CA2737921C - Methods for preparing purified alpha-helical peptidomimetic macrocycle compositions with low metal ppm levels - Google Patents
Methods for preparing purified alpha-helical peptidomimetic macrocycle compositions with low metal ppm levels Download PDFInfo
- Publication number
- CA2737921C CA2737921C CA2737921A CA2737921A CA2737921C CA 2737921 C CA2737921 C CA 2737921C CA 2737921 A CA2737921 A CA 2737921A CA 2737921 A CA2737921 A CA 2737921A CA 2737921 C CA2737921 C CA 2737921C
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- CA
- Canada
- Prior art keywords
- peptidomimetic macrocycle
- amino acid
- macrocycle
- pharmaceutically acceptable
- peptidomimetic
- Prior art date
- 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.)
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Classifications
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| US9909908P | 2008-09-22 | 2008-09-22 | |
| US61/099,099 | 2008-09-22 | ||
| PCT/US2009/057931 WO2010034032A2 (en) | 2008-09-22 | 2009-09-22 | Methods for preparing purified polypeptide compositions |
Publications (2)
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| CA2737921A1 CA2737921A1 (en) | 2010-03-25 |
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| CA2737921A Active CA2737921C (en) | 2008-09-22 | 2009-09-22 | Methods for preparing purified alpha-helical peptidomimetic macrocycle compositions with low metal ppm levels |
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| 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 |
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| 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 |
| 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 |
| PL2603600T3 (pl) | 2010-08-13 | 2019-06-28 | Aileron Therapeutics, Inc. | Makrocykle peptidomometyczne |
| 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 |
| CA2852468A1 (en) | 2011-10-18 | 2013-04-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocyles |
| MX362492B (es) * | 2012-02-15 | 2019-01-21 | Aileron Therapeutics Inc | Macrociclos peptidomiméticos. |
| HK1205454A1 (en) | 2012-02-15 | 2015-12-18 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| SG11201503052RA (en) | 2012-11-01 | 2015-05-28 | Aileron Therapeutics Inc | Disubstituted amino acids and methods of preparation and use thereof |
| WO2014138429A2 (en) | 2013-03-06 | 2014-09-12 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and use thereof in regulating hif1alpha |
| 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 |
| SG10201810496XA (en) * | 2013-10-28 | 2018-12-28 | Naurex Inc | Nmda receptor modulators and prodrugs, salts, and uses 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 |
| EP3126375B1 (en) * | 2014-04-02 | 2023-12-13 | University of Rochester | Macrocyclic peptidomimetics for alpha-helix mimicry |
| US10905739B2 (en) | 2014-09-24 | 2021-02-02 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and formulations thereof |
| SG11201702223UA (en) * | 2014-09-24 | 2017-04-27 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and uses thereof |
| AU2016235424A1 (en) | 2015-03-20 | 2017-10-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| 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 |
| EP3347372A4 (en) | 2015-09-10 | 2019-09-04 | Aileron Therapeutics, Inc. | PEPTIDOMIMETIC MACROCYCLES AS MODULATORS OF MCL-1 |
| 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 |
Family Cites Families (94)
| 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 |
| CN100590104C (zh) * | 2002-10-24 | 2010-02-17 | 陶氏环球技术公司 | 烯烃易位产物混合物的稳定 |
| 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 |
| PL2332968T3 (pl) * | 2003-11-05 | 2017-08-31 | Dana-Farber Cancer Institute, Inc. | Stabilizowane alfa-helikalne peptydy i ich zastosowania |
| 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 |
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| WO2010034032A3 (en) | 2010-05-20 |
| IL211837A0 (en) | 2011-06-30 |
| CN104961795A (zh) | 2015-10-07 |
| JP6196640B2 (ja) | 2017-09-13 |
| WO2010034032A2 (en) | 2010-03-25 |
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| JP2017155063A (ja) | 2017-09-07 |
| US9206223B2 (en) | 2015-12-08 |
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| EP2342221A2 (en) | 2011-07-13 |
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| AU2009294875B2 (en) | 2014-12-04 |
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