JP2012503025A - 精製されたポリペプチド組成物を調製するための方法 - Google Patents
精製されたポリペプチド組成物を調製するための方法 Download PDFInfo
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- JP2012503025A JP2012503025A JP2011528083A JP2011528083A JP2012503025A JP 2012503025 A JP2012503025 A JP 2012503025A JP 2011528083 A JP2011528083 A JP 2011528083A JP 2011528083 A JP2011528083 A JP 2011528083A JP 2012503025 A JP2012503025 A JP 2012503025A
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- amino acid
- peptidomimetic macrocycle
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- peptidomimetic
- macrocycle
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2015509940A (ja) * | 2012-02-15 | 2015-04-02 | エイルロン セラピューティクス，インコーポレイテッド | ペプチドミメティック大環状化合物 |
| JP2016537413A (ja) * | 2013-10-28 | 2016-12-01 | ノーレックス インコーポレイテッド | Ｎｍｄａ受容体モジュレーター及びプロドラッグ、塩、並びにこれらの使用 |
| JP2017513826A (ja) * | 2014-04-02 | 2017-06-01 | ユニバーシティー オブ ロチェスター | アルファヘリックスを模倣した大環状ペプチドミメティック |
| US10023613B2 (en) | 2015-09-10 | 2018-07-17 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles as modulators of MCL-1 |
| US10202431B2 (en) | 2007-01-31 | 2019-02-12 | Aileron Therapeutics, Inc. | Stabilized P53 peptides and uses thereof |
| US10227380B2 (en) | 2012-02-15 | 2019-03-12 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| US10246491B2 (en) | 2013-03-06 | 2019-04-02 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and use thereof in regulating HIF1alpha |
| US10253067B2 (en) | 2015-03-20 | 2019-04-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| US10301351B2 (en) | 2007-03-28 | 2019-05-28 | President And Fellows Of Harvard College | Stitched polypeptides |
| US10308699B2 (en) | 2011-10-18 | 2019-06-04 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US10471120B2 (en) | 2014-09-24 | 2019-11-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| US10703780B2 (en) | 2010-08-13 | 2020-07-07 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US10905739B2 (en) | 2014-09-24 | 2021-02-02 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and formulations thereof |
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| EP2094721B1 (en) | 2006-12-14 | 2018-02-14 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| US7981998B2 (en) * | 2006-12-14 | 2011-07-19 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| TWI433674B (zh) | 2006-12-28 | 2014-04-11 | Infinity Discovery Inc | 環杷明（ｃｙｃｌｏｐａｍｉｎｅ）類似物類 |
| US7981999B2 (en) | 2007-02-23 | 2011-07-19 | Aileron Therapeutics, Inc. | Triazole macrocycle systems |
| ES2610130T3 (es) | 2007-12-27 | 2017-04-26 | Infinity Pharmaceuticals, Inc. | Métodos para reducción estereoselectiva |
| BRPI0918948A2 (pt) | 2008-09-22 | 2015-12-15 | Aileron Therapeutics Inc | macrociclos peptidomiméticos |
| EP3492492A1 (en) * | 2008-09-22 | 2019-06-05 | Aileron Therapeutics, Inc. | Methods for preparing purified polypeptide compositions |
| CA2743177A1 (en) | 2008-11-24 | 2010-05-27 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with improved properties |
| CA2744088A1 (en) | 2009-01-14 | 2010-07-22 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| EP2462115B1 (en) | 2009-08-05 | 2016-01-06 | Infinity Pharmaceuticals, Inc. | Enzymatic transamination of cyclopamine analogs |
| CA2774973A1 (en) | 2009-09-22 | 2011-03-31 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US9394313B2 (en) | 2010-09-14 | 2016-07-19 | Infinity Pharmaceuticals, Inc. | Transfer hydrogenation of cyclopamine analogs |
| WO2012083078A2 (en) | 2010-12-15 | 2012-06-21 | The Research Foundation Of State University Of New York | Croos-linked peptides and proteins, methods of making same, and uses thereof |
| EP2714701B1 (en) * | 2011-06-03 | 2016-07-13 | Hetero Research Foundation | Process for fosaprepitant |
| SG11201503052RA (en) | 2012-11-01 | 2015-05-28 | Aileron Therapeutics Inc | Disubstituted amino acids and methods of preparation and use thereof |
| US10087221B2 (en) | 2013-03-21 | 2018-10-02 | Sanofi-Aventis Deutschland Gmbh | Synthesis of hydantoin containing peptide products |
| AU2014234314B2 (en) | 2013-03-21 | 2018-02-15 | Sanofi-Aventis Deutschland Gmbh | Synthesis of cyclic imide containing peptide products |
| US9890239B2 (en) | 2013-09-04 | 2018-02-13 | California Institute Of Technology | Functionalized linear and cyclic polyolefins |
| CA2924109A1 (en) | 2013-09-13 | 2015-03-19 | The California Institute For Biomedical Research | Modified therapeutic agents and compositions thereof |
| JP6572497B2 (ja) | 2013-12-18 | 2019-09-11 | ザ・スクリップス・リサーチ・インスティテュート | 修飾された治療剤、ステープル留めされたペプチド脂質複合体、及びそれらの組成物 |
| CA2988289C (en) | 2015-06-04 | 2023-12-05 | PellePharm, Inc. | Topical formulations for delivery of hedgehog inhibitor compounds and use thereof |
| WO2017004548A1 (en) | 2015-07-01 | 2017-01-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CN109414470A (zh) * | 2016-03-21 | 2019-03-01 | 艾瑞朗医疗公司 | 用于拟肽大环化合物的伴随诊断工具 |
| EP3706771A4 (en) | 2017-11-09 | 2022-05-18 | WNTRX Pharmaceuticals Inc. | BCL9 PEPTIDES AND VARIANTS THEREOF |
| US11091522B2 (en) | 2018-07-23 | 2021-08-17 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| CA3221611A1 (en) | 2021-06-09 | 2022-12-15 | Weijun Shen | Long-acting dual gip/glp-1 peptide conjugates and methods of use |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006503891A (ja) * | 2002-10-24 | 2006-02-02 | ダウ グローバル テクノロジーズ インコーポレイティド | オレフィン複分解生成混合物の安定化 |
| JP2008501623A (ja) * | 2003-11-05 | 2008-01-24 | ダナ−ファーバー キャンサー インスティテュート インク． | 安定化させたαヘリックスペプチドおよびその使用法 |
Family Cites Families (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4730006A (en) | 1986-01-27 | 1988-03-08 | Merrell Dow Pharmaceuticals Inc. | Derivatives of 2,6-diamino-3-haloheptanedioic acid |
| US5094951A (en) * | 1988-06-21 | 1992-03-10 | Chiron Corporation | Production of glucose oxidase in recombinant systems |
| US5120859A (en) * | 1989-09-22 | 1992-06-09 | Genentech, Inc. | Chimeric amino acid analogues |
| US5712418A (en) | 1989-10-23 | 1998-01-27 | Research Corporation Technologies, Inc. | Synthesis and use of amino acid fluorides as peptide coupling reagents |
| DE69118826T2 (de) * | 1990-11-27 | 1996-11-14 | Fuji Photo Film Co Ltd | Propenamidderivate, deren Polymere, Copolymere und deren Verwendung |
| US5364851A (en) | 1991-06-14 | 1994-11-15 | International Synthecon, Llc | Conformationally restricted biologically active peptides, methods for their production and uses thereof |
| US5312940A (en) | 1992-04-03 | 1994-05-17 | California Institute Of Technology | Ruthenium and osmium metal carbene complexes for olefin metathesis polymerization |
| EP0773948A4 (en) | 1992-04-03 | 1998-09-02 | California Inst Of Techn | HIGHLY ACTIVE RUTHENIUM OR OSMIUM METAL CARBEN COMPLEXES FOR OLEFIN METHETHESE REACTIONS AND THEIR SYNTHESIS |
| US5411860A (en) | 1992-04-07 | 1995-05-02 | The Johns Hopkins University | Amplification of human MDM2 gene in human tumors |
| WO1994011398A1 (en) * | 1992-11-18 | 1994-05-26 | The Du Pont Merck Pharmaceutical Company | CYCLIC COMPOUNDS LINKED BY A HETEROCYCLIC RING USEFUL AS INHIBITORS OF PLATELET GLYCOPROTEIN IIb/IIIa |
| US5446128A (en) | 1993-06-18 | 1995-08-29 | The Board Of Trustees Of The University Of Illinois | Alpha-helix mimetics and methods relating thereto |
| US5622852A (en) | 1994-10-31 | 1997-04-22 | Washington University | Bcl-x/Bcl-2 associated cell death regulator |
| US5824483A (en) | 1994-05-18 | 1998-10-20 | Pence Inc. | Conformationally-restricted combinatiorial library composition and method |
| US6407059B1 (en) | 1994-06-08 | 2002-06-18 | Peptor Limited | Conformationally constrained backbone cyclized peptide analogs |
| IL109943A (en) | 1994-06-08 | 2006-08-01 | Develogen Israel Ltd | Conformationally constrained backbone cyclized peptide analogs |
| US7553929B2 (en) | 1994-06-13 | 2009-06-30 | Vanderbilt University | Cell permeable peptides for inhibition of inflammatory reactions and methods of use |
| US5807746A (en) * | 1994-06-13 | 1998-09-15 | Vanderbilt University | Method for importing biologically active molecules into cells |
| US5770377A (en) | 1994-07-20 | 1998-06-23 | University Of Dundee | Interruption of binding of MDM2 and P53 protein and therapeutic application thereof |
| US5672584A (en) | 1995-04-25 | 1997-09-30 | The University Of Kansas | Cyclic prodrugs of peptides and peptide nucleic acids having improved metabolic stability and cell membrane permeability |
| US6184344B1 (en) * | 1995-05-04 | 2001-02-06 | The Scripps Research Institute | Synthesis of proteins by native chemical ligation |
| EP0832096B1 (en) | 1995-05-04 | 2001-07-18 | The Scripps Research Institute | Synthesis of proteins by native chemical ligation |
| US5730723A (en) | 1995-10-10 | 1998-03-24 | Visionary Medical Products Corporation, Inc. | Gas pressured needle-less injection device and method |
| US6051554A (en) | 1995-06-07 | 2000-04-18 | Peptor Limited | Conformationally constrained backbone cyclized somatostatin analogs |
| US5811515A (en) | 1995-06-12 | 1998-09-22 | California Institute Of Technology | Synthesis of conformationally restricted amino acids, peptides, and peptidomimetics by catalytic ring closing metathesis |
| US5831108A (en) | 1995-08-03 | 1998-11-03 | California Institute Of Technology | High metathesis activity ruthenium and osmium metal carbene complexes |
| EP0880357A4 (en) * | 1996-01-17 | 1999-05-12 | California Inst Of Techn | SYNTHESIS OF CONFORMATORICALLY RESTRICTED AMINO ACIDS, PEPTIDES AND PEPTIDOMIMETIC COMPOUNDS BY CATALYTIC RINGCLOSE METATHESIS |
| GB9607549D0 (en) | 1996-04-11 | 1996-06-12 | Weston Medical Ltd | Spring-powered dispensing device |
| US5663316A (en) | 1996-06-18 | 1997-09-02 | Clontech Laboratories, Inc. | BBC6 gene for regulation of cell death |
| US7083983B2 (en) | 1996-07-05 | 2006-08-01 | Cancer Research Campaign Technology Limited | Inhibitors of the interaction between P53 and MDM2 |
| US5955593A (en) | 1996-09-09 | 1999-09-21 | Washington University | BH3 interacting domain death agonist |
| US20020064546A1 (en) | 1996-09-13 | 2002-05-30 | J. Milton Harris | Degradable poly(ethylene glycol) hydrogels with controlled half-life and precursors therefor |
| US5965703A (en) | 1996-09-20 | 1999-10-12 | Idun Pharmaceuticals | Human bad polypeptides, encoding nucleic acids and methods of use |
| US5856445A (en) | 1996-10-18 | 1999-01-05 | Washington University | Serine substituted mutants of BCL-XL /BCL-2 associated cell death regulator |
| US6271198B1 (en) | 1996-11-06 | 2001-08-07 | Genentech, Inc. | Constrained helical peptides and methods of making same |
| JP2001504831A (ja) * | 1996-11-21 | 2001-04-10 | プロメガ・コーポレーション | アルキルペプチドアミドおよび適用 |
| AU8626698A (en) | 1997-06-25 | 1999-01-19 | Ciba Specialty Chemicals Holding Inc. | Ruthenium and osmium carbene catalysts |
| CA2304124A1 (en) | 1997-09-17 | 1999-03-25 | The Walter And Eliza Hall Institute Of Medical Research | Bci-2-like protein bim and methods of use thereof |
| US6165732A (en) | 1997-10-14 | 2000-12-26 | Washington University | Method for identifying apoptosis modulating compounds |
| US6875594B2 (en) * | 1997-11-13 | 2005-04-05 | The Rockefeller University | Methods of ligating expressed proteins |
| EP1053019B1 (en) | 1998-01-07 | 2003-12-03 | Debio Recherche Pharmaceutique S.A. | Degradable heterobifunctional poly(ethylene glycol) acrylates and gels and conjugates derived therefrom |
| IT1298087B1 (it) | 1998-01-08 | 1999-12-20 | Fiderm S R L | Dispositivo per il controllo della profondita' di penetrazione di un ago, in particolare applicabile ad una siringa per iniezioni |
| US6030997A (en) | 1998-01-21 | 2000-02-29 | Eilat; Eran | Acid labile prodrugs |
| AU767185B2 (en) * | 1998-03-23 | 2003-11-06 | President And Fellows Of Harvard College | Synthesis of compounds and libraries of compounds |
| DE19815275B4 (de) | 1998-04-06 | 2009-06-25 | Evonik Degussa Gmbh | Alkylidenkomplexe des Rutheniums mit N-heterozyklischen Carbenliganden und deren Verwendung als hochaktive, selektive Katalysatoren für die Olefin-Metathese |
| CA2325572A1 (en) * | 1998-04-15 | 1999-10-21 | Aventis Pharmaceuticals Products Inc. | Process for the preparation of resin-bound cyclic peptides |
| US6326354B1 (en) | 1998-08-19 | 2001-12-04 | Washington University | Modulation of apoptosis with bid |
| US7173005B2 (en) * | 1998-09-02 | 2007-02-06 | Antyra Inc. | Insulin and IGF-1 receptor agonists and antagonists |
| IL145406A0 (en) | 1999-03-29 | 2002-06-30 | Procter & Gamble | Melanocortin receptor ligands |
| US6713280B1 (en) | 1999-04-07 | 2004-03-30 | Thomas Jefferson University | Enhancement of peptide cellular uptake |
| US7192713B1 (en) | 1999-05-18 | 2007-03-20 | President And Fellows Of Harvard College | Stabilized compounds having secondary structure motifs |
| BR0010389B1 (pt) | 1999-05-24 | 2011-05-17 | catalisadores de metátese de carbeno metálico a base de imidazolidina. | |
| US6348558B1 (en) * | 1999-12-10 | 2002-02-19 | Shearwater Corporation | Hydrolytically degradable polymers and hydrogels made therefrom |
| US6495674B1 (en) * | 2000-02-25 | 2002-12-17 | The Salk Institute For Biological Studies | Evectins and their use |
| US7049290B2 (en) * | 2000-07-28 | 2006-05-23 | Universität Zürich | Essential downstream component of the wingless signaling pathway and therapeutic and diagnostic applications based thereon |
| WO2002014376A2 (en) | 2000-08-10 | 2002-02-21 | Trustees Of Boston College | Recyclable metathesis catalysts |
| WO2002013833A2 (en) | 2000-08-16 | 2002-02-21 | Georgetown University Medical Center | SMALL MOLECULE INHIBITORS TARGETED AT Bcl-2 |
| EP1343884A2 (en) | 2000-12-19 | 2003-09-17 | The Johns Hopkins University | Jfy1 protein induces rapid apoptosis |
| WO2003057158A2 (en) | 2001-12-31 | 2003-07-17 | Dana-Farber Cancer Institute, Inc. | Method of treating apoptosis and compositions thereof |
| JP4381826B2 (ja) * | 2002-04-22 | 2009-12-09 | ユニヴァーシティ オヴ フロリダ | 機能化されたナノ粒子及びその使用方法 |
| SE0201863D0 (en) | 2002-06-18 | 2002-06-18 | Cepep Ab | Cell penetrating peptides |
| JP2006516383A (ja) | 2002-09-09 | 2006-07-06 | デイナ−ファーバー キャンサー インスティチュート，インコーポレイテッド | Ｂｈ３ペプチドおよびその使用方法 |
| CA2503117C (en) | 2002-11-08 | 2010-12-21 | F. Hoffmann-La Roche Ag | Substituted 4-alkoxyoxazol derivatives as ppar agonists |
| US7166575B2 (en) | 2002-12-17 | 2007-01-23 | Nastech Pharmaceutical Company Inc. | Compositions and methods for enhanced mucosal delivery of peptide YY and methods for treating and preventing obesity |
| US20070032417A1 (en) | 2002-12-24 | 2007-02-08 | Walter And Eliza Hall Institute Of Medical Research | Peptides and therapeutic uses thereof |
| JP2007537989A (ja) | 2003-10-16 | 2007-12-27 | アプラーゲン ゲゼルシャフト ミット ベシュレンクテル ハフツング | 安定化ペプチド |
| GB0404731D0 (en) | 2004-03-03 | 2004-04-07 | Indp Administrative Inst Nims | Method and products for the selective degradation of proteins |
| US8193310B2 (en) | 2004-03-19 | 2012-06-05 | The University Of Queensland | Alpha helical mimics, their uses and methods for their production |
| WO2005118620A2 (en) * | 2004-05-27 | 2005-12-15 | New York University | Methods for preparing internally constraied peptides and peptidomimetics |
| WO2005118634A2 (en) | 2004-06-04 | 2005-12-15 | The Brigham And Women's Hospital, Inc. | Helical peptidomimetics with enhanced activity against beta-amyloid production |
| WO2006103666A2 (en) | 2005-03-28 | 2006-10-05 | Yeda Research And Development Co. Ltd. | Isolated bid polypeptides, polynucleotides encoding same and antibodies directed thereagainst and methods of using same for inducing cell cycle arrest or apoptosis |
| US7632772B2 (en) | 2005-07-04 | 2009-12-15 | Zheng-Yun James Zhan | Recyclable ruthenium catalysts for metathesis reactions |
| CN1907992B (zh) | 2005-07-04 | 2012-03-28 | 赞南科技(上海)有限公司 | 钌络合物配体、钌络合物、固载钌络合物催化剂及其制备方法和用途 |
| US7745573B2 (en) * | 2006-02-17 | 2010-06-29 | Polychip Pharmaceuticals Pty Ltd. | Conotoxin analogues and methods for synthesis of intramolecular dicarba bridge-containing peptides |
| US7538190B2 (en) | 2006-02-17 | 2009-05-26 | Polychip Pharmaceuticals Pty Ltd | Methods for the synthesis of two or more dicarba bridges in organic compounds |
| GB0611405D0 (en) | 2006-06-09 | 2006-07-19 | Univ Belfast | FKBP-L: A novel inhibitor of angiogenesis |
| EP2489360A1 (en) | 2006-11-15 | 2012-08-22 | Dana-Farber Cancer Institute, Inc. | Stabilized MAML peptides and uses thereof |
| US7981998B2 (en) | 2006-12-14 | 2011-07-19 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| EP2094721B1 (en) | 2006-12-14 | 2018-02-14 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| EP2952522B1 (en) * | 2007-01-31 | 2019-10-30 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| US7981999B2 (en) * | 2007-02-23 | 2011-07-19 | Aileron Therapeutics, Inc. | Triazole macrocycle systems |
| ES2430067T3 (es) | 2007-03-28 | 2013-11-18 | President And Fellows Of Harvard College | Polipéptidos cosidos |
| CA2700925C (en) | 2007-09-26 | 2016-08-23 | Dana Farber Cancer Institute | Methods and compositions for modulating bcl-2 family polypeptides |
| CN104474529A (zh) * | 2008-02-08 | 2015-04-01 | 爱勒让治疗公司 | 治疗性的拟肽大环化合物 |
| US20110144303A1 (en) * | 2008-04-08 | 2011-06-16 | Aileron Therapeutics, Inc. | Biologically Active Peptidomimetic Macrocycles |
| EP2310407A4 (en) * | 2008-04-08 | 2011-09-14 | Aileron Therapeutics Inc | BIOLOGICALLY ACTIVE PEPTIDOMIMETIC MACROCYCLES |
| EP3492492A1 (en) | 2008-09-22 | 2019-06-05 | Aileron Therapeutics, Inc. | Methods for preparing purified polypeptide compositions |
| WO2010034029A1 (en) | 2008-09-22 | 2010-03-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| BRPI0918948A2 (pt) | 2008-09-22 | 2015-12-15 | Aileron Therapeutics Inc | macrociclos peptidomiméticos |
| CA2743177A1 (en) | 2008-11-24 | 2010-05-27 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles with improved properties |
| CN102655875A (zh) * | 2009-10-14 | 2012-09-05 | 爱勒让治疗公司 | 改善的拟肽大环化合物 |
| MX362492B (es) * | 2012-02-15 | 2019-01-21 | Aileron Therapeutics Inc | Macrociclos peptidomiméticos. |
| EP3347372A4 (en) * | 2015-09-10 | 2019-09-04 | Aileron Therapeutics, Inc. | PEPTIDOMIMETIC MACROCYCLES AS MODULATORS OF MCL-1 |
-
2009
- 2009-09-22 EP EP18195669.9A patent/EP3492492A1/en not_active Withdrawn
- 2009-09-22 US US12/564,909 patent/US9206223B2/en active Active
- 2009-09-22 EP EP09736334.5A patent/EP2342221B1/en active Active
- 2009-09-22 WO PCT/US2009/057931 patent/WO2010034032A2/en not_active Ceased
- 2009-09-22 AU AU2009294875A patent/AU2009294875C1/en active Active
- 2009-09-22 JP JP2011528083A patent/JP2012503025A/ja not_active Withdrawn
- 2009-09-22 CN CN201510159021.2A patent/CN104961795A/zh active Pending
- 2009-09-22 CA CA2737921A patent/CA2737921C/en active Active
- 2009-09-22 BR BRPI0918838A patent/BRPI0918838A2/pt not_active Application Discontinuation
- 2009-09-22 CN CN2009801425171A patent/CN102203126A/zh active Pending
-
2011
- 2011-03-21 IL IL211837A patent/IL211837A/en active IP Right Grant
-
2012
- 2012-01-13 US US13/350,644 patent/US9394336B2/en not_active Expired - Fee Related
-
2015
- 2015-02-27 JP JP2015037711A patent/JP6196640B2/ja active Active
- 2015-10-23 US US14/921,573 patent/US20160115204A1/en not_active Abandoned
-
2017
- 2017-06-16 JP JP2017118507A patent/JP2017155063A/ja active Pending
- 2017-09-14 IL IL254498A patent/IL254498B/en active IP Right Grant
-
2019
- 2019-08-26 JP JP2019153604A patent/JP2019214614A/ja active Pending
- 2019-09-24 JP JP2019172908A patent/JP2020015748A/ja active Pending
-
2021
- 2021-07-23 US US17/383,675 patent/US20220017569A1/en not_active Abandoned
-
2023
- 2023-06-02 US US18/328,029 patent/US20240124518A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006503891A (ja) * | 2002-10-24 | 2006-02-02 | ダウ グローバル テクノロジーズ インコーポレイティド | オレフィン複分解生成混合物の安定化 |
| JP2008501623A (ja) * | 2003-11-05 | 2008-01-24 | ダナ−ファーバー キャンサー インスティテュート インク． | 安定化させたαヘリックスペプチドおよびその使用法 |
Non-Patent Citations (4)
| Title |
|---|
| EUROPEAN MEDICINES AGENCY, GUIDELINE ON THE SPECIFICATION LIMITS FOR RESIDUES OF METAL CATALYSTS OR METAL REGENTS, JPN6014045682, February 2008 (2008-02-01), pages 1 - 34, ISSN: 0002928823 * |
| ORGANIC LETTERS. 2003, VOL.5, NO.4, P.531-533, JPN6013057390, ISSN: 0002690496 * |
| ORGANIC LETTERS. 2007, VOL.9, NO.10, P.1955-1957, JPN6013057393, ISSN: 0002690497 * |
| 泉屋信夫 他, ペプチド合成の基礎と実験, JPN6014045679, 20 January 1985 (1985-01-20), pages 171, ISSN: 0002928822 * |
Cited By (16)
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| US10023613B2 (en) | 2015-09-10 | 2018-07-17 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles as modulators of MCL-1 |
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| EP2342221A2 (en) | 2011-07-13 |
| US20160115204A1 (en) | 2016-04-28 |
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