AU750701C - Alpha-O-linked glycoconjugates, methods of preparation and uses thereof - Google Patents
Alpha-O-linked glycoconjugates, methods of preparation and uses thereofInfo
- Publication number
- AU750701C AU750701C AU67792/98A AU6779298A AU750701C AU 750701 C AU750701 C AU 750701C AU 67792/98 A AU67792/98 A AU 67792/98A AU 6779298 A AU6779298 A AU 6779298A AU 750701 C AU750701 C AU 750701C
- Authority
- AU
- Australia
- Prior art keywords
- branched chain
- glycoconjugate
- independently
- linear
- hydrogen
- 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.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 109
- 238000002360 preparation method Methods 0.000 title description 34
- OGNJZVNNKBZFRM-UHFFFAOYSA-N 1-(5-methoxy-1H-indol-3-yl)-2-propanamine Chemical compound COC1=CC=C2NC=C(CC(C)N)C2=C1 OGNJZVNNKBZFRM-UHFFFAOYSA-N 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims description 127
- 229910052739 hydrogen Inorganic materials 0.000 claims description 120
- 125000003118 aryl group Chemical group 0.000 claims description 109
- 239000001257 hydrogen Substances 0.000 claims description 98
- 150000002431 hydrogen Chemical class 0.000 claims description 88
- 150000001720 carbohydrates Chemical class 0.000 claims description 83
- 206010028980 Neoplasm Diseases 0.000 claims description 60
- 150000004043 trisaccharides Chemical class 0.000 claims description 51
- -1 aryl carboxylic ester Chemical class 0.000 claims description 50
- 238000005859 coupling reaction Methods 0.000 claims description 50
- 230000008878 coupling Effects 0.000 claims description 48
- 238000010168 coupling process Methods 0.000 claims description 48
- 201000011510 cancer Diseases 0.000 claims description 43
- 108010015899 Glycopeptides Proteins 0.000 claims description 37
- 102000002068 Glycopeptides Human genes 0.000 claims description 37
- DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 claims description 28
- 125000002252 acyl group Chemical group 0.000 claims description 28
- 150000001875 compounds Chemical class 0.000 claims description 28
- UGJBHEZMOKVTIM-UHFFFAOYSA-N N-formylglycine Chemical compound OC(=O)CNC=O UGJBHEZMOKVTIM-UHFFFAOYSA-N 0.000 claims description 26
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 26
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
- 210000004027 cell Anatomy 0.000 claims description 24
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 24
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 23
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 21
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 21
- 239000002671 adjuvant Substances 0.000 claims description 18
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 17
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 17
- 150000004044 tetrasaccharides Chemical class 0.000 claims description 17
- 201000009030 Carcinoma Diseases 0.000 claims description 13
- 102000014914 Carrier Proteins Human genes 0.000 claims description 13
- 108010078791 Carrier Proteins Proteins 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 241000282414 Homo sapiens Species 0.000 claims description 10
- 230000001939 inductive effect Effects 0.000 claims description 10
- 241000894006 Bacteria Species 0.000 claims description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 9
- 229940098773 bovine serum albumin Drugs 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 102000004169 proteins and genes Human genes 0.000 claims description 9
- 108090000623 proteins and genes Proteins 0.000 claims description 9
- 108010039918 Polylysine Proteins 0.000 claims description 8
- 241001222774 Salmonella enterica subsp. enterica serovar Minnesota Species 0.000 claims description 8
- 239000000568 immunological adjuvant Substances 0.000 claims description 8
- 239000002502 liposome Substances 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 229920000656 polylysine Polymers 0.000 claims description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 claims description 7
- 150000002482 oligosaccharides Polymers 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 6
- 239000012634 fragment Substances 0.000 claims description 6
- 108010060969 sialosyl-T antigen Proteins 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- 238000001356 surgical procedure Methods 0.000 claims description 5
- 239000004971 Cross linker Substances 0.000 claims description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- UGUUDTWORXNLAK-UHFFFAOYSA-N azidoalcohol Chemical compound ON=[N+]=[N-] UGUUDTWORXNLAK-UHFFFAOYSA-N 0.000 claims description 4
- 150000002016 disaccharides Chemical class 0.000 claims description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 4
- 150000002772 monosaccharides Chemical class 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 210000004881 tumor cell Anatomy 0.000 claims description 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 claims description 3
- 229930182470 glycoside Natural products 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 230000001268 conjugating effect Effects 0.000 claims description 2
- 239000003431 cross linking reagent Substances 0.000 claims description 2
- 125000005432 dialkylcarboxamide group Chemical group 0.000 claims description 2
- 150000002338 glycosides Chemical class 0.000 claims description 2
- GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical compound [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 claims description 2
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 claims description 2
- 229910000103 lithium hydride Inorganic materials 0.000 claims description 2
- AHNJTQYTRPXLLG-UHFFFAOYSA-N lithium;diethylazanide Chemical compound [Li+].CC[N-]CC AHNJTQYTRPXLLG-UHFFFAOYSA-N 0.000 claims description 2
- 229920002601 oligoester Polymers 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 claims description 2
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims description 2
- 229910000105 potassium hydride Inorganic materials 0.000 claims description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- HEYWXOWEALDDOL-UHFFFAOYSA-N tetraethylazanium;azide Chemical compound [N-]=[N+]=[N-].CC[N+](CC)(CC)CC HEYWXOWEALDDOL-UHFFFAOYSA-N 0.000 claims description 2
- SUBUUGVBEKEFGW-UHFFFAOYSA-N tetramethylazanium;azide Chemical compound [N-]=[N+]=[N-].C[N+](C)(C)C SUBUUGVBEKEFGW-UHFFFAOYSA-N 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims description 2
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical group CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 claims description 2
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims 1
- 125000005392 carboxamide group Chemical class NC(=O)* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 239000000243 solution Substances 0.000 description 83
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 76
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
- 239000000203 mixture Substances 0.000 description 64
- 238000006243 chemical reaction Methods 0.000 description 61
- 239000000741 silica gel Substances 0.000 description 56
- 229910002027 silica gel Inorganic materials 0.000 description 56
- 239000002904 solvent Substances 0.000 description 53
- 235000014633 carbohydrates Nutrition 0.000 description 52
- 238000004587 chromatography analysis Methods 0.000 description 50
- 238000005481 NMR spectroscopy Methods 0.000 description 48
- 239000000386 donor Substances 0.000 description 47
- 239000011734 sodium Substances 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 35
- 235000019439 ethyl acetate Nutrition 0.000 description 35
- 239000000047 product Substances 0.000 description 32
- 238000001704 evaporation Methods 0.000 description 28
- 230000008020 evaporation Effects 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 239000012267 brine Substances 0.000 description 23
- 239000002808 molecular sieve Substances 0.000 description 23
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 22
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 20
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 239000004473 Threonine Substances 0.000 description 18
- 239000000370 acceptor Substances 0.000 description 18
- 229960002898 threonine Drugs 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 229960001153 serine Drugs 0.000 description 16
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 15
- 239000000427 antigen Substances 0.000 description 15
- 102000036639 antigens Human genes 0.000 description 15
- 108091007433 antigens Proteins 0.000 description 15
- 108090000765 processed proteins & peptides Proteins 0.000 description 15
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 14
- UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 description 14
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 14
- MTCFGRXMJLQNBG-UHFFFAOYSA-M serinate Chemical compound OCC(N)C([O-])=O MTCFGRXMJLQNBG-UHFFFAOYSA-M 0.000 description 14
- 229960005486 vaccine Drugs 0.000 description 14
- 102000003886 Glycoproteins Human genes 0.000 description 13
- 108090000288 Glycoproteins Proteins 0.000 description 13
- 108010063954 Mucins Proteins 0.000 description 13
- 102000015728 Mucins Human genes 0.000 description 13
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 13
- 238000010626 work up procedure Methods 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 150000002373 hemiacetals Chemical class 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000013459 approach Methods 0.000 description 11
- 238000002329 infrared spectrum Methods 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- 229940024606 amino acid Drugs 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000010511 deprotection reaction Methods 0.000 description 9
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 238000001819 mass spectrum Methods 0.000 description 9
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 229910004373 HOAc Inorganic materials 0.000 description 8
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 125000000837 carbohydrate group Chemical group 0.000 description 8
- 239000013058 crude material Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
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- 239000004480 active ingredient Substances 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
- VSTHIIUXGVJHDH-UHFFFAOYSA-N azido nitrate Chemical class [O-][N+](=O)ON=[N+]=[N-] VSTHIIUXGVJHDH-UHFFFAOYSA-N 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 230000021615 conjugation Effects 0.000 description 6
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 125000003147 glycosyl group Chemical group 0.000 description 6
- 229940051875 mucins Drugs 0.000 description 6
- DYMRYCZRMAHYKE-UHFFFAOYSA-N n-diazonitramide Chemical class [O-][N+](=O)N=[N+]=[N-] DYMRYCZRMAHYKE-UHFFFAOYSA-N 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 150000003354 serine derivatives Chemical class 0.000 description 6
- 238000002255 vaccination Methods 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 5
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 4
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- YVECGMZCTULTIS-HSUXUTPPSA-N D-galactal Chemical compound OC[C@H]1OC=C[C@@H](O)[C@H]1O YVECGMZCTULTIS-HSUXUTPPSA-N 0.000 description 4
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- DOVBXGDYENZJBJ-ONMPCKGSSA-N lactosamine Chemical compound O=C[C@H](N)[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O DOVBXGDYENZJBJ-ONMPCKGSSA-N 0.000 description 1
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- HPFQTCRYSOTMDJ-UHFFFAOYSA-M lithium;benzenethiolate Chemical compound [Li+].[S-]C1=CC=CC=C1 HPFQTCRYSOTMDJ-UHFFFAOYSA-M 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 1
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- COCAUCFPFHUGAA-MGNBDDOMSA-N n-[3-[(1s,7s)-5-amino-4-thia-6-azabicyclo[5.1.0]oct-5-en-7-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound C=1C=C(F)C([C@@]23N=C(SCC[C@@H]2C3)N)=CC=1NC(=O)C1=CC=C(Cl)C=N1 COCAUCFPFHUGAA-MGNBDDOMSA-N 0.000 description 1
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- 125000001151 peptidyl group Chemical group 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
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- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
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- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
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- 230000004083 survival effect Effects 0.000 description 1
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- 229940126577 synthetic vaccine Drugs 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
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- PSWFFKRAVBDQEG-YGQNSOCVSA-N thymopentin Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 PSWFFKRAVBDQEG-YGQNSOCVSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4727—Mucins, e.g. human intestinal mucin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
- C07K9/001—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence having less than 12 amino acids and not being part of a ring structure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4371397P | 1997-04-16 | 1997-04-16 | |
| US60/043713 | 1997-04-16 | ||
| PCT/US1998/006035 WO1998046246A1 (en) | 1997-04-16 | 1998-03-25 | α-O-LINKED GLYCOCONJUGATES WITH CLUSTERED (2,6)-ST EPITOPES, METHODS OF PREPARATION AND USES THEREOF |
Publications (3)
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|---|---|
| AU6779298A AU6779298A (en) | 1998-11-11 |
| AU750701B2 AU750701B2 (en) | 2002-07-25 |
| AU750701C true AU750701C (en) | 2003-03-20 |
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| AU67792/98A Expired AU750701C (en) | 1997-04-16 | 1998-03-25 | Alpha-O-linked glycoconjugates, methods of preparation and uses thereof |
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| Country | Link |
|---|---|
| US (2) | US6660714B1 (https=) |
| EP (1) | EP0996455B1 (https=) |
| JP (1) | JP4308918B2 (https=) |
| AU (1) | AU750701C (https=) |
| CA (1) | CA2286798C (https=) |
| WO (1) | WO1998046246A1 (https=) |
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| US7550146B2 (en) | 1997-04-16 | 2009-06-23 | Sloan-Kettering Institute For Cancer Research | Glycopeptide conjugates and uses thereof |
| EP0996455B1 (en) | 1997-04-16 | 2009-12-16 | Sloan-Kettering Institute For Cancer Research | Alpha-o-linked glycoconjugates with clustered (2,6)-st epitopes, methods of preparation and uses thereof |
| CA2324616A1 (en) * | 1998-03-25 | 1999-09-30 | Sloan-Kettering Institute For Cancer Research | Trimeric antigenic o-linked glycopeptide conjugates, methods of preparation and uses thereof |
| US7824687B2 (en) * | 1999-08-20 | 2010-11-02 | Sloan-Kettering Institute For Cancer Research | Clustered multi-antigenic carbohydrate constructs, methods for their preparation, and uses thereof |
| DE60027905T2 (de) | 1999-08-20 | 2007-05-10 | Sloan-Kettering Institute For Cancer Research | Glycokonjugate, glycoaminosäure, deren zwischenprodukte, und ihre verwendung |
| US7854934B2 (en) | 1999-08-20 | 2010-12-21 | Sloan-Kettering Institute For Cancer Research | Glycoconjugates, glycoamino acids, intermediates thereto, and uses thereof |
| EP1458242A4 (en) * | 2001-07-06 | 2006-06-07 | Sloan Kettering Inst Cancer | COMPREHENSIVE CONJUGATED VACCINE AGAINST CANCER |
| US7504364B2 (en) * | 2002-03-01 | 2009-03-17 | Receptors Llc | Methods of making arrays and artificial receptors |
| CA2486881A1 (en) * | 2002-05-20 | 2003-11-27 | Chemstop Pty Ltd | Process for the preparation and activation of substances and a means of producing same |
| US20060057625A1 (en) * | 2002-09-16 | 2006-03-16 | Carlson Robert E | Scaffold-based artificial receptors and methods |
| US7469076B2 (en) * | 2003-09-03 | 2008-12-23 | Receptors Llc | Sensors employing combinatorial artificial receptors |
| US20050037429A1 (en) * | 2003-03-28 | 2005-02-17 | Receptors Llc | Artificial receptors including reversibly immobilized building blocks and methods |
| WO2005003326A2 (en) * | 2003-03-28 | 2005-01-13 | Receptors Llc. | Artificial receptors including reversibly immobilized building blocks and methods |
| US20050037381A1 (en) * | 2002-09-16 | 2005-02-17 | Receptors Llc | Artificial receptors, building blocks, and methods |
| US20050136483A1 (en) * | 2003-09-03 | 2005-06-23 | Receptors Llc | Nanodevices employing combinatorial artificial receptors |
| US20060051802A1 (en) * | 2002-09-16 | 2006-03-09 | Receptors Llc | Artificial receptors, building blocks, and methods |
| US20040137481A1 (en) * | 2002-09-16 | 2004-07-15 | Receptors Llc | Artificial receptor building blocks, components, and kits |
| US20060035267A1 (en) * | 2003-04-09 | 2006-02-16 | Livingston Philip O | Optimal polyvalent vaccine for cancer |
| WO2005044841A1 (en) * | 2003-09-05 | 2005-05-19 | Sloan-Kettering Institute For Cancer Research | Method for preparing polyfunctionalized peptides and/or proteins via native chemical ligation |
| EP1789797A1 (en) * | 2004-09-03 | 2007-05-30 | Receptors LLC | Combinatorial artifical receptors including tether building blocks |
| WO2006029383A2 (en) | 2004-09-11 | 2006-03-16 | Receptors Llc | Combinatorial artificial receptors including peptide building blocks |
| JP4942014B2 (ja) * | 2004-09-14 | 2012-05-30 | 独立行政法人産業技術総合研究所 | Ｏ−結合型糖アミノ酸 |
| EP1808442B1 (en) | 2006-01-13 | 2011-05-11 | Institut Pasteur | Enzymatic large-scale synthesis of mucin glyconjugates, and immunogenic applications thereof |
| EP2010556B1 (en) | 2006-04-11 | 2015-09-23 | Sloan-Kettering Institute for Cancer Research | Homogeneous erythropoietin and method for their preparation |
| ES2477549T3 (es) | 2008-06-16 | 2014-07-17 | Academia Sinica | Diagnóstico del cáncer según la concentración de anticuerpos contra Globo H y sus fragmentos |
| CN102065868A (zh) * | 2008-06-16 | 2011-05-18 | 中央研究院 | 诱发对于Globo H及SSEA3的特异免疫反应的组合物以及其在癌症治疗中的用途 |
| EP2315771A4 (en) * | 2008-07-11 | 2012-02-01 | Sloan Kettering Inst Cancer | GLYCOPEPTIDE CONSTRUCTS AND USES THEREOF |
| CN105535955B (zh) * | 2009-06-16 | 2019-04-23 | 中央研究院 | Globo h及含新颖糖脂质佐剂的相关抗癌疫苗 |
| US9493580B2 (en) | 2010-06-11 | 2016-11-15 | Sloan-Kettering Institute For Cancer Research | Multivalent glycopeptide constructs and uses thereof |
| EP2500033A1 (en) * | 2011-03-17 | 2012-09-19 | Institut Pasteur | Method for preparing muliple antigen glycopeptide carbohydrate conjugates |
| US10942184B2 (en) | 2012-10-23 | 2021-03-09 | Caris Science, Inc. | Aptamers and uses thereof |
| AU2013340414B2 (en) | 2012-10-23 | 2019-05-02 | Caris Science, Inc. | Aptamers and uses thereof |
| EP2935628B1 (en) | 2012-12-19 | 2018-03-21 | Caris Life Sciences Switzerland Holdings GmbH | Compositions and methods for aptamer screening |
| JP6401380B2 (ja) | 2014-08-22 | 2018-10-10 | アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ | 新規のグリカンコンジュゲート及びその使用 |
| PT110526B (pt) | 2018-01-26 | 2021-02-04 | Univ Nova De Lisboa | Anticorpo, fragmento funcional ou sonda do mesmo contra antigénios tumorais |
| CN111303112A (zh) * | 2020-02-28 | 2020-06-19 | 南京工业大学 | 一种固定二氧化碳的方法 |
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| US4971795A (en) | 1986-07-08 | 1990-11-20 | Biomira, Inc. | Enhancement of the cellular immune response using carbohydrate primed DTH effector cells expressing the CD5+/CD8- phenotype |
| EP0823438A3 (en) | 1987-01-07 | 1999-09-15 | Imperial Cancer Research Technology Limited | Human mucin cone protein: peptide fragments and antibodies thereto, and uses thereof in diagnostic and therapeutic methods |
| US6222020B1 (en) | 1987-01-07 | 2001-04-24 | Imperial Cancer Research Technology Limited | Antigens derived from the core protein of the human mammary epithelial mucin |
| US5683674A (en) | 1987-01-07 | 1997-11-04 | Imperial Cancer Research Technology Ltd. | Antibody against human mucin core protein and method of preparing and using same |
| US5053489A (en) | 1988-01-29 | 1991-10-01 | Dana-Farber Cancer Institute, Inc. | Genetically engineered polypeptides with determinants of the human DF3 breast carcinoma-associated antigen |
| US5660834A (en) | 1988-03-11 | 1997-08-26 | The Biomembrane Institute | Monoclonal antibodies and vaccine development directed to human cancer-associated antigens by immunization with carbohydrate-carrier conjugates |
| US5229289A (en) | 1988-03-11 | 1993-07-20 | The Biomembrane Institute | Monoclonal antibodies and vaccine development directed to human cancer-associated antigens by immunization with animal and human and with synthetic carbohydrate-carrier conjugates |
| EP0395217A3 (en) | 1989-04-28 | 1991-01-23 | The Biomembrane Institute | Bio-organic synthesis of dimeric lex (difucosyl y2; iii3fucv3-funcnlc6cer) and analogues thereof |
| IL94872A (en) | 1989-06-30 | 1995-03-30 | Oncogen | Monoclonal or chimeric antibodies reactive with human carcinomas, recombinant proteins comprising their antigen binding region, pharmaceutical compositions and kits comprising said antibodies and methods for imaging human carcinoma using same |
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| IL105503A (en) | 1992-04-28 | 1999-05-09 | Astra Ab | Carbon peptide couplets capable of eliciting an immune response of T cells |
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| WO1995018781A1 (en) | 1994-01-06 | 1995-07-13 | Metabolix, Inc. | Methods for synthesizing oligomers containing hydroxy acid units |
| US5679769A (en) | 1994-03-15 | 1997-10-21 | Sloan-Kettering Institute For Cancer Research | Synthesis of asparagine-linked glycopeptides on a polymeric solid support |
| US6303120B1 (en) | 1994-03-15 | 2001-10-16 | Memorial Sloan-Kettering Institute For Cancer Research | Synthesis of glycoconjugates of the lewis y epitope and uses thereof |
| US5708163A (en) * | 1994-03-15 | 1998-01-13 | Sloan-Kettering Institute Of Cancer Research | Synthesis of the breast tumor-associated antigen defined by monoclonalantibody MBRL and uses thereof |
| CA2189356A1 (en) | 1994-05-02 | 1995-11-09 | Ting Chi Wong | Process for preparation of glycosides of tumor-associated carbohydrate antigens |
| DE4436164A1 (de) | 1994-10-10 | 1996-04-11 | Hoechst Ag | Neue Kohlenhydratkonjugate als Inhibitoren der Zelladhäsion |
| JP3139957B2 (ja) | 1995-03-17 | 2001-03-05 | 財団法人神奈川科学技術アカデミー | レクチンの固定化法及びそれを用いた細胞用基材 |
| US5871990A (en) | 1996-05-15 | 1999-02-16 | Clausen; Henrik | UDP-N-acetyl-α-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase, gAlnAc-T3 |
| WO1998030190A2 (en) | 1997-01-13 | 1998-07-16 | Sloan-Kettering Institute For Cancer Research | Colon cancer kh-1 and n3 antigens |
| EP0996455B1 (en) * | 1997-04-16 | 2009-12-16 | Sloan-Kettering Institute For Cancer Research | Alpha-o-linked glycoconjugates with clustered (2,6)-st epitopes, methods of preparation and uses thereof |
| US7550146B2 (en) | 1997-04-16 | 2009-06-23 | Sloan-Kettering Institute For Cancer Research | Glycopeptide conjugates and uses thereof |
| WO1999015201A1 (en) | 1997-09-25 | 1999-04-01 | Sloan-Kettering Institute For Cancer Research | Fucosyl gm1-klh conjugate vaccine against small cell lung cancer |
| CA2324616A1 (en) | 1998-03-25 | 1999-09-30 | Sloan-Kettering Institute For Cancer Research | Trimeric antigenic o-linked glycopeptide conjugates, methods of preparation and uses thereof |
| DE60027905T2 (de) | 1999-08-20 | 2007-05-10 | Sloan-Kettering Institute For Cancer Research | Glycokonjugate, glycoaminosäure, deren zwischenprodukte, und ihre verwendung |
| US7854934B2 (en) | 1999-08-20 | 2010-12-21 | Sloan-Kettering Institute For Cancer Research | Glycoconjugates, glycoamino acids, intermediates thereto, and uses thereof |
| US7824687B2 (en) | 1999-08-20 | 2010-11-02 | Sloan-Kettering Institute For Cancer Research | Clustered multi-antigenic carbohydrate constructs, methods for their preparation, and uses thereof |
-
1998
- 1998-03-25 EP EP98913180A patent/EP0996455B1/en not_active Expired - Lifetime
- 1998-03-25 JP JP54393498A patent/JP4308918B2/ja not_active Expired - Lifetime
- 1998-03-25 US US09/083,776 patent/US6660714B1/en not_active Expired - Lifetime
- 1998-03-25 WO PCT/US1998/006035 patent/WO1998046246A1/en not_active Ceased
- 1998-03-25 AU AU67792/98A patent/AU750701C/en not_active Expired
- 1998-03-25 CA CA2286798A patent/CA2286798C/en not_active Expired - Lifetime
-
2002
- 2002-07-25 US US10/205,021 patent/US7160856B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998046246A1 (en) | 1998-10-22 |
| EP0996455B1 (en) | 2009-12-16 |
| CA2286798A1 (en) | 1998-10-22 |
| CA2286798C (en) | 2014-01-07 |
| EP0996455A1 (en) | 2000-05-03 |
| JP2002515060A (ja) | 2002-05-21 |
| AU6779298A (en) | 1998-11-11 |
| US6660714B1 (en) | 2003-12-09 |
| US7160856B2 (en) | 2007-01-09 |
| JP4308918B2 (ja) | 2009-08-05 |
| AU750701B2 (en) | 2002-07-25 |
| US20030083235A1 (en) | 2003-05-01 |
| EP0996455A4 (en) | 2005-06-08 |
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