NO321720B1 - Insulinderivater og forloperproteiner, fremgangsmate for fremstilling inkludert DNA-sekvenser, ekspresjonsbaerer og vertsceller, samt deres anvendelse spesielt i farmasoytiske preparater for behandling av diabetes. - Google Patents

Insulinderivater og forloperproteiner, fremgangsmate for fremstilling inkludert DNA-sekvenser, ekspresjonsbaerer og vertsceller, samt deres anvendelse spesielt i farmasoytiske preparater for behandling av diabetes. Download PDF

Info

Publication number: NO321720B1
Authority: NO; Norway
Prior art keywords: amino acid; insulin; chain; insulin derivative; acceptable salt
Prior art date: 1997-06-20

Application number

NO19982860A

Other languages

English (en)

Norwegian (no)

Other versions

NO982860D0 (no

NO982860L (no

Inventor

Gerhard Seipke

Paul Habermann

Karl Geisen

Johann Ertl

Original Assignee

Sanofi Aventis Deutschland

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.)

1997-06-20

Filing date

1998-06-19

Publication date

2006-06-26

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=7833099&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO321720(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1998-06-19 Application filed by Sanofi Aventis Deutschland filed Critical Sanofi Aventis Deutschland

1998-06-19 Publication of NO982860D0 publication Critical patent/NO982860D0/no

1998-12-21 Publication of NO982860L publication Critical patent/NO982860L/no

2006-06-26 Publication of NO321720B1 publication Critical patent/NO321720B1/no

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 description 207
239000002243 precursor Substances 0.000 title claims description 26
238000000034 method Methods 0.000 title claims description 21
108091028043 Nucleic acid sequence Proteins 0.000 title claims description 14
239000000825 pharmaceutical preparation Substances 0.000 title claims description 12
238000002360 preparation method Methods 0.000 title description 13
206010012601 diabetes mellitus Diseases 0.000 title description 11
108090000623 proteins and genes Proteins 0.000 title description 6
239000000969 carrier Substances 0.000 title description 4
102000004169 proteins and genes Human genes 0.000 title description 4
239000004026 insulin derivative Substances 0.000 claims description 97
125000000539 amino acid group Chemical group 0.000 claims description 78
102000004877 Insulin Human genes 0.000 claims description 59
108090001061 Insulin Proteins 0.000 claims description 59
150000003839 salts Chemical class 0.000 claims description 54
229940125396 insulin Drugs 0.000 claims description 52
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 32
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 27
101000976075 Homo sapiens Insulin Proteins 0.000 claims description 25
PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 25
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 22
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 22
235000001014 amino acid Nutrition 0.000 claims description 19
229940024606 amino acid Drugs 0.000 claims description 18
150000001413 amino acids Chemical class 0.000 claims description 18
241001465754 Metazoa Species 0.000 claims description 17
238000004519 manufacturing process Methods 0.000 claims description 12
238000010276 construction Methods 0.000 claims description 11
108090000765 processed proteins & peptides Proteins 0.000 claims description 10
240000004808 Saccharomyces cerevisiae Species 0.000 claims description 8
235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 8
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 8
COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 8
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 7
235000004279 alanine Nutrition 0.000 claims description 7
241000894006 Bacteria Species 0.000 claims description 6
239000004472 Lysine Substances 0.000 claims description 6
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 6
230000002378 acidificating effect Effects 0.000 claims description 6
125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims description 6
230000007935 neutral effect Effects 0.000 claims description 6
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 5
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 5
239000004473 Threonine Substances 0.000 claims description 5
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 5
229960000310 isoleucine Drugs 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
102000007327 Protamines Human genes 0.000 claims description 4
108010007568 Protamines Proteins 0.000 claims description 4
125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 4
230000000694 effects Effects 0.000 claims description 4
235000013922 glutamic acid Nutrition 0.000 claims description 4
239000004220 glutamic acid Substances 0.000 claims description 4
241000588724 Escherichia coli Species 0.000 claims description 3
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 3
235000003704 aspartic acid Nutrition 0.000 claims description 3
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 3
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
239000004474 valine Substances 0.000 claims description 3
238000006911 enzymatic reaction Methods 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
229940102223 injectable solution Drugs 0.000 claims description 2
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 2
239000000126 substance Substances 0.000 claims description 2
DPEUWKZJZIPZKE-OFANTOPUSA-N 330936-69-1 Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)O)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@@H](N)CCSC)C1=CC=CC=C1 DPEUWKZJZIPZKE-OFANTOPUSA-N 0.000 claims 2
101000988651 Homo sapiens Humanin-like 1 Proteins 0.000 claims 2
102000011854 humanin Human genes 0.000 claims 2
229950008679 protamine sulfate Drugs 0.000 claims 2
125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 claims 1
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 24
239000008103 glucose Substances 0.000 description 24
235000002639 sodium chloride Nutrition 0.000 description 23
239000013612 plasmid Substances 0.000 description 18
239000008280 blood Substances 0.000 description 15
210000004369 blood Anatomy 0.000 description 15
108020004414 DNA Proteins 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
108010076181 Proinsulin Proteins 0.000 description 7
239000012634 fragment Substances 0.000 description 7
101000740205 Homo sapiens Sal-like protein 1 Proteins 0.000 description 6
102100037204 Sal-like protein 1 Human genes 0.000 description 6
239000004475 Arginine Substances 0.000 description 5
241000283973 Oryctolagus cuniculus Species 0.000 description 5
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
230000004071 biological effect Effects 0.000 description 5
238000003776 cleavage reaction Methods 0.000 description 5
108020001507 fusion proteins Proteins 0.000 description 5
102000037865 fusion proteins Human genes 0.000 description 5
230000007017 scission Effects 0.000 description 5
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
238000007920 subcutaneous administration Methods 0.000 description 5
241000282472 Canis lupus familiaris Species 0.000 description 4
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
125000003275 alpha amino acid group Chemical group 0.000 description 4
LEMUFSYUPGXXCM-JNEQYSBXSA-N caninsulin Chemical compound [Zn].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](CC3N=CN=C3)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(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)C1C=NC=N1 LEMUFSYUPGXXCM-JNEQYSBXSA-N 0.000 description 4
235000012054 meals Nutrition 0.000 description 4
239000000203 mixture Substances 0.000 description 4
230000003285 pharmacodynamic effect Effects 0.000 description 4
239000000047 product Substances 0.000 description 4
238000006467 substitution reaction Methods 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
102000005237 Isophane Insulin Human genes 0.000 description 3
108010081368 Isophane Insulin Proteins 0.000 description 3
238000010353 genetic engineering Methods 0.000 description 3
238000001802 infusion Methods 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
230000003914 insulin secretion Effects 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
235000018102 proteins Nutrition 0.000 description 3
238000002560 therapeutic procedure Methods 0.000 description 3
VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 2
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
108010075254 C-Peptide Proteins 0.000 description 2
241001646716 Escherichia coli K-12 Species 0.000 description 2
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
108010005991 Pork Regular Insulin Proteins 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
235000009582 asparagine Nutrition 0.000 description 2
229960001230 asparagine Drugs 0.000 description 2
IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin 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)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)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(C)C)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 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 2
230000000295 complement effect Effects 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
238000007169 ligase reaction Methods 0.000 description 2
RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
238000002156 mixing Methods 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
230000000291 postprandial effect Effects 0.000 description 2
229940048914 protamine Drugs 0.000 description 2
108091008146 restriction endonucleases Proteins 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000003860 storage Methods 0.000 description 2
229910021653 sulphate ion Inorganic materials 0.000 description 2
229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
201000004569 Blindness Diseases 0.000 description 1
101001011741 Bos taurus Insulin Proteins 0.000 description 1
102000003670 Carboxypeptidase B Human genes 0.000 description 1
108090000087 Carboxypeptidase B Proteins 0.000 description 1
108091026890 Coding region Proteins 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
102000005561 Human Isophane Insulin Human genes 0.000 description 1
108010084048 Human Isophane Insulin Proteins 0.000 description 1
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
101150005446 Pemt gene Proteins 0.000 description 1
208000001647 Renal Insufficiency Diseases 0.000 description 1
238000012300 Sequence Analysis Methods 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
208000021945 Tendon injury Diseases 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
230000003321 amplification Effects 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
239000007864 aqueous solution 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
239000012928 buffer substance Substances 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
235000018417 cysteine Nutrition 0.000 description 1
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
230000006378 damage Effects 0.000 description 1
108700025974 depot- insulin Proteins 0.000 description 1
238000011161 development Methods 0.000 description 1
230000029087 digestion Effects 0.000 description 1
230000001610 euglycemic effect Effects 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000000463 material Substances 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
230000035772 mutation Effects 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
238000005457 optimization Methods 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
-1 p-hydroxybenzoic acid ester Chemical class 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
230000035479 physiological effects, processes and functions Effects 0.000 description 1
230000007180 physiological regulation Effects 0.000 description 1
108010066381 preproinsulin Proteins 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
230000006920 protein precipitation Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000002994 raw material Substances 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000011160 research Methods 0.000 description 1
238000002741 site-directed mutagenesis Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
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 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
238000012795 verification Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Genetics & Genomics (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Zoology (AREA)
Diabetes (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Endocrinology (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biomedical Technology (AREA)
Gastroenterology & Hepatology (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Wood Science & Technology (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Toxicology (AREA)
Mycology (AREA)
Plant Pathology (AREA)
Microbiology (AREA)
Epidemiology (AREA)
Physics & Mathematics (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Obesity (AREA)
Hematology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Immunology (AREA)
Emergency Medicine (AREA)
Dermatology (AREA)
Peptides Or Proteins (AREA)

NO19982860A 1997-06-20 1998-06-19 Insulinderivater og forloperproteiner, fremgangsmate for fremstilling inkludert DNA-sekvenser, ekspresjonsbaerer og vertsceller, samt deres anvendelse spesielt i farmasoytiske preparater for behandling av diabetes. NO321720B1 (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19726167A DE19726167B4 (de)	1997-06-20	1997-06-20	Insulin, Verfahren zu seiner Herstellung und es enthaltende pharmazeutische Zubereitung

Publications (3)

Publication Number	Publication Date
NO982860D0 NO982860D0 (no)	1998-06-19
NO982860L NO982860L (no)	1998-12-21
NO321720B1 true NO321720B1 (no)	2006-06-26

Family

ID=7833099

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO19982860A NO321720B1 (no)	1997-06-20	1998-06-19	Insulinderivater og forloperproteiner, fremgangsmate for fremstilling inkludert DNA-sekvenser, ekspresjonsbaerer og vertsceller, samt deres anvendelse spesielt i farmasoytiske preparater for behandling av diabetes.
NO2006014C NO2006014I1 (no)	1997-06-20	2006-10-26	Insulin glulisin

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
NO2006014C NO2006014I1 (no)	1997-06-20	2006-10-26	Insulin glulisin

Country Status (31)

Country	Link
US (1)	US6221633B1 (fr)
EP (1)	EP0885961B1 (fr)
JP (1)	JP3676573B2 (fr)
KR (1)	KR100546225B1 (fr)
CN (1)	CN1195777C (fr)
AR (1)	AR015899A1 (fr)
AT (1)	ATE283919T1 (fr)
AU (1)	AU740344C (fr)
BR (1)	BRPI9803708B8 (fr)
CA (1)	CA2235443C (fr)
CY (1)	CY2005004I1 (fr)
CZ (1)	CZ295964B6 (fr)
DE (3)	DE19726167B4 (fr)
DK (1)	DK0885961T3 (fr)
ES (1)	ES2232900T3 (fr)
FR (1)	FR05C0009I2 (fr)
HU (1)	HU221176B1 (fr)
ID (1)	ID20462A (fr)
IL (1)	IL125006A (fr)
LU (1)	LU91138I2 (fr)
NL (1)	NL300170I2 (fr)
NO (2)	NO321720B1 (fr)
NZ (1)	NZ330700A (fr)
PL (1)	PL196626B1 (fr)
PT (1)	PT885961E (fr)
RU (1)	RU2207874C9 (fr)
SK (1)	SK285267B6 (fr)
TR (1)	TR199801144A2 (fr)
TW (1)	TW562806B (fr)
UA (1)	UA65529C2 (fr)
ZA (1)	ZA985363B (fr)

Families Citing this family (136)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE19947456A1 (de) *	1999-10-02	2001-04-05	Aventis Pharma Gmbh	C-Peptid zur verbesserten Herstellung von Insulin und Insulinanaloga
US7022674B2 (en)	1999-12-16	2006-04-04	Eli Lilly And Company	Polypeptide compositions with improved stability
US8623379B2 (en)	2000-03-02	2014-01-07	Emory University	Compositions and methods for generating an immune response
PT1372710E (pt)	2001-03-08	2009-12-21	Us Gov Health & Human Serv	Vam modificado que expressa os genes gag e pol do envelope de vih
DE10114178A1 (de) *	2001-03-23	2002-10-10	Aventis Pharma Gmbh	Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität
BR0212031A (pt) *	2001-08-22	2004-08-03	Aventis Pharma Gmbh	Preparados de combinação de derivados de 1,1-dióxido de 1-4-benzotiepina com outras substâncias ativas e seu emprego
CA2452044A1 (fr) *	2001-08-28	2003-03-13	Eli Lilly And Company	Pre-melanges de polypeptide glp-1 et d'insuline basale
US6884812B2 (en)	2001-08-31	2005-04-26	Aventis Pharma Deutschland Gmbh	Diarylcycloalkyl derivatives, processes for their preparation and their use as pharmaceuticals
US7399777B2 (en) *	2001-08-31	2008-07-15	Sanofi-Aventis Deutschland Gmbh	Diarylcycloalkyl derivatives, processes for their preparation and their use as pharmceuticals
JP4436129B2 (ja)	2001-08-31	2010-03-24	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	ジアリールシクロアルキル誘導体、その製造法及びｐｐａｒ−活性剤としてのその使用
CA2463803A1 (fr) *	2001-10-19	2003-05-01	Eli Lilly And Company	Melanges biphasiques de glp-1 et d'insuline
US20050250676A1 (en) *	2001-11-19	2005-11-10	Aventis Pharma Deutschland Gmbh	Method of activating insulin receptor substrate-2 to stimulate insulin production
AU2002346491A1 (en) *	2001-12-19	2003-07-09	Eli Lilly And Company	Crystalline compositions for controlling blood glucose
US7223796B2 (en) *	2002-04-11	2007-05-29	Sanofi-Aventis Deutschland Gmbh	Acyl-4-carboxyphenylurea derivatives, processes for preparing them and their use
US7078404B2 (en) *	2002-04-11	2006-07-18	Sanofi-Aventis Deutschland Gmbh	Acyl-3-carboxyphenylurea derivatives, processes for preparing them and their use
WO2003094956A1 (fr)	2002-05-07	2003-11-20	Novo Nordisk A/S	Preparations solubles comprenant de l'insuline monomere et de l'insuline acylee
US7049341B2 (en) *	2002-06-07	2006-05-23	Aventis Pharma Deutschland Gmbh	N-benzoylureidocinnamic acid derivatives, processes for preparing them and their use
DE10231370B4 (de) *	2002-07-11	2006-04-06	Sanofi-Aventis Deutschland Gmbh	Thiophenglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel
US7262220B2 (en) *	2002-07-11	2007-08-28	Sanofi-Aventis Deutschland Gmbh	Urea- and urethane-substituted acylureas, process for their preparation and their use
ATE452879T1 (de) *	2002-07-12	2010-01-15	Sanofi Aventis Deutschland	Heterozyklisch substituierte benzoylharnstoffe, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
US20040157922A1 (en) *	2002-10-04	2004-08-12	Aventis Pharma Deutschland Gmbh	Carboxyalkoxy-substituted acyl-carboxyphenylurea derivatives and their use as medicaments
US7208504B2 (en) *	2002-10-12	2007-04-24	Sanofi-Aventis Deutschland Gmbh	Bicyclic inhibitors of hormone sensitive lipase
US7193035B2 (en) *	2002-10-29	2007-03-20	Sanofi-Aventis Deutschland Gmbh	Crystals of insulin analogs and processes for their preparation
DE10250297A1 (de) *	2002-10-29	2004-05-19	Aventis Pharma Deutschland Gmbh	Kristalle von Insulinanaloga und Verfahren zu ihrer Herstellung
US20040138099A1 (en) *	2002-11-29	2004-07-15	Draeger Eberhard Kurt	Insulin administration regimens for the treatment of subjects with diabetes
DE10258008B4 (de) *	2002-12-12	2006-02-02	Sanofi-Aventis Deutschland Gmbh	Heterocyclische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel
DE10258007B4 (de) *	2002-12-12	2006-02-09	Sanofi-Aventis Deutschland Gmbh	Aromatische Fluorglycosidderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zur Herstellung dieser Arzneimittel
US20040242583A1 (en) *	2003-01-20	2004-12-02	Aventis Pharma Deutschland Gmbh	Pyrimido[5,4-e][1,2,4]triazine-5,7-diones, processes for preparing them and their use
US7179941B2 (en) *	2003-01-23	2007-02-20	Sanofi-Aventis Deutschland Gmbh	Carbonylamino-substituted acyl phenyl urea derivatives, process for their preparation and their use
DE10306250A1 (de)	2003-02-14	2004-09-09	Aventis Pharma Deutschland Gmbh	Substituierte N-Arylheterozyklen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
US7196114B2 (en) *	2003-02-17	2007-03-27	Sanofi-Aventis Deutschland Gmbh	Substituted 3-(benzoylureido) thiophene derivatives, processes for preparing them and their use
DE10308353A1 (de) *	2003-02-27	2004-12-02	Aventis Pharma Deutschland Gmbh	Diarylcycloalkylderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
DE10308351A1 (de) *	2003-02-27	2004-11-25	Aventis Pharma Deutschland Gmbh	1,3-substituierte Cycloalkylderivate mit sauren, meist heterocyclischen Gruppen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
US7173151B2 (en) *	2003-02-27	2007-02-06	Sanofi-Aventisdeutschand Gmbh	Cycloalkyl-substituted alkanoic acid derivatives, processes for their preparation and their use as pharmaceuticals
DE10308355A1 (de) *	2003-02-27	2004-12-23	Aventis Pharma Deutschland Gmbh	Aryl-cycloalkyl substituierte Alkansäurederivate, Verfahren zu ihrer Herstellung und ihre Anwendung als Arzneimittel
DE10308352A1 (de) *	2003-02-27	2004-09-09	Aventis Pharma Deutschland Gmbh	Arylcycloalkylderivate mit verzweigten Seitenketten, Verfahren zu ihrer Herstellung und ihre Anwendung als Arzneimittel
US7148246B2 (en) *	2003-02-27	2006-12-12	Sanofi-Aventis Deutschland Gmbh	Cycloalkyl derivatives having bioisosteric carboxylic acid groups, processes for their preparation and their use as pharmaceuticals
US7871607B2 (en) *	2003-03-05	2011-01-18	Halozyme, Inc.	Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases
US7501440B2 (en) *	2003-03-07	2009-03-10	Sanofi-Aventis Deutschland Gmbh	Substituted benzoylureidopyridylpiperidine-and-pyrrolidinecarboxylic acid derivatives, processes for preparing them and their use
DE10314610A1 (de) *	2003-04-01	2004-11-04	Aventis Pharma Deutschland Gmbh	Neues Diphenylazetidinon mit verbesserten physiologischen Eigenschaften, Verfahren zu dessen Herstellung, diese Verbindungen enthaltende Arzneimittel und dessen Verwendung
US20050054818A1 (en) *	2003-07-02	2005-03-10	Brader Mark Laurence	Crystalline compositions for controlling blood glucose
DE602004021603D1 (de) *	2003-07-25	2009-07-30	Conjuchem Biotechnologies Inc	Insulinderivative mit langanhaltender wirkung und verfahren zu deren herstellung
US7094800B2 (en) *	2003-07-25	2006-08-22	Sanofi-Aventis Deutschland Gmbh	Cyanopyrrolidides, process for their preparation and their use as medicaments
US7008957B2 (en) *	2003-07-25	2006-03-07	Sanofi-Aventis Deutschland Gmbh	Bicyclic cyanoheterocycles, process for their preparation and their use as medicaments
US7094794B2 (en) *	2003-07-28	2006-08-22	Sanofi-Aventis Deutschland Gmbh	Substituted thiazole-benzoisothiazole dioxide derivatives, process for their preparation and their use
DE10335092B3 (de) *	2003-08-01	2005-02-03	Aventis Pharma Deutschland Gmbh	Substituierte Benzoylureido-o-benzoylamide, Verfahren zu deren Herstellung und deren Verwendung
ES2472421T3 (es)	2003-08-05	2014-07-01	Novo Nordisk A/S	Nuevos derivados de insulina
US7241787B2 (en) *	2004-01-25	2007-07-10	Sanofi-Aventis Deutschland Gmbh	Substituted N-cycloexylimidazolinones, process for their preparation and their use as medicaments
US7402674B2 (en) *	2004-01-31	2008-07-22	Sanofi-Aventis Deutschland Gmbh,	7-Phenylamino-4-quinolone-3-carboxylic acid derivatives, process for their preparation and their use as medicaments
US7470706B2 (en) *	2004-01-31	2008-12-30	Sanofi-Aventis Deutschland Gmbh	Cycloalkyl-substituted 7-amino-4-quinolone-3-carboxylic acid derivatives, process for their preparation and their use as medicaments
US7498341B2 (en) *	2004-01-31	2009-03-03	Sanofi Aventis Deutschland Gmbh	Heterocyclically substituted 7-amino-4-quinolone-3-carboxylic acid derivatives, process for their preparation and their use as medicaments
DE102004005172A1 (de) *	2004-02-02	2005-08-18	Aventis Pharma Deutschland Gmbh	Indazolderivate als Inhibitoren der Hormon Sensitiven Lipase
EP1586573B1 (fr)	2004-04-01	2007-02-07	Sanofi-Aventis Deutschland GmbH	Oxadiazolones, procédé pour leur préparation, usage comme agents pharmaceutiques
GT200500063A (es)	2004-04-01	2005-10-14		Metodo para tratar la esquizofrenia y/o anormalidades glucoregulatorias
US7833513B2 (en)	2004-12-03	2010-11-16	Rhode Island Hospital	Treatment of Alzheimer's Disease
DE102005026762A1 (de)	2005-06-09	2006-12-21	Sanofi-Aventis Deutschland Gmbh	Azolopyridin-2-on-derivate als Inhibitoren von Lipasen und Phospholipasen
WO2007081824A2 (fr) *	2006-01-06	2007-07-19	Case Western Reserve University	Protéines résistantes à la fibrillation
EP1991575A1 (fr) *	2006-02-21	2008-11-19	Novo Nordisk A/S	Analogues d'insuline à chaîne unique et formules pharmaceutiques contenant lesdits analogues
WO2007106537A2 (fr) *	2006-03-13	2007-09-20	Activx Biosciences, Inc.	Aminoquinolones utilisées comme inhibiteurs de la gsk-3
DE102006028862A1 (de)	2006-06-23	2007-12-27	Merck Patent Gmbh	3-Amino-imidazo[1,2-a]pyridinderivate
BRPI0715160A2 (pt)	2006-08-08	2013-06-11	Sanofi Aventis	imidazolidina-2,4-dionas substituÍdas por arilamimoaril-alquil-, processo para preparÁ-las, medicamentos compeendendo estes compostos, e seu uso
WO2008043033A2 (fr)	2006-10-04	2008-04-10	Case Western Reserve University	Insuline et analogues de l'insuline résistants à la fibrillation
DE102007002260A1 (de) *	2007-01-16	2008-07-31	Sanofi-Aventis	Verwendung von substituierten Pyranonsäurederivaten zur Herstellung von Medikamenten zur Behandlung des Metabolischen Syndroms
DE102007005045B4 (de)	2007-01-26	2008-12-18	Sanofi-Aventis	Phenothiazin Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
DE102007008420A1 (de)	2007-02-21	2008-08-28	Merck Patent Gmbh	Benzimidazolderivate
EP2025674A1 (fr)	2007-08-15	2009-02-18	sanofi-aventis	Tetrahydronaphthaline substituée, son procédé de fabrication et son utilisation en tant que médicament
CN101855228B (zh) *	2007-09-11	2012-10-24	杏林制药株式会社	作为gsk-3抑制剂的氰基氨基喹诺酮和四唑并氨基喹诺酮
US8476261B2 (en)	2007-09-12	2013-07-02	Kyorin Pharmaceutical Co., Ltd.	Spirocyclic aminoquinolones as GSK-3 inhibitors
DE102007048716A1 (de)	2007-10-11	2009-04-23	Merck Patent Gmbh	Imidazo[1,2-a]pyrimidinderivate
DE102007054497B3 (de)	2007-11-13	2009-07-23	Sanofi-Aventis Deutschland Gmbh	Neue kristalline Diphenylazetidinonhydrate und Verfahren zu deren Herstellung
ES2632504T3 (es)	2007-11-20	2017-09-13	Ambrx, Inc.	Polipéptidos de insulina modificados y sus usos
AU2009203809B2 (en)	2008-01-09	2013-07-25	Sanofi-Aventis Deutschland Gmbh	Novel insulin derivatives having an extremely delayed time-action profile
BRPI0907119A2 (pt)	2008-01-09	2015-07-14	Sanofi Aventis Deutschland	Derivados de insulina tendo um perfil de ação de tempo extremamente retardado
WO2009097995A1 (fr) *	2008-02-07	2009-08-13	Sanofi-Aventis	Nouvelles imidazolidines substituées par un phényle, procédé de production, médicaments contenant ces composés et leur utilisation
DE102008017590A1 (de)	2008-04-07	2009-10-08	Merck Patent Gmbh	Glucopyranosidderivate
US8993516B2 (en) *	2008-04-14	2015-03-31	Case Western Reserve University	Meal-time insulin analogues of enhanced stability
WO2009132129A2 (fr) *	2008-04-22	2009-10-29	Case Western Reserve University	Analogues de l’insuline spécifiques à l’isoforme
TWI394580B (zh)	2008-04-28	2013-05-01	Halozyme Inc	超快起作用胰島素組成物
WO2010003624A2 (fr)	2008-07-09	2010-01-14	Sanofi-Aventis	Composés hétérocycliques, leurs procédés de préparation, médicaments comprenant lesdits composés et leur utilisation
US9200053B2 (en)	2008-07-31	2015-12-01	Case Western Reserve University	Insulin analogues containing penta-fluoro-Phenylalanine at position B24
KR20120129875A (ko) *	2008-07-31	2012-11-28	케이스 웨스턴 리저브 유니버시티	염소화 아미노산을 갖는 인슐린 유사체
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
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
WO2010068601A1 (fr)	2008-12-08	2010-06-17	Sanofi-Aventis	Hydrate de fluoroglycoside hétéroaromatique cristallin, ses procédés de fabrication, ses procédés d'utilisation et compositions pharmaceutiques le contenant
KR101748891B1 (ko) *	2009-03-11	2017-06-19	교린 세이야꾸 가부시키 가이샤	Ｇｓｋ-3 억제제로서의 7-시클로알킬아미노퀴놀론
KR101853606B1 (ko)	2009-07-06	2018-05-03	사노피-아벤티스 도이칠란트 게엠베하	메티오닌을 함유하는 수성 인슐린 제제
EP2451824A4 (fr) *	2009-07-09	2013-04-24	Biocon Ltd	Procédé chromatographique basé sur un gradient non-linéaire préparatif et ses produits purifiés
SG178193A1 (en)	2009-07-31	2012-03-29	Sanofi Aventis Deutschland	Prodrugs comprising an insulin linker conjugate
SG178195A1 (en)	2009-07-31	2012-03-29	Sanofi Aventis Deutschland	Long acting insulin composition
DK2470552T3 (en)	2009-08-26	2014-02-17	Sanofi Sa	NOVEL, CRYSTALLINE, heteroaromatic FLUORGLYCOSIDHYDRATER, MEDICINES COVERING THESE COMPOUNDS AND THEIR USE
US8399407B2 (en) *	2009-09-17	2013-03-19	Case Western Reserve University	Non-standard insulin analogues
MX2012003400A (es)	2009-10-02	2012-04-10	Sanofi Sa	Uso de compuestos con actividad inhibidora de sglt - 1/sglt - 2 para producir medicamentos para el tratamiento de enfermedades oseas.
KR101337322B1 (ko)	2009-11-13	2013-12-06	사노피-아벤티스 도이칠란트 게엠베하	Ｇｌｐ-1 효능제 및 메티오닌을 포함하는 약제학적 조성물
DK2498802T3 (en)	2009-11-13	2015-04-13	Sanofi Aventis Deutschland	Pharmaceutical composition comprising a GLP-1 agonist, insulin and a methionine
JP5866120B2 (ja)	2009-12-11	2016-02-17	ケースウェスタンリザーブユニバーシティＣａｓｅＷｅｓｔｅｒｎｒｅｓｅｒｖｅＵｎｉｖｅｒｓｉｔｙ	塩素化アミノ酸を有するインスリン類似体
WO2011107494A1 (fr)	2010-03-03	2011-09-09	Sanofi	Nouveaux dérivés aromatiques de glycoside, médicaments contenants ces composés, et leur utilisation
DE102010015123A1 (de)	2010-04-16	2011-10-20	Sanofi-Aventis Deutschland Gmbh	Benzylamidische Diphenylazetidinone, diese Verbindungen enthaltende Arzneimittel und deren Verwendung
US8530413B2 (en)	2010-06-21	2013-09-10	Sanofi	Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments
KR20130036290A (ko)	2010-06-23	2013-04-11	노보 노르디스크 에이/에스	추가 이황화 결합을 함유하는 인슐린 유도체
TW201215387A (en)	2010-07-05	2012-04-16	Sanofi Aventis	Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament
TW201215388A (en)	2010-07-05	2012-04-16	Sanofi Sa	(2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments
TW201221505A (en)	2010-07-05	2012-06-01	Sanofi Sa	Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament
SMT201900495T1 (it)	2010-08-17	2019-11-13	Ambrx Inc	Polipeptidi di relaxina modificati e loro usi
ES2606554T3 (es)	2010-08-30	2017-03-24	Sanofi-Aventis Deutschland Gmbh	Uso de AVE0010 para la fabricación de un medicamento para el tratamiento de la diabetes mellitus de tipo 2
EP2438930A1 (fr)	2010-09-17	2012-04-11	Sanofi-Aventis Deutschland GmbH	Promédicaments comprenant un conjugué de liaison d'exendine
SG192038A1 (en)	2011-01-20	2013-08-30	Zealand Pharma As	Combination of acylated glucagon analogues with insulin analogues
WO2012120050A1 (fr)	2011-03-08	2012-09-13	Sanofi	Nouveaux dérivés phényl-oxathiazine substitués, procédé pour leur préparation, médicaments contenant ces composés et leur utilisation
US8710050B2 (en)	2011-03-08	2014-04-29	Sanofi	Di and tri- substituted oxathiazine derivatives, method for the production, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120054A1 (fr)	2011-03-08	2012-09-13	Sanofi	Dérivés oxathiazine di- et tri-substitués, procédé pour leur préparation, utilisation en tant que médicament, agent pharmaceutique contenant ces dérivés et utilisation
US8809325B2 (en)	2011-03-08	2014-08-19	Sanofi	Benzyl-oxathiazine derivatives substituted with adamantane and noradamantane, medicaments containing said compounds and use thereof
WO2012120056A1 (fr)	2011-03-08	2012-09-13	Sanofi	Dérivés oxathiazine tétra-substitués, procédé pour leur préparation, utilisation en tant que médicament, agent pharmaceutique contenant ces dérivés et utilisation
EP2683703B1 (fr)	2011-03-08	2015-05-27	Sanofi	Nouveaux dérivés phényl-oxathiazine substitués, procédé pour leur préparation, agent pharmaceutique contenant ces composés et leur utilisation
WO2012120058A1 (fr)	2011-03-08	2012-09-13	Sanofi	Dérivés d'oxathiazine substitués par des groupes benzyle ou hétérométhylène, leur procédé de production, leur utilisation comme médicament ainsi que produits pharmaceutiques les contenant et leur utilisation
EP2683704B1 (fr)	2011-03-08	2014-12-17	Sanofi	Dérivés oxathiazine ramifiés, procédé pour leur préparation, utilisation en tant que médicament, agents pharmaceutiques contenant ces dérivés et leur utilisation
EP2766349B1 (fr)	2011-03-08	2016-06-01	Sanofi	Dérivés d'oxathiazine substitués par des carbocycles ou des hétérocycles, leur procédé de préparation, médicaments contenant ces composés et leur utilisation
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
US9487572B2 (en) *	2011-07-13	2016-11-08	Case Western Reserve University	Non-standard insulin analogues
US10995129B2 (en) *	2011-07-13	2021-05-04	Case Western Reserve University	Non-standard insulin analogues
PL2750699T3 (pl)	2011-08-29	2015-12-31	Sanofi Aventis Deutschland	Kombinacja farmaceutyczna do stosowania w kontroli glikemii u pacjentów z cukrzycą typu 2
AR087744A1 (es)	2011-09-01	2014-04-16	Sanofi Aventis Deutschland	Composicion farmaceutica para uso en el tratamiento de una enfermedad neurodegenerativa
WO2013037390A1 (fr)	2011-09-12	2013-03-21	Sanofi	Dérivés amides d'acide 6-(4-hydroxyphényl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylique en tant qu'inhibiteurs de kinase
EP2567959B1 (fr)	2011-09-12	2014-04-16	Sanofi	Dérivés d'amide d'acide 6-(4-hydroxy-phényl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylique en tant qu'inhibiteurs de kinase
WO2013045413A1 (fr)	2011-09-27	2013-04-04	Sanofi	Dérivés d'amide d'acide 6-(4-hydroxyphényl)-3-alkyl-1h-pyrazolo[3,4-b] pyridine-4-carboxylique utilisés comme inhibiteurs de kinase
WO2013151663A1 (fr) *	2012-04-02	2013-10-10	modeRNA Therapeutics	Polynucléotides modifiés pour la production de protéines membranaires
AR090843A1 (es) *	2012-05-09	2014-12-10	Lilly Co Eli	Tratamiento para diabetes comorbida con enfermedad renal cronica
WO2013173923A1 (fr)	2012-05-25	2013-11-28	Diamedica, Inc.	Formulations de kallikréine 1 de tissu humain pour l'administration parentérale et procédés associés
PT2854841T (pt)	2012-06-04	2017-05-15	Diamedica Inc	Isoformas de glicosilação da calicreína 1 em tecido humano
CA2961037A1 (fr)	2014-10-06	2016-04-14	Case Western Reserve University	Analogues de l'insuline a chaine unique biphasique
AU2015359376B2 (en)	2014-12-12	2021-09-09	Sanofi-Aventis Deutschland Gmbh	Insulin glargine/lixisenatide fixed ratio formulation
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
US11857608B2 (en)	2017-03-09	2024-01-02	Diamedica Inc.	Dosage forms of tissue kallikrein 1
AU2019318209B2 (en)	2018-08-10	2025-09-25	Diapin Therapeutics, Llc	Tri-peptides and treatment of metabolic, cardiovascular and inflammatory disorders

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3758683A (en) *	1971-04-30	1973-09-11	R Jackson	Insulin product
US3868358A (en)	1971-04-30	1975-02-25	Lilly Co Eli	Protamine-insulin product
US4783441A (en)	1979-04-30	1988-11-08	Hoechst Aktiengesellschaft	Aqueous protein solutions stable to denaturation
EP0018609B1 (fr)	1979-04-30	1983-09-21	Hoechst Aktiengesellschaft	Solutions aqueuses de protéines, stables à la dénaturation, procédé pour leur fabrication et leur utilisation
AU558474B2 (en)	1981-07-17	1987-01-29	Nordisk Insulinlaboratorium	A stable aqueous, therapeutic insulin preparation and a process for preparing it
NL193099C (nl)	1981-10-30	1998-11-03	Novo Industri As	Gestabiliseerde insuline-oplossing.
DE3440988A1 (de)	1984-11-09	1986-07-10	Hoechst Ag, 6230 Frankfurt	Verfahren zur spaltung von peptiden und proteinen an der methionyl-bindung
DE3526995A1 (de)	1985-07-27	1987-02-05	Hoechst Ag	Fusionsproteine, verfahren zu ihrer herstellung und ihre verwendung
PH25772A (en)	1985-08-30	1991-10-18	Novo Industri As	Insulin analogues, process for their preparation
DE3541856A1 (de)	1985-11-27	1987-06-04	Hoechst Ag	Eukaryotische fusionsproteine, ihre herstellung und verwendung sowie mittel zur durchfuehrung des verfahrens
DE3544295A1 (de)	1985-12-14	1987-06-19	Bayer Ag	Thermoplastische formmassen mit hoher kriechstromfestigkeit
DE3726655A1 (de)	1987-08-11	1989-02-23	Hoechst Ag	Verfahren zur isolierung basischer proteine aus proteingemischen, welche solche basischen proteine enthalten
DK257988D0 (da)	1988-05-11	1988-05-11	Novo Industri As	Nye peptider
AU641631B2 (en) *	1988-12-23	1993-09-30	Novo Nordisk A/S	Human insulin analogues
PT93057B (pt) *	1989-02-09	1995-12-29	Lilly Co Eli	Processo para a preparacao de analogos da insulina
US5358857A (en)	1989-08-29	1994-10-25	The General Hospital Corp.	Method of preparing fusion proteins
DK155690D0 (da)	1990-06-28	1990-06-28	Novo Nordisk As	Nye peptider
DK10191D0 (da) *	1991-01-22	1991-01-22	Novo Nordisk As	Hidtil ukendte peptider
SG46612A1 (en)	1992-12-02	1998-02-20	Hoechst Ag	Process for obtaining proinsulin in processing correctly linked cystine bridges
DE4405179A1 (de)	1994-02-18	1995-08-24	Hoechst Ag	Verfahren zur Gewinnung von Insulin mit korrekt verbundenen Cystinbrücken

1997
- 1997-06-20 DE DE19726167A patent/DE19726167B4/de not_active Expired - Lifetime
1998
- 1998-06-15 ES ES98110889T patent/ES2232900T3/es not_active Expired - Lifetime
- 1998-06-15 PT PT98110889T patent/PT885961E/pt unknown
- 1998-06-15 AT AT98110889T patent/ATE283919T1/de active
- 1998-06-15 EP EP98110889A patent/EP0885961B1/fr not_active Expired - Lifetime
- 1998-06-15 DE DE59812316T patent/DE59812316D1/de not_active Expired - Lifetime
- 1998-06-15 DE DE200412000049 patent/DE122004000049I2/de active Active
- 1998-06-15 DK DK98110889T patent/DK0885961T3/da active
- 1998-06-17 NZ NZ330700A patent/NZ330700A/xx not_active IP Right Cessation
- 1998-06-17 SK SK836-98A patent/SK285267B6/sk not_active IP Right Cessation
- 1998-06-18 TR TR1998/01144A patent/TR199801144A2/xx unknown
- 1998-06-18 RU RU98112109/14A patent/RU2207874C9/ru active Protection Beyond IP Right Term
- 1998-06-18 ID IDP980887A patent/ID20462A/id unknown
- 1998-06-18 AR ARP980102911A patent/AR015899A1/es active IP Right Grant
- 1998-06-18 CZ CZ19981934A patent/CZ295964B6/cs not_active IP Right Cessation
- 1998-06-18 UA UA98063193A patent/UA65529C2/uk unknown
- 1998-06-18 HU HU9801368A patent/HU221176B1/hu active Protection Beyond IP Right Term
- 1998-06-18 CA CA2235443A patent/CA2235443C/fr not_active Expired - Lifetime
- 1998-06-18 US US09/099,307 patent/US6221633B1/en not_active Expired - Lifetime
- 1998-06-19 JP JP17237998A patent/JP3676573B2/ja not_active Expired - Lifetime
- 1998-06-19 AU AU73064/98A patent/AU740344C/en not_active Expired
- 1998-06-19 CN CNB981149502A patent/CN1195777C/zh not_active Expired - Lifetime
- 1998-06-19 NO NO19982860A patent/NO321720B1/no not_active IP Right Cessation
- 1998-06-19 ZA ZA985363A patent/ZA985363B/xx unknown
- 1998-06-19 IL IL125006A patent/IL125006A/en not_active IP Right Cessation
- 1998-06-19 KR KR1019980023037A patent/KR100546225B1/ko not_active Expired - Lifetime
- 1998-06-20 PL PL326936A patent/PL196626B1/pl unknown
- 1998-06-22 BR BRPI9803708A patent/BRPI9803708B8/pt not_active IP Right Cessation
- 1998-07-10 TW TW087109743A patent/TW562806B/zh not_active IP Right Cessation
2005
- 2005-01-27 NL NL300170C patent/NL300170I2/nl unknown
- 2005-02-02 LU LU91138C patent/LU91138I2/fr unknown
- 2005-03-21 FR FR05C0009C patent/FR05C0009I2/fr active Active
- 2005-03-28 CY CY200500004C patent/CY2005004I1/el unknown
2006
- 2006-10-26 NO NO2006014C patent/NO2006014I1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
HU221176B1 (en)	2002-08-28
AU740344B2 (en)	2001-11-01
AU740344C (en)	2006-12-07
CY2005004I2 (el)	2009-11-04
BR9803708A (pt)	2000-03-28
DE59812316D1 (de)	2005-01-05
PL196626B1 (pl)	2008-01-31
CA2235443A1 (fr)	1998-12-20
BRPI9803708B1 (pt)	2016-09-27
NL300170I2 (nl)	2005-07-01
TR199801144A3 (tr)	1999-01-18
DE122004000049I1 (de)	2005-05-04
TR199801144A2 (xx)	1999-01-18
NO982860D0 (no)	1998-06-19
CZ295964B6 (cs)	2005-12-14
KR100546225B1 (ko)	2006-10-19
SK83698A3 (en)	1999-01-11
RU2207874C9 (ru)	2007-12-20
ZA985363B (en)	1999-01-19
HU9801368D0 (en)	1998-08-28
KR19990007117A (ko)	1999-01-25
ID20462A (id)	1998-12-24
JP3676573B2 (ja)	2005-07-27
DE19726167B4 (de)	2008-01-24
CA2235443C (fr)	2011-11-01
NO2006014I1 (no)	2006-11-13
NO2006014I2 (fr)	2012-02-13
JPH119291A (ja)	1999-01-19
FR05C0009I1 (fr)	2005-09-30
NZ330700A (en)	1999-11-29
ES2232900T3 (es)	2005-06-01
DE122004000049I2 (de)	2006-02-23
NL300170I1 (nl)	2005-04-01
CN1203238A (zh)	1998-12-30
DK0885961T3 (da)	2005-03-21
EP0885961A1 (fr)	1998-12-23
US6221633B1 (en)	2001-04-24
TW562806B (en)	2003-11-21
IL125006A0 (en)	1999-01-26
HK1016616A1 (en)	1999-11-05
NO982860L (no)	1998-12-21
HUP9801368A1 (hu)	1999-05-28
ATE283919T1 (de)	2004-12-15
IL125006A (en)	2006-12-31
BRPI9803708B8 (pt)	2021-05-25
CN1195777C (zh)	2005-04-06
LU91138I2 (fr)	2005-04-04
PT885961E (pt)	2005-03-31
SK285267B6 (sk)	2006-10-05
PL326936A1 (en)	1998-12-21
HUP9801368A3 (en)	1999-09-28
UA65529C2 (uk)	2004-04-15
CZ193498A3 (cs)	1999-11-17
DE19726167A1 (de)	1999-01-28
EP0885961B1 (fr)	2004-12-01
CY2005004I1 (el)	2009-11-04
AU7306498A (en)	1998-12-24
FR05C0009I2 (fr)	2007-07-27
RU2207874C2 (ru)	2003-07-10
AR015899A1 (es)	2001-05-30

Legal Events

Date	Code	Title	Description
2006-11-13	SPCF	Filing of supplementary protection certificate	Free format text: PRODUCT NAME: APIDRA (20041025 MA); NAT. REG. NO/DATE: EU104285001 20041025 Spc suppl protection certif: 2006014 Filing date: 20061026
2012-02-13	SPCG	Granted supplementary protection certificate	Free format text: PRODUCT NAME: APIDRA (20041025 MA); NAT. REG. NO/DATE: EU104285001 20041025 Spc suppl protection certif: 2006014 Filing date: 20061026 Extension date: 20190927
2016-02-29	SPCK	Change in the validity period of an spc	Free format text: PROTECTION PERIOD CHANGED TO: 20190929 Spc suppl protection certif: 2006014
2018-07-09	MK1K	Patent expired
2019-10-07	SPCX	Expiry of an spc	Spc suppl protection certif: 2006014

Publication	Publication Date	Title
CA2235443C (fr)	2011-11-01	Nouveaux derives d'insuline a action rapide
RU2524423C2 (ru)	2014-07-27	Новые производные инсулина с чрезвычайно замедленным профилем время/действие
JP5695909B2 (ja)	2015-04-08	極度に遅延した時間作用プロファイルを有する新規なインスリン誘導体
US8048854B2 (en)	2011-11-01	Amidated insulin glargine
US5268453A (en)	1993-12-07	Tissue-selective insulin analogs
RU2176646C2 (ru)	2001-12-10	Инсулин и его производные с повышенной способностью связывать цинк
IE901004L (en)	1990-09-20	Novel insulin compounds
JP4402296B2 (ja)	2010-01-20	亜鉛結合性が増大された新規なインスリン同族体
WO2025162138A1 (fr)	2025-08-07	Analogue d'insuline à action ultra-longue, son procédé de préparation et son utilisation
MXPA98004945A (en)	1999-06-01	New insulin derivatives with rapid initiation of efe
HK1036808B (en)	2013-03-28	Novel insulin analogs with enhanced zinc binding