CA2632106A1 - Method for modulating macrophage activation - Google Patents
Method for modulating macrophage activation Download PDFInfo
- Publication number
- CA2632106A1 CA2632106A1 CA002632106A CA2632106A CA2632106A1 CA 2632106 A1 CA2632106 A1 CA 2632106A1 CA 002632106 A CA002632106 A CA 002632106A CA 2632106 A CA2632106 A CA 2632106A CA 2632106 A1 CA2632106 A1 CA 2632106A1
- Authority
- CA
- Canada
- Prior art keywords
- acid
- compound
- anionic
- group
- anionic compound
- 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.)
- Abandoned
Links
- 210000002540 macrophage Anatomy 0.000 title claims abstract description 32
- 230000004913 activation Effects 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title description 34
- 150000001449 anionic compounds Chemical class 0.000 claims abstract description 117
- -1 sulfonates Chemical class 0.000 claims abstract description 87
- 150000001875 compounds Chemical class 0.000 claims abstract description 84
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 50
- 108010048112 Amyloidogenic Proteins Proteins 0.000 claims abstract description 24
- 102000009091 Amyloidogenic Proteins Human genes 0.000 claims abstract description 24
- 230000004054 inflammatory process Effects 0.000 claims abstract description 17
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 10
- 230000008021 deposition Effects 0.000 claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims description 47
- 125000000129 anionic group Chemical group 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 19
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 claims description 18
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 18
- 125000002091 cationic group Chemical group 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 15
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 claims description 12
- 206010061218 Inflammation Diseases 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 229960003080 taurine Drugs 0.000 claims description 9
- XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 claims description 7
- 230000003941 amyloidogenesis Effects 0.000 claims description 7
- YCRNRLUOZIMHNE-UHFFFAOYSA-N butane-1,4-diol;sulfo hydrogen sulfate Chemical compound OCCCCO.OS(=O)(=O)OS(O)(=O)=O YCRNRLUOZIMHNE-UHFFFAOYSA-N 0.000 claims description 7
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 7
- 229960005102 foscarnet Drugs 0.000 claims description 7
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims description 6
- WSYUEVRAMDSJKL-UHFFFAOYSA-N ethanolamine-o-sulfate Chemical compound NCCOS(O)(=O)=O WSYUEVRAMDSJKL-UHFFFAOYSA-N 0.000 claims description 6
- KHLVKKOJDHCJMG-QDBORUFSSA-L indigo carmine Chemical compound [Na+].[Na+].N/1C2=CC=C(S([O-])(=O)=O)C=C2C(=O)C\1=C1/NC2=CC=C(S(=O)(=O)[O-])C=C2C1=O KHLVKKOJDHCJMG-QDBORUFSSA-L 0.000 claims description 6
- 229960003988 indigo carmine Drugs 0.000 claims description 6
- 235000012738 indigotine Nutrition 0.000 claims description 6
- 239000004179 indigotine Substances 0.000 claims description 6
- IQGWPPQNIZBTBM-UHFFFAOYSA-N 2-aminoethanol;sulfuric acid Chemical compound NCCO.OS(O)(=O)=O IQGWPPQNIZBTBM-UHFFFAOYSA-N 0.000 claims description 3
- YEGPVWSPNYPPIK-UHFFFAOYSA-N 4-hydroxybutane-1-sulfonic acid Chemical compound OCCCCS(O)(=O)=O YEGPVWSPNYPPIK-UHFFFAOYSA-N 0.000 claims description 3
- KIWBPDUYBMNFTB-UHFFFAOYSA-N Ethyl hydrogen sulfate Chemical compound CCOS(O)(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-N 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- DFBAXFGODMNLMW-UHFFFAOYSA-N butane-1,4-diol;sulfuric acid Chemical compound OS(O)(=O)=O.OCCCCO DFBAXFGODMNLMW-UHFFFAOYSA-N 0.000 claims description 3
- VERAMNDAEAQRGS-UHFFFAOYSA-N butane-1,4-disulfonic acid Chemical compound OS(=O)(=O)CCCCS(O)(=O)=O VERAMNDAEAQRGS-UHFFFAOYSA-N 0.000 claims description 3
- QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical compound CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 claims description 3
- PAGQVVVNLJPSFU-UHFFFAOYSA-N ethane-1,2-diol;sulfo hydrogen sulfate Chemical compound OCCO.OS(=O)(=O)OS(O)(=O)=O PAGQVVVNLJPSFU-UHFFFAOYSA-N 0.000 claims description 3
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 claims description 3
- 239000012634 fragment Substances 0.000 claims description 3
- UNDBKFIFRQCZQF-UHFFFAOYSA-N heptane-4-sulfonic acid Chemical compound CCCC(S(O)(=O)=O)CCC UNDBKFIFRQCZQF-UHFFFAOYSA-N 0.000 claims description 3
- 230000019236 negative regulation of macrophage activation Effects 0.000 claims description 3
- YSGYUFXJQGXPBU-UHFFFAOYSA-N pentane-1,5-diol;sulfo hydrogen sulfate Chemical compound OCCCCCO.OS(=O)(=O)OS(O)(=O)=O YSGYUFXJQGXPBU-UHFFFAOYSA-N 0.000 claims description 3
- UNNFEYPNQVSVJX-UHFFFAOYSA-N pentane-3-sulfonic acid Chemical compound CCC(CC)S(O)(=O)=O UNNFEYPNQVSVJX-UHFFFAOYSA-N 0.000 claims description 3
- CHOCRVHTVJREPS-UHFFFAOYSA-N propan-1-ol;sulfuric acid Chemical compound CCCO.OS(O)(=O)=O CHOCRVHTVJREPS-UHFFFAOYSA-N 0.000 claims description 3
- FJEDAOMERWWOGQ-UHFFFAOYSA-N propane-1,3-diol;sulfo hydrogen sulfate Chemical compound OCCCO.OS(=O)(=O)OS(O)(=O)=O FJEDAOMERWWOGQ-UHFFFAOYSA-N 0.000 claims description 3
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 claims description 3
- HNDXKIMMSFCCFW-UHFFFAOYSA-N propane-2-sulphonic acid Chemical compound CC(C)S(O)(=O)=O HNDXKIMMSFCCFW-UHFFFAOYSA-N 0.000 claims description 3
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 claims 4
- LMMTVYUCEFJZLC-UHFFFAOYSA-N 1,3,5-pentanetriol Chemical compound OCCC(O)CCO LMMTVYUCEFJZLC-UHFFFAOYSA-N 0.000 claims 2
- PCKKWCFFXCFCKN-UHFFFAOYSA-N 1,7-dihydroxyheptane-4-sulfonic acid Chemical compound OCCCC(S(O)(=O)=O)CCCO PCKKWCFFXCFCKN-UHFFFAOYSA-N 0.000 claims 2
- KVGOXGQSTGQXDD-UHFFFAOYSA-N 1-decane-sulfonic-acid Chemical compound CCCCCCCCCCS(O)(=O)=O KVGOXGQSTGQXDD-UHFFFAOYSA-N 0.000 claims 2
- WQPMYSHJKXVTME-UHFFFAOYSA-N 3-hydroxypropane-1-sulfonic acid Chemical compound OCCCS(O)(=O)=O WQPMYSHJKXVTME-UHFFFAOYSA-N 0.000 claims 2
- PJWWRFATQTVXHA-UHFFFAOYSA-N Cyclohexylaminopropanesulfonic acid Chemical compound OS(=O)(=O)CCCNC1CCCCC1 PJWWRFATQTVXHA-UHFFFAOYSA-N 0.000 claims 2
- 150000003871 sulfonates Chemical class 0.000 abstract description 22
- 210000004556 brain Anatomy 0.000 abstract description 15
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 11
- 230000000903 blocking effect Effects 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 description 57
- 125000001931 aliphatic group Chemical group 0.000 description 46
- 125000003118 aryl group Chemical group 0.000 description 39
- 229920000642 polymer Chemical class 0.000 description 37
- 239000000203 mixture Substances 0.000 description 33
- 238000009472 formulation Methods 0.000 description 29
- 239000001257 hydrogen Substances 0.000 description 29
- 229910052739 hydrogen Inorganic materials 0.000 description 29
- 238000001994 activation Methods 0.000 description 25
- 229940024606 amino acid Drugs 0.000 description 21
- SNKZJIOFVMKAOJ-UHFFFAOYSA-N 3-Aminopropanesulfonate Chemical compound NCCCS(O)(=O)=O SNKZJIOFVMKAOJ-UHFFFAOYSA-N 0.000 description 19
- 125000000623 heterocyclic group Chemical group 0.000 description 19
- 150000002431 hydrogen Chemical group 0.000 description 19
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 19
- 235000001014 amino acid Nutrition 0.000 description 18
- 150000001413 amino acids Chemical class 0.000 description 18
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 16
- 150000001768 cations Chemical class 0.000 description 16
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 16
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- 230000001225 therapeutic effect Effects 0.000 description 15
- 229910052736 halogen Inorganic materials 0.000 description 14
- 150000002367 halogens Chemical class 0.000 description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
- 125000003545 alkoxy group Chemical group 0.000 description 12
- 210000002569 neuron Anatomy 0.000 description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
- 229910052708 sodium Inorganic materials 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 11
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- 125000004429 atom Chemical group 0.000 description 10
- 125000002723 alicyclic group Chemical group 0.000 description 9
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- 150000002632 lipids Chemical class 0.000 description 8
- 239000002502 liposome Substances 0.000 description 8
- 230000002459 sustained effect Effects 0.000 description 8
- 125000003282 alkyl amino group Chemical group 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 239000002158 endotoxin Substances 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 229920006008 lipopolysaccharide Polymers 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 229940002612 prodrug Drugs 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 230000004888 barrier function Effects 0.000 description 6
- 150000007942 carboxylates Chemical class 0.000 description 6
- 230000006727 cell loss Effects 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
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- 235000021317 phosphate Nutrition 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 5
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- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 5
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- 125000003396 thiol group Chemical class [H]S* 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
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- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
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- 150000008051 alkyl sulfates Chemical class 0.000 description 4
- 230000007541 cellular toxicity Effects 0.000 description 4
- POPFDXHLIUYQRL-UHFFFAOYSA-L disodium;pentane-1,5-disulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)CCCCCS([O-])(=O)=O POPFDXHLIUYQRL-UHFFFAOYSA-L 0.000 description 4
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- GWLWWNLFFNJPDP-UHFFFAOYSA-M sodium;2-aminoethanesulfonate Chemical compound [Na+].NCCS([O-])(=O)=O GWLWWNLFFNJPDP-UHFFFAOYSA-M 0.000 description 4
- GEDBQJUJNQVBHE-UHFFFAOYSA-M sodium;4-hydroxybutane-1-sulfonate Chemical compound [Na+].OCCCCS([O-])(=O)=O GEDBQJUJNQVBHE-UHFFFAOYSA-M 0.000 description 4
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- 208000037259 Amyloid Plaque Diseases 0.000 description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
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- 229910003827 NRaRb Inorganic materials 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
- A61P37/02—Immunomodulators
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
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| CA002320224A Division CA2320224C (en) | 1998-02-11 | 1999-02-11 | Method for modulating macrophage activation |
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| US5605938A (en) | 1991-05-31 | 1997-02-25 | Gliatech, Inc. | Methods and compositions for inhibition of cell invasion and fibrosis using dextran sulfate |
| AU3726299A (en) * | 1998-05-15 | 1999-12-06 | Neurochem, Inc. | Use of amyloid inhibitors for modulating neuronal cell death |
| US6310073B1 (en) | 1998-07-28 | 2001-10-30 | Queen's University At Kingston | Methods and compositions to treat glycosaminoglycan-associated molecular interactions |
| KR100822525B1 (ko) * | 1999-04-28 | 2008-04-16 | 뉴로겜 인터내셔널 리미티드 | 아밀로이드증 치료용 조성물 및 방법 |
| WO2001003680A2 (en) * | 1999-07-09 | 2001-01-18 | Isis Innovation Limited | Compounds for inhibiting diseases and preparing cells for transplantation |
| US6670399B2 (en) | 1999-12-23 | 2003-12-30 | Neurochem (International) Limited | Compounds and methods for modulating cerebral amyloid angiopathy |
| US7105336B2 (en) * | 2002-10-07 | 2006-09-12 | Biogaia Ab | Selection and use of lactic acid bacteria for reducing inflammation caused by Helicobacter |
| JP2006512417A (ja) * | 2002-12-24 | 2006-04-13 | ニューロケム （インターナショナル） リミテッド | β−アミロイド関連疾患の治療のための治療用製剤 |
| CN1753662A (zh) * | 2002-12-24 | 2006-03-29 | 神经化学（国际）有限公司 | 用于治疗β－淀粉状蛋白相关疾病的治疗制剂 |
| DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| US7253306B2 (en) | 2003-06-23 | 2007-08-07 | Neurochem (International) Limited | Pharmaceutical drug candidates and methods for preparation thereof |
| US20050142191A1 (en) * | 2003-06-23 | 2005-06-30 | Neurochem (International) Limited | Pharmaceutical formulations of amyloid inhibiting compounds |
| US7414076B2 (en) | 2003-06-23 | 2008-08-19 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| US7244764B2 (en) | 2003-06-23 | 2007-07-17 | Neurochem (International) Limited | Methods and compositions for treating amyloid-related diseases |
| MXPA05013607A (es) * | 2003-06-23 | 2006-04-06 | Neurochem Int Ltd | Candidatos de farmaco farmaceuticos mejorados y metodos para preparar los mismos. |
| CA2900876A1 (en) | 2004-12-22 | 2006-08-17 | Bhi Limited Partnership | Methods and compositions for treating amyloid-related diseases |
| TW200716088A (en) * | 2005-04-15 | 2007-05-01 | Neurochem Int Ltd | Formulations and methods for treating amyloidosis |
| SG10201706600VA (en) | 2005-11-30 | 2017-09-28 | Abbvie Inc | Monoclonal antibodies and uses thereof |
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| US5087618A (en) * | 1982-05-18 | 1992-02-11 | University Of Florida | Redox carriers for brain-specific drug delivery |
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| US5276059A (en) * | 1992-07-10 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibition of diseases associated with amyloid formation |
| US5840294A (en) * | 1993-03-29 | 1998-11-24 | Queen's University At Kingston | Method for treating amyloidosis |
| US5643562A (en) * | 1993-03-29 | 1997-07-01 | Queen's University Of Kingston | Method for treating amyloidosis |
| EP1060750B1 (en) * | 1993-03-29 | 2005-12-07 | Queen's University At Kingston | Propane-1,3-disulfonic acid and its pharmaceutically acceptable salts for treating amyloidosis |
| US5869469A (en) * | 1997-08-18 | 1999-02-09 | Queen's University At Kingston | Phosphonocarboxylate compounds for treating amyloidosis |
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1999
- 1999-02-11 NZ NZ550199A patent/NZ550199A/en not_active IP Right Cessation
- 1999-02-11 PT PT99903869T patent/PT1054664E/pt unknown
- 1999-02-11 AU AU24378/99A patent/AU2437899A/en not_active Abandoned
- 1999-02-11 CA CA002632106A patent/CA2632106A1/en not_active Abandoned
- 1999-02-11 EP EP99903869A patent/EP1054664B1/en not_active Expired - Lifetime
- 1999-02-11 NZ NZ568553A patent/NZ568553A/en unknown
- 1999-02-11 CA CA002320224A patent/CA2320224C/en not_active Expired - Lifetime
- 1999-02-11 MX MXPA00007815A patent/MXPA00007815A/es active IP Right Grant
- 1999-02-11 ES ES99903869T patent/ES2392391T3/es not_active Expired - Lifetime
- 1999-02-11 DK DK99903869.8T patent/DK1054664T3/da active
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- 1999-02-11 MX MX2008014823A patent/MX2008014823A/es active IP Right Grant
- 1999-02-11 WO PCT/IB1999/000354 patent/WO1999040909A1/en not_active Ceased
- 1999-02-11 JP JP2000531161A patent/JP4574845B2/ja not_active Expired - Lifetime
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| CY1113205T1 (el) | 2016-04-13 |
| JP2002502871A (ja) | 2002-01-29 |
| IL137751A0 (en) | 2001-10-31 |
| EP1054664B1 (en) | 2012-08-08 |
| WO1999040909A1 (en) | 1999-08-19 |
| JP4574845B2 (ja) | 2010-11-04 |
| NZ568553A (en) | 2010-02-26 |
| AU2437899A (en) | 1999-08-30 |
| EP1054664A1 (en) | 2000-11-29 |
| ES2392391T3 (es) | 2012-12-10 |
| CA2320224C (en) | 2008-08-12 |
| CA2320224A1 (en) | 1999-08-19 |
| HK1032915A1 (en) | 2001-08-10 |
| MX2008014823A (es) | 2009-03-06 |
| NZ550199A (en) | 2008-07-31 |
| DK1054664T3 (da) | 2012-11-05 |
| MXPA00007815A (es) | 2002-04-24 |
| PT1054664E (pt) | 2012-11-02 |
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