KR101984318B1 - 재조합 효소 및 다른 단백질의 단백질 발현 및 분비를 개선시키기 위한 신규 신호 서열 - Google Patents
재조합 효소 및 다른 단백질의 단백질 발현 및 분비를 개선시키기 위한 신규 신호 서열 Download PDFInfo
- Publication number
- KR101984318B1 KR101984318B1 KR1020137016110A KR20137016110A KR101984318B1 KR 101984318 B1 KR101984318 B1 KR 101984318B1 KR 1020137016110 A KR1020137016110 A KR 1020137016110A KR 20137016110 A KR20137016110 A KR 20137016110A KR 101984318 B1 KR101984318 B1 KR 101984318B1
- Authority
- KR
- South Korea
- Prior art keywords
- delete delete
- protein
- bip
- signal sequence
- heterologous polypeptide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 102000004190 Enzymes Human genes 0.000 title claims description 17
- 108090000790 Enzymes Proteins 0.000 title claims description 17
- 108010076504 Protein Sorting Signals Proteins 0.000 title abstract description 106
- 108090000623 proteins and genes Proteins 0.000 title description 95
- 102000004169 proteins and genes Human genes 0.000 title description 85
- 230000014509 gene expression Effects 0.000 title description 84
- 230000028327 secretion Effects 0.000 title description 33
- 229920001184 polypeptide Polymers 0.000 claims abstract description 63
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 63
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 63
- 239000012634 fragment Substances 0.000 claims abstract description 52
- 101000899240 Homo sapiens Endoplasmic reticulum chaperone BiP Proteins 0.000 claims abstract description 37
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 35
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 35
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 19
- 230000002608 insulinlike Effects 0.000 claims description 22
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 17
- 230000002378 acidificating effect Effects 0.000 claims description 16
- 102000014150 Interferons Human genes 0.000 claims description 14
- 108010050904 Interferons Proteins 0.000 claims description 14
- 108010076181 Proinsulin Proteins 0.000 claims description 14
- 229940079322 interferon Drugs 0.000 claims description 13
- 102100036717 Growth hormone variant Human genes 0.000 claims description 12
- 101710191157 Growth hormone variant Proteins 0.000 claims description 12
- 230000001225 therapeutic effect Effects 0.000 claims description 12
- 239000003053 toxin Substances 0.000 claims description 2
- 231100000765 toxin Toxicity 0.000 claims description 2
- 108700012359 toxins Proteins 0.000 claims description 2
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 claims 5
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 claims 5
- 230000008512 biological response Effects 0.000 claims 1
- 239000003607 modifier Substances 0.000 claims 1
- 108020004414 DNA Proteins 0.000 abstract description 60
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 235000018102 proteins Nutrition 0.000 description 65
- 238000004113 cell culture Methods 0.000 description 59
- 230000001965 increasing effect Effects 0.000 description 36
- 230000000694 effects Effects 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 31
- 239000013615 primer Substances 0.000 description 28
- 241000282414 Homo sapiens Species 0.000 description 26
- 235000015097 nutrients Nutrition 0.000 description 21
- 239000002253 acid Substances 0.000 description 14
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 12
- 230000002209 hydrophobic effect Effects 0.000 description 12
- 229940068935 insulin-like growth factor 2 Drugs 0.000 description 12
- 108010030291 alpha-Galactosidase Proteins 0.000 description 11
- 102000005840 alpha-Galactosidase Human genes 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 239000000758 substrate Substances 0.000 description 10
- 239000013598 vector Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000011543 agarose gel Substances 0.000 description 9
- 239000002299 complementary DNA Substances 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 230000014616 translation Effects 0.000 description 9
- 102100038803 Somatotropin Human genes 0.000 description 8
- 108050007673 Somatotropin Proteins 0.000 description 8
- 239000006180 TBST buffer Substances 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 239000000872 buffer Substances 0.000 description 7
- 239000006143 cell culture medium Substances 0.000 description 7
- 238000001243 protein synthesis Methods 0.000 description 7
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 6
- IXZHZUGGKLRHJD-DCAQKATOSA-N Ser-Leu-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O IXZHZUGGKLRHJD-DCAQKATOSA-N 0.000 description 6
- 235000004279 alanine Nutrition 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000007398 protein translocation Effects 0.000 description 6
- HSJIGJRZYUADSS-IHRRRGAJSA-N Met-Lys-Leu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O HSJIGJRZYUADSS-IHRRRGAJSA-N 0.000 description 5
- 102100029789 Urocortin-2 Human genes 0.000 description 5
- 210000000805 cytoplasm Anatomy 0.000 description 5
- 235000013336 milk Nutrition 0.000 description 5
- 239000008267 milk Substances 0.000 description 5
- 210000004080 milk Anatomy 0.000 description 5
- 230000009261 transgenic effect Effects 0.000 description 5
- 238000003146 transient transfection Methods 0.000 description 5
- 230000005945 translocation Effects 0.000 description 5
- 108010087967 type I signal peptidase Proteins 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 4
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 235000013861 fat-free Nutrition 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- VBDMWOKJZDCFJM-FXQIFTODSA-N Ala-Ala-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N VBDMWOKJZDCFJM-FXQIFTODSA-N 0.000 description 3
- 102100036826 Aldehyde oxidase Human genes 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 238000001712 DNA sequencing Methods 0.000 description 3
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 3
- 108010006519 Molecular Chaperones Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003636 conditioned culture medium Substances 0.000 description 3
- 230000001143 conditioned effect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 239000012470 diluted sample Substances 0.000 description 3
- 238000006911 enzymatic reaction Methods 0.000 description 3
- 238000001952 enzyme assay Methods 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- 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 3
- 230000008685 targeting Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 230000010474 transient expression Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 102000012410 DNA Ligases Human genes 0.000 description 2
- 108010061982 DNA Ligases Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 108010017544 Glucosylceramidase Proteins 0.000 description 2
- 101001018026 Homo sapiens Lysosomal alpha-glucosidase Proteins 0.000 description 2
- 101000616112 Homo sapiens Stress-associated endoplasmic reticulum protein 1 Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- RXGLHDWAZQECBI-SRVKXCTJSA-N Leu-Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O RXGLHDWAZQECBI-SRVKXCTJSA-N 0.000 description 2
- 102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102000005431 Molecular Chaperones Human genes 0.000 description 2
- 101100476756 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) sec-61 gene Proteins 0.000 description 2
- 101150083515 RPL17 gene Proteins 0.000 description 2
- 102000002278 Ribosomal Proteins Human genes 0.000 description 2
- 108010000605 Ribosomal Proteins Proteins 0.000 description 2
- 241000631463 Saara Species 0.000 description 2
- 102100021813 Stress-associated endoplasmic reticulum protein 1 Human genes 0.000 description 2
- -1 Subunits Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 102000045921 human GAA Human genes 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000029054 response to nutrient Effects 0.000 description 2
- 210000003705 ribosome Anatomy 0.000 description 2
- 239000007974 sodium acetate buffer Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000012096 transfection reagent Substances 0.000 description 2
- 239000003656 tris buffered saline Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical group OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- YUDPTGPSBJVHCN-JZYAIQKZSA-N 4-Methylumbelliferyl-alpha-D-glucopyranoside Chemical compound C1=CC=2C(C)=CC(=O)OC=2C=C1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O YUDPTGPSBJVHCN-JZYAIQKZSA-N 0.000 description 1
- YUDPTGPSBJVHCN-CHUNWDLHSA-N 4-methylumbelliferyl alpha-D-galactoside Chemical compound C1=CC=2C(C)=CC(=O)OC=2C=C1O[C@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O YUDPTGPSBJVHCN-CHUNWDLHSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 1
- HHGYNJRJIINWAK-FXQIFTODSA-N Ala-Ala-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N HHGYNJRJIINWAK-FXQIFTODSA-N 0.000 description 1
- VWEWCZSUWOEEFM-WDSKDSINSA-N Ala-Gly-Ala-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(O)=O VWEWCZSUWOEEFM-WDSKDSINSA-N 0.000 description 1
- 102100026277 Alpha-galactosidase A Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 108010089072 Dolichyl-diphosphooligosaccharide-protein glycotransferase Proteins 0.000 description 1
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 1
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 101000718525 Homo sapiens Alpha-galactosidase A Proteins 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 101000997662 Homo sapiens Lysosomal acid glucosylceramidase Proteins 0.000 description 1
- 101000713575 Homo sapiens Tubulin beta-3 chain Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 1
- FOBUGKUBUJOWAD-IHPCNDPISA-N Leu-Leu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C)C(O)=O)=CNC2=C1 FOBUGKUBUJOWAD-IHPCNDPISA-N 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 101800000135 N-terminal protein Proteins 0.000 description 1
- 101100342977 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-1 gene Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- XDMCWZFLLGVIID-SXPRBRBTSA-N O-(3-O-D-galactosyl-N-acetyl-beta-D-galactosaminyl)-L-serine Chemical compound CC(=O)N[C@H]1[C@H](OC[C@H]([NH3+])C([O-])=O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 XDMCWZFLLGVIID-SXPRBRBTSA-N 0.000 description 1
- 101800001452 P1 proteinase Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 1
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 1
- 108010044843 Peptide Initiation Factors Proteins 0.000 description 1
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 102000006010 Protein Disulfide-Isomerase Human genes 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 102000018673 SEC Translocation Channels Human genes 0.000 description 1
- 108010091732 SEC Translocation Channels Proteins 0.000 description 1
- ZUGXSSFMTXKHJS-ZLUOBGJFSA-N Ser-Ala-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O ZUGXSSFMTXKHJS-ZLUOBGJFSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 102100036790 Tubulin beta-3 chain Human genes 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 102000016679 alpha-Glucosidases Human genes 0.000 description 1
- 108010028144 alpha-Glucosidases Proteins 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000010001 cellular homeostasis Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000012444 downstream purification process Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002729 effect on secretion Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000043404 human GLA Human genes 0.000 description 1
- 102000057877 human IGF2 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229940068924 human insulin-like growth factor 2 Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 108010045758 lysosomal proteins Proteins 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 108020003519 protein disulfide isomerase Proteins 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 108010000633 signal peptide receptor Proteins 0.000 description 1
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 150000008505 β-D-glucopyranosides Chemical class 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0002—Antibodies with enzymatic activity, e.g. abzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2405—Glucanases
- C12N9/2434—Glucanases acting on beta-1,4-glucosidic bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/036—Fusion polypeptide containing a localisation/targetting motif targeting to the medium outside of the cell, e.g. type III secretion
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01022—Alpha-galactosidase (3.2.1.22)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01045—Glucosylceramidase (3.2.1.45), i.e. beta-glucocerebrosidase
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Plant Pathology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41592610P | 2010-11-22 | 2010-11-22 | |
| US61/415,926 | 2010-11-22 | ||
| PCT/US2011/061862 WO2012071422A2 (en) | 2010-11-22 | 2011-11-22 | Novel signal sequences to improve protein expressions and secretion of recombinant enzymes and other proteins |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197015057A Division KR20190060888A (ko) | 2010-11-22 | 2011-11-22 | 재조합 효소 및 다른 단백질의 단백질 발현 및 분비를 개선시키기 위한 신규 신호 서열 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20130121878A KR20130121878A (ko) | 2013-11-06 |
| KR101984318B1 true KR101984318B1 (ko) | 2019-05-31 |
Family
ID=46146394
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020137016110A Active KR101984318B1 (ko) | 2010-11-22 | 2011-11-22 | 재조합 효소 및 다른 단백질의 단백질 발현 및 분비를 개선시키기 위한 신규 신호 서열 |
| KR1020197015057A Ceased KR20190060888A (ko) | 2010-11-22 | 2011-11-22 | 재조합 효소 및 다른 단백질의 단백질 발현 및 분비를 개선시키기 위한 신규 신호 서열 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197015057A Ceased KR20190060888A (ko) | 2010-11-22 | 2011-11-22 | 재조합 효소 및 다른 단백질의 단백질 발현 및 분비를 개선시키기 위한 신규 신호 서열 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US9279007B2 (enExample) |
| EP (2) | EP3461905B1 (enExample) |
| JP (1) | JP2014503198A (enExample) |
| KR (2) | KR101984318B1 (enExample) |
| CN (1) | CN103328649B (enExample) |
| BR (1) | BR112013012671B1 (enExample) |
| CA (1) | CA2818689C (enExample) |
| CY (1) | CY1121049T1 (enExample) |
| DK (2) | DK3461905T3 (enExample) |
| ES (2) | ES2687415T3 (enExample) |
| HR (1) | HRP20181315T1 (enExample) |
| HU (1) | HUE039070T2 (enExample) |
| LT (1) | LT2643468T (enExample) |
| PL (1) | PL2643468T3 (enExample) |
| PT (1) | PT2643468T (enExample) |
| RS (1) | RS57601B1 (enExample) |
| SI (1) | SI2643468T1 (enExample) |
| SM (1) | SMT201800466T1 (enExample) |
| WO (1) | WO2012071422A2 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20192243T1 (hr) | 2014-07-03 | 2020-03-06 | F. Hoffmann - La Roche Ag | Polipeptidni ekspresijski sustavi |
| WO2017180587A2 (en) | 2016-04-11 | 2017-10-19 | Obsidian Therapeutics, Inc. | Regulated biocircuit systems |
| CN110809583A (zh) | 2017-06-07 | 2020-02-18 | 瑞泽恩制药公司 | 用于内化酶的组合物和方法 |
| TW201927825A (zh) * | 2017-11-30 | 2019-07-16 | 美商阿米庫斯醫療股份有限公司 | Cdkl5 表現變體和cdkl5 融合蛋白 |
| KR20200118151A (ko) | 2018-02-07 | 2020-10-14 | 리제너론 파마슈티칼스 인코포레이티드 | 치료 단백질 전달을 위한 방법 및 조성물 |
| BR112020021962A2 (pt) * | 2018-04-30 | 2021-01-26 | Amicus Therapeutics, Inc. | construtos para terapia gênica e métodos de uso |
| MX2020012350A (es) | 2018-05-17 | 2021-01-29 | Regeneron Pharma | Anticuerpos anti-cd63, conjugados y usos de estos. |
| WO2019241315A1 (en) | 2018-06-12 | 2019-12-19 | Obsidian Therapeutics, Inc. | Pde5 derived regulatory constructs and methods of use in immunotherapy |
| EP3863663A2 (en) | 2018-10-10 | 2021-08-18 | Amicus Therapeutics, Inc. | Disulfide bond stabilized polypeptide compositions and methods of use |
| WO2020086742A1 (en) | 2018-10-24 | 2020-04-30 | Obsidian Therapeutics, Inc. | Er tunable protein regulation |
| KR20210105382A (ko) * | 2018-12-19 | 2021-08-26 | 베르사멥 아게 | 단백질을 코딩하는 rna |
| KR20210149251A (ko) | 2019-03-08 | 2021-12-08 | 옵시디안 테라퓨틱스, 인크. | 조율가능한 조절을 위한 인간 탄산 무수화효소 2 조성물 및 방법 |
| BR112021021720A2 (pt) * | 2019-04-30 | 2021-12-28 | Univ Pennsylvania | Composições úteis para tratamento de doença de pompe |
| EP3983538A1 (en) | 2019-06-12 | 2022-04-20 | Obsidian Therapeutics, Inc. | Ca2 compositions and methods for tunable regulation |
| WO2020252404A1 (en) | 2019-06-12 | 2020-12-17 | Obsidian Therapeutics, Inc. | Ca2 compositions and methods for tunable regulation |
| US20220348937A1 (en) | 2019-09-06 | 2022-11-03 | Obsidian Therapeutics, Inc. | Compositions and methods for dhfr tunable protein regulation |
| CN112342247B (zh) * | 2020-11-10 | 2022-03-11 | 江苏科技大学 | 一种提高家蚕细胞表达外源蛋白分泌率的方法 |
| CA3200192A1 (en) | 2020-12-01 | 2022-06-09 | Justin PERCIVAL | Compositions and uses thereof for treatment of angelman syndrome |
| US20250034533A1 (en) | 2021-11-12 | 2025-01-30 | Amicus Therapeutics, Inc. | Compositions And Methods For Treating Mucopolysaccharidosis IIIA |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2352286C (en) * | 1998-11-24 | 2011-07-12 | Bristol-Myers Squibb Company | Intracellular targeted delivery of compounds by 70 kd heat shock protein |
| US7279564B2 (en) * | 2003-11-06 | 2007-10-09 | Genencor International, Inc. | Expression in filamentous fungi of protease inhibitors and variants thereof |
| DE602007007923D1 (de) * | 2006-04-11 | 2010-09-02 | Csl Behring Gmbh | Verfahren zur erhöhung der in-vivo-gewinnung therapeutischer polypeptide |
-
2011
- 2011-11-22 EP EP18181451.8A patent/EP3461905B1/en active Active
- 2011-11-22 ES ES11843849.8T patent/ES2687415T3/es active Active
- 2011-11-22 ES ES18181451T patent/ES2829199T3/es active Active
- 2011-11-22 SM SM20180466T patent/SMT201800466T1/it unknown
- 2011-11-22 HR HRP20181315TT patent/HRP20181315T1/hr unknown
- 2011-11-22 EP EP11843849.8A patent/EP2643468B1/en active Active
- 2011-11-22 PT PT11843849T patent/PT2643468T/pt unknown
- 2011-11-22 BR BR112013012671-0A patent/BR112013012671B1/pt not_active IP Right Cessation
- 2011-11-22 DK DK18181451.8T patent/DK3461905T3/da active
- 2011-11-22 SI SI201131554T patent/SI2643468T1/sl unknown
- 2011-11-22 RS RS20180986A patent/RS57601B1/sr unknown
- 2011-11-22 CA CA2818689A patent/CA2818689C/en active Active
- 2011-11-22 CN CN201180065369.5A patent/CN103328649B/zh active Active
- 2011-11-22 JP JP2013541026A patent/JP2014503198A/ja not_active Withdrawn
- 2011-11-22 DK DK11843849.8T patent/DK2643468T3/en active
- 2011-11-22 KR KR1020137016110A patent/KR101984318B1/ko active Active
- 2011-11-22 PL PL11843849T patent/PL2643468T3/pl unknown
- 2011-11-22 HU HUE11843849A patent/HUE039070T2/hu unknown
- 2011-11-22 WO PCT/US2011/061862 patent/WO2012071422A2/en not_active Ceased
- 2011-11-22 KR KR1020197015057A patent/KR20190060888A/ko not_active Ceased
- 2011-11-22 LT LTEP11843849.8T patent/LT2643468T/lt unknown
- 2011-11-22 US US13/988,946 patent/US9279007B2/en active Active
-
2018
- 2018-09-12 CY CY181100941T patent/CY1121049T1/el unknown
Non-Patent Citations (1)
| Title |
|---|
| Protein Expr. Purif., 2007년, Vol.56, No.1, pp.8-19 |
Also Published As
| Publication number | Publication date |
|---|---|
| BR112013012671A2 (pt) | 2016-10-11 |
| WO2012071422A3 (en) | 2012-08-02 |
| CA2818689C (en) | 2021-09-21 |
| PT2643468T (pt) | 2018-10-11 |
| BR112013012671B1 (pt) | 2022-03-03 |
| HUE039070T2 (hu) | 2018-12-28 |
| CY1121049T1 (el) | 2019-12-11 |
| DK2643468T3 (en) | 2018-09-24 |
| EP2643468A2 (en) | 2013-10-02 |
| EP2643468B1 (en) | 2018-07-04 |
| ES2829199T3 (es) | 2021-05-31 |
| ES2687415T3 (es) | 2018-10-25 |
| PL2643468T3 (pl) | 2018-11-30 |
| LT2643468T (lt) | 2018-09-10 |
| KR20190060888A (ko) | 2019-06-03 |
| KR20130121878A (ko) | 2013-11-06 |
| JP2014503198A (ja) | 2014-02-13 |
| HRP20181315T1 (hr) | 2018-10-19 |
| EP3461905A1 (en) | 2019-04-03 |
| US20140045216A1 (en) | 2014-02-13 |
| EP2643468A4 (en) | 2014-12-24 |
| EP3461905B1 (en) | 2020-08-05 |
| CN103328649A (zh) | 2013-09-25 |
| DK3461905T3 (da) | 2020-11-02 |
| WO2012071422A2 (en) | 2012-05-31 |
| CN103328649B (zh) | 2016-06-22 |
| CA2818689A1 (en) | 2012-05-31 |
| US9279007B2 (en) | 2016-03-08 |
| SMT201800466T1 (it) | 2018-11-09 |
| RS57601B1 (sr) | 2018-11-30 |
| SI2643468T1 (sl) | 2018-10-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101984318B1 (ko) | 재조합 효소 및 다른 단백질의 단백질 발현 및 분비를 개선시키기 위한 신규 신호 서열 | |
| Saunders et al. | Secretion of human serum albumin from Bacillus subtilis | |
| Kollmann et al. | Identification of novel lysosomal matrix proteins by proteome analysis | |
| US6136564A (en) | Process for the production of peptides by way of streptavidin fusion proteins | |
| JPH09504166A (ja) | リーダー配列なしに細胞質外に輸送される融合ポリペプチドの発現 | |
| KR20210032972A (ko) | 전사인자를 사용하여 단백질 발현을 증가시키는 수단 및 방법 | |
| JP4809227B2 (ja) | タンパク質の産生に使用するためのリーダー配列 | |
| AU2018348518B2 (en) | Method for manufacturing protein | |
| EP0422049A4 (en) | Vector for secretion of proteins directly into periplasm or culture medium | |
| US7741075B2 (en) | Pichia pastoris PIR1 secretion signal peptide for recombinant protein expression and Pichia pastoris PIR1 and PIR2 anchor domain peptides for recombinant surface display | |
| Ide et al. | Effects of pre-and pro-sequence of thaumatin on the secretion by Pichia pastoris | |
| JPH0272892A (ja) | 蛋白質の製造方法 | |
| WO2012052170A1 (en) | Secretion of recombinant polypeptides in the extracellular medium of diatoms | |
| De Sutter et al. | Production of enzymatically active rat protein disulfide isomerase in Escherichia coli | |
| Schuster et al. | Protein expression in yeast; comparison of two expression strategies regarding protein maturation | |
| JPH0746988A (ja) | 組換体ｄｎａ構造とこれを含むプラスミド媒介体とこのような組換体ｄｎａ構造を保持するグラム陰性菌 | |
| HK40006980A (en) | Novel signal sequences to improve protein expression and secretion of recombinant enzymes and other proteins | |
| Eskridge et al. | The NH2 terminus of preproinsulin directs the translocation and glycosylation of a bacterial cytoplasmic protein by mammalian microsomal membranes. | |
| HK1189913B (en) | Novel signal sequences to improve protein expressions and secretion of recombinant enzymes and other proteins | |
| HK1189913A (en) | Novel signal sequences to improve protein expressions and secretion of recombinant enzymes and other proteins | |
| Rao et al. | Transgenic expression in tobacco of a poly-proctolin construct leading to production of the bioactive peptide | |
| Hüsken et al. | Overexpression in Escherichia coli of a methionine‐free designed interleukin‐2 receptor (Tac protein) based on a chemically cleavable fusion protein | |
| Xuejun et al. | Production of a functional single-chain Fv protein in transgenic tobacco root exudates | |
| Chen et al. | Regulated secretion of prolactin by the mouse insulinoma cell line βTC-3 | |
| JPH0670790A (ja) | カルシトニンの製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20130621 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| N231 | Notification of change of applicant | ||
| PN2301 | Change of applicant |
Patent event date: 20160712 Comment text: Notification of Change of Applicant Patent event code: PN23011R01D |
|
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20161107 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20180219 Patent event code: PE09021S01D |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20180814 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20190225 |
|
| PA0104 | Divisional application for international application |
Comment text: Divisional Application for International Patent Patent event code: PA01041R01D Patent event date: 20190524 |
|
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20190524 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20190524 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20220415 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20230418 Start annual number: 5 End annual number: 5 |
|
| PR1001 | Payment of annual fee |
Payment date: 20250403 Start annual number: 7 End annual number: 7 |