CS275613B6 - Process for preparing insulin analogs - Google Patents

Process for preparing insulin analogs Download PDF

Info

Publication number: CS275613B6
Authority: CS; Czechoslovakia
Prior art keywords: asp; glu; human insulin; insulin; ala
Prior art date: 1985-08-30

Application number

CS866310A

Other languages

Czech (cs)

English (en)

Other versions

CS8606310A2 (en

Inventor

Jens Jorgen Veilgaard Brange

Kjeld Norris

Mogens Trier Hansen

Original Assignee

Novo Nordisk As

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1985-08-30

Filing date

1986-08-29

Publication date

1992-03-18

1985-08-30 Priority claimed from DK395685A external-priority patent/DK395685D0/da

1985-10-14 Priority claimed from DK467785A external-priority patent/DK467785D0/da

1986-08-29 Application filed by Novo Nordisk As filed Critical Novo Nordisk As

1990-09-12 Publication of CS8606310A2 publication Critical patent/CS8606310A2/cs

1992-03-18 Publication of CS275613B6 publication Critical patent/CS275613B6/cs

Links

NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class 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 176
238000004519 manufacturing process Methods 0.000 title description 10
PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical class 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 claims abstract description 76
101000976075 Homo sapiens Insulin Proteins 0.000 claims abstract description 53
125000000539 amino acid group Chemical group 0.000 claims abstract description 42
238000002360 preparation method Methods 0.000 claims abstract description 13
150000001413 amino acids Chemical group 0.000 claims abstract description 12
102000004877 Insulin Human genes 0.000 claims description 73
108090001061 Insulin Proteins 0.000 claims description 73
229940125396 insulin Drugs 0.000 claims description 72
238000000034 method Methods 0.000 claims description 37
239000002243 precursor Substances 0.000 claims description 34
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 31
239000004026 insulin derivative Substances 0.000 claims description 16
239000004473 Threonine Substances 0.000 claims description 13
229960002898 threonine Drugs 0.000 claims description 13
-1 threonine ester Chemical class 0.000 claims description 13
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 10
102000004142 Trypsin Human genes 0.000 claims description 9
108090000631 Trypsin Proteins 0.000 claims description 9
229940024606 amino acid Drugs 0.000 claims description 9
239000012588 trypsin Substances 0.000 claims description 9
238000006243 chemical reaction Methods 0.000 claims description 8
230000007062 hydrolysis Effects 0.000 claims description 5
238000006460 hydrolysis reaction Methods 0.000 claims description 5
108090000765 processed proteins & peptides Proteins 0.000 claims description 5
239000011541 reaction mixture Substances 0.000 claims description 5
IASQBRJGRVXNJI-YUMQZZPRSA-N Leu-Cys-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)NCC(O)=O IASQBRJGRVXNJI-YUMQZZPRSA-N 0.000 claims description 4
QCWJKJLNCFEVPQ-WHFBIAKZSA-N Asn-Gln Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O QCWJKJLNCFEVPQ-WHFBIAKZSA-N 0.000 claims description 3
ZOKVLMBYDSIDKG-CSMHCCOUSA-N Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCCN ZOKVLMBYDSIDKG-CSMHCCOUSA-N 0.000 claims description 3
239000007864 aqueous solution Substances 0.000 claims description 3
210000004899 c-terminal region Anatomy 0.000 claims description 3
102100032378 Carboxypeptidase E Human genes 0.000 claims description 2
108010058255 Carboxypeptidase H Proteins 0.000 claims description 2
YXQDRIRSAHTJKM-IMJSIDKUSA-N Cys-Ser Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(O)=O YXQDRIRSAHTJKM-IMJSIDKUSA-N 0.000 claims description 2
FRYULLIZUDQONW-IMJSIDKUSA-N Asp-Asp Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FRYULLIZUDQONW-IMJSIDKUSA-N 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 1
108010040443 aspartyl-aspartic acid Proteins 0.000 claims 1
238000006467 substitution reaction Methods 0.000 abstract description 23
239000000539 dimer Substances 0.000 abstract description 13
229920000642 polymer Polymers 0.000 abstract description 9
230000007935 neutral effect Effects 0.000 abstract description 7
229940123452 Rapid-acting insulin Drugs 0.000 abstract 1
108010026951 Short-Acting Insulin Proteins 0.000 abstract 1
239000013612 plasmid Substances 0.000 description 44
239000012634 fragment Substances 0.000 description 25
108090000623 proteins and genes Proteins 0.000 description 21
239000000203 mixture Substances 0.000 description 20
239000000243 solution Substances 0.000 description 18
230000009466 transformation Effects 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
238000010276 construction Methods 0.000 description 16
240000004808 Saccharomyces cerevisiae Species 0.000 description 15
108020004414 DNA Proteins 0.000 description 12
230000027455 binding Effects 0.000 description 10
230000000694 effects Effects 0.000 description 10
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 8
241000588724 Escherichia coli Species 0.000 description 8
108010076504 Protein Sorting Signals Proteins 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
230000035772 mutation Effects 0.000 description 8
239000000600 sorbitol Substances 0.000 description 8
239000011701 zinc Substances 0.000 description 8
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
239000000047 product Substances 0.000 description 6
239000006228 supernatant Substances 0.000 description 6
238000005119 centrifugation Methods 0.000 description 5
206010012601 diabetes mellitus Diseases 0.000 description 5
102000053602 DNA Human genes 0.000 description 4
108020004682 Single-Stranded DNA Proteins 0.000 description 4
108700005078 Synthetic Genes Proteins 0.000 description 4
238000010521 absorption reaction Methods 0.000 description 4
230000004071 biological effect Effects 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
239000000178 monomer Substances 0.000 description 4
230000002035 prolonged effect Effects 0.000 description 4
238000010254 subcutaneous injection Methods 0.000 description 4
239000007929 subcutaneous injection Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
229920001817 Agar Polymers 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
101710163270 Nuclease Proteins 0.000 description 3
108091028043 Nucleic acid sequence Proteins 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
239000007983 Tris buffer Substances 0.000 description 3
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 3
239000008272 agar Substances 0.000 description 3
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 3
229960000723 ampicillin Drugs 0.000 description 3
238000005571 anion exchange chromatography Methods 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
108010052305 exodeoxyribonuclease III Proteins 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000008103 glucose Substances 0.000 description 3
230000003914 insulin secretion Effects 0.000 description 3
231100000219 mutagenic Toxicity 0.000 description 3
230000003505 mutagenic effect Effects 0.000 description 3
238000000746 purification Methods 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
108020004638 Circular DNA Proteins 0.000 description 2
102000012410 DNA Ligases Human genes 0.000 description 2
108010061982 DNA Ligases Proteins 0.000 description 2
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 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
241001524679 Escherichia virus M13 Species 0.000 description 2
101001027925 Homo sapiens Metastasis-associated protein MTA1 Proteins 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
102000003960 Ligases Human genes 0.000 description 2
108090000364 Ligases Proteins 0.000 description 2
102100037517 Metastasis-associated protein MTA1 Human genes 0.000 description 2
108091034117 Oligonucleotide Proteins 0.000 description 2
238000012300 Sequence Analysis Methods 0.000 description 2
101000993800 Sus scrofa Insulin Proteins 0.000 description 2
PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 2
229940041514 candida albicans extract Drugs 0.000 description 2
238000012512 characterization method Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
230000006240 deamidation Effects 0.000 description 2
230000029087 digestion Effects 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
239000013613 expression plasmid Substances 0.000 description 2
238000000605 extraction Methods 0.000 description 2
239000012467 final product Substances 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
238000009396 hybridization Methods 0.000 description 2
238000001802 infusion Methods 0.000 description 2
RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
239000012528 membrane Substances 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
238000002156 mixing Methods 0.000 description 2
231100000350 mutagenesis Toxicity 0.000 description 2
238000002703 mutagenesis Methods 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
230000003248 secreting effect Effects 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000001509 sodium citrate Substances 0.000 description 2
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000012138 yeast extract Substances 0.000 description 2
BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
FJVAQLJNTSUQPY-CIUDSAMLSA-N Ala-Ala-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN FJVAQLJNTSUQPY-CIUDSAMLSA-N 0.000 description 1
SONUFGRSSMFHFN-IMJSIDKUSA-N Asn-Ser Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(O)=O SONUFGRSSMFHFN-IMJSIDKUSA-N 0.000 description 1
108010023063 Bacto-peptone Proteins 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
206010010071 Coma Diseases 0.000 description 1
230000004568 DNA-binding Effects 0.000 description 1
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
LKDIBBOKUAASNP-FXQIFTODSA-N Glu-Ala-Glu Chemical group OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LKDIBBOKUAASNP-FXQIFTODSA-N 0.000 description 1
108091027305 Heteroduplex Proteins 0.000 description 1
101500025353 Homo sapiens Insulin A chain Proteins 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
108010092217 Long-Acting Insulin Proteins 0.000 description 1
102000016261 Long-Acting Insulin Human genes 0.000 description 1
229940100066 Long-acting insulin Drugs 0.000 description 1
239000001888 Peptone Substances 0.000 description 1
108010080698 Peptones Proteins 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
108010076181 Proinsulin Proteins 0.000 description 1
241000282887 Suidae Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
PNVLWFYAPWAQMU-CIUDSAMLSA-N Val-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)C(C)C PNVLWFYAPWAQMU-CIUDSAMLSA-N 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
239000011543 agarose gel Substances 0.000 description 1
230000000890 antigenic effect Effects 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
239000000872 buffer Substances 0.000 description 1
VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
239000001639 calcium acetate Substances 0.000 description 1
235000011092 calcium acetate Nutrition 0.000 description 1
229960005147 calcium acetate Drugs 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000007979 citrate buffer Substances 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000006471 dimerization reaction Methods 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
238000012869 ethanol precipitation Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
235000013305 food Nutrition 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
239000000499 gel Substances 0.000 description 1
229910002804 graphite Inorganic materials 0.000 description 1
239000010439 graphite Substances 0.000 description 1
238000003505 heat denaturation Methods 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
230000003345 hyperglycaemic effect Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
108010033606 insulin dimers Proteins 0.000 description 1
229950004152 insulin human Drugs 0.000 description 1
210000002660 insulin-secreting cell Anatomy 0.000 description 1
238000011835 investigation Methods 0.000 description 1
238000009630 liquid culture Methods 0.000 description 1
239000008176 lyophilized powder Substances 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
239000002609 medium Substances 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
238000010369 molecular cloning Methods 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
239000008188 pellet Substances 0.000 description 1
235000019319 peptone Nutrition 0.000 description 1
150000008300 phosphoramidites Chemical class 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
238000006116 polymerization reaction Methods 0.000 description 1
239000005373 porous glass Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
239000007261 sc medium Substances 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
229940087562 sodium acetate trihydrate Drugs 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000000844 transformation Methods 0.000 description 1
YZYKBQUWMPUVEN-UHFFFAOYSA-N zafuleptine Chemical compound OC(=O)CCCCCC(C(C)C)NCC1=CC=C(F)C=C1 YZYKBQUWMPUVEN-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—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
- 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
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
- C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Genetics & Genomics (AREA)
Organic Chemistry (AREA)
Zoology (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Molecular Biology (AREA)
Wood Science & Technology (AREA)
Biomedical Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
Mycology (AREA)
General Engineering & Computer Science (AREA)
Biotechnology (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Toxicology (AREA)
Gastroenterology & Hepatology (AREA)
Medicinal Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Physics & Mathematics (AREA)
Plant Pathology (AREA)
Microbiology (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

CS866310A 1985-08-30 1986-08-29 Process for preparing insulin analogs CS275613B6 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DK395685A DK395685D0 (da)	1985-08-30	1985-08-30	Peptider
DK467785A DK467785D0 (da)	1985-10-14	1985-10-14	Peptider

Publications (2)

Publication Number	Publication Date
CS8606310A2 CS8606310A2 (en)	1990-09-12
CS275613B6 true CS275613B6 (en)	1992-03-18

Family

ID=26067291

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS866310A CS275613B6 (en)	1985-08-30	1986-08-29	Process for preparing insulin analogs

Country Status (25)

Country	Link
US (1)	US5618913A (fr)
EP (1)	EP0214826B1 (fr)
JP (1)	JP2662390B2 (fr)
KR (1)	KR940000756B1 (fr)
CN (1)	CN1029977C (fr)
AR (1)	AR241801A1 (fr)
AT (1)	ATE113061T1 (fr)
AU (1)	AU593274B2 (fr)
CA (1)	CA1306212C (fr)
CS (1)	CS275613B6 (fr)
DD (1)	DD268976A5 (fr)
DE (2)	DE10075008I2 (fr)
ES (1)	ES2001624A6 (fr)
FI (1)	FI102182B (fr)
GR (1)	GR862233B (fr)
HU (1)	HU206518B (fr)
IE (1)	IE66138B1 (fr)
IL (1)	IL79887A (fr)
LU (1)	LU90484I2 (fr)
NL (1)	NL990042I2 (fr)
NO (2)	NO177009C (fr)
NZ (1)	NZ217406A (fr)
PH (1)	PH25772A (fr)
PT (1)	PT83278B (fr)
YU (2)	YU46023B (fr)

Families Citing this family (221)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK437786D0 (da) *	1986-09-12	1986-09-12	Nordisk Gentofte	Insulinprecursorer
ES2053723T3 (es) *	1987-02-25	1994-08-01	Novo Nordisk As	Nuevos derivados de insulina.
US4992418A (en) *	1987-07-17	1991-02-12	Mount Sinai School Of Medicine	Superactive human insulin analogue-[10-Aspartic Acid-B]Human Insulin
US4992417A (en) *	1987-07-17	1991-02-12	Mount Sinai School Of Medicine	Superactive human insulin analogues
CA1340772C (fr)	1987-12-30	1999-09-28	Patricia Tekamp-Olson	Expression et secretion de proteines heterologues dans une levure au moyen de sequences leader tronquees du facteur alpha
WO1990001038A1 (fr) *	1988-07-20	1990-02-08	Nordisk Gentofte A/S	Analogues d'insuline humaine et preparations les contenant
DE3837825A1 (de) *	1988-11-08	1990-05-10	Hoechst Ag	Neue insulinderivate, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung
US5716927A (en) *	1988-12-23	1998-02-10	Novo Nordisk A/S	Insulin analogs having a modified B-chain
HUT56857A (en) *	1988-12-23	1991-10-28	Novo Nordisk As	Human insulin analogues
US5514646A (en) *	1989-02-09	1996-05-07	Chance; Ronald E.	Insulin analogs modified at position 29 of the B chain
FI914898A0 (fi) *	1989-04-20	1991-10-17	Sinai School Medicine	Leverspecifika insulinanaloger.
US5208217A (en) *	1989-04-20	1993-05-04	Mount Sinai School Of Medicine Of The City University Of New York	Hepatospecific insulin analogues
DK155690D0 (da) *	1990-06-28	1990-06-28	Novo Nordisk As	Nye peptider
DK158390D0 (da) *	1990-07-02	1990-07-02	Novo Nordisk As	Nye peptider
DK10191D0 (da) *	1991-01-22	1991-01-22	Novo Nordisk As	Hidtil ukendte peptider
DK33591D0 (fr) *	1991-02-27	1991-02-27	Novo Nordisk As
IL102240A0 (en) *	1991-06-21	1993-01-14	Lilly Co Eli	Insulin analogs
CA2151134A1 (fr) *	1992-12-18	1994-07-07	Ronald Eugene Chance	Analogues de l'insuline
EP0705275B1 (fr) *	1993-06-21	1999-02-03	Novo Nordisk A/S	Cristaux d'insuline asp-b28
DK72793D0 (da) *	1993-06-21	1993-06-21	Novo Nordisk As	Nyt produkt
US5461031A (en) *	1994-06-16	1995-10-24	Eli Lilly And Company	Monomeric insulin analog formulations
US5474978A (en) *	1994-06-16	1995-12-12	Eli Lilly And Company	Insulin analog formulations
US5504188A (en) *	1994-06-16	1996-04-02	Eli Lilly And Company	Preparation of stable zinc insulin analog crystals
US5547929A (en)	1994-09-12	1996-08-20	Eli Lilly And Company	Insulin analog formulations
WO1996010417A1 (fr) *	1994-10-04	1996-04-11	Novo Nordisk A/S	Preparations contenant l'insuline humaine aspb28 et du nicotinamide
US5597893A (en) *	1994-10-31	1997-01-28	Eli Lilly And Company	Preparation of stable insulin analog crystals
US5693609A (en) *	1994-11-17	1997-12-02	Eli Lilly And Company	Acylated insulin analogs
US5646242A (en) *	1994-11-17	1997-07-08	Eli Lilly And Company	Selective acylation of epsilon-amino groups
AR002976A1 (es) *	1995-03-31	1998-05-27	Lilly Co Eli	Formulaciones farmaceuticas parenterales de efecto prolongado de insulina; cristales de dichos analogos aplicables en dichas formulaciones yprocedimiento de las formulaciones mencionadas
US5700904A (en) *	1995-06-07	1997-12-23	Eli Lilly And Company	Preparation of an acylated protein powder
US5631347A (en) *	1995-06-07	1997-05-20	Eli Lilly And Company	Reducing gelation of a fatty acid-acylated protein
HU228094B1 (en) *	1996-06-20	2012-10-29	Novo Nordisk As	Insulin preparations containing nacl
AR012894A1 (es) *	1997-06-13	2000-11-22	Lilly Co Eli	Formulacion de insulina en solucion estable, su uso para preparar un medicamento y proceso para la preparacion de la misma.
DE19726167B4 (de)	1997-06-20	2008-01-24	Sanofi-Aventis Deutschland Gmbh	Insulin, Verfahren zu seiner Herstellung und es enthaltende pharmazeutische Zubereitung
HUP0004169A3 (en)	1997-10-24	2001-06-28	Lilly Co Eli	Insoluble insulin compositions and process for production thereof
CO4970787A1 (es) *	1997-12-23	2000-11-07	Lilly Co Eli	Composiciones insolubles de insulina y derivados de insulina que controlan la glucosa sanguinea
CN1241942C (zh) *	1998-02-23	2006-02-15	纽罗克里恩生物科学有限公司	使用胰岛素的肽类似物治疗糖尿病的方法
DE19825447A1 (de) *	1998-06-06	1999-12-09	Hoechst Marion Roussel De Gmbh	Neue Insulinanaloga mit erhöhter Zinkbildung
AUPP609198A0 (en) *	1998-09-22	1998-10-15	Curtin University Of Technology	Use of non-peptidyl compounds for the treatment of insulin related ailments
US6933272B1 (en)	1998-09-22	2005-08-23	Erik Helmerhorst	Use of non-peptidyl compounds for the treatment of insulin related ailments
ES2329220T3 (es)	1999-01-06	2009-11-24	Genentech, Inc.	Variantes mutantes del factor de crecimiento similar a insulina (igf) i.
AU762351B2 (en)	1999-01-06	2003-06-26	Genentech Inc.	Insulin-like growth factor (IGF) I mutant variants
US6746853B1 (en) *	1999-05-19	2004-06-08	Xencor, Inc.	Proteins with insulin-like activity useful in the treatment of diabetes
CN1125081C (zh) *	1999-09-08	2003-10-22	中国科学院上海生物化学研究所	重组天然和新型人胰岛素及其制备方法
US7022674B2 (en) *	1999-12-16	2006-04-04	Eli Lilly And Company	Polypeptide compositions with improved stability
AU4935701A (en)	2000-03-24	2001-10-08	Genentech Inc	Use of insulin for the treatment of cartilagenous disorders
EP1292324A2 (fr) *	2000-05-05	2003-03-19	Novo Nordisk A/S	Neurophaties en maladies graves
AU2001263215A1 (en)	2000-05-16	2001-11-26	Genentech Inc.	Method for treating cartilage disorders
AR025646A1 (es) *	2000-09-13	2002-12-04	Beta Lab Sa	Cepa de levaduras metilotroficas recombinantes productoras de un precursor de insulina, construcciones de adn y metodo para obtener la cepa.
US7638618B2 (en)	2001-02-20	2009-12-29	Sanofi-Aventis Deutschland Gmbh	Nucleic acids encoding a hirudin and pro-insulin as superscretable peptides and for parallel improvement of the exported forms of one or more polypeptides of interest
US7202059B2 (en)	2001-02-20	2007-04-10	Sanofi-Aventis Deutschland Gmbh	Fusion proteins capable of being secreted into a fermentation medium
DE10114178A1 (de)	2001-03-23	2002-10-10	Aventis Pharma Gmbh	Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität
WO2003031432A1 (fr)	2001-10-12	2003-04-17	Novo Nordisk A/S	Nouvelles piperidines substituees
CA2464616C (fr)	2001-11-19	2012-07-24	Are Bogsnes	Elaboration de composes insuliniques
GB0206792D0 (en)	2002-03-22	2002-05-01	Leuven K U Res & Dev	Normoglycemia
DE10227232A1 (de)	2002-06-18	2004-01-15	Aventis Pharma Deutschland Gmbh	Saure Insulinzubereitungen mit verbesserter Stabilität
US7193035B2 (en)	2002-10-29	2007-03-20	Sanofi-Aventis Deutschland Gmbh	Crystals of insulin analogs and processes for their preparation
US7871607B2 (en) *	2003-03-05	2011-01-18	Halozyme, Inc.	Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases
DE602004027171D1 (de)	2003-04-11	2010-06-24	High Point Pharmaceuticals Llc	Verbindungen mit Aktivität an der 11Beta-Hydroxasteroiddehydrogenase
WO2005000580A1 (fr)	2003-06-27	2005-01-06	Novo Nordisk A/S	Contenant a fort effet de barriere contre l'humidite pour compositions medicales liquides
US20060183667A1 (en) *	2003-07-11	2006-08-17	Novo Nordisk A/S	Stabilised insulin compositions
EP1644411A2 (fr) *	2003-07-11	2006-04-12	Novo Nordisk A/S	Compositions d'insuline stabilisee
SI1648933T1 (sl) *	2003-07-25	2010-01-29	Conjuchem Biotechnologies Inc	Dolgo delujoäś inzulinski derivat in metoda zanj
AU2004261353B2 (en)	2003-08-05	2009-12-10	Novo Nordisk A/S	Novel insulin derivatives
ES2472421T3 (es)	2003-08-05	2014-07-01	Novo Nordisk A/S	Nuevos derivados de insulina
JP4800959B2 (ja) *	2003-11-13	2011-10-26	ノヴォノルディスクアー／エス	糖尿病及び過食症を治療するためのｇｌｐ−１ペプチド及び短時間作用型インスリンペプチドを含む、非経口投与用の可溶性医薬組成物
US20060287221A1 (en)	2003-11-13	2006-12-21	Novo Nordisk A/S	Soluble pharmaceutical compositions for parenteral administration comprising a GLP-1 peptide and an insulin peptide of short time action for treatment of diabetes and bulimia
KR101243648B1 (ko)	2003-11-20	2013-03-14	노보 노르디스크 에이/에스	제조 및 주사 장치용에 최적인 프로필렌 글리콜 함유펩티드 제제
ES2369895T3 (es)	2003-12-03	2011-12-07	Novo Nordisk A/S	Insulina monocatenaria.
DE602004029496D1 (de)	2003-12-22	2010-11-18	Novo Nordisk As	Offbehälter zur lagerung von pharmazeutischen flüssigkeiten
EP2033662B1 (fr)	2004-01-21	2012-10-17	Novo Nordisk Health Care AG	Conjugaison de peptides induite par la transglutaminase.
CN101027318B (zh)	2004-07-19	2016-05-25	比奥孔有限公司	胰岛素-低聚物共轭物，制剂及其用途
KR101284944B1 (ko)	2004-11-04	2013-07-15	헌터더글라스인코포레이티드	건축물 개방구용의 단일 트랙의 스태킹 패널 커버링
US7833513B2 (en)	2004-12-03	2010-11-16	Rhode Island Hospital	Treatment of Alzheimer's Disease
ES2435522T3 (es)	2005-02-02	2013-12-20	Novo Nordisk A/S	Derivados de insulina
WO2006082204A1 (fr)	2005-02-02	2006-08-10	Novo Nordisk A/S	Derives d'insuline
CN103110635A (zh)	2005-07-04	2013-05-22	海波因特制药有限责任公司	组胺h3受体拮抗剂
ES2426345T3 (es)	2005-07-20	2013-10-22	Eli Lilly And Company	Compuesto unidos en posición 1-amino
ATE513921T1 (de)	2005-08-16	2011-07-15	Novo Nordisk As	Verfahren zur herstellung reifer insulinpolypeptide
ATE517919T1 (de)	2005-09-14	2011-08-15	Sanofi Aventis Deutschland	Spaltung von insulinvorstufen durch eine trypsinvariante
CN101312940B (zh)	2005-11-17	2012-11-14	伊莱利利公司	胰高血糖素受体拮抗剂、制备和治疗用途
EP1969004B1 (fr)	2005-12-28	2011-08-10	Novo Nordisk A/S	Compositions renfermant une insuline acylée et du zinc et procédé de fabrication des dites compositions
US8343914B2 (en) *	2006-01-06	2013-01-01	Case Western Reserve University	Fibrillation resistant proteins
WO2007096332A1 (fr) *	2006-02-21	2007-08-30	Novo Nordisk A/S	Analogues d'insuline à chaîne unique et formules pharmaceutiques contenant lesdits analogues
JP5202338B2 (ja)	2006-02-27	2013-06-05	ノボ・ノルデイスク・エー／エス	新規インシュリン誘導体
EP2241327A1 (fr)	2006-03-15	2010-10-20	Novo Nordisk A/S	Melange d'amyline et d'insuline
NZ570524A (en)	2006-03-28	2011-08-26	High Point Pharmaceuticals Llc	Benzothiazoles having histamine H3 receptor activity
ATE543798T1 (de)	2006-04-24	2012-02-15	Lilly Co Eli	Cyclohexyl-substituierte pyrrolidinone als hemmer von 11-beta-hydroxysteroiddehydrogenase 1
WO2007128815A1 (fr)	2006-05-09	2007-11-15	Novo Nordisk A/S	Dérivé insulinique
AU2007247109B2 (en)	2006-05-09	2012-03-15	Novo Nordisk A/S	Insulin derivative
ATE538116T1 (de)	2006-05-29	2012-01-15	High Point Pharmaceuticals Llc	3-(1,3-benyodioxol-5-yl)-6- (4- cyclopropylpiperazin-1-yl)-pyridazin, dessen salze und solvate und dessen verwendung als histamin-h3-rezeptorantagonist
WO2007140619A1 (fr) *	2006-06-08	2007-12-13	Diabecore Medical Inc.	Oligomères d'insuline dérivés
DE102006031955A1 (de) *	2006-07-11	2008-01-17	Sanofi-Aventis Deutschland Gmbh	Verfahren zur Herstellung von Insulinanaloga mit dibasischem B-Kettenende
DE102006031962A1 (de)	2006-07-11	2008-01-17	Sanofi-Aventis Deutschland Gmbh	Amidiertes Insulin Glargin
CN101573133B (zh)	2006-07-31	2014-08-27	诺沃-诺迪斯克有限公司	Peg化延长的胰岛素
CN101541830A (zh) *	2006-09-22	2009-09-23	诺沃-诺迪斯克有限公司	蛋白酶抗性的胰岛素类似物
EP2074140B8 (fr) *	2006-10-04	2015-10-28	Case Western Reserve University	Insuline et analogues de l'insuline résistants à la fibrillation
WO2008049711A1 (fr) *	2006-10-27	2008-05-02	Novo Nordisk A/S	Insuline à peptide ajouté
US20120214963A1 (en) *	2011-02-23	2012-08-23	Elona Biotechnologies	Aspart proinsulin compositions and methods of producing aspart insulin analogs therefrom
US10100098B2 (en)	2006-12-13	2018-10-16	Stelis Biopharma Private Limited	Insulin production methods and proinsulin constructs
WO2008132224A2 (fr)	2007-04-30	2008-11-06	Novo Nordisk A/S	Procédé de déshydratation d'une composition de protéine, composition de protéine déshydratée et composition pharmaceutique contenant la protéine déshydratée
WO2008139496A1 (fr) *	2007-05-16	2008-11-20	Bigtec Private Limited	Insuline humaine de recombinaison et méthode associée
AU2008257505B2 (en)	2007-06-01	2013-05-16	Novo Nordisk A/S	Stable non-aqueous pharmaceutical compositions
EP2514406A1 (fr)	2007-06-01	2012-10-24	Novo Nordisk A/S	Préconcentrés spontanément dispersibles comprenant un médicament peptidique dans un support solide ou semi-solide
JP5552046B2 (ja)	2007-06-13	2014-07-16	ノボ・ノルデイスク・エー／エス	インスリン誘導体を含有する薬学的製剤
CN101796071A (zh) *	2007-08-13	2010-08-04	诺沃-诺迪斯克有限公司	快速作用的胰岛素类似物
US8575096B2 (en)	2007-08-13	2013-11-05	Novo Nordisk A/S	Rapid acting insulin analogues
AU2008288413B2 (en)	2007-08-15	2013-09-26	Novo Nordisk A/S	Insulin analogues with an acyl and aklylene glycol moiety
WO2009022006A1 (fr)	2007-08-15	2009-02-19	Novo Nordisk A/S	Insulines avec une fraction acyle comprenant des unités répétitives d'alkylène glycol contenant des acides aminés
CA2703830A1 (fr)	2007-11-20	2009-05-28	Ambrx, Inc.	Polypeptides d'insuline modifies et leurs utilisations
RU2524423C2 (ru)	2008-01-09	2014-07-27	Санофи-Авентис Дойчланд Гмбх	Новые производные инсулина с чрезвычайно замедленным профилем время/действие
HUE032284T2 (en)	2008-03-18	2017-09-28	Novo Nordisk As	Protease-stabilized, acylated insulin analogues
EP2262539B1 (fr)	2008-04-01	2015-07-15	Novo Nordisk A/S	Conjugués insuline-albumine
WO2009129250A2 (fr) *	2008-04-14	2009-10-22	Case Western Reserve University	Analogues de l'insuline à prendre au moment des repas de stabilité améliorée
AU2009240636A1 (en) *	2008-04-22	2009-10-29	Case Western Reserve University	Isoform-specific insulin analogues
TWI394580B (zh)	2008-04-28	2013-05-01	Halozyme Inc	超快起作用胰島素組成物
TWI451876B (zh)	2008-06-13	2014-09-11	Lilly Co Eli	聚乙二醇化之離脯胰島素化合物
KR20120129875A (ko)	2008-07-31	2012-11-28	케이스 웨스턴 리저브 유니버시티	염소화 아미노산을 갖는 인슐린 유사체
US9200053B2 (en)	2008-07-31	2015-12-01	Case Western Reserve University	Insulin analogues containing penta-fluoro-Phenylalanine at position B24
ES2570937T3 (es)	2008-08-07	2016-05-23	Biocon Ltd	Un proceso para la preparación de compuestos de insulina
DE102008051834A1 (de)	2008-10-17	2010-04-22	Sanofi-Aventis Deutschland Gmbh	Kombination von einem Insulin und einem GLP-1-Agonisten
PT3228320T (pt)	2008-10-17	2020-03-26	Sanofi Aventis Deutschland	Combinação de uma insulina e de um agonista do glp-1
DE102008053048A1 (de)	2008-10-24	2010-04-29	Sanofi-Aventis Deutschland Gmbh	Kombination von einem Insulin und einem GLP-1-Agonisten
DE102009038210A1 (de)	2009-08-20	2011-03-03	Sanofi-Aventis Deutschland Gmbh	Kombination von einem Insulin und einem GLP-1-Agonisten
CN102202683A (zh)	2008-10-30	2011-09-28	诺沃-诺迪斯克有限公司	用少于每日一次的注射频率注射胰岛素来治疗糖尿病
BRPI0921299A2 (pt)	2008-11-21	2015-08-25	High Point Pharmaceuticals Llc	Compostos de benzamida adamantila
US9018190B2 (en)	2009-03-27	2015-04-28	Adocia	Functionalized oligosaccharides
FR2943538B1 (fr)	2009-03-27	2011-05-20	Adocia	Formulation a action rapide d'insuline recombinante humaine
PH12011502708B1 (en)	2009-07-06	2017-11-10	Sanofi Aventis Deutschland	Insulin preparations containing methionine
WO2011003820A1 (fr)	2009-07-06	2011-01-13	Sanofi-Aventis Deutschland Gmbh	Préparations d'insuline stables à la chaleur et aux agitations
EP2451471A1 (fr)	2009-07-06	2012-05-16	Sanofi-Aventis Deutschland GmbH	Préparations d'insuline à effet retard
DK2459171T3 (en)	2009-07-31	2017-09-25	Sanofi Aventis Deutschland	Long-acting insulin composition
KR20120089843A (ko)	2009-07-31	2012-08-14	사노피-아벤티스 도이칠란트 게엠베하	인슐린 링커 접합체를 포함한 프로드럭
US8399407B2 (en) *	2009-09-17	2013-03-19	Case Western Reserve University	Non-standard insulin analogues
SG10201500871TA (en)	2009-11-13	2015-04-29	Sanofi Aventis Deutschland	Pharmaceutical composition comprising a glp-1 agonist and methionine
JP5832439B2 (ja)	2009-11-13	2015-12-16	サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング	Ｇｌｐ−１アゴニスト、インスリン及びメチオニンを含む薬学的組成物
US8637096B2 (en)	2009-12-04	2014-01-28	Curtis C. Stojan	Compositions and method for enhancing insulin activity
RU2012123642A (ru)	2009-12-11	2014-01-20	Кейз Вестерн Ризев Юнивесити	Аналоги инсулина, содержащие хлорированные аминокислоты
EP2460527A1 (fr)	2010-01-21	2012-06-06	Sanofi	Composition pharmaceutique pour le traitement d'un syndrome métabolique
TW201141513A (en)	2010-04-14	2011-12-01	Sanofi Aventis	Insulin-siRNA conjugates
AU2011252127B2 (en) *	2010-05-10	2014-02-20	Novo Nordisk A/S	Process for the preparation of insulin-zinc complexes
JP5969469B2 (ja)	2010-06-16	2016-08-17	インディアナユニバーシティーリサーチアンドテクノロジーコーポレーションＩｎｄｉａｎａＵｎｉｖｅｒｓｉｔｙＲｅｓｅａｒｃｈＡｎｄＴｅｃｈｎｏｌｏｇｙＣｏｒｐｏｒａｔｉｏｎ	インスリン受容体に対して高い活性を示す単鎖インスリンアゴニスト
CA2802510A1 (fr)	2010-06-23	2011-12-29	Novo Nordisk A/S	Derives d'insuline contenant des liaisons disulfure supplementaires
PE20140160A1 (es)	2010-08-17	2014-02-08	Ambrx Inc	Polipeptidos de relaxina modificados y sus usos
CN103179978A (zh)	2010-08-30	2013-06-26	赛诺菲-安万特德国有限公司	Ave0010用于制造供治疗2型糖尿病用的药物的用途
EP2438930A1 (fr)	2010-09-17	2012-04-11	Sanofi-Aventis Deutschland GmbH	Promédicaments comprenant un conjugué de liaison d'exendine
DK2632478T3 (da)	2010-10-27	2019-10-07	Novo Nordisk As	Behandling af diabetes melitus under anvendelse af insulinindsprøjtninger indgivet med varierende indsprøjtningsintervaller
KR20130139297A (ko)	2010-10-27	2013-12-20	노보 노르디스크 에이/에스	다양한 주사 간격으로 투여된 인슐린 주사를 이용한 진성 당뇨병의 치료
WO2012080320A1 (fr)	2010-12-14	2012-06-21	Novo Nordisk A/S	Insuline à action rapide en combinaison avec une insuline à longue durée d'action
AU2012213432B2 (en) *	2011-02-01	2016-10-13	Novo Nordisk A/S	Purification of insulin
WO2012104834A1 (fr)	2011-02-03	2012-08-09	Pharmedica Ltd.	Nouveaux films à dissolution orale pour administration d'insuline, pour traitement du diabète
WO2012115637A1 (fr) *	2011-02-23	2012-08-30	Elona Biotechnologies	Compositions de pro-insuline aspart et procédés de production d'analogues de l'insuline aspart
WO2012115638A1 (fr)	2011-02-23	2012-08-30	Elona Biotechnologies	Compositions de pro-insuline glargine et procédés de production d'analogues de l'insuline glargine à partir de celles-ci
CN103533952B (zh)	2011-03-15	2017-02-15	诺沃—诺迪斯克有限公司	包含半胱氨酸置换的人胰岛素类似物和衍生物
US9821032B2 (en)	2011-05-13	2017-11-21	Sanofi-Aventis Deutschland Gmbh	Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin
US9993529B2 (en)	2011-06-17	2018-06-12	Halozyme, Inc.	Stable formulations of a hyaluronan-degrading enzyme
EP2548570A1 (fr)	2011-07-19	2013-01-23	Sanofi	Composition pharmaceutique pour le traitement d'un syndrome métabolique
JP6367115B2 (ja)	2011-08-29	2018-08-01	サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング	２型糖尿病患者の血糖コントロールに使用する組合せ医薬
TWI559929B (en)	2011-09-01	2016-12-01	Sanofi Aventis Deutschland	Pharmaceutical composition for use in the treatment of a neurodegenerative disease
US20130231281A1 (en)	2011-11-02	2013-09-05	Adocia	Rapid acting insulin formulation comprising an oligosaccharide
CN104788556A (zh) *	2011-12-15	2015-07-22	上海恒瑞医药有限公司	人胰岛素类似物及其酰化衍生物
CN104114183A (zh)	2011-12-20	2014-10-22	印第安纳大学研究及科技有限公司	用于治疗糖尿病的基于ctp的胰岛素类似物
EP2836508B1 (fr)	2012-04-11	2016-06-29	Novo Nordisk A/S	Formulations à base d'insuline
EP2844274B1 (fr)	2012-05-01	2019-03-20	Novo Nordisk A/S	Composition pharmaceutique
US20130315891A1 (en)	2012-05-25	2013-11-28	Matthew Charles	Formulations of human tissue kallikrein-1 for parenteral delivery and related methods
US20130323222A1 (en)	2012-06-04	2013-12-05	Matthew Charles	Human tissue kallikrein 1 glycosylation isoforms
CN108383902A (zh)	2012-09-26	2018-08-10	印第安纳大学研究及科技有限公司	胰岛素类似物二聚体
EP2919804B1 (fr)	2012-11-13	2018-01-31	Adocia	Formulation à action rapide d'insuline comprenant un composé anionique substitué
EP2925345B1 (fr)	2012-12-03	2018-09-05	Merck Sharp & Dohme Corp.	Méthode de préparation d'insuline et d'analogues d'insuline à base du peptide de la partie terminale carboxy (ctp) o-glycosylé
US9867869B2 (en)	2012-12-12	2018-01-16	Massachusetts Institute Of Technology	Insulin derivatives for diabetes treatment
MX360420B (es)	2012-12-19	2018-10-31	Wockhardt Ltd	Una composicion acuosa estable que comprende insulina humana o un analogo o derivado de la misma.
MX2015006997A (es)	2012-12-26	2015-09-23	Wockhardt Ltd	Composicion farmaceutica.
TWI780236B (zh)	2013-02-04	2022-10-11	法商賽諾菲公司	胰島素類似物及/或胰島素衍生物之穩定化醫藥調配物
JP6538645B2 (ja)	2013-03-14	2019-07-03	インディアナユニバーシティーリサーチアンドテクノロジーコーポレーションＩｎｄｉａｎａＵｎｉｖｅｒｓｉｔｙＲｅｓｅａｒｃｈＡｎｄＴｅｃｈｎｏｌｏｇｙＣｏｒｐｏｒａｔｉｏｎ	インスリン‐インクレチン複合物
EP2991672A1 (fr)	2013-04-30	2016-03-09	Novo Nordisk A/S	Schéma d'administration d'un nouveau type
EP3052114A1 (fr)	2013-09-30	2016-08-10	Wockhardt Limited	Composition pharmaceutique
CA2926701A1 (fr)	2013-10-07	2015-04-16	Novo Nordisk A/S	Nouveau derive d'un analogue de l'insuline
JP6641280B2 (ja)	2014-01-09	2020-02-05	サノフイＳａｎｏｆｉ	インスリンアナログおよび／またはインスリン誘導体の安定化された医薬製剤
CA2932873A1 (fr)	2014-01-09	2015-07-16	Sanofi	Formulations pharmaceutiques stabilisees d'insuline asparte
KR20160104726A (ko)	2014-01-09	2016-09-05	사노피	인슐린 유사체 및/또는 인슐린 유도체의 안정화된 무글리세롤 약제학적 제형
FR3020947B1 (fr)	2014-05-14	2018-08-31	Adocia	Composition aqueuse comprenant au moins une proteine et un agent solubilisant, sa preparation et ses utilisations
US9795678B2 (en)	2014-05-14	2017-10-24	Adocia	Fast-acting insulin composition comprising a substituted anionic compound and a polyanionic compound
WO2015196174A1 (fr)	2014-06-20	2015-12-23	Greene Howard E	Dispositifs et procédés d'administration de perfusion
WO2016001862A1 (fr)	2014-07-04	2016-01-07	Wockhardt Limited	Formulations à libération prolongée d'insulines
CN108271356A (zh)	2014-09-24	2018-07-10	印第安纳大学研究及科技有限公司	肠降血糖素-胰岛素缀合物
AU2015328222B9 (en)	2014-10-06	2020-12-24	Case Western Reserve University	Biphasic single-chain insulin analogues
AU2015349890B2 (en)	2014-11-21	2018-08-30	Merck Sharp & Dohme Llc	Insulin receptor partial agonists
CN107206058A (zh)	2014-12-12	2017-09-26	赛诺菲-安万特德国有限公司	甘精胰岛素/利西拉来固定比率配制剂
AR102869A1 (es)	2014-12-16	2017-03-29	Lilly Co Eli	Composiciones de insulina de rápida acción
CN105884879A (zh) *	2015-01-26	2016-08-24	漳州博欣生物技术有限公司	一种胰岛素类似物的化学合成方法
TWI748945B (zh)	2015-03-13	2021-12-11	德商賽諾菲阿凡提斯德意志有限公司	第２型糖尿病病患治療
TW201705975A (zh)	2015-03-18	2017-02-16	賽諾菲阿凡提斯德意志有限公司	第２型糖尿病病患之治療
BR112018002416A2 (pt)	2015-08-25	2018-09-18	Novo Nordisk As	derivados de insulina e seus usos médicos
JO3749B1 (ar)	2015-08-27	2021-01-31	Lilly Co Eli	تركيبات إنسولين سريعة المفعول
FR3043557B1 (fr)	2015-11-16	2019-05-31	Adocia	Composition a action rapide d'insuline comprenant un citrate substitue
US20190142963A1 (en)	2016-04-15	2019-05-16	Richard D. DiMarchi	Fgf21 c-terminal peptide optimization
GB201607918D0 (en)	2016-05-06	2016-06-22	Arecor Ltd	Novel formulations
WO2017205191A1 (fr)	2016-05-24	2017-11-30	Merck Sharp & Dohme Corp.	Agonistes partiels du récepteur de l'insuline et analogues du glp-1
US10689430B2 (en)	2016-05-25	2020-06-23	Merck Sharp & Dohme Corp.	Insulin receptor partial agonists
US10815287B2 (en)	2016-08-02	2020-10-27	Jiangsu Hengrui Medicine Co., Ltd.	Acylated derivative of human insulin or analogue thereof
EP4265296A3 (fr)	2016-09-29	2023-12-20	Arecor Limited	Composition pharmaceutique comprenant des composés de l'insuline
ES2886837T3 (es)	2016-12-16	2021-12-21	Novo Nordisk As	Composiciones farmacéuticas que contienen insulina
AU2018230478B2 (en)	2017-03-09	2025-01-23	Diamedica Inc.	Dosage forms of tissue kallikrein 1
GB201707187D0 (en)	2017-05-05	2017-06-21	Arecor Ltd	Novel formulations
GB201707188D0 (en)	2017-05-05	2017-06-21	Arecor Ltd	Novel formulations
GB201707189D0 (en)	2017-05-05	2017-06-21	Arecor Ltd	Novel formulations
CA3065308C (fr)	2017-06-01	2022-05-17	Eli Lilly And Company	Compositions d'insuline a action rapide
CA3071686A1 (fr)	2017-08-17	2019-02-21	Novo Nordisk A/S	Nouveaux analogues d'insuline acyles et leurs utilisations
EP3773474B1 (fr)	2018-04-04	2026-01-07	Arecor Limited	Système de pompe à perfusion médicale pour l'administration d'un composé d'insuline
EP3773473B1 (fr)	2018-04-04	2026-07-01	Arecor Limited	Système de pompe à perfusion médicale pour l'administration d'un composé d'insuline
JP7465813B2 (ja)	2018-04-04	2024-04-11	アレコルリミテッド	インスリン化合物の送達のための医療用注入ポンプシステム
US10335464B1 (en)	2018-06-26	2019-07-02	Novo Nordisk A/S	Device for titrating basal insulin
EP3845240B1 (fr) *	2018-09-12	2024-11-06	Amphastar Nanjing Pharmaceuticals, Inc.	Structure de pro-insuline asparte et procédé de préparation d'insuline asparte
KR20200082618A (ko)	2018-12-31	2020-07-08	주식회사 폴루스	인슐린 과발현용 램프 태그 및 이를 이용한 인슐린의 제조방법
CN114096269B (zh)	2019-07-12	2024-06-11	诺和诺德股份有限公司	高浓度胰岛素制剂
MA58093B1 (fr) *	2019-12-11	2024-09-30	Novo Nordisk A/S	Nouveaux analogues d'insuline et leurs utilisations
AU2020418207A1 (en)	2019-12-30	2022-08-25	Gan & Lee Pharmaceuticals Co., Ltd.	Long-acting GLP-1 compound
BR112022013009A2 (pt)	2019-12-30	2022-09-06	Gan & Lee Pharmaceuticals Co Ltd	Derivados de insulina, composição farmacêutica, uso do derivado da insulina e métodos para tratar ou prevenir diabetes, para aumentar a capacidade de um derivado de insulina e para aumentar a potência de um derivado de insulina
GB202004814D0 (en)	2020-04-01	2020-05-13	Arecor Ltd	Novel formulations
WO2023143458A1 (fr)	2022-01-28	2023-08-03	甘李药业股份有限公司	Insuline acylée
PE20251287A1 (es)	2022-05-18	2025-05-14	Protomer Tech Inc	Compuestos aromaticos que contienen boro y analogos de insulina relacionados

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2252157C3 (de) *	1972-10-25	1976-03-18	Hoechst Ag	Zwischenprodukte zur herstellung von insulin, insulin-analogen und -derivaten und verfahren zur herstellung von insulin, insulin analogen und derivaten
US4652525A (en) *	1978-04-19	1987-03-24	The Regents Of The University Of California	Recombinant bacterial plasmids containing the coding sequences of insulin genes
US4565785A (en) *	1978-06-08	1986-01-21	The President And Fellows Of Harvard College	Recombinant DNA molecule
US4411994A (en) *	1978-06-08	1983-10-25	The President And Fellows Of Harvard College	Protein synthesis
JPS55138391A (en) *	1979-04-13	1980-10-29	Shionogi & Co Ltd	New synthetic method of peptide derivative
IE50892B1 (en) *	1980-02-11	1986-08-06	Novo Industri As	Process for preparing insulin esters
US4340674A (en) *	1980-05-05	1982-07-20	The Upjohn Company	Cointegrate plasmids and their construction from plasmids of Escherichia and Streptomyces
US4351901A (en) *	1980-03-24	1982-09-28	Cetus Corporation	Method for single nucleotide alteration
DK319780A (da) *	1980-07-24	1982-01-25	Forenede Bryggerier As	Fremgangsmaade til enzymatisk udskiftning af b-30 aminosyren i insuliner
ZA824218B (en) *	1981-06-29	1983-04-27	Cetus Corp	Plasmid for producing human insulin
DK58285D0 (da) *	1984-05-30	1985-02-08	Novo Industri As	Peptider samt fremstilling og anvendelse deraf
US5008241A (en) *	1985-03-12	1991-04-16	Novo Nordisk A/S	Novel insulin peptides
DK129385A (da) *	1985-03-22	1986-09-23	Novo Industri As	Peptider og fremstilling deraf
DK134189D0 (da) *	1989-03-20	1989-03-20	Nordisk Gentofte	Insulinforbindelser
US5559094A (en) *	1994-08-02	1996-09-24	Eli Lilly And Company	AspB1 insulin analogs

1986
- 1986-08-22 PH PH34177A patent/PH25772A/en unknown
- 1986-08-26 YU YU148486A patent/YU46023B/sh unknown
- 1986-08-28 CN CN86106574A patent/CN1029977C/zh not_active Expired - Lifetime
- 1986-08-29 IE IE231786A patent/IE66138B1/en not_active IP Right Cessation
- 1986-08-29 HU HU863754A patent/HU206518B/hu unknown
- 1986-08-29 AU AU62066/86A patent/AU593274B2/en not_active Expired
- 1986-08-29 DE DE2000175008 patent/DE10075008I2/de active Active
- 1986-08-29 US US06/901,821 patent/US5618913A/en not_active Expired - Lifetime
- 1986-08-29 PT PT83278A patent/PT83278B/pt unknown
- 1986-08-29 KR KR1019860007225A patent/KR940000756B1/ko not_active Expired - Lifetime
- 1986-08-29 AT AT86306721T patent/ATE113061T1/de active
- 1986-08-29 CS CS866310A patent/CS275613B6/cs not_active IP Right Cessation
- 1986-08-29 GR GR862233A patent/GR862233B/el unknown
- 1986-08-29 IL IL79887A patent/IL79887A/xx not_active IP Right Cessation
- 1986-08-29 NO NO863474A patent/NO177009C/no not_active IP Right Cessation
- 1986-08-29 NZ NZ217406A patent/NZ217406A/xx unknown
- 1986-08-29 DE DE3650101T patent/DE3650101T2/de not_active Expired - Lifetime
- 1986-08-29 ES ES8601507A patent/ES2001624A6/es not_active Expired
- 1986-08-29 DD DD29398186A patent/DD268976A5/de unknown
- 1986-08-29 FI FI863512A patent/FI102182B/fi not_active IP Right Cessation
- 1986-08-29 CA CA000517255A patent/CA1306212C/fr not_active Expired - Lifetime
- 1986-08-29 AR AR86305098A patent/AR241801A1/es active
- 1986-08-29 JP JP61201906A patent/JP2662390B2/ja not_active Expired - Lifetime
- 1986-08-29 EP EP86306721A patent/EP0214826B1/fr not_active Expired - Lifetime
1988
- 1988-01-11 YU YU4188A patent/YU46857B/sh unknown
1999
- 1999-12-06 NL NL990042C patent/NL990042I2/nl unknown
- 1999-12-21 LU LU90484C patent/LU90484I2/fr unknown
2000
- 2000-07-21 NO NO2000005C patent/NO2000005I1/no unknown

Also Published As

Publication number	Publication date
FI863512L (fi)	1987-03-01
YU46023B (sh)	1992-12-21
KR940000756B1 (ko)	1994-01-29
FI102182B1 (fi)	1998-10-30
EP0214826A2 (fr)	1987-03-18
IL79887A (en)	1991-11-21
IL79887A0 (en)	1986-11-30
CN1029977C (zh)	1995-10-11
EP0214826A3 (en)	1987-06-03
GR862233B (en)	1986-12-31
YU4188A (en)	1990-06-30
FI102182B (fi)	1998-10-30
NL990042I1 (nl)	2000-02-01
KR870002165A (ko)	1987-03-30
PH25772A (en)	1991-10-18
CA1306212C (fr)	1992-08-11
AU593274B2 (en)	1990-02-08
ATE113061T1 (de)	1994-11-15
ES2001624A6 (es)	1988-06-01
CS8606310A2 (en)	1990-09-12
JPS6253999A (ja)	1987-03-09
JP2662390B2 (ja)	1997-10-08
NZ217406A (en)	1989-05-29
IE862317L (en)	1987-02-28
FI863512A0 (fi)	1986-08-29
NO177009B (no)	1995-03-27
IE66138B1 (en)	1995-12-13
NO177009C (no)	1995-07-05
HUT42526A (en)	1987-07-28
NL990042I2 (nl)	2000-03-01
US5618913A (en)	1997-04-08
EP0214826B1 (fr)	1994-10-19
HU206518B (en)	1992-11-30
NO863474D0 (no)	1986-08-29
AU6206686A (en)	1987-03-05
NO2000005I1 (no)	2000-07-21
NO863474L (no)	1987-03-02
DE3650101T2 (de)	1995-02-23
PT83278B (pt)	1989-03-30
LU90484I2 (fr)	2000-02-21
DE3650101D1 (de)	1994-11-24
DE10075008I1 (de)	2000-05-18
YU46857B (sh)	1994-06-24
DD268976A5 (de)	1989-06-14
CN86106574A (zh)	1988-08-03
YU148486A (en)	1991-04-30
DE10075008I2 (de)	2004-10-21
PT83278A (en)	1986-09-01
AR241801A1 (es)	1992-12-30

Legal Events

Date	Code	Title	Description
2000-06-30	IF00	In force as of 2000-06-30 in czech republic
2009-01-21	MK4A	Patent expired	Effective date: 20060829

Publication	Publication Date	Title
KR940000756B1 (ko)	1994-01-29	인슈린 유사체의 제조방법
EP0419504B1 (fr)	1994-01-26	Analogues d'insuline
EP0463072B1 (fr)	1995-01-04	Nouveaux composes d'insuline
AU648670B2 (en)	1994-04-28	A-C-B Proinsulin, method of manufacturing and using same, and intermediates in insulin production
JP2766999B2 (ja)	1998-06-18	プロペプチド
JP4519324B2 (ja)	2010-08-04	共有結合で架橋されたインスリンダイマー
RU2176646C2 (ru)	2001-12-10	Инсулин и его производные с повышенной способностью связывать цинк
CA2006578A1 (fr)	1990-06-23	Analogues de l'insuline humaine
CA2330183C (fr)	2009-10-20	Nouveaux analogues de l'insuline presentant un pouvoir de liaison accru avec le zinc
WO1988010299A1 (fr)	1988-12-29	Procede de preparation d'une proteine ou d'un polypeptide, sequence d'adn codant pour le polypeptide, microorganisme contenant la sequence d'adn et le polypeptide et utilisation du polypeptide comme preparation pharmaceutique
RU2104305C1 (ru)	1998-02-10	Аналоги инсулина человека, способ их получения, раствор для инъекций
WO1992015611A1 (fr)	1992-09-17	Nouveaux derives d'insuline
DK159274B (da)	1990-09-24	Hurtigt virkende human insulinanaloger og injicerbare oploesninger med hurtigt indsaettende virkning indeholdende saadanne insulinanaloger