CA2101337A1 - Methode de production de fragments f(ab') d'immunoglobulines - Google Patents
Methode de production de fragments f(ab') d'immunoglobulinesInfo
- Publication number
- CA2101337A1 CA2101337A1 CA 2101337 CA2101337A CA2101337A1 CA 2101337 A1 CA2101337 A1 CA 2101337A1 CA 2101337 CA2101337 CA 2101337 CA 2101337 A CA2101337 A CA 2101337A CA 2101337 A1 CA2101337 A1 CA 2101337A1
- Authority
- CA
- Canada
- Prior art keywords
- fragments
- fab
- medium
- immunoglobulin
- accordance
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000012634 fragment Substances 0.000 title claims abstract description 121
- 108060003951 Immunoglobulin Proteins 0.000 title claims abstract description 100
- 102000018358 immunoglobulin Human genes 0.000 title claims abstract description 100
- 229940072221 immunoglobulins Drugs 0.000 title claims abstract description 29
- 238000000034 method Methods 0.000 title claims description 53
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 72
- 239000003636 conditioned culture medium Substances 0.000 claims abstract description 34
- 210000004408 hybridoma Anatomy 0.000 claims abstract description 30
- 238000004519 manufacturing process Methods 0.000 claims abstract description 15
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 7
- 239000002609 medium Substances 0.000 claims description 36
- 230000029087 digestion Effects 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 210000002966 serum Anatomy 0.000 claims description 21
- 230000001143 conditioned effect Effects 0.000 claims description 19
- 241000283707 Capra Species 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 16
- 230000002829 reductive effect Effects 0.000 claims description 14
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 12
- 239000001963 growth medium Substances 0.000 claims description 11
- 238000011534 incubation Methods 0.000 claims description 11
- 102000004169 proteins and genes Human genes 0.000 claims description 11
- 108090000623 proteins and genes Proteins 0.000 claims description 11
- 238000006722 reduction reaction Methods 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 238000003776 cleavage reaction Methods 0.000 claims description 8
- 230000007017 scission Effects 0.000 claims description 8
- 241000282414 Homo sapiens Species 0.000 claims description 7
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 6
- 235000011009 potassium phosphates Nutrition 0.000 claims description 6
- 230000001419 dependent effect Effects 0.000 claims description 4
- 238000011026 diafiltration Methods 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 3
- 241000700159 Rattus Species 0.000 claims description 3
- 230000008859 change Effects 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000003104 tissue culture media Substances 0.000 claims 4
- 239000010755 BS 2869 Class G Substances 0.000 claims 2
- 241000699666 Mus <mouse, genus> Species 0.000 claims 2
- 210000003719 b-lymphocyte Anatomy 0.000 claims 2
- 238000000184 acid digestion Methods 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 239000013627 low molecular weight specie Substances 0.000 claims 1
- 230000003472 neutralizing effect Effects 0.000 claims 1
- 102000035195 Peptidases Human genes 0.000 abstract description 41
- 108091005804 Peptidases Proteins 0.000 abstract description 41
- 230000016784 immunoglobulin production Effects 0.000 abstract description 2
- 239000004365 Protease Substances 0.000 description 42
- 235000019419 proteases Nutrition 0.000 description 31
- 230000000694 effects Effects 0.000 description 29
- 239000000499 gel Substances 0.000 description 23
- 239000000047 product Substances 0.000 description 17
- 239000002158 endotoxin Substances 0.000 description 13
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 102000003908 Cathepsin D Human genes 0.000 description 9
- 108090000258 Cathepsin D Proteins 0.000 description 9
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 8
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 8
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 8
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 8
- 102000057297 Pepsin A Human genes 0.000 description 8
- 108090000284 Pepsin A Proteins 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 229940111202 pepsin Drugs 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 108010091212 pepstatin Proteins 0.000 description 6
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 239000002753 trypsin inhibitor Substances 0.000 description 6
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 229940122618 Trypsin inhibitor Drugs 0.000 description 5
- 101710162629 Trypsin inhibitor Proteins 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000000356 contaminant Substances 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 229950000964 pepstatin Drugs 0.000 description 5
- 229940093916 potassium phosphate Drugs 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 4
- 102000005600 Cathepsins Human genes 0.000 description 4
- 108010084457 Cathepsins Proteins 0.000 description 4
- 108090000526 Papain Proteins 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 229940001593 sodium carbonate Drugs 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 229920000936 Agarose Polymers 0.000 description 3
- 102000004411 Antithrombin III Human genes 0.000 description 3
- 108090000935 Antithrombin III Proteins 0.000 description 3
- 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 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 101710097834 Thiol protease Proteins 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 229960005348 antithrombin iii Drugs 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- 238000011109 contamination Methods 0.000 description 3
- 229960002433 cysteine Drugs 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000000760 immunoelectrophoresis Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000037230 mobility Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 229940055729 papain Drugs 0.000 description 3
- 235000019834 papain Nutrition 0.000 description 3
- 238000005464 sample preparation method Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 3
- 229960001322 trypsin Drugs 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- 108091005508 Acid proteases Proteins 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108090001069 Chymopapain Proteins 0.000 description 2
- 102000006395 Globulins Human genes 0.000 description 2
- 108010044091 Globulins Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101000985214 Mus musculus 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108010065081 Phosphorylase b Proteins 0.000 description 2
- ISWQCIVKKSOKNN-UHFFFAOYSA-L Tiron Chemical compound [Na+].[Na+].OC1=CC(S([O-])(=O)=O)=CC(S([O-])(=O)=O)=C1O ISWQCIVKKSOKNN-UHFFFAOYSA-L 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229960002319 barbital Drugs 0.000 description 2
- 102000005936 beta-Galactosidase Human genes 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960002976 chymopapain Drugs 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 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
- 238000002955 isolation Methods 0.000 description 2
- 230000002132 lysosomal effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229940092253 ovalbumin Drugs 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 238000012421 spiking Methods 0.000 description 2
- 229940033663 thimerosal Drugs 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- JVIPLYCGEZUBIO-UHFFFAOYSA-N 2-(4-fluorophenyl)-1,3-dioxoisoindole-5-carboxylic acid Chemical compound O=C1C2=CC(C(=O)O)=CC=C2C(=O)N1C1=CC=C(F)C=C1 JVIPLYCGEZUBIO-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- 208000035404 Autolysis Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000003846 Carbonic anhydrases Human genes 0.000 description 1
- 108090000209 Carbonic anhydrases Proteins 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 101000952982 Conus striatus Conopressin-S Proteins 0.000 description 1
- 229920001425 Diethylaminoethyl cellulose Polymers 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 108090000270 Ficain Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 238000011050 LAL assay Methods 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108090000143 Mouse Proteins Proteins 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 241000609499 Palicourea Species 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 241000208474 Protea Species 0.000 description 1
- 101100156763 Schizosaccharomyces pombe (strain 972 / ATCC 24843) wos2 gene Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000013584 assay control Substances 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 101150061829 bre-3 gene Proteins 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- OYFJQPXVCSSHAI-QFPUQLAESA-N enalapril maleate Chemical compound OC(=O)\C=C/C(O)=O.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 OYFJQPXVCSSHAI-QFPUQLAESA-N 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 235000019836 ficin Nutrition 0.000 description 1
- POTUGHMKJGOKRI-UHFFFAOYSA-N ficin Chemical compound FI=CI=N POTUGHMKJGOKRI-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940098197 human immunoglobulin g Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- IZXGZAJMDLJLMF-UHFFFAOYSA-N methylaminomethanol Chemical compound CNCO IZXGZAJMDLJLMF-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 1
- VBEGHXKAFSLLGE-UHFFFAOYSA-N n-phenylnitramide Chemical compound [O-][N+](=O)NC1=CC=CC=C1 VBEGHXKAFSLLGE-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 210000004493 neutrocyte Anatomy 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 238000000275 quality assurance Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000011363 radioimmunotherapy Methods 0.000 description 1
- 230000001869 rapid Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028043 self proteolysis Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
- C07K16/065—Purification, fragmentation
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64974991A | 1991-02-01 | 1991-02-01 | |
| US649,749 | 1991-02-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2101337A1 true CA2101337A1 (fr) | 1992-08-02 |
Family
ID=24606069
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2101337 Abandoned CA2101337A1 (fr) | 1991-02-01 | 1992-01-29 | Methode de production de fragments f(ab') d'immunoglobulines |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0569525A1 (fr) |
| JP (1) | JPH06505731A (fr) |
| AU (1) | AU1331892A (fr) |
| CA (1) | CA2101337A1 (fr) |
| WO (1) | WO1992013876A1 (fr) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2606142B1 (fr) * | 2010-08-20 | 2018-02-28 | Boehringer Ingelheim International GmbH | Procédé d'inactivation de protéases dans un fluide obtenu à partir d'une culture de cellules par modification du ph |
| WO2014031662A2 (fr) | 2012-08-21 | 2014-02-27 | Ortho-Clinical Diagnostics, Inc | Anticorps dirigés contre l'olanzapine et leur utilisation |
| CA2882595C (fr) * | 2012-08-21 | 2019-06-04 | Ortho-Clinical Diagnostics, Inc. | Anticorps diriges contre des haptenes d'olanzapine et leur utilisation |
| US10376582B2 (en) | 2013-10-16 | 2019-08-13 | Outlook Therapeutics, Inc. | Buffer formulations for enhanced antibody stability |
| WO2016118707A1 (fr) | 2015-01-21 | 2016-07-28 | Oncobiologics, Inc. | Modulation de variants de charge dans une composition d'anticorps monoclonaux |
| EP3400242A1 (fr) * | 2016-01-06 | 2018-11-14 | Oncobiologics, Inc. | Réduction des espèces de masse moléculaire élevée, des espèces de charge acide, et des fragments dans une composition d'anticorps monoclonaux |
| AU2017213775A1 (en) | 2016-02-03 | 2018-08-16 | Outlook Therapeutics, Inc. | Buffer formulations for enhanced antibody stability |
-
1992
- 1992-01-29 CA CA 2101337 patent/CA2101337A1/fr not_active Abandoned
- 1992-01-29 EP EP19920906060 patent/EP0569525A1/fr not_active Withdrawn
- 1992-01-29 AU AU13318/92A patent/AU1331892A/en not_active Abandoned
- 1992-01-29 JP JP4506284A patent/JPH06505731A/ja active Pending
- 1992-01-29 WO PCT/US1992/000768 patent/WO1992013876A1/fr not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO1992013876A1 (fr) | 1992-08-20 |
| AU1331892A (en) | 1992-09-07 |
| EP0569525A1 (fr) | 1993-11-18 |
| JPH06505731A (ja) | 1994-06-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0419574B1 (fr) | Anticorps monoclonaux contre la region a chaine legere du facteur humain xii et procedes de preparation et d'utilisation de ces anticorps | |
| Ploug et al. | Ligand interaction between urokinase-type plasminogen activator and its receptor probed with 8-anilino-1-naphthalenesulfonate. Evidence for a hydrophobic binding site exposed only on the intact receptor | |
| Mortensen et al. | Purification and characterization of an immunoglobulin A1 protease from Bacteroides melaninogenicus | |
| Girma et al. | Limited proteolysis of human von Willebrand factor by Staphylococcus aureus V-8 protease: isolation and partial characterization of a platelet-binding domain | |
| Solomon et al. | Bence-Jones proteins and light chains of immunoglobulins | |
| Clark et al. | Antibodies prepared to Bacillus cereus phospholipase C crossreact with a phosphatidylcholine preferring phosoholipase C in mammalian cells | |
| Sekiguchi et al. | Differences in domain structure between human fibronectins isolated from plasma and from culture supernatants of normal and transformed fibroblasts. Studies with domain-specific antibodies. | |
| Schielen et al. | The sequence A alpha-(148-160) in fibrin, but not in fibrinogen, is accessible to monoclonal antibodies. | |
| Matsuura et al. | Amidase activity of human Bence Jones proteins | |
| CA1341506C (fr) | Polypeptides coagulants analogues au facteur viii ainsi que des anticorps monoclonaux que leur sont specifiques | |
| Masson | A naturally occurring molecular form of human plasma cholinesterase is an albumin conjugate | |
| Hubbard et al. | Vitamin K-dependent carboxylase: affinity purification from bovine liver by using a synthetic propeptide containing the gamma-carboxylation recognition site. | |
| PL166810B1 (pl) | Sposób oczyszczania chymopapalny PL PL PL PL PL PL PL | |
| CA2006684C (fr) | Anticorps monoclonaux contre la proteine c | |
| CA2101337A1 (fr) | Methode de production de fragments f(ab') d'immunoglobulines | |
| Ishidoh et al. | Multiple Processing of Procathepsin L to Cathepsin Lin Vivo | |
| AU650419B2 (en) | Polyvalent metal ion-containing antibody combining site catalysts | |
| Haeffner-Cavaillon et al. | Studies on the Fcγ Receptor of the Murine Macrophage-Like Cell Line P388D1: II. Binding of Human IgG Subclass Proteins and Their Proteolytic Fragments | |
| Laurell et al. | Characterization of monoclonal antibodies against human protein C specific for the calcium ion‐induced conformation or for the activation peptide region | |
| EP0139447B1 (fr) | Procéde pour la préparation du Zymogène d'urokinase | |
| Sugo et al. | Anti-human factor IX monoclonal antibodies specific for calcium ion-induced conformations | |
| Solomon et al. | Bence Jones Proteins and Light Chains of Immunoglobulins: XIII. Effect of Elastase-like and Chymotrypsin-like Neutral Proteases Derived from Human Granulocytes on Bence Jones Proteins | |
| US4683221A (en) | Lymphocyte-activating polypeptides | |
| US5688919A (en) | Process for the purification of factor XIII, monoclonal antibodies against factor XIIIA, the preparation and use thereof | |
| FI80293B (fi) | Foerfarande foer framstaellning av intakt rekombinent humanimmuninterferon. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |