AR044776A1 - Proteinas de fusion analogas glp-1 - Google Patents
Proteinas de fusion analogas glp-1Info
- Publication number
- AR044776A1 AR044776A1 ARP040102037A ARP040102037A AR044776A1 AR 044776 A1 AR044776 A1 AR 044776A1 AR P040102037 A ARP040102037 A AR P040102037A AR P040102037 A ARP040102037 A AR P040102037A AR 044776 A1 AR044776 A1 AR 044776A1
- Authority
- AR
- Argentina
- Prior art keywords
- glu
- ser
- val
- gly
- lys
- Prior art date
Links
- 102000037865 fusion proteins Human genes 0.000 title abstract 6
- 108020001507 fusion proteins Proteins 0.000 title abstract 6
- 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 title abstract 3
- 230000002401 inhibitory effect Effects 0.000 abstract 3
- 102000040430 polynucleotide Human genes 0.000 abstract 2
- 108091033319 polynucleotide Proteins 0.000 abstract 2
- 239000002157 polynucleotide Substances 0.000 abstract 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 abstract 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 abstract 1
- 108060003951 Immunoglobulin Proteins 0.000 abstract 1
- 208000008589 Obesity Diseases 0.000 abstract 1
- 230000003247 decreasing effect Effects 0.000 abstract 1
- 206010012601 diabetes mellitus Diseases 0.000 abstract 1
- 239000012636 effector Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000037406 food intake Effects 0.000 abstract 1
- 235000012631 food intake Nutrition 0.000 abstract 1
- 230000002496 gastric effect Effects 0.000 abstract 1
- 230000030135 gastric motility Effects 0.000 abstract 1
- 239000008103 glucose Substances 0.000 abstract 1
- 230000005847 immunogenicity Effects 0.000 abstract 1
- 102000018358 immunoglobulin Human genes 0.000 abstract 1
- 230000000968 intestinal effect Effects 0.000 abstract 1
- 230000008991 intestinal motility Effects 0.000 abstract 1
- 208000002551 irritable bowel syndrome Diseases 0.000 abstract 1
- 235000020824 obesity Nutrition 0.000 abstract 1
- 230000001575 pathological effect Effects 0.000 abstract 1
- 238000011282 treatment Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
-
- 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
-
- 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
-
- 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
- C07K14/475—Growth factors; Growth regulators
- C07K14/50—Fibroblast growth factor [FGF]
- C07K14/503—Fibroblast growth factor [FGF] basic FGF [bFGF]
-
- 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
-
- 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
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Endocrinology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Se proporciona análogos GLP-1 específicos fusionados a derivados IgG4-Fc específicos. Estas proteínas de fusión tiene un período de vida media aumentado, una inmunogenicidad disminuida y una actividad efectora reducida. Las proteínas de fusión son útiles en los tratamientos para la diabetes, obesidad, síndrome del colon irritable y otros estados patológicos que podrían beneficiarse por medio de la baja de la glucosa en plasma, inhibiendo la motilidad gástrica y/o intestinal e inhibiendo la evacuación gástrica y/o intestinal, o inhibiendo la ingesta de alimentos. Reivindicación 1: Una proteína de fusión heteróloga que comprende un análogo GLP-1, que comprende una secuencia seleccionada del grupo que consiste de: a) (SEQ ID NO: 1) His-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Gly-Gly, donde Xaa8 es seleccionado de Gly y Val; b) (SEQ ID NO: 2) His-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Lys-Asn-Gly-Gly-Gly, donde Xaa8 es seleccionado de Gly y Val: c) (SEQ ID NO: 3) His-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Gly-Pro, donde Xaa8 es seleccionado de Gly y Val; d) (SEQ ID NO: 4) His-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Lys-Asn-Gly-Gly-Pro, donde Xaa8 es seleccionado de Gly y Val; e) (SEQ ID NO: 5) His-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Gly, donde Xaa8 es seleccionado de Gly y Val; f) (SEQ ID NO: 6) His-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Lys-Asn-Gly-Gly, donde Xaa8 es seleccionado de Gly y Val; fusionado a la porción Fc de una inmunoglobulina que comprende la secuencia de SEQ ID IN: 7 Ala-Glu-Ser-Lys-Tyr-Gly-Pro-Pro-Cys-Pro-Pro-Cys-Pro-Ala-Pro-Xaa16-Xaa17-Xaa18-Gly-Gly-Pro-Ser-Val-Phe-Leu-Phe-Pro-Pro-Lys-Pro-Lys-Asp-Thr-Leu-Met-Ile-Ser-Arg-Thr-Pro-Glu-Val-Thr-Cys-Val-Val- Val-Asp-Val-Ser-Gln-Glu-Asp-Pro-Glu-Val-Gln-Phe-Asn-Trp-Tyr-Val-Asp-Gly-Val-Glu-Val-His-Asn-Ala-Lys-Thr-Lys-Pro-Arg-Glu-Glu-Gln-Phe-Xaa80-Ser-Thr-Tyr-Arg-Val-Val-Ser-Val-Leu-Thr-Val-Leu-His-Gln-Asp-Trp-Leu-Asn-Gly-Lys-Glu-Tyr-Lys-Cys-Lys-Val-Ser-Asn- Lys-Gly-Leu-Pro-Ser-Ser-Ile-Glu-Lys-Thr-Ile-Ser-Lys-Ala-Lys-Gly-Gln-Pro-Arg-Glu-Pro-Gln-Val-Tyr-Thr-Leu-Pro-Pro-Ser-Gln-Glu-Glu-Met-Thr-Lys-Asn-Gln-Val-Ser-Leu-Thr-Cys-Leu-Val-Lys-Gly-Phe-Tyr-Pro-Ser-Asp-Ile-Ala-Val-Glu-Trp-Glu-Ser-Asn-Gly-Gln-Pro- Glu-Asn-Asn-Tyr-Lys-Thr-Thr-Pro-Pro-Val-Leu-Asp-Ser-Asp-Gly-Ser-Phe-Phe-Leu-Tyr-Ser-Arg-Leu-Thr-Val-Asp-Lys-Ser-Arg-Trp-Gln-Glu-Gly-Asn-Val-Phe-Ser-Cys-Ser-Val-Met-His-Glu-Ala-Leu-His-Asn-His-Tyr-Thr-Gln-Lys-Ser-Leu-Ser-Leu-Ser-Leu-Gly-Xaa230 (SEQ IDNO: 7), donde: Xaa en la posición 16 es Pro o Glu; Xaa en la posición 17 es Phe, Val, o Ala; Xaa en la posición 18 es Leu, Glu, o Ala; Xaa en la posición 80 es Asn o Ala; y Xaa en la posición 230 es Lys o está ausente. Reivindicación 9: Un polinucleótido que codifica la proteína de fusión heteróloga de cualquiera de las reivindicaciones 1 a 8. Reivindicación 10: Un vector que comprende el polinucleótido de la reivindicación 9. Reivindicación 12: Una célula huésped que expresa al menos una proteína de fusión heteróloga de cualquiera de las reivindicaciones 1 a 8.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US47788003P | 2003-06-12 | 2003-06-12 |
Publications (1)
Publication Number | Publication Date |
---|---|
AR044776A1 true AR044776A1 (es) | 2005-10-05 |
Family
ID=33551775
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ARP040102037A AR044776A1 (es) | 2003-06-12 | 2004-06-11 | Proteinas de fusion analogas glp-1 |
Country Status (29)
Country | Link |
---|---|
US (2) | US7452966B2 (es) |
EP (2) | EP1641823B1 (es) |
JP (1) | JP4629047B2 (es) |
KR (1) | KR100758755B1 (es) |
CN (2) | CN101974090B (es) |
AR (1) | AR044776A1 (es) |
AT (1) | ATE525395T1 (es) |
AU (1) | AU2004251145C1 (es) |
BE (1) | BE2015C007I2 (es) |
BR (1) | BRPI0411132B8 (es) |
CA (1) | CA2528591C (es) |
CY (2) | CY1111991T1 (es) |
DK (1) | DK1641823T3 (es) |
EA (1) | EA008831B1 (es) |
ES (1) | ES2371072T3 (es) |
FR (1) | FR15C0010I2 (es) |
HK (1) | HK1149566A1 (es) |
HR (1) | HRP20110714T1 (es) |
HU (1) | HUS1500024I1 (es) |
IL (1) | IL171926A (es) |
LT (1) | LTC1641823I2 (es) |
MX (1) | MXPA05013565A (es) |
NZ (1) | NZ543292A (es) |
PL (1) | PL1641823T3 (es) |
PT (1) | PT1641823E (es) |
SI (1) | SI1641823T1 (es) |
TW (1) | TW200507870A (es) |
UA (1) | UA87458C2 (es) |
WO (1) | WO2005000892A2 (es) |
Families Citing this family (166)
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DK1463751T3 (da) | 2001-12-21 | 2013-08-26 | Human Genome Sciences Inc | Albuminfusionsproteiner. |
US20070161087A1 (en) * | 2003-05-29 | 2007-07-12 | Wolfgang Glaesner | Glp-1 fusion proteins |
EA008831B1 (ru) * | 2003-06-12 | 2007-08-31 | Эли Лилли Энд Компани | Слитые белки аналогов glp-1 |
EP1729795B1 (en) | 2004-02-09 | 2016-02-03 | Human Genome Sciences, Inc. | Albumin fusion proteins |
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CN101578102B (zh) * | 2007-01-05 | 2013-07-17 | 印第安纳大学研究及科技有限公司 | 在生理性pH缓冲液中显示增强的溶解性的胰高血糖素类似物 |
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EP2109457B1 (en) | 2007-02-12 | 2016-01-06 | CSL Behring GmbH | Therapeutic application of kazal-type serine protease inhibitors |
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US8563527B2 (en) * | 2007-08-20 | 2013-10-22 | Pharmain Corporation | Oligonucleotide core carrier compositions for delivery of nucleic acid-containing therapeutic agents, methods of making and using the same |
EP2031064A1 (de) * | 2007-08-29 | 2009-03-04 | Boehringer Ingelheim Pharma GmbH & Co. KG | Verfahren zur Steigerung von Proteintitern |
EP2217701B9 (en) | 2007-10-30 | 2015-02-18 | Indiana University Research and Technology Corporation | Glucagon antagonists |
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EP2307038A4 (en) | 2008-06-27 | 2013-03-27 | Univ Duke | THERAPEUTIC AGENTS COMPRISING ELASTINE-LIKE PEPTIDES |
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WO2010148089A1 (en) | 2009-06-16 | 2010-12-23 | Indiana University Research And Technology Corporation | Gip receptor-active glucagon compounds |
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SE9802080D0 (sv) | 1998-06-11 | 1998-06-11 | Hellstroem | Pharmaceutical composition for the treatment of functional dyspepsia and/or irritable bowel syndrome and new use of substances therein |
WO2000007617A1 (en) | 1998-07-31 | 2000-02-17 | Novo Nordisk A/S | Use of glp-1 and analogues for preventing type ii diabetes |
MY155270A (en) | 1998-09-24 | 2015-09-30 | Lilly Co Eli | Use of glp-1 or analogs in treatment of stroke |
US6376653B1 (en) | 1998-09-28 | 2002-04-23 | Smithkline Beecham Plc | Tie2 antagonist antibodies |
PT1180121E (pt) | 1999-05-17 | 2004-03-31 | Conjuchem Inc | Peptidos insulinotropicos de longa duracao |
HU229108B1 (en) | 2000-06-16 | 2013-09-30 | Lilly Co Eli | Glucagon-like peptide-1 analogs |
SI1355942T1 (sl) * | 2000-12-07 | 2009-02-28 | Lilly Co Eli | Glp-1 fuzijski proteini |
US6992174B2 (en) | 2001-03-30 | 2006-01-31 | Emd Lexigen Research Center Corp. | Reducing the immunogenicity of fusion proteins |
US6900292B2 (en) | 2001-08-17 | 2005-05-31 | Lee-Hwei K. Sun | Fc fusion proteins of human erythropoietin with increased biological activities |
DK1463751T3 (da) | 2001-12-21 | 2013-08-26 | Human Genome Sciences Inc | Albuminfusionsproteiner. |
EA008831B1 (ru) * | 2003-06-12 | 2007-08-31 | Эли Лилли Энд Компани | Слитые белки аналогов glp-1 |
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