JP2008543738A - 第VIII因子及びvonWillebrand’s因子のためのアフィニティー吸着剤 - Google Patents
第VIII因子及びvonWillebrand’s因子のためのアフィニティー吸着剤 Download PDFInfo
- Publication number
- JP2008543738A JP2008543738A JP2008510633A JP2008510633A JP2008543738A JP 2008543738 A JP2008543738 A JP 2008543738A JP 2008510633 A JP2008510633 A JP 2008510633A JP 2008510633 A JP2008510633 A JP 2008510633A JP 2008543738 A JP2008543738 A JP 2008543738A
- Authority
- JP
- Japan
- Prior art keywords
- adsorbent
- use according
- formula
- factor
- factor viii
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229960001134 von willebrand factor Drugs 0.000 title claims abstract description 20
- 108010054218 Factor VIII Proteins 0.000 title claims abstract description 18
- 102000001690 Factor VIII Human genes 0.000 title claims abstract description 18
- 239000003463 adsorbent Substances 0.000 title claims abstract description 18
- 229960000301 factor viii Drugs 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 9
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000000746 purification Methods 0.000 claims abstract description 7
- -1 β-phenylethyl Chemical group 0.000 claims abstract description 6
- 239000011159 matrix material Substances 0.000 claims abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 4
- 125000006850 spacer group Chemical group 0.000 claims abstract description 4
- 125000006414 CCl Chemical group ClC* 0.000 claims abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
- 238000002955 isolation Methods 0.000 claims abstract description 3
- 230000007935 neutral effect Effects 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims abstract 6
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims abstract 3
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims abstract 2
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract 2
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims abstract 2
- 238000012512 characterization method Methods 0.000 claims abstract 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims abstract 2
- 229930195733 hydrocarbon Natural products 0.000 claims abstract 2
- 238000011002 quantification Methods 0.000 claims abstract 2
- 125000001453 quaternary ammonium group Chemical group 0.000 claims abstract 2
- 238000000926 separation method Methods 0.000 claims abstract 2
- 125000001302 tertiary amino group Chemical group 0.000 claims abstract 2
- 239000007787 solid Substances 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims 3
- 125000003277 amino group Chemical group 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 108010047303 von Willebrand Factor Proteins 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 102100026735 Coagulation factor VIII Human genes 0.000 description 15
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000003446 ligand Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 5
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 208000034158 bleeding Diseases 0.000 description 3
- 230000000740 bleeding effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 2
- WITMXBRCQWOZPX-UHFFFAOYSA-N 1-phenylpyrazole Chemical compound C1=CC=NN1C1=CC=CC=C1 WITMXBRCQWOZPX-UHFFFAOYSA-N 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 201000003542 Factor VIII deficiency Diseases 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 208000009292 Hemophilia A Diseases 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- CJWGCBRQAHCVHW-SSDOTTSWSA-N (1r)-1-(3-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC([C@@H](C)N)=C1 CJWGCBRQAHCVHW-SSDOTTSWSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- JCBPETKZIGVZRE-UHFFFAOYSA-N 2-aminobutan-1-ol Chemical compound CCC(N)CO JCBPETKZIGVZRE-UHFFFAOYSA-N 0.000 description 1
- KRQUHMFZMVSALZ-UHFFFAOYSA-N 4-amino-2-(diethylaminomethyl)phenol Chemical compound CCN(CC)CC1=CC(N)=CC=C1O KRQUHMFZMVSALZ-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 101000782195 Homo sapiens von Willebrand factor Proteins 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- OCFIEIDMUHJKKM-LLVKDONJSA-N N-[(1R)-2,2-dichloro-1-(3-methoxyphenyl)ethyl]triazin-4-amine Chemical compound ClC([C@@H](C1=CC(=CC=C1)OC)NC1=NN=NC=C1)Cl OCFIEIDMUHJKKM-LLVKDONJSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- QOHMWDJIBGVPIF-UHFFFAOYSA-N n',n'-diethylpropane-1,3-diamine Chemical compound CCN(CC)CCCN QOHMWDJIBGVPIF-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
- B01J20/289—Phases chemically bonded to a substrate, e.g. to silica or to polymers bonded via a spacer
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
- B01J20/3206—Organic carriers, supports or substrates
- B01J20/3208—Polymeric carriers, supports or substrates
- B01J20/3212—Polymeric carriers, supports or substrates consisting of a polymer obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3214—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the method for obtaining this coating or impregnating
- B01J20/3217—Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond
- B01J20/3219—Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond involving a particular spacer or linking group, e.g. for attaching an active group
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3244—Non-macromolecular compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3244—Non-macromolecular compounds
- B01J20/3246—Non-macromolecular compounds having a well defined chemical structure
- B01J20/3248—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such
- B01J20/3251—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3244—Non-macromolecular compounds
- B01J20/3246—Non-macromolecular compounds having a well defined chemical structure
- B01J20/3248—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such
- B01J20/3253—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such comprising a cyclic structure not containing any of the heteroatoms nitrogen, oxygen or sulfur, e.g. aromatic structures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3244—Non-macromolecular compounds
- B01J20/3246—Non-macromolecular compounds having a well defined chemical structure
- B01J20/3248—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such
- B01J20/3255—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such comprising a cyclic structure containing at least one of the heteroatoms nitrogen, oxygen or sulfur, e.g. heterocyclic or heteroaromatic structures
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/48—Two nitrogen atoms
- C07D251/50—Two nitrogen atoms with a halogen atom attached to the third ring carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/54—Three nitrogen atoms
- C07D251/70—Other substituted melamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/54—Sorbents specially adapted for analytical or investigative chromatography
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/58—Use in a single column
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/745—Assays involving non-enzymic blood coagulation factors
- G01N2333/755—Factors VIII, e.g. factor VIII C [AHF], factor VIII Ag [VWF]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
- Y10T436/255—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.] including use of a solid sorbent, semipermeable membrane, or liquid extraction
Abstract
Aは、スペーサーによりトリアジン環に場合により連結された支持マトリックスであり;
YはO,S又はNR2であり;
ZはO,S又はN−R3であり;
R2とR3は各々H、C1-6アルキル、C1-6ヒドロキシアルキル、ベンジル又はβ−フェニルエチルであり;
BとWは各々、1〜10個の炭素原子を含む場合により置換された炭化水素連結であり;
DはH,OH又は第一アミノ、第二アミノ、第三アミノ、第四アンモニウム、イミダゾール、グアニジノ又はアミジノ基であり;又は
B−Dは、−CHCOOH−(CH2)3-4−NH2であり;そして
R7は、中性pHにおいて正電荷をもつ基である。}で表される化合物であるアフィニティー吸着剤を使用する。
Description
本発明は、化合物、及びアフィニティー・リガンドとしてのそれらの使用に関する。
(抗血友病因子として先に知られていた)第VIII因子は、約200ng/mLのレベルで循環血漿中に存在する糖タンパク質である。天然の成熟1本鎖タンパク質は、糖添加に依存して265〜270kDaの間の異質な分子量をもつ。但し、170〜280kDaの広いレンジの分子量のタンパク質が、対立遺伝子の変動、糖添加、修飾、及びインビボにおける断片化に依存して、血漿中で観察される。多数の組換え第VIII因子産物が入手可能であり、そしてまた、タンパク質構造及び分子量においてかなり変動している。
1のXはNであり、そして他のXはN,C−Cl又はC−CNであり;
YはO,S又はNR2であり;
ZはO,S又はNR3であり;
R2とR3は各々H、アルキル、ヒドロキシアルキル、ベンジル又はβ−フェニルエチルであり;
Qは、ベンゼン、ナフタレン、ベンズチアゾール、ベンズオキサゾール、1−フェニルピラゾール、インダゾール又はベンズイミダゾールであり;
R4,R5とR6は各々、H,OH、アルキル、アルコキシ、アミノ、NH2、アシルオキシ、アシルアミノ、CO2H、スルホン酸、カルバモイル、スルファモイル、アルキルスルフォニル又はハロゲンであり;
nは0〜6であり;
pは0〜20であり;そして
Aは、スペーサーによりトリアジン環に場合により連結された支持マトリックスである。}で表されるトリアジン−ベースの化合物を開示する。
驚ろくべきことに、その内の多くが新規である特定の化合物がvWF/FVIIIのアフィニティー−ベースの単離のために有用であることが発見された。これらの化合物は以下の式(II):
R7は、中性pHにおいて正電荷をもつ基であり;
Wは、任意的リンカーであり;
Vは、Qのために先に記載したものと同じであるが、節構造であってもよく;そして
R8とR9は、R4,R5とR6のために定義したものと同じであるが、環構造をさらに含むか、又はR8とR9は連結して、当該環構造を形成する。}を有する。
WO97/10887,WO00/67900、及びWO03/097112は、リガンドのコンビナトリアル・ライブラリーが固体支持体上でどのようにして構築されうるかということを開示する。本発明に共通する態様及び手順の例を含むそれらの開示を、本明細書中に援用する。供給原料としてプールされたヒト血漿を用いてこれらのコンビナトリアル・ライブラリーのセットをスクリーニングする間、ヒトvWF/FVIIIに選択的に結合し、かつ、これを溶出することができるものとして多数のリガンドが同定された。
TはO,S又は−NR7−であり;
mは0又は1であり;
V1は2〜20個のC原子の場合により置換された炭化水素基であり;そして
V2はO,S,−COO−,−CONH−,−NHCO−,−PO3H−,−NH−アリーレン−SO2−CH2−CH2−又は−NR8−であり;そして
R7とR8は各々独立にH又はC1-6アルキルである。
以下の実施例は本発明を説明する。
アセトン(35mL)中に溶解した塩化シアヌール酸(5.0g)を0℃に冷却し、その後、アセトン(50ml)中に溶解した(R)−1−(3−メトキシフェニル)エチルアミン(4.1g)を冷却しながら30分間にわたり滴下して添加して、その温度が5℃を上廻らないようにした。次いで、10M水酸化ナトリウム(2.71mL)をゆっくりと添加した。45分後、反応混合物を撹拌しながら氷水(20g)に添加した。油状生成物をジクロロメタン(150mL)中に抽出し、無水硫酸マグネシウム上で乾燥させ、そして蒸発させて黄色油(7.96g)として生成物を得た。
アミノ−Sepharose CL−4B(水中沈殿475g−16μmol/g置換)に、ジメチルホルムアミド(DMF)(475mL)を添加した。ジイソプロピルエチルアミン(4.37mL)を添加し、混合物を15分間撹拌し、その後、DMF(250mL)中に溶解したジクロロトリアジニル−(R)−1−(3−メトキシフェニル)−エチルアミン(7.57g)を反応混合物に添加した。この混合物を3時間にわたり撹拌し、その後、ゲルを、70%水性DMF(4×500mL)、50%水性DMF(2×500mL)、及び水(11×500mL)で洗浄した。水(75mL)中にスラリー化した上記材料150gを、60℃で水(75mL)中N,N−ジエチル−1,3−プロパンジアミン(3.8mL)の溶液に分割して添加した。添加後、混合物を60℃に温め、そして19時間にわたりこの温度で撹拌した。次いで、ゲルを濾過し、そして水(12×150mL)で洗浄し、その後、20%水性エタノール保存液中で保存した。
実施例2(150g沈殿)からの中間体ゲル生成物を、水(75mL)中にスラリー化し、そして60℃における水(75mL)中の2−(2−アミノエチル)−1−メチルピロリジン(3.5mL)の溶液に分割して添加した。添加後、混合物を再び60℃に温め、そして19時間にわたりこの温度で撹拌した。次いで、このゲルを濾過し、そして水(12×150mL)で洗浄し、その後、20%水性エタノール保存液中で保存した。
アミノ−Sepharose CL−4B(水中沈殿100g−16μmol/g置換)を、1Mリン酸カリウムpH7.0(100mL)中に懸濁し、次いで排水した。その後このゲルに、1Mリン酸カリウムpH7.0(25mL)、及びRO水(250mL)を添加した。このスラリーを激しく撹拌し、同時にアセトン(50mL)を添加した。30分間にわたり氷/塩浴内で冷却した後、冷アセトン(25mL)中塩化シアヌール酸(2.5g)を一部で添加した。この混合物を1時間にわたり0℃で撹拌し、その後、50%水性アセトン(5×100mL)、RO水(5×100mL)、50%水性アセトン(5×100mL)、及びRO水(10×100mL)で洗浄した。この沈殿ゲルをその後、4時間にわたり室温で、2−アミノブタノール(1g)を含む50%水性DMF(100mL)でスラリー化した。このスラリーを濾過し、次いで50%水性DMF(5×100mL)及びRO水(10×100mL)で洗浄した。次いでこの沈殿ゲルを、4−アミノ−a−ジエチルアミノ−o−クレゾールジヒドロクロリド(4.2g)を含む50%水性DMF(100mL)でスラリー化し、そして60℃で一夜撹拌した。このスラリーを濾過し、その後、50%水性DMF(5×100mL)とRO水(10×100mL)で洗浄した。このゲルを40℃で3日間にわたり0.5M NaOH/25%エタノールの最終濃度でインキュベートし、0.5M NaOH/25%エタノール(5×100mL)で洗浄し、その後RO水(10×100mL)で洗浄した。最終洗浄液を重力下で放置して排水した後、1.0M NaOH(100mL)を添加し、そして混合物を3日間40℃でインキュベートした。その後、ゲルを0.5M NaOH(5×100mL)で、次いでRO水(10×100mL)で洗浄した。0.1M PBS pH7.0(3×100mL)で洗浄した後、ゲルをさらにRO水(10×100mL)で洗浄し、その後、20%v/v水性エタノール中4℃で冷却室内で保存した。
低圧クロマトグラフィー・システム(Kipp & Zonen平床チャート−レコーダー、Gilsonミニプラス3蠕動ポンプ、及びGilson UV検出器)を用いた20mLカラム容量をもつ1.6cm直径XK16/20カラムを用いて、クロマトグラフィー実験を実施した。カラムを、80cm/時間において、20mM Tris−HCl、20mMクエン酸ナトリウム、140mM塩化ナトリウムpH7.5の5カラム容量で平衡化した。ヒト起源血漿を、20mM Tris−HCl及び100mM塩化ナトリウム(最終濃度)で処理した。処理した血漿200mLを10μmで濾過し、次いで、80cm/時間でロードした。ロード後洗浄を20mM Tris−HCl、20mMクエン酸ナトリウム、及び140mM塩化ナトリウムpH7.5で行い、ベースライン吸光度までもっていった。次いでこのカラムを20mM Tris−HCl、20mMクエン酸ナトリウム、3mM CaCl2、30%エチレングリコール、及び500mM塩化ナトリウム、及び0.01% Tween 80 pH7.5で溶出した。溶出後、カラムを8M尿素pH7.0で殺菌洗浄した。その後、カラムを0.5M水酸化ナトリウムで洗浄した。ロード、非結合、及び溶出フラクションを、比濁計、vWF ELISA、及び第VIII因子発色活性アッセイにより分析して回収率を測定した。SDS PAGEも実施して純度を調べた。
回収率を以下の表1に報告する。
vWF結果はELISAにより測定された。
Claims (10)
- 第VIII因子、von Willebrand’s因子又はいずれかのアナログであるタンパク質の分離、除去、単離、精製、特徴付け、同定又は定量のためのアフィニティー吸着剤の使用であって、当該アフィニティー吸着剤が、以下の式(II):
Aは、スペーサーによりトリアジン環に場合により連結された支持マトリックスであり;
YはO,S又はNR2であり;
ZはO,S又はN−R3であり;
R2とR3は各々H、C1-6アルキル、C1-6ヒドロキシアルキル、ベンジル又はβ−フェニルエチルであり;
BとWは各々、1〜10個の炭素原子を含む場合により置換された炭化水素連結であり;
DはH,OH又は第一アミノ、第二アミノ、第三アミノ、第四アンモニウム、イミダゾール、グアニジノ又はアミジノ基であり;又は
B−Dは、−CHCOOH−(CH2)3-4−NH2であり;そして
R7は、中性pHにおいて正電荷をもつ基である。}で表される化合物である前記使用。 - R7が第二又は第三アミンである、請求項1に記載の使用。
- 前記アミンが環の一部を形成する、請求項2に記載の使用。
- B又はWが、芳香族基を含む、請求項1〜3のいずれか1項に記載の使用。
- 前記吸着剤が式(III)を有する、請求項1に記載の使用。
- 前記吸着剤が式(IV)を有する、請求項1に記載の使用。
- 前記吸着剤が式(V)を有する、請求項1に記載の使用。
- 前記吸着剤が血漿のサンプルと接触する、請求項1〜7のいずれか1項に記載の使用。
- 請求項1〜8のいずれか1項に記載される式(II)を有する新規化合物。
- Aが、トリアジン環に直接又は間接的に連結された官能基により置換される、請求項9に記載の化合物の前駆体である化合物であって、それにより固体支持体上での当該前駆体の固定化が可能にされている前記前駆体である化合物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0509443.8A GB0509443D0 (en) | 2005-05-09 | 2005-05-09 | Affinity adsorbents for factor VIII and von willebrand's factor |
GB0509443.8 | 2005-05-09 | ||
PCT/GB2006/001693 WO2006120427A1 (en) | 2005-05-09 | 2006-05-09 | Affinity adsorbents for factor viii and von willebrand's factor |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2008543738A true JP2008543738A (ja) | 2008-12-04 |
JP4933536B2 JP4933536B2 (ja) | 2012-05-16 |
Family
ID=34685318
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008510633A Active JP4933536B2 (ja) | 2005-05-09 | 2006-05-09 | 第VIII因子及びvonWillebrand’s因子のためのアフィニティー吸着剤 |
Country Status (15)
Country | Link |
---|---|
US (1) | US7960182B2 (ja) |
EP (1) | EP1885486B1 (ja) |
JP (1) | JP4933536B2 (ja) |
CN (1) | CN101171076B (ja) |
AU (1) | AU2006245579B2 (ja) |
BR (1) | BRPI0611237A2 (ja) |
CA (1) | CA2607858C (ja) |
DK (1) | DK1885486T3 (ja) |
ES (1) | ES2573454T3 (ja) |
GB (1) | GB0509443D0 (ja) |
MX (1) | MX2007013949A (ja) |
NO (1) | NO20075760L (ja) |
NZ (1) | NZ563166A (ja) |
PT (1) | PT1885486E (ja) |
WO (1) | WO2006120427A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010532864A (ja) * | 2007-07-06 | 2010-10-14 | ケンブリッジ エンタープライズ リミテッド | 生体分子結合リガンド |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0509442D0 (en) * | 2005-05-09 | 2005-06-15 | Prometic Biosciences Ltd | Affinity adsorbents for fibrinogen |
JP5614930B2 (ja) * | 2005-06-10 | 2014-10-29 | プロメティック バイオサイエンシズ,リミテッド | タンパク質結合性リガンドとしてのトリアジン |
NZ586383A (en) * | 2007-12-28 | 2012-11-30 | Baxter Int | Recombinant vwf formulations |
US11197916B2 (en) | 2007-12-28 | 2021-12-14 | Takeda Pharmaceutical Company Limited | Lyophilized recombinant VWF formulations |
EP2601932A1 (en) * | 2008-10-21 | 2013-06-12 | Baxter International Inc. | Lyophilized recombinant VWF formulations |
WO2014077762A1 (en) | 2012-11-13 | 2014-05-22 | Ge Healthcare Bio-Sciences Ab | Multimodal anion exchange matrices |
CN104147596A (zh) * | 2013-05-14 | 2014-11-19 | 李荣秀 | 生物药非共价结合聚合物延长治疗浓度的方法及用途 |
EP3008085A4 (en) * | 2013-06-13 | 2017-05-10 | Biogen MA Inc. | Anti-factor viii antibodies or uses thereof |
JP6778111B2 (ja) * | 2014-01-20 | 2020-10-28 | オクタファルマ・アーゲー | FVIII:C/FVIII:Agの改良された比を有する第VIII因子を製造するための方法 |
CN114302878A (zh) | 2019-07-03 | 2022-04-08 | 大日本住友制药肿瘤公司 | 酪氨酸激酶非受体1(tnk1)抑制剂及其用途 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002543898A (ja) * | 1999-05-10 | 2002-12-24 | プロメティック バイオサイエンシズ リミティド | 新規トリアジン型解毒剤およびそれらの使用 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5110907A (en) * | 1989-08-01 | 1992-05-05 | Alpha Therapeutic Corporation | Factor viii complex purification using heparin affinity chromatography |
GB9519197D0 (en) * | 1995-09-20 | 1995-11-22 | Affinity Chromatography Ltd | Novel affinity ligands and their use |
-
2005
- 2005-05-09 GB GBGB0509443.8A patent/GB0509443D0/en not_active Ceased
-
2006
- 2006-05-09 AU AU2006245579A patent/AU2006245579B2/en active Active
- 2006-05-09 CA CA2607858A patent/CA2607858C/en active Active
- 2006-05-09 ES ES06727055.3T patent/ES2573454T3/es active Active
- 2006-05-09 MX MX2007013949A patent/MX2007013949A/es active IP Right Grant
- 2006-05-09 WO PCT/GB2006/001693 patent/WO2006120427A1/en not_active Application Discontinuation
- 2006-05-09 US US11/913,508 patent/US7960182B2/en active Active
- 2006-05-09 NZ NZ563166A patent/NZ563166A/en unknown
- 2006-05-09 EP EP06727055.3A patent/EP1885486B1/en active Active
- 2006-05-09 CN CN2006800159187A patent/CN101171076B/zh active Active
- 2006-05-09 DK DK06727055.3T patent/DK1885486T3/en active
- 2006-05-09 BR BRPI0611237-4A patent/BRPI0611237A2/pt not_active IP Right Cessation
- 2006-05-09 PT PT06727055T patent/PT1885486E/pt unknown
- 2006-05-09 JP JP2008510633A patent/JP4933536B2/ja active Active
-
2007
- 2007-11-12 NO NO20075760A patent/NO20075760L/no not_active Application Discontinuation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002543898A (ja) * | 1999-05-10 | 2002-12-24 | プロメティック バイオサイエンシズ リミティド | 新規トリアジン型解毒剤およびそれらの使用 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010532864A (ja) * | 2007-07-06 | 2010-10-14 | ケンブリッジ エンタープライズ リミテッド | 生体分子結合リガンド |
Also Published As
Publication number | Publication date |
---|---|
CA2607858A1 (en) | 2006-11-16 |
ES2573454T3 (es) | 2016-06-08 |
GB0509443D0 (en) | 2005-06-15 |
AU2006245579B2 (en) | 2010-01-28 |
CN101171076B (zh) | 2010-11-24 |
BRPI0611237A2 (pt) | 2010-08-24 |
PT1885486E (pt) | 2016-06-02 |
US7960182B2 (en) | 2011-06-14 |
EP1885486B1 (en) | 2016-03-23 |
CA2607858C (en) | 2016-04-12 |
DK1885486T3 (en) | 2016-06-06 |
WO2006120427A1 (en) | 2006-11-16 |
US20090275141A1 (en) | 2009-11-05 |
EP1885486A1 (en) | 2008-02-13 |
AU2006245579A1 (en) | 2006-11-16 |
MX2007013949A (es) | 2008-02-05 |
JP4933536B2 (ja) | 2012-05-16 |
NO20075760L (no) | 2007-12-07 |
CN101171076A (zh) | 2008-04-30 |
NZ563166A (en) | 2011-01-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4933536B2 (ja) | 第VIII因子及びvonWillebrand’s因子のためのアフィニティー吸着剤 | |
JP4933535B2 (ja) | プラスミノーゲンのためのアフィニティー吸着剤 | |
US9221768B2 (en) | Affinity adsorbents for fibrinogen |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110412 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110701 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110920 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111213 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120117 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120216 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4933536 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150224 Year of fee payment: 3 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S303 | Written request for registration of pledge or change of pledge |
Free format text: JAPANESE INTERMEDIATE CODE: R316303 |
|
S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S803 | Written request for registration of cancellation of provisional registration |
Free format text: JAPANESE INTERMEDIATE CODE: R316803 |
|
R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
R371 | Transfer withdrawn |
Free format text: JAPANESE INTERMEDIATE CODE: R371 |
|
S803 | Written request for registration of cancellation of provisional registration |
Free format text: JAPANESE INTERMEDIATE CODE: R316803 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |