AU2013255752B2 - Glucagon-like-peptide-2 (GLP-2) analogues - Google Patents

Glucagon-like-peptide-2 (GLP-2) analogues Download PDF

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Publication number: AU2013255752B2
Authority: AU; Australia
Prior art keywords: glp; gly; analogue; ser; absent
Prior art date: 2012-05-03
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.): Ceased

Application number

AU2013255752A

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English (en)

Other versions

AU2013255752A1 (en

Inventor

Kirsten Lindegaard BOVBJERG

Rasmus JUST

Ditte Riber

Wayne Shaun RUSSELL

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.)

Zealand Pharma AS

Original Assignee

Zealand Pharma AS

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.)

2012-05-03

Filing date

2013-05-03

Publication date

2017-11-09

2013-05-03 Application filed by Zealand Pharma AS filed Critical Zealand Pharma AS

2014-12-18 Publication of AU2013255752A1 publication Critical patent/AU2013255752A1/en

2017-11-09 Application granted granted Critical

2017-11-09 Publication of AU2013255752B2 publication Critical patent/AU2013255752B2/en

Status Ceased legal-status Critical Current

2033-05-03 Anticipated expiration legal-status Critical

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Classifications

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Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Epidemiology (AREA)
Zoology (AREA)
Immunology (AREA)
Biomedical Technology (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Cell Biology (AREA)
Gastroenterology & Hepatology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Developmental Biology & Embryology (AREA)
Insects & Arthropods (AREA)
Hematology (AREA)
Obesity (AREA)
Virology (AREA)
Biotechnology (AREA)
Reproductive Health (AREA)
Molecular Biology (AREA)
Toxicology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Cardiology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Heart & Thoracic Surgery (AREA)

AU2013255752A 2012-05-03 2013-05-03 Glucagon-like-peptide-2 (GLP-2) analogues Ceased AU2013255752B2 (en)

Applications Claiming Priority (5)

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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
PCT/EP2013/059320 WO2013164484A1 (en)	2012-05-03	2013-05-03	Glucagon-like-peptide-2 (glp-2) analogues

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AU2013255752B2 true AU2013255752B2 (en)	2017-11-09

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US (3)	US9453064B2 (2)
EP (1)	EP2844670B1 (2)
JP (1)	JP6298044B2 (2)
KR (1)	KR20150006052A (2)
CN (1)	CN104540850B (2)
AU (1)	AU2013255752B2 (2)
BR (1)	BR112014027345A2 (2)
CA (1)	CA2872315A1 (2)
EA (1)	EA028929B1 (2)
IN (1)	IN2014DN09782A (2)
MX (1)	MX356958B (2)
TR (1)	TR201802689T4 (2)
WO (1)	WO2013164484A1 (2)

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CN101573376B (zh)	2006-11-08	2013-11-06	西兰制药公司	选择性胰高血糖素样肽-2（glp-2）类似物
CN104540850B (zh)	2012-05-03	2018-05-18	西兰制药公司	胰高血糖素样肽2(glp-2)类似物
IN2015DN00544A (2)	2012-07-23	2015-06-26	Zealand Pharma As
UA116217C2 (uk)	2012-10-09	2018-02-26	Санофі	Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону
AU2013366692B2 (en)	2012-12-21	2017-11-23	Sanofi	Dual GLP1/GIP or trigonal GLP1/GIP/Glucagon agonists
PL3057984T3 (pl)	2013-10-17	2018-12-31	Zealand Pharma A/S	Acylowane analogi glukagonu
US9988429B2 (en)	2013-10-17	2018-06-05	Zealand Pharma A/S	Glucagon analogues
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
WO2015067715A2 (en)	2013-11-06	2015-05-14	Zealand Pharma A/S	Gip-glp-1 dual agonist compounds and methods
WO2015086728A1 (en)	2013-12-13	2015-06-18	Sanofi	Exendin-4 peptide analogues as dual glp-1/gip receptor agonists
EP3080152A1 (en)	2013-12-13	2016-10-19	Sanofi	Non-acylated exendin-4 peptide analogues
EP3080154B1 (en)	2013-12-13	2018-02-07	Sanofi	Dual glp-1/gip receptor agonists
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
WO2015086733A1 (en)	2013-12-13	2015-06-18	Sanofi	Dual glp-1/glucagon receptor agonists
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
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
KR102620911B1 (ko)	2014-10-29	2024-01-05	질랜드 파마 에이/에스	Gip 효능제 화합물 및 방법
US20180280480A1 (en) *	2014-10-31	2018-10-04	Gubra Aps	Compositions and peptides having dual glp-1r and glp-2r agonist activity
DK3283507T3 (da)	2015-04-16	2020-01-02	Zealand Pharma As	Acyleret glucagonanalog
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
CN108697768B (zh)	2015-12-23	2022-07-22	约翰霍普金斯大学	长效glp-1r激动剂作为神经系统病状和神经退行性病状的治疗方法
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
WO2018104559A1 (en)	2016-12-09	2018-06-14	Zealand Pharma A/S	Glp-1/glp-2 dual agonists
CA3044915A1 (en) *	2016-12-09	2018-06-14	Zealand Pharma A/S	Glp-1/glp-2 dual agonists
EP3551651B1 (en)	2016-12-09	2024-03-06	Zealand Pharma A/S	Acylated 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
WO2018103868A1 (en)	2016-12-09	2018-06-14	Zealand Pharma A/S	Acylated glp-1/glp-2 dual agonists
IL299864B2 (en) *	2017-06-16	2024-06-01	Zealand Pharma As	Dosage regimes for the administration of glucagon-like-peptide-2 (glp-2) analogues
GB201710822D0 (en) *	2017-07-05	2017-08-16	Zealand Pharma As	Methods and medical uses relating to the treatment of hypoglycaemia
WO2019090209A1 (en)	2017-11-06	2019-05-09	Shire-Nps Pharmaceuticals, Inc.	Glp-2 analogs and peptibodies for administration before during, or after surgery
WO2020020904A1 (en)	2018-07-23	2020-01-30	Zealand Pharma A/S	Therapeutic uses of glp-2 agonists
CA3129576A1 (en)	2019-02-11	2020-08-20	Opko Biologics Ltd.	Long-acting glp-2 analogs
SG11202111311WA (en)	2019-06-14	2021-12-30	Zealand Pharma As	Pharmaceutical parenteral composition of dual glp1/2 agonist
KR20220150270A (ko)	2019-10-07	2022-11-10	칼리오페, 인크.	Gpr119 효능제
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
WO2021236617A1 (en)	2020-05-19	2021-11-25	Kallyope, Inc.	Ampk activators
BR112022025141A2 (pt)	2020-06-09	2023-04-25	Vectivbio Ag	Fabricação, formulação e dosagem de apraglutida
CN116390925A (zh)	2020-06-26	2023-07-04	卡尔优普公司	Ampk活化剂
IL319599A (en)	2022-09-19	2025-05-01	Zealand Pharma As	Combination therapy
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)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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
US5834428A (en)	1995-04-14	1998-11-10	1149336 Ontario Inc.	Glucagon-like peptide-2 and its therapeutic use
US5990077A (en)	1995-04-14	1999-11-23	1149336 Ontario Inc.	Glucagon-like peptide-2 and its therapeutic use
US5789379A (en)	1995-04-14	1998-08-04	Allelix Biopharmaceutical Inc.	Glucagon-like peptide-2 analogs
US5912229A (en)	1996-03-01	1999-06-15	Novo Nordisk Als	Use of a pharmaceutical composition comprising an appetite-suppressing peptide
DE69740176D1 (de)	1996-03-01	2011-05-26	Novo Nordisk As	Appetithemmendes Peptid, Zusammensetzung und Verwendung
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
IL128332A0 (en)	1996-08-30	2000-01-31	Novo Nordisk As	GLP-1 derivatives
US20020025933A1 (en)	1996-08-30	2002-02-28	Knudsen Liselotte Bjerre	GLP-2 derivatives
AU723268B2 (en)	1996-09-09	2000-08-24	Zealand Pharma A/S	Improved solid-phase peptide synthesis and agent for use in such synthesis
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
CA2289652C (en)	1997-05-16	2012-02-28	1149336 Ontario Inc.	Methods of enhancing functioning of the upper gastrointestinal tract
US6051557A (en)	1997-05-16	2000-04-18	1149336 Ontario Inc.	Methods of enhancing functioning of the upper gastrointestinal tract
EP2583675A1 (en)	1998-02-02	2013-04-24	Trustees Of Tufts College	Use of dipeptidylpeptidase inhibitors to regulate glucose metabolism
NZ506839A (en)	1998-03-09	2003-05-30	Zealand Pharma As	Pharmacologically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis
AU7421598A (en)	1998-05-11	1999-11-29	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
CZ20013018A3 (cs)	1999-03-17	2002-02-13	Novo Nordisk A/S	Způsob pro acylování aminoskupiny peptidu nebo proteinu a sloučenina
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
EP1970072A1 (en)	2000-09-18	2008-09-17	Sanos Bioscience A/S	Use of GLP-2 peptides for the treatment of hyperparathyroidism
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
DK1360202T3 (da)	2001-02-16	2008-09-22	Conjuchem Biotechnologies Inc	Langvarigt glucagon-lignende peptid 2 (GLP-2) til behandling af gastrointestinale sygdomme og lidelser
AU2002308706A1 (en)	2001-06-01	2002-12-16	Eli Lilly And Company	Glp-1 formulations with protracted time action
WO2004035624A2 (en)	2002-10-14	2004-04-29	Novo Nordisk A/S	Glucagon - like peptide - 2 variants
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
CA2502324A1 (en) *	2002-10-14	2004-04-29	Lars Thim	Glucagon - like peptide - 2 variants
BR122019021416A2 (2)	2003-09-19	2019-12-21
WO2005082404A2 (en) *	2004-02-27	2005-09-09	Novo Nordisk A/S	Glp-2 derivatives modified by lipophilic substituents
EP1809318B1 (en)	2004-11-01	2013-06-12	NPS Pharmaceuticals, Inc.	Treatment of short bowel syndrome patients with colon-in-continuity
UA95235C2 (en)	2005-05-04	2011-07-25	Зииланд Фарма А/С	Glucagon-like-peptide-2 (glp-2) analogues
CN101573376B (zh)	2006-11-08	2013-11-06	西兰制药公司	选择性胰高血糖素样肽-2（glp-2）类似物
DK2710031T3 (en) *	2011-05-18	2018-01-02	Mederis Diabetes Llc	IMPROVED PEPTID MEDICINALS FOR INSULIN RESISTANCE
CN104540850B (zh)	2012-05-03	2018-05-18	西兰制药公司	胰高血糖素样肽2(glp-2)类似物

2013
- 2013-05-03 CN CN201380029907.4A patent/CN104540850B/zh not_active Expired - Fee Related
- 2013-05-03 BR BR112014027345A patent/BR112014027345A2/pt not_active Application Discontinuation
- 2013-05-03 JP JP2015509462A patent/JP6298044B2/ja not_active Expired - Fee Related
- 2013-05-03 TR TR2018/02689T patent/TR201802689T4/tr unknown
- 2013-05-03 EP EP13721953.1A patent/EP2844670B1/en active Active
- 2013-05-03 US US14/398,297 patent/US9453064B2/en active Active
- 2013-05-03 EA EA201491934A patent/EA028929B1/ru not_active IP Right Cessation
- 2013-05-03 KR KR1020147033951A patent/KR20150006052A/ko not_active Abandoned
- 2013-05-03 CA CA2872315A patent/CA2872315A1/en not_active Abandoned
- 2013-05-03 MX MX2014013319A patent/MX356958B/es active IP Right Grant
- 2013-05-03 WO PCT/EP2013/059320 patent/WO2013164484A1/en not_active Ceased
- 2013-05-03 AU AU2013255752A patent/AU2013255752B2/en not_active Ceased
2014
- 2014-11-19 IN IN9782DEN2014 patent/IN2014DN09782A/en unknown
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- 2016-08-16 US US15/238,126 patent/US9969787B2/en not_active Expired - Fee Related
2018
- 2018-04-11 US US15/950,235 patent/US10253080B2/en not_active Expired - Fee Related

Patent Citations (2)

* Cited by examiner, † Cited by third party
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

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AU2013255752A1 (en)	2014-12-18
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EP2844670B1 (en)	2017-12-06
US9453064B2 (en)	2016-09-27
US20180298077A1 (en)	2018-10-18
IN2014DN09782A (2)	2015-07-31
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CA2872315A1 (en)	2013-11-07
CN104540850A (zh)	2015-04-22
US20160355563A1 (en)	2016-12-08
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BR112014027345A2 (pt)	2019-09-03
EP2844670A1 (en)	2015-03-11
US9969787B2 (en)	2018-05-15
TR201802689T4 (tr)	2018-03-21
EA028929B1 (ru)	2018-01-31
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US20150125431A1 (en)	2015-05-07
US10253080B2 (en)	2019-04-09
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US10092648B2 (en)	2018-10-09	Selective glucagon-like-peptide-2 (GLP-2) analogues
US20160347813A1 (en)	2016-12-01	Glucagon analogues
US20150376257A1 (en)	2015-12-31	Glucagon analogues
HK1208238B (en)	2018-10-05	Glucagon-like-peptide-2 (glp-2) analogues