LT4701B - Tiesioginė peptidų ekspresija į augimo terpė - Google Patents
Tiesioginė peptidų ekspresija į augimo terpė Download PDFInfo
- Publication number
- LT4701B LT4701B LT99-133A LT99133A LT4701B LT 4701 B LT4701 B LT 4701B LT 99133 A LT99133 A LT 99133A LT 4701 B LT4701 B LT 4701B
- Authority
- LT
- Lithuania
- Prior art keywords
- peptide
- peptide product
- vector
- medium
- psct
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 154
- 239000001963 growth medium Substances 0.000 title claims abstract description 34
- 102000004196 processed proteins & peptides Human genes 0.000 title description 21
- 210000004027 cell Anatomy 0.000 claims abstract description 124
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 68
- 238000000034 method Methods 0.000 claims abstract description 54
- 239000004471 Glycine Substances 0.000 claims abstract description 38
- 239000002243 precursor Substances 0.000 claims abstract description 21
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims abstract description 8
- 125000003277 amino group Chemical group 0.000 claims abstract description 6
- 210000004899 c-terminal region Anatomy 0.000 claims abstract description 6
- 239000013598 vector Substances 0.000 claims description 76
- 239000002609 medium Substances 0.000 claims description 62
- 108090000623 proteins and genes Proteins 0.000 claims description 43
- 241000588724 Escherichia coli Species 0.000 claims description 41
- 238000004519 manufacturing process Methods 0.000 claims description 40
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 37
- 239000001301 oxygen Substances 0.000 claims description 37
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- 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 claims description 32
- 229960003773 calcitonin (salmon synthetic) Drugs 0.000 claims description 29
- 108010068072 salmon calcitonin Proteins 0.000 claims description 29
- 108091026890 Coding region Proteins 0.000 claims description 26
- 239000013604 expression vector Substances 0.000 claims description 24
- 230000012010 growth Effects 0.000 claims description 23
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 22
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 239000011541 reaction mixture Substances 0.000 claims description 21
- 108020004707 nucleic acids Proteins 0.000 claims description 19
- 102000039446 nucleic acids Human genes 0.000 claims description 19
- 150000007523 nucleic acids Chemical class 0.000 claims description 19
- 238000005277 cation exchange chromatography Methods 0.000 claims description 16
- 238000013518 transcription Methods 0.000 claims description 15
- 230000035897 transcription Effects 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 102100039087 Peptidyl-alpha-hydroxyglycine alpha-amidating lyase Human genes 0.000 claims description 10
- 108010007262 peptidylglycine monooxygenase Proteins 0.000 claims description 10
- 238000012258 culturing Methods 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 6
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 238000002955 isolation Methods 0.000 claims description 4
- 108010075850 pro-calcitonin gene-related peptide Proteins 0.000 claims description 4
- 108010074633 Mixed Function Oxygenases Proteins 0.000 claims description 3
- 102000008109 Mixed Function Oxygenases Human genes 0.000 claims description 3
- 229920001192 peptidylglycine Polymers 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 239000006143 cell culture medium Substances 0.000 claims 2
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims 1
- 230000000580 secretagogue effect Effects 0.000 claims 1
- 150000001408 amides Chemical class 0.000 abstract description 3
- 238000000855 fermentation Methods 0.000 description 85
- 230000004151 fermentation Effects 0.000 description 85
- 239000000047 product Substances 0.000 description 78
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
- 239000012634 fragment Substances 0.000 description 25
- 238000010276 construction Methods 0.000 description 24
- 238000003776 cleavage reaction Methods 0.000 description 23
- 230000007017 scission Effects 0.000 description 23
- 230000010261 cell growth Effects 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 18
- 230000028327 secretion Effects 0.000 description 18
- 238000007112 amidation reaction Methods 0.000 description 16
- 239000000411 inducer Substances 0.000 description 16
- 239000001488 sodium phosphate Substances 0.000 description 16
- 229910000162 sodium phosphate Inorganic materials 0.000 description 16
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000003752 polymerase chain reaction Methods 0.000 description 15
- 239000013612 plasmid Substances 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- 239000012528 membrane Substances 0.000 description 13
- 210000001322 periplasm Anatomy 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 230000001965 increasing effect Effects 0.000 description 12
- 239000008215 water for injection Substances 0.000 description 12
- 238000011534 incubation Methods 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 230000006698 induction Effects 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000010586 diagram Methods 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 230000009466 transformation Effects 0.000 description 9
- 241000549435 Pria Species 0.000 description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 8
- 210000000805 cytoplasm Anatomy 0.000 description 8
- 230000004927 fusion Effects 0.000 description 8
- 239000001632 sodium acetate Substances 0.000 description 8
- 235000017281 sodium acetate Nutrition 0.000 description 8
- 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 7
- 238000005341 cation exchange Methods 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 108020001507 fusion proteins Proteins 0.000 description 7
- 102000037865 fusion proteins Human genes 0.000 description 7
- 229930027917 kanamycin Natural products 0.000 description 7
- 229960000318 kanamycin Drugs 0.000 description 7
- 229930182823 kanamycin A Natural products 0.000 description 7
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 230000009435 amidation Effects 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 239000003623 enhancer Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 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 6
- 238000005406 washing Methods 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 108010054278 Lac Repressors Proteins 0.000 description 5
- 239000007987 MES buffer Substances 0.000 description 5
- 108010079246 OMPA outer membrane proteins Proteins 0.000 description 5
- 108091005804 Peptidases Proteins 0.000 description 5
- 239000004365 Protease Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 5
- 238000011068 loading method Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 238000006277 sulfonation reaction Methods 0.000 description 5
- 102000003982 Parathyroid hormone Human genes 0.000 description 4
- 108090000445 Parathyroid hormone Proteins 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 230000002708 enhancing effect Effects 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000012499 inoculation medium Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 239000000199 parathyroid hormone Substances 0.000 description 4
- 229960001319 parathyroid hormone Drugs 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 3
- 102000055006 Calcitonin Human genes 0.000 description 3
- 108060001064 Calcitonin Proteins 0.000 description 3
- 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 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 229940072107 ascorbate Drugs 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229960004015 calcitonin Drugs 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000011067 equilibration Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 235000015243 ice cream Nutrition 0.000 description 3
- 230000031700 light absorption Effects 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000002797 proteolythic effect Effects 0.000 description 3
- 238000004153 renaturation Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 101150114545 secE gene Proteins 0.000 description 3
- 101150059374 secY gene Proteins 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 230000005945 translocation Effects 0.000 description 3
- 108090000204 Dipeptidase 1 Proteins 0.000 description 2
- 241001522878 Escherichia coli B Species 0.000 description 2
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 229930195722 L-methionine Natural products 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 101800001442 Peptide pr Proteins 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 101100408135 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) phnA gene Proteins 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 108010000605 Ribosomal Proteins Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 108091003202 SecA Proteins Proteins 0.000 description 2
- 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 2
- 230000003321 amplification Effects 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000009295 crossflow filtration Methods 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000003000 inclusion body Anatomy 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000012092 media component Substances 0.000 description 2
- 229960004452 methionine Drugs 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 101150073640 ompF gene Proteins 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- -1 polypropylene Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 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 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000005030 transcription termination Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 101150044170 trpE gene Proteins 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- DSLBDPPHINVUID-REOHCLBHSA-N (2s)-2-aminobutanediamide Chemical compound NC(=O)[C@@H](N)CC(N)=O DSLBDPPHINVUID-REOHCLBHSA-N 0.000 description 1
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 1
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 1
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 description 1
- 101150033839 4 gene Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 101100295756 Acinetobacter baumannii (strain ATCC 19606 / DSM 30007 / JCM 6841 / CCUG 19606 / CIP 70.34 / NBRC 109757 / NCIMB 12457 / NCTC 12156 / 81) omp38 gene Proteins 0.000 description 1
- 101100136076 Aspergillus oryzae (strain ATCC 42149 / RIB 40) pel1 gene Proteins 0.000 description 1
- 101150076489 B gene Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000510930 Brachyspira pilosicoli Species 0.000 description 1
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 1
- 102000004414 Calcitonin Gene-Related Peptide Human genes 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 101150013191 E gene Proteins 0.000 description 1
- 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 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- 102400001370 Galanin Human genes 0.000 description 1
- 101800002068 Galanin Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 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 1
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 108010006464 Hemolysin Proteins Proteins 0.000 description 1
- 101500024092 Homo sapiens Beta-endorphin Proteins 0.000 description 1
- 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 1
- 101710116435 Outer membrane protein Proteins 0.000 description 1
- 241000588701 Pectobacterium carotovorum Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 102100022831 Somatoliberin Human genes 0.000 description 1
- 101710142969 Somatoliberin Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 102000055135 Vasoactive Intestinal Peptide Human genes 0.000 description 1
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000002862 amidating effect Effects 0.000 description 1
- 229960000723 ampicillin Drugs 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
- 101150042295 arfA gene Proteins 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 101150117416 cas2 gene Proteins 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007813 chromatographic assay Methods 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 150000001945 cysteines Chemical class 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000003228 hemolysin Substances 0.000 description 1
- 101150023479 hsdS gene Proteins 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000007154 intracellular accumulation Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000008384 membrane barrier Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- SLZIZIJTGAYEKK-CIJSCKBQSA-N molport-023-220-247 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CNC=N1 SLZIZIJTGAYEKK-CIJSCKBQSA-N 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 231100001160 nonlethal Toxicity 0.000 description 1
- 101150087557 omcB gene Proteins 0.000 description 1
- 101150115693 ompA gene Proteins 0.000 description 1
- 101150093139 ompT gene Proteins 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 101150040383 pel2 gene Proteins 0.000 description 1
- 101150050446 pelB gene Proteins 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 230000003234 polygenic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000010349 pulsation Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 231100000817 safety factor Toxicity 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- HAEPBEMBOAIUPN-UHFFFAOYSA-L sodium tetrathionate Chemical compound O.O.[Na+].[Na+].[O-]S(=O)(=O)SSS([O-])(=O)=O HAEPBEMBOAIUPN-UHFFFAOYSA-L 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/23—Calcitonins
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/461—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from fish
-
- 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
- C07K14/585—Calcitonins
-
- 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
- C07K14/635—Parathyroid hormone (parathormone); Parathyroid hormone-related peptides
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
- C12N15/71—Expression systems using regulatory sequences derived from the trp-operon
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
- C12N15/72—Expression systems using regulatory sequences derived from the lac-operon
-
- 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
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4370097P | 1997-04-16 | 1997-04-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LT99133A LT99133A (en) | 2000-04-25 |
| LT4701B true LT4701B (lt) | 2000-09-25 |
Family
ID=21928441
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LT99-133A LT4701B (lt) | 1997-04-16 | 1999-11-10 | Tiesioginė peptidų ekspresija į augimo terpė |
Country Status (14)
| Country | Link |
|---|---|
| US (5) | US6103495A (fr) |
| EP (2) | EP1005526B1 (fr) |
| JP (2) | JP4907751B2 (fr) |
| AT (2) | ATE522598T1 (fr) |
| AU (1) | AU742270B2 (fr) |
| CA (1) | CA2285658C (fr) |
| DE (1) | DE69841939D1 (fr) |
| DK (2) | DK2088188T3 (fr) |
| ES (1) | ES2375330T3 (fr) |
| HU (1) | HUP0001272A3 (fr) |
| LT (1) | LT4701B (fr) |
| NO (1) | NO327325B1 (fr) |
| RU (1) | RU2218407C2 (fr) |
| WO (1) | WO1998046722A1 (fr) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE522598T1 (de) * | 1997-04-16 | 2011-09-15 | Unigene Lab Inc | Direkte expression von peptiden in nährmedien |
| KR100385298B1 (ko) * | 2000-09-05 | 2003-05-23 | 한국생명공학연구원 | 단백질 생산방법 |
| US7166575B2 (en) * | 2002-12-17 | 2007-01-23 | Nastech Pharmaceutical Company Inc. | Compositions and methods for enhanced mucosal delivery of peptide YY and methods for treating and preventing obesity |
| TW200411053A (en) | 2002-12-30 | 2004-07-01 | Ind Tech Res Inst | Nucleic acid encoding recombinant salmon calcitionin, expression vector thereof, and method for producing recombinant salmon calcitonin therewith |
| US8088734B2 (en) | 2003-01-21 | 2012-01-03 | Unigene Laboratories Inc. | Oral delivery of peptides |
| US20050215476A1 (en) * | 2004-01-21 | 2005-09-29 | Unigene Laboratories Inc. | Amidated parathyroid hormone fragments and uses thereof |
| US8227241B2 (en) | 2004-03-12 | 2012-07-24 | Unigene Laboratories, Inc. | Bacterial host cell for the direct expression of peptides |
| US7648965B2 (en) * | 2004-05-14 | 2010-01-19 | Unigene Laboratories Inc. | Method for fostering bone formation and preservation |
| US7531518B2 (en) * | 2004-05-14 | 2009-05-12 | Unigene Laboratories Inc. | Method for fostering bone formation and preservation |
| US20060089723A1 (en) * | 2004-10-25 | 2006-04-27 | Murphy Kieran P | Method for bone augmentation |
| US7445911B2 (en) * | 2004-11-24 | 2008-11-04 | Unigene Laboratories Inc. | Enzymatic reactions in the presence of keto acids |
| PA8660701A1 (es) | 2005-02-04 | 2006-09-22 | Pfizer Prod Inc | Agonistas de pyy y sus usos |
| US20060293667A1 (en) * | 2005-05-19 | 2006-12-28 | Agnes Vignery | Bone implant device and methods of using same |
| US7825231B2 (en) | 2005-06-01 | 2010-11-02 | Darren P. Wolfe | Method of amidated peptide biosynthesis and delivery in vivo: endomorphin-2 for pain therapy |
| US20060275812A1 (en) * | 2005-06-01 | 2006-12-07 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Assay for agonists and antagonists of ion channels and for regulators of genetic expression |
| JP4856177B2 (ja) | 2005-06-24 | 2012-01-18 | ユニジーン・ラボラトリーズ・インコーポレーテッド | アミド化生成物の調製に有用な酵素を発現させるための細胞株 |
| EP2046826B1 (fr) | 2006-07-24 | 2011-09-14 | Biorexis Pharmaceutical Corporation | Protéines de fusion d'extendine |
| US8377863B2 (en) | 2007-05-29 | 2013-02-19 | Unigene Laboratories Inc. | Peptide pharmaceutical for oral delivery |
| RU2370280C2 (ru) * | 2007-10-08 | 2009-10-20 | Институт физико-химической биологии им. А.Н.Белозерского | СПОСОБ СУПЕРПРОДУКЦИИ В РАСТЕНИИ АНТИТЕЛ ПРОТИВ ОНКОГЕНА HER2/neu |
| US9399773B2 (en) | 2012-08-10 | 2016-07-26 | Shi-Lung Lin | Production and extraction of MicroRNA precursor as drug for cancer therapy |
| US9422559B2 (en) | 2010-06-02 | 2016-08-23 | Shi-Lung Lin | Production and utilization of a novel anti-cancer drug in therapy |
| CA2750035C (fr) | 2009-01-22 | 2018-02-27 | Unigene Laboratories Inc. | Traitement de l'obesite |
| EP2720707B1 (fr) | 2011-06-15 | 2018-12-19 | ResoTher Pharma ApS | Produits pharmaceutiques anti-inflammatoires |
| JP6185468B2 (ja) | 2011-08-12 | 2017-08-23 | メロ バイオテクノロジー インコーポレイテッドＭｅｌｌｏ Ｂｉｏｔｅｃｈｎｏｌｏｇｙ，Ｉｎｃ． | 原核細胞内においてヘアピン様ｒｎａを発現させる方法及び組成物 |
| PT3095484T (pt) | 2011-11-02 | 2018-06-20 | Keybioscience Ag | Miméticas de calcitonina para tratar doenças e distúrbios |
| CA2854175A1 (fr) | 2011-11-02 | 2013-05-10 | Keybioscience Ag | Utilisation de mimetiques de la calcitonine pour le traitement de certaines maladies et affections |
| US10414808B2 (en) | 2012-05-18 | 2019-09-17 | Janssen Biotech, Inc. | Huwentoxin-IV variants and methods of use |
| US9102751B2 (en) * | 2012-05-18 | 2015-08-11 | Janssen Biotech, Inc. | Huwentoxin-IV variants and methods of use |
| US10196662B2 (en) | 2012-08-10 | 2019-02-05 | Mello Biotechnology, Inc. | Composition for producing microRNA precursors as drugs for enhancing wound healing and production method of the microRNA precursors |
| EP2964193B1 (fr) | 2013-03-05 | 2019-12-11 | Enteris BioPharma, Inc. | Produits pharmaceutiques pour une administration par voie orale |
| CN105793277B (zh) | 2013-10-03 | 2020-09-15 | 詹森生物科技公司 | 原毒素-ii变体及其使用方法 |
| PL3321278T3 (pl) | 2013-11-14 | 2019-06-28 | Keybioscience Ag | Mimetyki kalcytoniny do leczenia chorób i zaburzeń |
| CN103709236B (zh) * | 2013-12-23 | 2015-04-15 | 江南大学 | 一种可提高分泌效率的信号肽及其应用 |
| KR102294577B1 (ko) | 2015-01-12 | 2021-08-26 | 엔터리스 바이오파마, 인크. | 고체 경구 제형 |
| MA41642A (fr) | 2015-03-03 | 2018-01-09 | Janssen Biotech Inc | Variants de protoxine ii et méthodes d'utilisation |
| JP6985151B2 (ja) | 2015-04-02 | 2021-12-22 | ヤンセン バイオテツク，インコーポレーテツド | プロトキシン−ｉｉ変異体及びその使用方法 |
| WO2017095458A1 (fr) | 2015-12-02 | 2017-06-08 | Chih-Li Lin | Composition et méthode d'utilisation de précurseurs de mir-302 en tant que médicaments pour le traitement de la maladie d'alzheimer |
| CN108431227A (zh) | 2015-12-02 | 2018-08-21 | 林希龙 | 使用微核醣核酸前驱物作为诱导cd34阳性成体干细胞增殖的药物 |
| GB201704429D0 (en) | 2017-03-21 | 2017-05-03 | Keybioscience Ag | Calcitonin mimetics for treating diseases and disorders |
| GB201707955D0 (en) | 2017-05-18 | 2017-07-05 | Keybioscience Ag | Dual amylin and calcitonin receptor agonists for treating diseases and disorders |
| GB201813677D0 (en) | 2018-08-22 | 2018-10-03 | Keybioscience Ag | Calcitonin mimetics for treating diseases and disorders |
| GB201813678D0 (en) | 2018-08-22 | 2018-10-03 | Keybioscience Ag | Acylated calcitonin mimetics |
| GB202001024D0 (en) | 2020-01-24 | 2020-03-11 | Key Bioscience Ag | Oxyntomodulin mimetics |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0177343A1 (fr) | 1984-10-05 | 1986-04-09 | Genentech, Inc. | ADN, cultures de cellules et méthodes pour sécréter des protéines hétérologiques et récupérer des protéines périplasmiques |
| US4595658A (en) | 1982-09-13 | 1986-06-17 | The Rockefeller University | Method for facilitating externalization of proteins synthesized in bacteria |
| US4708934A (en) | 1984-09-27 | 1987-11-24 | Unigene Laboratories, Inc. | α-amidation enzyme |
| EP0308067A2 (fr) | 1987-08-14 | 1989-03-22 | Unigene Laboratories Inc. | Compositions contenant des enzymes d'alpha amidation et procédés de production et d'utilisation |
| EP0382403A2 (fr) | 1989-02-06 | 1990-08-16 | Unigene Laboratories Inc. | Systèmes d'expression pour un enzyme d'amidation |
| US5223407A (en) | 1988-08-31 | 1993-06-29 | Allelix Inc. | Excretion of heterologous proteins from e. coli |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5332664A (en) * | 1981-07-15 | 1994-07-26 | Celltech Limited | Human calcitonin precursor polyprotein structural gene |
| US4620948A (en) * | 1982-12-22 | 1986-11-04 | Genentech, Inc. | Purification and activity assurance of precipitated heterologous proteins |
| US4962055A (en) * | 1983-03-08 | 1990-10-09 | Rikagaku Kenkyusho | Plasmid, method for construction of the same, microorganisms carrying the plasmid and method for cultivation of the microorganism |
| US4757013A (en) * | 1983-07-25 | 1988-07-12 | The Research Foundation Of State University Of New York | Cloning vehicles for polypeptide expression in microbial hosts |
| US5747281A (en) * | 1984-09-28 | 1998-05-05 | Cornell Research Foundation, Inc. | System useful for the production of proteins from recombinant DNA in single celled organisms |
| DE3632037A1 (de) | 1986-09-20 | 1988-04-07 | Hoechst Ag | Gentechnisches verfahren zur herstellung von salm-calcitonin sowie mittel zur durchfuehrung dieses verfahrens |
| US5089406A (en) * | 1987-01-07 | 1992-02-18 | Allied-Signal Inc. | Method of producing a gene cassette coding for polypeptides with repeating amino acid sequences |
| US4946790A (en) * | 1987-02-06 | 1990-08-07 | Mitsui Toatsu Chemicals, Inc. | Recombinant plasmid for the expression of L-phenylalanine ammonia-lyase and transformed strain carrying same |
| JP2551399B2 (ja) * | 1989-08-15 | 1996-11-06 | 株式会社資生堂 | Ｃ末端アミド化に関与する酵素並びにその製造方法及びその使用 |
| US5240831A (en) * | 1991-01-10 | 1993-08-31 | Board Of Regents, The University Of Texas | Methods and compositions for the expression of biologically active eukaryotic cytochrome p45os in bacteria |
| US5547862A (en) * | 1993-07-29 | 1996-08-20 | Ambion Inc. | Vectors containing multiple promoters in the same orientation |
| US5589364A (en) * | 1994-07-29 | 1996-12-31 | Magainin Pharmaceuticals Inc. | Recombinant production of biologically active peptides and proteins |
| ATE522598T1 (de) * | 1997-04-16 | 2011-09-15 | Unigene Lab Inc | Direkte expression von peptiden in nährmedien |
-
1998
- 1998-04-15 AT AT09006784T patent/ATE522598T1/de not_active IP Right Cessation
- 1998-04-15 EP EP98918334A patent/EP1005526B1/fr not_active Expired - Lifetime
- 1998-04-15 AU AU71279/98A patent/AU742270B2/en not_active Ceased
- 1998-04-15 ES ES09006784T patent/ES2375330T3/es not_active Expired - Lifetime
- 1998-04-15 DK DK09006784.4T patent/DK2088188T3/da active
- 1998-04-15 CA CA2285658A patent/CA2285658C/fr not_active Expired - Fee Related
- 1998-04-15 WO PCT/US1998/007723 patent/WO1998046722A1/fr active IP Right Grant
- 1998-04-15 HU HU0001272A patent/HUP0001272A3/hu unknown
- 1998-04-15 AT AT98918334T patent/ATE484572T1/de not_active IP Right Cessation
- 1998-04-15 DE DE69841939T patent/DE69841939D1/de not_active Expired - Lifetime
- 1998-04-15 RU RU99124196/13A patent/RU2218407C2/ru active
- 1998-04-15 DK DK98918334.8T patent/DK1005526T3/da active
- 1998-04-15 EP EP09006784A patent/EP2088188B1/fr not_active Expired - Lifetime
- 1998-04-15 JP JP54430898A patent/JP4907751B2/ja not_active Expired - Lifetime
- 1998-04-15 US US09/060,765 patent/US6103495A/en not_active Expired - Lifetime
-
1999
- 1999-10-14 NO NO19995014A patent/NO327325B1/no not_active IP Right Cessation
- 1999-11-10 LT LT99-133A patent/LT4701B/lt not_active IP Right Cessation
-
2000
- 2000-02-08 US US09/500,009 patent/US6210925B1/en not_active Expired - Lifetime
-
2001
- 2001-02-09 US US09/780,643 patent/US6737250B2/en not_active Expired - Lifetime
- 2001-02-09 US US09/780,878 patent/US6627438B2/en not_active Expired - Lifetime
-
2004
- 2004-04-05 US US10/818,966 patent/US7968311B2/en not_active Expired - Fee Related
-
2011
- 2011-11-09 JP JP2011245398A patent/JP5634971B2/ja not_active Expired - Lifetime
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4595658A (en) | 1982-09-13 | 1986-06-17 | The Rockefeller University | Method for facilitating externalization of proteins synthesized in bacteria |
| US4708934A (en) | 1984-09-27 | 1987-11-24 | Unigene Laboratories, Inc. | α-amidation enzyme |
| EP0177343A1 (fr) | 1984-10-05 | 1986-04-09 | Genentech, Inc. | ADN, cultures de cellules et méthodes pour sécréter des protéines hétérologiques et récupérer des protéines périplasmiques |
| EP0308067A2 (fr) | 1987-08-14 | 1989-03-22 | Unigene Laboratories Inc. | Compositions contenant des enzymes d'alpha amidation et procédés de production et d'utilisation |
| US5223407A (en) | 1988-08-31 | 1993-06-29 | Allelix Inc. | Excretion of heterologous proteins from e. coli |
| EP0382403A2 (fr) | 1989-02-06 | 1990-08-16 | Unigene Laboratories Inc. | Systèmes d'expression pour un enzyme d'amidation |
Non-Patent Citations (6)
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| LT4701B (lt) | Tiesioginė peptidų ekspresija į augimo terpė | |
| EP0177343B1 (fr) | ADN, cultures de cellules et méthodes pour sécréter des protéines hétérologiques et récupérer des protéines périplasmiques | |
| JP2608870B2 (ja) | 組換えｄｎａ技術によるヒトｉｇｆの製造 | |
| US6471500B1 (en) | Process for producing erythropoietin containing no animal proteins | |
| EP1733039B1 (fr) | Ameliorations apportees a une cellule hote bacterienne destinee a l'expression directe de peptides | |
| EP2173768B1 (fr) | Nouveau procédé orthogonal pour la purification de l'hormone parathyroïdienne humaine recombinante (rhpth) (1-34) | |
| LT4077B (en) | Expression systems for amidating enzyme | |
| NO175870B (fr) | ||
| CA1340091C (fr) | Production amelioree de proteines chez les bacteries grace a de nouveau x sites de fixation des ribosomes | |
| IE904294A1 (en) | Novel process for the production of unfused protein in E. coli | |
| Ohsuye et al. | Expression of chemically synthesized α-neo-endorphin gene fused to E. coli alkaline phosphatase | |
| EP0225860A2 (fr) | Méthode pour transmettre des produits de gènes à un milieu de croissance de bactéries gram-négatives | |
| AU781978B2 (en) | Direct expression of peptides into culture media | |
| AU2005201901B2 (en) | Direct expression of peptides into culture media | |
| GB2214508A (en) | Plasmid vector for the efficient expression of foreign genes fused with newly conceived transcriptional and translational signal sequences. | |
| KR970009082B1 (ko) | 인간 알파 아트리알 나트리 우레틱 인자(human α-arterial natriuretic factor; α-hANF)의 미생물학적 제조방법 | |
| JPH01160488A (ja) | ポリペプチド類を生産するための新規ベクターおよび発現配列 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM9A | Lapsed patents |
Effective date: 20130415 |