JP7360794B2 - ペプチド類似体 - Google Patents
ペプチド類似体 Download PDFInfo
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- JP7360794B2 JP7360794B2 JP2018553861A JP2018553861A JP7360794B2 JP 7360794 B2 JP7360794 B2 JP 7360794B2 JP 2018553861 A JP2018553861 A JP 2018553861A JP 2018553861 A JP2018553861 A JP 2018553861A JP 7360794 B2 JP7360794 B2 JP 7360794B2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/57527—Calcitonin gene related peptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662274638P | 2016-01-04 | 2016-01-04 | |
| US62/274,638 | 2016-01-04 | ||
| PCT/US2017/012171 WO2017120220A1 (en) | 2016-01-04 | 2017-01-04 | Peptide analogs |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019504119A JP2019504119A (ja) | 2019-02-14 |
| JP2019504119A5 JP2019504119A5 (enExample) | 2020-01-09 |
| JP7360794B2 true JP7360794B2 (ja) | 2023-10-13 |
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| JP2018553861A Active JP7360794B2 (ja) | 2016-01-04 | 2017-01-04 | ペプチド類似体 |
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| Country | Link |
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| US (2) | US11034745B2 (enExample) |
| EP (1) | EP3400237A4 (enExample) |
| JP (1) | JP7360794B2 (enExample) |
| CN (2) | CN109311959A (enExample) |
| TW (1) | TW201734035A (enExample) |
| WO (1) | WO2017120220A1 (enExample) |
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| EP3707157A4 (en) * | 2017-11-06 | 2021-08-18 | Auckland Uniservices Limited | PEPTIDIC CONJUGATES AS ANAGONISTS OF THE CGRP RECEIVER, THEIR PREPARATION METHODS AND THEIR USES |
| US20210332083A1 (en) * | 2018-12-12 | 2021-10-28 | The Regents Of The University Of California | Netrin-1 Compounds and Compositions Thereof for Treating Pulmonary Hypertension |
| CN114686427B (zh) * | 2022-05-23 | 2022-07-29 | 中国人民解放军总医院第一医学中心 | 一种脾脏调节型b淋巴细胞及其制备方法与应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009504681A (ja) | 2005-08-11 | 2009-02-05 | アミリン・ファーマシューティカルズ,インコーポレイテッド | 選択可能な特性を有するハイブリッドポリペプチド |
| JP2014511862A (ja) | 2011-04-07 | 2014-05-19 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | 持続性ペプチド類似体 |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5869602A (en) | 1995-03-17 | 1999-02-09 | Novo Nordisk A/S | Peptide derivatives |
| WO1996029432A1 (en) | 1995-03-22 | 1996-09-26 | Trustees Of Boston University | Methods for the detection of paracoccidioides |
| US6440421B1 (en) | 1996-04-18 | 2002-08-27 | Auchkland Uniservices Limited | Treatment of bone disorders with adrenomedullin or adrenomedullin agonists |
| IL118003A0 (en) | 1996-04-23 | 1996-08-04 | Yeda Res & Dev | Novel vip fragments and pharmaceutical compositions comprising them |
| US6268474B1 (en) | 1998-04-30 | 2001-07-31 | Creighton University | Peptide antagonists of CGRP-receptor superfamily and methods of use |
| US20090175821A1 (en) | 1999-05-17 | 2009-07-09 | Bridon Dominique P | Modified therapeutic peptides with extended half-lives in vivo |
| US6965013B2 (en) * | 2002-11-26 | 2005-11-15 | The Board Of Trustees Of The Leland Stanford Junior University | Intermedin and its uses |
| US20080026995A1 (en) | 2003-07-25 | 2008-01-31 | Ac Immune Sa | Therapeutic vaccine targeted against p-glycoprotein 170 for inhibiting multidrug resistance in the treatment of cancers |
| US8076288B2 (en) | 2004-02-11 | 2011-12-13 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides having glucose lowering activity |
| BRPI0507623A (pt) | 2004-02-11 | 2007-07-03 | Amylin Pharmaceuticals Inc | peptìdeos da famìlia da amilina e métodos para prepará-los e empregá-los |
| ZA200700359B (en) | 2004-07-21 | 2008-12-31 | Ambrx Inc | Biosynthetic polypeptides utilizing non-naturally encoded amino acids |
| US7638299B2 (en) | 2004-07-21 | 2009-12-29 | Ambrx, Inc. | Biosynthetic polypeptides utilizing non-naturally encoded amino acids |
| WO2006042242A2 (en) | 2004-10-08 | 2006-04-20 | Amylin Pharmaceuticals, Inc. | Amylin family polypeptide- 6 (afp- 6) analogs and methods of making and using them |
| TWI376234B (en) | 2005-02-01 | 2012-11-11 | Msd Oss Bv | Conjugates of a polypeptide and an oligosaccharide |
| BRPI0606992A2 (pt) | 2005-02-11 | 2009-07-28 | Amylin Pharmaceuticals Inc | análogo e polipeptìdeos hìbridos de gip com propriedades selecionáveis |
| US8168592B2 (en) | 2005-10-21 | 2012-05-01 | Amgen Inc. | CGRP peptide antagonists and conjugates |
| JP5412273B2 (ja) | 2006-03-21 | 2014-02-12 | アミリン・ファーマシューティカルズ,リミテッド・ライアビリティ・カンパニー | ペプチド−ぺプチダーゼ阻害剤及びその使用 |
| US8497240B2 (en) | 2006-08-17 | 2013-07-30 | Amylin Pharmaceuticals, Llc | DPP-IV resistant GIP hybrid polypeptides with selectable properties |
| EP2059529A2 (en) | 2006-08-22 | 2009-05-20 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Screening method for gpcr ligands |
| CN104193815A (zh) | 2006-09-08 | 2014-12-10 | Ambrx公司 | 经修饰的人类血浆多肽或Fc骨架和其用途 |
| US7956035B2 (en) | 2007-03-01 | 2011-06-07 | Csl Limited | Treatment of endothelial dysfunction in diabetic patients |
| US8372830B2 (en) | 2007-05-15 | 2013-02-12 | Otsuka Pharmaceutical Co., Ltd. | Methods for using vasopressin antagonists with anthracycline chemotherapy agents to reduce cardiotoxicity and/or improve survival |
| US7960336B2 (en) | 2007-08-03 | 2011-06-14 | Pharmain Corporation | Composition for long-acting peptide analogs |
| WO2011083153A2 (en) * | 2010-01-08 | 2011-07-14 | Profibrix Bv | Fibrinogen preparations enriched in fibrinogen with an extended alpha chain |
| JP5852660B2 (ja) * | 2010-10-12 | 2016-02-03 | アライアンス フォー サステイナブル エナジー リミテッド ライアビリティ カンパニー | 高効率なオプトエレクトロニクスのための大きなバンドギャップをもつiii−v族化合物 |
| CN108997490A (zh) * | 2012-01-26 | 2018-12-14 | 克里斯托弗·J·索尔斯 | 肽激素的降钙素cgrp家族的肽拮抗剂和它们的用途 |
| EP3416676B1 (en) * | 2016-02-09 | 2021-12-08 | Adepthera LLC | Dosing and use of long-acting clr/ramp agonists |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009504681A (ja) | 2005-08-11 | 2009-02-05 | アミリン・ファーマシューティカルズ,インコーポレイテッド | 選択可能な特性を有するハイブリッドポリペプチド |
| JP2014511862A (ja) | 2011-04-07 | 2014-05-19 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | 持続性ペプチド類似体 |
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| WO2017120220A1 (en) | 2017-07-13 |
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| TW201734035A (zh) | 2017-10-01 |
| CN109311959A (zh) | 2019-02-05 |
| EP3400237A1 (en) | 2018-11-14 |
| CN116063580A (zh) | 2023-05-05 |
| US20190010203A1 (en) | 2019-01-10 |
| JP2019504119A (ja) | 2019-02-14 |
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