-08 |
| KR100580541B1 (en) | 2006-05-16 |
| HUP0103601A2 (en) | 2002-01-28 |
| AU4260599A (en) | 1999-11-29 |
| JP4549533B2 (en) | 2010-09-22 |
| DK1084146T3 (en) | 2003-02-03 |
| JP2002514659A (en) | 2002-05-21 |
| ES2187200T3 (en) | 2003-05-16 |
| IL139478A0 (en) | 2001-11-25 |
| PL201879B1 (en) | 2009-05-29 |
| NO20005637L (en) | 2000-11-08 |
| CN1241945C (en) | 2006-02-15 |
| HUP0103601A3 (en) | 2004-06-28 |
| CZ20004161A3 (en) | 2001-04-11 |
| PL344752A1 (en) | 2001-11-19 |
| HK1036994A1 (en) | 2002-01-25 |
| MXPA00011148A (en) | 2003-04-22 |
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