AU781336B2 - Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation - Google Patents
Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation Download PDFInfo
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- AU781336B2 AU781336B2 AU64230/99A AU6423099A AU781336B2 AU 781336 B2 AU781336 B2 AU 781336B2 AU 64230/99 A AU64230/99 A AU 64230/99A AU 6423099 A AU6423099 A AU 6423099A AU 781336 B2 AU781336 B2 AU 781336B2
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- Australia
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- peg
- poly
- alkyl
- polymer
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- 229920001223 polyethylene glycol Polymers 0.000 title claims description 138
- 238000000034 method Methods 0.000 title claims description 94
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical class OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 title claims description 19
- 238000002360 preparation method Methods 0.000 title description 49
- 229920000642 polymer Polymers 0.000 claims description 151
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 128
- 125000000524 functional group Chemical group 0.000 claims description 96
- 125000000217 alkyl group Chemical group 0.000 claims description 94
- -1 poly(acryloylmorpholine) Polymers 0.000 claims description 68
- 239000004305 biphenyl Substances 0.000 claims description 64
- 235000010290 biphenyl Nutrition 0.000 claims description 64
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 62
- 239000000203 mixture Substances 0.000 claims description 58
- 229920002521 macromolecule Polymers 0.000 claims description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 27
- 229910001868 water Inorganic materials 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 19
- 208000021596 pentasomy X Diseases 0.000 claims description 18
- 229940079593 drug Drugs 0.000 claims description 17
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 15
- 108090000623 proteins and genes Proteins 0.000 claims description 15
- 102000004169 proteins and genes Human genes 0.000 claims description 15
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 15
- 125000006242 amine protecting group Chemical group 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 10
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 9
- 150000004676 glycans Chemical class 0.000 claims description 9
- 229920001282 polysaccharide Polymers 0.000 claims description 9
- 239000005017 polysaccharide Substances 0.000 claims description 9
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 8
- 150000002632 lipids Chemical class 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 230000003197 catalytic effect Effects 0.000 claims description 6
- 230000001268 conjugating effect Effects 0.000 claims description 6
- 229920001584 poly(acrylomorpholines) Polymers 0.000 claims description 6
- 229920000233 poly(alkylene oxides) Polymers 0.000 claims description 6
- 229920001583 poly(oxyethylated polyols) Polymers 0.000 claims description 6
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 238000011210 chromatographic step Methods 0.000 claims description 5
- 229920001577 copolymer Polymers 0.000 claims description 5
- 230000009257 reactivity Effects 0.000 claims description 5
- 229920000547 conjugated polymer Polymers 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 238000009740 moulding (composite fabrication) Methods 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 229920001400 block copolymer Polymers 0.000 claims description 2
- 229920001519 homopolymer Polymers 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 229920005604 random copolymer Polymers 0.000 claims description 2
- 229920001897 terpolymer Polymers 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 108091034117 Oligonucleotide Proteins 0.000 claims 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
- 239000000243 solution Substances 0.000 description 99
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 66
- 238000001914 filtration Methods 0.000 description 48
- 239000000047 product Substances 0.000 description 46
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- 239000002904 solvent Substances 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 11
- 238000006116 polymerization reaction Methods 0.000 description 10
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 9
- 101150065749 Churc1 gene Proteins 0.000 description 9
- 102100038239 Protein Churchill Human genes 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000005227 gel permeation chromatography Methods 0.000 description 4
- 238000002390 rotary evaporation Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- 238000011097 chromatography purification Methods 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- VBSYMODXUFYOLA-UHFFFAOYSA-N 5-phenylpenta-2,4-dienoyl chloride Chemical compound ClC(=O)C=CC=CC1=CC=CC=C1 VBSYMODXUFYOLA-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920002271 DEAE-Sepharose Polymers 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 125000005002 aryl methyl group Chemical group 0.000 description 2
- 238000005574 benzylation reaction Methods 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229920000765 poly(2-oxazolines) Polymers 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- FEIQOMCWGDNMHM-KBXRYBNXSA-N (2e,4e)-5-phenylpenta-2,4-dienoic acid Chemical compound OC(=O)\C=C\C=C\C1=CC=CC=C1 FEIQOMCWGDNMHM-KBXRYBNXSA-N 0.000 description 1
- KPPVNWGJXFMGAM-UUILKARUSA-N (e)-2-methyl-1-(6-methyl-3,4-dihydro-2h-quinolin-1-yl)but-2-en-1-one Chemical compound CC1=CC=C2N(C(=O)C(/C)=C/C)CCCC2=C1 KPPVNWGJXFMGAM-UUILKARUSA-N 0.000 description 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
- ASERXEZXVIJBRO-UHFFFAOYSA-N 3,3-diethoxypropan-1-ol Chemical compound CCOC(CCO)OCC ASERXEZXVIJBRO-UHFFFAOYSA-N 0.000 description 1
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 101100274575 Caenorhabditis elegans clh-3 gene Proteins 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical class C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001274216 Naso Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-NQAPHZHOSA-N Sorbitol Polymers OCC(O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-NQAPHZHOSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010539 anionic addition polymerization reaction Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
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- 239000013043 chemical agent Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- FEIQOMCWGDNMHM-UHFFFAOYSA-N cinnamylideneacetic acid Natural products OC(=O)C=CC=CC1=CC=CC=C1 FEIQOMCWGDNMHM-UHFFFAOYSA-N 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 150000002303 glucose derivatives Polymers 0.000 description 1
- 150000002304 glucoses Polymers 0.000 description 1
- 125000002791 glucosyl group Polymers C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 150000002314 glycerols Polymers 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229920001427 mPEG Polymers 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 238000003328 mesylation reaction Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- HXYAUPPXLDCEMQ-UHFFFAOYSA-N oxolane-2,5-dione;pyridine Chemical compound C1=CC=NC=C1.O=C1CCC(=O)O1 HXYAUPPXLDCEMQ-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 101150005399 sod2 gene Proteins 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 125000005039 triarylmethyl group Chemical group 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
-
- 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
- A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Polyethers (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1999/023536 WO2001026692A1 (en) | 1999-10-08 | 1999-10-08 | Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU6423099A AU6423099A (en) | 2001-04-23 |
| AU781336B2 true AU781336B2 (en) | 2005-05-19 |
Family
ID=22273776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU64230/99A Expired AU781336B2 (en) | 1999-10-08 | 1999-10-08 | Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP1455839B1 (https=) |
| JP (1) | JP4344110B2 (https=) |
| KR (1) | KR100499655B1 (https=) |
| CN (1) | CN1284603C (https=) |
| AU (1) | AU781336B2 (https=) |
| BR (1) | BR9917517A (https=) |
| CA (1) | CA2386762C (https=) |
| CY (1) | CY1114128T1 (https=) |
| DK (1) | DK1455839T3 (https=) |
| ES (1) | ES2404685T3 (https=) |
| HU (1) | HU228491B1 (https=) |
| IL (2) | IL148890A0 (https=) |
| MX (1) | MXPA02003540A (https=) |
| NO (1) | NO331781B1 (https=) |
| NZ (1) | NZ518143A (https=) |
| PT (1) | PT1455839E (https=) |
| WO (1) | WO2001026692A1 (https=) |
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|---|---|---|---|---|
| KR100361933B1 (ko) | 1993-09-08 | 2003-02-14 | 라 졸라 파마슈티칼 컴파니 | 화학적으로정의된비중합성결합가플랫폼분자및그것의콘주게이트 |
| CN1434726A (zh) | 2000-06-08 | 2003-08-06 | 拉卓拉药物公司 | 包含高分子量聚环氧乙烷的多价平台分子 |
| US6761824B2 (en) | 2000-08-17 | 2004-07-13 | Reeve Lorraine E | Process for the fractionation of polymers |
| US7118737B2 (en) | 2000-09-08 | 2006-10-10 | Amylin Pharmaceuticals, Inc. | Polymer-modified synthetic proteins |
| US7829074B2 (en) | 2001-10-18 | 2010-11-09 | Nektar Therapeutics | Hydroxypatite-targeting poly(ethylene glycol) and related polymers |
| US7053150B2 (en) | 2000-12-18 | 2006-05-30 | Nektar Therapeutics Al, Corporation | Segmented polymers and their conjugates |
| TW593427B (en) * | 2000-12-18 | 2004-06-21 | Nektar Therapeutics Al Corp | Synthesis of high molecular weight non-peptidic polymer derivatives |
| US7550512B2 (en) | 2001-11-28 | 2009-06-23 | Keio University | Medical polymers and uses thereof |
| JP3493608B2 (ja) * | 2001-11-28 | 2004-02-03 | 学校法人慶應義塾 | 医用高分子及びその用途 |
| GB0209539D0 (en) | 2002-04-26 | 2002-06-05 | Avecia Ltd | Monomer Polymer and process |
| WO2004012773A1 (en) | 2002-07-24 | 2004-02-12 | F. Hoffmann-La Roche Ag | Polyalkylene glycol acid additives |
| US20040062748A1 (en) | 2002-09-30 | 2004-04-01 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| US8129330B2 (en) | 2002-09-30 | 2012-03-06 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof |
| WO2004035657A1 (en) * | 2002-10-15 | 2004-04-29 | Baxter International Inc. | Process for the preparation of polyethylene glycol bis amine |
| US8034900B2 (en) | 2002-12-30 | 2011-10-11 | Amylin Pharmaceuticals, Inc. | Water-soluble thioester and selenoester compounds and methods for making and using the same |
| EP1578843B1 (en) | 2002-12-31 | 2008-07-09 | Nektar Therapeutics Al, Corporation | Methods for the formation of hydrogels using thiosulfonate compositions and uses thereof |
| CA2521381C (en) | 2003-04-11 | 2020-05-26 | Rezolute, Inc. | Method for preparation of site-specific protein conjugates |
| EP1725572B1 (de) | 2003-11-05 | 2017-05-31 | AGCT GmbH | Makromolekulare nukleotidverbindungen und methoden zu deren anwendung |
| US20050214250A1 (en) * | 2003-11-06 | 2005-09-29 | Harris J M | Method of preparing carboxylic acid functionalized polymers |
| CA2602654A1 (en) | 2005-04-05 | 2006-10-12 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa | Method for shielding functional sites or epitopes on proteins |
| EP2045282B1 (en) * | 2005-08-26 | 2011-03-23 | Novo Nordisk A/S | A method of modifying a macromolecular system |
| EP2049148B1 (en) | 2006-07-06 | 2016-09-28 | Daewoong Co., Ltd. | A stable liquid formulation of human growth hormone |
| US7985783B2 (en) | 2006-09-21 | 2011-07-26 | The Regents Of The University Of California | Aldehyde tags, uses thereof in site-specific protein modification |
| JP2013501033A (ja) | 2009-08-05 | 2013-01-10 | ピエリス アーゲー | リポカリン突然変異タンパク質の制御放出製剤 |
| EP2494073B1 (de) | 2009-10-26 | 2017-11-29 | AGCT GmbH | Konjugate von nukleotiden und methoden zu deren anwendung |
| ES2582869T3 (es) | 2011-07-05 | 2016-09-15 | Bioasis Technologies Inc | Conjugados de P97-anticuerpo |
| ES2647082T3 (es) | 2012-07-31 | 2017-12-19 | Bioasis Technologies Inc | Proteínas desfosforiladas de la enfermedad de depósito lisosómico y métodos de uso de las mismas |
| AU2013341711A1 (en) | 2012-11-12 | 2015-05-21 | Redwood Bioscience, Inc. | Compounds and methods for producing a conjugate |
| US9310374B2 (en) | 2012-11-16 | 2016-04-12 | Redwood Bioscience, Inc. | Hydrazinyl-indole compounds and methods for producing a conjugate |
| CN104870423A (zh) | 2012-11-16 | 2015-08-26 | 加利福尼亚大学董事会 | 用于蛋白质化学修饰的pictet-spengler连接反应 |
| CN103044677A (zh) * | 2012-12-28 | 2013-04-17 | 上海景宇生物科技有限公司 | 一种异端基遥爪聚乙二醇及其制备方法 |
| JP6586412B2 (ja) | 2013-03-13 | 2019-10-02 | バイオアシス テクノロジーズ インコーポレイテッド | ｐ９７のフラグメントおよびその使用 |
| US20150093399A1 (en) | 2013-08-28 | 2015-04-02 | Bioasis Technologies, Inc. | Cns-targeted conjugates having modified fc regions and methods of use thereof |
| WO2015081282A1 (en) | 2013-11-27 | 2015-06-04 | Redwood Bioscience, Inc. | Hydrazinyl-pyrrolo compounds and methods for producing a conjugate |
| CN104774161B (zh) * | 2014-01-13 | 2017-08-25 | 成都福瑞康生物科技有限公司 | 多肽、蛋白质peg修饰剂合成方法 |
| PL3636691T3 (pl) * | 2015-10-07 | 2021-09-27 | Elementis Specialties, Inc. | Środek zwilżający i przeciwpieniący |
| KR102783230B1 (ko) | 2015-11-09 | 2025-03-19 | 알.피.쉐러 테크놀러지즈 엘엘씨 | 항-cd22 항체-메이탄신 콘쥬게이트 및 그것의 사용 방법 |
| KR102247701B1 (ko) | 2016-02-26 | 2021-05-03 | 한미정밀화학주식회사 | 폴리에틸렌글리콜 디알데히드 유도체의 제조방법 |
| EP4610656A3 (en) | 2016-04-15 | 2025-11-19 | Beckman Coulter, Inc. | Photoactive macromolecules and uses thereof |
| KR20230159629A (ko) | 2016-12-12 | 2023-11-21 | 벡톤 디킨슨 앤드 컴퍼니 | 수용성 중합체 염료 |
| CN119286279A (zh) | 2017-12-26 | 2025-01-10 | 贝克顿·迪金森公司 | 深紫外线可激发的水溶剂化聚合物染料 |
| CN119220109A (zh) | 2018-03-30 | 2024-12-31 | 贝克顿·迪金森公司 | 含侧基发色团的水溶性聚合染料 |
| US20220162336A1 (en) | 2018-07-22 | 2022-05-26 | Bioasis Technologies, Inc. | Treatment of lymphatic metastases |
| JP7342757B2 (ja) * | 2019-03-29 | 2023-09-12 | 日油株式会社 | ヘテロ型単分散ポリエチレングリコール誘導体の製造方法 |
| US20210355468A1 (en) | 2020-05-18 | 2021-11-18 | Bioasis Technologies, Inc. | Compositions and methods for treating lewy body dementia |
| US20210393787A1 (en) | 2020-06-17 | 2021-12-23 | Bioasis Technologies, Inc. | Compositions and methods for treating frontotemporal dementia |
| CN113583230A (zh) * | 2021-06-30 | 2021-11-02 | 苏州欣影生物医药技术有限公司 | 一种peg双胺选择性反应制备异双官能团的方法 |
| EP4155349A1 (en) | 2021-09-24 | 2023-03-29 | Becton, Dickinson and Company | Water-soluble yellow green absorbing dyes |
| EP4547759A2 (en) | 2022-07-01 | 2025-05-07 | Beckman Coulter, Inc. | Novel fluorescent dyes and polymers from dihydrophenanthrene derivatives |
| WO2024044327A1 (en) | 2022-08-26 | 2024-02-29 | Beckman Coulter, Inc. | Dhnt monomers and polymer dyes with modified photophysical properties |
| CN115959992A (zh) * | 2022-12-13 | 2023-04-14 | 武汉翱飞科技有限公司 | 一种单分子量聚乙二醇单乙酸的合成方法 |
| CN120936679A (zh) | 2023-03-17 | 2025-11-11 | 贝克曼库尔特有限公司 | 苯并噻吩并吡咯花菁染料 |
| WO2025064842A1 (en) | 2023-09-21 | 2025-03-27 | Beckman Coulter, Inc. | Dihydrophenanthrene (dhp) bridged dyes for use in flow cytometry |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0867190B1 (en) * | 1995-05-10 | 2007-12-26 | Kyowa Hakko Kogyo Co., Ltd. | Cytotoxin complexes comprising dipeptides |
| US5672662A (en) * | 1995-07-07 | 1997-09-30 | Shearwater Polymers, Inc. | Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications |
| US20020064546A1 (en) * | 1996-09-13 | 2002-05-30 | J. Milton Harris | Degradable poly(ethylene glycol) hydrogels with controlled half-life and precursors therefor |
| JP3786832B2 (ja) * | 1998-01-07 | 2006-06-14 | デビオ ルシェルシュ ファルマシュティーク ソシエテ アノニム | 分解性のヘテロ二官能性ポリ（エチレングリコール）アクリレート及びそれから誘導されるゲル及び複合体 |
| DK1411075T3 (da) * | 1998-03-12 | 2008-10-27 | Nektar Therapeutics Al Corp | Fremgangsmåde til fremstilling af polymerkonjugater |
-
1999
- 1999-10-08 CN CNB998169714A patent/CN1284603C/zh not_active Expired - Lifetime
- 1999-10-08 WO PCT/US1999/023536 patent/WO2001026692A1/en not_active Ceased
- 1999-10-08 HU HU0203149A patent/HU228491B1/hu unknown
- 1999-10-08 PT PT99951885T patent/PT1455839E/pt unknown
- 1999-10-08 JP JP2001529753A patent/JP4344110B2/ja not_active Expired - Lifetime
- 1999-10-08 CA CA002386762A patent/CA2386762C/en not_active Expired - Lifetime
- 1999-10-08 NZ NZ518143A patent/NZ518143A/en not_active IP Right Cessation
- 1999-10-08 DK DK99951885.5T patent/DK1455839T3/da active
- 1999-10-08 KR KR10-2002-7004507A patent/KR100499655B1/ko not_active Expired - Lifetime
- 1999-10-08 BR BR9917517-7A patent/BR9917517A/pt not_active Application Discontinuation
- 1999-10-08 ES ES99951885T patent/ES2404685T3/es not_active Expired - Lifetime
- 1999-10-08 IL IL14889099A patent/IL148890A0/xx active IP Right Grant
- 1999-10-08 AU AU64230/99A patent/AU781336B2/en not_active Expired
- 1999-10-08 MX MXPA02003540A patent/MXPA02003540A/es active IP Right Grant
- 1999-10-08 EP EP99951885A patent/EP1455839B1/en not_active Expired - Lifetime
-
2002
- 2002-03-26 IL IL148890A patent/IL148890A/en not_active IP Right Cessation
- 2002-04-02 NO NO20021555A patent/NO331781B1/no not_active IP Right Cessation
-
2013
- 2013-04-23 CY CY20131100332T patent/CY1114128T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1455839A1 (en) | 2004-09-15 |
| JP2003511422A (ja) | 2003-03-25 |
| NO20021555L (no) | 2002-06-04 |
| PT1455839E (pt) | 2013-04-24 |
| KR100499655B1 (ko) | 2005-07-07 |
| CY1114128T1 (el) | 2016-07-27 |
| IL148890A (en) | 2007-09-20 |
| CN1284603C (zh) | 2006-11-15 |
| KR20020040841A (ko) | 2002-05-30 |
| HUP0203149A2 (en) | 2002-12-28 |
| NO331781B1 (no) | 2012-03-26 |
| JP4344110B2 (ja) | 2009-10-14 |
| AU6423099A (en) | 2001-04-23 |
| BR9917517A (pt) | 2002-07-30 |
| ES2404685T3 (es) | 2013-05-28 |
| WO2001026692A1 (en) | 2001-04-19 |
| CA2386762C (en) | 2009-06-16 |
| CA2386762A1 (en) | 2001-04-19 |
| DK1455839T3 (da) | 2013-05-06 |
| CN1374875A (zh) | 2002-10-16 |
| HU228491B1 (en) | 2013-03-28 |
| IL148890A0 (en) | 2002-09-12 |
| NO20021555D0 (no) | 2002-04-02 |
| EP1455839B1 (en) | 2013-01-23 |
| NZ518143A (en) | 2004-04-30 |
| MXPA02003540A (es) | 2003-09-12 |
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Legal Events
| Date | Code | Title | Description |
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| TC | Change of applicant's name (sec. 104) |
Owner name: NEKTAR THERAPEUTICS AL, CORPORATION Free format text: FORMER NAME: SHEARWATER CORPORATION |
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| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |