JPH05501360A - IgAプロテアーゼによる組み換えタンパク質の酵素的切断法 - Google Patents
IgAプロテアーゼによる組み換えタンパク質の酵素的切断法Info
- Publication number
- JPH05501360A JPH05501360A JP3503102A JP50310291A JPH05501360A JP H05501360 A JPH05501360 A JP H05501360A JP 3503102 A JP3503102 A JP 3503102A JP 50310291 A JP50310291 A JP 50310291A JP H05501360 A JPH05501360 A JP H05501360A
- Authority
- JP
- Japan
- Prior art keywords
- pro
- protein
- cleavage
- amino acid
- fusion
- 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
- 238000003776 cleavage reaction Methods 0.000 title claims abstract description 122
- 230000007017 scission Effects 0.000 title claims abstract description 121
- 108010002231 IgA-specific serine endopeptidase Proteins 0.000 title claims abstract description 45
- 238000000034 method Methods 0.000 title claims description 91
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 title claims description 9
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 title claims description 9
- 230000002255 enzymatic effect Effects 0.000 title abstract description 10
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 149
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 133
- 150000001413 amino acids Chemical class 0.000 claims abstract description 72
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 57
- 108020001507 fusion proteins Proteins 0.000 claims description 93
- 102000037865 fusion proteins Human genes 0.000 claims description 93
- 108091005804 Peptidases Proteins 0.000 claims description 50
- 239000004365 Protease Substances 0.000 claims description 47
- 210000004027 cell Anatomy 0.000 claims description 41
- 239000013598 vector Substances 0.000 claims description 29
- 230000004927 fusion Effects 0.000 claims description 28
- 108020004414 DNA Proteins 0.000 claims description 25
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 24
- 230000014509 gene expression Effects 0.000 claims description 22
- 239000000047 product Substances 0.000 claims description 21
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 14
- 108020004511 Recombinant DNA Proteins 0.000 claims description 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 13
- 229920001184 polypeptide Polymers 0.000 claims description 12
- RWCOTTLHDJWHRS-YUMQZZPRSA-N Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 RWCOTTLHDJWHRS-YUMQZZPRSA-N 0.000 claims description 10
- 239000013612 plasmid Substances 0.000 claims description 10
- 108010077112 prolyl-proline Proteins 0.000 claims description 10
- 241000606790 Haemophilus Species 0.000 claims description 8
- 239000002244 precipitate Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- FELJDCNGZFDUNR-WDSKDSINSA-N Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 FELJDCNGZFDUNR-WDSKDSINSA-N 0.000 claims description 6
- 210000001236 prokaryotic cell Anatomy 0.000 claims description 6
- 241000588652 Neisseria gonorrhoeae Species 0.000 claims description 5
- 230000001413 cellular effect Effects 0.000 claims description 5
- 239000002773 nucleotide Substances 0.000 claims description 5
- 125000003729 nucleotide group Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- CGBYDGAJHSOGFQ-LPEHRKFASA-N Pro-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 CGBYDGAJHSOGFQ-LPEHRKFASA-N 0.000 claims description 4
- ICTZKEXYDDZZFP-SRVKXCTJSA-N Pro-Arg-Pro Chemical compound N([C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(O)=O)C(=O)[C@@H]1CCCN1 ICTZKEXYDDZZFP-SRVKXCTJSA-N 0.000 claims description 4
- 230000001717 pathogenic effect Effects 0.000 claims description 4
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 claims description 3
- 241000588653 Neisseria Species 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 230000006037 cell lysis Effects 0.000 claims description 3
- 238000010348 incorporation Methods 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- LQJAALCCPOTJGB-YUMQZZPRSA-N Arg-Pro Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O LQJAALCCPOTJGB-YUMQZZPRSA-N 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 108010060035 arginylproline Proteins 0.000 claims description 2
- 102000005936 beta-Galactosidase Human genes 0.000 claims description 2
- 108010005774 beta-Galactosidase Proteins 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 230000004048 modification Effects 0.000 claims description 2
- 238000012986 modification Methods 0.000 claims description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims 11
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims 3
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 2
- 241001501603 Haemophilus aegyptius Species 0.000 claims 1
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 claims 1
- 241000588650 Neisseria meningitidis Species 0.000 claims 1
- -1 auxiliaries Substances 0.000 claims 1
- 239000000945 filler Substances 0.000 claims 1
- 229940052778 neisseria meningitidis Drugs 0.000 claims 1
- KUUVQVSHGLHAKZ-UHFFFAOYSA-N thionine Chemical group C=1C=CC=CSC=CC=1 KUUVQVSHGLHAKZ-UHFFFAOYSA-N 0.000 claims 1
- 238000010353 genetic engineering Methods 0.000 abstract description 9
- 235000018102 proteins Nutrition 0.000 description 99
- 102000035195 Peptidases Human genes 0.000 description 48
- 235000019419 proteases Nutrition 0.000 description 34
- 230000012743 protein tagging Effects 0.000 description 30
- 102000014914 Carrier Proteins Human genes 0.000 description 18
- 108010078791 Carrier Proteins Proteins 0.000 description 18
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 18
- 229930182817 methionine Natural products 0.000 description 18
- 241000894006 Bacteria Species 0.000 description 17
- 102000004190 Enzymes Human genes 0.000 description 16
- 108090000790 Enzymes Proteins 0.000 description 16
- 239000012634 fragment Substances 0.000 description 16
- 229940088598 enzyme Drugs 0.000 description 15
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 14
- 108091034117 Oligonucleotide Proteins 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- 241000588724 Escherichia coli Species 0.000 description 13
- 239000000872 buffer Substances 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 9
- 244000005700 microbiome Species 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000005520 cutting process Methods 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 230000014616 translation Effects 0.000 description 7
- 102000009016 Cholera Toxin Human genes 0.000 description 6
- 108010049048 Cholera Toxin Proteins 0.000 description 6
- 238000010276 construction Methods 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- QOLYAJSZHIJCTO-VQVTYTSYSA-N Thr-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(O)=O QOLYAJSZHIJCTO-VQVTYTSYSA-N 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000012228 culture supernatant Substances 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 238000005063 solubilization Methods 0.000 description 5
- 230000007928 solubilization Effects 0.000 description 5
- 102000029816 Collagenase Human genes 0.000 description 4
- 108060005980 Collagenase Proteins 0.000 description 4
- 108010048188 MS2 polymerase Proteins 0.000 description 4
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 238000013452 biotechnological production Methods 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 238000004925 denaturation Methods 0.000 description 4
- 230000036425 denaturation Effects 0.000 description 4
- 210000003714 granulocyte Anatomy 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 description 4
- 235000011009 potassium phosphates Nutrition 0.000 description 4
- 238000004153 renaturation Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000001131 transforming effect Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- WPWUFUBLGADILS-WDSKDSINSA-N Ala-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WPWUFUBLGADILS-WDSKDSINSA-N 0.000 description 3
- 108010016626 Dipeptides Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010074860 Factor Xa Proteins 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 108010087924 alanylproline Proteins 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 229960002424 collagenase Drugs 0.000 description 3
- 229960000789 guanidine hydrochloride Drugs 0.000 description 3
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 235000019833 protease Nutrition 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000000527 sonication Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- PVPBBTJXIKFICP-UHFFFAOYSA-N (7-aminophenothiazin-3-ylidene)azanium;chloride Chemical compound [Cl-].C1=CC(=[NH2+])C=C2SC3=CC(N)=CC=C3N=C21 PVPBBTJXIKFICP-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 101710140962 Capsid scaffolding protein Proteins 0.000 description 2
- 241000701959 Escherichia virus Lambda Species 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000000646 Interleukin-3 Human genes 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 108010086093 Mung Bean Nuclease Proteins 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 241000194017 Streptococcus Species 0.000 description 2
- 239000008049 TAE buffer Substances 0.000 description 2
- WTMPKZWHRCMMMT-KZVJFYERSA-N Thr-Pro-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O WTMPKZWHRCMMMT-KZVJFYERSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Chemical group CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Chemical group 0.000 description 2
- HGEVZDLYZYVYHD-UHFFFAOYSA-N acetic acid;2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound CC(O)=O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O HGEVZDLYZYVYHD-UHFFFAOYSA-N 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000005277 cation exchange chromatography Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229940076264 interleukin-3 Drugs 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229960000274 lysozyme Drugs 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
- 235000010335 lysozyme Nutrition 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 239000008057 potassium phosphate buffer Substances 0.000 description 2
- 230000009465 prokaryotic expression Effects 0.000 description 2
- 238000000734 protein sequencing Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000032258 transport Effects 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
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000004400 Aminopeptidases Human genes 0.000 description 1
- 108090000915 Aminopeptidases Proteins 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- 101710081722 Antitrypsin Proteins 0.000 description 1
- YCYXHLZRUSJITQ-SRVKXCTJSA-N Arg-Pro-Pro Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 YCYXHLZRUSJITQ-SRVKXCTJSA-N 0.000 description 1
- 108090000624 Cathepsin L Proteins 0.000 description 1
- 102000004172 Cathepsin L Human genes 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 241001112695 Clostridiales Species 0.000 description 1
- 102000003712 Complement factor B Human genes 0.000 description 1
- 108090000056 Complement factor B Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- 101000658545 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) Type I restriction enyme HindI endonuclease subunit Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 description 1
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 241001082241 Lythrum hyssopifolia Species 0.000 description 1
- 102100026964 M1-specific T cell receptor beta chain Human genes 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101710085938 Matrix protein Proteins 0.000 description 1
- 101710127721 Membrane protein Proteins 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102000009890 Osteonectin Human genes 0.000 description 1
- 108010077077 Osteonectin Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000384942 Premna serratifolia Species 0.000 description 1
- NHDVNAKDACFHPX-GUBZILKMSA-N Pro-Arg-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O NHDVNAKDACFHPX-GUBZILKMSA-N 0.000 description 1
- 241000208474 Protea Species 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 101710182223 Toxin B Proteins 0.000 description 1
- 244000250129 Trigonella foenum graecum Species 0.000 description 1
- 235000001484 Trigonella foenum graecum Nutrition 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 108010087408 alpha-beta T-Cell Antigen Receptors Proteins 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001475 anti-trypsic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 108010029539 arginyl-prolyl-proline Proteins 0.000 description 1
- 230000000468 autoproteolytic effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000010352 biotechnological method Methods 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 108090001092 clostripain Proteins 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000002281 colonystimulating effect Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000007796 conventional method 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
- 238000012258 culturing Methods 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003398 denaturant Substances 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 229940066758 endopeptidases Drugs 0.000 description 1
- 238000012407 engineering method Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 102000044890 human EPO Human genes 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- KIALCSMRIHRFPL-UHFFFAOYSA-N n-(2,5-diphenylpyrazol-3-yl)-4-nitrobenzamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)NC1=CC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 KIALCSMRIHRFPL-UHFFFAOYSA-N 0.000 description 1
- 230000001452 natriuretic effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008023 pharmaceutical filler Substances 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000007065 protein hydrolysis Effects 0.000 description 1
- 238000001814 protein method Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000007026 protein scission Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000012536 storage buffer Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- WEQHQGJDZLDFID-UHFFFAOYSA-J thorium(iv) chloride Chemical compound Cl[Th](Cl)(Cl)Cl WEQHQGJDZLDFID-UHFFFAOYSA-J 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical compound NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5403—IL-3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/28—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Vibrionaceae (F)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/53—Colony-stimulating factor [CSF]
- C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5409—IL-5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/55—IL-2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Toxicology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.融合タンパク質を酵素的に切断し、これらの融合タンパク質の目的成分を単 離する方法であって、 (1)融合タンパク質の2つの成分が一緒に結合される結合部を遺伝子工学的手 法により修飾して、この結合部にアミノ酸配列Y−Pro・!・X−Pro(こ こでXはアミノ酸であり、Yは1個または数個の任意のアミノ酸である)を有す るIgAプロテアーゼ認識部位を少なくとも1つ形成し、(2)段階(1)から 得られた融合タンパク質を・!・で示した認識部位中の位置でIgAプロテアー ゼにより切断し、そして(3)切断後、融合タンパク質の1つまたはいくつかの 目的成分を単離する ことを特徴とする方法。 2.融合タンパク質の結合部をIgAプロテアーゼ認識部位またはその一部をコ ードするヌクレオチド配列の組み込みにより修飾し、その際融合タンパク質の目 的成分をコードする1つまたはいくつかのDNAセクションの前および/または 後に該ヌクレオチド配列を組み込む、請求項1記載の方法。 3.もともと天然IgA認識部位をもっていない融合タンパク質を修飾する、請 求項1または2記載の方法。 4.目的成分のほかに1つまたはいくつかの担体成分を含む融合タンパク質の結 合部を修飾する、請求項1−3のいずれか1つに記載の方法。 5.融合タンパク質の担体成分はβ−ガラクトシダーゼの一部を含む、請求項4 記載の方法。 6.融合タンパク質の担体成分はいくつかの荷電アミノ酸および/または特定の 物質に高い親和性で結合するタンパク質またはポリペプチドを含む、請求項4記 載の方法。 7.XはSer、ThrまたはAlaを表す、請求項1−6のいずれか1つに記 載の方法。 XはSerまたはThrを表す、請求項7記載の方法。 Yは配列Pro、Pro−Ala、Arg−Pro、Pro−Arg−Pro、 Ala−Pro−Arg−ProまたはPro−Ala−Pro−Arg−Pr oで終わる、請求項1−8のいずれか1つに記載の方法。 10.IgAプロテアーゼ認識部位は次のアミノ酸配列:a)Pro−Ala− Pro・!・Ser−Prob)Pro−Pro・!・Ser−Proc)Pr o−Arg−Pro−Pro・!・Ala−Prod)Pro−Pro・!・T hr−Proe)Ala−Pro−Arg−Pro−Pro・!・Thr−Pr oまたはf)Pro−Ala−Pro−Arg−Pro−Pro・!・Thr− Proを有する、請求項9記載の方法。 11.(1)結合部に少なくとも1つのIgAプロテアーゼ認識部位を含む融合 タンパク質をコードする少なくとも1コピーの遺伝子を保有する組み換えDNA または組み換えベクターで細胞を形質転換し、(2)適当な培地で該形質転換細 胞を培養し、(3)該形質転換細胞において融合タンパク質をコードする遺伝子 を発現させ、 (4)該融合タンパク質をIgAプロテアーゼで切断し、そして(5)該融合タ ンパク質の1つまたはいくつかの目的成分を単離する、 ことから成る、請求項1−10のいずれか1つに記載の方法。 12.融合タンパク質は細胞溶解後および/または細胞タンパク質の除去後にI gAプロテアーゼを使って培地中で切断する、請求項11記載の方法。 13.融合タンパク質の切断のために、ナイセリア属、特に淋菌(Neisse ria gonorrhoeae)および髄膜炎菌(Neisseriamen ingitidis)またはヘモフィルス属、特にインフルエンザ菌(Haem ophilus influenzae)およびエジプトヘモフィルス(Hae mophilus aegypticus)の病原菌種から誘導されるIgAプ ロテアーゼ、あるいは該IgAプロテアーゼの修飾により誘導されるタンパク質 を使用する、請求項1−12のいずれか1つに記載の方法。 14.融合タンパク質の切断のために、過剰生産性の非病原菌株から得られるI gAプロテアーゼを使用する、請求項13記載の方法。 15.融合タンパク質の切断のために、固定化されたIgAプロテアーゼを使用 する、請求項13または14記載の方法。 16.可溶性形態、不溶性形態、膜に結合したまたは細胞に結合した形態で存在 する融合タンパク質を切断する、請求項11−15のいずれか1つに記載の方法 。 17.不溶性沈殿体として存在する融合タンパク質を切断する、請求項16記載 の方法。 18.N−末端メチオニン残基を含まない原核細胞由来の組み換えタンパク質の 生産のために、配列Met−Y−Pro・!・X−Pro−A(ここでXはいず れかのアミノ酸を表し、Yは1個または数個の任意のアミノ酸を表し、そしてA はアミノ酸配列を表す)を有する融合タンパク質をIgAプロテアーゼで切断し 、これによりアミノ酸配列X−Pro−Aを有するタンパク質またはペプチドを 切断産物として得る、請求項1−17のいずれか1つに記載の方法。 19.融合タンパク質の目的成分はアミノ酸配列X−Proで始まる、請求項1 8記載の方法。 20.X−Pro−Aはヒト顆粒球コロニー刺激因子(G−CSF)またはその 誘導体を表す、請求項1−19のいずれか1つに記載の方法。 21.IgAプロテアーゼで切断した後、別の工程において融合タンパク質の目 的成分をジペプチジルアミノペプチダーゼで処理し、この方法によりN−末端配 列X−Proを切断する、請求項18記載の方法。 22.X−Pro−ジペプチジルアミノペプチダーゼを使ってN−末端配列X− Proを切断する、請求項21記載の方法。 23.それぞれのポリペプチド成分間の少なくとも1つの結合部に、アミノ酸配 列Y−Pro・!・X−Pro(ここでXはいずれかのアミノ酸、好ましくはS er、ThrまたはAlaを表し、Yは1個または数個の任意のアミノ酸を表す )で表される1つまたはいくつかのIgAプロテアーゼ認識部位を有する、いく つかのポリペプチド成分を含む融合タンパク質。 24.アミノ酸配列Met−Y−Pro・!・X−Pro−A(ここでXとYは 上記の意味を有し、Aはアミノ酸配列を表す)を有する、請求項23記載の融合 タンパク質。 25.Yはその末端に配列Pro、Pro−Ala、Pro−Arg−Pro、 Ala−Pro−Arg−ProまたはPro−Ala−Pro−Arg−Pr oを含む、請求項23または24記載の融合タンパク質。 26.アミノ酸配列X−Pro−Aは顆粒球コロニー刺激因子(G−CSF)ま たはその誘導体を表す、請求項23−25のいずれか1つに記載の融合タンパク 質。 27.N−末端メチオニン残基を有するG−CSFを本質的に定量的に含まない 、請求項26記載の組み換えG−CSF。 28.他のタンパク質によって0.1%未満汚染されている、請求項26または 27記載の組み換えG−CSF。 29.他のタンパク質によって10−2%未満汚染されており、かつN−末端メ チオニン残基を有するG−CSFを定量的に含まない、請求項26または27記 載の組み換えG−CSF。 30.活性物質としての請求項26−29のいずれか1つに記載したG−CSF またはG−CSF誘導体および、所望により、慣用の製剤上の添加剤、補助剤お よび/または担体を含有してなる医薬組成物。 31.所望により、慣用の製剤上の添加剤、補助剤、充填剤および/または担体 を加えた医薬組成物を調製するための、請求項26−29のいずれか1つに記載 したG−CSF誘導体の使用。 32.請求項23−29のいずれか1つに記載した融合タンパク質をコードする 、組み換えDNA。 33.請求項32に記載した組み換えDNAの1つまたはいくつかのコピーを含 む、組み換えベクター。 34.組み換えDNAは誘導可能な発現シグナルの制御下にある、請求項33記 載の組み換えベクター。 35.原核生物のベクターである、請求項33または34記載の組み換えベクタ ー。 36.プラスミドである、請求項32−34のいずれか1つに記載の組み換えベ クター。 37.請求項32に記載したDNAまたは請求項33−36に記載したベクター で形質転換された細胞。 38.原核生物の細胞である、請求項37記載の細胞。
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4003149.7 | 1990-02-03 | ||
DE4003149 | 1990-02-03 | ||
DE4015922.1 | 1990-05-17 | ||
DE4015921 | 1990-05-17 | ||
DE4015922A DE4015922A1 (de) | 1990-05-17 | 1990-05-17 | Verfahren zur enzymatischen prozessierung von proteinen unter verwendung von iga-proteasen (igase) |
DE4015921.3 | 1990-05-17 | ||
DE4039415.8 | 1990-12-10 | ||
DE4039415A DE4039415A1 (de) | 1990-02-03 | 1990-12-10 | Verfahren zur herstellung rekombinanter proteine ohne n-terminalen methioninrest |
PCT/EP1991/000192 WO1991011520A1 (de) | 1990-02-03 | 1991-02-01 | VERFAHREN ZUR ENZYMATISCHEN SPALTUNG REKOMBINANTER PROTEINE UNTER VERWENDUNG VON IgA-PROTEASEN |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP7000120A Division JP2766621B2 (ja) | 1990-02-03 | 1995-01-04 | 組み換えg−csf |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH05501360A true JPH05501360A (ja) | 1993-03-18 |
JPH0789952B2 JPH0789952B2 (ja) | 1995-10-04 |
Family
ID=27434868
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP3503102A Expired - Lifetime JPH0789952B2 (ja) | 1990-02-03 | 1991-02-01 | IgAプロテアーゼによる組み換えタンパク質の酵素的切断法 |
JP7000120A Expired - Lifetime JP2766621B2 (ja) | 1990-02-03 | 1995-01-04 | 組み換えg−csf |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP7000120A Expired - Lifetime JP2766621B2 (ja) | 1990-02-03 | 1995-01-04 | 組み換えg−csf |
Country Status (19)
Country | Link |
---|---|
US (1) | US5427927A (ja) |
EP (2) | EP0602688B1 (ja) |
JP (2) | JPH0789952B2 (ja) |
KR (1) | KR960011919B1 (ja) |
AT (2) | ATE219518T1 (ja) |
AU (1) | AU638309B2 (ja) |
CA (1) | CA2074943C (ja) |
CZ (1) | CZ284774B6 (ja) |
DK (1) | DK0513073T3 (ja) |
ES (2) | ES2177536T3 (ja) |
FI (1) | FI109810B (ja) |
HU (1) | HU217103B (ja) |
IE (1) | IE64938B1 (ja) |
IL (1) | IL97119A0 (ja) |
LV (1) | LV10309B (ja) |
NO (1) | NO311142B1 (ja) |
NZ (1) | NZ236819A (ja) |
PT (1) | PT96658B (ja) |
WO (1) | WO1991011520A1 (ja) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8476232B2 (en) | 2006-08-31 | 2013-07-02 | Hoffman-La Roche Inc. | Method for the production of conjugates of insulin-like growth factor-1 and poly(ethylene glycol) |
US8552158B2 (en) | 2006-08-31 | 2013-10-08 | Hoffmann-La Roche Inc. | Method for the production of insulin-like growth factor-1 |
JP2016518855A (ja) * | 2013-05-24 | 2016-06-30 | ノヴォ ノルディスク アー/エス | 融合プロテアーゼ |
JP2017500040A (ja) * | 2013-12-20 | 2017-01-05 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 改良された、組換えポリペプチド作製方法 |
JP6456579B1 (ja) * | 2017-06-09 | 2019-01-23 | 三菱電機株式会社 | フェーズドアレイアンテナ |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5718893A (en) * | 1984-04-15 | 1998-02-17 | Foster; Preston F. | Use of G-CSF to reduce acute rejection |
DE4344350C2 (de) * | 1993-12-23 | 1995-09-21 | Max Planck Gesellschaft | Bakterien zur Herstellung stabiler Fusionsproteine und Verfahren zu deren Nachweis |
US5536495A (en) * | 1994-04-15 | 1996-07-16 | Foster; Preston F. | Use of G-CSF to reduce acute rejection |
WO1996009395A2 (de) * | 1994-09-21 | 1996-03-28 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Arzneimittel zur prophylaxe und behandlung von und diagnostika zur erkennung von autoimmunkrankheiten und viralen erkrankungen |
AT404838B (de) * | 1995-11-24 | 1999-03-25 | Immuno Ag | Herstellung von proteinen aus pro-proteinen durch fusionsproteine abgeleitet von furin oder furinanalogen |
DE19549232C2 (de) * | 1995-12-20 | 1998-05-20 | Boehringer Mannheim Gmbh | Verwendung von G-CSF in Kombination mit einem Chemotherapeutikum bei der Behandlung von Erkrankungen, die eine periphere Stammzelltransplantation erfordern |
GB9618960D0 (en) | 1996-09-11 | 1996-10-23 | Medical Science Sys Inc | Proteases |
US6444202B1 (en) | 1996-11-25 | 2002-09-03 | Bundesrepublic Deutschland, Vertreten Durch Den Bundesminister Fur Gesundheit | Processed polypeptides with IL-16 activity, processes for their production and their use |
US20030190740A1 (en) * | 1998-10-13 | 2003-10-09 | The University Of Georgia Research Foundation, Inc | Stabilized bioactive peptides and methods of identification, synthesis, and use |
JP2002534059A (ja) * | 1998-10-13 | 2002-10-15 | ザ ユニバーシティ オブ ジョージア リサーチファウンデーション,インコーポレイティド | 安定化された生物活性ペプチドおよび同定、合成および使用方法 |
KR100356140B1 (ko) * | 1999-07-08 | 2002-10-19 | 한미약품공업 주식회사 | 인간 과립구 콜로니 자극인자 변이체 및 이의 생산 방법 |
US20030190644A1 (en) * | 1999-10-13 | 2003-10-09 | Andreas Braun | Methods for generating databases and databases for identifying polymorphic genetic markers |
US7820378B2 (en) * | 2002-11-27 | 2010-10-26 | Sequenom, Inc. | Fragmentation-based methods and systems for sequence variation detection and discovery |
JP4833056B2 (ja) * | 2003-04-23 | 2011-12-07 | アナフォア インコーポレイテッド | グランザイムbプロテアーゼを使用した融合タンパク質の開裂 |
EP1618216A2 (en) * | 2003-04-25 | 2006-01-25 | Sequenom, Inc. | Fragmentation-based methods and systems for de novo sequencing |
US9394565B2 (en) * | 2003-09-05 | 2016-07-19 | Agena Bioscience, Inc. | Allele-specific sequence variation analysis |
KR20060116825A (ko) | 2003-10-23 | 2006-11-15 | 일루미겐 바이오사이언시스, 인코포레이티드 | 바이러스 감염에 대한 저항성과 관련된 유전자인oas1에서의 돌연변이의 검출 |
US7220407B2 (en) | 2003-10-27 | 2007-05-22 | Amgen Inc. | G-CSF therapy as an adjunct to reperfusion therapy in the treatment of acute myocardial infarction |
SI21639A (sl) * | 2003-12-23 | 2005-06-30 | LEK farmacevtska dru�ba d.d. | Farmacevtski pripravek, ki vsebuje nemicelarne sulfobetaine |
US7608394B2 (en) | 2004-03-26 | 2009-10-27 | Sequenom, Inc. | Methods and compositions for phenotype identification based on nucleic acid methylation |
WO2005098050A2 (en) * | 2004-03-26 | 2005-10-20 | Sequenom, Inc. | Base specific cleavage of methylation-specific amplification products in combination with mass analysis |
EP1802772A4 (en) * | 2004-09-10 | 2008-12-31 | Sequenom Inc | METHOD FOR NUCLEIC ACID SEQUENCE ANALYSIS WITH GREAT RANGE |
EP1817047B1 (en) | 2004-11-05 | 2012-02-08 | Northwestern University | Use of scf and g-csf in the treatment of cerebral ischemia and neurological disorders |
UA95446C2 (ru) | 2005-05-04 | 2011-08-10 | Іллюміджен Байосайєнсіз, Інк. | Мутаци в генах oas1 |
CA2684217C (en) * | 2007-04-13 | 2016-12-13 | Sequenom, Inc. | Comparative sequence analysis processes and systems |
DE102007040932A1 (de) | 2007-08-27 | 2009-03-05 | Biogenerix Ag | Flüssigformulierung von G-CSF |
AU2008291309B2 (en) | 2007-08-27 | 2013-10-17 | Ratiopharm Gmbh | Liquid formulation of G-CSF |
US8501449B2 (en) | 2007-12-04 | 2013-08-06 | Proteon Therapeutics, Inc. | Recombinant elastase proteins and methods of manufacturing and use thereof |
WO2009121551A1 (en) * | 2008-04-03 | 2009-10-08 | F. Hoffmann-La Roche Ag | Pegylated insulin-like-growth-factor assay |
AU2009231394B2 (en) * | 2008-04-03 | 2013-09-05 | F. Hoffmann-La Roche Ag | Use of PEGylated IGF-I variants for the treatment of neuromuscular disorders |
US8053222B2 (en) * | 2009-02-12 | 2011-11-08 | Academia Sinica, Taiwan | Protein expression system involving mutated severe respiratory syndrome-associated coronavirus 3C-like protease |
US20110152188A1 (en) * | 2009-12-23 | 2011-06-23 | Hanns-Christian Mahler | Pharmaceutical compositions of igf/i proteins |
EP2525787B1 (en) | 2010-01-19 | 2017-03-15 | Hanmi Science Co., Ltd. | Liquid formulations for long-acting g-csf conjugate |
KR20130059404A (ko) * | 2010-08-30 | 2013-06-05 | 에프. 호프만-라 로슈 아게 | 원핵생물 발현 구축물 |
PE20221007A1 (es) | 2015-06-24 | 2022-06-15 | Hoffmann La Roche | Anticuerpos anti-receptor de transferrina con afinidad disenada |
AR106189A1 (es) | 2015-10-02 | 2017-12-20 | Hoffmann La Roche | ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO |
CN114031689A (zh) | 2015-10-02 | 2022-02-11 | 豪夫迈·罗氏有限公司 | 双特异性抗人cd20/人转铁蛋白受体抗体及使用方法 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL60184A (en) * | 1979-05-31 | 1984-05-31 | Schering Ag | Process for the specific cleavage of protein sequences from proteins |
JPS62129298A (ja) * | 1985-12-02 | 1987-06-11 | Chugai Pharmaceut Co Ltd | 新規ポリペプチド |
EP0215126B1 (en) * | 1985-02-08 | 1991-07-31 | Chugai Seiyaku Kabushiki Kaisha | Human granulocyte colony stimulating factor |
US5087564A (en) * | 1985-06-20 | 1992-02-11 | Monsanto Company | Release of recombinant peptides from polypeptides using V8 endopeptidase |
DE3681551D1 (de) * | 1985-09-30 | 1991-10-24 | Chugai Pharmaceutical Co Ltd | Menschlicher granulozyten-colony stimulierender faktor. |
DE3545568A1 (de) * | 1985-12-21 | 1987-07-16 | Hoechst Ag | Gm-csf-protein, seine derivate, herstellung solcher proteine und ihre verwendung |
FR2594846B1 (fr) * | 1986-02-21 | 1989-10-20 | Genetica | Procede de preparation de la serum albumine humaine mature |
US4828988A (en) * | 1986-05-15 | 1989-05-09 | Smith Kline - Rit | Hybrid polypeptides comprising somatocrinine and alpha1 -antitrypsin, method for their production from bacterial clones and use thereof for the production of somatocrinine |
DE3622221A1 (de) * | 1986-07-02 | 1988-01-14 | Max Planck Gesellschaft | Verfahren zur gentechnologischen gewinnung von proteinen unter verwendung gramnegativer wirtszellen |
EP0256843A1 (en) * | 1986-08-11 | 1988-02-24 | Cetus Corporation | Expression of g-csf and muteins thereof and their use |
IT1223577B (it) * | 1987-12-22 | 1990-09-19 | Eniricerche Spa | Procedimento migliorato per la preparazione dell'ormone della crescita umano naturale in forma pura |
ES2063783T3 (es) * | 1988-06-03 | 1995-01-16 | Chugai Pharmaceutical Co Ltd | Factor de cristalino humano de estimulacion de colonias de granulocitos y procedimiento para su preparacion. |
JPH04503301A (ja) * | 1988-12-01 | 1992-06-18 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ノース カロライナ | 合成インターロイキン―6 |
US5055555A (en) * | 1989-01-05 | 1991-10-08 | Helmut Sassenfeld | Purification of G-CSF |
US5073627A (en) * | 1989-08-22 | 1991-12-17 | Immunex Corporation | Fusion proteins comprising GM-CSF and IL-3 |
-
1991
- 1991-01-18 NZ NZ236819A patent/NZ236819A/xx unknown
- 1991-01-31 IL IL97119A patent/IL97119A0/xx not_active IP Right Cessation
- 1991-02-01 ES ES93121015T patent/ES2177536T3/es not_active Expired - Lifetime
- 1991-02-01 EP EP93121015A patent/EP0602688B1/de not_active Expired - Lifetime
- 1991-02-01 CA CA002074943A patent/CA2074943C/en not_active Expired - Lifetime
- 1991-02-01 AT AT93121015T patent/ATE219518T1/de not_active IP Right Cessation
- 1991-02-01 ES ES91902956T patent/ES2076521T3/es not_active Expired - Lifetime
- 1991-02-01 AU AU71496/91A patent/AU638309B2/en not_active Ceased
- 1991-02-01 PT PT96658A patent/PT96658B/pt not_active IP Right Cessation
- 1991-02-01 DK DK91902956.1T patent/DK0513073T3/da active
- 1991-02-01 US US07/917,034 patent/US5427927A/en not_active Expired - Lifetime
- 1991-02-01 CZ CS91241A patent/CZ284774B6/cs not_active IP Right Cessation
- 1991-02-01 JP JP3503102A patent/JPH0789952B2/ja not_active Expired - Lifetime
- 1991-02-01 AT AT91902956T patent/ATE124456T1/de not_active IP Right Cessation
- 1991-02-01 KR KR1019920701858A patent/KR960011919B1/ko not_active IP Right Cessation
- 1991-02-01 EP EP91902956A patent/EP0513073B1/de not_active Expired - Lifetime
- 1991-02-01 HU HU9202511A patent/HU217103B/hu unknown
- 1991-02-01 IE IE35891A patent/IE64938B1/en not_active IP Right Cessation
- 1991-02-01 WO PCT/EP1991/000192 patent/WO1991011520A1/de active IP Right Grant
-
1992
- 1992-07-30 NO NO19923010A patent/NO311142B1/no unknown
- 1992-07-31 FI FI923463A patent/FI109810B/fi active
-
1993
- 1993-09-24 LV LVP-93-1094A patent/LV10309B/lv unknown
-
1995
- 1995-01-04 JP JP7000120A patent/JP2766621B2/ja not_active Expired - Lifetime
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8476232B2 (en) | 2006-08-31 | 2013-07-02 | Hoffman-La Roche Inc. | Method for the production of conjugates of insulin-like growth factor-1 and poly(ethylene glycol) |
US8552158B2 (en) | 2006-08-31 | 2013-10-08 | Hoffmann-La Roche Inc. | Method for the production of insulin-like growth factor-1 |
JP2016518855A (ja) * | 2013-05-24 | 2016-06-30 | ノヴォ ノルディスク アー/エス | 融合プロテアーゼ |
JP2017500040A (ja) * | 2013-12-20 | 2017-01-05 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 改良された、組換えポリペプチド作製方法 |
JP6456579B1 (ja) * | 2017-06-09 | 2019-01-23 | 三菱電機株式会社 | フェーズドアレイアンテナ |
US10446928B2 (en) | 2017-06-09 | 2019-10-15 | Mitsubishi Electric Corporation | Phased array antenna |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2766621B2 (ja) | 組み換えg−csf | |
CA1338642C (en) | Bacterial methionine n-terminal peptidase | |
FR2518572A1 (fr) | Plasmide d'expression permettant l'insertion appropriee d'adn heterologue | |
AU679427B2 (en) | DNA sequences encoding gelonin polypeptide | |
US4828988A (en) | Hybrid polypeptides comprising somatocrinine and alpha1 -antitrypsin, method for their production from bacterial clones and use thereof for the production of somatocrinine | |
JPH08510899A (ja) | 宿主細胞中でのタンパク質の過剰発現のための方法およびdna発現システム | |
JP7449000B2 (ja) | 可溶性の組換えタンパク質の生成 | |
RU2120475C1 (ru) | Способ получения представляющего интерес полипептида, гибридная днк (варианты), слитый белок (варианты) | |
AU777408B2 (en) | Production of pancreatic procarboxy-peptidase B, isoforms and muteins thereof, and their use | |
RU2108386C1 (ru) | Рекомбинантный гранулоцит-колониестимулирующий фактор (g - csf) без дополнительного остатка метионина на n-конце | |
IE914559A1 (en) | RECOMBINANT IgA PROTEASE | |
JPS62226998A (ja) | ヒトカルシトニン前駆体ペプチド及びその製造方法 | |
RU2143492C1 (ru) | Рекомбинантная плазмида, кодирующая гибридный белок - предшественник инсулина человека (варианты), штамм бактерий e.coli - продуцент гибридного белка - предшественника инсулина человека (варианты), способ получения инсулина человека | |
JPH01273591A (ja) | ヒト成長ホルモン分泌プラスミド、ならびにそれを用いた形質転換体および蛋白質分泌生産法 | |
US20230242961A1 (en) | Production of Soluble Recombinant Protein | |
US20210348174A1 (en) | Production of Soluble Recombinant Proteins without N-Terminal Methionine in E-Coli | |
JPH0728746B2 (ja) | 新規プラスミド、微生物細胞及びヒト免疫グロブリンG Fc領域蛋白質の製造法 | |
JPH1014578A (ja) | 入れ換え変異体遺伝子dnaの構築 | |
JPH02291294A (ja) | ポリペプチドの製造方法 | |
JPH0213382A (ja) | グラムネガテイブ微生物での構造遺伝子の調節発現法 | |
JPH04126083A (ja) | プロテアーゼインヒビター遺伝子及び該遺伝子を保有する微生物並びに該微生物を用いるプロテアーゼインヒビターの製造法 | |
JPH0588110B2 (ja) | ||
JPS61212288A (ja) | 蛋白製造法 | |
JPS63263084A (ja) | ヒトインスリン様成長因子iの製造法 | |
JPS61152297A (ja) | 蛋白質の製造法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
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 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20081004 Year of fee payment: 13 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20081004 Year of fee payment: 13 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20091004 Year of fee payment: 14 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20091004 Year of fee payment: 14 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20101004 Year of fee payment: 15 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111004 Year of fee payment: 16 |
|
EXPY | Cancellation because of completion of term | ||
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111004 Year of fee payment: 16 |