CA2468374C - Glp-1 derivatives - Google Patents
Glp-1 derivatives Download PDFInfo
- Publication number
- CA2468374C CA2468374C CA2468374A CA2468374A CA2468374C CA 2468374 C CA2468374 C CA 2468374C CA 2468374 A CA2468374 A CA 2468374A CA 2468374 A CA2468374 A CA 2468374A CA 2468374 C CA2468374 C CA 2468374C
- Authority
- CA
- Canada
- Prior art keywords
- glp
- arg26
- derivative
- arg
- lys
- 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.)
- Expired - Lifetime
Links
- 101100337060 Caenorhabditis elegans glp-1 gene Proteins 0.000 title 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims abstract description 211
- 101800004266 Glucagon-like peptide 1(7-37) Proteins 0.000 claims abstract description 19
- 230000009471 action Effects 0.000 claims abstract description 13
- 102400000324 Glucagon-like peptide 1(7-37) Human genes 0.000 claims abstract 2
- 125000001424 substituent group Chemical group 0.000 claims description 114
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 claims description 97
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 83
- 125000000539 amino acid group Chemical group 0.000 claims description 51
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 46
- 125000006850 spacer group Chemical group 0.000 claims description 44
- 125000003277 amino group Chemical group 0.000 claims description 33
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 claims description 28
- 108010016626 Dipeptides Proteins 0.000 claims description 24
- 108010015792 glycyllysine Proteins 0.000 claims description 22
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 20
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 13
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000000729 N-terminal amino-acid group Chemical group 0.000 claims description 9
- 101001015516 Homo sapiens Glucagon-like peptide 1 receptor Proteins 0.000 claims description 8
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 8
- IKAIKUBBJHFNBZ-LURJTMIESA-N Gly-Lys Chemical group NCCCC[C@@H](C(O)=O)NC(=O)CN IKAIKUBBJHFNBZ-LURJTMIESA-N 0.000 claims description 7
- 239000000556 agonist Substances 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 4
- 101800001707 Spacer peptide Proteins 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 3
- 229930195729 fatty acid Natural products 0.000 claims description 3
- 239000000194 fatty acid Substances 0.000 claims description 3
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims description 2
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 claims 4
- 125000005480 straight-chain fatty acid group Chemical group 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 197
- 150000001413 amino acids Chemical class 0.000 description 193
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 160
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 148
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 121
- 239000000203 mixture Substances 0.000 description 103
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 102
- 102100040918 Pro-glucagon Human genes 0.000 description 99
- 108090000623 proteins and genes Proteins 0.000 description 97
- 102000004169 proteins and genes Human genes 0.000 description 94
- 239000000243 solution Substances 0.000 description 94
- FBNPMTNBFFAMMH-UHFFFAOYSA-N Leu-Val-Arg Natural products CC(C)CC(N)C(=O)NC(C(C)C)C(=O)NC(C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-UHFFFAOYSA-N 0.000 description 80
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 78
- 239000011541 reaction mixture Substances 0.000 description 77
- LLWQVJNHMYBLLK-CDMKHQONSA-N Gly-Thr-Phe Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LLWQVJNHMYBLLK-CDMKHQONSA-N 0.000 description 63
- IVDFVBVIVLJJHR-LKXGYXEUSA-N Thr-Ser-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IVDFVBVIVLJJHR-LKXGYXEUSA-N 0.000 description 62
- KSCVLGXNQXKUAR-JYJNAYRXSA-N Tyr-Leu-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O KSCVLGXNQXKUAR-JYJNAYRXSA-N 0.000 description 59
- 150000001875 compounds Chemical class 0.000 description 59
- PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 58
- CQZDZKRHFWJXDF-WDSKDSINSA-N Gly-Gln-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CN CQZDZKRHFWJXDF-WDSKDSINSA-N 0.000 description 57
- WUGMRIBZSVSJNP-UHFFFAOYSA-N N-L-alanyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C)C(O)=O)=CNC2=C1 WUGMRIBZSVSJNP-UHFFFAOYSA-N 0.000 description 54
- VZFPYFRVHMSSNA-JURCDPSOSA-N Phe-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC1=CC=CC=C1 VZFPYFRVHMSSNA-JURCDPSOSA-N 0.000 description 54
- WMBFONUKQXGLMU-WDSOQIARSA-N Trp-Leu-Val Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N WMBFONUKQXGLMU-WDSOQIARSA-N 0.000 description 52
- SVBXIUDNTRTKHE-CIUDSAMLSA-N Ala-Arg-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O SVBXIUDNTRTKHE-CIUDSAMLSA-N 0.000 description 48
- KFMBRBPXHVMDFN-UWVGGRQHSA-N Gly-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCNC(N)=N KFMBRBPXHVMDFN-UWVGGRQHSA-N 0.000 description 47
- 230000015572 biosynthetic process Effects 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 47
- AFPFGFUGETYOSY-HGNGGELXSA-N His-Ala-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AFPFGFUGETYOSY-HGNGGELXSA-N 0.000 description 46
- 238000003786 synthesis reaction Methods 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- HQIZDMIGUJOSNI-IUCAKERBSA-N Arg-Gly-Arg Chemical compound N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O HQIZDMIGUJOSNI-IUCAKERBSA-N 0.000 description 43
- 239000000047 product Substances 0.000 description 41
- -1 : . calatoniri Chemical compound 0.000 description 40
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 38
- 150000001793 charged compounds Chemical class 0.000 description 35
- 239000004471 Glycine Substances 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
- 238000004440 column chromatography Methods 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- SKTGPBFTMNLIHQ-KKUMJFAQSA-N Arg-Glu-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SKTGPBFTMNLIHQ-KKUMJFAQSA-N 0.000 description 26
- 108010080629 tryptophan-leucine Proteins 0.000 description 26
- WZPIKDWQVRTATP-SYWGBEHUSA-N Ile-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)[C@@H](C)CC)C(O)=O)=CNC2=C1 WZPIKDWQVRTATP-SYWGBEHUSA-N 0.000 description 24
- YJIUYQKQBBQYHZ-ACZMJKKPSA-N Gln-Ala-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O YJIUYQKQBBQYHZ-ACZMJKKPSA-N 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
- FBNPMTNBFFAMMH-AVGNSLFASA-N Leu-Val-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-AVGNSLFASA-N 0.000 description 22
- HOYQLNNGMHXZDW-KKUMJFAQSA-N Phe-Glu-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O HOYQLNNGMHXZDW-KKUMJFAQSA-N 0.000 description 22
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- 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
- C07K14/605—Glucagons
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- A—HUMAN NECESSITIES
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- 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
- A61K38/26—Glucagons
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- A—HUMAN NECESSITIES
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- 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
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- 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
- A61K47/51—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 the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Obesity (AREA)
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- Molecular Biology (AREA)
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- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Vehicle Interior And Exterior Ornaments, Soundproofing, And Insulation (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK0931/96 | 1996-08-30 | ||
| DK93196 | 1996-08-30 | ||
| DK1259/96 | 1996-11-08 | ||
| DK125996 | 1996-11-08 | ||
| DK147096 | 1996-12-20 | ||
| DK1470/96 | 1996-12-20 | ||
| CA002264243A CA2264243C (en) | 1996-08-30 | 1997-08-22 | Glp-1 derivatives |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002264243A Division CA2264243C (en) | 1996-08-30 | 1997-08-22 | Glp-1 derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2468374A1 CA2468374A1 (en) | 1998-03-05 |
| CA2468374C true CA2468374C (en) | 2010-12-21 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2468374A Expired - Lifetime CA2468374C (en) | 1996-08-30 | 1997-08-22 | Glp-1 derivatives |
| CA002264243A Expired - Lifetime CA2264243C (en) | 1996-08-30 | 1997-08-22 | Glp-1 derivatives |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002264243A Expired - Lifetime CA2264243C (en) | 1996-08-30 | 1997-08-22 | Glp-1 derivatives |
Country Status (21)
| Country | Link |
|---|---|
| EP (2) | EP1826216A1 (enExample) |
| JP (3) | JP3149958B2 (enExample) |
| KR (1) | KR100556067B1 (enExample) |
| CN (1) | CN1271086C (enExample) |
| AT (1) | ATE356830T1 (enExample) |
| BR (1) | BRPI9711437B8 (enExample) |
| CA (2) | CA2468374C (enExample) |
| CZ (1) | CZ300837B6 (enExample) |
| DE (3) | DE69737479T4 (enExample) |
| DK (1) | DK0944648T3 (enExample) |
| ES (1) | ES2283025T3 (enExample) |
| FR (1) | FR09C0054I2 (enExample) |
| HU (1) | HU227021B1 (enExample) |
| IL (3) | IL128332A0 (enExample) |
| NL (1) | NL300422I2 (enExample) |
| NO (3) | NO325273B1 (enExample) |
| PL (1) | PL192359B1 (enExample) |
| PT (1) | PT944648E (enExample) |
| RU (1) | RU2214419C2 (enExample) |
| UA (1) | UA72181C2 (enExample) |
| WO (1) | WO1998008871A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2001501593A (ja) | 1996-08-08 | 2001-02-06 | アミリン・ファーマシューティカルズ，インコーポレイテッド | 胃腸運動を調節するための方法 |
| US6268343B1 (en) | 1996-08-30 | 2001-07-31 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| ES2283025T3 (es) * | 1996-08-30 | 2007-10-16 | Novo Nordisk A/S | Derivados de glp-1.1. |
| US7235627B2 (en) | 1996-08-30 | 2007-06-26 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| US6458924B2 (en) | 1996-08-30 | 2002-10-01 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| UA65549C2 (uk) | 1996-11-05 | 2004-04-15 | Елі Ліллі Енд Компані | Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція |
| US6380357B2 (en) | 1997-12-16 | 2002-04-30 | Eli Lilly And Company | Glucagon-like peptide-1 crystals |
| AU2610799A (en) * | 1998-02-27 | 1999-09-15 | Novo Nordisk A/S | Glp-1 derivatives with helix-content exceeding 25 per cent, forming partially structured micellar-like aggregates |
| DE69942307D1 (de) | 1998-02-27 | 2010-06-10 | Novo Nordisk As | N-terminal veränderte glp-1 abkömmlinge |
| WO1999043708A1 (en) * | 1998-02-27 | 1999-09-02 | Novo Nordisk A/S | Glp-1 derivatives of glp-1 and exendin with protracted profile of action |
| ATE466027T1 (de) | 1998-02-27 | 2010-05-15 | Novo Nordisk As | Abkömmlinge von glp-1 analogen |
| WO1999043705A1 (en) * | 1998-02-27 | 1999-09-02 | Novo Nordisk A/S | N-terminally truncated glp-1 derivatives |
| ATE466026T1 (de) * | 1998-02-27 | 2010-05-15 | Novo Nordisk As | Derivate von glp-1 und exendin mit verlängertem wirkdauer-profil |
| EP1950224A3 (en) | 1998-03-09 | 2008-12-17 | Zealand Pharma A/S | Pharmacologically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| JP2002523333A (ja) * | 1998-07-31 | 2002-07-30 | ノボ ノルディスク アクティーゼルスカブ | Ｉｉ型糖尿病を予防するためのｇｌｐ−１及び類似体の利用 |
| EA200100289A1 (ru) * | 1998-08-28 | 2001-10-22 | Эли Лилли Энд Компани | Способ введения инсулинотропных пептидов |
| US6720407B1 (en) | 1998-08-28 | 2004-04-13 | Eli Lilly And Company | Method for administering insulinotropic peptides |
| EP1666054A1 (en) * | 1998-08-28 | 2006-06-07 | Eli Lilly & Company | Method for administering insulinotropic peptides |
| EP1113799A4 (en) | 1998-09-17 | 2004-06-09 | Lilly Co Eli | PROTEIN-BASED PREPARATION |
| MY155270A (en) * | 1998-09-24 | 2015-09-30 | Lilly Co Eli | Use of glp-1 or analogs in treatment of stroke |
| SG125915A1 (en) * | 1998-12-07 | 2006-10-30 | Sod Conseils Rech Applic | Analogues of glp-1 |
| BR9916027A (pt) * | 1998-12-07 | 2001-08-28 | Sod Conseils Rech Applic | Análogos de glp-1 |
| CA2778047A1 (en) * | 1998-12-07 | 2000-06-15 | Ipsen Pharma S.A.S | Analogues of glp-1 |
| AU777564B2 (en) * | 1999-01-14 | 2004-10-21 | Amylin Pharmaceuticals, Inc. | Novel exendin agonist formulations and methods of administration thereof |
| US6451987B1 (en) | 1999-03-15 | 2002-09-17 | Novo Nordisk A/S | Ion exchange chromatography of proteins and peptides |
| US6444788B1 (en) | 1999-03-15 | 2002-09-03 | Novo Nordisk A/S | Ion exchange chromatography of GLP-1, analogs and derivatives thereof |
| EP1163268B1 (en) * | 1999-03-15 | 2011-05-11 | Novo Nordisk A/S | Ion exchange chromatographic separation of glp-1 and related peptides |
| JP4949557B2 (ja) * | 1999-03-17 | 2012-06-13 | ノヴォ ノルディスク アー／エス | ペプチドのアシル化方法及び新規アシル化剤 |
| US6451974B1 (en) | 1999-03-17 | 2002-09-17 | Novo Nordisk A/S | Method of acylating peptides and novel acylating agents |
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| WO2000066629A1 (en) * | 1999-04-30 | 2000-11-09 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
| US6924264B1 (en) | 1999-04-30 | 2005-08-02 | Amylin Pharmaceuticals, Inc. | Modified exendins and exendin agonists |
| US6329336B1 (en) | 1999-05-17 | 2001-12-11 | Conjuchem, Inc. | Long lasting insulinotropic peptides |
| US6514500B1 (en) | 1999-10-15 | 2003-02-04 | Conjuchem, Inc. | Long lasting synthetic glucagon like peptide {GLP-!} |
| US6528486B1 (en) | 1999-07-12 | 2003-03-04 | Zealand Pharma A/S | Peptide agonists of GLP-1 activity |
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