IL107712A - A method of producing a polypeptide by fermenting bacteria - Google Patents

A method of producing a polypeptide by fermenting bacteria

Info

Publication number: IL107712A
Authority: IL; Israel
Prior art keywords: cytochrome; oxidase; fermentation; gene; dna
Prior art date: 1992-11-23

Application number

IL10771293A

Other languages

English (en)

Hebrew (he)

Other versions

IL107712A0 (en

Original Assignee

Genentech Inc

Priority date (The priority date 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 date listed.)

1992-11-23

Filing date

1993-11-22

Publication date

2002-09-12

1993-11-22 Application filed by Genentech Inc filed Critical Genentech Inc

1994-02-27 Publication of IL107712A0 publication Critical patent/IL107712A0/xx

2002-09-12 Publication of IL107712A publication Critical patent/IL107712A/en

Links

230000001580 bacterial effect Effects 0.000 title claims abstract description 51
238000000855 fermentation Methods 0.000 title claims description 76
230000004151 fermentation Effects 0.000 title claims description 76
108090000765 processed proteins & peptides Proteins 0.000 title claims description 56
102000004196 processed proteins & peptides Human genes 0.000 title claims description 55
229920001184 polypeptide Polymers 0.000 title claims description 54
238000004519 manufacturing process Methods 0.000 title description 33
238000000034 method Methods 0.000 claims abstract description 76
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 43
229910052760 oxygen Inorganic materials 0.000 claims abstract description 42
239000001301 oxygen Substances 0.000 claims abstract description 41
238000012217 deletion Methods 0.000 claims description 36
230000037430 deletion Effects 0.000 claims description 36
241000588724 Escherichia coli Species 0.000 claims description 32
108010077128 cytochrome o oxidase Proteins 0.000 claims description 32
108010022613 Cytochrome d Group Proteins 0.000 claims description 29
102000004316 Oxidoreductases Human genes 0.000 claims description 29
108090000854 Oxidoreductases Proteins 0.000 claims description 29
150000007523 nucleic acids Chemical class 0.000 claims description 25
239000002773 nucleotide Substances 0.000 claims description 24
125000003729 nucleotide group Chemical group 0.000 claims description 24
108020004707 nucleic acids Proteins 0.000 claims description 22
102000039446 nucleic acids Human genes 0.000 claims description 22
230000008569 process Effects 0.000 claims description 16
101100390711 Escherichia coli (strain K12) fhuA gene Proteins 0.000 claims description 15
238000012546 transfer Methods 0.000 claims description 9
108091005804 Peptidases Proteins 0.000 claims description 7
230000002068 genetic effect Effects 0.000 claims description 7
230000001771 impaired effect Effects 0.000 claims description 7
239000004365 Protease Substances 0.000 claims description 6
108010051696 Growth Hormone Proteins 0.000 claims description 5
102000018997 Growth Hormone Human genes 0.000 claims description 5
230000004075 alteration Effects 0.000 claims description 5
239000000122 growth hormone Substances 0.000 claims description 5
230000010355 oscillation Effects 0.000 claims description 5
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
229910001882 dioxygen Inorganic materials 0.000 claims description 4
230000002950 deficient Effects 0.000 claims description 3
230000003252 repetitive effect Effects 0.000 claims description 3
239000000758 substrate Substances 0.000 claims description 3
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
238000004113 cell culture Methods 0.000 abstract description 7
239000008103 glucose Substances 0.000 description 79
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 78
239000013612 plasmid Substances 0.000 description 75
108020004414 DNA Proteins 0.000 description 74
108090000623 proteins and genes Proteins 0.000 description 72
210000004027 cell Anatomy 0.000 description 67
239000012634 fragment Substances 0.000 description 65
108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 52
239000000523 sample Substances 0.000 description 45
239000013598 vector Substances 0.000 description 44
102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 40
108091006149 Electron carriers Proteins 0.000 description 38
230000035772 mutation Effects 0.000 description 37
102000004169 proteins and genes Human genes 0.000 description 35
235000018102 proteins Nutrition 0.000 description 34
150000001413 amino acids Chemical group 0.000 description 29
108010076504 Protein Sorting Signals Proteins 0.000 description 27
241000894006 Bacteria Species 0.000 description 26
235000001014 amino acid Nutrition 0.000 description 26
238000010276 construction Methods 0.000 description 25
239000002609 medium Substances 0.000 description 24
229940024606 amino acid Drugs 0.000 description 22
108091034117 Oligonucleotide Proteins 0.000 description 20
239000004098 Tetracycline Substances 0.000 description 20
229960002180 tetracycline Drugs 0.000 description 20
229930101283 tetracycline Natural products 0.000 description 20
235000019364 tetracycline Nutrition 0.000 description 20
150000003522 tetracyclines Chemical class 0.000 description 20
229910052799 carbon Inorganic materials 0.000 description 19
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 18
238000002703 mutagenesis Methods 0.000 description 18
231100000350 mutagenesis Toxicity 0.000 description 18
230000014509 gene expression Effects 0.000 description 16
239000000543 intermediate Substances 0.000 description 16
230000037361 pathway Effects 0.000 description 16
239000000047 product Substances 0.000 description 16
230000003247 decreasing effect Effects 0.000 description 14
238000002474 experimental method Methods 0.000 description 14
229930027917 kanamycin Natural products 0.000 description 14
229960000318 kanamycin Drugs 0.000 description 14
SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 14
229930182823 kanamycin A Natural products 0.000 description 14
238000006467 substitution reaction Methods 0.000 description 14
235000019687 Lamb Nutrition 0.000 description 13
229910019142 PO4 Inorganic materials 0.000 description 13
239000010452 phosphate Substances 0.000 description 13
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
238000003780 insertion Methods 0.000 description 12
230000037431 insertion Effects 0.000 description 12
230000027721 electron transport chain Effects 0.000 description 11
230000029058 respiratory gaseous exchange Effects 0.000 description 11
102000002260 Alkaline Phosphatase Human genes 0.000 description 10
108020004774 Alkaline Phosphatase Proteins 0.000 description 10
108050008072 Cytochrome c oxidase subunit IV Proteins 0.000 description 10
230000007423 decrease Effects 0.000 description 10
230000012010 growth Effects 0.000 description 10
230000002103 transcriptional effect Effects 0.000 description 10
238000010361 transduction Methods 0.000 description 10
230000026683 transduction Effects 0.000 description 10
HYPYXGZDOYTYDR-HAJWAVTHSA-N 2-methyl-3-[(2e,6e,10e,14e)-3,7,11,15,19-pentamethylicosa-2,6,10,14,18-pentaenyl]naphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 HYPYXGZDOYTYDR-HAJWAVTHSA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
239000000306 component Substances 0.000 description 9
230000009466 transformation Effects 0.000 description 9
235000019143 vitamin K2 Nutrition 0.000 description 9
239000011728 vitamin K2 Substances 0.000 description 9
229940041603 vitamin k 3 Drugs 0.000 description 9
108020004705 Codon Proteins 0.000 description 8
108091028043 Nucleic acid sequence Proteins 0.000 description 8
238000010586 diagram Methods 0.000 description 8
230000000694 effects Effects 0.000 description 8
108091026890 Coding region Proteins 0.000 description 7
102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 description 7
101000867232 Escherichia coli Heat-stable enterotoxin II Proteins 0.000 description 7
101100407828 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) ptr-3 gene Proteins 0.000 description 7
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 7
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 7
230000006870 function Effects 0.000 description 7
239000006166 lysate Substances 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
230000010076 replication Effects 0.000 description 7
108010052832 Cytochromes Proteins 0.000 description 6
102000018832 Cytochromes Human genes 0.000 description 6
102000035195 Peptidases Human genes 0.000 description 6
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 6
230000004103 aerobic respiration Effects 0.000 description 6
238000012258 culturing Methods 0.000 description 6
239000013604 expression vector Substances 0.000 description 6
239000012528 membrane Substances 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
230000032258 transport Effects 0.000 description 6
102000053602 DNA Human genes 0.000 description 5
108020004511 Recombinant DNA Proteins 0.000 description 5
241000607142 Salmonella Species 0.000 description 5
229960000723 ampicillin Drugs 0.000 description 5
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 5
238000013459 approach Methods 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
230000000295 complement effect Effects 0.000 description 5
101150105228 dap gene Proteins 0.000 description 5
101150018266 degP gene Proteins 0.000 description 5
239000001963 growth medium Substances 0.000 description 5
239000002054 inoculum Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
230000001404 mediated effect Effects 0.000 description 5
239000000203 mixture Substances 0.000 description 5
235000015097 nutrients Nutrition 0.000 description 5
239000012071 phase Substances 0.000 description 5
238000002708 random mutagenesis Methods 0.000 description 5
108091008146 restriction endonucleases Proteins 0.000 description 5
238000010561 standard procedure Methods 0.000 description 5
ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
241000276495 Melanogrammus aeglefinus Species 0.000 description 4
101100178822 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) htrA1 gene Proteins 0.000 description 4
102100029268 Neurotrophin-3 Human genes 0.000 description 4
108090000099 Neurotrophin-4 Proteins 0.000 description 4
101100277437 Rhizobium meliloti (strain 1021) degP1 gene Proteins 0.000 description 4
229940041514 candida albicans extract Drugs 0.000 description 4
210000000349 chromosome Anatomy 0.000 description 4
235000017471 coenzyme Q10 Nutrition 0.000 description 4
ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 4
230000004927 fusion Effects 0.000 description 4
238000009396 hybridization Methods 0.000 description 4
239000008101 lactose Substances 0.000 description 4
230000000813 microbial effect Effects 0.000 description 4
238000012544 monitoring process Methods 0.000 description 4
101150093139 ompT gene Proteins 0.000 description 4
-1 or NT-6) Proteins 0.000 description 4
235000019419 proteases Nutrition 0.000 description 4
238000011084 recovery Methods 0.000 description 4
NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 4
230000027756 respiratory electron transport chain Effects 0.000 description 4
238000001890 transfection Methods 0.000 description 4
229940035936 ubiquinone Drugs 0.000 description 4
241001515965 unidentified phage Species 0.000 description 4
239000012138 yeast extract Substances 0.000 description 4
229920001817 Agar Polymers 0.000 description 3
102000004594 DNA Polymerase I Human genes 0.000 description 3
108010017826 DNA Polymerase I Proteins 0.000 description 3
102000016911 Deoxyribonucleases Human genes 0.000 description 3
108010053770 Deoxyribonucleases Proteins 0.000 description 3
241001646716 Escherichia coli K-12 Species 0.000 description 3
241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 description 3
241000702191 Escherichia virus P1 Species 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
102000004877 Insulin Human genes 0.000 description 3
108090001061 Insulin Proteins 0.000 description 3
108010025020 Nerve Growth Factor Proteins 0.000 description 3
101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 3
108020004682 Single-Stranded DNA Proteins 0.000 description 3
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 3
238000009825 accumulation Methods 0.000 description 3
230000009603 aerobic growth Effects 0.000 description 3
239000008272 agar Substances 0.000 description 3
238000012867 alanine scanning Methods 0.000 description 3
230000003466 anti-cipated effect Effects 0.000 description 3
238000004422 calculation algorithm Methods 0.000 description 3
230000001413 cellular effect Effects 0.000 description 3
230000008859 change Effects 0.000 description 3
238000010367 cloning Methods 0.000 description 3
230000029087 digestion Effects 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
230000010354 integration Effects 0.000 description 3
239000007791 liquid phase Substances 0.000 description 3
239000003550 marker Substances 0.000 description 3
210000001322 periplasm Anatomy 0.000 description 3
238000000746 purification Methods 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
230000035806 respiratory chain Effects 0.000 description 3
230000004044 response Effects 0.000 description 3
230000028327 secretion Effects 0.000 description 3
238000002741 site-directed mutagenesis Methods 0.000 description 3
230000001960 triggered effect Effects 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
YCIHPQHVWDULOY-FMZCEJRJSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O YCIHPQHVWDULOY-FMZCEJRJSA-N 0.000 description 2
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
241000203069 Archaea Species 0.000 description 2
108010077805 Bacterial Proteins Proteins 0.000 description 2
102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 2
108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 2
102000014914 Carrier Proteins Human genes 0.000 description 2
108010078791 Carrier Proteins Proteins 0.000 description 2
108010055166 Chemokine CCL5 Proteins 0.000 description 2
108010073254 Colicins Proteins 0.000 description 2
102000007644 Colony-Stimulating Factors Human genes 0.000 description 2
108010071942 Colony-Stimulating Factors Proteins 0.000 description 2
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
230000005526 G1 to G0 transition Effects 0.000 description 2
239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 2
101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 2
108010000521 Human Growth Hormone Proteins 0.000 description 2
102000002265 Human Growth Hormone Human genes 0.000 description 2
239000000854 Human Growth Hormone Substances 0.000 description 2
108010063738 Interleukins Proteins 0.000 description 2
102000015696 Interleukins Human genes 0.000 description 2
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
108010052285 Membrane Proteins Proteins 0.000 description 2
102000006746 NADH Dehydrogenase Human genes 0.000 description 2
108010086428 NADH Dehydrogenase Proteins 0.000 description 2
229910017974 NH40H Inorganic materials 0.000 description 2
108090000742 Neurotrophin 3 Proteins 0.000 description 2
102000003683 Neurotrophin-4 Human genes 0.000 description 2
102100033857 Neurotrophin-4 Human genes 0.000 description 2
108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
101100084022 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) lapA gene Proteins 0.000 description 2
102400000834 Relaxin A chain Human genes 0.000 description 2
101800000074 Relaxin A chain Proteins 0.000 description 2
240000004808 Saccharomyces cerevisiae Species 0.000 description 2
241000607720 Serratia Species 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
101710142969 Somatoliberin Proteins 0.000 description 2
102100022831 Somatoliberin Human genes 0.000 description 2
108020005038 Terminator Codon Proteins 0.000 description 2
108010000499 Thromboplastin Proteins 0.000 description 2
102100033571 Tissue-type plasminogen activator Human genes 0.000 description 2
108010009583 Transforming Growth Factors Proteins 0.000 description 2
102000009618 Transforming Growth Factors Human genes 0.000 description 2
102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 2
108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
239000002253 acid Substances 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000009471 action Effects 0.000 description 2
238000013019 agitation Methods 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000000427 antigen Substances 0.000 description 2
108091007433 antigens Proteins 0.000 description 2
102000036639 antigens Human genes 0.000 description 2
239000011942 biocatalyst Substances 0.000 description 2
239000003114 blood coagulation factor Substances 0.000 description 2
229940112869 bone morphogenetic protein Drugs 0.000 description 2
238000004364 calculation method Methods 0.000 description 2
238000012219 cassette mutagenesis Methods 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
229940047120 colony stimulating factors Drugs 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
230000001276 controlling effect Effects 0.000 description 2
210000000805 cytoplasm Anatomy 0.000 description 2
238000009795 derivation Methods 0.000 description 2
238000013461 design Methods 0.000 description 2
229940088598 enzyme Drugs 0.000 description 2
239000013613 expression plasmid Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
108010067006 heat stable toxin (E coli) Proteins 0.000 description 2
150000004688 heptahydrates Chemical class 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
239000005556 hormone Substances 0.000 description 2
102000044162 human IGF1 Human genes 0.000 description 2
239000002596 immunotoxin Substances 0.000 description 2
231100000608 immunotoxin Toxicity 0.000 description 2
229940051026 immunotoxin Drugs 0.000 description 2
230000002637 immunotoxin Effects 0.000 description 2
230000002779 inactivation Effects 0.000 description 2
238000011534 incubation Methods 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
229940047122 interleukins Drugs 0.000 description 2
229910052742 iron Inorganic materials 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000004066 metabolic change Effects 0.000 description 2
230000003278 mimic effect Effects 0.000 description 2
238000002156 mixing Methods 0.000 description 2
239000003900 neurotrophic factor Substances 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
230000036284 oxygen consumption Effects 0.000 description 2
101150009573 phoA gene Proteins 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
238000009877 rendering Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
238000007423 screening assay Methods 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
239000007787 solid Substances 0.000 description 2
241000894007 species Species 0.000 description 2
239000013589 supplement Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
229960005356 urokinase Drugs 0.000 description 2
GMKMEZVLHJARHF-UHFFFAOYSA-N (2R,6R)-form-2.6-Diaminoheptanedioic acid Natural products OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 1
QRXMUCSWCMTJGU-UHFFFAOYSA-L (5-bromo-4-chloro-1h-indol-3-yl) phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP([O-])(=O)[O-])=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-L 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
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
208000030507 AIDS Diseases 0.000 description 1
108010059616 Activins Proteins 0.000 description 1
102000005606 Activins Human genes 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
108010005853 Anti-Mullerian Hormone Proteins 0.000 description 1
KLKHFFMNGWULBN-VKHMYHEASA-N Asn-Gly Chemical compound NC(=O)C[C@H](N)C(=O)NCC(O)=O KLKHFFMNGWULBN-VKHMYHEASA-N 0.000 description 1
108090001008 Avidin Proteins 0.000 description 1
241000589151 Azotobacter Species 0.000 description 1
241000193830 Bacillus <bacterium> Species 0.000 description 1
108700023313 Bacteriophage Receptors Proteins 0.000 description 1
102000015081 Blood Coagulation Factors Human genes 0.000 description 1
108010039209 Blood Coagulation Factors Proteins 0.000 description 1
241000908115 Bolivar Species 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
102100032367 C-C motif chemokine 5 Human genes 0.000 description 1
108010009575 CD55 Antigens Proteins 0.000 description 1
102000055006 Calcitonin Human genes 0.000 description 1
108060001064 Calcitonin Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
102100025570 Cancer/testis antigen 1 Human genes 0.000 description 1
108020004638 Circular DNA Proteins 0.000 description 1
102100022641 Coagulation factor IX Human genes 0.000 description 1
241000186226 Corynebacterium glutamicum Species 0.000 description 1
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
238000001712 DNA sequencing Methods 0.000 description 1
108090000204 Dipeptidase 1 Proteins 0.000 description 1
206010059866 Drug resistance Diseases 0.000 description 1
241000588914 Enterobacter Species 0.000 description 1
241000702224 Enterobacteria phage M13 Species 0.000 description 1
241000588921 Enterobacteriaceae Species 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
241000588698 Erwinia Species 0.000 description 1
102000003951 Erythropoietin Human genes 0.000 description 1
108090000394 Erythropoietin Proteins 0.000 description 1
241000588722 Escherichia 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
108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
108010057573 Flavoproteins Proteins 0.000 description 1
102000003983 Flavoproteins Human genes 0.000 description 1
102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
108700007698 Genetic Terminator Regions Proteins 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
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
101100508941 Halobacterium salinarum (strain ATCC 700922 / JCM 11081 / NRC-1) ppa gene Proteins 0.000 description 1
108091027305 Heteroduplex Proteins 0.000 description 1
101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 1
102000008100 Human Serum Albumin Human genes 0.000 description 1
108091006905 Human Serum Albumin Proteins 0.000 description 1
102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
108090001117 Insulin-Like Growth Factor II Proteins 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
229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
241000588748 Klebsiella Species 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
108090001030 Lipoproteins Proteins 0.000 description 1
102000004895 Lipoproteins Human genes 0.000 description 1
239000006137 Luria-Bertani broth Substances 0.000 description 1
108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
102000004083 Lymphotoxin-alpha Human genes 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
102000018697 Membrane Proteins Human genes 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
229930193140 Neomycin Natural products 0.000 description 1
108090000028 Neprilysin Proteins 0.000 description 1
102000003729 Neprilysin Human genes 0.000 description 1
102000015336 Nerve Growth Factor Human genes 0.000 description 1
108090000095 Neurotrophin-6 Proteins 0.000 description 1
238000000636 Northern blotting Methods 0.000 description 1
241001057811 Paracoccus <mealybug> Species 0.000 description 1
102000003982 Parathyroid hormone Human genes 0.000 description 1
108090000445 Parathyroid hormone Proteins 0.000 description 1
108010087702 Penicillinase Proteins 0.000 description 1
108090000316 Pitrilysin Proteins 0.000 description 1
102000001938 Plasminogen Activators Human genes 0.000 description 1
108010001014 Plasminogen Activators Proteins 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
108010076181 Proinsulin Proteins 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
101800004937 Protein C Proteins 0.000 description 1
241000588769 Proteus <enterobacteria> Species 0.000 description 1
241000589516 Pseudomonas Species 0.000 description 1
102000004879 Racemases and epimerases Human genes 0.000 description 1
108090001066 Racemases and epimerases Proteins 0.000 description 1
108090000103 Relaxin Proteins 0.000 description 1
102000003743 Relaxin Human genes 0.000 description 1
102400000610 Relaxin B chain Human genes 0.000 description 1
101710109558 Relaxin B chain Proteins 0.000 description 1
108090000783 Renin Proteins 0.000 description 1
102100028255 Renin Human genes 0.000 description 1
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
102400000827 Saposin-D Human genes 0.000 description 1
101800001700 Saposin-D Proteins 0.000 description 1
101100262433 Schizosaccharomyces pombe (strain 972 / ATCC 24843) ptr3 gene 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
241000607768 Shigella Species 0.000 description 1
102000013275 Somatomedins Human genes 0.000 description 1
238000002105 Southern blotting Methods 0.000 description 1
108091081024 Start codon Proteins 0.000 description 1
108010056079 Subtilisins Proteins 0.000 description 1
102000005158 Subtilisins Human genes 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
229930006000 Sucrose Natural products 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
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
108090000190 Thrombin Proteins 0.000 description 1
102000002262 Thromboplastin Human genes 0.000 description 1
102000036693 Thrombopoietin Human genes 0.000 description 1
108010041111 Thrombopoietin Proteins 0.000 description 1
102000011923 Thyrotropin Human genes 0.000 description 1
108010061174 Thyrotropin Proteins 0.000 description 1
108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
108050006955 Tissue-type plasminogen activator Proteins 0.000 description 1
102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
108090001012 Transforming Growth Factor beta Proteins 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
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
102100039037 Vascular endothelial growth factor A Human genes 0.000 description 1
241000863000 Vitreoscilla Species 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
239000000488 activin Substances 0.000 description 1
238000005273 aeration Methods 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
239000000908 ammonium hydroxide Substances 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
230000003321 amplification Effects 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000001455 anti-clotting effect Effects 0.000 description 1
239000000868 anti-mullerian hormone Substances 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
230000001746 atrial effect Effects 0.000 description 1
244000052616 bacterial pathogen Species 0.000 description 1
230000010310 bacterial transformation Effects 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
238000011021 bench scale process Methods 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
102000005936 beta-Galactosidase Human genes 0.000 description 1
108010005774 beta-Galactosidase Proteins 0.000 description 1
102000006635 beta-lactamase Human genes 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000001851 biosynthetic effect Effects 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin 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
210000000988 bone and bone Anatomy 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
108010006025 bovine growth hormone Proteins 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
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000003729 cation exchange resin Substances 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
239000013592 cell lysate Substances 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
108010088172 chelatin Proteins 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
238000011098 chromatofocusing Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000013611 chromosomal DNA Substances 0.000 description 1
230000002759 chromosomal effect Effects 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
230000007547 defect Effects 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
230000006735 deficit Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000010432 diamond Substances 0.000 description 1
150000004683 dihydrates Chemical class 0.000 description 1
ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000004520 electroporation Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
238000001976 enzyme digestion Methods 0.000 description 1
229940105423 erythropoietin Drugs 0.000 description 1
238000012869 ethanol precipitation Methods 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
229960004222 factor ix Drugs 0.000 description 1
229940126864 fibroblast growth factor Drugs 0.000 description 1
238000005187 foaming Methods 0.000 description 1
229940028334 follicle stimulating hormone Drugs 0.000 description 1
238000005194 fractionation Methods 0.000 description 1
239000007792 gaseous phase Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
108091008053 gene clusters Proteins 0.000 description 1
102000034356 gene-regulatory proteins Human genes 0.000 description 1
108091006104 gene-regulatory proteins Proteins 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
239000002622 gonadotropin Substances 0.000 description 1
230000002607 hemopoietic effect Effects 0.000 description 1
229940076153 heptahydrate zinc sulfate Drugs 0.000 description 1
150000004687 hexahydrates Chemical class 0.000 description 1
238000002744 homologous recombination Methods 0.000 description 1
230000006801 homologous recombination Effects 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
230000002706 hydrostatic effect Effects 0.000 description 1
101150020087 ilvG gene Proteins 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000000893 inhibin 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
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229910052816 inorganic phosphate Inorganic materials 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
102000028416 insulin-like growth factor binding Human genes 0.000 description 1
108091022911 insulin-like growth factor binding Proteins 0.000 description 1
230000002608 insulinlike Effects 0.000 description 1
102000006495 integrins Human genes 0.000 description 1
108010044426 integrins Proteins 0.000 description 1
230000003993 interaction Effects 0.000 description 1
229940079322 interferon Drugs 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
229960000310 isoleucine Drugs 0.000 description 1
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
229940066294 lung surfactant Drugs 0.000 description 1
239000003580 lung surfactant Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
230000007257 malfunction Effects 0.000 description 1
ISPYRSDWRDQNSW-UHFFFAOYSA-L manganese(II) sulfate monohydrate Chemical compound O.[Mn+2].[O-]S([O-])(=O)=O ISPYRSDWRDQNSW-UHFFFAOYSA-L 0.000 description 1
239000012533 medium component Substances 0.000 description 1
GMKMEZVLHJARHF-SYDPRGILSA-N meso-2,6-diaminopimelic acid Chemical compound [O-]C(=O)[C@@H]([NH3+])CCC[C@@H]([NH3+])C([O-])=O GMKMEZVLHJARHF-SYDPRGILSA-N 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
229940045641 monobasic sodium phosphate Drugs 0.000 description 1
229960004927 neomycin Drugs 0.000 description 1
229940053128 nerve growth factor Drugs 0.000 description 1
229940032018 neurotrophin 3 Drugs 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
230000002138 osteoinductive effect Effects 0.000 description 1
239000000199 parathyroid hormone Substances 0.000 description 1
229960001319 parathyroid hormone Drugs 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
229950009506 penicillinase Drugs 0.000 description 1
150000004686 pentahydrates Chemical class 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000013600 plasmid vector Substances 0.000 description 1
229940127126 plasminogen activator Drugs 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
108010054442 polyalanine Proteins 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
108091033319 polynucleotide Proteins 0.000 description 1
102000040430 polynucleotide Human genes 0.000 description 1
239000002157 polynucleotide Substances 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 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
239000013587 production medium Substances 0.000 description 1
108010087851 prorelaxin Proteins 0.000 description 1
229960000856 protein c Drugs 0.000 description 1
230000012743 protein tagging Effects 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
101150019467 purE gene Proteins 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000003362 replicative effect Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
230000007017 scission Effects 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
239000011684 sodium molybdate Substances 0.000 description 1
235000015393 sodium molybdate Nutrition 0.000 description 1
TVXXNOYZHKPKGW-UHFFFAOYSA-N sodium molybdate (anhydrous) Chemical compound [Na+].[Na+].[O-][Mo]([O-])(=O)=O TVXXNOYZHKPKGW-UHFFFAOYSA-N 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 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
229960004072 thrombin Drugs 0.000 description 1
229940113082 thymine Drugs 0.000 description 1
229940034208 thyroxine Drugs 0.000 description 1
XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
108700012359 toxins Proteins 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
230000007704 transition Effects 0.000 description 1
230000014616 translation Effects 0.000 description 1
IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
229960001082 trimethoprim Drugs 0.000 description 1
239000002753 trypsin inhibitor Substances 0.000 description 1
239000012137 tryptone Substances 0.000 description 1
108010087967 type I signal peptidase Proteins 0.000 description 1
241001148471 unidentified anaerobic bacterium Species 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
229940035893 uracil Drugs 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
230000003612 virological effect Effects 0.000 description 1

Classifications

- 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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
- C12M41/34—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/20—Mixing gases with liquids
- B01F23/23—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids
- B01F23/233—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using driven stirrers with completely immersed stirring elements
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
- B01F35/20—Measuring; Control or regulation
- B01F35/21—Measuring
- B01F35/213—Measuring of the properties of the mixtures, e.g. temperature, density or colour
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
- B01F35/20—Measuring; Control or regulation
- B01F35/21—Measuring
- B01F35/2132—Concentration, pH, pOH, p(ION) or oxygen-demand
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
- B01F35/20—Measuring; Control or regulation
- B01F35/22—Control or regulation
- B01F35/221—Control or regulation of operational parameters, e.g. level of material in the mixer, temperature or pressure
- B01F35/2211—Amount of delivered fluid during a period
- 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
- C07K14/575—Hormones
- C07K14/65—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
- 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
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/02—Stirrer or mobile mixing elements
- 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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/28—Means for regulation, monitoring, measurement or control, e.g. flow regulation of redox potential
- 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
- C12N15/01—Preparation of mutants without inserting foreign genetic material therein; Screening processes therefor
- 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
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0053—Oxidoreductases (1.) acting on a heme group of donors (1.9)
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/20—Mixing gases with liquids
- B01F23/23—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids
- B01F23/233—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using driven stirrers with completely immersed stirring elements
- B01F23/2331—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using driven stirrers with completely immersed stirring elements characterised by the introduction of the gas along the axis of the stirrer or along the stirrer elements
- B01F23/23316—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using driven stirrers with completely immersed stirring elements characterised by the introduction of the gas along the axis of the stirrer or along the stirrer elements through a separate hollow guide substantially parallel with the stirrer element
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/20—Mixing gases with liquids
- B01F23/23—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids
- B01F23/233—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using driven stirrers with completely immersed stirring elements
- B01F23/2336—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using driven stirrers with completely immersed stirring elements characterised by the location of the place of introduction of the gas relative to the stirrer
- B01F23/23362—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using driven stirrers with completely immersed stirring elements characterised by the location of the place of introduction of the gas relative to the stirrer the gas being introduced under the stirrer
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/20—Mixing gases with liquids
- B01F23/23—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids
- B01F23/237—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids characterised by the physical or chemical properties of gases or vapours introduced in the liquid media
- B01F23/2376—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids characterised by the physical or chemical properties of gases or vapours introduced in the liquid media characterised by the gas being introduced
- B01F23/23761—Aerating, i.e. introducing oxygen containing gas in liquids
- B01F23/237612—Oxygen

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Zoology (AREA)
Engineering & Computer Science (AREA)
Wood Science & Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
General Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
Microbiology (AREA)
Molecular Biology (AREA)
Sustainable Development (AREA)
Biophysics (AREA)
Medicinal Chemistry (AREA)
Analytical Chemistry (AREA)
Gastroenterology & Hepatology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Toxicology (AREA)
Physics & Mathematics (AREA)
Plant Pathology (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Apparatus Associated With Microorganisms And Enzymes (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

IL10771293A 1992-11-23 1993-11-22 A method of producing a polypeptide by fermenting bacteria IL107712A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US07/989,844 US5342763A (en)	1992-11-23	1992-11-23	Method for producing polypeptide via bacterial fermentation

Publications (2)

Publication Number	Publication Date
IL107712A0 IL107712A0 (en)	1994-02-27
IL107712A true IL107712A (en)	2002-09-12

Family

ID=25535522

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10771293A IL107712A (en)	1992-11-23	1993-11-22	A method of producing a polypeptide by fermenting bacteria

Country Status (12)

Country	Link
US (3)	US5342763A (de)
EP (2)	EP0668906B1 (de)
JP (2)	JP3513875B2 (de)
AT (2)	ATE280223T1 (de)
AU (2)	AU669414B2 (de)
CA (1)	CA2147468C (de)
DE (2)	DE69333671T2 (de)
DK (2)	DK1524316T3 (de)
ES (2)	ES2326802T3 (de)
IL (1)	IL107712A (de)
PT (2)	PT1524316E (de)
WO (1)	WO1994012630A2 (de)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5342763A (en) *	1992-11-23	1994-08-30	Genentech, Inc.	Method for producing polypeptide via bacterial fermentation
US6274369B1 (en) *	1996-02-02	2001-08-14	Invitrogen Corporation	Method capable of increasing competency of bacterial cell transformation
AU2660397A (en) *	1996-04-05	1997-10-29	Board Of Regents, The University Of Texas System	Methods for producing soluble, biologically-active disulfide bond-containing eukaryotic proteins in bacterial cells
ZA979496B (en) *	1996-10-31	1999-04-23	Genentech Inc	Assay using marked microbial host cell strains
US6114137A (en) *	1996-10-31	2000-09-05	Genentech Inc	Assay using marked microbial host cell strains
KR20000068934A (ko) *	1996-11-08	2000-11-25	스티븐 로쓰	개선된 발현 벡터
US6083715A (en) *	1997-06-09	2000-07-04	Board Of Regents, The University Of Texas System	Methods for producing heterologous disulfide bond-containing polypeptides in bacterial cells
JP2002535967A (ja) *	1999-01-06	2002-10-29	ジェネンテック・インコーポレーテッド	インシュリン様成長因子（ｉｇｆ）ｉ変異体
AU762351B2 (en) *	1999-01-06	2003-06-26	Genentech Inc.	Insulin-like growth factor (IGF) I mutant variants
ATE389416T1 (de) *	2000-05-16	2008-04-15	Genentech Inc	Behandlung von knorpelerkrankungen
SE0003958D0 (sv)	2000-10-31	2000-10-31	Biogaia Fermentation Ab	Method for growth of microorganisms
DK1332222T3 (da)	2000-11-03	2009-07-06	Genentech Inc	Stofskifteændringer i fermenteringer der udtrykker rekombinante proteiner
WO2002072780A2 (en) *	2001-03-14	2002-09-19	Genentech, Inc.	Igf antagonist peptides
EP1590445A4 (de) *	2003-01-16	2006-02-01	Fredric R Bloom	Bakterien für hochleistungsklonen
US7249880B2 (en)	2003-10-14	2007-07-31	Advanced Technology Materials, Inc.	Flexible mixing bag for mixing solids, liquids and gases
BRPI0507233B8 (pt) *	2004-03-11	2021-05-25	Genentech Inc	processo para a produção de um polipeptídeo heterólogo em e. coli
US7078201B2 (en) *	2004-12-01	2006-07-18	Burmaster Brian M	Ethanol fermentation using oxidation reduction potential
EP2290087A3 (de)	2004-12-22	2011-06-15	Genentech, Inc.	Verfahren zur Herstellung von Löslichen Multi-Membranproteinen
CN101287945B (zh) *	2005-04-15	2012-01-25	加勒特·W·布朗	平衡支撑装置
JP4358785B2 (ja) *	2005-05-27	2009-11-04	麒麟麦酒株式会社	密封容器内の酸素量の測定方法及びこれに用いる密封容器のピアス装置
KR20080074896A (ko) *	2005-10-26	2008-08-13	레브테크 인크.	혼합기와 분사기를 구비한 생물 반응기
BRPI0621124A2 (pt)	2005-12-22	2011-11-29	Genentech Inc	métodos para recuperação de uma proteìna de ligação à heparina
DE102006001623B4 (de) *	2006-01-11	2009-05-07	Sartorius Stedim Biotech Gmbh	Behälter und Verfahren zum Mischen von Medien
EP2010310A4 (de)	2006-04-21	2010-03-31	Advanced Tech Materials	Systeme und vorrichtung zur mischung von substanzen und herstellungsverfahren dafür
EP2018416B1 (de) *	2006-05-13	2018-10-24	Pall Life Sciences Belgium	Einweg-bioreaktor
JP2009072133A (ja) *	2007-09-21	2009-04-09	Hitachi Plant Technologies Ltd	培養槽装置、細胞培養方法及び物質生産方法
EP2216395A1 (de)	2009-02-09	2010-08-11	Lonza Biologics plc.	Bioreaktor zur Kultivierung von Säugetierzellen
CN102458629B (zh)	2009-06-05	2014-12-24	弗·哈夫曼-拉罗切有限公司	组合搅动器
AU2010275687A1 (en)	2009-07-24	2012-01-12	F. Hoffmann-La Roche Ag	Stirrer system
US20140024090A1 (en) *	2011-12-19	2014-01-23	Shell Oil Company	Method and apparatus for converting a carbon source into a hydrocarbon or hydrocarbon precursor
EP4051657A4 (de) *	2019-10-30	2025-08-27	Genomatica Inc	Mikroorganismen und verfahren zur verringerung von nebenprodukten

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3384553A (en) *	1965-04-08	1968-05-21	Ceskoslovenska Akademie Ved	Method and equipment for aerobic fermentation on liquid culture mediums
US3445342A (en) *	1966-02-11	1969-05-20	New Brunswick Scientific Co	Fermentation apparatus
US3445341A (en) *	1966-06-17	1969-05-20	New Brunswick Scientific Co	Fermentation apparatus with sterilization capabilities
US4116778A (en) *	1974-01-10	1978-09-26	Viktor Vasilievich Belousov	Plant for continuous cultivation of microorganisms
US4064015A (en) *	1975-05-12	1977-12-20	New Brunswick Scientific Co., Inc.	Control of biosynthesis in submerged culture
US4468455A (en) *	1980-12-02	1984-08-28	Phillips Petroleum Company	Cell culture control
US4476224A (en) *	1982-05-10	1984-10-09	Adler Howard I	Material and method for promoting the growth of anaerobic bacteria
US4762784A (en) *	1985-07-15	1988-08-09	International Minerals & Chemical Corp.	Fermemtation process for the high level production of bovine growth hormone
US5049493A (en) *	1987-10-23	1991-09-17	California Institute Of Technology	Enhancement of cell growth by expression of a cloned hemoglobin gene
US4882283A (en) *	1987-11-17	1989-11-21	Phillips Petroleum Company	Heat exchange apparatus
US5182195A (en) *	1987-11-13	1993-01-26	Takeda Chemical Industries, Ltd.	Method for increasing gene expression using protease deficient yeasts
BR9105208A (pt) *	1990-11-30	1992-07-21	Ajinomoto Kk	Processo para o cultivo aerobico de um microorganismo em uma cultura alimentada em batelada,cultura continua ou cultura continua com reciclagem de celulas,aparelho para controlar a concentracao da fonte de carbono do substrato e processo para produzir l-lisina por fermentacao
US5342763A (en) *	1992-11-23	1994-08-30	Genentech, Inc.	Method for producing polypeptide via bacterial fermentation

1992
- 1992-11-23 US US07/989,844 patent/US5342763A/en not_active Expired - Lifetime
1993
- 1993-11-19 WO PCT/US1993/011297 patent/WO1994012630A2/en not_active Ceased
- 1993-11-19 ES ES04017942T patent/ES2326802T3/es not_active Expired - Lifetime
- 1993-11-19 ES ES94901628T patent/ES2231771T3/es not_active Expired - Lifetime
- 1993-11-19 CA CA002147468A patent/CA2147468C/en not_active Expired - Fee Related
- 1993-11-19 EP EP94901628A patent/EP0668906B1/de not_active Expired - Lifetime
- 1993-11-19 DK DK04017942T patent/DK1524316T3/da active
- 1993-11-19 AT AT94901628T patent/ATE280223T1/de active
- 1993-11-19 DK DK94901628T patent/DK0668906T3/da active
- 1993-11-19 DE DE69333671T patent/DE69333671T2/de not_active Expired - Lifetime
- 1993-11-19 AT AT04017942T patent/ATE432344T1/de active
- 1993-11-19 PT PT04017942T patent/PT1524316E/pt unknown
- 1993-11-19 EP EP04017942A patent/EP1524316B1/de not_active Expired - Lifetime
- 1993-11-19 AU AU56150/94A patent/AU669414B2/en not_active Ceased
- 1993-11-19 PT PT94901628T patent/PT668906E/pt unknown
- 1993-11-19 DE DE69334286T patent/DE69334286D1/de not_active Expired - Lifetime
- 1993-11-19 JP JP51329394A patent/JP3513875B2/ja not_active Expired - Fee Related
- 1993-11-22 IL IL10771293A patent/IL107712A/en not_active IP Right Cessation
1994
- 1994-05-09 US US08/240,121 patent/US5487980A/en not_active Expired - Lifetime
1995
- 1995-05-25 US US08/451,241 patent/US5633165A/en not_active Expired - Lifetime
1996
- 1996-07-12 AU AU59461/96A patent/AU679880B2/en not_active Ceased
2003
- 2003-10-23 JP JP2003362819A patent/JP3674705B2/ja not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US5633165A (en)	1997-05-27
AU5946196A (en)	1996-09-05
DE69333671D1 (de)	2004-11-25
DK1524316T3 (da)	2009-09-07
JPH08503611A (ja)	1996-04-23
AU5615094A (en)	1994-06-22
DE69333671T2 (de)	2006-01-19
EP1524316B1 (de)	2009-05-27
IL107712A0 (en)	1994-02-27
US5342763A (en)	1994-08-30
AU679880B2 (en)	1997-07-10
EP0668906A1 (de)	1995-08-30
EP0668906B1 (de)	2004-10-20
ES2231771T3 (es)	2005-05-16
EP1524316A3 (de)	2005-04-27
JP3513875B2 (ja)	2004-03-31
PT668906E (pt)	2005-02-28
ATE280223T1 (de)	2004-11-15
DK0668906T3 (da)	2005-02-07
WO1994012630A2 (en)	1994-06-09
EP1524316A2 (de)	2005-04-20
ATE432344T1 (de)	2009-06-15
WO1994012630A3 (en)	1994-10-13
ES2326802T3 (es)	2009-10-20
JP2004121256A (ja)	2004-04-22
JP3674705B2 (ja)	2005-07-20
CA2147468A1 (en)	1994-06-09
US5487980A (en)	1996-01-30
DE69334286D1 (de)	2009-07-09
AU669414B2 (en)	1996-06-06
CA2147468C (en)	2006-05-16
PT1524316E (pt)	2009-08-13

Legal Events

Date	Code	Title
2003-02-12	FF	Patent granted
2003-04-10	KB	Patent renewed
2004-01-04	KB	Patent renewed
2008-01-06	KB	Patent renewed
2011-11-30	KB	Patent renewed
2014-07-31	EXP	Patent expired

Publication	Publication Date	Title
AU669414B2 (en)	1996-06-06	Method for producing polypeptide via bacterial fermentation
CA2145388C (en)	2004-08-10	Method of controlling polypeptide production in bacteria
JP3749257B2 (ja)	2006-02-22	ジスルフィド結合を有する異種ポリペプチドの細菌による産生方法
US5789199A (en)	1998-08-04	Process for bacterial production of polypeptides
JP5372061B2 (ja)	2013-12-18	アミノペプチダーゼ
JP4878724B2 (ja)	2012-02-15	組み換えタンパク質を発現する発酵における代謝速度シフト
KR20000068934A (ko)	2000-11-25	개선된 발현 벡터
EP0196061B1 (de)	1993-06-09	Verfahren und Gerät zur Kultivierungssteuerung
US20060030022A1 (en)	2006-02-09	Compositions and methods for production of disulfide bond containing proteins in host cells
CN1914330B (zh)	2012-10-24	通过大肠杆菌发酵大规模生产质粒dna的方法
US6617130B1 (en)	2003-09-09	DNA construct for regulating the expression of a polypeptide coding sequence in a transformed bacterial host cell
SU1703690A1 (ru)	1992-01-07	Рекомбинантна плазмидна ДНК @ 22, кодирующа синтез интерферона @ -11 человека, и штамм бактерии РSеUDомоNаS Sp. -продуцент- интерферона @ -11 человека
MXPA99004331A (es)	2002-05-09	Vectores de expresion mejorados
EP0628634A2 (de)	1994-12-14	Verfahren zur Herstellung von Serin-Hydromethyltransferase
AU2002239440A1 (en)	2002-08-01	Metabolic rate shifts in fermentations expressing recombinant proteins