JP2011524420A5 - - Google Patents

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JP2011524420A5
JP2011524420A5 JP2011514735A JP2011514735A JP2011524420A5 JP 2011524420 A5 JP2011524420 A5 JP 2011524420A5 JP 2011514735 A JP2011514735 A JP 2011514735A JP 2011514735 A JP2011514735 A JP 2011514735A JP 2011524420 A5 JP2011524420 A5 JP 2011524420A5
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amino acid
analog
seq
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substitution
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JP6108659B2 (ja
JP2011524420A (ja
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Priority claimed from PCT/US2009/047447 external-priority patent/WO2010011439A2/en
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JP2011514735A 2008-06-17 2009-06-16 代謝疾患および肥満の治療のためのgipに基づいた混合アゴニスト Active JP6108659B2 (ja)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US7327408P 2008-06-17 2008-06-17
US61/073,274 2008-06-17
US7817108P 2008-07-03 2008-07-03
US61/078,171 2008-07-03
US9044808P 2008-08-20 2008-08-20
US61/090,448 2008-08-20
US15134909P 2009-02-10 2009-02-10
US61/151,349 2009-02-10
PCT/US2009/047447 WO2010011439A2 (en) 2008-06-17 2009-06-16 Gip-based mixed agonists for treatment of metabolic disorders and obesity

Related Child Applications (1)

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JP2015076371A Division JP6174071B2 (ja) 2008-06-17 2015-04-02 代謝疾患および肥満の治療のためのgipに基づいた混合アゴニスト

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JP2011524420A JP2011524420A (ja) 2011-09-01
JP2011524420A5 true JP2011524420A5 (enExample) 2012-10-25
JP6108659B2 JP6108659B2 (ja) 2017-04-05

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JP2011514735A Active JP6108659B2 (ja) 2008-06-17 2009-06-16 代謝疾患および肥満の治療のためのgipに基づいた混合アゴニスト
JP2015076371A Active JP6174071B2 (ja) 2008-06-17 2015-04-02 代謝疾患および肥満の治療のためのgipに基づいた混合アゴニスト

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JP2015076371A Active JP6174071B2 (ja) 2008-06-17 2015-04-02 代謝疾患および肥満の治療のためのgipに基づいた混合アゴニスト

Country Status (27)

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US (2) US9062124B2 (enExample)
EP (2) EP2300035B1 (enExample)
JP (2) JP6108659B2 (enExample)
KR (1) KR20110040760A (enExample)
CN (2) CN102105159B (enExample)
AR (1) AR072159A1 (enExample)
AU (1) AU2009274425B2 (enExample)
BR (1) BRPI0915282A2 (enExample)
CA (1) CA2729296A1 (enExample)
CL (1) CL2009001425A1 (enExample)
CO (1) CO6280539A2 (enExample)
CR (1) CR11849A (enExample)
DK (1) DK2300035T3 (enExample)
EA (1) EA020326B9 (enExample)
EC (1) ECSP10010684A (enExample)
ES (2) ES2558842T3 (enExample)
HU (1) HUE028072T2 (enExample)
IL (1) IL209666A (enExample)
MA (1) MA32397B1 (enExample)
MX (1) MX2010013453A (enExample)
NZ (2) NZ603445A (enExample)
PE (1) PE20100056A1 (enExample)
PL (1) PL2300035T3 (enExample)
SG (1) SG192405A1 (enExample)
TW (1) TWI474835B (enExample)
WO (1) WO2010011439A2 (enExample)
ZA (1) ZA201008807B (enExample)

Families Citing this family (143)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8338368B2 (en) 2005-11-07 2012-12-25 Indiana University Research And Technology Corporation Glucagon analogs exhibiting physiological solubility and stability
WO2008086086A2 (en) 2007-01-05 2008-07-17 Indiana University Research And Technology Corporation Glucagon analogs exhibiting enhanced solubility in physiological ph buffers
JP6017754B2 (ja) 2007-02-15 2016-11-02 インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation グルカゴン/glp−1受容体コアゴニスト
EP2217701B9 (en) 2007-10-30 2015-02-18 Indiana University Research and Technology Corporation Glucagon antagonists
CA2702289A1 (en) 2007-10-30 2009-05-07 Indiana University Research And Technology Corporation Compounds exhibiting glucagon antagonist and glp-1 agonist activity
EP2249853A4 (en) * 2008-01-30 2012-12-26 Univ Indiana Res & Tech Corp ESTER BASED PEPTIDE PRODRUGS
RU2504373C2 (ru) 2008-03-26 2014-01-20 ОРАМЕД Лтд. Способы и композиции для перорального введения протеинов
CN105903005A (zh) 2008-05-05 2016-08-31 奥拉姆德有限公司 用于口服给予艾塞那肽的方法和组合物
JP5753779B2 (ja) * 2008-06-17 2015-07-22 インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation 生理学的pHの緩衝液中で向上した溶解性及び安定性を示すグルカゴン類縁体
BRPI0915282A2 (pt) 2008-06-17 2017-02-07 Univ Indiana Res & Tech Corp agonistas mistos baseados no gip para o tratamento de distúrbios metabólicos e obesidade
AU2009260302B2 (en) 2008-06-17 2014-10-23 Indiana University Research And Technology Corporation Glucagon/GLP-1 receptor co-agonists
AU2009327418A1 (en) 2008-12-19 2010-06-24 Indiana University Research And Technology Corporation Amide based glucagon superfamily peptide prodrugs
US8992886B2 (en) * 2009-04-06 2015-03-31 Board Of Regents, The University Of Texas System Cyclic peptide analogues for non-invasive imaging of pancreatic beta-cells
US9150632B2 (en) * 2009-06-16 2015-10-06 Indiana University Research And Technology Corporation GIP receptor-active glucagon compounds
ME02220B (me) 2009-07-13 2016-02-20 Zealand Pharma As Analozi acilovanog glukagona
WO2011075393A2 (en) 2009-12-18 2011-06-23 Indiana University Research And Technology Corporation Glucagon/glp-1 receptor co-agonists
RU2012136450A (ru) 2010-01-27 2014-03-10 Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн Конъюгаты антагонист глюкагона - агонист gip и композиции для лечения метаболических расстройств и ожирения
AR080592A1 (es) 2010-03-26 2012-04-18 Lilly Co Eli Peptido con actividad para el gip-r y glp-1-r, formulacion famaceutica que lo comprende, su uso para preparar un medicamento util para el tratamiento de diabetes mellitus y para inducir la perdida de peso
EP2569000B1 (en) 2010-05-13 2017-09-27 Indiana University Research and Technology Corporation Glucagon superfamily peptides exhibiting nuclear hormone receptor activity
US9145451B2 (en) 2010-05-13 2015-09-29 Indiana University Research And Technology Corporation Glucagon superfamily peptides exhbiting G protein coupled receptor activity
EP2588126A4 (en) 2010-06-24 2015-07-08 Univ Indiana Res & Tech Corp AMID-BASED GLUCAGON SUPERFAMILY PEPTIDE PRODRUGS
US9023986B2 (en) 2010-10-25 2015-05-05 Hoffmann-La Roche Inc. Glucose-dependent insulinotropic peptide analogs
JP5894174B2 (ja) 2010-11-03 2016-03-23 アレコー リミテッド グルカゴンを含む新規組成物
CA2821766A1 (en) * 2010-12-22 2012-06-28 Indiana University Research And Technology Corporation Glucagon analogs exhibiting gip receptor activity
SG191252A1 (en) * 2010-12-22 2013-07-31 Marcadia Biotech Inc Methods for treating metabolic disorders and obesity with gip and glp-1 receptor-active glucagon-based peptides
KR20140020292A (ko) 2011-03-28 2014-02-18 노보 노르디스크 에이/에스 신규 글루카곤 유사체
DK2694095T3 (en) 2011-04-05 2018-05-28 Longevity Biotech Inc COMPOSITIONS COMPREHENSIVE GLUCAGON ANALOGS AND METHODS FOR PREPARING AND USING THE SAME
WO2012167744A1 (en) * 2011-06-10 2012-12-13 Beijing Hanmi Pharmaceutical Co., Ltd. Glucose dependent insulinotropic polypeptide analogs, pharmaceutical compositions and use thereof
BR112013032717A2 (pt) 2011-06-22 2017-01-24 Univ Indiana Res & Tech Corp coagonistas do receptor de glucagon/glp-1
EA031230B1 (ru) 2011-06-22 2018-12-28 Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн Агонисты глюкагонового рецептора/glp-1-рецептора
US9944687B2 (en) 2011-07-04 2018-04-17 Imperial Innovations Limited Compounds and their effects on feeding behaviour
JP6352806B2 (ja) 2011-09-23 2018-07-04 ノヴォ ノルディスク アー/エス 新規のグルカゴン類似体
CA2847246A1 (en) 2011-11-17 2013-05-23 Indiana University Research And Technology Corporation Glucagon superfamily peptides exhibiting glucocorticoid receptor activity
CN112755002A (zh) 2012-02-01 2021-05-07 奥拉姆德有限公司 含有蛋白酶抑制物的组合物、包含前者的组合物和用于产生和使用前者的方法
WO2013164483A1 (en) 2012-05-03 2013-11-07 Zealand Pharma A/S Gip-glp-1 dual agonist compounds and methods
US9745359B2 (en) 2012-05-18 2017-08-29 Adda Biotech Inc. Protein and protein conjugate for diabetes treatment, and applications thereof
RU2015101697A (ru) 2012-06-21 2016-08-10 Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн Аналоги глюкагона, обладающие активностью рецептора gip
TW201402611A (zh) 2012-06-21 2014-01-16 Univ Indiana Res & Tech Corp 具有改變之fc效應子功能之腸促胰島素受體配體多肽fc區融合多肽及結合物
JP6300239B2 (ja) 2012-06-21 2018-03-28 インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation Gip受容体活性を示すグルカゴンアナローグ
MY170671A (en) 2012-07-23 2019-08-26 Zealand Pharma As Glucagon analogues
TWI608013B (zh) 2012-09-17 2017-12-11 西蘭製藥公司 升糖素類似物
AR092873A1 (es) 2012-09-26 2015-05-06 Cadila Healthcare Ltd Peptidos como agonistas triples de los receptores de gip, glp-1 y glugagon
UA116217C2 (uk) 2012-10-09 2018-02-26 Санофі Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону
SG10201705097PA (en) 2012-12-21 2017-07-28 Sanofi Sa Functionalized exendin-4 derivatives
EP2941267B1 (en) * 2013-01-03 2022-11-16 Oramed Ltd. Compositions for use in treating nafld
WO2014158900A1 (en) 2013-03-14 2014-10-02 Indiana University Research And Technology Corporation Insulin-incretin conjugates
EP2986314A4 (en) * 2013-03-15 2016-04-13 Univ Indiana Res & Tech Corp PRODRUGS WITH EXTENDED EFFECT
ES2623979T3 (es) 2013-03-21 2017-07-12 Sanofi-Aventis Deutschland Gmbh Síntesis de productos peptídicos que contienen hidantoína
ES2624961T3 (es) 2013-03-21 2017-07-18 Sanofi-Aventis Deutschland Gmbh Síntesis de productos de péptido que contienen imida cíclica
AR095986A1 (es) 2013-04-03 2015-11-25 Sanofi Sa Proteínas modificadas que regulan glucosa en sangre con perfil alterado de actividad farmacológica y preparación de las mismas
PL2986313T3 (pl) 2013-04-18 2019-12-31 Novo Nordisk A/S Stabilni, dłużej działający współagoniści receptora glp-1/glukagonu do zastosowań medycznych
LT3004155T (lt) 2013-05-28 2021-12-27 Takeda Pharmaceutical Company Limited Peptidų junginys
WO2015022420A1 (en) * 2013-08-16 2015-02-19 Medimmune Limited Gip and glp-1 receptor dual-agonists for the treatment of diabetes
WO2015035419A1 (en) * 2013-09-09 2015-03-12 Hoffmann-La Roche Inc. Dosages of gip/glp-1 co-agonist peptides for human administration
SI3057984T1 (sl) 2013-10-17 2018-10-30 Zealand Pharma A/S Acilirani glukagonski analogi
US9988429B2 (en) 2013-10-17 2018-06-05 Zealand Pharma A/S Glucagon analogues
US10093713B2 (en) * 2013-11-06 2018-10-09 Zealand Pharma A/S GIP-GLP-1 dual agonist compounds and methods
EA035688B1 (ru) * 2013-11-06 2020-07-27 Зилэнд Фарма А/С Соединения, которые представляют собой тройные агонисты глюкагона, glp-1 и gip
WO2015081891A1 (en) 2013-12-06 2015-06-11 Baikang (Suzhou) Co., Ltd Bioreversable promoieties for nitrogen-containing and hydroxyl-containing drugs
EP3080149A1 (en) 2013-12-13 2016-10-19 Sanofi Dual glp-1/glucagon receptor agonists
EP3080151A1 (en) * 2013-12-13 2016-10-19 Sanofi Exendin-4 peptide analogues
WO2015086730A1 (en) * 2013-12-13 2015-06-18 Sanofi Non-acylated exendin-4 peptide analogues
WO2015086731A1 (en) * 2013-12-13 2015-06-18 Sanofi Exendin-4 peptide analogues as dual glp-1/glucagon receptor agonists
TW201609795A (zh) 2013-12-13 2016-03-16 賽諾菲公司 作為雙重glp-1/gip受體促效劑的艾塞那肽-4(exendin-4)胜肽類似物
WO2015086729A1 (en) 2013-12-13 2015-06-18 Sanofi Dual glp-1/gip receptor agonists
CA2933701C (en) 2013-12-18 2022-05-31 The California Institute For Biomedical Research Modified therapeutic agents, stapled peptide lipid conjugates, and compositions thereof
AR098614A1 (es) 2013-12-18 2016-06-01 Lilly Co Eli Compuesto para el tratamiento de hipoglicemia severa
WO2015095684A1 (en) 2013-12-20 2015-06-25 Indiana University Research And Technology Corporation Lipidated incretin receptor ligand human immunoglobulin fc-region fusion polypeptides
AR100306A1 (es) 2014-02-18 2016-09-28 Novo Nordisk As Análogos de glucagón estables y uso para el tratamiento de la hipoglucemia
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
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
EP3151852A1 (en) 2014-06-04 2017-04-12 Novo Nordisk A/S Glp-1/glucagon receptor co-agonists for medical use
US9932381B2 (en) 2014-06-18 2018-04-03 Sanofi Exendin-4 derivatives as selective glucagon receptor agonists
ES2822994T3 (es) * 2014-09-24 2021-05-05 Univ Indiana Res & Tech Corp Conjugados de incretina-insulina
CN107108715A (zh) 2014-10-24 2017-08-29 默沙东公司 胰高血糖素和glp‑1受体的共激动剂
TWI705973B (zh) 2014-10-29 2020-10-01 丹麥商西蘭製藥公司 Gip促效劑化合物及方法
WO2016077220A1 (en) * 2014-11-10 2016-05-19 Mb2 Llc Gip/glp-1 co-agonist peptides for human administration
JP2018012644A (ja) * 2014-11-26 2018-01-25 武田薬品工業株式会社 ペプチド化合物
TN2017000271A1 (en) 2014-12-30 2018-10-19 Hanmi Pharm Ind Co Ltd Glucagon derivative having improved stability
TWI707867B (zh) 2015-04-16 2020-10-21 丹麥商西蘭製藥公司 醯化之昇糖素類似物
AR105319A1 (es) 2015-06-05 2017-09-27 Sanofi Sa Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico
WO2016198624A1 (en) 2015-06-12 2016-12-15 Sanofi Exendin-4 derivatives as trigonal glp-1/glucagon/gip receptor agonists
TN2017000555A1 (en) 2015-06-30 2019-04-12 Hanmi Pharm Ind Co Ltd Glucagon derivative and a composition comprising a long acting conjugate of the same
AR105284A1 (es) 2015-07-10 2017-09-20 Sanofi Sa Derivados de exendina-4 como agonistas peptídicos duales específicos de los receptores de glp-1 / glucagón
TWI622596B (zh) 2015-10-26 2018-05-01 美國禮來大藥廠 升糖素受體促效劑
PH12018501409B1 (en) * 2015-12-31 2023-03-10 Hanmi Pharmaceutical Co Ltd Triple glucagon/glp-1/gip receptor agonist
CN109477094B (zh) 2016-05-24 2022-04-26 武田药品工业株式会社 肽化合物
GB201611077D0 (en) 2016-06-24 2016-08-10 Arecor Ltd Novel composition
JP7208020B2 (ja) * 2016-06-29 2023-01-18 ハンミ ファーマシューティカル カンパニー リミテッド グルカゴン誘導体、その結合体、及びそれを含む組成物、並びにその治療的用途
CN109200273B (zh) * 2017-07-04 2021-02-19 中国药科大学 一种多肽用于制备预防或治疗脂肪肝病药物的用途
AR110301A1 (es) 2016-12-02 2019-03-13 Sanofi Sa Compuestos como agonistas peptídicos de receptores de glp1 / glucagón / gip
AR110300A1 (es) 2016-12-02 2019-03-13 Sanofi Sa Compuestos como agonistas peptídicos trigonales de los receptores de glp1 / glucagón / gip
GB201620611D0 (en) * 2016-12-05 2017-01-18 Univ Of Lancaster Treatment of neurological diseases
US11285180B2 (en) 2016-12-06 2022-03-29 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods of enhancing the potency of incretin-based drugs in subjects in need thereof
JOP20180028A1 (ar) 2017-03-31 2019-01-30 Takeda Pharmaceuticals Co مركب ببتيد
AR113486A1 (es) * 2017-12-21 2020-05-06 Lilly Co Eli Análogos de incretina y sus usos
EA202092269A1 (ru) * 2018-03-23 2020-12-14 Кармот Терапьютикс, Инк. Модуляторы сопряженных с g-белком рецепторов
BR112020020647A2 (pt) 2018-04-10 2021-02-23 Sanofi-Aventis Deutschland Gmbh síntese de lixisenatida com capeamento
KR102793451B1 (ko) 2018-04-10 2025-04-11 사노피-아벤티스 도이칠란트 게엠베하 고체상으로부터 고체상-결합된 펩타이드를 절단하는 방법
TWI707865B (zh) 2018-05-04 2020-10-21 丹麥商諾佛 儂迪克股份有限公司 Gip衍生物及其用途
TW202015735A (zh) 2018-05-30 2020-05-01 法商賽諾菲公司 包含glp-1/升糖素/gip三重受體促效劑、連接子及透明質酸之接合物
EP3856339A1 (en) 2018-09-24 2021-08-04 Takeda Pharmaceutical Company Limited Gip receptor agonist peptide compounds and uses thereof
WO2021083306A1 (zh) * 2019-10-31 2021-05-06 东莞市东阳光生物药研发有限公司 Glp-1/gcg双受体激动剂多肽
FI4097099T3 (fi) 2020-02-07 2024-07-30 Gasherbrum Bio Inc Heterosyklisiä glp-1-agonisteja
WO2021169512A1 (zh) * 2020-02-24 2021-09-02 中山大学 多肽化合物及其在预防或治疗糖尿病或糖尿病并发症中的应用
PL4143183T3 (pl) 2020-04-29 2026-03-02 Gasherbrum Bio, Inc. Heterocykliczni agoniści glp-1
CA3184717A1 (en) 2020-07-22 2022-01-27 Patrick J. KNERR Co-agonists at glp-1 and gip receptors suitable for oral delivery
WO2022018185A1 (en) 2020-07-22 2022-01-27 Novo Nordisk A/S Glp-1 and gip receptor co-agonists
JP2023550594A (ja) * 2020-10-30 2023-12-04 ノヴォ ノルディスク アー/エス Glp-1、gip、およびグルカゴン受容体三重作動薬
CN114617956B (zh) * 2020-12-10 2023-10-03 江苏中新医药有限公司 一种高效降糖的蛋白质药物
CN117980325A (zh) 2021-05-13 2024-05-03 卡莫特治疗学股份有限公司 G-蛋白偶联受体的调节剂
CN117794946A (zh) * 2021-06-09 2024-03-29 斯克利普斯研究所 长效双重gip/glp-1肽缀合物及使用方法
WO2023030444A1 (zh) * 2021-09-02 2023-03-09 广东东阳光药业有限公司 Glp-1/gip双靶多肽、融合蛋白及其应用
TW202330584A (zh) 2022-01-20 2023-08-01 丹麥商諾佛 儂迪克股份有限公司 前藥及其用途
WO2023169456A1 (en) 2022-03-09 2023-09-14 Gasherbrum Bio , Inc. Heterocyclic glp-1 agonists
EP4496797A1 (en) 2022-03-21 2025-01-29 Gasherbrum Bio, Inc. 5,8-dihydro-1,7-naphthyridine derivatives as glp-1 agonists for the treatment of diabetes
US20250250269A1 (en) 2022-04-14 2025-08-07 Gasherbrum Bio, Inc. Heterocyclic glp-1 agonists
CN115490760B (zh) * 2022-07-04 2023-04-14 北京惠之衡生物科技有限公司 一种glp-1受体和gcg受体共激动多肽衍生物
JP2026501171A (ja) 2022-12-15 2026-01-14 ガシャーブラム・バイオ・インコーポレイテッド Glp-1アゴニスト活性を有する化合物の塩および固体形態
EP4638440A1 (en) 2022-12-22 2025-10-29 Gasherbrum Bio, Inc. Heterocyclic glp-1 agonists
EP4638455A1 (en) 2022-12-22 2025-10-29 Gasherbrum Bio, Inc. Heterocyclic glp-1 agonists
CN118255864A (zh) * 2022-12-26 2024-06-28 杭州中美华东制药有限公司 Gip受体激动剂及其用途
WO2024165571A2 (en) 2023-02-06 2024-08-15 E-Therapeutics Plc Inhibitors of expression and/or function
AU2024222719A1 (en) 2023-02-16 2025-08-21 Gasherbrum Bio, Inc. Heterocyclic glp-1 agonists
US20250019389A1 (en) 2023-06-30 2025-01-16 Gasherbrum Bio, Inc. Heterocyclic agonists
TW202521528A (zh) 2023-07-13 2025-06-01 美商雅空嘉閣生物公司 化合物、組合物及方法
WO2025015269A1 (en) 2023-07-13 2025-01-16 Aconcagua Bio, Inc. Compounds, compositions, and methods
WO2025016303A1 (zh) * 2023-07-14 2025-01-23 北京拓界生物医药科技有限公司 Glp-1、gip和gcg受体三激动剂及其应用
WO2025045208A1 (en) 2023-08-31 2025-03-06 Gasherbrum Bio, Inc. Heteroaryl-heterocycloalkyl-based glp-1 agonists
CN117186206B (zh) * 2023-10-20 2024-07-23 广东药科大学 新型不同glp1类似肽共价聚合体及其制备方法和应用
CN120349392A (zh) * 2023-11-06 2025-07-22 成都奥达生物科技有限公司 一种gip激动剂化合物
TW202540155A (zh) 2023-11-30 2025-10-16 丹麥商諾佛 儂迪克股份有限公司 Glp-1、gip及澱粉素受體之三重促效劑
WO2025125576A2 (en) 2023-12-15 2025-06-19 E-Therapeutics Plc Inhibitors of expression and/or function
WO2025137307A1 (en) 2023-12-20 2025-06-26 Gasherbrum Bio, Inc. Heterocyclic glp-1 agonists
WO2025133348A1 (en) 2023-12-22 2025-06-26 E-Therapeutics Plc Inhibitors of expression and/or function
EP4686757A1 (en) 2024-07-31 2026-02-04 e-therapeutics PLC Inhibitors of expression and/or function
WO2025171341A2 (en) 2024-02-08 2025-08-14 Aconcagua Bio, Inc. Compounds and compositions for treating conditions associated with calcitonin receptor and/or amylin receptor activity
WO2025171340A1 (en) 2024-02-08 2025-08-14 Aconcagua Bio, Inc. The treatment of calcitonin- and/or amylin-receptor associated conditions
WO2025189141A1 (en) 2024-03-08 2025-09-12 Annapurna Bio, Inc. Methods for treating obesity and increasing weight loss
WO2025196502A1 (en) 2024-03-20 2025-09-25 North Carolina Agricultural & Technical State University Choline kinase inhibitors as a therapeutic treatment for obesity
WO2026041075A1 (en) 2024-08-21 2026-02-26 Gasherbrum Bio, Inc. Gpl-1 agonists
WO2026051998A1 (en) 2024-09-04 2026-03-12 Aconcagua Bio, Inc. Compounds, compositions, and methods

Family Cites Families (132)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4275152A (en) * 1977-02-03 1981-06-23 Eastman Kodak Company Hydrolysis of protein-bound cholesterol esters
PT83613B (en) 1985-10-28 1988-11-21 Lilly Co Eli Process for the selective chemical removal of a protein amino-terminal residue
EP0272253A4 (en) 1986-03-07 1990-02-05 Massachusetts Inst Technology METHOD FOR IMPROVING GLYCOPROTE INSTABILITY.
ES2075196T3 (es) * 1989-02-17 1995-10-01 Chiron Mimotopes Pty Ltd Metodo para el uso y la sintesis de peptidos.
US5545618A (en) * 1990-01-24 1996-08-13 Buckley; Douglas I. GLP-1 analogs useful for diabetes treatment
DE69129226T2 (de) 1990-01-24 1998-07-30 Douglas I. Woodside Calif. Buckley Glp-1-analoga verwendbar in der diabetesbehandlung
CA2024855C (en) 1990-09-07 1997-12-09 Boehringer Ingelheim (Canada) Ltd./ Boehringer Ingelheim (Canada) Ltee Process and intermediates for producing glucagon
JPH04145099A (ja) 1990-10-05 1992-05-19 Sanwa Kagaku Kenkyusho Co Ltd Gip様活性を有するポリペプチド誘導体及びその用途
ATE135372T1 (de) * 1991-01-17 1996-03-15 Zymogenetics Inc Verfahren zum nachweis von glucagon-antagonisten
US5510459A (en) * 1991-01-17 1996-04-23 Zymogenetics, Inc. Glucagon antagonists
US5359030A (en) * 1993-05-10 1994-10-25 Protein Delivery, Inc. Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same
US5480867A (en) * 1993-12-29 1996-01-02 The Rockefeller University Glucagon analogs with serine replacements
US5512549A (en) * 1994-10-18 1996-04-30 Eli Lilly And Company Glucagon-like insulinotropic peptide analogs, compositions, and methods of use
US5869602A (en) * 1995-03-17 1999-02-09 Novo Nordisk A/S Peptide derivatives
JPH0940699A (ja) * 1995-07-28 1997-02-10 Sanwa Kagaku Kenkyusho Co Ltd ポリペプチド及びその用途
DE19530865A1 (de) 1995-08-22 1997-02-27 Michael Dr Med Nauck Wirkstoff sowie Mittel zur parenteralen Ernährung
JP2001503963A (ja) 1996-02-06 2001-03-27 イーライ・リリー・アンド・カンパニー 糖尿病治療
JP2000516912A (ja) 1996-06-05 2000-12-19 ロシュ ダイアグノスティクス ゲゼルシャフト ミット ベシュレンクテル ハフツング エキセンジン類似体、それらの製造方法およびそれらを含有する製剤
NZ334595A (en) 1996-09-09 2000-08-25 Zealand Pharmaceuticals As Peptide prodrugs containing an alpha-hydroxyacid linker that have increased stability against enzymatic cleavage
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
AU5518798A (en) 1996-12-03 1998-06-29 Trustees Of Boston University Specific antagonists for glucose-dependent insulinotropic polypeptide (gip)
JP4394279B2 (ja) 1998-03-09 2010-01-06 ジーランド ファーマ アクティーゼルスカブ 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体
DE19828113A1 (de) 1998-06-24 2000-01-05 Probiodrug Ges Fuer Arzneim Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV
US20030236190A1 (en) * 1998-09-02 2003-12-25 Renuka Pillutla Isulin and IGF-1 receptor agonists and antagonists
AU6294899A (en) 1998-10-07 2000-04-26 Medical College Of Georgia Research Institute, Inc. Glucose-dependent insulinotropic peptide for use as an osteotropic hormone
CN1495198A (zh) * 1998-12-07 2004-05-12 �о���Ӧ�ÿ�ѧЭ��ɷ����޹�˾ 胰高血糖素样肽-1的类似物
WO2000042026A1 (en) 1999-01-15 2000-07-20 Novo Nordisk A/S Non-peptide glp-1 agonists
GB0404124D0 (en) 2004-02-25 2004-03-31 Univ Ulster Antagonists of GIP
US6921748B1 (en) * 1999-03-29 2005-07-26 Uutech Limited Analogs of gastric inhibitory polypeptide and their use for treatment of diabetes
EP1180121B9 (en) 1999-05-17 2004-09-08 Conjuchem, Inc. Long lasting insulinotropic peptides
EP1076066A1 (en) * 1999-07-12 2001-02-14 Zealand Pharmaceuticals A/S Peptides for lowering blood glucose levels
CA2405900A1 (en) 2000-04-27 2001-11-01 Bionebraska, Inc. Gastric inhibitory polypeptide diagnostic test for detecting susceptibility to type-2 diabetes, impaired glucose tolerance, or impaired fasting glucose
US6677136B2 (en) * 2000-05-03 2004-01-13 Amgen Inc. Glucagon antagonists
AU2001269833A1 (en) * 2000-06-14 2001-12-24 Cytovax Biotechnologies, Inc. Use of coiled-coil structural scaffold to generate structure-specific peptides
AU6479101A (en) 2000-06-16 2002-01-02 Lilly Co Eli Glucagon-like peptide-1 analogs
CN1454214A (zh) * 2000-08-02 2003-11-05 赛莱技术公司 具有增高功效的修饰生物肽
US20020045572A1 (en) 2000-08-15 2002-04-18 Cpd, Llc Method of treating the syndrome of type 2 diabetes in humans
US6846831B2 (en) 2000-08-15 2005-01-25 Cpd, Llc Method of treating the syndrome of lipodystrophy
US6262062B1 (en) 2000-08-15 2001-07-17 Cpd, Llc Method of treating the syndrome of coronary heart disease risk factors in humans
US6528520B2 (en) 2000-08-15 2003-03-04 Cpd, Llc Method of treating the syndrome of coronary heart disease risk factors in humans
WO2002026265A2 (en) * 2000-09-29 2002-04-04 Schering Corporation Pegylated interleukin-10
AU2002228608A1 (en) 2000-12-13 2002-06-24 Eli Lilly And Company Amidated glucagon-like peptide-1
CA2455963C (en) 2001-07-31 2017-07-04 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
US20040002468A1 (en) * 2001-08-08 2004-01-01 Genzyme Corporation Methods of treating diabetes and other blood sugar disorders
WO2003020201A2 (en) 2001-08-28 2003-03-13 Eli Lilly And Company Pre-mixes of glp-1 and basal insulin
GB0121709D0 (en) * 2001-09-07 2001-10-31 Imp College Innovations Ltd Food inhibition agent
AR036711A1 (es) * 2001-10-05 2004-09-29 Bayer Corp Peptidos que actuan como agonistas del receptor del glp-1 y como antagonistas del receptor del glucagon y sus metodos de uso farmacologico
US7041646B2 (en) * 2001-10-05 2006-05-09 Bayer Pharmaceuticals Corporation Methods of treating type 2 diabetes with peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists
US6864069B2 (en) 2001-10-05 2005-03-08 Bayer Pharmaceuticals Corporation Peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists and their pharmacological methods of use
HUP0700151A2 (en) * 2001-10-18 2007-05-29 Bristol Myers Squibb Co Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions
JP2005508360A (ja) 2001-10-19 2005-03-31 イーライ・リリー・アンド・カンパニー Glp−1およびインスリンの二相混合物
JP2005518408A (ja) * 2001-12-29 2005-06-23 ノボ ノルディスク アクティーゼルスカブ 異常脂肪血症を治療するための、glp−1化合物と他の薬物との組み合わせ使用
MXPA04006679A (es) 2002-01-08 2004-11-10 Lilly Co Eli Analogos extendidos de peptido-1 de tipo glucagon.
US20030232761A1 (en) * 2002-03-28 2003-12-18 Hinke Simon A. Novel analogues of glucose-dependent insulinotropic polypeptide
EP1575490A4 (en) 2002-06-04 2007-08-08 Lilly Co Eli MODIFIED ANALOGUES OF GLUCAGON-LIKE PEPTIDE-1 (GLP-1)
WO2003103697A2 (en) 2002-06-11 2003-12-18 Cell Therapeutics Scandinavia Ab Use of compounds having gip activity for the treatment of disorders associated with abnormal loss of cells and/or for the treatment of obesity
US20040029805A1 (en) 2002-06-15 2004-02-12 Wolfe M. Michael Prevention and treatment of nonalcoholic fatty liver disease (NAFLD) by antagonism of the receptor to glucose-dependent insulinotropic polypeptide (GIP)
CA2497794A1 (en) 2002-09-06 2004-03-18 Bayer Pharmaceuticals Corporation Modified glp-1 receptor agonists and their pharmacological methods of use
US7192922B2 (en) * 2002-11-19 2007-03-20 Allegheny-Singer Research Institute Method of treating left ventricular dysfunction
EP2368578A1 (en) 2003-01-09 2011-09-28 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
WO2004067548A2 (en) 2003-01-31 2004-08-12 Theratechnologies Inc. Chemically modified metabolites of regulatory peptides and methods of producing and using same
CN1750842A (zh) * 2003-02-19 2006-03-22 研究及应用科学协会股份有限公司 Glp-1的类似物
WO2004078777A2 (en) 2003-03-04 2004-09-16 Biorexis Pharmaceutical Corporation Dipeptidyl-peptidase protected proteins
EA009366B1 (ru) * 2003-03-19 2007-12-28 Эли Лилли Энд Компани Связанные с полиэтиленгликолем соединения гпп-1
CA2843439A1 (en) * 2003-04-08 2004-10-21 Yeda Research And Development Co. Ltd Reversible pegylated drugs
TWI353991B (en) 2003-05-06 2011-12-11 Syntonix Pharmaceuticals Inc Immunoglobulin chimeric monomer-dimer hybrids
CN1822851B (zh) 2003-05-15 2011-04-13 塔夫茨大学信托人 肽和多肽药物的稳定类似物
PL1633390T3 (pl) 2003-06-03 2012-06-29 Novo Nordisk As Stabilizowane kompozycje farmaceutyczne peptydu glp-1
EP1633391B1 (en) 2003-06-03 2011-10-19 Novo Nordisk A/S Stabilized pharmaceutical peptide compositions
EA008831B1 (ru) * 2003-06-12 2007-08-31 Эли Лилли Энд Компани Слитые белки аналогов glp-1
US20050124550A1 (en) * 2003-06-18 2005-06-09 Peri Krishna G. Compounds that modulate the glucagon response and uses thereof
CA2539253A1 (en) * 2003-09-19 2005-03-31 Novo Nordisk A/S Albumin-binding derivatives of therapeutic peptides
US7364875B2 (en) * 2003-10-30 2008-04-29 Cresent Innovations, Inc. Method for producing medical and commercial grade poly-gamma-glutamic acid of high molecular weight
AU2004298424A1 (en) * 2003-12-18 2005-06-30 Novo Nordisk A/S Novel GLP-1 compounds
US20060286129A1 (en) * 2003-12-19 2006-12-21 Emisphere Technologies, Inc. Oral GLP-1 formulations
US20080318837A1 (en) * 2003-12-26 2008-12-25 Nastech Pharmaceutical Company Inc. Pharmaceutical Formation For Increased Epithelial Permeability of Glucose-Regulating Peptide
US8527752B2 (en) 2004-06-16 2013-09-03 Dormarke Assets Limited Liability Graduated authentication in an identity management system
JP4666342B2 (ja) 2004-07-26 2011-04-06 ルネサスエレクトロニクス株式会社 半導体集積回路装置
US20080305986A1 (en) * 2004-08-16 2008-12-11 Killian Waldemar Conde Fieboes Multimers of Peptides
US7442682B2 (en) * 2004-10-19 2008-10-28 Nitto Denko Corporation Transepithelial delivery of peptides with incretin hormone activities
US8263545B2 (en) * 2005-02-11 2012-09-11 Amylin Pharmaceuticals, Inc. GIP analog and hybrid polypeptides with selectable properties
US20090286723A1 (en) 2005-02-11 2009-11-19 Amylin Pharmaceuticals, Inc. Hybrid Polypeptides with Selectable Properties
EP1853627A2 (en) 2005-02-11 2007-11-14 Amylin Pharmaceuticals, Inc. Gip analog and hybrid polypeptides with selectable properties
EP1863537A2 (en) * 2005-03-18 2007-12-12 Novo Nordisk A/S Dimeric peptide agonists of the glp-1 receptor
WO2006121904A1 (en) 2005-05-06 2006-11-16 Bayer Pharmaceuticals Corporation Glucose-dependent insulinotropic polypeptide (gip) receptor agonists and their pharmacological methods of use
KR101011081B1 (ko) 2005-05-13 2011-01-25 일라이 릴리 앤드 캄파니 Peg화된 glp-1 화합물
DK1891105T3 (da) 2005-06-13 2012-07-16 Imp Innovations Ltd Hidtil ukendte forbindelser og deres påvirkninger på spiseadfærd
US7360772B2 (en) 2005-07-20 2008-04-22 Koch Hal D Child transport air filtering system
EP1943274A2 (en) 2005-09-08 2008-07-16 Uutech Limited Treatment of diabetes related obesity
US20090286722A1 (en) 2005-09-08 2009-11-19 Utech Limited Analogs of Gastric Inhibitory Polypeptide as a Treatment for Age Related Decreased Pancreatic Beta Cell Function
US8338368B2 (en) * 2005-11-07 2012-12-25 Indiana University Research And Technology Corporation Glucagon analogs exhibiting physiological solubility and stability
WO2007100535A2 (en) 2006-02-22 2007-09-07 Merck & Co., Inc. Oxyntomodulin derivatives
ES2397659T3 (es) * 2006-03-15 2013-03-08 Novo Nordisk A/S Mezclas de amilina e insulina
CN101432025B (zh) 2006-03-21 2012-04-04 安米林药品公司 肽-肽酶抑制剂结合物及其使用方法
MX2008013304A (es) 2006-04-20 2008-10-27 Amgen Inc Compuestos de peptido 1 tipo glucagon.
WO2008022015A2 (en) 2006-08-11 2008-02-21 Trustees Of Tufts College Retro-inverso incretin analogues, and methods of use thereof
WO2008021560A2 (en) 2006-08-17 2008-02-21 Amylin Pharmaceuticals, Inc. Dpp-iv resistant gip hybrid polypeptides with selectable properties
US20090318353A1 (en) 2006-08-25 2009-12-24 Novo Nordisk A/S Acylated Exendin-4 Compounds
US20080053857A1 (en) 2006-08-31 2008-03-06 Paul Vincent Enriquez Albano Package having two different views for increased awareness in display
DK2615108T3 (en) * 2006-09-08 2017-01-30 Ambrx Inc Modified human plasma polypeptide or fc scaffolds and their applications
EP2102355B1 (en) 2006-12-14 2016-03-02 Bolder Biotechnology, Inc. Long acting proteins and peptides and methods of making and using the same
WO2008086086A2 (en) 2007-01-05 2008-07-17 Indiana University Research And Technology Corporation Glucagon analogs exhibiting enhanced solubility in physiological ph buffers
JP6017754B2 (ja) * 2007-02-15 2016-11-02 インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation グルカゴン/glp−1受容体コアゴニスト
DK2158214T3 (da) * 2007-06-15 2011-12-05 Zealand Pharma As Glukagonanaloger
US7859468B2 (en) * 2007-08-30 2010-12-28 Research In Motion Limited Mobile wireless communications device including a folded monopole multi-band antenna and related methods
US20100292133A1 (en) 2007-09-05 2010-11-18 Novo Nordisk A/S Truncated glp-1 derivaties and their therapeutical use
ES2672770T3 (es) 2007-09-05 2018-06-18 Novo Nordisk A/S Derivados del péptido-1 similar al glucagón y su uso farmacéutico
EP2200626A4 (en) 2007-09-07 2012-02-15 Ipsen Pharma Sas ANALOGUE OF EXENDIN-4 AND EXENDIN-3
CN101854948A (zh) 2007-09-11 2010-10-06 诺沃-诺迪斯克有限公司 含有胰岛淀粉样多肽类和长效胰岛素的合剂
EP2036923A1 (en) 2007-09-11 2009-03-18 Novo Nordisk A/S Improved derivates of amylin
EP2036539A1 (en) 2007-09-11 2009-03-18 Novo Nordisk A/S Stable formulations of amylin and its analogues
CA2702289A1 (en) 2007-10-30 2009-05-07 Indiana University Research And Technology Corporation Compounds exhibiting glucagon antagonist and glp-1 agonist activity
EP2217701B9 (en) 2007-10-30 2015-02-18 Indiana University Research and Technology Corporation Glucagon antagonists
CN101918027A (zh) 2007-11-02 2010-12-15 森托科尔奥索生物科技公司 半合成GLP-1肽-Fc融合构造、方法及其用途
EP2249853A4 (en) 2008-01-30 2012-12-26 Univ Indiana Res & Tech Corp ESTER BASED PEPTIDE PRODRUGS
CN101980725B (zh) 2008-02-01 2013-06-12 阿森迪斯药物股份有限公司 包含可自裂解的连接体的前药
AU2009260302B2 (en) * 2008-06-17 2014-10-23 Indiana University Research And Technology Corporation Glucagon/GLP-1 receptor co-agonists
JP5753779B2 (ja) * 2008-06-17 2015-07-22 インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation 生理学的pHの緩衝液中で向上した溶解性及び安定性を示すグルカゴン類縁体
BRPI0915282A2 (pt) 2008-06-17 2017-02-07 Univ Indiana Res & Tech Corp agonistas mistos baseados no gip para o tratamento de distúrbios metabólicos e obesidade
KR20110114568A (ko) 2008-12-19 2011-10-19 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 디펩티드 링크된 약효 물질
AU2009327418A1 (en) 2008-12-19 2010-06-24 Indiana University Research And Technology Corporation Amide based glucagon superfamily peptide prodrugs
WO2010096052A1 (en) 2009-02-19 2010-08-26 Merck Sharp & Dohme Corp. Oxyntomodulin analogs
US9150632B2 (en) 2009-06-16 2015-10-06 Indiana University Research And Technology Corporation GIP receptor-active glucagon compounds
WO2011075393A2 (en) 2009-12-18 2011-06-23 Indiana University Research And Technology Corporation Glucagon/glp-1 receptor co-agonists
AR079345A1 (es) 2009-12-22 2012-01-18 Lilly Co Eli Analogo peptidico de oxintomodulina
AR079344A1 (es) 2009-12-22 2012-01-18 Lilly Co Eli Analogo peptidico de oxintomodulina, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para tratar diabetes no insulinodependiente y/u obesidad
RU2012136450A (ru) 2010-01-27 2014-03-10 Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн Конъюгаты антагонист глюкагона - агонист gip и композиции для лечения метаболических расстройств и ожирения
AR080592A1 (es) 2010-03-26 2012-04-18 Lilly Co Eli Peptido con actividad para el gip-r y glp-1-r, formulacion famaceutica que lo comprende, su uso para preparar un medicamento util para el tratamiento de diabetes mellitus y para inducir la perdida de peso
EP2569000B1 (en) 2010-05-13 2017-09-27 Indiana University Research and Technology Corporation Glucagon superfamily peptides exhibiting nuclear hormone receptor activity
US9145451B2 (en) 2010-05-13 2015-09-29 Indiana University Research And Technology Corporation Glucagon superfamily peptides exhbiting G protein coupled receptor activity
EP2588126A4 (en) 2010-06-24 2015-07-08 Univ Indiana Res & Tech Corp AMID-BASED GLUCAGON SUPERFAMILY PEPTIDE PRODRUGS
WO2011163473A1 (en) 2010-06-25 2011-12-29 Indiana University Research And Technology Corporation Glucagon analogs exhibiting enhanced solubility and stability in physiological ph buffers

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