JP2015522019A - 生体分子の精製 - Google Patents
生体分子の精製 Download PDFInfo
- Publication number
- JP2015522019A JP2015522019A JP2015520324A JP2015520324A JP2015522019A JP 2015522019 A JP2015522019 A JP 2015522019A JP 2015520324 A JP2015520324 A JP 2015520324A JP 2015520324 A JP2015520324 A JP 2015520324A JP 2015522019 A JP2015522019 A JP 2015522019A
- Authority
- JP
- Japan
- Prior art keywords
- flow
- chromatography
- protein
- sample
- purification
- 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
- 238000000746 purification Methods 0.000 title claims description 162
- 238000000034 method Methods 0.000 claims abstract description 340
- 102000004169 proteins and genes Human genes 0.000 claims description 216
- 108090000623 proteins and genes Proteins 0.000 claims description 216
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 181
- 239000000523 sample Substances 0.000 claims description 149
- 238000010828 elution Methods 0.000 claims description 139
- 238000004587 chromatography analysis Methods 0.000 claims description 117
- 230000027455 binding Effects 0.000 claims description 107
- 238000009739 binding Methods 0.000 claims description 107
- 239000012535 impurity Substances 0.000 claims description 99
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 97
- 241000700605 Viruses Species 0.000 claims description 91
- 238000000926 separation method Methods 0.000 claims description 90
- 229920000642 polymer Polymers 0.000 claims description 89
- 238000012545 processing Methods 0.000 claims description 82
- 238000004113 cell culture Methods 0.000 claims description 76
- 239000002609 medium Substances 0.000 claims description 73
- 230000003068 static effect Effects 0.000 claims description 61
- 238000011100 viral filtration Methods 0.000 claims description 61
- 230000002779 inactivation Effects 0.000 claims description 57
- 238000011210 chromatographic step Methods 0.000 claims description 51
- 238000005571 anion exchange chromatography Methods 0.000 claims description 50
- 239000000654 additive Substances 0.000 claims description 49
- 239000003446 ligand Substances 0.000 claims description 49
- 239000012528 membrane Substances 0.000 claims description 49
- 239000011780 sodium chloride Substances 0.000 claims description 48
- 239000000872 buffer Substances 0.000 claims description 47
- 238000005341 cation exchange Methods 0.000 claims description 47
- 238000005277 cation exchange chromatography Methods 0.000 claims description 45
- 238000005349 anion exchange Methods 0.000 claims description 43
- 230000003750 conditioning effect Effects 0.000 claims description 42
- 230000008569 process Effects 0.000 claims description 41
- 239000012530 fluid Substances 0.000 claims description 40
- 239000012501 chromatography medium Substances 0.000 claims description 38
- 239000003795 chemical substances by application Substances 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 32
- 230000008859 change Effects 0.000 claims description 31
- 230000000996 additive effect Effects 0.000 claims description 27
- 238000001914 filtration Methods 0.000 claims description 27
- 238000001042 affinity chromatography Methods 0.000 claims description 26
- 238000011403 purification operation Methods 0.000 claims description 26
- 238000005119 centrifugation Methods 0.000 claims description 23
- 230000001376 precipitating effect Effects 0.000 claims description 23
- 238000004891 communication Methods 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 17
- 239000000835 fiber Substances 0.000 claims description 16
- 239000011159 matrix material Substances 0.000 claims description 16
- 239000012521 purified sample Substances 0.000 claims description 15
- 239000003599 detergent Substances 0.000 claims description 14
- 230000000415 inactivating effect Effects 0.000 claims description 12
- 238000011026 diafiltration Methods 0.000 claims description 11
- 229920000083 poly(allylamine) Polymers 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 9
- 238000011437 continuous method Methods 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 9
- 238000012434 mixed-mode chromatography Methods 0.000 claims description 9
- 238000004440 column chromatography Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- 239000004094 surface-active agent Substances 0.000 claims description 7
- 229920000936 Agarose Polymers 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 229920001289 polyvinyl ether Polymers 0.000 claims description 6
- 238000011146 sterile filtration Methods 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 5
- 239000008394 flocculating agent Substances 0.000 claims description 5
- 238000013329 compounding Methods 0.000 claims description 4
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 4
- 239000011324 bead Substances 0.000 claims description 3
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 claims description 2
- 229960002446 octanoic acid Drugs 0.000 claims description 2
- 239000005289 controlled pore glass Substances 0.000 claims 1
- 238000013327 media filtration Methods 0.000 claims 1
- 235000002639 sodium chloride Nutrition 0.000 description 77
- 230000014759 maintenance of location Effects 0.000 description 64
- 239000000243 solution Substances 0.000 description 63
- 238000010977 unit operation Methods 0.000 description 42
- 239000000463 material Substances 0.000 description 41
- 210000004027 cell Anatomy 0.000 description 39
- 238000005406 washing Methods 0.000 description 31
- 238000002474 experimental method Methods 0.000 description 29
- 238000011118 depth filtration Methods 0.000 description 28
- 238000001556 precipitation Methods 0.000 description 25
- 239000000047 product Substances 0.000 description 24
- 239000002245 particle Substances 0.000 description 23
- 230000000717 retained effect Effects 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- -1 ICAM Proteins 0.000 description 20
- 239000011347 resin Substances 0.000 description 19
- 229920005989 resin Polymers 0.000 description 19
- 230000006870 function Effects 0.000 description 17
- 239000007983 Tris buffer Substances 0.000 description 16
- 239000006167 equilibration buffer Substances 0.000 description 16
- 230000003993 interaction Effects 0.000 description 16
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 16
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 239000011521 glass Substances 0.000 description 15
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000011148 porous material Substances 0.000 description 13
- 238000011067 equilibration Methods 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 10
- 238000000108 ultra-filtration Methods 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 239000012504 chromatography matrix Substances 0.000 description 9
- 230000002209 hydrophobic effect Effects 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 238000005342 ion exchange Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 238000007796 conventional method Methods 0.000 description 8
- 239000012149 elution buffer Substances 0.000 description 8
- 230000000670 limiting effect Effects 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 239000013621 viresolve pro solution Substances 0.000 description 8
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 7
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 230000002776 aggregation Effects 0.000 description 7
- 238000004140 cleaning Methods 0.000 description 7
- 238000011062 flow through chromatography Methods 0.000 description 7
- 239000007791 liquid phase Substances 0.000 description 7
- 239000000178 monomer Substances 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 230000001954 sterilising effect Effects 0.000 description 7
- STMDPCBYJCIZOD-UHFFFAOYSA-N 2-(2,4-dinitroanilino)-4-methylpentanoic acid Chemical compound CC(C)CC(C(O)=O)NC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O STMDPCBYJCIZOD-UHFFFAOYSA-N 0.000 description 6
- 229920002684 Sepharose Polymers 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000004220 aggregation Methods 0.000 description 6
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 6
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 6
- 235000011130 ammonium sulphate Nutrition 0.000 description 6
- 235000012970 cakes Nutrition 0.000 description 6
- 229920002678 cellulose Polymers 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 238000010979 pH adjustment Methods 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 229920001184 polypeptide Polymers 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 238000004062 sedimentation Methods 0.000 description 6
- 150000003384 small molecules Chemical class 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000010924 continuous production Methods 0.000 description 5
- 238000009295 crossflow filtration Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 239000007790 solid phase Substances 0.000 description 5
- 238000004659 sterilization and disinfection Methods 0.000 description 5
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 5
- IRLPACMLTUPBCL-KQYNXXCUSA-N 5'-adenylyl sulfate Chemical group C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OS(O)(=O)=O)[C@@H](O)[C@H]1O IRLPACMLTUPBCL-KQYNXXCUSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 239000012541 Fractogel® Substances 0.000 description 4
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 4
- 108090000099 Neurotrophin-4 Proteins 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 239000002250 absorbent Substances 0.000 description 4
- 230000002745 absorbent Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 229920001577 copolymer Polymers 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- 230000000937 inactivator Effects 0.000 description 4
- 238000004255 ion exchange chromatography Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 229920000867 polyelectrolyte Polymers 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000001742 protein purification Methods 0.000 description 4
- 239000012465 retentate Substances 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- 102000007072 Nerve Growth Factors Human genes 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 101710120037 Toxin CcdB Proteins 0.000 description 3
- 238000003916 acid precipitation Methods 0.000 description 3
- 239000003463 adsorbent Substances 0.000 description 3
- 239000012491 analyte Substances 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 3
- 229960001950 benzethonium chloride Drugs 0.000 description 3
- 229960000074 biopharmaceutical Drugs 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 230000003196 chaotropic effect Effects 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000005352 clarification Methods 0.000 description 3
- 239000000356 contaminant Substances 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000012561 harvest cell culture fluid Substances 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 125000001165 hydrophobic group Chemical group 0.000 description 3
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 238000011045 prefiltration Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000007873 sieving Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 2
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 2
- 101100075830 Caenorhabditis elegans mab-5 gene Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 2
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 2
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 239000012605 Fractogel® EMD TMAE Substances 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 2
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 2
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 102000003683 Neurotrophin-4 Human genes 0.000 description 2
- 102100033857 Neurotrophin-4 Human genes 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 108090000103 Relaxin Proteins 0.000 description 2
- 102000003743 Relaxin Human genes 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000004931 aggregating effect Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000010923 batch production Methods 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- NZQQFMVULBBDSP-FPLPWBNLSA-N bis(4-methylpentan-2-yl) (z)-but-2-enedioate Chemical compound CC(C)CC(C)OC(=O)\C=C/C(=O)OC(C)CC(C)C NZQQFMVULBBDSP-FPLPWBNLSA-N 0.000 description 2
- 229940112869 bone morphogenetic protein Drugs 0.000 description 2
- 239000003575 carbonaceous material Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- 150000003841 chloride salts Chemical class 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 239000012539 chromatography resin Substances 0.000 description 2
- 229940047120 colony stimulating factors Drugs 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 2
- 229940038472 dicalcium phosphate Drugs 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 235000021463 dry cake Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000012510 hollow fiber Substances 0.000 description 2
- 229940072221 immunoglobulins Drugs 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
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 2
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 2
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 2
- 239000012092 media component Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 239000003900 neurotrophic factor Substances 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000013618 particulate matter Substances 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920002492 poly(sulfone) Polymers 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229940068977 polysorbate 20 Drugs 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 238000011112 process operation Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 239000010865 sewage Substances 0.000 description 2
- 235000021391 short chain fatty acids Nutrition 0.000 description 2
- 150000004666 short chain fatty acids Chemical class 0.000 description 2
- 238000011080 single-pass tangential flow filtration Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000012799 strong cation exchange Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-M 1,1-dioxo-1,2-benzothiazol-3-olate Chemical compound C1=CC=C2C([O-])=NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-M 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- IWSZDQRGNFLMJS-UHFFFAOYSA-N 2-(dibutylamino)ethanol Chemical compound CCCCN(CCO)CCCC IWSZDQRGNFLMJS-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- DIHXSRXTECMMJY-MURFETPASA-N 2-[dimethyl-[(9z,12z)-octadeca-9,12-dienyl]azaniumyl]acetate Chemical group CCCCC\C=C/C\C=C/CCCCCCCC[N+](C)(C)CC([O-])=O DIHXSRXTECMMJY-MURFETPASA-N 0.000 description 1
- MPNXSZJPSVBLHP-UHFFFAOYSA-N 2-chloro-n-phenylpyridine-3-carboxamide Chemical group ClC1=NC=CC=C1C(=O)NC1=CC=CC=C1 MPNXSZJPSVBLHP-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- FAZUUZXVFVVIIQ-UHFFFAOYSA-N 2-methylquinolin-1-ium-4-amine;chloride Chemical compound Cl.C1=CC=CC2=NC(C)=CC(N)=C21 FAZUUZXVFVVIIQ-UHFFFAOYSA-N 0.000 description 1
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 1
- NUFBIAUZAMHTSP-UHFFFAOYSA-N 3-(n-morpholino)-2-hydroxypropanesulfonic acid Chemical compound OS(=O)(=O)CC(O)CN1CCOCC1 NUFBIAUZAMHTSP-UHFFFAOYSA-N 0.000 description 1
- DIROHOMJLWMERM-UHFFFAOYSA-N 3-[dimethyl(octadecyl)azaniumyl]propane-1-sulfonate Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O DIROHOMJLWMERM-UHFFFAOYSA-N 0.000 description 1
- JMTNOKRGERWNME-UHFFFAOYSA-L 6-[dimethyl-[4-(2,2,6-trimethylcyclohexyl)butan-2-yl]azaniumyl]hexyl-dimethyl-[4-(2,2,6-trimethylcyclohexyl)butan-2-yl]azanium;dichloride Chemical compound [Cl-].[Cl-].CC1CCCC(C)(C)C1CCC(C)[N+](C)(C)CCCCCC[N+](C)(C)C(C)CCC1C(C)CCCC1(C)C JMTNOKRGERWNME-UHFFFAOYSA-L 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 108010059616 Activins Proteins 0.000 description 1
- 102000005606 Activins Human genes 0.000 description 1
- 102100034613 Annexin A2 Human genes 0.000 description 1
- 108090000668 Annexin A2 Proteins 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical group OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000013585 Bombesin Human genes 0.000 description 1
- 108010051479 Bombesin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102100031092 C-C motif chemokine 3 Human genes 0.000 description 1
- 101710155856 C-C motif chemokine 3 Proteins 0.000 description 1
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 108010009575 CD55 Antigens Proteins 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- CXRFDZFCGOPDTD-UHFFFAOYSA-M Cetrimide Chemical compound [Br-].CCCCCCCCCCCCCC[N+](C)(C)C CXRFDZFCGOPDTD-UHFFFAOYSA-M 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- OJIYIVCMRYCWSE-UHFFFAOYSA-M Domiphen bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CCOC1=CC=CC=C1 OJIYIVCMRYCWSE-UHFFFAOYSA-M 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 1
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- 102100025390 Integrin beta-2 Human genes 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102100039064 Interleukin-3 Human genes 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 1
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 239000012901 Milli-Q water Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108090000742 Neurotrophin 3 Proteins 0.000 description 1
- 102000004230 Neurotrophin 3 Human genes 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 102000017975 Protein C Human genes 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102100022831 Somatoliberin Human genes 0.000 description 1
- 101710142969 Somatoliberin Proteins 0.000 description 1
- 101000582398 Staphylococcus aureus Replication initiation protein Proteins 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 1
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 1
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- LDLCEGCJYSDJLX-UHFFFAOYSA-N ac1l2fck Chemical compound C1N(C2)CN3CN2C[N+]1(CC=CCl)C3 LDLCEGCJYSDJLX-UHFFFAOYSA-N 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000488 activin Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000000274 adsorptive effect Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000005211 alkyl trimethyl ammonium group Chemical group 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000003011 anion exchange membrane Substances 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 238000007630 basic procedure Methods 0.000 description 1
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical class NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000002551 biofuel Substances 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 1
- DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 150000003842 bromide salts Chemical class 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 229940115457 cetyldimethylethylammonium bromide Drugs 0.000 description 1
- 229960004830 cetylpyridinium Drugs 0.000 description 1
- DVBJBNKEBPCGSY-UHFFFAOYSA-M cetylpyridinium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 DVBJBNKEBPCGSY-UHFFFAOYSA-M 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000004320 controlled atmosphere Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 108700001680 des-(1-3)- insulin-like growth factor 1 Proteins 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940078672 didecyldimethylammonium Drugs 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- NLFTWRWHIFBVRC-UHFFFAOYSA-M dodecyl-dimethyl-octylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)CCCCCCCC NLFTWRWHIFBVRC-UHFFFAOYSA-M 0.000 description 1
- JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 description 1
- XJWSAJYUBXQQDR-UHFFFAOYSA-M dodecyltrimethylammonium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)C XJWSAJYUBXQQDR-UHFFFAOYSA-M 0.000 description 1
- 238000010894 electron beam technology Methods 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- VUFOSBDICLTFMS-UHFFFAOYSA-M ethyl-hexadecyl-dimethylazanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)CC VUFOSBDICLTFMS-UHFFFAOYSA-M 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 239000012527 feed solution Substances 0.000 description 1
- WHDGWKAJBYRJJL-UHFFFAOYSA-K ferbam Chemical compound [Fe+3].CN(C)C([S-])=S.CN(C)C([S-])=S.CN(C)C([S-])=S WHDGWKAJBYRJJL-UHFFFAOYSA-K 0.000 description 1
- 239000002657 fibrous material Substances 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 229940028334 follicle stimulating hormone Drugs 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 description 1
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 1
- ZWGTVKDEOPDFGW-UHFFFAOYSA-N hexadecylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[NH3+] ZWGTVKDEOPDFGW-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940051250 hexylene glycol Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000005661 hydrophobic surface Effects 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229960001388 interferon-beta Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000012500 ion exchange media Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 229940087875 leukine Drugs 0.000 description 1
- 239000003580 lung surfactant Substances 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012516 mab select resin Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 235000019988 mead Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000009285 membrane fouling Methods 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 238000012806 monitoring device Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000001728 nano-filtration Methods 0.000 description 1
- 238000004848 nephelometry Methods 0.000 description 1
- 229940032018 neurotrophin 3 Drugs 0.000 description 1
- 229940097998 neurotrophin 4 Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 238000009928 pasteurization Methods 0.000 description 1
- 239000003415 peat Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940085991 phosphate ion Drugs 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 238000007517 polishing process Methods 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920003213 poly(N-isopropyl acrylamide) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000011027 product recovery Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108010087851 prorelaxin Proteins 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 108010038379 sargramostim Proteins 0.000 description 1
- 239000013017 sartobind Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000013535 sea water Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 description 1
- FBEVECUEMUUFKM-UHFFFAOYSA-M tetrapropylazanium;chloride Chemical compound [Cl-].CCC[N+](CCC)(CCC)CCC FBEVECUEMUUFKM-UHFFFAOYSA-M 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940124598 therapeutic candidate Drugs 0.000 description 1
- 229920005992 thermoplastic resin Polymers 0.000 description 1
- 229920001187 thermosetting polymer Polymers 0.000 description 1
- 229950006389 thiodiglycol Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 108010042974 transforming growth factor beta4 Proteins 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229950010254 triclobisonium chloride Drugs 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 102100036537 von Willebrand factor Human genes 0.000 description 1
- 229960001134 von willebrand factor Drugs 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 238000012784 weak cation exchange Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/12—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the preparation of the feed
- B01D15/125—Pre-filtration
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/18—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns
- B01D15/1864—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns using two or more columns
- B01D15/1871—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns using two or more columns placed in series
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
- B01D15/361—Ion-exchange
- B01D15/362—Cation-exchange
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
- B01D15/361—Ion-exchange
- B01D15/363—Anion-exchange
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/30—Extraction; Separation; Purification by precipitation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/04—Filters; Permeable or porous membranes or plates, e.g. dialysis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M43/00—Combinations of bioreactors or fermenters with other apparatus
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/12—Purification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
- B01D15/3804—Affinity chromatography
- B01D15/3809—Affinity chromatography of the antigen-antibody type, e.g. protein A, G, L chromatography
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
- B01D15/3847—Multimodal interactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Sustainable Development (AREA)
- Immunology (AREA)
- Virology (AREA)
- Peptides Or Proteins (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Epoxy Compounds (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
本出願は、出願日が2012年6月29日の米国仮特許出願第61/666,521号、出願日が2012年6月29日の米国仮特許出願第61/666,561号、出願日が2012年6月29日の米国仮特許出願第61/666,329号、および出願日が2012年7月2日の欧州特許出願EP12004909.3の優先権の利益を主張し、それぞれ、この全体が本明細書に参考として組み込まれる。
本発明を詳細に記載する前に、本発明が、変動し得る特定の組成または処理工程に限定されないことを理解すべきである。本明細書および添付の特許請求の範囲に使用される場合、この内容が他の意味であると明確に示されていない限り、単数形「1つの(a)」、「1つの(an)」および「この(the)」が、複数の対象物を含むことに留意されたい。従って、例えば、「1つのリガンド(a ligand)」に対する言及は、複数のリガンドを含み、「1つの抗体(an antibody)」に対する言及は、複数の抗体を含む、など。
上述のように、本発明は、標的分子および1種類以上の不純物を含むサンプル(例えば、細胞培養供給物)から標的分子を精製するための新規で改良された方法を提供する。本明細書に記載する方法は、当分野で使用する既存の方法と比較して、方法の実施に必要な全体的な時間フレームを短くし(数日間に対し、12から24時間)、ほとんどの従来法と比較して、工程が少なく、ユニット操作が少ないという観点で方法全体の物理的なフットプリントが減り、従来の方法よりも実行が容易であるという点で、非常に改良されたものである。さらに、ある実施形態では、本発明の方法は、使い捨てであってもよいデバイスを使用する。
本明細書に記載する方法およびシステムの第1の処理工程(またはユニット操作)の1つは、典型的には、浄化である。浄化は、標的分子から1種類以上の可溶性および/または不溶性の不純物を分離することを意図している。ある実施形態では、細胞および細胞片のような不溶性不純物は、サンプルから除去され、溶液中に標的分子を含む浄化された流体および他の可溶性不純物が得られる。浄化は、典型的には、望ましい標的分子の捕捉を含む工程の前に行われる。浄化の別の鍵となる態様は、後に精製方法の滅菌フィルタの汚染が生じ得るサンプル中の可溶性および/または不溶性不純物の除去であり、これによって、全体的な精製方法をより経済的にする。
本明細書に記載する種々の実施形態では、方法およびシステムは、捕捉のためにたった1つの結合および溶出のクロマトグラフィー処理工程を含み、典型的には、浄化の後に行う。結合および溶出のクロマトグラフィーは、標的分子に結合することを意図しており、一方、1種類以上の不純物は、流れる(「捕捉工程」とも呼ばれる。)。結合した標的分子は、その後、溶出し、溶出物または結合および溶出のクロマトグラフィー工程からの出力に、さらに精製工程を行ってもよい。
本明細書に記載する方法およびシステムの幾つかの実施形態では、結合および溶出のクロマトグラフィーの後に、ウイルス不活性化(VI)を行う。ウイルス不活性化は、必ずしも行われなくてもよいが、任意であると考えられると理解される。
本明細書に記載する種々の実施形態では、結合および溶出のクロマトグラフィーからの出力に対し、フロースルー精製操作を直接行うか、または、ウイルス不活性化の後に行う。ある実施形態では、本明細書に記載する方法およびシステムに使用されるフロースルー精製操作は、ウイルス不活性化を用いるか、または用いずに、結合および溶出のクロマトグラフィーからの出力で存在する1種類以上の不純物を除去することを意図した、フロースルー精製を達成するための2つ以上の処理工程またはデバイスまたは方法を使用する。
上述のように、ある実施形態では、サンプルについて、ウイルス濾過の後に、1つ以上のさらなる処理工程を行う。
本発明は、さらに、標的分子を精製するためのシステムも提供し、このシステムは、互いに流体連結するように接続し、この結果、連続的な様式または半連続的な様式で標的分子を精製するための方法を行うように、2つ以上のユニット操作を含む。それぞれのユニット操作は、ユニット操作の意図した目的を達成するために1つ以上のデバイスを使用してもよい。従って、ある実施形態では、本明細書に記載するシステムは、連続的な様式または半連続的な様式で精製方法を行うことができるように接続した幾つかのデバイスを含む。
モノクローナル抗体を精製するための方法
この代表的な実施例では、モノクローナル抗体の精製は、精製方法を連続的な様式で用いて達成され、種々のユニット操作は、連続して操作する様式で接続する。例示的な方法を図2に示す。
モノクローナル抗体を精製するための方法
この代表的な実施例では、モノクローナル抗体の精製は、精製方法を用いて達成され、種々のユニット操作は、以下に記載する配列で接続する。
バッチプロテインAクロマトグラフィーの後のフロースルー精製方法
この代表的な実験では、バッチプロテインAによってすでに精製されたモノクローナル抗体溶液を、最終的な純度および収率の目的を満たすように、フロースルー精製を用いてさらに精製する。これは、以下の工程をフロースルー様式で行うことによって行われる。活性炭:アニオン交換クロマトグラフィー;ライン内のpH変化;カチオン交換クロマトグラフィーおよびウイルス濾過。
プロテインAクロマトグラフィーに接続する浄化
この代表的な実施例では、浄化を、連続的な様式でプロテインAクロマトグラフィーに接続する。
刺激応答性ポリマーを用いた浄化
この代表的な実験では、2つの異なる方法を用い、刺激応答性ポリマーを用いて浄化を行う。
プロテインAクロマトグラフィーの溶出性能に対する、沈殿を用いた浄化の効果
この代表的な実験では、プロテインAクロマトグラフィーの溶出性能に対する、MAb04を産生するCHO系細胞培養物で行われる浄化の種類の効果を観察する。
活性炭を用いたアフィニティ捕捉溶出物からの可溶性および不溶性の不純物の同時除去
この代表的な実験では、活性炭は、セルロース媒体に充填されると、プロテインAの結合および溶出のクロマトグラフィー工程(即ち、捕捉工程)からの溶出物から得た不溶性(即ち、粒状)および可溶性の不純物を除去することができることを示した。
活性炭によって除去される不純物に対する滞留時間の効果
この代表的な実験では、活性炭を連続方法で使用するとき、本明細書で記載するように、連続的な様式で使用しないときと比較して、不純物を大きく除去することを示す。特に、活性炭を連続方法で使用するとき、本明細書で記載するように、通常は、上流のプロテインAの結合および溶出のクロマトグラフィー工程と、下流のアニオン交換クロマトグラフィー媒体とを流体連結し、活性炭を単独操作で別個に使用したときと比較して、ゆっくりとした(即ち、長い滞留時間を有する。)流速でサンプルを活性炭に流す。
フロースルー精製処理の工程で調整槽を用いる利点
この代表的な実験では、本明細書に記載するように、フロースルー精製処理工程で調整槽を用いる1つ以上の利点を示す。
連続的な様式でフロースルー精製処理工程を行うことが、生成物の純度に悪影響を与えない
この代表的な実験では、連続的な様式でフロースルー精製方法を行うことが、生成物の純度に悪影響を与えないことを示す。言い換えると、連続的な様式で行うフロースルー精製処理工程からの生成物の純度と、個々の工程を別個に行う場合とを比較することによって、生成物の純度に悪影響がないことを示す。
活性炭とアニオン交換クロマトグラフィーデバイス(例えば、ChromaSorb(商標))を、ウイルスプレフィルタおよびウイルス濾過デバイスとして作用するカチオン交換クロマトグラフィーデバイスに直列で接続し、全体的なフロースルー精製処理工程を連続的に操作することによって、活性炭とアニオン交換クロマトグラフィーデバイスをカチオン交換クロマトグラフィーデバイスおよびウイルス濾過デバイスと切り離したときと比較して、同様の能力のウイルスフィルタが得られることを示す。
ウイルス濾過膜の性能に対する滞留時間の効果
この代表的な実験では、ウイルス濾過の性能に対する滞留時間の効果を観察する。フロースルー精製処理工程中、カチオン交換クロマトグラフィー工程およびウイルス濾過工程を通る流速を遅くすると、ウイルスフィルタの高いスループットが得られることが観察される。
AMPS/DMAMグラフト接合コポリマーで改質された強カチオン交換(CEX)樹脂を用いた、MAb供給物からの種々の滞留時間での凝集物の除去
250mLのガラス瓶に、Toyopearl HW75−Fクロマトグラフィー樹脂の64mlの濡れたケーキを加えた。次に、115gの5M水酸化ナトリウム、18.75gの硫酸ナトリウム、4mLのアリルグリシジルエーテル(AGE)を、樹脂の入った瓶に加えた。次いで、中程度の速度で回転させつつ、この瓶をハイブリダイザーに50℃で一晩入れた。次の日に、焼結ガラスフィルタアセンブリ(EMD Millipore Corporation.Billerica、MA)に、樹脂をフィルタから排出させ、濡れたケーキをメタノールで洗浄し、次いで、脱イオン水ですすいだ。ガラスバイアルに、AGE活性化樹脂の10mLの濡れたケーキを加えた。このガラスバイアルに、0.2gの過硫酸アンモニウム、0.3gのAMPS、1.2gのDMAMおよび48gの脱イオン水を加え、このバイアルを16時間で60℃まで加熱した。次の日に、焼結ガラスフィルタアセンブリ(EMD Millipore Corporation.Billerica、MA)に、樹脂をフィルタから排出させ、濡れたケーキを、メタノールと脱イオン水の溶液で洗浄し、この樹脂をロット番号1712とラベル付けした。
AMPS/DMAMグラフト接合コポリマーで改質された翼状部を有するカチオン交換(CEX)繊維を用いた、MAb供給物からの凝集物の除去
この代表的な実験では、翼状部を有するカチオン交換繊維を固体支持体として使用した。
プロテインA溶出プールの純度に対する、刺激応答性ポリマーの浄化と、浄化した細胞培養物へのNaClの添加を合わせた効果
この代表的な実験では、MAb04細胞培養液を、デプス濾過または沈殿工程を用い、具体的には、刺激応答性ポリマー(即ち、改質されたポリアリルアミン)を用いて浄化する。得られた浄化された溶液を、ProSep(登録商標)Ultra Plus樹脂を含むカラムに入れるか、または、カラムに入れる前に、最終濃度が0.5M NaClになるようにNaClを加える。NaClを加えない状態で、保持前にカラムを1×TBSで平衡化し、一方、NaClを加えた状態で、平衡バッファーは、1×TBS、0.5M NaClである。すべてのカラムに、樹脂1リットルあたり、約30gのMAb04を入れ、次いで、2CVの平衡バッファーで洗浄し、次いで、25mMのトリス(pH7.0)を含む3CVで洗浄する。結合したMAb04を、25mMグリシンHCl、25mM酢酸(pH2.5)溶液で溶出させ、次いで、適切な平衡バッファーで再平衡化させる前に、5CVの0.15Mリン酸(pH1.6)で洗浄する。
中間洗浄工程中の異なるNaCl濃度の効果と、保持溶液中に存在する0.5M NaClの効果との比較
この代表的な実験では、プロテインAクロマトグラフィーによって達成されたモノクローナル抗体(MAb)溶出プールの純度に対する中間洗浄工程中の異なるNaCl濃度の影響を、プロテインAクロマトグラフィーカラムに入れたサンプル中の0.5M NaClの影響と直接比較する。
添加剤が含まれる間、プロテインA精製工程に基づいて達成される生成物の精製の比較
この代表的な実験では、中間洗浄のみに存在する添加剤を含むプロテインAクロマトグラフィーによって達成される精製と、平衡バッファーおよび保持される細胞培養物サンプル中の添加剤を用いて達成された精製との直接的な比較を行う。
Claims (48)
- 標的分子を精製するための方法であって、
(a)標的分子および1種類以上の不純物を含むサンプルを提供する工程と、
(b)サンプルに少なくとも1種類の沈殿剤を加え、1種類以上の不純物を除去し、これによって、浄化されたサンプルを回収する工程と、
(c)工程(b)から得た浄化されたサンプルに対し、少なくとも2種類の分離ユニットを含む結合および溶出のクロマトグラフィー工程を行い、これによって、標的分子を含む溶出物を得る工程と、
(d)溶出物に対し、2種類以上の媒体の使用を含むフロースルー精製を行う工程と
を含み、少なくとも2つの工程が、これらの経過時間の少なくとも一部で同時に行われ、方法が、1つの結合および溶出のクロマトグラフィー工程のみを含む、方法。 - 方法が、連続方法である、請求項1に記載の方法。
- 工程(c)と(d)の間にウイルス不活性化工程を含む、請求項1に記載の方法。
- ウイルス不活性化工程は、酸、洗剤、溶媒および温度変化から選択されるウイルス不活性化剤の使用を含む、請求項3に記載の方法。
- ウイルス不活性化工程は、1つ以上のインラインスタティックミキサの使用を含む、請求項3に記載の方法。
- ウイルス不活性化は、1つ以上の調整槽の使用を含む、請求項3に記載の方法。
- 標的分子が抗体である、請求項1に記載の方法。
- 抗体は、モノクローナル抗体またはポリクローナル抗体から選択される、請求項7に記載の方法。
- 工程(b)の沈殿剤は、刺激応答性ポリマーである、請求項1に記載の方法。
- 刺激応答性ポリマーは、改質されたポリアリルアミンポリマーである、請求項9に記載の方法。
- 工程(b)の沈殿剤は、酸、カプリル酸、凝集剤および塩からなる群から選択される、請求項1に記載の方法。
- 工程(b)の不純物の除去は、1つ以上のデプスフィルタの使用を含む、請求項1に記載の方法。
- 工程(b)の不純物の除去は、遠心分離の使用を含む、請求項1に記載の方法。
- (c)の結合および溶出のクロマトグラフィー工程は、連続的なマルチカラムクロマトグラフィーを使用する、請求項1に記載の方法。
- (c)の結合および溶出のクロマトグラフィー工程は、アフィニティクロマトグラフィー、カチオン交換クロマトグラフィーおよび混合モードのクロマトグラフィーからなる群から選択される、請求項1に記載の方法。
- (c)の結合および溶出のクロマトグラフィー工程は、プロテインAアフィニティクロマトグラフィーを使用する、請求項1に記載の方法。
- プロテインAアフィニティクロマトグラフィーは、硬質親水性ポリビニルエーテルポリマー、孔径が制御されたガラスおよびアガロースからなる群から選択されるマトリックスに接続したプロテインAリガンドを使用する、請求項16に記載の方法。
- 工程(a)のサンプルは、細胞培養物である、請求項1に記載の方法。
- 細胞培養物が、バイオリアクター内で提供される、請求項18に記載の方法。
- バイオリアクターは、シングルユースバイオリアクターである、請求項19に記載の方法。
- 細胞培養物は、バイオリアクター以外の容器内で提供される、請求項18に記載の方法。
- 工程(b)の沈殿剤を、細胞培養物を含むバイオリアクターに加える、請求項1に記載の方法。
- スタティックミキサを用いて沈殿剤を加える、請求項22に記載の方法。
- 工程(b)の沈殿剤を、標的分子を含むサンプルを含む、バイオリアクター以外の容器に加える、請求項1に記載の方法。
- 工程(d)のフロースルー精製が、活性炭、アニオン交換クロマトグラフィー媒体およびカチオン交換クロマトグラフィー媒体から選択される2種類以上の媒体を使用する、請求項1に記載の方法。
- 工程(d)のフロースルー精製が、ウイルス濾過膜の使用をさらに含む、請求項25に記載の方法。
- カチオン交換クロマトグラフィー媒体が、膜、ビーズまたは繊維の形態である、請求項25に記載の方法。
- 1つ以上の調整槽の使用を含み、および処理工程間で貯留槽を使用しない、請求項1に記載の方法。
- 配合工程をさらに含む、請求項1に記載の方法。
- 配合は、透析濾過、濃縮および滅菌濾過を含む、請求項29に記載の方法。
- プロテインA溶出物から標的分子を精製するためのフロースルー方法であって、
(a)プロテインAクロマトグラフィーカラムから回収した溶出物を活性炭と接触させる工程と、
(b)工程(a)から得たフロースルーサンプルをアニオン交換クロマトグラフィー媒体と接触させる工程と、
(c)工程(b)から得たフロースルーサンプルをカチオン交換クロマトグラフィー媒体と接触させる工程と、
(d)標的分子を含む工程(c)からのフロースルーサンプルを得る工程と
を含み、溶出物は、工程(a)から(c)まで連続的に流れ、(d)のフロースルーサンプル中の1種類以上の不純物のレベルは、工程(a)の溶出物でのレベルよりも低い、方法。 - 工程(c)から得たフロースルーサンプルに対し、ウイルス濾過を行うことをさらに含む、請求項31に記載のフロースルー方法。
- pHを変えるために、工程(b)と(c)の間で、インラインスタティックミキサおよび/または調整槽の使用をさらに含む、請求項31に記載のフロースルー方法。
- 方法が、1個のスキッドを使用する、請求項31または32または33に記載のフロースルー方法。
- プロテインAクロマトグラフィーカラムから得た溶出物に対し、活性炭と接触させる前にウイルス不活性化を行う、請求項31に記載のフロースルー方法。
- 工程(a)から(c)を任意の順序で行ってもよい、請求項31に記載の方法。
- プロテインA溶出物から標的分子を精製するためのフロースルー精製方法であって、溶出物を活性炭、アニオン交換媒体、カチオン交換媒体およびウイルス濾過媒体から選択される2種類以上の媒体と接触させることを含み、溶出物の流れが連続的である、方法。
- 精製方法で使用するためのシステムであって、
(a)バイオリアクターと、
(b)1つ以上のデプスフィルタを含む濾過デバイスと、
(c)1個の結合および溶出のクロマトグラフィー装置と、
(d)少なくともフロースルーアニオン交換デバイスを少なくとも含むフロースルー精製システムと
を含み、(a)から(d)のデバイスは互いに流体連結するように接続し、この結果、サンプルがシステム全体を連続して流れることができる、システム。 - (a)のバイオリアクターが、シングルユースバイオリアクターである、請求項38に記載のシステム。
- システムが、滅菌環境に囲まれている、請求項38に記載のシステム。
- (c)の結合および溶出のクロマトグラフィー装置が、少なくとも2つの分離ユニットを含み、それぞれのユニットが、同じクロマトグラフィー媒体を含み、2つの分離ユニットは、サンプルがユニットから次のユニットへ次から次へと流れることができるように接続している、請求項38に記載のシステム。
- 請求項38に記載のシステムであって、
(c)の結合および溶出のクロマトグラフィー装置が、同じクロマトグラフィー媒体を含む3つ以上の分離ユニットを含み、3つ以上の分離ユニットは、液体が分離ユニットから次の分離ユニットへ、および最後の分離ユニットから最初の分離ユニットへ次から次へと流れることができるように接続している、システム。 - 工程(d)のフロースルー精製は、活性炭デバイス、カチオン交換クロマトグラフィーデバイスおよびウイルス濾過デバイスから選択されるデバイスをさらに含む、請求項38に記載のシステム。
- 工程(d)のフロースルー精製システムは、1個のスキッドを使用する、請求項38に記載のシステム。
- サンプルから標的分子を精製するための方法であって、
(a)細胞培養物を含むバイオリアクターを提供する工程と、
(b)バイオリアクターに沈殿剤を加え、1種類以上の不純物を除去し、これによって浄化されたサンプルを得る工程と、
(c)浄化されたサンプルを、少なくとも2種類の分離ユニットを使用するプロテインAアフィニティクロマトグラフィー工程に連続的に移し、これによって溶出物を得る工程と、
(d)溶出物を1種類以上のウイルス不活性化剤と混合するために、工程(c)から得た溶出物を、インラインスタティックミキサまたは調整槽に連続的に移す工程と、
(e)フロースルーモードの溶出物を活性炭と接触させ、続いてアニオン交換クロマトグラフィー媒体と接触させ、続いてインラインスタティックミキサおよび/または調整槽と接触させてpHを変え、続いてカチオン交換クロマトグラフィー媒体と接触させ、続いてウイルス濾過媒体と接触させることを含む、工程(d)の後の溶出物を、フロースルー精製操作に連続的に移す工程と、
(f)工程(e)から得たフロースルーサンプルを、望ましいバッファー中、望ましい濃度で配合する工程と
を含み、処理工程は、互いに流体連結するように接続し、この結果、サンプルがひとつの処理工程から次の処理工程へと連続して流れることができ、および(b)から(f)の少なくとも2つの処理工程が、これらの経過時間の少なくとも一部で同時に行われる、方法。 - サンプルから標的分子を精製するための方法であって、
(a)細胞培養物を含むバイオリアクターを提供する工程と、
(b)バイオリアクターに沈殿剤を加え、1種類以上の不純物を除去し、これによって、浄化されたサンプルを得る工程と、
(c)浄化されたサンプルに、塩、洗剤、界面活性剤およびポリマーからなる群から選択される1種類以上の添加剤を加える工程と、
(d)浄化されたサンプルに対し、少なくとも2種類の分離ユニットを使用するプロテインAアフィニティクロマトグラフィー工程を行い、これによって溶出物を得る工程と、
(e)工程(d)から得た溶出物を、インラインスタティックミキサまたは調整槽を用いてウイルス不活性化薬剤にさらす工程と、
(f)フロースルーモードの溶出物を活性炭と接触させ、続いてアニオン交換クロマトグラフィー媒体と接触させ、続いてインラインスタティックミキサおよび/または調整槽と接触させてpHを変え、続いてカチオン交換クロマトグラフィー媒体と接触させ、続いてウイルス濾過媒体と接触させることを含む、ウイルス不活性化後の溶出物をフロースルー精製操作に接触させる工程と、
(g)工程(f)から得たフロースルーサンプルを、望ましいバッファー中、望ましい濃度で配合する工程と
を含み、処理工程は、互いに流体連結するように接続し、この結果、サンプルがひとつの処理工程から次の処理工程へと連続して流れることができ、および(b)から(g)の少なくとも2つの処理工程が、これらの経過時間の少なくとも一部で同時に行われる、方法。 - 添加剤が塩である、請求項46に記載の方法。
- 塩が、0.5M NaClである、請求項47に記載の方法。
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261666561P | 2012-06-29 | 2012-06-29 | |
US201261666329P | 2012-06-29 | 2012-06-29 | |
US201261666521P | 2012-06-29 | 2012-06-29 | |
US61/666,329 | 2012-06-29 | ||
US61/666,521 | 2012-06-29 | ||
US61/666,561 | 2012-06-29 | ||
EP12004909.3A EP2682168A1 (en) | 2012-07-02 | 2012-07-02 | Purification of biological molecules |
EP12004909.3 | 2012-07-02 | ||
PCT/US2013/046995 WO2014004281A1 (en) | 2012-06-29 | 2013-06-21 | Purification of biological molecules |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017008140A Division JP6471183B2 (ja) | 2012-06-29 | 2017-01-20 | 生体分子の精製 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2015522019A true JP2015522019A (ja) | 2015-08-03 |
JP6484169B2 JP6484169B2 (ja) | 2019-03-13 |
Family
ID=46458134
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015520324A Active JP6484169B2 (ja) | 2012-06-29 | 2013-06-21 | 生体分子の精製 |
JP2017008140A Active JP6471183B2 (ja) | 2012-06-29 | 2017-01-20 | 生体分子の精製 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017008140A Active JP6471183B2 (ja) | 2012-06-29 | 2017-01-20 | 生体分子の精製 |
Country Status (8)
Country | Link |
---|---|
US (2) | US20150133636A1 (ja) |
EP (3) | EP2682168A1 (ja) |
JP (2) | JP6484169B2 (ja) |
CN (2) | CN104395341B (ja) |
CA (1) | CA2882552C (ja) |
ES (1) | ES2936084T3 (ja) |
SG (2) | SG10201804869UA (ja) |
WO (1) | WO2014004281A1 (ja) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017132757A (ja) * | 2016-01-22 | 2017-08-03 | 旭化成メディカル株式会社 | 生理活性物質の連続的な定流速精製方法 |
JP2018526357A (ja) * | 2015-08-13 | 2018-09-13 | アムジエン・インコーポレーテツド | 抗原結合タンパク質の荷電深層ろ過 |
KR20200026955A (ko) * | 2017-07-10 | 2020-03-11 | 박스알타 인코퍼레이티드 | 액체를 인큐베이션하고 바이러스를 불활성화시키는 방법 |
JP2020507593A (ja) * | 2017-02-16 | 2020-03-12 | リフォーム バイオロジクス、エルエルシー | タンパク質処理用賦形剤化合物 |
KR20210038640A (ko) * | 2018-07-27 | 2021-04-07 | 이엠디 밀리포어 코포레이션 | 생물학적 액체를 처리하기 위한 설비 |
JP2021519303A (ja) * | 2018-03-27 | 2021-08-10 | サノフイSanofi | 組換えタンパク質を精製するための完全フロースルー方法 |
JP2022527517A (ja) * | 2019-04-01 | 2022-06-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 一体型かつ連続した組換えタンパク質の製造 |
US11357857B2 (en) | 2014-06-20 | 2022-06-14 | Comera Life Sciences, Inc. | Excipient compounds for protein processing |
US11660343B2 (en) | 2014-06-20 | 2023-05-30 | Comera Life Sciences, Inc. | Viscosity-reducing excipient compounds for protein formulations |
US11696951B2 (en) | 2014-06-20 | 2023-07-11 | Comera Life Sciences, Inc. | Viscosity-reducing compounds for protein formulations |
Families Citing this family (84)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9249407B2 (en) | 2006-02-03 | 2016-02-02 | Opko Biologics Ltd. | Long-acting coagulation factors and methods of producing same |
US20150038413A1 (en) | 2006-02-03 | 2015-02-05 | Opko Biologics Ltd. | Long-acting polypeptides and methods of producing and administering same |
FR2902799B1 (fr) | 2006-06-27 | 2012-10-26 | Millipore Corp | Procede et unite de preparation d'un echantillon pour l'analyse microbiologique d'un liquide |
US8362217B2 (en) | 2006-12-21 | 2013-01-29 | Emd Millipore Corporation | Purification of proteins |
WO2008079302A2 (en) | 2006-12-21 | 2008-07-03 | Millipore Corporation | Purification of proteins |
US8569464B2 (en) | 2006-12-21 | 2013-10-29 | Emd Millipore Corporation | Purification of proteins |
JP2012511929A (ja) | 2008-12-16 | 2012-05-31 | イー・エム・デイー・ミリポア・コーポレイシヨン | 攪拌タンク反応器及び方法 |
KR101551295B1 (ko) | 2010-05-17 | 2015-09-08 | 이엠디 밀리포어 코포레이션 | 생체분자 정제용 자극 반응성 중합체 |
US9096648B2 (en) * | 2011-08-19 | 2015-08-04 | Emd Millipore Corporation | Methods of reducing level of one or more impurities in a sample during protein purification |
WO2014004103A1 (en) * | 2012-06-29 | 2014-01-03 | Emd Millipore Corporation | Methods for inactivating viruses during a protein purification process |
CN104718450B (zh) * | 2012-10-18 | 2018-12-14 | 捷恩智株式会社 | 抗体精制用阳离子交换色谱法载体及抗体医药的制程中生产的抗体单体与其聚合物的分离法 |
WO2014133741A1 (en) * | 2013-02-26 | 2014-09-04 | Emd Millipore Corporation | Selective removal of a protein from a mixture of proteins using activated carbon by adjusting solution conditions |
MX2015012114A (es) * | 2013-03-08 | 2016-01-12 | Genzyme Corp | Fabricacion continua integrada de principios activos proteinicos terapeuticos. |
JP6141524B2 (ja) * | 2013-07-12 | 2017-06-07 | メルク パテント ゲーエムベーハー | 活性炭を用いた標的タンパク質含有サンプルからのフラグメントの除去 |
TWI709570B (zh) | 2014-01-17 | 2020-11-11 | 美商健臻公司 | 無菌層析法及製法 |
TWI709569B (zh) * | 2014-01-17 | 2020-11-11 | 美商健臻公司 | 無菌層析樹脂及其用於製造方法的用途 |
US10429359B2 (en) | 2014-02-14 | 2019-10-01 | Ge Healthcare Bio-Sciences Ab | Automated multi-step purification system |
US10435670B2 (en) | 2014-04-15 | 2019-10-08 | Boehringer Ingelheim International Gmbh | Methods, apparatuses, and systems for continuously inactivating a virus during manufacture of a biological product |
EP3142775A2 (en) * | 2014-05-13 | 2017-03-22 | Amgen Inc. | Process control systems and methods for use with filters and filtration processes |
US10550148B2 (en) * | 2014-06-16 | 2020-02-04 | Emd Millipore Corporation | Methods for increasing the capacity of flow-through processes |
US10207225B2 (en) | 2014-06-16 | 2019-02-19 | Emd Millipore Corporation | Single-pass filtration systems and processes |
EP2986361B1 (en) | 2014-06-25 | 2019-06-12 | EMD Millipore Corporation | Compact spiral-wound membrane filter elements |
CN105745009B (zh) | 2014-08-29 | 2018-09-28 | Emd 密理博公司 | 单程切向流过滤***和具有渗余物的再循环的切向流过滤*** |
KR102061553B1 (ko) | 2014-08-29 | 2020-02-11 | 이엠디 밀리포어 코포레이션 | 잔류물의 재순환에 의한 싱글 패스 접선 유동 여과 시스템 및 접선 유동 여과 시스템을 사용하여 액체를 여과하는 공정 |
US20160097073A1 (en) * | 2014-10-06 | 2016-04-07 | Therapeutic Proteins International, LLC | Purification and separation treatment assembly (pasta) for biological products |
SG11201703265XA (en) * | 2014-10-24 | 2017-05-30 | Genzyme Corp | Integrated continuous isolation of fluid streams from sterile process vessels |
CA2966764C (en) | 2014-11-06 | 2022-10-18 | Merck Patent Gmbh | Activated carbon for the removal of leachables and/or extractables |
US11566082B2 (en) | 2014-11-17 | 2023-01-31 | Cytiva Bioprocess R&D Ab | Mutated immunoglobulin-binding polypeptides |
PE20171380A1 (es) * | 2014-12-10 | 2017-09-15 | Opko Biologics Ltd | Metodos de produccion de polipeptidos de hormona de crecimiento modificada por ctp de accion prolongada |
FR3035799B1 (fr) * | 2015-05-06 | 2017-05-05 | Elicityl | Support pour la purification de liquides biologiques |
FR3035794B1 (fr) * | 2015-05-06 | 2017-05-05 | Elicityl | Procede pour la purification du sang total ou d'un produit issu du sang |
EP3015542A1 (de) * | 2015-05-07 | 2016-05-04 | Bayer Technology Services GmbH | Modulare anlage und verfahren zur kontinuierlichen, keimreduzierten produktion und/oder aufbereitung eines produktes |
EP3093335A1 (de) * | 2015-05-13 | 2016-11-16 | Bayer Technology Services GmbH | Prozessleitsystem zur regelung und steuerung einer modular aufgebauten anlage zur produktion von biopharmazeutischen und biologischen makromolekularen produkten |
EP3037513A1 (de) * | 2015-05-13 | 2016-06-29 | Bayer Technology Services GmbH | Verfahren zur kontinuierlichen elution eines produktes von chromatographiesäulen |
DE102015114766B4 (de) | 2015-09-03 | 2019-04-25 | Sartorius Stedim Biotech Gmbh | Vorrichtung und Verfahren zur Herstellung einer Lösung |
US20170066839A1 (en) | 2015-09-08 | 2017-03-09 | Merck Patent Gmbh | Novel affinity chromatography media for removal of anti-a and/or anti-b antibodies |
HUE049756T2 (hu) | 2015-11-09 | 2020-10-28 | Biological E Ltd | Ipari méretekben is alkalmazható eljárás biológiailag aktív, rekombináns hordozófehérjék kinyerésére |
US11014962B2 (en) * | 2016-04-01 | 2021-05-25 | UCB Biopharma SRL | Method for protein purification |
EP3440518A1 (en) * | 2016-04-04 | 2019-02-13 | Boehringer Ingelheim RCV GmbH & Co KG | Real time monitoring of product purification |
US10703774B2 (en) | 2016-09-30 | 2020-07-07 | Ge Healthcare Bioprocess R&D Ab | Separation method |
CN109311949B (zh) | 2016-05-11 | 2022-09-16 | 思拓凡生物工艺研发有限公司 | 储存分离基质的方法 |
US10889615B2 (en) | 2016-05-11 | 2021-01-12 | Cytiva Bioprocess R&D Ab | Mutated immunoglobulin-binding polypeptides |
WO2017194597A1 (en) | 2016-05-11 | 2017-11-16 | Ge Healthcare Bioprocess R&D Ab | Separation matrix |
US10730908B2 (en) | 2016-05-11 | 2020-08-04 | Ge Healthcare Bioprocess R&D Ab | Separation method |
US10654887B2 (en) | 2016-05-11 | 2020-05-19 | Ge Healthcare Bio-Process R&D Ab | Separation matrix |
EP3455241B1 (en) | 2016-05-11 | 2022-02-23 | Cytiva BioProcess R&D AB | Method of cleaning and/or sanitizing a separation matrix |
US11353433B2 (en) * | 2016-08-26 | 2022-06-07 | Puridify Ltd. | Chromatography system |
US11446613B2 (en) | 2016-09-09 | 2022-09-20 | 3M Innovative Properties Company | Functionalized copolymers and use thereof |
EP3141594A3 (en) * | 2016-11-11 | 2017-06-14 | Bayer Pharma Aktiengesellschaft | Method for sampling fluid streams for monitoring contaminants in a continuous flow |
US20190359930A1 (en) * | 2016-11-11 | 2019-11-28 | Bayer Aktiengesellschaft | Method for sampling fluid streams for monitoring contaminants in a continuous flow |
JP7078952B2 (ja) * | 2017-02-08 | 2022-06-01 | 信和化工株式会社 | 液体クロマトグラフィー用分離剤ならびに分離カラム、及びこれらを用いた生体高分子の分離精製方法 |
EP3431173A1 (en) * | 2017-07-19 | 2019-01-23 | Bayer Pharma Aktiengesellschaft | Continuous manufacture of guidance molecule drug conjugates |
EP3668977A4 (en) | 2017-08-18 | 2021-04-21 | Modernatx, Inc. | HPLC ANALYTICAL PROCESSES |
EP3710141A1 (en) * | 2017-11-13 | 2020-09-23 | EMD Millipore Corporation | Continuous diafiltration by means of tank cycling |
WO2019183334A1 (en) | 2018-03-21 | 2019-09-26 | Waters Technologies Corporation | Non-antibody high-affinity-based sample preparation, sorbents, devices and methods |
CN110317832B (zh) * | 2018-03-28 | 2022-07-05 | 西比曼生物科技(香港)有限公司 | Gmp级规模化制备重组慢病毒载体的纯化制剂的方法 |
CN110317791A (zh) | 2018-03-29 | 2019-10-11 | 西比曼生物科技(香港)有限公司 | Gmp级无血清悬浮细胞大规模生产慢病毒的方法 |
TW202003832A (zh) * | 2018-05-04 | 2020-01-16 | 美商健臻公司 | 具有過濾系統的灌注式生物反應器 |
US10792618B2 (en) | 2018-06-19 | 2020-10-06 | Sartorius Stedim Biotech Gmbh | Particle separation and/or purification of a fluid |
IL267923B2 (en) | 2018-08-02 | 2023-06-01 | Grifols Worldwide Operations Ltd | The composition containing the most concentrated alpha-1 type protein inhibitor and a method for obtaining it |
JP2021536353A (ja) | 2018-08-31 | 2021-12-27 | ジェンザイム・コーポレーション | 無菌クロマトグラフィー樹脂および製造方法におけるその使用 |
CN109336970A (zh) * | 2018-11-09 | 2019-02-15 | 杭州奕安济世生物药业有限公司 | 阳离子交换层析法纯化抗体的方法 |
CN109336967A (zh) * | 2018-11-09 | 2019-02-15 | 杭州奕安济世生物药业有限公司 | 基于混合填料的抗体纯化方法 |
CN109320603A (zh) * | 2018-12-17 | 2019-02-12 | 杭州奕安济世生物药业有限公司 | 一种连续化提纯抗体的***及方法 |
KR20240042237A (ko) * | 2018-12-20 | 2024-04-01 | 이엠디 밀리포어 코포레이션 | 결합 및 용리 크로마토그래피 정제의 부피 부하 유량을 감소시키고 생산성을 증가시키기 위한 인-라인 생성물 농축 |
KR20210118815A (ko) * | 2019-01-23 | 2021-10-01 | 다이이찌 산쿄 가부시키가이샤 | 활성탄 재료를 사용하는 공정을 포함하는 항체 정제 방법 |
US10981950B2 (en) | 2019-01-31 | 2021-04-20 | Joanna Pezzini | Therapeutic protein flow kit for a continuous purification system |
US20220135619A1 (en) | 2019-02-24 | 2022-05-05 | Bristol-Myers Squibb Company | Methods of isolating a protein |
HUP1900112A1 (hu) | 2019-04-04 | 2020-10-28 | Richter Gedeon Nyrt | Immunglobulinok affinitás kromatográfiájának fejlesztése kötést megelõzõ flokkulálás alkalmazásával |
US20220259259A1 (en) * | 2019-07-11 | 2022-08-18 | Plantible Foods, Inc. | Process for isolating a high purity protein preparation from plant material and products thereof |
FR3099066B1 (fr) * | 2019-07-26 | 2021-08-13 | Novasep Process | Procédé de purification d’une substance cible avec inactivation virale |
WO2021021260A1 (en) * | 2019-08-01 | 2021-02-04 | Regeneron Pharmaceuticals, Inc. | Method for viral inactivation |
GB201911687D0 (en) * | 2019-08-15 | 2019-10-02 | Fujifilm Diosynth Biotechnologies Uk Ltd | Apparatus for purifying a liquid comprising a target substance |
US20220348608A1 (en) | 2019-10-04 | 2022-11-03 | Merck Patent Gmbh | Purification of proteins and viral inactivation |
EP4073083A1 (en) * | 2019-12-12 | 2022-10-19 | EMD Millipore Corporation | Intensified virus filtration using diafiltration buffer |
WO2021163696A1 (en) * | 2020-02-14 | 2021-08-19 | The General Hospital Corporation | Integrated dual-mode chromatography to enrich extracellular vesicles from plasma |
WO2021197249A1 (zh) * | 2020-03-30 | 2021-10-07 | 上海复宏汉霖生物技术股份有限公司 | 一种用于靶分子连续纯化的***和方法 |
CN115397834A (zh) * | 2020-04-13 | 2022-11-25 | 3M创新有限公司 | 用于纯化目标分子的流通方法和装置 |
JP2023533508A (ja) * | 2020-06-29 | 2023-08-03 | ブリストル-マイヤーズ スクイブ カンパニー | バイオリアクタからのサンプルを分析するための自動システム及び方法 |
TW202321446A (zh) * | 2021-08-13 | 2023-06-01 | 美商現代公司 | 多管柱層析mRNA純化 |
GB202117844D0 (en) * | 2021-12-09 | 2022-01-26 | Oxford Biomedica Ltd | Purification method |
WO2023165947A1 (en) | 2022-03-03 | 2023-09-07 | Chromacon Ag | Chromatographic purification method and uses thereof |
WO2023170553A1 (en) | 2022-03-07 | 2023-09-14 | Takeda Pharmaceutical Company Limited | Affinity chromatographic production of clinical human igg products |
WO2023247798A1 (de) * | 2022-06-24 | 2023-12-28 | Bilfinger Life Science Gmbh | Modulare vorrichtung und verfahren zur kontinuierlichen herstellung von biotechnologischen produkten |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09500015A (ja) * | 1993-06-23 | 1997-01-07 | ニューヨーク ブラッド センター,インコーポレイティド | 血液のウィルス不活性化のためのシステム |
JP2000511795A (ja) * | 1996-06-05 | 2000-09-12 | アイアトロス リミテッド | 流体、特に体内流体用照射装置および方法 |
JP2002526169A (ja) * | 1998-10-02 | 2002-08-20 | コモン サービシィーズ エージェンシィ | 生物学的液体の処理装置 |
WO2006024497A1 (en) * | 2004-08-30 | 2006-03-09 | Lonza Biologics Plc. | Affinity- plus ion exchange- chromatography for purifying antibodies |
JP2007525412A (ja) * | 2003-02-28 | 2007-09-06 | ロンザ・バイオロジクス・ピーエルシー | プロテインaおよびイオン交換クロマトグラフィーによる抗体精製 |
JP2010528076A (ja) * | 2007-06-01 | 2010-08-19 | エフ.ホフマン−ラ ロシュ アーゲー | 免疫グロブリン精製 |
WO2011146394A1 (en) * | 2010-05-17 | 2011-11-24 | Millipore Corporation | Stimulus responsive polymers for the purification of biomolecules |
WO2012051147A1 (en) * | 2010-10-11 | 2012-04-19 | Abbott Laboratories | Processes for purification of proteins |
WO2012078677A2 (en) * | 2010-12-06 | 2012-06-14 | Tarpon Biosystems, Inc. | Continuous processing methods for biological products |
Family Cites Families (141)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US1007849A (en) | 1905-11-20 | 1911-11-07 | Nat Sewing Machine Co | Lubricator. |
US1419177A (en) | 1920-06-28 | 1922-06-13 | Firm Luftschiffbau Zeppelin Gm | Safety valve |
US4434157A (en) | 1979-12-18 | 1984-02-28 | The Ohio State University Research Foundation | Method of recovering cell antigen and preparation of feline leukemia vaccine therefrom |
US4490937A (en) | 1981-12-07 | 1985-01-01 | Amcor Ltd. | Insect electrocution device |
US4480034A (en) | 1982-06-10 | 1984-10-30 | Celanese Corporation | Continuous fermentation process and bioconversion-product recovery |
DD232723A5 (de) | 1984-02-03 | 1986-02-05 | ���k�K@���������@����k�� | Verfahren zur gewinnung von citronensaeure |
US5256694A (en) | 1984-09-22 | 1993-10-26 | Basf Aktiengesellschaft | Diarylacetylenes, their preparation and their use |
US4808523A (en) | 1984-11-07 | 1989-02-28 | Yeda Research And Development Co., Ltd. | Constitutive production of human IFN-β1 by mammalian cells transformed by the IFN-β1 gene fused to an SV40 early promoter |
US4699718A (en) | 1986-01-21 | 1987-10-13 | Millipore Corporation | Ion chromatography method and apparatus |
US5091178A (en) | 1986-02-21 | 1992-02-25 | Oncogen | Tumor therapy with biologically active anti-tumor antibodies |
JPH0648990B2 (ja) * | 1987-01-14 | 1994-06-29 | 味の素株式会社 | トリプトフアンの精製方法 |
US4765903A (en) | 1987-10-06 | 1988-08-23 | Interferon Sciences, Inc. | Purification of monomeric interferon |
US4921792A (en) | 1987-11-27 | 1990-05-01 | Miles Inc. | Continuous cell dispersion, cultivation and substance recovery process |
EP0455757B1 (en) | 1989-08-04 | 1999-03-31 | GRANDICS, Peter | An integrated cell culture-protein purification system for the automated production and purification of cell culture products |
JPH0778025B2 (ja) * | 1990-03-20 | 1995-08-23 | 日本赤十字社 | 免疫グロブリンgの製造方法 |
US5173164A (en) | 1990-09-11 | 1992-12-22 | Bioseparations, Inc. | Multi-modality electrical separator apparatus and method |
US6663780B2 (en) | 1993-01-26 | 2003-12-16 | Danisco Finland Oy | Method for the fractionation of molasses |
WO1994025552A1 (en) | 1993-04-29 | 1994-11-10 | Norsk Hydro A.S | Processes for chromatographic fractionation of fatty acids and their derivatives |
SE9304246L (sv) | 1993-12-22 | 1995-06-23 | Asea Brown Boveri | Förfarande vid övervakning av multivariata processer |
US6197553B1 (en) | 1994-07-15 | 2001-03-06 | Merck & Co., Inc. | Method for large scale plasmid purification |
US6359114B1 (en) | 1995-06-07 | 2002-03-19 | Aphton Corp. | System for method for the modification and purification of proteins |
US6054051A (en) | 1996-01-17 | 2000-04-25 | Genentech, Inc. | Tangential-flow filtration system |
US6171638B1 (en) | 1996-03-13 | 2001-01-09 | Archer Daniels Midland Company | Production of isoflavone enriched fractions from soy protein extracts |
US6573366B1 (en) | 1996-06-07 | 2003-06-03 | Gruppo Lepetit S.P.A. | Process for the purification of human interleukin-1 receptor antagonist from recombinant E. coli |
WO1997047650A1 (en) | 1996-06-07 | 1997-12-18 | Gruppo Lepetit S.P.A. | Process for the purification of human interleukin-1 receptor antagonist from recombinant e. coli |
US7807822B2 (en) | 1996-08-01 | 2010-10-05 | Robert Bridenbaugh | Methods for purifying nucleic acids |
HUP0003855A3 (en) | 1997-08-08 | 2001-11-28 | Procter & Gamble | Improved processes for making surfactants via adsorptive separation and products thereof |
US6989264B2 (en) | 1997-09-05 | 2006-01-24 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
WO1999037754A2 (en) | 1998-01-26 | 1999-07-29 | Pharm-Eco Laboratories, Inc. | Enzyme activated supports for enantiomeric separations |
US6906172B2 (en) | 1998-03-10 | 2005-06-14 | Large Scale Biology Corporation | Flexible processing apparatus for isolating and purifying viruses, soluble proteins and peptides from plant sources |
US6315900B1 (en) | 1998-06-03 | 2001-11-13 | Accurate Polymers | Static separation method using non-porous cellulose beads |
ES2527915T3 (es) | 1998-06-09 | 2015-02-02 | Csl Behring Ag | Producto de inmunoglobulina G (IgG) líquido |
AU753468B2 (en) | 1998-06-09 | 2002-10-17 | Csl Behring Ag | Process for producing immunoglobulins for intravenous administration and other immunoglobulin products |
FR2781388B1 (fr) | 1998-07-24 | 2000-08-25 | Inst Francais Du Petrole | Dispositif de regulation en continu de la composition d'un melange de composants et systeme de separation de constituants incorporant ce dispositif d'analyse |
DE19858892A1 (de) | 1998-12-19 | 2000-06-21 | Merck Patent Gmbh | Kontinuierliches Verfahren zur Trennung von Stoffen nach Molekülgröße |
CA2361545C (en) | 1999-02-22 | 2009-01-27 | Henry Kopf | Purification of biological substances |
US6214221B1 (en) | 1999-02-22 | 2001-04-10 | Henry B. Kopf | Method and apparatus for purification of biological substances |
WO2000060128A1 (en) | 1999-04-07 | 2000-10-12 | Aeci Limited | Treatment of sugar juice |
US6372494B1 (en) | 1999-05-14 | 2002-04-16 | Advanced Tissue Sciences, Inc. | Methods of making conditioned cell culture medium compositions |
EP1175931A1 (en) | 2000-07-25 | 2002-01-30 | Computer Cell Culture Center S.A. | Integration of high cell density bioreactor operation with ultra fast on-line downstream processing |
FI20002792A0 (fi) | 2000-12-20 | 2000-12-20 | Hydrios Biotechnology Oy | Menetelmä D-mannitolin tuottamiseksi |
EP1351949B1 (en) | 2000-12-22 | 2005-05-18 | Eastman Chemical Company | Continuous process for producing l-ascorbic acid |
DE60113158T2 (de) | 2000-12-22 | 2006-06-08 | Eastman Chemical Co., Kingsport | Verfahren zur herstellung von ascorbinsäure in gegenwart eines sulfits |
US8414774B2 (en) | 2001-04-25 | 2013-04-09 | Agilent Technologies, Inc. | Systems and methods for high-throughput screening of fluidic samples |
EP1419177B1 (en) | 2001-08-14 | 2008-04-30 | Statens Serum Institut | A purification process for large scale production of gc-globulin, product obtained thereby and their use in medicine |
US6806355B2 (en) | 2001-08-14 | 2004-10-19 | Statens Serum Institut | Purification process for large scale production of Gc-globulin, the Gc-globulin produced hereby, a use of Gc.globulin and a Gc-globulin medicinal product |
US6875459B2 (en) | 2001-09-10 | 2005-04-05 | Henry B. Kopf | Method and apparatus for separation of milk, colostrum, and whey |
EP1306127B2 (en) | 2001-10-26 | 2011-09-07 | OctoPlus PolyActive Sciences B.V. | Method for the preparation of purified microparticles |
AU2003212912A1 (en) | 2002-02-04 | 2003-09-02 | Millipore Corporation | Process for removing protein aggregates and virus from a protein solution |
WO2003066662A2 (en) | 2002-02-05 | 2003-08-14 | Genentech, Inc. | Protein purification |
US6802967B2 (en) | 2002-03-06 | 2004-10-12 | Shimadzu Corporation | Multi-dimension liquid chromatography separation system |
US20060234226A1 (en) | 2002-04-26 | 2006-10-19 | Fahner Robert L | Non-affinity purification of proteins |
DE60231861D1 (de) * | 2002-06-11 | 2009-05-20 | Good Biotech Corp | Verfahren zur Isolierung von IgY Antikörpern von Anseriformen Vögel |
DE10237082B4 (de) | 2002-08-09 | 2014-12-31 | Sartorius Stedim Biotech Gmbh | Verfahren und Vorrichtung zur biotechnologischen Herstellung von Wertstoffen |
EP2261230B1 (en) | 2002-09-11 | 2017-05-10 | Chugai Seiyaku Kabushiki Kaisha | Protein purification method |
US7314746B2 (en) | 2002-09-13 | 2008-01-01 | Valentis, Inc. | Apparatus and method for preparative scale purification of nucleic acids |
CA2457262A1 (fr) | 2003-02-11 | 2004-08-11 | Centre National En Electrochimie Et En Technologies Environnementales In C. | Procede et dispositif pour la production de biomolecules en continu |
WO2005000226A2 (en) | 2003-06-06 | 2005-01-06 | Diversa Corporation | Mixed bed multi-dimensional chromatography systems and methods of making and using them |
CA2529385A1 (en) | 2003-06-17 | 2005-01-27 | Centocor, Inc. | Method and apparatus for filtration of bioreactor recombinant proteins |
US20050061744A1 (en) | 2003-07-16 | 2005-03-24 | Kearney Michael M. | Method for the recovery of acids from hydrometallurgy process solutions |
EP1649068B1 (en) | 2003-07-16 | 2012-09-26 | Amalgamated Research, Inc. | Method for purification of high purity sucrose material |
WO2005100542A1 (en) | 2004-04-19 | 2005-10-27 | Centelion | Method for purifying plasmid dna |
BRPI0413907A (pt) | 2003-09-17 | 2006-10-24 | Centelion | método de preparação de plasmìdeo dna de grau farmacêutico |
JP4076978B2 (ja) | 2003-11-20 | 2008-04-16 | ミリポア・コーポレイション | プラスミドdna清浄化 |
US7396519B2 (en) | 2004-01-26 | 2008-07-08 | San Fu Chemical Company, Ltd. | Preparation of a high purity and high concentration hydroxylamine free base |
EP1719025B1 (en) | 2004-02-03 | 2019-10-23 | GE Healthcare Bio-Sciences Corp. | System and method for manufacturing |
US7390403B2 (en) | 2004-03-19 | 2008-06-24 | Millipore Corporation | Prefilter system for biological systems |
US7875162B2 (en) | 2004-03-26 | 2011-01-25 | Board Of Regents, University Of Houston | Monitored separation device |
SE0400886D0 (sv) | 2004-04-02 | 2004-04-02 | Amersham Biosciences Ab | Process of purification |
WO2005113119A1 (en) | 2004-05-21 | 2005-12-01 | Wisconsin Alumni Research Foundation | Membrane cascade-based separation |
US8152999B2 (en) | 2004-05-21 | 2012-04-10 | Wisconsin Alumni Research Foundation | Membrane cascade-based separation |
US20080004205A1 (en) | 2006-06-30 | 2008-01-03 | Millipore Corporation | Ultrafiltration membranes and methods of making |
US8003352B2 (en) | 2004-07-16 | 2011-08-23 | Iogen Energy Corporation | Method of obtaining a product sugar stream from cellulosic biomass |
PL1807101T3 (pl) | 2004-09-30 | 2016-11-30 | Urządzenia i sposoby do zintegrowanego wytwarzania cząsteczek biologicznych w sposób ciągły | |
WO2006063041A2 (en) | 2004-12-08 | 2006-06-15 | Chia-Hui Shieh | Integrated column, related system and method for liquid chromatography |
CN100429233C (zh) * | 2005-02-03 | 2008-10-29 | 上海长海医院 | 一种重组融合蛋白及其制备方法及用途 |
US7875464B2 (en) | 2005-08-25 | 2011-01-25 | The University Of Wyoming Research Corporation | Processing and analysis techniques involving in-vessel material generation |
FI120590B (fi) | 2005-10-28 | 2009-12-15 | Danisco Sweeteners Oy | Erotusmenetelmä |
US7966227B2 (en) | 2005-11-21 | 2011-06-21 | Ge Healthcare Bio-Sciences Ab | System for configuring a chemical separation system |
CA2632519A1 (en) * | 2005-12-06 | 2007-07-05 | Amgen Inc. | Polishing steps used in multi-step protein purification processes |
WO2007071072A1 (en) | 2005-12-22 | 2007-06-28 | Corporation De L'ecole Polytechnique De Montreal | High-rate perfusion bioreactor |
JP5268890B2 (ja) | 2006-04-28 | 2013-08-21 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | Aavの規模適応性の製造方法 |
FI20065363A0 (fi) | 2006-05-30 | 2006-05-30 | Danisco Sweeteners Oy | Erotusmenetelmä |
US20070281349A1 (en) | 2006-06-06 | 2007-12-06 | West Virginia University | Industrial bioreactor and method of use in continuous protein and lipid recovery system |
EP2069387A4 (en) | 2006-06-14 | 2011-02-02 | Glaxosmithkline Llc | METHODS OF PURIFYING ANTIBODIES USING HYDROXYAPATITE CERAMIC |
WO2007144476A1 (fr) | 2006-06-16 | 2007-12-21 | Groupe Novasep | Procede de separation sequence multicolonnes |
AU2007291282B2 (en) | 2006-08-28 | 2011-10-20 | Ares Trading S.A. | Process for the purification of Fc-fusion proteins |
WO2008025748A1 (en) | 2006-08-28 | 2008-03-06 | Ares Trading S.A. | Process for the purification of fc-containing proteins |
US20080207487A1 (en) | 2006-11-02 | 2008-08-28 | Neose Technologies, Inc. | Manufacturing process for the production of polypeptides expressed in insect cell-lines |
US8362217B2 (en) | 2006-12-21 | 2013-01-29 | Emd Millipore Corporation | Purification of proteins |
US8569464B2 (en) | 2006-12-21 | 2013-10-29 | Emd Millipore Corporation | Purification of proteins |
WO2008079302A2 (en) | 2006-12-21 | 2008-07-03 | Millipore Corporation | Purification of proteins |
WO2008085988A1 (en) * | 2007-01-05 | 2008-07-17 | Amgen Inc. | Methods of purifying proteins |
AU2008206923A1 (en) | 2007-01-17 | 2008-07-24 | Merck Serono S.A. | Process for the purification of Fc-containing proteins |
US7947813B2 (en) | 2007-01-22 | 2011-05-24 | Genentech, Inc. | Polyelectrolyte precipitation and purification of proteins |
US8247200B2 (en) | 2007-01-25 | 2012-08-21 | Iogen Energy Corporation | Method of obtaining inorganic salt and acetate salt from cellulosic biomass |
CN101029077B (zh) * | 2007-02-02 | 2010-09-29 | 广东东阳光药业有限公司 | 基因重组胰岛素前体纯化方法 |
PL212099B1 (pl) | 2007-02-09 | 2012-08-31 | Inst Immunologii I Terapii Doświadczalnej Pan | Oczyszczony preparat bakteriofagowy, sposób jego otrzymywania i zastosowanie |
AU2008231721B8 (en) | 2007-03-28 | 2013-01-31 | Patheon Holdings I B.V. | Expanded bed column and disposable chromatography |
US7674073B2 (en) | 2007-04-19 | 2010-03-09 | Conocophillips Company | Modular concrete substructures |
EP2014760A1 (en) | 2007-06-13 | 2009-01-14 | CMC Biopharmaceuticals A/S | A method for producing a biopolymer (e.g. polypeptide) in a continuous fermentation process |
CN101687119B (zh) * | 2007-06-15 | 2013-06-12 | 通用电气健康护理生物科学股份公司 | 色谱方法 |
US9109193B2 (en) | 2007-07-30 | 2015-08-18 | Ge Healthcare Bio-Sciences Corp. | Continuous perfusion bioreactor system |
US9433922B2 (en) | 2007-08-14 | 2016-09-06 | Emd Millipore Corporation | Media for membrane ion exchange chromatography based on polymeric primary amines, sorption device containing that media, and chromatography scheme and purification method using the same |
WO2009040746A1 (en) | 2007-09-28 | 2009-04-02 | Koninklijke Philips Electronics N.V. | Sensor device for the detection of target components |
WO2009045897A1 (en) | 2007-10-03 | 2009-04-09 | Dyax Corp. | Systems and methods for purifying proteins |
JP2011509685A (ja) | 2008-01-25 | 2011-03-31 | エクセレレックス インク. | バイオリアクタシステムと製造施設における情報取得、管理システム及び方法 |
WO2009099804A2 (en) | 2008-02-01 | 2009-08-13 | Lanxess Sybron Chemicals Inc. | A process for the purification of crude glycerin utilizing ion exclusion chromatorgraphy and glycerin concentration |
US7622308B2 (en) | 2008-03-07 | 2009-11-24 | Mks Instruments, Inc. | Process control using process data and yield data |
CN103396480A (zh) * | 2008-05-15 | 2013-11-20 | 诺沃—诺迪斯克有限公司 | 抗体纯化方法 |
US8137361B2 (en) | 2008-10-16 | 2012-03-20 | Biomet Manufacturing Corp. | Method and apparatus for constant force tensor/ligament balancer |
AU2009307737B2 (en) | 2008-10-20 | 2015-07-23 | Abbvie Inc. | Viral inactivation during purification of antibodies |
WO2010053636A1 (en) | 2008-11-06 | 2010-05-14 | Tate & Lyle Technology Ltd | Enhanced production and purification of a natural high intensity sweetener |
US20110020327A1 (en) | 2008-12-16 | 2011-01-27 | Millipore Corporation | Purification of proteins |
SG195555A1 (en) | 2008-12-24 | 2013-12-30 | Emd Millipore Corp | Caustic stable chromatography ligands |
AU2010203836B2 (en) | 2009-01-08 | 2015-05-28 | Cytiva Bioprocess R&D Ab | Separation method using single polymer phase systems |
US9069345B2 (en) | 2009-01-23 | 2015-06-30 | Mks Instruments, Inc. | Controlling a manufacturing process with a multivariate model |
JP5762313B2 (ja) | 2009-02-25 | 2015-08-12 | デュポン ニュートリション バイオサイエンシーズ エーピーエス | 分離方法 |
US20130056415A1 (en) | 2009-02-27 | 2013-03-07 | Mikhail Kozlov | Negatively charged porous medium for removing protein aggregates |
WO2010124159A1 (en) | 2009-04-23 | 2010-10-28 | Xcellerex, Inc. | System and method for variable speed feedback control chromatography loading |
ES2817802T3 (es) | 2009-08-07 | 2021-04-08 | Emd Millipore Corp | Métodos para purificar una proteína objetivo de una o más impurezas en una muestra |
WO2011035282A1 (en) | 2009-09-21 | 2011-03-24 | Ge Healthcare Bio-Sciences Ab | Dual capture separation |
US20130116413A1 (en) * | 2009-12-29 | 2013-05-09 | Dr. Reddy's Laboratories, Inc. | Purification of proteins |
US20130131318A1 (en) | 2010-02-12 | 2013-05-23 | Diderik Reinder Kremer | Single unit antibody purification |
WO2011130809A2 (en) | 2010-04-21 | 2011-10-27 | Katholieke Universifeit Leuven | Fractionation of ions from aqueous solutions by electrodialysis using monovalent selective membranes |
WO2011156073A1 (en) | 2010-06-08 | 2011-12-15 | Millipore Corporation | Removal of protein aggregates from biopharmaceutical preparations using calcium phosphate salts |
EP2583973B1 (en) | 2010-06-21 | 2018-03-21 | Kyowa Hakko Kirin Co., Ltd. | Method for purifying protein using amino acid |
US20130196375A1 (en) | 2010-06-23 | 2013-08-01 | Strobbe Tech A/S | Biopharmaceutical process apparatuses assembled into a column |
WO2012014183A1 (en) | 2010-07-30 | 2012-02-02 | Pfizer Inc. | Tandem purification of proteins |
US8785376B2 (en) | 2010-12-20 | 2014-07-22 | Virginia Tech Intellectual Properties | Isolation, identification, and uses of antifungal compounds |
SG10201604559TA (en) | 2011-06-08 | 2016-07-28 | Emd Millipore Corp | Chromatography matrices including novel staphylococcus aureus protein a based ligands |
JP5925307B2 (ja) | 2011-06-30 | 2016-05-25 | オーエフエス ファイテル,エルエルシー | 1550nmの波長範囲における使用のためのファイバストレッチャモジュール |
KR102157227B1 (ko) | 2011-07-08 | 2020-09-17 | 이엠디 밀리포어 코포레이션 | 일회용 생명공학적 공정용의 개선된 심층 필터 |
CN103732253A (zh) | 2011-08-19 | 2014-04-16 | Emd密理博公司 | 小分子在纯化生物分子的方法中的用途 |
US9096648B2 (en) * | 2011-08-19 | 2015-08-04 | Emd Millipore Corporation | Methods of reducing level of one or more impurities in a sample during protein purification |
EP2578286A1 (en) | 2011-10-04 | 2013-04-10 | Merck Patent GmbH | Method and apparatus for chromatographic purification |
CN104023743B (zh) * | 2011-10-25 | 2017-05-03 | 普罗西纳治疗有限公司 | 抗体制剂和方法 |
SG10201701224UA (en) * | 2012-03-12 | 2017-04-27 | Merck Patent Gmbh | Removal of protein aggregates from biopharmaceutical preparations in a flowthrough mode |
SG11201402999UA (en) * | 2012-03-26 | 2014-07-30 | Emd Millipore Corp | Use of charged fluorocarbon compositions in methods for purification of biomolecules |
EP2656892A1 (en) | 2012-04-23 | 2013-10-30 | Merck Patent GmbH | Chromatography method |
WO2014004103A1 (en) | 2012-06-29 | 2014-01-03 | Emd Millipore Corporation | Methods for inactivating viruses during a protein purification process |
-
2012
- 2012-07-02 EP EP12004909.3A patent/EP2682168A1/en not_active Ceased
-
2013
- 2013-06-21 US US14/400,389 patent/US20150133636A1/en not_active Abandoned
- 2013-06-21 SG SG10201804869UA patent/SG10201804869UA/en unknown
- 2013-06-21 JP JP2015520324A patent/JP6484169B2/ja active Active
- 2013-06-21 WO PCT/US2013/046995 patent/WO2014004281A1/en active Application Filing
- 2013-06-21 SG SG11201406408RA patent/SG11201406408RA/en unknown
- 2013-06-21 CN CN201380034774.XA patent/CN104395341B/zh active Active
- 2013-06-21 EP EP13808723.4A patent/EP2867256A4/en active Pending
- 2013-06-21 CA CA2882552A patent/CA2882552C/en active Active
- 2013-06-21 ES ES16181909T patent/ES2936084T3/es active Active
- 2013-06-21 EP EP16181909.9A patent/EP3130384B1/en active Active
- 2013-06-21 CN CN201710636612.3A patent/CN107383161B/zh active Active
-
2017
- 2017-01-20 JP JP2017008140A patent/JP6471183B2/ja active Active
- 2017-07-20 US US15/654,876 patent/US10865224B2/en active Active
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09500015A (ja) * | 1993-06-23 | 1997-01-07 | ニューヨーク ブラッド センター,インコーポレイティド | 血液のウィルス不活性化のためのシステム |
JP2000511795A (ja) * | 1996-06-05 | 2000-09-12 | アイアトロス リミテッド | 流体、特に体内流体用照射装置および方法 |
JP2002526169A (ja) * | 1998-10-02 | 2002-08-20 | コモン サービシィーズ エージェンシィ | 生物学的液体の処理装置 |
JP2007525412A (ja) * | 2003-02-28 | 2007-09-06 | ロンザ・バイオロジクス・ピーエルシー | プロテインaおよびイオン交換クロマトグラフィーによる抗体精製 |
WO2006024497A1 (en) * | 2004-08-30 | 2006-03-09 | Lonza Biologics Plc. | Affinity- plus ion exchange- chromatography for purifying antibodies |
JP2010528076A (ja) * | 2007-06-01 | 2010-08-19 | エフ.ホフマン−ラ ロシュ アーゲー | 免疫グロブリン精製 |
WO2011146394A1 (en) * | 2010-05-17 | 2011-11-24 | Millipore Corporation | Stimulus responsive polymers for the purification of biomolecules |
WO2012051147A1 (en) * | 2010-10-11 | 2012-04-19 | Abbott Laboratories | Processes for purification of proteins |
WO2012078677A2 (en) * | 2010-12-06 | 2012-06-14 | Tarpon Biosystems, Inc. | Continuous processing methods for biological products |
Non-Patent Citations (2)
Title |
---|
BIO PROCESS INTERNATIONAL, vol. 7, no. 5, JPN6015046541, June 2009 (2009-06-01), pages 18 - 23, ISSN: 0003198636 * |
PROSEP (R) ULTRA PLUS CHROMATOGRAPHY MEDIA DATA SHEET, JPN6015046542, 2009, ISSN: 0003198637 * |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11672865B2 (en) | 2014-06-20 | 2023-06-13 | Comera Life Sciences, Inc. | Viscosity-reducing excipient compounds for protein formulations |
US11696951B2 (en) | 2014-06-20 | 2023-07-11 | Comera Life Sciences, Inc. | Viscosity-reducing compounds for protein formulations |
US11660343B2 (en) | 2014-06-20 | 2023-05-30 | Comera Life Sciences, Inc. | Viscosity-reducing excipient compounds for protein formulations |
US11357857B2 (en) | 2014-06-20 | 2022-06-14 | Comera Life Sciences, Inc. | Excipient compounds for protein processing |
US11806399B2 (en) | 2014-06-20 | 2023-11-07 | Comera Life Sciences, Inc. | Excipient compounds for biopolymer formulations |
JP2018526357A (ja) * | 2015-08-13 | 2018-09-13 | アムジエン・インコーポレーテツド | 抗原結合タンパク質の荷電深層ろ過 |
JP2017132757A (ja) * | 2016-01-22 | 2017-08-03 | 旭化成メディカル株式会社 | 生理活性物質の連続的な定流速精製方法 |
JP7032046B2 (ja) | 2016-01-22 | 2022-03-08 | 旭化成メディカル株式会社 | 生理活性物質の連続的な定流速精製方法 |
JP2020507593A (ja) * | 2017-02-16 | 2020-03-12 | リフォーム バイオロジクス、エルエルシー | タンパク質処理用賦形剤化合物 |
KR20200026955A (ko) * | 2017-07-10 | 2020-03-11 | 박스알타 인코퍼레이티드 | 액체를 인큐베이션하고 바이러스를 불활성화시키는 방법 |
JP2020526210A (ja) * | 2017-07-10 | 2020-08-31 | バクスアルタ インコーポレイテッド | 液体をインキュベートおよびウイルスを不活化するための方法 |
KR102623471B1 (ko) * | 2017-07-10 | 2024-01-09 | 다케다 야쿠힌 고교 가부시키가이샤 | 액체를 인큐베이션하고 바이러스를 불활성화시키는 방법 |
JP7218344B2 (ja) | 2017-07-10 | 2023-02-06 | 武田薬品工業株式会社 | 液体をインキュベートおよびウイルスを不活化するための方法 |
JP2021519303A (ja) * | 2018-03-27 | 2021-08-10 | サノフイSanofi | 組換えタンパク質を精製するための完全フロースルー方法 |
JP7396997B2 (ja) | 2018-03-27 | 2023-12-12 | サノフイ | 組換えタンパク質を精製するための完全フロースルー方法 |
KR20210038640A (ko) * | 2018-07-27 | 2021-04-07 | 이엠디 밀리포어 코포레이션 | 생물학적 액체를 처리하기 위한 설비 |
KR102541230B1 (ko) * | 2018-07-27 | 2023-06-13 | 이엠디 밀리포어 코포레이션 | 생물학적 액체를 처리하기 위한 설비 |
JP7232316B2 (ja) | 2018-07-27 | 2023-03-02 | イー・エム・デイー・ミリポア・コーポレイシヨン | 生物学的液体を処理するための設備 |
JP2021531028A (ja) * | 2018-07-27 | 2021-11-18 | イー・エム・デイー・ミリポア・コーポレイシヨン | 生物学的液体を処理するための設備 |
US11970687B2 (en) | 2018-07-27 | 2024-04-30 | Emd Millipore Corporation | Installation for treating biological liquid |
JP2022527517A (ja) * | 2019-04-01 | 2022-06-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 一体型かつ連続した組換えタンパク質の製造 |
Also Published As
Publication number | Publication date |
---|---|
CN107383161B (zh) | 2021-08-17 |
EP3130384B1 (en) | 2022-12-21 |
JP2017110017A (ja) | 2017-06-22 |
US20170320909A1 (en) | 2017-11-09 |
CN107383161A (zh) | 2017-11-24 |
CA2882552C (en) | 2023-01-24 |
EP2867256A1 (en) | 2015-05-06 |
CA2882552A1 (en) | 2014-01-03 |
ES2936084T3 (es) | 2023-03-14 |
SG10201804869UA (en) | 2018-07-30 |
WO2014004281A1 (en) | 2014-01-03 |
US20150133636A1 (en) | 2015-05-14 |
SG11201406408RA (en) | 2014-11-27 |
EP2682168A1 (en) | 2014-01-08 |
CN104395341B (zh) | 2018-06-26 |
JP6471183B2 (ja) | 2019-02-13 |
EP2867256A4 (en) | 2016-09-21 |
JP6484169B2 (ja) | 2019-03-13 |
EP3130384A1 (en) | 2017-02-15 |
US10865224B2 (en) | 2020-12-15 |
CN104395341A (zh) | 2015-03-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6471183B2 (ja) | 生体分子の精製 | |
JP6580650B2 (ja) | フロースルー式での生物製剤からのタンパク質凝集体の除去 | |
US11590434B2 (en) | Method and apparatus for chromatographic purification | |
KR101415660B1 (ko) | 샘플 중의 1 이상의 불순물로부터 표적 단백질을 정제하는 방법 | |
KR102070566B1 (ko) | 크로마토그래피 방법 | |
TWI574975B (zh) | 用於減少蛋白質純化期間樣本中一或多種雜質含量之方法 | |
WO2019149693A1 (en) | Protein purification process and platform |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20151117 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160215 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160516 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20160920 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170120 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20170309 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20170414 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180405 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180709 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181203 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190215 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6484169 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
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 |