AR038102A1 - Analogos extendidos de peptido 1 de tipo glucagon - Google Patents

Analogos extendidos de peptido 1 de tipo glucagon

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Publication number
AR038102A1
AR038102A1 ARP030100014A ARP030100014A AR038102A1 AR 038102 A1 AR038102 A1 AR 038102A1 AR P030100014 A ARP030100014 A AR P030100014A AR P030100014 A ARP030100014 A AR P030100014A AR 038102 A1 AR038102 A1 AR 038102A1
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AR
Argentina
Prior art keywords
ser
lys
gly
pro
ala
Prior art date
Application number
ARP030100014A
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English (en)
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Lilly Co Eli
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Application filed by Lilly Co Eli filed Critical Lilly Co Eli
Publication of AR038102A1 publication Critical patent/AR038102A1/es

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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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Toxicology (AREA)
  • Hematology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Cardiology (AREA)
  • Obesity (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Emergency Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

La invención incluye péptidos GLP-1 con modificaciones en diversas posiciones unidas a un terminación C extendida que proporcionan una estabilidad aumentada. Reivindicación 1: Un péptido GLP-1 extendido que comprende una secuencia aminoacídica de fórmula: Xaa7-Xaa8-Glu-Gly-Thr-Xaa12-Thr-Ser-Asp-Xaa16-Ser-Xaa18-Xaa19-Xaa20-Glu-Xaa22-GLn-Ala-Xaa25-Lys-Xaa27-Phe-Ile-Xaa30-Trp-Leu-Xaa33-Xaa34-Gly-Xaa36-Xaa37-Xaa38-Xaa39-Xaa40-Xaa41-Xaa42-Xaa43-Xaa44-Xaa45-Xaa46-Xaa47-Xaa48-Xaa49-Xaa50 fórmula (1) (SEC N° ID 1) en al que: Xaa7 es: L-histidina, D-histidina, desaminohistidinina, 2-aminohistidina, beta-hidroxihistidina, homohistidina, alfa-fluorometilhistidina, o alfa-metilhistidina; Xaa8 es: Ala, Gly, Val, Leu, Ile, Ser o Thr; Xaa12 es: Phe, Trp o Tyr; Xaa16 es: Val, Trp Ile, Leu, Phe o Tyr; Xaa18 es: Ser, Trp, Tyr, Phe, Lys, Ile, Leu, Val; Xaa19 es: Tyr, Trp, o Phe; Xaa20 es: Leu, Phe, Tyr o Trp; Xaa22 es: Gly, Glu, Asp o Lys; Xaa25 es: Ala, Val, Ile, o Leu; Xaa27 es: Glu; Ile o Ala; Xaa30 es: Ala o Glu; Xaa33 es: Val o Ile; Xaa34 es: Lys, Asp, Arg o Glu; Xaa36 es: Gly, Pro o Arg; Xaa37 es: Gly, Pro o Ser; Xaa38 es: Ser, Pro o His; Xaa39 es: Ser, Arg, Thr, Trp o Lys; Xaa40 es: Ser o Gly; Xaa41 es: Ala, Asp, Arg, Glu, Lys o Gly; Xaa42 es: Pro, Ala, NH2 o está ausente; Xaa43 es: Pro, Ala, NH2 o está ausente; Xaa44 es: Pro, Ala, Arg, Lys, His, NH2 o está ausente; Xaa45 es: Ser, His, Pro, Lys, Arg, NH2 o está ausente; Xaa46 es: His, Ser, Arg, Lys, NH2 o está ausente; y Xaa47 es: His, Ser, Arg, Lys, NH2 o está ausente; con la condición de que si Xaa42, Xaa43, Xaa44, Xaa45, Xaa46, o Xaa47 está ausente, cada aminoácido cadena abajo está ausente, y con la condición además de que si Xaa36 es Agr y Xaa37 es Gly o Ser, el péptido GLP-1 no tiene la siguiente extensión de aminoácidos C-terminales empezando en Xaa38: Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2. Reivindicación 21: Un péptido GLP-1 extendido que comprende la secuencia aminoacídica de fórmula: Xaa7-Xaa8-Glu-Gly-Thr-Ser-Asp-Xaa16-Ser-Ser-Tyr-Lys-Glu-Xaa22-GLn-Ala-Xaa25-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Xaa33-Xaa34-Gly-Xaa36-Xaa37-Xaa38-Xaa39-Xaa40-Xaa41-Xaa42-Xaa43-Xaa44-Xaa45-Xaa46-Xaa47; fórmula (3) (SEC N° ID 3) en al que: Xaa7 es: L-histidina, D-histidina, desaminohistidinina, 2-aminohistidina, beta-hidroxihistidina, homohistidina, alfa-fluorometilhistidina, o alfa-metilhistidina; Xaa8 es: Gly, Val, Leu, Ile, Ser o Thr; Xaa16 es: Val, Trp Ile, Leu, Phe o Tyr; Xaa22 es: Gly, Glu, Asp o Lys; Xaa25 es: Ala, Val, Ile, o Leu; Xaa33 es: Val o Ile; Xaa34 es: Lys, Asp, Arg o Glu; Xaa36 es: Gly Pro o Arg; Xaa37 es: Gly, Pro o Ser; Xaa38 es: Ser, Pro o His; Xaa39 es: Ser, Arg, Thr, Trp o Lys; Xaa40 es: Ser o Gly; Xaa41 es: Ala, Asp, Arg, Glu, Lys o Gly; Xaa42 es: Pro o Ala, NH2 o está ausente; Xaa43 es: Pro o Ala, NH2 o está ausente; Xaa44 es: Pro, Ala, Arg, Lys, His, NH2 o está ausente; Xaa45 es: Ser, His, Pro, Lys, Arg, NH2 o está ausente; Xaa46 es: His, Ser, Arg, Lys, NH2 o está ausente; y Xaa47 es: His, Ser, Arg, Lys, NH2 o está ausente; con la condición de que si Xaa42, Xaa43, Xaa44, Xaa45, Xaa46, o Xaa47 está ausente, cada aminoácido cadena abajo está ausente, y con la condición además de que si Xaa36 es Agr y Xaa37 es Gly o Ser, el péptido GLP-1 no tiene la siguiente extensión de aminoácidos C-terminales empezando en Xaa38: Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2. Reivindicación 27: Un péptido GLP-1 extendido que comprende la secuencia aminoácido de fórmula Xaa7-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Lys-Glu-Xaa22-GLn-Ala-Xaa25-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Xaa33-Lys-Gly-Gly-Pro-Xaa38-Xaa39-Xaa40-Xaa41-Xaa42-Xaa43-Xaa44-Xaa45-Xaa46-Xaa47; fórmula (4) (SEC N° ID 4) en al que: Xaa7 es: L-histidina, D-histidina, desaminohistidinina, 2-aminohistidina, beta-hidroxihistidina, homohistidina, alfa-fluorometilhistidina, o alfa-metilhistidina; Xaa8 es: Gly, Val, Leu, Ile, Ser o Thr; Xaa22 es: Gly, Glu, Asp o Lys; Xaa25 es: Ala, Val, Ile, o Leu; Xaa33 es: Val o Ile; Xaa38 es: Ser, Pro o His; Xaa39 es: Ser, Arg, Thr, Trp o Lys; Xaa40 es: Ser o Gly; Xaa41 es: Ala, Asp, Arg, Glu, Lys o Gly; Xaa42 es: Pro, Ala; Xaa43 es: Pro o Ala; Xaa44 es: Pro, Ala, Arg, Lys, His, NH2 o está ausente; Xaa45 es: Ser, His, Pro, Lys, Arg, NH2 o está ausente; Xaa46 es: His, Ser, Arg, Lys, NH2 o está ausente; y Xaa47 es: His, Ser, Arg, Lys, NH2 o está ausente; con la condición de que si Xaa44, Xaa45, Xaa46, o Xaa47 está ausente. Reivindicación 33: Un péptido GLP-1 extendido que comprende una secuencia aminoacídica de fórmula: His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Gly-Pro-Xaa38-Xaa39-Xaa40-Xaa41-Xaa42-Xaa43-Xaa44-Xaa45-Xaa46-Xaa47-Xaa48-Xaa49-Xaa50; fórmula 5 (SEC N° ID 60) en al que: Xaa38 es Ser, Pro o His; Xaa39 es: Ser, Arg, Thr, Trp o Lys; Xaa40 es: Ser o Gly; Xaa41 es: Ala, Asp, Arg, Glu, Lys o Gly; Xaa42 es: Pro, Ala, NH2 o está ausente; Xaa43 es: Pro o Ala o está ausente; Xaa44 es: Pro, Ala, Arg, Lys, His, NH2 o está ausente; Xaa45 es: Ser, His, Pro, Lys, Arg, Gly, NH2 o está ausente; Xaa46 es: His, Ser, Arg, Lys, Pro, Gly, NH2 o está ausente; y Xaa47 es: His, Ser, Arg, Lys, NH2 o está ausente; Xaa48 es: Gly, His, NH2 o está ausente; Xaa49 es: Pro, His , NH2 o está ausente; y Xaa50 es: Ser, His, Ser-NH2, His-NH2 o está ausente; en al que el citado péptido GLP-1 comprende de una a seis sustituciones adicionales, y con la condición de que si Xaa42, Xaa43, Xaa44, Xaa45, Xaa46, Xaa47, Xaa48 o Xaa49 está ausente, cada aminoácido cadena abajo está ausente. Reivindicación 36: Un procedimiento de estimulación del receptor de GLP-1 en un sujeto necesitado de normalización de la glucosa en sangre, comprendiendo dicho procedimiento la etapa de administrar al sujeto una cantidad eficaz del péptido GLP-1 de una cualquiera de las reivindicaciones 1 a 35. Reivindicación 37: El procedimiento de la reivindicación 36, en el que el sujeto se está tratando de diabetes no insulinodependiente. Reivindicación 39: Un procedimiento de reducción o mantenimiento del peso corporal en un sujeto necesitado de ello, que comprende administrar al sujeto una cantidad eficaz de un compuesto GLP-1 de una cualquiera de las reivindicaciones 1 a 35. Reivindicación 41: Un procedimiento de tratamiento de apoplejía, infarto de miocardio, hiperglucemia inducida por el estrés o síndrome del intestino irritable en un sujeto necesitado de ello, que comprende administrar al sujeto una cantidad eficaz de un compuesto GLP-1 de una cualquiera de las reivindicaciones 1 a 35.
ARP030100014A 2002-01-08 2003-01-03 Analogos extendidos de peptido 1 de tipo glucagon AR038102A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US34647402P 2002-01-08 2002-01-08
US40509702P 2002-08-21 2002-08-21

Publications (1)

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AR038102A1 true AR038102A1 (es) 2004-12-29

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US (1) US7482321B2 (es)
EP (1) EP1585959A4 (es)
JP (1) JP4282485B2 (es)
AR (1) AR038102A1 (es)
AU (1) AU2003200839B2 (es)
BR (1) BR0306706A (es)
CA (1) CA2468700A1 (es)
MX (1) MXPA04006679A (es)
PE (1) PE20030820A1 (es)
TW (1) TW200306202A (es)
WO (1) WO2003058203A2 (es)

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AU2002317599B2 (en) * 2001-07-31 2008-04-03 The Government Of The United States Of America As Represented By The Secretary, Department Of Health And Human Services GLP-1 exendin-4 peptide analogs and uses thereof
MXPA04001560A (es) * 2001-08-28 2004-05-17 Lilly Co Eli Premezclas de glp-1 e insulina basal.
WO2003035099A1 (en) * 2001-10-19 2003-05-01 Eli Lilly And Company Biphasic mixtures of glp-1 and insulin

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US7482321B2 (en) 2009-01-27
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EP1585959A2 (en) 2005-10-19
JP4282485B2 (ja) 2009-06-24
PE20030820A1 (es) 2003-10-04
WO2003058203A2 (en) 2003-07-17
US20060014241A1 (en) 2006-01-19
BR0306706A (pt) 2007-03-27
JP2005528337A (ja) 2005-09-22
CA2468700A1 (en) 2003-07-17
EP1585959A4 (en) 2007-11-14
MXPA04006679A (es) 2004-11-10
TW200306202A (en) 2003-11-16

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