AU2013255752B2 - Glucagon-like-peptide-2 (GLP-2) analogues - Google Patents
Glucagon-like-peptide-2 (GLP-2) analogues Download PDFInfo
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- AU2013255752B2 AU2013255752B2 AU2013255752A AU2013255752A AU2013255752B2 AU 2013255752 B2 AU2013255752 B2 AU 2013255752B2 AU 2013255752 A AU2013255752 A AU 2013255752A AU 2013255752 A AU2013255752 A AU 2013255752A AU 2013255752 B2 AU2013255752 B2 AU 2013255752B2
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- glp
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Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261642447P | 2012-05-03 | 2012-05-03 | |
| US61/642,447 | 2012-05-03 | ||
| US201361785852P | 2013-03-14 | 2013-03-14 | |
| US61/785,852 | 2013-03-14 | ||
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Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2051995B1 (en) | 2006-11-08 | 2017-02-08 | Zealand Pharma A/S | Selective glucagon-like-peptide-2 (glp-2) analogues |
| EP2844670B1 (en) | 2012-05-03 | 2017-12-06 | Zealand Pharma A/S | Glucagon-like-peptide-2 (glp-2) analogues |
| MX356957B (es) | 2012-07-23 | 2018-06-20 | Zealand Pharma As | Analogos del glucagon. |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| MX362190B (es) | 2012-12-21 | 2019-01-08 | Sanofi Sa | Agonistas duales de glp1/gip o trigonales de glp1/gip/glucagon. |
| CA2926314C (en) | 2013-10-17 | 2023-08-29 | Zealand Pharma A/S | Acylated glucagon analogues |
| US9988429B2 (en) | 2013-10-17 | 2018-06-05 | Zealand Pharma A/S | Glucagon analogues |
| AU2014345569B2 (en) | 2013-11-06 | 2020-08-13 | Zealand Pharma A/S | GIP-GLP-1 dual agonist compounds and methods |
| CN105829339B (zh) | 2013-11-06 | 2021-03-12 | 西兰制药公司 | 胰高血糖素-glp-1-gip三重激动剂化合物 |
| TW201609800A (zh) * | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 做為雙重ｇｌｐ－１／升糖素受體促效劑之艾塞那肽－４胜肽類似物 |
| WO2015086729A1 (en) * | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/gip receptor agonists |
| WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| TW201609796A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 非醯化之艾塞那肽－４（ｅｘｅｎｄｉｎ－４）胜肽類似物 |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| 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 |
| 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 |
| 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 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| EP3212218B1 (en) | 2014-10-29 | 2021-06-30 | Zealand Pharma A/S | Gip agonist compounds and methods |
| KR20170078668A (ko) * | 2014-10-31 | 2017-07-07 | 구브라 에이피에스 | 이중 glp-1r 및 glp-2r 작용제 활성을 갖는 조성물 및 펩티드 |
| CA2980978A1 (en) | 2015-04-16 | 2016-10-20 | Zealand Pharma A/S | Acylated glucagon analogue |
| 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 |
| KR102508651B1 (ko) | 2015-12-23 | 2023-03-13 | 더 존스 홉킨스 유니버시티 | 신경계 및 신경변성 상태의 요법으로서 장기간 작용하는 glf-1r 작용제 |
| JP6700150B2 (ja) * | 2016-10-03 | 2020-05-27 | 東京エレクトロン株式会社 | パーティクル捕集装置、パーティクル捕集方法、およびパーティクル捕集システム |
| WO2018103868A1 (en) | 2016-12-09 | 2018-06-14 | Zealand Pharma A/S | Acylated glp-1/glp-2 dual agonists |
| WO2018104559A1 (en) | 2016-12-09 | 2018-06-14 | Zealand Pharma A/S | Glp-1/glp-2 dual agonists |
| WO2018104558A1 (en) | 2016-12-09 | 2018-06-14 | Zealand Pharma A/S | Acylated glp-1/glp-2 dual agonists |
| RU2753193C2 (ru) * | 2016-12-09 | 2021-08-12 | Зилэнд Фарма А/С | Ацилированные двойные агонисты glp-1/glp-2 |
| BR112019011859A2 (pt) * | 2016-12-09 | 2019-10-29 | Zealand Pharma As | agonista duplo de glp-1/glp-2, composição, método para aumentar massa intestinal, método de profilaxia ou tratamento de má-absorção intestinal e uso de um agonista duplo |
| ES2894629T3 (es) * | 2017-06-16 | 2022-02-15 | Zealand Pharma As | Pautas posológicas para la administración de análogos del péptido 2 similar al glucagón (GLP-2) |
| GB201710822D0 (en) * | 2017-07-05 | 2017-08-16 | Zealand Pharma As | Methods and medical uses relating to the treatment of hypoglycaemia |
| KR102825098B1 (ko) | 2017-11-06 | 2025-06-26 | 다케다 야쿠힌 고교 가부시키가이샤 | 수술전, 수술동안 또는 수술후 투여용 glp-2 유사체 및 펩티바디 |
| WO2020020904A1 (en) | 2018-07-23 | 2020-01-30 | Zealand Pharma A/S | Therapeutic uses of glp-2 agonists |
| EP3924369A1 (en) | 2019-02-11 | 2021-12-22 | OPKO Biologics Ltd. | Long-acting glp-2 analogs |
| EP3982920A1 (en) | 2019-06-14 | 2022-04-20 | Zealand Pharma A/S | Pharmaceutical parenteral composition of dual glp1/2 agonist |
| WO2021071837A1 (en) | 2019-10-07 | 2021-04-15 | Kallyope, Inc. | Gpr119 agonists |
| CN111329995B (zh) * | 2020-02-18 | 2022-11-11 | 河南中医药大学 | Glp-2类似物在制备防治pd药物中的应用及防治pd的药物 |
| TW202140440A (zh) | 2020-02-28 | 2021-11-01 | 美商克力歐普股份有限公司 | Gpr40激動劑 |
| WO2021201654A1 (ko) * | 2020-04-03 | 2021-10-07 | 한미약품 주식회사 | Glp-2 유도체 또는 이의 지속형 결합체를 포함하는 방사선요법, 화학요법, 또는 이들의 조합으로 유발된 점막염의 예방 또는 치료용 약학적 조성물 |
| EP4153589A4 (en) | 2020-05-19 | 2024-06-12 | Kallyope, Inc. | AMPK ACTIVATORS |
| WO2021252659A1 (en) | 2020-06-09 | 2021-12-16 | Vectivbio Ag | Manufacture, formulation and dosing of apraglutide |
| WO2021263039A1 (en) | 2020-06-26 | 2021-12-30 | Kallyope, Inc. | Ampk activators |
| CN119923269A (zh) | 2022-09-19 | 2025-05-02 | 西兰制药公司 | 组合治疗 |
| CN116478269A (zh) * | 2023-04-28 | 2023-07-25 | 成都奥达生物科技有限公司 | 一种长效替度鲁肽化合物 |
| CN118146350B (zh) * | 2024-03-13 | 2024-10-22 | 北京泽勤生物医药有限公司 | Glp-2肽类似物的制备方法及应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010070251A1 (en) * | 2008-12-15 | 2010-06-24 | Zealand Pharma A/S | Glucagon analogues |
| WO2011160630A2 (en) * | 2010-06-23 | 2011-12-29 | Zealand Pharma A/S | Glucagon analogues |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA811368B (en) | 1980-03-24 | 1982-04-28 | Genentech Inc | Bacterial polypedtide expression employing tryptophan promoter-operator |
| JP2961045B2 (ja) | 1993-02-24 | 1999-10-12 | 日清製粉株式会社 | 腸管粘膜増強促進剤 |
| US6184208B1 (en) | 1994-06-29 | 2001-02-06 | Immunotech Developments Inc. | Peptide, a method for its preparation and a pharmaceutical composition containing the peptide |
| US6184201B1 (en) | 1995-04-14 | 2001-02-06 | Nps Allelix Corp. | Intestinotrophic glucagon-like peptide-2 analogs |
| US5789379A (en) | 1995-04-14 | 1998-08-04 | Allelix Biopharmaceutical Inc. | Glucagon-like peptide-2 analogs |
| US5990077A (en) | 1995-04-14 | 1999-11-23 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
| US5834428A (en) | 1995-04-14 | 1998-11-10 | 1149336 Ontario Inc. | Glucagon-like peptide-2 and its therapeutic use |
| DK0891378T3 (da) | 1996-03-01 | 2003-01-06 | Novo Nordisk As | Anvendelse af farmaceutisk formulering omfattende et appetitundertrykkende peptid |
| US5912229A (en) | 1996-03-01 | 1999-06-15 | Novo Nordisk Als | Use of a pharmaceutical composition comprising an appetite-suppressing peptide |
| EP1231219B1 (en) | 1996-04-12 | 2010-08-25 | 1149336 Ontario Inc. | GLucagon-like peptide-2 analogs |
| US5994500A (en) | 1996-07-19 | 1999-11-30 | 1149336 Ontario Inc. | Antagonists of intestinotrophic GLP-2 peptides |
| US20020025933A1 (en) | 1996-08-30 | 2002-02-28 | Knudsen Liselotte Bjerre | GLP-2 derivatives |
| JP3149958B2 (ja) | 1996-08-30 | 2001-03-26 | ノボ ノルディスク アクティーゼルスカブ | Ｇｌｐ―１誘導体 |
| IL128829A (en) | 1996-09-09 | 2005-08-31 | Zealand Pharma As | Solid phase sythesis of peptides with pre-sequences |
| US5952301A (en) | 1996-12-10 | 1999-09-14 | 1149336 Ontario Inc. | Compositions and methods for enhancing intestinal function |
| CA2236519C (en) | 1997-05-02 | 2011-09-13 | 1149336 Ontario Inc. | Methods of enhancing functioning of the large intestine |
| US6051557A (en) | 1997-05-16 | 2000-04-18 | 1149336 Ontario Inc. | Methods of enhancing functioning of the upper gastrointestinal tract |
| BR9808804A (pt) | 1997-05-16 | 2001-09-18 | Ontario Inc | Processos para tratar um indivìduo para melhorar o funcionamento do trato gastrointestinal superior incluindo o esÈfago e o estÈmago, para tratar um indivìduo para proliferar o tecido do trato gastrointestinal superior, para identificar peptìdeos utilizável para tratar condições inflamatórias, para identificar peptìdeos, utilizável para evitar ou melhorar as condições inflamatórias, utilizável para identificar peptìdeos capazes de proliferar tecido do trato gastrointestinal superior, para tratar profilaticamente um indivìduo, para melhorar o crescimento do tecido do trato gastrointestinal superior em um mamìfero, e para tratar um indivìduo para melhorar o funcionamento do trato gastrointestinal superior, kit, processos para promover o crescimento de tecido do trato gastrointestinal superior ou células, para tratar um paciente para restaurar o trato gastrointestinal superior, para determinar a atividade de um hormÈnio quando usado em combinação com glp-2, para tratar um indivìduo tendo úlceras peptìdicas |
| WO1999038501A2 (en) | 1998-02-02 | 1999-08-05 | Trustees Of Tufts College | Method of regulating glucose metabolism, and reagents related thereto |
| IL138214A0 (en) | 1998-03-09 | 2001-10-31 | Zealand Pharmaceuticals As | Pharmacolgically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| WO1999058144A1 (en) | 1998-05-11 | 1999-11-18 | 1149336 Ontario Inc. | Methods of enhancing functioning of the large intestine |
| US6451987B1 (en) | 1999-03-15 | 2002-09-17 | Novo Nordisk A/S | Ion exchange chromatography of proteins and peptides |
| EP1956000B1 (en) | 1999-03-17 | 2016-10-05 | Novo Nordisk A/S | Acylating agents useful for acylating peptides |
| EP1076066A1 (en) | 1999-07-12 | 2001-02-14 | Zealand Pharmaceuticals A/S | Peptides for lowering blood glucose levels |
| AU2020501A (en) | 1999-12-08 | 2001-06-18 | 1149336 Ontario Inc. | Chemotherapy treatment |
| US7371721B2 (en) | 2000-09-18 | 2008-05-13 | Sanos Bioscience A/S | Use of GLP-2 and related compounds for the treatment, prevention, diagnosis, and prognosis of bone-related disorders and calcium homeostasis related syndromes |
| DK1326630T3 (da) | 2000-09-18 | 2008-09-15 | Sanos Bioscience As | Anvendelse af GLP-2-peptider |
| US7186683B2 (en) | 2000-09-18 | 2007-03-06 | Sanos Bioscience A/S | Use of GLP for the treatment, prevention, diagnosis, and prognosis of bone-related and nutrition-related disorders |
| WO2002066062A2 (en) | 2001-02-01 | 2002-08-29 | Drucker Daniel J | Enhancement of glp-2 activity |
| US7112567B2 (en) | 2001-02-16 | 2006-09-26 | Conjuchem Inc. | Long lasting glucagon-like peptide 2 (glp-2) for the treatment of gastrointestinal diseases and disorders |
| EP1542712A2 (en) | 2001-06-01 | 2005-06-22 | Eli Lilly And Company | Glp-1 formulations with protracted time action |
| CN1705681A (zh) * | 2002-10-14 | 2005-12-07 | 诺沃挪第克公司 | Glp－2化合物、制剂及其用途 |
| WO2004035624A2 (en) | 2002-10-14 | 2004-04-29 | Novo Nordisk A/S | Glucagon - like peptide - 2 variants |
| KR20050059258A (ko) * | 2002-10-14 | 2005-06-17 | 노보 노르디스크 에이/에스 | Ｇｌｐ-2 화합물, 제제, 및 그것의 사용 |
| KR101241862B1 (ko) | 2003-09-19 | 2013-03-13 | 노보 노르디스크 에이/에스 | 신규 ｇｌｐ-1 유도체 |
| WO2005082404A2 (en) * | 2004-02-27 | 2005-09-09 | Novo Nordisk A/S | Glp-2 derivatives modified by lipophilic substituents |
| DK1809318T3 (da) | 2004-11-01 | 2013-09-08 | Nps Pharma Inc | Behandling af korttarmssyndrom-patienter med tyktarmskontinuitet |
| AU2006242998B2 (en) | 2005-05-04 | 2012-03-22 | Zealand Pharma A/S | Glucagon-like-peptide-2 (GLP-2) analogues |
| EP2051995B1 (en) | 2006-11-08 | 2017-02-08 | Zealand Pharma A/S | Selective glucagon-like-peptide-2 (glp-2) analogues |
| EP2710031B9 (en) * | 2011-05-18 | 2018-02-28 | Mederis Diabetes, LLC | Improved peptide pharmaceuticals for insulin resistance |
| EP2844670B1 (en) | 2012-05-03 | 2017-12-06 | Zealand Pharma A/S | Glucagon-like-peptide-2 (glp-2) analogues |
-
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|---|---|---|---|---|
| WO2010070251A1 (en) * | 2008-12-15 | 2010-06-24 | Zealand Pharma A/S | Glucagon analogues |
| WO2011160630A2 (en) * | 2010-06-23 | 2011-12-29 | Zealand Pharma A/S | Glucagon analogues |
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| US20150125431A1 (en) | 2015-05-07 |
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| US20160355563A1 (en) | 2016-12-08 |
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| CA2872315A1 (en) | 2013-11-07 |
| MX356958B (es) | 2018-06-20 |
| TR201802689T4 (tr) | 2018-03-21 |
| BR112014027345A2 (pt) | 2019-09-03 |
| US10253080B2 (en) | 2019-04-09 |
| IN2014DN09782A (OSRAM) | 2015-07-31 |
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