CA2111110A1 - Production et recuperation de neurotrophines recombinantes - Google Patents

Production et recuperation de neurotrophines recombinantes

Info

Publication number: CA2111110A1
Authority: CA; Canada
Prior art keywords: neurotrophin; seq; biologically active; sequence; recombinant
Prior art date: 1991-06-12
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002111110A

Other languages

English (en)

Inventor

Nikos Panayotatos

James P. Fandl

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Regeneron Pharmaceuticals Inc

Original Assignee

Individual

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.)

1991-06-12

Filing date

1992-06-11

Publication date

1992-12-23

1991-11-21 Priority claimed from US07/796,106 external-priority patent/US5389529A/en

1992-06-11 Application filed by Individual filed Critical Individual

1992-12-23 Publication of CA2111110A1 publication Critical patent/CA2111110A1/fr

Status Abandoned legal-status Critical Current

Links

108010025020 Nerve Growth Factor Proteins 0.000 title claims abstract description 161
102000007072 Nerve Growth Factors Human genes 0.000 title claims abstract description 145
238000004519 manufacturing process Methods 0.000 title abstract description 17
238000011084 recovery Methods 0.000 title description 12
238000000034 method Methods 0.000 claims abstract description 103
230000008569 process Effects 0.000 claims abstract description 85
108090000099 Neurotrophin-4 Proteins 0.000 claims abstract description 69
102000003683 Neurotrophin-4 Human genes 0.000 claims abstract description 68
108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 47
230000014509 gene expression Effects 0.000 claims abstract description 44
239000003795 chemical substances by application Substances 0.000 claims abstract description 38
150000001413 amino acids Chemical class 0.000 claims abstract description 30
102000053602 DNA Human genes 0.000 claims abstract description 20
108020004511 Recombinant DNA Proteins 0.000 claims abstract description 14
238000012258 culturing Methods 0.000 claims abstract description 11
229940097998 neurotrophin 4 Drugs 0.000 claims abstract description 11
241001465754 Metazoa Species 0.000 claims abstract description 10
108091005804 Peptidases Proteins 0.000 claims abstract description 9
102000035195 Peptidases Human genes 0.000 claims abstract description 8
239000004365 Protease Substances 0.000 claims abstract description 8
239000003638 chemical reducing agent Substances 0.000 claims abstract description 8
230000015556 catabolic process Effects 0.000 claims abstract description 7
238000006731 degradation reaction Methods 0.000 claims abstract description 7
230000003381 solubilizing effect Effects 0.000 claims abstract description 5
108090000623 proteins and genes Proteins 0.000 claims description 106
108010076504 Protein Sorting Signals Proteins 0.000 claims description 48
239000013612 plasmid Substances 0.000 claims description 48
108020004414 DNA Proteins 0.000 claims description 36
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 36
235000019687 Lamb Nutrition 0.000 claims description 33
241000588724 Escherichia coli Species 0.000 claims description 32
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 31
239000004202 carbamide Substances 0.000 claims description 20
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 20
101100020591 Mus musculus Lamc1 gene Proteins 0.000 claims description 18
230000002209 hydrophobic effect Effects 0.000 claims description 16
101100398650 Mus musculus Lamb1 gene Proteins 0.000 claims description 14
125000000539 amino acid group Chemical group 0.000 claims description 14
101000996663 Homo sapiens Neurotrophin-4 Proteins 0.000 claims description 12
241000894006 Bacteria Species 0.000 claims description 10
239000013600 plasmid vector Substances 0.000 claims description 10
108090000765 processed proteins & peptides Proteins 0.000 claims description 10
230000035939 shock Effects 0.000 claims description 10
230000004927 fusion Effects 0.000 claims description 8
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 6
ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 claims description 6
SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 claims description 6
150000007523 nucleic acids Chemical class 0.000 claims description 6
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 5
239000004473 Threonine Substances 0.000 claims description 5
102000039446 nucleic acids Human genes 0.000 claims description 5
108020004707 nucleic acids Proteins 0.000 claims description 5
241001515965 unidentified phage Species 0.000 claims description 5
108700005075 Regulator Genes Proteins 0.000 claims description 4
238000004113 cell culture Methods 0.000 claims description 4
239000003475 metalloproteinase inhibitor Substances 0.000 claims description 4
-1 alkali metal thiocyanate Chemical class 0.000 claims description 3
239000003617 indole-3-acetic acid Substances 0.000 claims description 3
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 2
229910052783 alkali metal Inorganic materials 0.000 claims description 2
101710170181 Metalloproteinase inhibitor Proteins 0.000 claims 2
229940126170 metalloproteinase inhibitor Drugs 0.000 claims 2
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims 1
125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
230000001580 bacterial effect Effects 0.000 abstract description 6
239000000137 peptide hydrolase inhibitor Substances 0.000 abstract description 3
229940124158 Protease/peptidase inhibitor Drugs 0.000 abstract description 2
102000004169 proteins and genes Human genes 0.000 description 62
235000018102 proteins Nutrition 0.000 description 61
210000004027 cell Anatomy 0.000 description 55
101001111439 Homo sapiens Beta-nerve growth factor Proteins 0.000 description 33
102000046917 human NGF Human genes 0.000 description 33
239000000243 solution Substances 0.000 description 30
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
239000012634 fragment Substances 0.000 description 20
235000001014 amino acid Nutrition 0.000 description 17
239000000872 buffer Substances 0.000 description 17
210000003594 spinal ganglia Anatomy 0.000 description 17
230000000694 effects Effects 0.000 description 16
239000011780 sodium chloride Substances 0.000 description 14
102000015336 Nerve Growth Factor Human genes 0.000 description 13
229940053128 nerve growth factor Drugs 0.000 description 13
239000002609 medium Substances 0.000 description 12
239000008188 pellet Substances 0.000 description 12
238000003752 polymerase chain reaction Methods 0.000 description 12
238000003786 synthesis reaction Methods 0.000 description 11
230000015572 biosynthetic process Effects 0.000 description 10
108020001507 fusion proteins Proteins 0.000 description 10
102000037865 fusion proteins Human genes 0.000 description 10
238000000746 purification Methods 0.000 description 10
230000014616 translation Effects 0.000 description 10
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 9
238000007792 addition Methods 0.000 description 9
239000002773 nucleotide Substances 0.000 description 9
125000003729 nucleotide group Chemical group 0.000 description 9
238000013518 transcription Methods 0.000 description 9
230000035897 transcription Effects 0.000 description 9
238000013519 translation Methods 0.000 description 9
239000003814 drug Substances 0.000 description 8
108020004999 messenger RNA Proteins 0.000 description 8
229920002684 Sepharose Polymers 0.000 description 7
239000000284 extract Substances 0.000 description 7
210000002569 neuron Anatomy 0.000 description 7
239000013615 primer Substances 0.000 description 7
230000010076 replication Effects 0.000 description 7
108020004705 Codon Proteins 0.000 description 6
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 6
239000002299 complementary DNA Substances 0.000 description 6
PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 6
238000003780 insertion Methods 0.000 description 6
230000037431 insertion Effects 0.000 description 6
210000002161 motor neuron Anatomy 0.000 description 6
230000014511 neuron projection development Effects 0.000 description 6
210000001322 periplasm Anatomy 0.000 description 6
102000004196 processed proteins & peptides Human genes 0.000 description 6
238000012545 processing Methods 0.000 description 6
239000000047 product Substances 0.000 description 6
238000006467 substitution reaction Methods 0.000 description 6
BAQCROVBDNBEEB-UBYUBLNFSA-N Metrizamide Chemical compound CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C(=O)N[C@@H]2[C@H]([C@H](O)[C@@H](CO)OC2O)O)=C1I BAQCROVBDNBEEB-UBYUBLNFSA-N 0.000 description 5
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 5
108091034117 Oligonucleotide Proteins 0.000 description 5
102000007056 Recombinant Fusion Proteins Human genes 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
238000003556 assay Methods 0.000 description 5
238000005119 centrifugation Methods 0.000 description 5
238000010276 construction Methods 0.000 description 5
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
239000003398 denaturant Substances 0.000 description 5
239000013604 expression vector Substances 0.000 description 5
229960000554 metrizamide Drugs 0.000 description 5
230000000508 neurotrophic effect Effects 0.000 description 5
230000007935 neutral effect Effects 0.000 description 5
229920001184 polypeptide Polymers 0.000 description 5
210000000278 spinal cord Anatomy 0.000 description 5
108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 4
102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
239000003155 DNA primer Substances 0.000 description 4
241000287828 Gallus gallus Species 0.000 description 4
238000012408 PCR amplification Methods 0.000 description 4
240000004808 Saccharomyces cerevisiae Species 0.000 description 4
101710137500 T7 RNA polymerase Proteins 0.000 description 4
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 4
229960000723 ampicillin Drugs 0.000 description 4
230000004071 biological effect Effects 0.000 description 4
229940077737 brain-derived neurotrophic factor Drugs 0.000 description 4
210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
231100000673 dose–response relationship Toxicity 0.000 description 4
210000002257 embryonic structure Anatomy 0.000 description 4
210000003000 inclusion body Anatomy 0.000 description 4
230000001965 increasing effect Effects 0.000 description 4
230000001939 inductive effect Effects 0.000 description 4
238000002955 isolation Methods 0.000 description 4
239000006166 lysate Substances 0.000 description 4
239000000203 mixture Substances 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
239000002243 precursor Substances 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
230000004083 survival effect Effects 0.000 description 4
239000013598 vector Substances 0.000 description 4
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 3
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
101100404651 Mus musculus Ngf gene Proteins 0.000 description 3
238000009825 accumulation Methods 0.000 description 3
238000013459 approach Methods 0.000 description 3
239000006285 cell suspension Substances 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
230000002950 deficient Effects 0.000 description 3
238000012217 deletion Methods 0.000 description 3
230000037430 deletion Effects 0.000 description 3
238000000502 dialysis Methods 0.000 description 3
230000012010 growth Effects 0.000 description 3
238000003306 harvesting Methods 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
229930182817 methionine Natural products 0.000 description 3
230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 3
108091008146 restriction endonucleases Proteins 0.000 description 3
238000004007 reversed phase HPLC Methods 0.000 description 3
101150106872 rpoH gene Proteins 0.000 description 3
239000000523 sample Substances 0.000 description 3
230000007017 scission Effects 0.000 description 3
230000028327 secretion Effects 0.000 description 3
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
241000894007 species Species 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
108091026890 Coding region Proteins 0.000 description 2
241000701867 Enterobacteria phage T7 Species 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
101000634196 Homo sapiens Neurotrophin-3 Proteins 0.000 description 2
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 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
108020005038 Terminator Codon Proteins 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
108090000631 Trypsin Proteins 0.000 description 2
102000004142 Trypsin Human genes 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000002585 base Substances 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
210000004899 c-terminal region Anatomy 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
230000030833 cell death Effects 0.000 description 2
230000008859 change Effects 0.000 description 2
238000010367 cloning Methods 0.000 description 2
230000000295 complement effect Effects 0.000 description 2
239000000356 contaminant Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000001086 cytosolic effect Effects 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
238000005194 fractionation Methods 0.000 description 2
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
229910001385 heavy metal Inorganic materials 0.000 description 2
102000057714 human NTF3 Human genes 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
230000001976 improved effect 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
239000008101 lactose Substances 0.000 description 2
210000001161 mammalian embryo Anatomy 0.000 description 2
244000005700 microbiome Species 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000001737 promoting effect Effects 0.000 description 2
235000019419 proteases Nutrition 0.000 description 2
238000001243 protein synthesis Methods 0.000 description 2
KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
230000002441 reversible effect Effects 0.000 description 2
238000012163 sequencing technique Methods 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
239000012588 trypsin Substances 0.000 description 2
108010087967 type I signal peptidase Proteins 0.000 description 2
238000011144 upstream manufacturing Methods 0.000 description 2
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
206010003497 Asphyxia Diseases 0.000 description 1
241000193830 Bacillus <bacterium> Species 0.000 description 1
101100348491 Bos taurus NGF gene Proteins 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
101710132601 Capsid protein Proteins 0.000 description 1
108010058699 Choline O-acetyltransferase Proteins 0.000 description 1
102100023460 Choline O-acetyltransferase Human genes 0.000 description 1
101710094648 Coat protein Proteins 0.000 description 1
108091035707 Consensus sequence Proteins 0.000 description 1
229920002271 DEAE-Sepharose Polymers 0.000 description 1
230000004543 DNA replication Effects 0.000 description 1
102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
108010053770 Deoxyribonucleases Proteins 0.000 description 1
102000016911 Deoxyribonucleases Human genes 0.000 description 1
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
239000006145 Eagle's minimal essential medium Substances 0.000 description 1
241000701959 Escherichia virus Lambda Species 0.000 description 1
241001524679 Escherichia virus M13 Species 0.000 description 1
108010001515 Galectin 4 Proteins 0.000 description 1
102100039556 Galectin-4 Human genes 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
101100175482 Glycine max CG-3 gene Proteins 0.000 description 1
102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
101000739876 Homo sapiens Brain-derived neurotrophic factor Proteins 0.000 description 1
101001030211 Homo sapiens Myc proto-oncogene protein Proteins 0.000 description 1
101100404649 Homo sapiens NGF gene Proteins 0.000 description 1
101500028867 Homo sapiens Neurotensin Proteins 0.000 description 1
102000002265 Human Growth Hormone Human genes 0.000 description 1
108010000521 Human Growth Hormone Proteins 0.000 description 1
239000000854 Human Growth Hormone Substances 0.000 description 1
241000257303 Hymenoptera Species 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
241001527806 Iti Species 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
ZTUWCZQOKOJGEX-DCAQKATOSA-N Leu-Ala-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O ZTUWCZQOKOJGEX-DCAQKATOSA-N 0.000 description 1
239000006137 Luria-Bertani broth Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
101710125418 Major capsid protein Proteins 0.000 description 1
101710169972 Menin Proteins 0.000 description 1
102100030550 Menin Human genes 0.000 description 1
102000005741 Metalloproteases Human genes 0.000 description 1
108010006035 Metalloproteases Proteins 0.000 description 1
108010059724 Micrococcal Nuclease Proteins 0.000 description 1
102000016943 Muramidase Human genes 0.000 description 1
108010014251 Muramidase Proteins 0.000 description 1
108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
230000004988 N-glycosylation Effects 0.000 description 1
101150064037 NGF gene Proteins 0.000 description 1
101710141454 Nucleoprotein Proteins 0.000 description 1
108010079246 OMPA outer membrane proteins Proteins 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
102000011755 Phosphoglycerate Kinase Human genes 0.000 description 1
241000235648 Pichia Species 0.000 description 1
101710182846 Polyhedrin Proteins 0.000 description 1
101710083689 Probable capsid protein Proteins 0.000 description 1
239000005700 Putrescine Substances 0.000 description 1
108020005067 RNA Splice Sites Proteins 0.000 description 1
101000634201 Rattus norvegicus Neurotrophin-3 Proteins 0.000 description 1
241000235070 Saccharomyces Species 0.000 description 1
241000831652 Salinivibrio sharmensis Species 0.000 description 1
102000004002 Secretory Leukocyte Peptidase Inhibitor Human genes 0.000 description 1
108010082545 Secretory Leukocyte Peptidase Inhibitor Proteins 0.000 description 1
238000012300 Sequence Analysis Methods 0.000 description 1
241000187747 Streptomyces Species 0.000 description 1
101000933315 Sus scrofa Brain-derived neurotrophic factor Proteins 0.000 description 1
244000166490 Tetrameles nudiflora Species 0.000 description 1
101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 1
102000004338 Transferrin Human genes 0.000 description 1
108090000901 Transferrin Proteins 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
241000700605 Viruses Species 0.000 description 1
241001376713 Xenops Species 0.000 description 1
241000269370 Xenopus <genus> Species 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
239000002253 acid Substances 0.000 description 1
238000005273 aeration Methods 0.000 description 1
230000032683 aging Effects 0.000 description 1
239000003513 alkali Substances 0.000 description 1
230000004075 alteration Effects 0.000 description 1
238000012870 ammonium sulfate precipitation Methods 0.000 description 1
230000003698 anagen phase Effects 0.000 description 1
238000005349 anion exchange Methods 0.000 description 1
238000000137 annealing Methods 0.000 description 1
230000000692 anti-sense effect Effects 0.000 description 1
230000000890 antigenic effect Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
210000004958 brain cell Anatomy 0.000 description 1
244000309464 bull Species 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
238000005341 cation exchange Methods 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
210000003837 chick embryo Anatomy 0.000 description 1
229960001231 choline Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
210000000349 chromosome Anatomy 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
239000003636 conditioned culture medium Substances 0.000 description 1
239000012228 culture supernatant Substances 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
238000011026 diafiltration Methods 0.000 description 1
239000000539 dimer Substances 0.000 description 1
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 1
238000002224 dissection Methods 0.000 description 1
230000006334 disulfide bridging Effects 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
238000009585 enzyme analysis Methods 0.000 description 1
ONKUMRGIYFNPJW-KIEAKMPYSA-N ethynodiol diacetate Chemical compound C1C[C@]2(C)[C@@](C#C)(OC(C)=O)CC[C@H]2[C@@H]2CCC3=C[C@@H](OC(=O)C)CC[C@@H]3[C@H]21 ONKUMRGIYFNPJW-KIEAKMPYSA-N 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000013613 expression plasmid Substances 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
230000001605 fetal effect Effects 0.000 description 1
230000005714 functional activity Effects 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
102000051542 human BDNF Human genes 0.000 description 1
102000053563 human MYC Human genes 0.000 description 1
229940077456 human brain-derived neurotrophic factor Drugs 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
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 1
YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
230000002934 lysing effect Effects 0.000 description 1
239000004325 lysozyme Substances 0.000 description 1
229960000274 lysozyme Drugs 0.000 description 1
235000010335 lysozyme Nutrition 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
239000000463 material Substances 0.000 description 1
230000035800 maturation Effects 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
230000000869 mutational effect Effects 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
210000000584 nodose ganglion Anatomy 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
229920001778 nylon Polymers 0.000 description 1
229940046166 oligodeoxynucleotide Drugs 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
229940056360 penicillin g Drugs 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
210000001428 peripheral nervous system Anatomy 0.000 description 1
210000002826 placenta Anatomy 0.000 description 1
238000007747 plating Methods 0.000 description 1
108010055896 polyornithine Proteins 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
239000000186 progesterone Substances 0.000 description 1
229960003387 progesterone Drugs 0.000 description 1
230000009465 prokaryotic expression Effects 0.000 description 1
238000000164 protein isolation Methods 0.000 description 1
230000020978 protein processing Effects 0.000 description 1
238000004153 renaturation Methods 0.000 description 1
JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
229960001225 rifampicin Drugs 0.000 description 1
210000003079 salivary gland Anatomy 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
239000013606 secretion vector Substances 0.000 description 1
210000000413 sensory ganglia Anatomy 0.000 description 1
210000001044 sensory neuron Anatomy 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
229960001471 sodium selenite Drugs 0.000 description 1
235000015921 sodium selenite Nutrition 0.000 description 1
239000011781 sodium selenite Substances 0.000 description 1
VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
210000001913 submandibular gland Anatomy 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000002889 sympathetic effect Effects 0.000 description 1
210000002820 sympathetic nervous system Anatomy 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
230000002103 transcriptional effect Effects 0.000 description 1
239000012581 transferrin Substances 0.000 description 1
230000009466 transformation Effects 0.000 description 1
230000005945 translocation Effects 0.000 description 1
238000001665 trituration Methods 0.000 description 1
238000012784 weak cation exchange Methods 0.000 description 1
238000001262 western blot Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K14/245—Escherichia (G)
- 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
- C07K14/475—Growth factors; Growth regulators
- 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
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Genetics & Genomics (AREA)
Zoology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Medicinal Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biomedical Technology (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Gastroenterology & Hepatology (AREA)
Wood Science & Technology (AREA)
Microbiology (AREA)
Physics & Mathematics (AREA)
Plant Pathology (AREA)
Toxicology (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Peptides Or Proteins (AREA)

CA002111110A 1991-06-12 1992-06-11 Production et recuperation de neurotrophines recombinantes Abandoned CA2111110A1 (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US71518591A	1991-06-12	1991-06-12
US715,185		1991-06-12
US796,106		1991-11-21
US07/796,106 US5389529A (en)	1991-06-12	1991-11-21	Modified lamβ signal sequence and processes for producing recombinant neurotrophins

Publications (1)

Publication Number	Publication Date
CA2111110A1 true CA2111110A1 (fr)	1992-12-23

Family

ID=27109290

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002111110A Abandoned CA2111110A1 (fr)	1991-06-12	1992-06-11	Production et recuperation de neurotrophines recombinantes

Country Status (9)

Country	Link
EP (1)	EP0590059A4 (fr)
JP (1)	JPH06508036A (fr)
AU (1)	AU2238792A (fr)
CA (1)	CA2111110A1 (fr)
IE (1)	IE921888A1 (fr)
IL (1)	IL102170A0 (fr)
NZ (1)	NZ243084A (fr)
PT (1)	PT100580A (fr)
WO (1)	WO1992022665A1 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5169764A (en) *	1990-08-08	1992-12-08	Regeneron Pharmaceuticals, Inc.	Multitrophic and multifunctional chimeric neurotrophic factors, and nucleic acids and plasmids encoding the chimeras
ATE140966T1 (de) *	1990-09-25	1996-08-15	Genentech Inc	Neuer neurotropischer faktor
WO1995016910A1 (fr) *	1993-12-17	1995-06-22	Perkin-Elmer Corporation	Polymeres non charges destines a la separation de biomolecules par electrophorese capillaire
US5534615A (en) *	1994-04-25	1996-07-09	Genentech, Inc.	Cardiac hypertrophy factor and uses therefor
CA2188017C (fr) *	1994-04-25	2010-09-28	Joffre Baker	Cardiotrophine et ses utilisations
US6472585B1 (en)	1994-04-25	2002-10-29	Genentech, Inc.	Cardiotrophin-1 defective mouse
US7258983B2 (en)	1994-04-25	2007-08-21	Genentech, Inc.	Cardiotrophin-1 compositions and methods for the treatment of tumor
FR2729972B1 (fr) *	1995-01-31	1997-04-18	Sanofi Sa	Procede d'extraction de proteines periplasmiques de microorganismes procaryotes en presence d'arginine
JP4671372B2 (ja) *	1996-11-15	2011-04-13	ジェネンテック，インコーポレイテッド	ニューロトロフィンの精製
DE19944870A1 (de) *	1999-09-18	2001-03-29	Aventis Pharma Gmbh	Signalsequenzen zur Herstellung von Leu-Hirudin über Sekretion durch E. coli in das Kulturmedium

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4511502A (en) *	1982-12-22	1985-04-16	Genentech, Inc.	Purification and activity assurance of precipitated heterologous proteins
DK161152C (da) *	1983-03-03	1991-11-11	Genentech Inc	Polypeptid med egenskaber som human beta-nervevaekstfaktor og fremgangsmaade til fremstilling deraf, dna-isolat omfattende en sekvens som koder for polypeptidet, replicerbar udtrykkelsesvektor for dna-sekvensen, rekombinant vaertscelle transformeret med vektoren, farmaceutisk praeparat indeholdende polypeptidet og fremg. der omfatter anvendelsen af polypeptidet til fremst. af et farmaceutisk praeparat
AU4803890A (en) *	1988-12-15	1990-07-10	Invitron Corporation	Use of basic amino acids to solubilize immunoglobulins
US5235043A (en) *	1990-04-06	1993-08-10	Synergen, Inc.	Production of biologically active, recombinant members of the ngf/bdnf family of neurotrophic proteins
ATE140966T1 (de) *	1990-09-25	1996-08-15	Genentech Inc	Neuer neurotropischer faktor

1992
- 1992-06-09 NZ NZ243084A patent/NZ243084A/en not_active IP Right Cessation
- 1992-06-09 PT PT100580A patent/PT100580A/pt not_active Application Discontinuation
- 1992-06-11 CA CA002111110A patent/CA2111110A1/fr not_active Abandoned
- 1992-06-11 JP JP5501050A patent/JPH06508036A/ja active Pending
- 1992-06-11 EP EP92914222A patent/EP0590059A4/en not_active Withdrawn
- 1992-06-11 IL IL102170A patent/IL102170A0/xx unknown
- 1992-06-11 WO PCT/US1992/005006 patent/WO1992022665A1/fr not_active Ceased
- 1992-06-11 AU AU22387/92A patent/AU2238792A/en not_active Abandoned
- 1992-07-01 IE IE188892A patent/IE921888A1/en not_active Application Discontinuation

Also Published As

Publication number	Publication date
WO1992022665A1 (fr)	1992-12-23
NZ243084A (en)	1995-08-28
IL102170A0 (en)	1993-01-14
AU2238792A (en)	1993-01-12
PT100580A (pt)	1993-09-30
EP0590059A1 (fr)	1994-04-06
JPH06508036A (ja)	1994-09-14
EP0590059A4 (en)	1995-09-06
IE921888A1 (en)	1992-12-16

Publication	Publication Date	Title
US5389529A (en)	1995-02-14	Modified lamβ signal sequence and processes for producing recombinant neurotrophins
DE69233008T2 (de)	2004-01-22	Fusionierung von Peptiden und Proteinen mit Thioredoxin und thioredoxin-ähnlichen Molekülen
US5100784A (en)	1992-03-31	Process for the preparation of mature human serum albumin
EP0772627B1 (fr)	2004-09-01	Production de proteine neurotrophique recombinee biologiquement active
EP0205475B2 (fr)	2002-09-04	Procedes de production par recombinaison d'inhibiteurs de protease de serine; sequences d'adn utiles a ces procedes
CN110128521A (zh)	2019-08-16	用于生产重组融合蛋白的辅助蛋白、编码基因、重组融合蛋白、重组表达载体及制备方法
JPH1129598A (ja)	1999-02-02	精製した毛様体神経栄養因子
US6773899B2 (en)	2004-08-10	Phage-dependent superproduction of biologically active protein and peptides
JPH0753118B2 (ja)	1995-06-07	原核宿主生物によるジスルフィド架橋された蛋白質の分泌の際に天然蛋白質の立体配座の形成を向上させる方法
CA2111110A1 (fr)	1992-12-23	Production et recuperation de neurotrophines recombinantes
WO1991018101A1 (fr)	1991-11-28	Procede de production d'une proteine
JP2002527062A (ja)	2002-08-27	活性なβ−ＮＧＦを得るための方法
AU2001284914A1 (en)	2002-05-23	Phage-dependent Superproduction of Biologically Active Protein and Peptides
WO2007112677A1 (fr)	2007-10-11	Procédé de préparation d'hormone parathyroïdienne humaine 1-34
JP2001008697A (ja)	2001-01-16	Ｅ．コリでの非融合タンパク質の調製方法
EP0495398B1 (fr)	1998-12-16	Méthode pour la production de protéase IgA recombinante.
EP1706494B1 (fr)	2012-07-04	Procede de production d'hormone de croissance de recombinaison sous forme de proteine hybride
RU2143492C1 (ru)	1999-12-27	Рекомбинантная плазмида, кодирующая гибридный белок - предшественник инсулина человека (варианты), штамм бактерий e.coli - продуцент гибридного белка - предшественника инсулина человека (варианты), способ получения инсулина человека
Ghasemi et al.	2004	Using L-arabinose for production of human growth hormone in Escherichia coli, studying the processing of gIII:: hGH precursor
CN114561395A (zh)	2022-05-31	无融合标签的rhIL-11及其突变体的可溶表达及高效纯化方法
CN100484958C (zh)	2009-05-06	含有人甲状旁腺素1-34的融合蛋白及其表达载体
Koyama et al.	1994	A novel procedure for the preparation of biologically active recombinant peptides using a cyanylation reaction
RU2144082C1 (ru)	2000-01-10	Рекомбинантная плазмида, кодирующая гибридный белок-предшественник инсулина человека (варианты), штамм бактерий e.coli - продуцент гибридного белка-предшественника инсулина человека (варианты) и способ получения инсулина человека
CA2000368A1 (fr)	1990-04-11	Constructions de plasmides pour la production a grande echelle de proteines eucariotes
MONTAZER et al.	2004	Frequency of bovine lymphocyte antigen DRB3. 2 alleles in Sarabi cows

Legal Events

Date	Code	Title	Description
1995-12-11	FZDE	Discontinued
2023-05-26	FZDE	Discontinued	Effective date: 19951211