FI64640C - Foerfarande foer framstaellning av en kombinations-dna-molekylsom innehaoller en foer insulin kodande nukleotidsekvens hocsom kan anvaendas vid framstaellning av en insulin produ rcende mikroorganism - Google Patents
Foerfarande foer framstaellning av en kombinations-dna-molekylsom innehaoller en foer insulin kodande nukleotidsekvens hocsom kan anvaendas vid framstaellning av en insulin produ rcende mikroorganism Download PDFInfo
- Publication number
- FI64640C FI64640C FI781675A FI781675A FI64640C FI 64640 C FI64640 C FI 64640C FI 781675 A FI781675 A FI 781675A FI 781675 A FI781675 A FI 781675A FI 64640 C FI64640 C FI 64640C
- Authority
- FI
- Finland
- Prior art keywords
- dna
- insulin
- cdna
- mrna
- sequence
- Prior art date
Links
- 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 title claims abstract description 53
- 108090001061 Insulin Proteins 0.000 title claims abstract description 29
- 102000004877 Insulin Human genes 0.000 title claims abstract description 26
- 229940125396 insulin Drugs 0.000 title claims abstract description 26
- 244000005700 microbiome Species 0.000 title claims abstract description 17
- 108020004414 DNA Proteins 0.000 claims abstract description 121
- 239000002299 complementary DNA Substances 0.000 claims abstract description 49
- 108020004999 messenger RNA Proteins 0.000 claims abstract description 46
- 239000002773 nucleotide Substances 0.000 claims abstract description 38
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 38
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 11
- 102100031780 Endonuclease Human genes 0.000 claims description 31
- 102000053602 DNA Human genes 0.000 claims description 26
- 102000004190 Enzymes Human genes 0.000 claims description 26
- 108090000790 Enzymes Proteins 0.000 claims description 26
- 108091008146 restriction endonucleases Proteins 0.000 claims description 22
- 102000006382 Ribonucleases Human genes 0.000 claims description 17
- 108010083644 Ribonucleases Proteins 0.000 claims description 17
- 210000004153 islets of langerhan Anatomy 0.000 claims description 17
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 claims description 15
- 229910019142 PO4 Inorganic materials 0.000 claims description 12
- 108020004511 Recombinant DNA Proteins 0.000 claims description 12
- 239000013600 plasmid vector Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- 238000011534 incubation Methods 0.000 claims description 10
- 102000012410 DNA Ligases Human genes 0.000 claims description 9
- 108010061982 DNA Ligases Proteins 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 102000002260 Alkaline Phosphatase Human genes 0.000 claims description 8
- 108020004774 Alkaline Phosphatase Proteins 0.000 claims description 8
- 230000003301 hydrolyzing effect Effects 0.000 claims description 8
- 239000010452 phosphate Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 claims description 7
- ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 claims description 7
- 238000005859 coupling reaction Methods 0.000 claims description 5
- 230000015556 catabolic process Effects 0.000 claims description 4
- 238000006731 degradation reaction Methods 0.000 claims description 4
- 238000000265 homogenisation Methods 0.000 claims description 4
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 claims description 3
- 230000004927 fusion Effects 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 210000004923 pancreatic tissue Anatomy 0.000 claims description 3
- 101710141795 Ribonuclease inhibitor Proteins 0.000 claims description 2
- 229940122208 Ribonuclease inhibitor Drugs 0.000 claims description 2
- 102100037968 Ribonuclease inhibitor Human genes 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 150000007523 nucleic acids Chemical group 0.000 claims description 2
- 239000003161 ribonuclease inhibitor Substances 0.000 claims description 2
- 239000003086 colorant Substances 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 abstract description 63
- 238000012546 transfer Methods 0.000 abstract description 23
- 239000013598 vector Substances 0.000 abstract description 22
- 108020004635 Complementary DNA Proteins 0.000 abstract description 7
- 101000976075 Homo sapiens Insulin Proteins 0.000 abstract description 6
- 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 abstract description 6
- 238000010804 cDNA synthesis Methods 0.000 abstract description 4
- 239000000122 growth hormone Substances 0.000 abstract description 4
- 108010051696 Growth Hormone Proteins 0.000 abstract description 3
- 108010000521 Human Growth Hormone Proteins 0.000 abstract description 2
- 238000000855 fermentation Methods 0.000 abstract description 2
- 230000004151 fermentation Effects 0.000 abstract description 2
- 102000018997 Growth Hormone Human genes 0.000 abstract 1
- 102000002265 Human Growth Hormone Human genes 0.000 abstract 1
- 239000000854 Human Growth Hormone Substances 0.000 abstract 1
- 238000000034 method Methods 0.000 description 67
- 239000013612 plasmid Substances 0.000 description 66
- 210000004027 cell Anatomy 0.000 description 57
- 235000018102 proteins Nutrition 0.000 description 31
- 102000004169 proteins and genes Human genes 0.000 description 31
- 108010042407 Endonucleases Proteins 0.000 description 27
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 25
- 229940088598 enzyme Drugs 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 19
- 239000012634 fragment Substances 0.000 description 18
- 239000004098 Tetracycline Substances 0.000 description 17
- 229960002180 tetracycline Drugs 0.000 description 17
- 229930101283 tetracycline Natural products 0.000 description 17
- 235000019364 tetracycline Nutrition 0.000 description 17
- 150000003522 tetracyclines Chemical class 0.000 description 17
- 241000700159 Rattus Species 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 150000001413 amino acids Chemical group 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 12
- 102000004533 Endonucleases Human genes 0.000 description 11
- 238000003776 cleavage reaction Methods 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 230000000295 complement effect Effects 0.000 description 10
- -1 guanylguanidinium Chemical compound 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 241000588724 Escherichia coli Species 0.000 description 9
- 238000002955 isolation Methods 0.000 description 9
- 210000000496 pancreas Anatomy 0.000 description 9
- 230000007017 scission Effects 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 239000001226 triphosphate Substances 0.000 description 9
- 235000011178 triphosphate Nutrition 0.000 description 9
- 229960000723 ampicillin Drugs 0.000 description 8
- 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 8
- 238000000605 extraction Methods 0.000 description 8
- 230000002068 genetic effect Effects 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- 239000003398 denaturant Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 230000009466 transformation Effects 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000003196 chaotropic effect Effects 0.000 description 6
- 239000007795 chemical reaction product Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 229940088597 hormone Drugs 0.000 description 6
- 239000005556 hormone Substances 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- 235000021317 phosphate Nutrition 0.000 description 6
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 6
- 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 5
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- 108010076181 Proinsulin Proteins 0.000 description 5
- 229920005654 Sephadex Polymers 0.000 description 5
- 239000012507 Sephadex™ Substances 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000004925 denaturation Methods 0.000 description 5
- 230000036425 denaturation Effects 0.000 description 5
- 238000012869 ethanol precipitation Methods 0.000 description 5
- 238000001502 gel electrophoresis Methods 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 5
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
- 239000012981 Hank's balanced salt solution Substances 0.000 description 4
- 101710163270 Nuclease Proteins 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 210000002808 connective tissue Anatomy 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 150000003013 phosphoric acid derivatives Chemical group 0.000 description 4
- 229920002401 polyacrylamide Polymers 0.000 description 4
- 230000006798 recombination Effects 0.000 description 4
- 238000005215 recombination Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 102000029816 Collagenase Human genes 0.000 description 3
- 108060005980 Collagenase Proteins 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 3
- 229920001917 Ficoll Polymers 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- 102000003960 Ligases Human genes 0.000 description 3
- 108090000364 Ligases Proteins 0.000 description 3
- 108020004682 Single-Stranded DNA Proteins 0.000 description 3
- 102100038803 Somatotropin Human genes 0.000 description 3
- 108020004566 Transfer RNA Proteins 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 3
- 229960002424 collagenase Drugs 0.000 description 3
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Natural products NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 229930024421 Adenine Natural products 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000713838 Avian myeloblastosis virus Species 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000283074 Equus asinus Species 0.000 description 2
- 108010012003 GGCC-specific type II deoxyribonucleases Proteins 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- 241000606790 Haemophilus Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 108010067035 Pancrelipase Proteins 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 101000868151 Rattus norvegicus Somatotropin Proteins 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 101710162629 Trypsin inhibitor Proteins 0.000 description 2
- 229940122618 Trypsin inhibitor Drugs 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 229940104302 cytosine Drugs 0.000 description 2
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 2
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 2
- RGWHQCVHVJXOKC-SHYZEUOFSA-N dCTP Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO[P@](O)(=O)O[P@](O)(=O)OP(O)(O)=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-N 0.000 description 2
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 2
- 239000005549 deoxyribonucleoside Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000000813 peptide hormone Substances 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 108010066381 preproinsulin Proteins 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
- 229960001860 salicylate Drugs 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 229940113082 thymine Drugs 0.000 description 2
- 239000002753 trypsin inhibitor Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- GMKMEZVLHJARHF-UHFFFAOYSA-N (2R,6R)-form-2.6-Diaminoheptanedioic acid Natural products OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 240000006439 Aspergillus oryzae Species 0.000 description 1
- 235000002247 Aspergillus oryzae Nutrition 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 108010055991 BglII endonuclease Proteins 0.000 description 1
- 101001011741 Bos taurus Insulin Proteins 0.000 description 1
- 241000208199 Buxus sempervirens Species 0.000 description 1
- 101100148606 Caenorhabditis elegans pst-1 gene Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 102000004594 DNA Polymerase I Human genes 0.000 description 1
- 108010017826 DNA Polymerase I Proteins 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 208000034454 F12-related hereditary angioedema with normal C1Inh Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- SQSPRWMERUQXNE-UHFFFAOYSA-N Guanylurea Chemical compound NC(=N)NC(N)=O SQSPRWMERUQXNE-UHFFFAOYSA-N 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 241000193159 Hathewaya histolytica Species 0.000 description 1
- 101500025353 Homo sapiens Insulin A chain Proteins 0.000 description 1
- 101500025354 Homo sapiens Insulin B chain Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000015731 Peptide Hormones Human genes 0.000 description 1
- 108010038988 Peptide Hormones Proteins 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- 108010005991 Pork Regular Insulin Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- RZCIEJXAILMSQK-JXOAFFINSA-N TTP Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 RZCIEJXAILMSQK-JXOAFFINSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 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 1
- CTCBPRXHVPZNHB-VQFZJOCSSA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate;(2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O.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 CTCBPRXHVPZNHB-VQFZJOCSSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008346 aqueous phase Substances 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
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000013377 clone selection method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000002481 ethanol extraction Methods 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 208000016861 hereditary angioedema type 3 Diseases 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- GMKMEZVLHJARHF-SYDPRGILSA-N meso-2,6-diaminopimelic acid Chemical compound [O-]C(=O)[C@@H]([NH3+])CCC[C@@H]([NH3+])C([O-])=O GMKMEZVLHJARHF-SYDPRGILSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000000277 pancreatic duct Anatomy 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 238000013492 plasmid preparation Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 108010005636 polypeptide C Proteins 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000034005 thiol-disulfide exchange Effects 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 238000012090 tissue culture technique Methods 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- 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
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1096—Processes for the isolation, preparation or purification of DNA or RNA cDNA Synthesis; Subtracted cDNA library construction, e.g. RT, RT-PCR
-
- 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
- C07K14/57518—Placental lactogen; Chorionic somatomammotropin
-
- 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
- C07K14/62—Insulins
-
- 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
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Computational Biology (AREA)
- Pregnancy & Childbirth (AREA)
- Diabetes (AREA)
- Crystallography & Structural Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI810692A FI810692L (fi) | 1978-04-19 | 1978-05-26 | Mikroorganism innehaollande tillvaexthormon |
FI810691A FI810691L (fi) | 1977-05-27 | 1978-05-26 | Mikroorganism innehaollande insulin |
FI810687A FI65446C (fi) | 1977-05-27 | 1981-03-05 | Foerfarande foer framstaellning av en bakterie som innehaolleren foer insulin kodande nukleotidsekvens |
FI810688A FI65447C (fi) | 1977-05-27 | 1981-03-05 | Foerfarande foer framstaellning av en bakterie som innehaolleren foer tillvaexthormon kodande nukleotidsekvens |
FI810689A FI75185C (fi) | 1977-05-27 | 1981-03-05 | Dna-oeverfoeringsvektor, vilken innehaoller en foer insulin kodande nukleotidsekvens. |
FI810686A FI64953C (fi) | 1977-05-27 | 1981-03-05 | Foerfarande foer framstaellning av en rekombinant-dna-molekyl som innehaoller en foer tillvaexthormon kodande nukleotidsekvens och som kan anvaendas vid framstaellning av en tillvaexthormon producerande mikroorganism |
FI810690A FI74732C (fi) | 1978-04-19 | 1981-03-05 | Dna-oeverfoeringsvektor, vilken innehaoller en nukleotidsekvens som kodar foer tillvaexthormon. |
Applications Claiming Priority (14)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US80134377A | 1977-05-27 | 1977-05-27 | |
US80134377 | 1977-05-27 | ||
US80502377A | 1977-06-09 | 1977-06-09 | |
US80502377 | 1977-06-09 | ||
US89770978A | 1978-04-19 | 1978-04-19 | |
US89771078 | 1978-04-19 | ||
US89770978 | 1978-04-19 | ||
US05897710 US4363877B1 (en) | 1977-09-23 | 1978-04-19 | Recombinant dna transfer vectors |
US05/898,887 US4264731A (en) | 1977-05-27 | 1978-04-21 | DNA Joining method |
US89888778 | 1978-04-21 | ||
US89900278A | 1978-04-26 | 1978-04-26 | |
US89900378A | 1978-04-26 | 1978-04-26 | |
US89900278 | 1978-04-26 | ||
US89900378 | 1978-04-26 |
Publications (3)
Publication Number | Publication Date |
---|---|
FI781675A7 FI781675A7 (fi) | 1978-11-28 |
FI64640B FI64640B (fi) | 1983-08-31 |
FI64640C true FI64640C (fi) | 1983-12-12 |
Family
ID=27569921
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI781675A FI64640C (fi) | 1977-05-27 | 1978-05-26 | Foerfarande foer framstaellning av en kombinations-dna-molekylsom innehaoller en foer insulin kodande nukleotidsekvens hocsom kan anvaendas vid framstaellning av en insulin produ rcende mikroorganism |
Country Status (21)
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZA782933B (en) * | 1977-09-23 | 1979-05-30 | Univ California | Purification of nucleotide sequences suitable for expression in bacteria |
FR2422717B1 (fr) * | 1977-11-08 | 1985-12-06 | Genentech Inc | Procede permettant l'expression microbienne de polypeptides et moyens appropries |
FI792481A7 (fi) * | 1978-08-11 | 1981-01-01 | The Regents Of The Univ Of | Enkaroyyttisen proteiinin synteesi mikro-organismia käyttäen. |
US6297355B1 (en) | 1978-12-22 | 2001-10-02 | Biogen, Inc. | Polypeptides displaying HBV antigenicity or hbv antigen specificity |
JPS55150883A (en) * | 1979-05-11 | 1980-11-25 | Nakano Vinegar Co Ltd | Method of storing "mozuku" |
GR68404B (enrdf_load_stackoverflow) * | 1979-06-01 | 1981-12-29 | Univ California | |
FR2458584A1 (fr) * | 1979-06-08 | 1981-01-02 | Pasteur Institut | Vecteurs pour le transfert et l'expression de materiel genetique dans une cellule eucaryote et procede pour la production d'une proteine determinee dans des cellules eucaryotes |
US4342832A (en) * | 1979-07-05 | 1982-08-03 | Genentech, Inc. | Method of constructing a replicable cloning vehicle having quasi-synthetic genes |
GR70279B (enrdf_load_stackoverflow) * | 1979-09-12 | 1982-09-03 | Univ California | |
IL58765A (en) * | 1979-11-21 | 1986-09-30 | Yeda Res & Dev | Process for the production of essentially pure messenger rna of human fibroblast interferon and process for the production of interferon beta |
DE3001928A1 (de) * | 1980-01-19 | 1981-08-06 | Hoechst Ag, 6000 Frankfurt | Genprodukt eines hoeheren organismus aus einem dieses gen enthaltenden mikroorganismus |
IL61982A (en) * | 1980-02-15 | 1984-01-31 | Cpc International Inc | Genetically engineered microorganisms for massive production of amyloytic enzymes and process for preparing same using the corresponding recombinant dnas containing amylase coding genes |
US4350764A (en) * | 1980-03-10 | 1982-09-21 | The Regents Of The University Of California | Microbiological synthesis of beta endorphin |
CA1202581A (en) * | 1980-03-27 | 1986-04-01 | Saran A. Narang | Adaptor molecules for dna and their application to synthesis of gene-derived products |
US4370417A (en) * | 1980-04-03 | 1983-01-25 | Abbott Laboratories | Recombinant deoxyribonucleic acid which codes for plasminogen activator |
US4338397A (en) | 1980-04-11 | 1982-07-06 | President And Fellows Of Harvard College | Mature protein synthesis |
ATE22327T1 (de) * | 1980-12-12 | 1986-10-15 | Unilever Nv | Dna-sequenzen fuer verschiedene allele formen des reifen thaumatins, diese sequenzen enthaltende rekombinante plasmide, verfahren zur herstellung dieser plasmide, diese rekombinante plasmide enthaltende bakterielle kulturen und verfahren zur herstellung von reifen thaumatin. |
DE3177281T2 (de) * | 1980-12-12 | 1992-12-10 | Unilever Nv | Strukturgene, die fuer die verschiedenen allelischen und reifungsformen von praeprothaumatin und deren mutanten kodieren, diese strukturgene enthaltende klonierungsvektoren und deren expression in mikrobiellen wirtzellen. |
US4695543A (en) * | 1982-03-23 | 1987-09-22 | Bristol-Myers Company | Alpha Interferon GX-1 |
US4748233A (en) * | 1982-03-23 | 1988-05-31 | Bristol-Myers Company | Alpha-interferon Gx-1 |
CA1224432A (en) * | 1982-08-17 | 1987-07-21 | Gary N. Buell | Dna sequences, recombinant dna molecules and processes for producing bovine growth hormone-like polypeptides in high yield |
US5474980A (en) * | 1984-10-04 | 1995-12-12 | Monsanto Company | Prolonged release of biologically active somatotropins |
US5411951A (en) * | 1984-10-04 | 1995-05-02 | Monsanto Company | Prolonged release of biologically active somatotropin |
DK257988D0 (da) * | 1988-05-11 | 1988-05-11 | Novo Industri As | Nye peptider |
DE4034702A1 (de) * | 1990-10-31 | 1992-05-07 | Siemens Ag | Verfahren und vorrichtung zur pruefung der aktiven werkzeuge von gesenkbiegemaschinen, insbesondere von biegestempeln |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1521032A (en) * | 1974-08-08 | 1978-08-09 | Ici Ltd | Biological treatment |
-
1978
- 1978-05-17 NZ NZ187300A patent/NZ187300A/xx unknown
- 1978-05-23 NL NL7805591A patent/NL7805591A/ not_active Application Discontinuation
- 1978-05-23 AR AR272286A patent/AR225404A1/es active
- 1978-05-23 GR GR56309A patent/GR73552B/el unknown
- 1978-05-24 DE DE19782822568 patent/DE2822568A1/de active Granted
- 1978-05-24 BE BE187995A patent/BE867424A/xx not_active IP Right Cessation
- 1978-05-24 PT PT68082A patent/PT68082B/pt unknown
- 1978-05-24 DE DE2858357A patent/DE2858357C2/de not_active Expired - Lifetime
- 1978-05-25 AU AU36488/78A patent/AU521903B2/en not_active Expired
- 1978-05-25 DD DD78205588A patent/DD145927A5/de unknown
- 1978-05-25 FR FR7815596A patent/FR2392033B1/fr not_active Expired
- 1978-05-25 GB GB22417/78A patent/GB1565190A/en not_active Expired
- 1978-05-26 LU LU79714A patent/LU79714A1/xx unknown
- 1978-05-26 IL IL54790A patent/IL54790A/xx unknown
- 1978-05-26 CH CH581078A patent/CH642680A5/de not_active IP Right Cessation
- 1978-05-26 FI FI781675A patent/FI64640C/fi not_active IP Right Cessation
- 1978-05-26 SE SE7806086A patent/SE451461B/xx unknown
- 1978-05-26 DK DK782332A patent/DK233278A/da not_active Application Discontinuation
- 1978-05-27 JP JP53063756A patent/JPH0659218B2/ja not_active Expired - Lifetime
- 1978-05-27 BG BG039878A patent/BG40319A3/xx unknown
- 1978-05-27 PL PL1978207176A patent/PL140200B1/pl unknown
- 1978-05-29 IT IT23930/78A patent/IT1094934B/it active
-
1983
- 1983-09-29 SE SE8305328A patent/SE8305328L/sv not_active Application Discontinuation
- 1983-09-29 SE SE8305329A patent/SE455794B/sv not_active Application Discontinuation
- 1983-09-29 SE SE8305327A patent/SE8305327D0/xx not_active Application Discontinuation
-
1991
- 1991-01-04 DK DK000791A patent/DK791D0/da not_active Application Discontinuation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
FI64640C (fi) | Foerfarande foer framstaellning av en kombinations-dna-molekylsom innehaoller en foer insulin kodande nukleotidsekvens hocsom kan anvaendas vid framstaellning av en insulin produ rcende mikroorganism | |
US4440859A (en) | Method for producing recombinant bacterial plasmids containing the coding sequences of higher organisms | |
EP0020147B2 (en) | A dna transfer vector for human pre-growth hormone, a microorganism transformed thereby, and a method of cloning therefor | |
US4652525A (en) | Recombinant bacterial plasmids containing the coding sequences of insulin genes | |
CS250655B2 (en) | Method of microorganisme's viable culture's cultivation with means content for asexual regeneration | |
KR920003787B1 (ko) | 신규 플라스미드 제조 및 그를 함유한 균주를 배양하여 아이 지 에프-1(igf-1)을 생산하는 방법 | |
FI86993C (fi) | Foerfarande foer skyddande av en bakterie mot en i naturen foerekommande bakteriofag | |
JP2637393B2 (ja) | プロインシュリンおよびプレプロインシュリン産生暗号を有するヒト遺伝子 | |
EP0259891B1 (en) | [Leu 13] motilin, DNAs coding for same and methods for producing same | |
CS235069B2 (en) | Method of cdna fragment cleaning with specific nucleotide sequence | |
US4447538A (en) | Microorganism containing gene for human chorionic somatomammotropin | |
JPS58201798A (ja) | アルフア−インタ−フエロンGx−1 | |
FI75185C (fi) | Dna-oeverfoeringsvektor, vilken innehaoller en foer insulin kodande nukleotidsekvens. | |
FI65446C (fi) | Foerfarande foer framstaellning av en bakterie som innehaolleren foer insulin kodande nukleotidsekvens | |
FI65447C (fi) | Foerfarande foer framstaellning av en bakterie som innehaolleren foer tillvaexthormon kodande nukleotidsekvens | |
GB2067574A (en) | Microbiologically prepared polypeptide with the amino acid sequence of proinsulin of a primate, DNA and plasmids which code for this sequence, microorganisms which contain this genetic information, and processes for their preparation | |
FI74732B (fi) | Dna-oeverfoeringsvektor, vilken innehaoller en nukleotidsekvens som kodar foer tillvaexthormon. | |
CA1156166A (en) | Recombinant bacterial plasmids containing the coding sequences of insulin genes | |
KR840001441B1 (ko) | 고등생물의 특정 단백질에 대한 뉴클레오티드 배열을 함유하는 dna전달 매개체의 제조방법 | |
SU1205777A3 (ru) | Способ получени вектора,имеющего нуклеотидную последовательность,кодирующую протеин | |
FI68261C (fi) | Foerfarande foer framstaellning av en rekombinations-dna-molekyl vilken har en humant korionsomatomammotropin kodande nukleotidsekvens | |
CS227002B2 (cs) | Způsob výroby vektoru pro přenos DNA | |
IE47274B1 (en) | Recombinant dna transfer vector and micro-organism containing a gene from a higher organism | |
CS227013B2 (cs) | Způsob výroby vektoru pro přenos DNA | |
HU193866B (en) | Process for preparing plasmid and e.coli bakterium comprising dna sequence and coding humane growth hormone |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM | Patent lapsed |
Owner name: THE REGENTS OF THE UNIVERSITY |