DE69918691D1 - Glucagonähnliches peptid 1 (glp-1) verbessert die beta zellen antwort auf glukose in patienten mit verminderter glukosetoleranz - Google Patents

Glucagonähnliches peptid 1 (glp-1) verbessert die beta zellen antwort auf glukose in patienten mit verminderter glukosetoleranz

Info

Publication number
DE69918691D1
DE69918691D1 DE69918691T DE69918691T DE69918691D1 DE 69918691 D1 DE69918691 D1 DE 69918691D1 DE 69918691 T DE69918691 T DE 69918691T DE 69918691 T DE69918691 T DE 69918691T DE 69918691 D1 DE69918691 D1 DE 69918691D1
Authority
DE
Germany
Prior art keywords
glucosetolerance
glp
glucagon
peptide
glucose
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.)
Revoked
Application number
DE69918691T
Other languages
English (en)
Other versions
DE69918691T2 (de
Inventor
Burkhard Goke
Maria Byrne
R Thomas
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Amylin Pharmaceuticals LLC
Original Assignee
Amylin Pharmaceuticals LLC
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.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22215287&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DE69918691(D1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Amylin Pharmaceuticals LLC filed Critical Amylin Pharmaceuticals LLC
Application granted granted Critical
Publication of DE69918691D1 publication Critical patent/DE69918691D1/de
Publication of DE69918691T2 publication Critical patent/DE69918691T2/de
Anticipated expiration legal-status Critical
Revoked legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22Hormones
    • A61K38/2278Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22Hormones
    • A61K38/26Glucagons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Zoology (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Emergency Medicine (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
DE69918691T 1998-06-12 1999-05-07 Glucagonähnliches peptid 1 (glp-1) verbessert die beta zellen antwort auf glukose in patienten mit verminderter glukosetoleranz Revoked DE69918691T2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US8904498P 1998-06-12 1998-06-12
US89044P 1998-06-12
PCT/US1999/010040 WO1999064061A1 (en) 1998-06-12 1999-05-07 GLUCAGON-LIKE PEPTIDE-1 IMPROVES β-CELL RESPONSE TO GLUCOSE IN SUBJECTS WITH IMPAIRED GLUCOSE TOLERANCE

Publications (2)

Publication Number Publication Date
DE69918691D1 true DE69918691D1 (de) 2004-08-19
DE69918691T2 DE69918691T2 (de) 2005-07-21

Family

ID=22215287

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69918691T Revoked DE69918691T2 (de) 1998-06-12 1999-05-07 Glucagonähnliches peptid 1 (glp-1) verbessert die beta zellen antwort auf glukose in patienten mit verminderter glukosetoleranz

Country Status (30)

Country Link
US (1) US7265087B1 (de)
EP (2) EP1419783A3 (de)
JP (1) JP2002517469A (de)
KR (1) KR20010052800A (de)
CN (1) CN1209166C (de)
AP (1) AP2001002027A0 (de)
AT (1) ATE270897T1 (de)
AU (2) AU758825B2 (de)
BG (1) BG64975B1 (de)
BR (1) BR9911112A (de)
CA (1) CA2334872C (de)
CZ (1) CZ294848B6 (de)
DE (1) DE69918691T2 (de)
DK (1) DK1083924T3 (de)
EA (1) EA004538B1 (de)
ES (1) ES2224659T3 (de)
GE (1) GEP20033015B (de)
HU (1) HUP0102193A2 (de)
ID (1) ID28617A (de)
IL (2) IL140223A0 (de)
MX (1) MXPA00012286A (de)
NO (1) NO20006336L (de)
NZ (2) NZ527473A (de)
OA (1) OA11694A (de)
PL (1) PL195662B1 (de)
PT (1) PT1083924E (de)
SK (1) SK19042000A3 (de)
TR (1) TR200100079T2 (de)
UA (1) UA69412C2 (de)
WO (1) WO1999064061A1 (de)

Families Citing this family (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2686899B1 (fr) 1992-01-31 1995-09-01 Rhone Poulenc Rorer Sa Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant.
US6344180B1 (en) 1999-06-15 2002-02-05 Bionebraska, Inc. GLP-1 as a diagnostic test to determine β-cell function and the presence of the condition of IGT and type II diabetes
US20020025306A1 (en) * 2000-01-07 2002-02-28 Baetge Edward E. Methods of increasing the glucose responsiveness of pancreatic ss-cells
EP1803730A1 (de) 2000-04-12 2007-07-04 Human Genome Sciences, Inc. Albuminfusionsproteine
DE60136958D1 (de) 2000-12-01 2009-01-22 Takeda Pharmaceutical Verfahren zur herstellung einer zubereitung mit einer bioaktiven substanz
EP1997829A1 (de) 2001-12-21 2008-12-03 Human Genome Sciences, Inc. Albumin Fusionsproteine
ATE385193T1 (de) 2002-03-20 2008-02-15 Mannkind Corp Inhalationsgerät
US7731947B2 (en) 2003-11-17 2010-06-08 Intarcia Therapeutics, Inc. Composition and dosage form comprising an interferon particle formulation and suspending vehicle
CA2513213C (en) 2003-01-22 2013-07-30 Human Genome Sciences, Inc. Albumin fusion proteins
US8921311B2 (en) * 2003-08-01 2014-12-30 Mannkind Corporation Method for treating hyperglycemia
BRPI0514263B8 (pt) 2004-08-20 2021-05-25 Mannkind Corp método para a síntese de bis-3,6-[4-aminobutil]-2,5-dicetopiperazina n-protegida
CN104436170B (zh) 2004-08-23 2018-02-23 曼金德公司 用于药物输送的二酮哌嗪盐
WO2006083761A2 (en) 2005-02-03 2006-08-10 Alza Corporation Solvent/polymer solutions as suspension vehicles
US11246913B2 (en) 2005-02-03 2022-02-15 Intarcia Therapeutics, Inc. Suspension formulation comprising an insulinotropic peptide
WO2006126688A1 (ja) * 2005-05-27 2006-11-30 Asubio Pharma Co., Ltd. インスリン抵抗性改善剤
AU2006290870B2 (en) 2005-09-14 2013-02-28 Mannkind Corporation Method of drug formulation based on increasing the affinity of active agents for crystalline microparticle surfaces
JP5599975B2 (ja) 2006-02-22 2014-10-01 マンカインド コーポレイション ジケトピペラジン及び活性薬剤を含有する微粒子の製剤特性の改善方法
WO2007124461A2 (en) 2006-04-20 2007-11-01 Amgen Inc. Glp-1 compounds
AU2007266475B2 (en) 2006-05-30 2009-12-03 Intarcia Therapeutics, Inc. Two-piece, internal-channel osmotic delivery system flow modulator
JP5048773B2 (ja) 2006-08-09 2012-10-17 インターシア セラピューティクス,インコーポレイティド 浸透圧式デリバリーシステム及びピストンアセンブリー
RU2413528C2 (ru) 2007-01-18 2011-03-10 Открытое Акционерное Общество "Валента Фармацевтика" Лекарственный препарат для лечения сахарного диабета на основе экзенатида и даларгина, применение и способ лечения
AU2008244523B2 (en) 2007-04-23 2012-02-16 Intarcia Therapeutics, Inc. Suspension formulations of insulinotropic peptides and uses thereof
WO2009033747A2 (en) * 2007-09-11 2009-03-19 Mondobiotech Laboratories Ag Use of a peptide as a therapeutic agent
US20100204117A1 (en) * 2007-09-11 2010-08-12 Dorian Bevec Cgrp as a therapeutic agent
DK2240155T3 (da) 2008-02-13 2012-09-17 Intarcia Therapeutics Inc Indretninger, formuleringer og fremgangsmåder til levering af flere gavnlige midler
US8499757B2 (en) 2008-06-13 2013-08-06 Mannkind Corporation Dry powder inhaler and system for drug delivery
US8485180B2 (en) 2008-06-13 2013-07-16 Mannkind Corporation Dry powder drug delivery system
ES2904623T3 (es) 2008-06-20 2022-04-05 Mannkind Corp Aparato interactivo para establecer un perfil en tiempo real de esfuerzos de inhalación
US20120058105A1 (en) * 2008-06-27 2012-03-08 Martin Kean Chong Ng Method of treatment of vascular complications
US8314106B2 (en) 2008-12-29 2012-11-20 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
SMT201700583T1 (it) 2009-09-28 2018-01-11 Intarcia Therapeutics Inc Instaurazione e/o terminazione rapida di erogazione di farmaci in modo sostanzialmente stazionario
MX359281B (es) 2010-06-21 2018-09-21 Mannkind Corp Sistema y metodos para suministrar un farmaco en polvo seco.
US20120208755A1 (en) 2011-02-16 2012-08-16 Intarcia Therapeutics, Inc. Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers
US8925726B2 (en) 2011-04-01 2015-01-06 Mannkind Corporation Blister package for pharmaceutical cartridges
WO2012174472A1 (en) 2011-06-17 2012-12-20 Mannkind Corporation High capacity diketopiperazine microparticles
BR112014009686A2 (pt) 2011-10-24 2018-08-07 Mannkind Corp composição analgésica inalável, pó seco e método para tratar dor
EP2873422A4 (de) 2012-07-10 2015-12-30 Takeda Pharmaceutical Pharmazeutische zubereitung zur injektion
MX354163B (es) 2012-07-12 2018-02-15 Mannkind Corp Sistemas y métodos de suministro de fármaco en polvo seco.
UA116217C2 (uk) 2012-10-09 2018-02-26 Санофі Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону
LT2934568T (lt) 2012-12-21 2018-02-12 Sanofi Dvigubi glp1/gip arba trigubi glp/gip/gliukagono agonistai
KR102321339B1 (ko) 2013-07-18 2021-11-02 맨카인드 코포레이션 열-안정성 건조 분말 약제학적 조성물 및 방법
CA2920488C (en) 2013-08-05 2022-04-26 Mannkind Corporation Insufflation apparatus and methods
EP3080150B1 (de) 2013-12-13 2018-08-01 Sanofi Exendin-4-peptidanaloga als duale glp-1/gip-rezeptoragonisten
EP3080152A1 (de) 2013-12-13 2016-10-19 Sanofi Nicht-acylierte exendin-4-peptidanaloga
WO2015086729A1 (en) 2013-12-13 2015-06-18 Sanofi Dual glp-1/gip receptor agonists
TW201609797A (zh) 2013-12-13 2016-03-16 賽諾菲公司 雙重glp-1/升糖素受體促效劑
US10307464B2 (en) 2014-03-28 2019-06-04 Mannkind Corporation Use of ultrarapid acting insulin
TW201625668A (zh) 2014-04-07 2016-07-16 賽諾菲公司 作為胜肽性雙重glp-1/昇糖素受體激動劑之艾塞那肽-4衍生物
TW201625669A (zh) 2014-04-07 2016-07-16 賽諾菲公司 衍生自艾塞那肽-4(Exendin-4)之肽類雙重GLP-1/升糖素受體促效劑
TW201625670A (zh) 2014-04-07 2016-07-16 賽諾菲公司 衍生自exendin-4之雙重glp-1/升糖素受體促效劑
US9932381B2 (en) 2014-06-18 2018-04-03 Sanofi Exendin-4 derivatives as selective glucagon receptor agonists
RU2573933C1 (ru) 2014-08-21 2016-01-27 Дафот Энтерпрайсис Лимитед Пептид для лечения сахарного диабета 2-го типа и его осложнений
CN104267194B (zh) * 2014-09-23 2016-01-13 上海市东方医院 人胰高血糖素样肽-1、抗体及其试剂盒
US9889085B1 (en) 2014-09-30 2018-02-13 Intarcia Therapeutics, Inc. Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c
US10561806B2 (en) 2014-10-02 2020-02-18 Mannkind Corporation Mouthpiece cover for an inhaler
US10925639B2 (en) 2015-06-03 2021-02-23 Intarcia Therapeutics, Inc. Implant placement and removal systems
AR105319A1 (es) 2015-06-05 2017-09-27 Sanofi Sa Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico
TW201706291A (zh) 2015-07-10 2017-02-16 賽諾菲公司 作為選擇性肽雙重glp-1/升糖素受體促效劑之新毒蜥外泌肽(exendin-4)衍生物
KR20240037175A (ko) 2016-05-16 2024-03-21 인타르시아 세라퓨틱스 인코포레이티드 글루카곤-수용체 선택적 폴리펩티드 및 이들의 이용 방법
USD840030S1 (en) 2016-06-02 2019-02-05 Intarcia Therapeutics, Inc. Implant placement guide
USD860451S1 (en) 2016-06-02 2019-09-17 Intarcia Therapeutics, Inc. Implant removal tool
MX2019008006A (es) 2017-01-03 2019-08-29 Intarcia Therapeutics Inc Metodos que comprenden la administracion continua de un agonista del receptor de glp-1 y la co-administracion de un farmaco.
KR102779458B1 (ko) 2018-11-12 2025-03-12 톈진 인스티튜트 오브 파마슈티컬 리서치 씨오., 엘티디. 글루카곤 유도 펩티드 및 이의 용도
CN113430154A (zh) * 2021-05-21 2021-09-24 深圳市前海金卓生物技术有限公司 分泌glp-1的蛋白表达系统及其制备方法和应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2257119A1 (en) 1996-06-05 1997-12-11 Boehringer Mannheim Gmbh Exendin analogues, processes for their production and pharmaceutical preparations containing them
US6277819B1 (en) * 1996-08-30 2001-08-21 Eli Lilly And Company Use of GLP-1 or analogs in treatment of myocardial infarction
US6344180B1 (en) * 1999-06-15 2002-02-05 Bionebraska, Inc. GLP-1 as a diagnostic test to determine β-cell function and the presence of the condition of IGT and type II diabetes

Also Published As

Publication number Publication date
SK19042000A3 (sk) 2001-11-06
ID28617A (id) 2001-06-21
CA2334872A1 (en) 1999-12-16
DE69918691T2 (de) 2005-07-21
IL140223A0 (en) 2002-02-10
MXPA00012286A (es) 2002-10-17
NO20006336L (no) 2001-02-12
PT1083924E (pt) 2004-10-29
UA69412C2 (uk) 2004-09-15
CZ294848B6 (cs) 2005-03-16
NZ527473A (en) 2005-02-25
CA2334872C (en) 2014-08-19
HUP0102193A2 (hu) 2001-10-28
PL345212A1 (en) 2001-12-03
TR200100079T2 (tr) 2001-06-21
EP1083924A1 (de) 2001-03-21
DK1083924T3 (da) 2004-11-22
ES2224659T3 (es) 2005-03-01
AU2003212050B2 (en) 2006-02-16
BG105079A (en) 2001-09-28
OA11694A (en) 2005-01-12
EA200100029A1 (ru) 2001-10-22
WO1999064061A1 (en) 1999-12-16
CN1311687A (zh) 2001-09-05
CZ20004614A3 (en) 2001-06-13
EA004538B1 (ru) 2004-06-24
GEP20033015B (en) 2003-07-25
US7265087B1 (en) 2007-09-04
AP2001002027A0 (en) 2001-03-31
KR20010052800A (ko) 2001-06-25
PL195662B1 (pl) 2007-10-31
EP1419783A3 (de) 2005-01-12
AU2003212050A1 (en) 2003-08-14
NZ508823A (en) 2003-10-31
JP2002517469A (ja) 2002-06-18
CN1209166C (zh) 2005-07-06
EP1419783A2 (de) 2004-05-19
BR9911112A (pt) 2001-11-27
ATE270897T1 (de) 2004-07-15
AU3889999A (en) 1999-12-30
EP1083924B1 (de) 2004-07-14
NO20006336D0 (no) 2000-12-12
IL140223A (en) 2010-12-30
AU758825B2 (en) 2003-04-03
BG64975B1 (bg) 2006-11-30

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8331 Complete revocation