CA2858253A1 - Human insulin analogue and acylated derivative thereof - Google Patents
Human insulin analogue and acylated derivative thereof Download PDFInfo
- Publication number
- CA2858253A1 CA2858253A1 CA2858253A CA2858253A CA2858253A1 CA 2858253 A1 CA2858253 A1 CA 2858253A1 CA 2858253 A CA2858253 A CA 2858253A CA 2858253 A CA2858253 A CA 2858253A CA 2858253 A1 CA2858253 A1 CA 2858253A1
- Authority
- CA
- Canada
- Prior art keywords
- chain
- human insulin
- seq
- insulin
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 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 title claims abstract description 417
- 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 claims abstract description 165
- 238000002360 preparation method Methods 0.000 claims abstract description 56
- 239000004026 insulin derivative Substances 0.000 claims abstract description 34
- 239000003814 drug Substances 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 349
- 239000002243 precursor Substances 0.000 claims description 206
- 229940125396 insulin Drugs 0.000 claims description 62
- 102000004877 Insulin Human genes 0.000 claims description 60
- 108090001061 Insulin Proteins 0.000 claims description 60
- 239000013604 expression vector Substances 0.000 claims description 59
- 238000000034 method Methods 0.000 claims description 52
- 230000000694 effects Effects 0.000 claims description 29
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 26
- 238000006911 enzymatic reaction Methods 0.000 claims description 17
- 102220092852 rs754853086 Human genes 0.000 claims description 17
- 125000000539 amino acid group Chemical group 0.000 claims description 15
- 239000013598 vector Substances 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 230000006320 pegylation Effects 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 9
- 229910052700 potassium Inorganic materials 0.000 claims description 9
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 239000004472 Lysine Substances 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 6
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 5
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
- 102000007079 Peptide Fragments Human genes 0.000 claims description 4
- 108010033276 Peptide Fragments Proteins 0.000 claims description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 4
- 230000007774 longterm Effects 0.000 claims description 4
- 201000001421 hyperglycemia Diseases 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 2
- 241000894006 Bacteria Species 0.000 claims description 2
- 241000588724 Escherichia coli Species 0.000 claims description 2
- 208000031773 Insulin resistance syndrome Diseases 0.000 claims description 2
- 241000235058 Komagataella pastoris Species 0.000 claims description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- 125000000729 N-terminal amino-acid group Chemical group 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 235000004279 alanine Nutrition 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000002288 cocrystallisation Methods 0.000 claims description 2
- 229940102223 injectable solution Drugs 0.000 claims description 2
- 238000002715 modification method Methods 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 229910018830 PO3H Inorganic materials 0.000 claims 1
- 229910006069 SO3H Inorganic materials 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 30
- 229940124597 therapeutic agent Drugs 0.000 abstract description 4
- 239000000047 product Substances 0.000 description 218
- 238000000855 fermentation Methods 0.000 description 97
- 230000004151 fermentation Effects 0.000 description 97
- 239000012634 fragment Substances 0.000 description 97
- 239000000243 solution Substances 0.000 description 74
- 238000003752 polymerase chain reaction Methods 0.000 description 64
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 61
- 229920001223 polyethylene glycol Polymers 0.000 description 52
- 238000000746 purification Methods 0.000 description 48
- 239000012071 phase Substances 0.000 description 44
- 238000006243 chemical reaction Methods 0.000 description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- 238000004458 analytical method Methods 0.000 description 32
- 238000002741 site-directed mutagenesis Methods 0.000 description 32
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 230000003321 amplification Effects 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 30
- 108020004414 DNA Proteins 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 230000006862 enzymatic digestion Effects 0.000 description 26
- 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 25
- 238000012300 Sequence Analysis Methods 0.000 description 25
- 239000008103 glucose Substances 0.000 description 25
- 239000013612 plasmid Substances 0.000 description 25
- 239000012074 organic phase Substances 0.000 description 22
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 21
- 239000008280 blood Substances 0.000 description 21
- 210000004369 blood Anatomy 0.000 description 21
- 102000003746 Insulin Receptor Human genes 0.000 description 20
- 108010001127 Insulin Receptor Proteins 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000000872 buffer Substances 0.000 description 17
- 238000001727 in vivo Methods 0.000 description 16
- 238000011534 incubation Methods 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 238000003199 nucleic acid amplification method Methods 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 238000004520 electroporation Methods 0.000 description 14
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 14
- 238000004007 reversed phase HPLC Methods 0.000 description 14
- 230000009466 transformation Effects 0.000 description 14
- 102000053602 DNA Human genes 0.000 description 13
- 108020004682 Single-Stranded DNA Proteins 0.000 description 13
- 102000004142 Trypsin Human genes 0.000 description 13
- 108090000631 Trypsin Proteins 0.000 description 13
- 238000012512 characterization method Methods 0.000 description 13
- 238000010367 cloning Methods 0.000 description 13
- 238000010276 construction Methods 0.000 description 13
- 238000002955 isolation Methods 0.000 description 13
- 238000005457 optimization Methods 0.000 description 13
- 238000003259 recombinant expression Methods 0.000 description 13
- 238000012216 screening Methods 0.000 description 13
- 238000006467 substitution reaction Methods 0.000 description 13
- 239000012588 trypsin Substances 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 108700002854 polyethylene glycol(B1)- insulin Proteins 0.000 description 11
- 239000012528 membrane Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- -1 Insulin Analogue Insulin Analogue Chemical class 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000027455 binding Effects 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 8
- 108010052285 Membrane Proteins Proteins 0.000 description 8
- 239000013641 positive control Substances 0.000 description 8
- 230000002441 reversible effect Effects 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- QQHJDPROMQRDLA-UHFFFAOYSA-N hexadecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCC(O)=O QQHJDPROMQRDLA-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 102000018697 Membrane Proteins Human genes 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000005923 long-lasting effect Effects 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 239000011543 agarose gel Substances 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 229960003948 insulin detemir Drugs 0.000 description 5
- UGOZVNFCFYTPAZ-IOXYNQHNSA-N levemir Chemical compound CCCCCCCCCCCCCC(=O)NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2C=CC(O)=CC=2)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=2N=CNC=2)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=2C=CC=CC=2)C(C)C)CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)CSSC[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)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=2C=CC(O)=CC=2)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=C(O)C=C1 UGOZVNFCFYTPAZ-IOXYNQHNSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 4
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 4
- 101710184277 Insulin-like growth factor 1 receptor Proteins 0.000 description 4
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 4
- 239000001888 Peptone Substances 0.000 description 4
- 108010080698 Peptones Proteins 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 125000003275 alpha amino acid group Chemical group 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 235000020958 biotin Nutrition 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 229940041514 candida albicans extract Drugs 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229920001427 mPEG Polymers 0.000 description 4
- KPNBUPJZFJCCIQ-LURJTMIESA-N methyl L-lysinate Chemical compound COC(=O)[C@@H](N)CCCCN KPNBUPJZFJCCIQ-LURJTMIESA-N 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 235000019319 peptone Nutrition 0.000 description 4
- 238000000159 protein binding assay Methods 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 238000007127 saponification reaction Methods 0.000 description 4
- 239000012138 yeast extract Substances 0.000 description 4
- 102000004584 Somatomedin Receptors Human genes 0.000 description 3
- 108010017622 Somatomedin Receptors Proteins 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 238000005341 cation exchange Methods 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 125000002228 disulfide group Chemical group 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229940084769 humulin r Drugs 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000012264 purified product Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- UGAGPNKCDRTDHP-UHFFFAOYSA-N 16-hydroxyhexadecanoic acid Chemical compound OCCCCCCCCCCCCCCCC(O)=O UGAGPNKCDRTDHP-UHFFFAOYSA-N 0.000 description 2
- 102100036826 Aldehyde oxidase Human genes 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 2
- 101000619708 Homo sapiens Peroxiredoxin-6 Proteins 0.000 description 2
- SEWIYICDCVPBEW-BYPYZUCNSA-N L-glutamate methyl ester Chemical compound COC(=O)[C@@H](N)CCC(O)=O SEWIYICDCVPBEW-BYPYZUCNSA-N 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 102100022239 Peroxiredoxin-6 Human genes 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 108091006629 SLC13A2 Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000008057 potassium phosphate buffer Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 229960002317 succinimide Drugs 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- QOESZBMMAKUZHL-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-methylhexadecanoate Chemical compound CCCCCCCCCCCCCCC(C)C(=O)ON1C(=O)CCC1=O QOESZBMMAKUZHL-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 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
- 238000009010 Bradford assay Methods 0.000 description 1
- 102000003670 Carboxypeptidase B Human genes 0.000 description 1
- 108090000087 Carboxypeptidase B Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 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 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 108010090613 Human Regular Insulin Proteins 0.000 description 1
- 102000013266 Human Regular Insulin Human genes 0.000 description 1
- FYZPCMFQCNBYCY-WIWKJPBBSA-N Insulin degludec Chemical compound CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=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](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC(O)=O)C(O)=O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC FYZPCMFQCNBYCY-WIWKJPBBSA-N 0.000 description 1
- 101710186630 Insulin-1 Proteins 0.000 description 1
- 241001506991 Komagataella phaffii GS115 Species 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 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
- 101001018085 Lysobacter enzymogenes Lysyl endopeptidase Proteins 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 101150051118 PTM1 gene Proteins 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 239000012564 Q sepharose fast flow resin Substances 0.000 description 1
- 101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940127095 analogue insulin Drugs 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 229940127003 anti-diabetic drug Drugs 0.000 description 1
- 101150031623 aox gene Proteins 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 108010037721 cytase Proteins 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011841 epidemiological investigation Methods 0.000 description 1
- 238000009207 exercise therapy Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000006481 glucose medium Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229940103471 humulin Drugs 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 108010050259 insulin degludec Proteins 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000010503 organ complication Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—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)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Mycology (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110422095 | 2011-12-15 | ||
| CN201110422095.2 | 2011-12-15 | ||
| PCT/CN2012/085054 WO2013086927A1 (zh) | 2011-12-15 | 2012-11-22 | 人胰岛素类似物及其酰化衍生物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2858253A1 true CA2858253A1 (en) | 2013-06-20 |
Family
ID=48611849
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2858253A Abandoned CA2858253A1 (en) | 2011-12-15 | 2012-11-22 | Human insulin analogue and acylated derivative thereof |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US9458219B2 (enExample) |
| EP (1) | EP2784085A4 (enExample) |
| JP (1) | JP6153206B2 (enExample) |
| KR (1) | KR20140104994A (enExample) |
| CN (2) | CN104788556A (enExample) |
| AU (1) | AU2012350586B2 (enExample) |
| BR (1) | BR112014013483A2 (enExample) |
| CA (1) | CA2858253A1 (enExample) |
| IN (1) | IN2014MN00933A (enExample) |
| MX (1) | MX2014006698A (enExample) |
| RU (1) | RU2014127270A (enExample) |
| TW (1) | TW201323439A (enExample) |
| WO (1) | WO2013086927A1 (enExample) |
| ZA (1) | ZA201404417B (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112018002416A2 (pt) | 2015-08-25 | 2018-09-18 | Novo Nordisk As | derivados de insulina e seus usos médicos |
| CN106496322A (zh) * | 2015-09-07 | 2017-03-15 | 江苏恒瑞医药股份有限公司 | 人胰岛素或其类似物的酰化衍生物的制备方法 |
| CN105491227A (zh) * | 2015-11-20 | 2016-04-13 | 努比亚技术有限公司 | 一种消息排列方法和终端 |
| EP3260548A1 (en) | 2016-06-21 | 2017-12-27 | Enzypep B.V. | Enzymatic coupling of (oligo)peptides to the b-chain of an insulin receptor ligand |
| JP7432361B2 (ja) * | 2016-08-02 | 2024-02-16 | 江蘇恒瑞医薬股▲ふん▼有限公司 | ヒトインスリンまたはそのアナログのアシル化誘導体 |
| CN111315766B (zh) * | 2018-02-01 | 2023-05-12 | 江苏恒瑞医药股份有限公司 | 含人胰岛素类似物的酰化衍生物的药物组合物及其制备方法 |
| US20210032307A1 (en) * | 2018-02-09 | 2021-02-04 | Jiangsu Hengrui Medicine Co., Ltd. | Codon optimized precursor gene and signal peptide gene of human insulin analogue |
| TW202039539A (zh) | 2018-12-11 | 2020-11-01 | 法商賽諾菲公司 | 具有經降低胰島素受體結合親和力的胰島素類似物 |
| CN111909255A (zh) * | 2019-05-10 | 2020-11-10 | 宁波鲲鹏生物科技有限公司 | 胰岛素衍生物及其制备方法 |
| TWI773009B (zh) | 2019-12-11 | 2022-08-01 | 丹麥商諾佛 儂迪克股份有限公司 | 新穎之胰島素類似物及其用途 |
| CN118206632A (zh) | 2019-12-30 | 2024-06-18 | 甘李药业股份有限公司 | 胰岛素衍生物 |
| CN113773398B (zh) * | 2020-06-10 | 2023-05-23 | 宁波鲲鹏生物科技有限公司 | 一种德谷胰岛素衍生物及其应用 |
| EP4347632A4 (en) * | 2021-05-24 | 2025-03-26 | Sunshine Lake Pharma Co., Ltd. | A novel acylated insulin analog |
| AU2022300061A1 (en) | 2021-06-25 | 2024-02-01 | Gan & Lee Pharmaceuticals Co., Ltd. | Acylated insulin-containing pharmaceutical composition |
| US20250340610A1 (en) | 2022-01-28 | 2025-11-06 | Gan & Lee Pharmaceuticals Co., Ltd. | Acylated insulin |
| CN118063589A (zh) * | 2024-02-04 | 2024-05-24 | 乐普健糖药业(重庆)有限公司 | 一种超长效胰岛素类似物及其制备方法和用途 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5008241A (en) | 1985-03-12 | 1991-04-16 | Novo Nordisk A/S | Novel insulin peptides |
| PH25772A (en) * | 1985-08-30 | 1991-10-18 | Novo Industri As | Insulin analogues, process for their preparation |
| DK257988D0 (da) | 1988-05-11 | 1988-05-11 | Novo Industri As | Nye peptider |
| FI910286A0 (fi) | 1988-07-20 | 1991-01-18 | Nordisk Gentofte | Analoger av humant insulin och preparat innehaollande dessa. |
| FI913037A7 (fi) | 1988-12-23 | 1991-06-20 | Novo Nordisk As | Ihmisen insuliinianalogit |
| RU2164520C2 (ru) * | 1993-09-17 | 2001-03-27 | Ново Нордиск А/С | Производное инсулина, растворимая пролонгированная фармацевтическая композиция, способ пролонгирования гипогликемического действия при лечении диабета |
| CN1195777A (zh) | 1997-05-28 | 1998-10-14 | 姚维明 | 电力拖动实验仪 |
| JP4773023B2 (ja) * | 1999-12-29 | 2011-09-14 | ノボ ノルディスク アクティーゼルスカブ | インスリン前駆体及びインスリン前駆体類似体の製造方法 |
| US7060675B2 (en) * | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
| US6770625B2 (en) * | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
| US7193035B2 (en) | 2002-10-29 | 2007-03-20 | Sanofi-Aventis Deutschland Gmbh | Crystals of insulin analogs and processes for their preparation |
| CN1780854A (zh) | 2003-04-29 | 2006-05-31 | 伊莱利利公司 | 具有延长时间作用的胰岛素类似物 |
| SI2107069T1 (sl) * | 2003-08-05 | 2013-04-30 | Novo Nordisk A/S | Novi inzulinski derivati |
| JP4463814B2 (ja) * | 2003-08-05 | 2010-05-19 | ノボ ノルディスク アクティーゼルスカブ | 新規のインスリン誘導体 |
| CN101721712A (zh) * | 2008-10-21 | 2010-06-09 | 何明磊 | 一种双链聚乙二醇－胰岛素复合物及其制备方法 |
-
2012
- 2012-11-22 WO PCT/CN2012/085054 patent/WO2013086927A1/zh not_active Ceased
- 2012-11-22 EP EP12857862.2A patent/EP2784085A4/en not_active Withdrawn
- 2012-11-22 CA CA2858253A patent/CA2858253A1/en not_active Abandoned
- 2012-11-22 US US14/363,328 patent/US9458219B2/en not_active Expired - Fee Related
- 2012-11-22 IN IN933MUN2014 patent/IN2014MN00933A/en unknown
- 2012-11-22 BR BR112014013483A patent/BR112014013483A2/pt not_active IP Right Cessation
- 2012-11-22 JP JP2014546293A patent/JP6153206B2/ja not_active Expired - Fee Related
- 2012-11-22 CN CN201510174792.9A patent/CN104788556A/zh active Pending
- 2012-11-22 MX MX2014006698A patent/MX2014006698A/es unknown
- 2012-11-22 AU AU2012350586A patent/AU2012350586B2/en not_active Ceased
- 2012-11-22 RU RU2014127270A patent/RU2014127270A/ru not_active Application Discontinuation
- 2012-11-22 KR KR1020147018616A patent/KR20140104994A/ko not_active Withdrawn
- 2012-11-22 CN CN201280011736.8A patent/CN103443122B/zh active Active
- 2012-11-30 TW TW101144976A patent/TW201323439A/zh unknown
-
2014
- 2014-06-17 ZA ZA2014/04417A patent/ZA201404417B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20140329745A1 (en) | 2014-11-06 |
| JP6153206B2 (ja) | 2017-06-28 |
| EP2784085A4 (en) | 2015-07-08 |
| MX2014006698A (es) | 2014-07-09 |
| CN103443122A (zh) | 2013-12-11 |
| ZA201404417B (en) | 2016-07-27 |
| US9458219B2 (en) | 2016-10-04 |
| IN2014MN00933A (enExample) | 2015-05-01 |
| AU2012350586A1 (en) | 2014-07-03 |
| EP2784085A1 (en) | 2014-10-01 |
| HK1188795A1 (zh) | 2014-05-16 |
| WO2013086927A1 (zh) | 2013-06-20 |
| RU2014127270A (ru) | 2016-02-10 |
| KR20140104994A (ko) | 2014-08-29 |
| CN103443122B (zh) | 2016-05-11 |
| CN104788556A (zh) | 2015-07-22 |
| TW201323439A (zh) | 2013-06-16 |
| BR112014013483A2 (pt) | 2019-09-24 |
| JP2015501819A (ja) | 2015-01-19 |
| AU2012350586B2 (en) | 2017-02-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2858253A1 (en) | Human insulin analogue and acylated derivative thereof | |
| DE60003182T2 (de) | Exendin-4 konjugate und ihre medizinische verwendung | |
| CA2878991C (en) | Glucagon analogues | |
| JP2662390B2 (ja) | インシユリン類似体 | |
| EP0894095B1 (en) | Insulin derivatives and their use | |
| CN101993485A (zh) | 促胰岛素分泌肽类似物同源二聚体及其用途 | |
| KR20120062777A (ko) | 변형된 혈관활성 장 펩티드 | |
| EP2700654A1 (en) | Human insulin and analog conjugate thereof | |
| WO2008056726A1 (en) | Glp-1 derivative and use thereof | |
| WO2018011803A1 (en) | Fusion proteins with extended serum half life | |
| US7595294B2 (en) | Vasoactive intestinal polypeptide pharmaceuticals | |
| JP4402296B2 (ja) | 亜鉛結合性が増大された新規なインスリン同族体 | |
| WO2025162138A1 (zh) | 一种超长效胰岛素类似物及其制备方法和用途 | |
| Lin et al. | Site-specific N-terminal PEGylation-based controlled release of biotherapeutics: An application for GLP-1 delivery to improve pharmacokinetics and prolong hypoglycemic effects | |
| KR100890989B1 (ko) | 폴리에틸렌글리콜 또는 이의 유도체로 단일 수식된 엑센딘,이의 제조방법 및 이의 용도 | |
| CN101328221A (zh) | 一种降糖多肽融合蛋白及其衍生物的结构及用途 | |
| US20020025933A1 (en) | GLP-2 derivatives | |
| CN110759991A (zh) | 吉非罗齐-非洲爪蟾胰高血糖素样肽-1衍生物及其应用 | |
| CN101824388A (zh) | 一种糖尿病食疗酵母及其构建方法 | |
| HK1188795B (en) | Human insulin analogue and acylated derivative thereof | |
| JP2025527307A (ja) | 長時間作用型のインスリン化合物 | |
| EP4255469A1 (en) | Acylated single-chain insulin analogues | |
| HK1036808B (en) | Novel insulin analogs with enhanced zinc binding |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20181122 |