OA11453A - Methods for treatment of diabetes using peptide analogues of insulin. - Google Patents
Methods for treatment of diabetes using peptide analogues of insulin. Download PDFInfo
- Publication number
- OA11453A OA11453A OA1200000229A OA1200000229A OA11453A OA 11453 A OA11453 A OA 11453A OA 1200000229 A OA1200000229 A OA 1200000229A OA 1200000229 A OA1200000229 A OA 1200000229A OA 11453 A OA11453 A OA 11453A
- Authority
- OA
- OAPI
- Prior art keywords
- peptide
- chain
- insulin
- cells
- nbi
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 195
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| OA1200000229A OA11453A (en) | 1998-02-23 | 2000-08-22 | Methods for treatment of diabetes using peptide analogues of insulin. |
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| US6562942B1 (en) * | 1999-02-23 | 2003-05-13 | Neurocrine Biosciences, Inc. | Methods for treatment of diabetes using peptide analogues of insulin |
| CN1125081C (zh) * | 1999-09-08 | 2003-10-22 | 中国科学院上海生物化学研究所 | 重组天然和新型人胰岛素及其制备方法 |
| US7462486B2 (en) * | 2000-05-12 | 2008-12-09 | Oregon Health & Science University | Methods of selecting T cell receptor V peptides for therapeutic use |
| US7371385B2 (en) * | 2000-05-12 | 2008-05-13 | Oregon Health & Science University | Method of treating immune pathologies with low dose estrogen |
| US20020103131A1 (en) * | 2001-01-26 | 2002-08-01 | Jacobson Jill D. | Prevention of diabetes by administration of GnRH antagonists |
| US20040138116A1 (en) * | 2002-08-30 | 2004-07-15 | Vincent Geenen | Tolerogenic approach for type 1 diabetes |
| US20070172453A1 (en) * | 2002-08-30 | 2007-07-26 | Vincent Geenen | Tolerogenic approach for type 1 diabetes |
| CN100582085C (zh) | 2002-10-10 | 2010-01-20 | 耶达研究及发展有限公司 | 脂肪醇的碱性酯及它们作为抗炎药或免疫调节剂的用途 |
| CN1798569A (zh) * | 2003-06-02 | 2006-07-05 | 莫西亚药物公司 | 用于治疗1型糖尿病的治疗性疫苗组合物 |
| CA2575604A1 (en) * | 2004-07-30 | 2006-02-02 | Oregon Health And Science University | Methods for detecting and treating autoimmune disorders |
| US7833513B2 (en) | 2004-12-03 | 2010-11-16 | Rhode Island Hospital | Treatment of Alzheimer's Disease |
| RU2524423C2 (ru) | 2008-01-09 | 2014-07-27 | Санофи-Авентис Дойчланд Гмбх | Новые производные инсулина с чрезвычайно замедленным профилем время/действие |
| DE102008003566A1 (de) * | 2008-01-09 | 2009-07-16 | Sanofi-Aventis Deutschland Gmbh | Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil |
| US20110065633A1 (en) | 2008-01-30 | 2011-03-17 | Indiana University Research And Technology Corporation | Ester-based peptide prodrugs |
| PT3228320T (pt) | 2008-10-17 | 2020-03-26 | Sanofi Aventis Deutschland | Combinação de uma insulina e de um agonista do glp-1 |
| JP5789515B2 (ja) * | 2008-12-19 | 2015-10-07 | 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 | インスリン類似体 |
| US8697632B2 (en) | 2008-12-19 | 2014-04-15 | Indiana University Research And Technology Corporation | Amide based insulin prodrugs |
| WO2011056226A1 (en) | 2009-11-05 | 2011-05-12 | Mercia Pharma Llc | Adjuvanted nanoparticulate influenza vaccine |
| SG10201500871TA (en) | 2009-11-13 | 2015-04-29 | Sanofi Aventis Deutschland | Pharmaceutical composition comprising a glp-1 agonist and methionine |
| JP5832439B2 (ja) | 2009-11-13 | 2015-12-16 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Ｇｌｐ−１アゴニスト、インスリン及びメチオニンを含む薬学的組成物 |
| US20110311536A1 (en) * | 2010-06-11 | 2011-12-22 | Dana-Farber Cancer Institute, Inc. | Prevention of type 1 diabetes by treg vaccination with an insulin mimetope |
| JP5969469B2 (ja) | 2010-06-16 | 2016-08-17 | 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 | インスリン受容体に対して高い活性を示す単鎖インスリンアゴニスト |
| CA2803164C (en) | 2010-06-24 | 2018-08-21 | Indiana University Research And Technology Corporation | Amide-based insulin prodrugs |
| CN103179978A (zh) | 2010-08-30 | 2013-06-26 | 赛诺菲-安万特德国有限公司 | Ave0010用于制造供治疗2型糖尿病用的药物的用途 |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
| UA113626C2 (xx) * | 2011-06-02 | 2017-02-27 | Композиція для лікування діабету, що містить кон'югат інсуліну тривалої дії та кон'югат інсулінотропного пептиду тривалої дії | |
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
| CN104114183A (zh) | 2011-12-20 | 2014-10-22 | 印第安纳大学研究及科技有限公司 | 用于治疗糖尿病的基于ctp的胰岛素类似物 |
| CN108383902A (zh) | 2012-09-26 | 2018-08-10 | 印第安纳大学研究及科技有限公司 | 胰岛素类似物二聚体 |
| JP6538645B2 (ja) | 2013-03-14 | 2019-07-03 | 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 | インスリン‐インクレチン複合物 |
| EP3197912B1 (en) | 2014-09-24 | 2023-01-04 | Indiana University Research & Technology Corporation | Lipidated amide-based insulin prodrugs |
| CN108271356A (zh) | 2014-09-24 | 2018-07-10 | 印第安纳大学研究及科技有限公司 | 肠降血糖素-胰岛素缀合物 |
| CN107206058A (zh) | 2014-12-12 | 2017-09-26 | 赛诺菲-安万特德国有限公司 | 甘精胰岛素/利西拉来固定比率配制剂 |
| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患治療 |
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患之治療 |
| CN111925420B (zh) * | 2019-12-11 | 2022-04-01 | 山东大学 | 一种多肽作为嗅觉受体Olfr109激动剂配体的应用 |
| USD1043348S1 (en) * | 2021-09-24 | 2024-09-24 | H.J. Heinz Company Brands Llc | Bottle |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5008241A (en) * | 1985-03-12 | 1991-04-16 | Novo Nordisk A/S | Novel insulin peptides |
| PH25772A (en) * | 1985-08-30 | 1991-10-18 | Novo Industri As | Insulin analogues, process for their preparation |
| US5559094A (en) * | 1994-08-02 | 1996-09-24 | Eli Lilly And Company | AspB1 insulin analogs |
| US5594100A (en) * | 1995-02-22 | 1997-01-14 | Regents Of The University Of Colorado | Epitope for prevention of type I diabetes |
| EP0835129B1 (en) * | 1995-06-30 | 2003-10-29 | Novo Nordisk A/S | Prevention of a disease having the characteristics of diabetes |
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1999
- 1999-02-23 CN CNB998042765A patent/CN1241942C/zh not_active Expired - Fee Related
- 1999-02-23 TR TR2000/03048T patent/TR200003048T2/xx unknown
- 1999-02-23 CA CA002321929A patent/CA2321929A1/en not_active Abandoned
- 1999-02-23 NZ NZ506447A patent/NZ506447A/xx unknown
- 1999-02-23 KR KR1020007009330A patent/KR20010041238A/ko not_active Abandoned
- 1999-02-23 SK SK1241-2000A patent/SK12412000A3/sk unknown
- 1999-02-23 US US09/255,668 patent/US6197926B1/en not_active Expired - Fee Related
- 1999-02-23 EP EP99908385A patent/EP1056776A1/en not_active Withdrawn
- 1999-02-23 AU AU27831/99A patent/AU741037B2/en not_active Ceased
- 1999-02-23 JP JP2000532434A patent/JP2002504491A/ja active Pending
- 1999-02-23 PL PL99342517A patent/PL342517A1/xx not_active Application Discontinuation
- 1999-02-23 EA EA200000872A patent/EA003944B1/ru not_active IP Right Cessation
- 1999-02-23 AP APAP/P/2000/001888A patent/AP2000001888A0/en unknown
- 1999-02-23 ID IDW20001917A patent/ID26788A/id unknown
- 1999-02-23 IL IL13790499A patent/IL137904A0/xx unknown
- 1999-02-23 WO PCT/US1999/003915 patent/WO1999042482A1/en not_active Ceased
- 1999-02-23 HU HU0100928A patent/HUP0100928A3/hu unknown
- 1999-02-23 BR BR9908178-4A patent/BR9908178A/pt not_active IP Right Cessation
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2000
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- 2000-08-22 NO NO20004198A patent/NO20004198L/no unknown
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|---|---|
| CN1294597A (zh) | 2001-05-09 |
| TR200003048T2 (tr) | 2000-12-21 |
| EP1056776A1 (en) | 2000-12-06 |
| HUP0100928A3 (en) | 2001-11-28 |
| IL137904A0 (en) | 2001-10-31 |
| JP2002504491A (ja) | 2002-02-12 |
| SK12412000A3 (sk) | 2002-05-09 |
| ID26788A (id) | 2001-02-08 |
| NO20004198D0 (no) | 2000-08-22 |
| CN1241942C (zh) | 2006-02-15 |
| KR20010041238A (ko) | 2001-05-15 |
| NO20004198L (no) | 2000-10-20 |
| US6197926B1 (en) | 2001-03-06 |
| PL342517A1 (en) | 2001-06-18 |
| CA2321929A1 (en) | 1999-08-26 |
| EA200000872A1 (ru) | 2001-02-26 |
| AU2783199A (en) | 1999-09-06 |
| EA003944B1 (ru) | 2003-10-30 |
| NZ506447A (en) | 2002-11-26 |
| BR9908178A (pt) | 2002-01-15 |
| WO1999042482A1 (en) | 1999-08-26 |
| AU741037B2 (en) | 2001-11-22 |
| AP2000001888A0 (en) | 2000-09-30 |
| HUP0100928A2 (hu) | 2001-08-28 |
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