AU725468B2 - Long-acting drugs and pharmaceutical compositions comprising them - Google Patents
Long-acting drugs and pharmaceutical compositions comprising them Download PDFInfo
- Publication number
- AU725468B2 AU725468B2 AU37060/97A AU3706097A AU725468B2 AU 725468 B2 AU725468 B2 AU 725468B2 AU 37060/97 A AU37060/97 A AU 37060/97A AU 3706097 A AU3706097 A AU 3706097A AU 725468 B2 AU725468 B2 AU 725468B2
- Authority
- AU
- Australia
- Prior art keywords
- insulin
- fmoc
- radical
- drugs
- lysb
- 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.)
- Ceased
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 13
- 239000003509 long acting drug Substances 0.000 title description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 364
- 229940125396 insulin Drugs 0.000 claims description 220
- 102000004877 Insulin Human genes 0.000 claims description 135
- 108090001061 Insulin Proteins 0.000 claims description 135
- 239000004026 insulin derivative Substances 0.000 claims description 51
- 229940079593 drug Drugs 0.000 claims description 49
- 239000003814 drug Substances 0.000 claims description 49
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 35
- 229940106164 cephalexin Drugs 0.000 claims description 34
- 229940002612 prodrug Drugs 0.000 claims description 32
- 239000000651 prodrug Substances 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 30
- -1 amino, carboxyl Chemical group 0.000 claims description 25
- 206010012601 diabetes mellitus Diseases 0.000 claims description 25
- 101100400201 Drosophila melanogaster LysB gene Proteins 0.000 claims description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
- 229920000024 polymyxin B Polymers 0.000 claims description 18
- 229960005266 polymyxin b Drugs 0.000 claims description 18
- 229960003712 propranolol Drugs 0.000 claims description 18
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- 125000003277 amino group Chemical group 0.000 claims description 14
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- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000000524 functional group Chemical group 0.000 claims description 10
- 238000010254 subcutaneous injection Methods 0.000 claims description 10
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 10
- 230000000844 anti-bacterial effect Effects 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229940088710 antibiotic agent Drugs 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 8
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- 239000007929 subcutaneous injection Substances 0.000 claims description 7
- 101000981881 Brevibacillus parabrevis ATP-dependent glycine adenylase Proteins 0.000 claims description 6
- 101000981889 Brevibacillus parabrevis Linear gramicidin-PCP reductase Proteins 0.000 claims description 6
- 239000000674 adrenergic antagonist Substances 0.000 claims description 6
- 239000003242 anti bacterial agent Substances 0.000 claims description 6
- 230000004962 physiological condition Effects 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 239000003472 antidiabetic agent Substances 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 229960002292 piperacillin Drugs 0.000 claims description 5
- WCMIIGXFCMNQDS-IDYPWDAWSA-M piperacillin sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 WCMIIGXFCMNQDS-IDYPWDAWSA-M 0.000 claims description 5
- 239000002220 antihypertensive agent Substances 0.000 claims description 4
- 229940127088 antihypertensive drug Drugs 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 4
- 229940041181 antineoplastic drug Drugs 0.000 claims description 4
- 239000003443 antiviral agent Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 241000283690 Bos taurus Species 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 3
- 230000000202 analgesic effect Effects 0.000 claims description 3
- 230000000326 anti-hypercholesterolaemic effect Effects 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 3
- 101001011741 Bos taurus Insulin Proteins 0.000 claims description 2
- 108010000521 Human Growth Hormone Proteins 0.000 claims description 2
- 108010005991 Pork Regular Insulin Proteins 0.000 claims description 2
- VRKCDEWVVXAWCZ-UHFFFAOYSA-N amino(nitro)sulfamic acid Chemical compound [O-][N+](=O)N(N)S(O)(=O)=O VRKCDEWVVXAWCZ-UHFFFAOYSA-N 0.000 claims description 2
- 229940035676 analgesics Drugs 0.000 claims description 2
- 230000003266 anti-allergic effect Effects 0.000 claims description 2
- 229940127003 anti-diabetic drug Drugs 0.000 claims description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 2
- 239000000043 antiallergic agent Substances 0.000 claims description 2
- 239000000924 antiasthmatic agent Substances 0.000 claims description 2
- 108010006025 bovine growth hormone Proteins 0.000 claims description 2
- IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 claims description 2
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- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical class C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 claims 2
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- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 abstract 2
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Classifications
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- A61K47/555—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 an organic compound pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
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Landscapes
- Health & Medical Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- Medicinal Chemistry (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL11902996A IL119029A0 (en) | 1996-08-07 | 1996-08-07 | Long-acting drugs and pharamaceutical compositions comprising them |
| IL119029 | 1996-08-07 | ||
| PCT/IL1997/000265 WO1998005361A2 (en) | 1996-08-07 | 1997-08-05 | Long-acting drugs and pharmaceutical compositions comprising them |
Publications (2)
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| AU3706097A AU3706097A (en) | 1998-02-25 |
| AU725468B2 true AU725468B2 (en) | 2000-10-12 |
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| AU37060/97A Ceased AU725468B2 (en) | 1996-08-07 | 1997-08-05 | Long-acting drugs and pharmaceutical compositions comprising them |
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| IL139400A0 (en) * | 2000-11-01 | 2001-11-25 | Yeda Res & Dev | Long-acting cytokine derivatives and pharmaceutical compositions comprising them |
| AU2002239384B2 (en) * | 2000-12-13 | 2007-01-11 | Eli Lilly And Company | Chronic treatment regimen using glucagon-like insulinotropic peptides |
| EP1446103B1 (en) * | 2001-10-19 | 2015-12-23 | Idexx Laboratories, Inc. | Injectable compositions for the controlled delivery of pharmacologically active compound |
| US6946137B2 (en) * | 2001-10-19 | 2005-09-20 | Idexx Laboratories, Inc. | Methods for the controlled delivery of pharmacologically active compounds |
| US20030171285A1 (en) * | 2001-11-20 | 2003-09-11 | Finn Rory F. | Chemically-modified human growth hormone conjugates |
| BE1015608A6 (fr) * | 2003-07-15 | 2005-06-07 | Messadek Jallal | Traitement des arterites. |
| JP4033382B2 (ja) * | 2002-04-08 | 2008-01-16 | 久光製薬株式会社 | インスリン投与装置 |
| WO2004064972A2 (en) * | 2003-01-16 | 2004-08-05 | Hk Pharmaceuticals, Inc. | Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions |
| PL1620118T3 (pl) * | 2003-04-08 | 2014-11-28 | Yeda Res & Dev | Leki odwracalnie pegylowane |
| DK1615632T3 (da) * | 2003-04-17 | 2007-04-10 | Jallal Messadek | Flydende orale formularer for kontrolleret udskillelse af betain |
| WO2005012347A2 (en) | 2003-08-05 | 2005-02-10 | Novo Nordisk A/S | Novel insulin derivatives |
| BE1016128A6 (fr) * | 2004-07-22 | 2006-03-07 | Messadek Jallal | Combinaisons therapeutiques |
| US7282487B2 (en) * | 2004-10-28 | 2007-10-16 | Idexx Laboratories | Method for treating bacterial infections in horses or pigs with tilmicosin |
| WO2006050581A2 (en) * | 2004-11-10 | 2006-05-18 | Jallal Messadek | Betaine as agent against arthropod - or mosquito -borne diseases |
| CN101180073A (zh) * | 2005-04-27 | 2008-05-14 | 贾拉尔·梅萨德克 | 胰岛素组合 |
| DK1969004T3 (da) * | 2005-12-28 | 2011-11-28 | Novo Nordisk As | Insulinsammensætninger og metode til at lave en sammensætning |
| US9034818B2 (en) | 2007-06-13 | 2015-05-19 | Novo Nordisk A/S | Pharmaceutical formulations comprising an insulin derivative |
| WO2009065193A1 (en) * | 2007-11-21 | 2009-05-28 | Jallal Messadek | Treatment of aspirin resistance with betaine and/or betaine enriched molasses |
| KR101755434B1 (ko) | 2008-03-18 | 2017-07-10 | 노보 노르디스크 에이/에스 | 프로테아제 안정화되고, 아실화된 인슐린 유사체 |
| CN102076331B (zh) | 2008-06-26 | 2013-12-18 | 普罗林科斯有限责任公司 | 具有可控的药物释放速率的前药和药物-大分子轭合物 |
| WO2010033220A2 (en) * | 2008-09-19 | 2010-03-25 | Nektar Therapeutics | Modified therapeutics peptides, methods of their preparation and use |
| WO2010033240A2 (en) * | 2008-09-19 | 2010-03-25 | Nektar Therapeutics | Carbohydrate-based drug delivery polymers and conjugates thereof |
| AU2009307729B2 (en) | 2008-10-21 | 2015-09-17 | Nektar Therapeutics | Methods for determining active ingredients in pro-drug PEG protein conjugates with releasable PEG reagents (in vitro de-PEGylation) |
| BRPI0919946A2 (pt) * | 2008-10-30 | 2016-02-16 | Novo Nordisk As | tratamento de diabetes melito usando injeções de insulina com frequência de injeção menor que diariamente |
| RU2011140219A (ru) | 2009-03-05 | 2013-04-10 | Асцендис Фарма Ас | Пролекарства интерферона альфа на носителе |
| WO2011013128A2 (en) | 2009-07-31 | 2011-02-03 | Yeda Research And Development Co. Ltd. | Vectors for delivery of neurotherapeutics to the central nervous system |
| JP5977229B2 (ja) * | 2010-05-05 | 2016-08-24 | プロリンクス リミテッド ライアビリティ カンパニー | 巨大分子共役体からの徐放 |
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- 1997-08-05 KR KR1019997000941A patent/KR20000029806A/ko not_active Withdrawn
- 1997-08-05 WO PCT/IL1997/000265 patent/WO1998005361A2/en not_active Ceased
- 1997-08-05 BR BR9711045A patent/BR9711045A/pt not_active IP Right Cessation
- 1997-08-05 US US09/242,026 patent/US6504005B1/en not_active Expired - Lifetime
- 1997-08-05 IL IL12827497A patent/IL128274A0/xx active IP Right Grant
- 1997-08-05 DE DE69734607T patent/DE69734607T2/de not_active Expired - Lifetime
- 1997-08-05 CZ CZ99369A patent/CZ36999A3/cs unknown
- 1997-08-05 ES ES97933828T patent/ES2252787T3/es not_active Expired - Lifetime
- 1997-08-05 NZ NZ333845A patent/NZ333845A/xx unknown
- 1997-08-05 CA CA002261835A patent/CA2261835C/en not_active Expired - Lifetime
- 1997-08-05 JP JP50777098A patent/JP4416184B2/ja not_active Expired - Lifetime
- 1997-08-05 DK DK97933828T patent/DK1019089T3/da active
- 1997-08-05 EP EP97933828A patent/EP1019089B1/en not_active Expired - Lifetime
- 1997-08-05 HU HU0000809A patent/HUP0000809A2/hu unknown
- 1997-08-05 CN CN97197122A patent/CN1227501A/zh active Pending
- 1997-08-05 AT AT97933828T patent/ATE308998T1/de active
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- 1999-02-04 NO NO990518A patent/NO990518L/no not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
|---|---|
| US6504005B1 (en) | 2003-01-07 |
| HUP0000809A2 (hu) | 2000-11-28 |
| CN1227501A (zh) | 1999-09-01 |
| DK1019089T3 (da) | 2006-03-13 |
| BR9711045A (pt) | 1999-08-17 |
| CA2261835C (en) | 2008-07-29 |
| CA2261835A1 (en) | 1998-02-12 |
| IL128274A0 (en) | 1999-11-30 |
| IL128274A (en) | 2006-08-01 |
| IL119029A0 (en) | 1996-11-14 |
| EP1019089B1 (en) | 2005-11-09 |
| WO1998005361A2 (en) | 1998-02-12 |
| NZ333845A (en) | 2000-09-29 |
| EP1019089A2 (en) | 2000-07-19 |
| NO990518L (no) | 1999-04-06 |
| JP2000515542A (ja) | 2000-11-21 |
| WO1998005361A3 (en) | 1998-06-18 |
| KR20000029806A (ko) | 2000-05-25 |
| ATE308998T1 (de) | 2005-11-15 |
| CZ36999A3 (cs) | 1999-07-14 |
| JP4416184B2 (ja) | 2010-02-17 |
| DE69734607T2 (de) | 2006-08-03 |
| AU3706097A (en) | 1998-02-25 |
| DE69734607D1 (de) | 2005-12-15 |
| NO990518D0 (no) | 1999-02-04 |
| ES2252787T3 (es) | 2006-05-16 |
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