EA017417B1 - КОНСТРУКТ ОДНОДОМЕННОГО АНТИТЕЛА, КОТОРЫЙ СВЯЗЫВАЕТСЯ С ЧЕЛОВЕЧЕСКИМ TNF-α, И ЕГО ПРИМЕНЕНИЕ - Google Patents
КОНСТРУКТ ОДНОДОМЕННОГО АНТИТЕЛА, КОТОРЫЙ СВЯЗЫВАЕТСЯ С ЧЕЛОВЕЧЕСКИМ TNF-α, И ЕГО ПРИМЕНЕНИЕ Download PDFInfo
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2007019620A1 (en) * | 2005-08-15 | 2007-02-22 | Arana Therapeutics Limited | Engineered antibodies with new world primate framework regions |
| JP2009519983A (ja) * | 2005-12-20 | 2009-05-21 | アラーナ・テラピューティクス・リミテッド | 部分的な新世界ザル結合領域を有するキメラ抗体 |
| EA017417B1 (ru) | 2006-02-01 | 2012-12-28 | Сефалон Астралия Пти Лтд. | КОНСТРУКТ ОДНОДОМЕННОГО АНТИТЕЛА, КОТОРЫЙ СВЯЗЫВАЕТСЯ С ЧЕЛОВЕЧЕСКИМ TNF-α, И ЕГО ПРИМЕНЕНИЕ |
| US20080139790A1 (en) * | 2006-12-08 | 2008-06-12 | Jennings Philip A | Chimeric antibodies |
| WO2008092209A1 (en) * | 2007-02-01 | 2008-08-07 | Arana Therapeutics Limited | Protein construct with improved properties |
| EP2036980A1 (de) * | 2007-09-14 | 2009-03-18 | Gruber, Jens | Herabregulation der Genexpression mittels Nukleinsäure-beladener virusähnlicher Partikel |
| EP2238165B1 (en) | 2008-01-07 | 2017-07-05 | Government of the United States of America, as represented by the Secretary, Department of Health and Human Services | Anti-hiv domain antibodies and method of making and using same |
| US20110152173A1 (en) * | 2008-07-02 | 2011-06-23 | Emergent Product Development Seattle ,LLC | TNF-a ANTAGONIST MULTI-TARGET BINDING PROTEINS |
| US20110319597A1 (en) * | 2008-08-14 | 2011-12-29 | Caphalon Australia Pty. Ltd. | Variant domain antibodies |
| CN102224169A (zh) * | 2008-11-26 | 2011-10-19 | 葛兰素集团有限公司 | 多肽、抗体可变结构域和拮抗剂 |
| US8133979B2 (en) * | 2008-12-16 | 2012-03-13 | Hoffmann-La Roche Inc. | Antibodies against human angiopoietin 2 |
| EP2210902A1 (en) | 2009-01-14 | 2010-07-28 | TcL Pharma | Recombinant monovalent antibodies |
| IT1394281B1 (it) * | 2009-01-19 | 2012-06-06 | Zardi | Processo per la produzione di proteine di fusione polivalenti e polispecifiche utilizzando come struttura portante l'uteroglobina e prodotti cosi' ottenuti. |
| BRPI1012524A2 (pt) * | 2009-04-16 | 2020-09-29 | Abbott Biotherapeutics Corp | anticorpos anti-tnf-alfa e seus usos |
| CA2849409A1 (en) * | 2011-09-23 | 2013-03-28 | Technophage, Investigacao E Desenvolvimento Em Biotecnologia, Sa | Anti-tumor necrosis factor-alpha agents and uses thereof |
| CN104045715B (zh) * | 2013-03-15 | 2018-05-01 | 兰州大学 | 二聚体化融合蛋白的制备及应用 |
| ES3020458T3 (en) | 2015-08-07 | 2025-05-22 | Imaginab Inc | Antigen binding constructs to target molecules |
| US11266745B2 (en) | 2017-02-08 | 2022-03-08 | Imaginab, Inc. | Extension sequences for diabodies |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989001974A1 (en) * | 1987-09-04 | 1989-03-09 | Celltech Limited | Recombinant antibody |
| WO1989007142A1 (en) * | 1988-02-05 | 1989-08-10 | Morrison Sherie L | Domain-modified constant region antibodies |
| US5892019A (en) * | 1987-07-15 | 1999-04-06 | The United States Of America, As Represented By The Department Of Health And Human Services | Production of a single-gene-encoded immunoglobulin |
| WO2002077029A2 (en) * | 2000-11-07 | 2002-10-03 | City Of Hope | Cd19-specific redirected immune cells |
| US20030215427A1 (en) * | 2001-04-11 | 2003-11-20 | Michael Jensen | CE7-specific redirected immune cells |
| US20030232971A1 (en) * | 1989-08-07 | 2003-12-18 | Rathjen Deborah Ann | Tumour necrosis factor binding ligands |
Family Cites Families (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4002531A (en) * | 1976-01-22 | 1977-01-11 | Pierce Chemical Company | Modifying enzymes with polyethylene glycol and product produced thereby |
| US4816567A (en) * | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5225539A (en) * | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| DE3785186T2 (de) | 1986-09-02 | 1993-07-15 | Enzon Lab Inc | Bindungsmolekuele mit einzelpolypeptidkette. |
| EP1997891A1 (en) | 1988-09-02 | 2008-12-03 | Dyax Corporation | Generation and selection of recombinant varied binding proteins |
| US5223409A (en) * | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5349052A (en) * | 1988-10-20 | 1994-09-20 | Royal Free Hospital School Of Medicine | Process for fractionating polyethylene glycol (PEG)-protein adducts and an adduct for PEG and granulocyte-macrophage colony stimulating factor |
| WO1990005144A1 (en) | 1988-11-11 | 1990-05-17 | Medical Research Council | Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors |
| US5530101A (en) * | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5324844A (en) * | 1989-04-19 | 1994-06-28 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| JP3443119B2 (ja) * | 1989-08-07 | 2003-09-02 | ペプテック リミテッド | 腫瘍壊死因子結合リガンド |
| US5977307A (en) * | 1989-09-07 | 1999-11-02 | Alkermes, Inc. | Transferrin receptor specific ligand-neuropharmaceutical agent fusion proteins |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| AU665190B2 (en) | 1990-07-10 | 1995-12-21 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| GB9015198D0 (en) * | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| WO1992002551A1 (en) | 1990-08-02 | 1992-02-20 | B.R. Centre Limited | Methods for the production of proteins with a desired function |
| WO1992009690A2 (en) | 1990-12-03 | 1992-06-11 | Genentech, Inc. | Enrichment method for variant proteins with altered binding properties |
| US5994510A (en) | 1990-12-21 | 1999-11-30 | Celltech Therapeutics Limited | Recombinant antibodies specific for TNFα |
| GB9109645D0 (en) | 1991-05-03 | 1991-06-26 | Celltech Ltd | Recombinant antibodies |
| BR9206313A (pt) | 1991-07-25 | 1995-04-11 | Idec Pharma Corp | Anticorpos recombinantes para terapia humana. |
| ATE408012T1 (de) * | 1991-12-02 | 2008-09-15 | Medical Res Council | Herstellung von autoantikörpern auf phagenoberflächen ausgehend von antikörpersegmentbibliotheken |
| GB9317618D0 (en) | 1993-08-24 | 1993-10-06 | Royal Free Hosp School Med | Polymer modifications |
| CA2229043C (en) | 1995-08-18 | 2016-06-07 | Morphosys Gesellschaft Fur Proteinoptimierung Mbh | Protein/(poly)peptide libraries |
| US6090382A (en) * | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
| DE69721548T2 (de) | 1996-02-09 | 2004-04-01 | Abbott Laboratories(Bermuda)Ltd. | HUMANE ANTIKÖRPER WELCHE AN HUMANEN TNFalpha BINDEN |
| WO1997034631A1 (en) | 1996-03-18 | 1997-09-25 | Board Of Regents, The University Of Texas System | Immunoglobin-like domains with increased half lives |
| US6300065B1 (en) | 1996-05-31 | 2001-10-09 | Board Of Trustees Of The University Of Illinois | Yeast cell surface display of proteins and uses thereof |
| PT971946E (pt) | 1997-01-21 | 2006-11-30 | Gen Hospital Corp | Selecção de proteínas utilizando fusões arn-proteína |
| EP0921817B1 (en) | 1997-01-29 | 2001-03-28 | PolyMASC Pharmaceuticals plc | Pegylation process |
| US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| WO1998049286A2 (en) | 1997-05-01 | 1998-11-05 | Board Of Regents, The University Of Texas System | Directed evolution of enzymes and antibodies |
| IES80929B2 (en) | 1997-11-26 | 1999-06-30 | Donal Richard Mcgoey | Filter with form-retaining stabilizing means |
| CA2341029A1 (en) * | 1998-08-17 | 2000-02-24 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
| GB9900298D0 (en) | 1999-01-07 | 1999-02-24 | Medical Res Council | Optical sorting method |
| BR0008758A (pt) | 1999-01-15 | 2001-12-04 | Genentech Inc | Variantes de polipeptìdeos parentais com funçãoefetora alterada, polipeptìdeos, composição ácidonucleico isolado, vetor, célula hospedeira,método para produzir uma variante depolipeptìdeo, método para o tratamento de umadesordem em mamìferos e método para produziruma região fc variante |
| US7235643B2 (en) * | 2000-11-07 | 2007-06-26 | Morphotek, Inc. | Antibodies and methods for generating genetically altered antibodies with high affinity |
| GB0029407D0 (en) | 2000-12-01 | 2001-01-17 | Affitech As | Product |
| US7754208B2 (en) * | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
| US20060073141A1 (en) * | 2001-06-28 | 2006-04-06 | Domantis Limited | Compositions and methods for treating inflammatory disorders |
| US20050271663A1 (en) * | 2001-06-28 | 2005-12-08 | Domantis Limited | Compositions and methods for treating inflammatory disorders |
| WO2004006955A1 (en) * | 2001-07-12 | 2004-01-22 | Jefferson Foote | Super humanized antibodies |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| MXPA04009418A (es) | 2002-03-29 | 2005-06-08 | Schering Corp | Anticuerpos monoclonales humanos par interleucina-5, y metodos y composiciones que comprenden los mismos. |
| US20080241166A1 (en) * | 2002-06-28 | 2008-10-02 | Domantis Limited | Ligands that bind a receptor |
| US7696320B2 (en) * | 2004-08-24 | 2010-04-13 | Domantis Limited | Ligands that have binding specificity for VEGF and/or EGFR and methods of use therefor |
| DK1517921T3 (da) | 2002-06-28 | 2006-10-09 | Domantis Ltd | Immunglobulin-enkeltvariable antigen-bindende domæner og dobbeltspecifikke konstruktioner deraf |
| EP1558647B1 (en) * | 2002-11-08 | 2015-06-10 | Ablynx N.V. | Single domain antibodies directed against tumour necrosis factor-alpha and uses therefor |
| US20060034845A1 (en) | 2002-11-08 | 2006-02-16 | Karen Silence | Single domain antibodies directed against tumor necrosis factor alpha and uses therefor |
| CA2511910A1 (en) | 2002-12-27 | 2004-07-15 | Domantis Limited | Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand |
| GB0230201D0 (en) | 2002-12-27 | 2003-02-05 | Domantis Ltd | Retargeting |
| GB0230203D0 (en) | 2002-12-27 | 2003-02-05 | Domantis Ltd | Fc fusion |
| JP2007533595A (ja) | 2003-03-26 | 2007-11-22 | アポゲニクス ゲゼルシャフト ミット ベシュレンクテル ハフツング | ウィルス感染の治療 |
| KR20060034650A (ko) | 2003-06-27 | 2006-04-24 | 바이오렌 인코포레이티드 | 룩-스루 돌연변이 |
| DK1639011T3 (da) | 2003-06-30 | 2009-02-16 | Domantis Ltd | Pegylerede enkelt-domæne antistoffer (dAb) |
| GB0316294D0 (en) * | 2003-07-11 | 2003-08-13 | Polytherics Ltd | Conjugated biological molecules and their preparation |
| RS53476B (sr) * | 2003-07-18 | 2014-12-31 | Amgen Fremont Inc. | Sredstva za specifično vezivanje faktora rasta hepatocita |
| CA2543631A1 (en) | 2003-11-07 | 2005-05-26 | Amgen Inc. | Monkey immunoglobulin sequences |
| WO2005052002A2 (en) | 2003-11-20 | 2005-06-09 | Massachusetts Institute Of Technology | Single-domain antibodies and uses thereof |
| WO2005063816A2 (en) | 2003-12-19 | 2005-07-14 | Genentech, Inc. | Monovalent antibody fragments useful as therapeutics |
| US7381794B2 (en) | 2004-03-08 | 2008-06-03 | Zymogenetics, Inc. | Dimeric fusion proteins and materials and methods for producing them |
| US6979473B2 (en) | 2004-03-15 | 2005-12-27 | Boston Scientific Scimed, Inc. | Method for fine bore orifice spray coating of medical devices and pre-filming atomization |
| BRPI0511448A (pt) | 2004-07-06 | 2007-12-26 | Bioren Inc | anticorpos anti-tnf-alfa de alta afinidade, método para a geração dos mesmos e biblioteca de seqüências |
| EP1869084A2 (en) | 2005-03-04 | 2007-12-26 | Biogen Idec MA Inc. | Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues |
| JP5255435B2 (ja) | 2005-04-26 | 2013-08-07 | メディミューン,エルエルシー | ヒンジドメイン操作による抗体エフェクター機能の調節 |
| MX2007013924A (es) | 2005-05-09 | 2008-01-28 | Glycart Biotechnology Ag | Moleculas que unen antigeno que tienen regiones fc modificadas y union alterada a receptores fc. |
| WO2007019620A1 (en) | 2005-08-15 | 2007-02-22 | Arana Therapeutics Limited | Engineered antibodies with new world primate framework regions |
| AU2006281981A1 (en) | 2005-08-15 | 2007-02-22 | Cephalon Australia Pty Ltd | Chimeric antibodies with new world primate regions |
| JP2009519983A (ja) * | 2005-12-20 | 2009-05-21 | アラーナ・テラピューティクス・リミテッド | 部分的な新世界ザル結合領域を有するキメラ抗体 |
| EA017417B1 (ru) * | 2006-02-01 | 2012-12-28 | Сефалон Астралия Пти Лтд. | КОНСТРУКТ ОДНОДОМЕННОГО АНТИТЕЛА, КОТОРЫЙ СВЯЗЫВАЕТСЯ С ЧЕЛОВЕЧЕСКИМ TNF-α, И ЕГО ПРИМЕНЕНИЕ |
| AU2007212147A1 (en) | 2006-02-03 | 2007-08-16 | Medimmune, Llc | Protein formulations |
| CN101466733A (zh) | 2006-04-14 | 2009-06-24 | 特鲁比昂药品公司 | 包含免疫球蛋白铰链区和Fc效应子功能改变了的Fc区的结合蛋白 |
| US20080139790A1 (en) * | 2006-12-08 | 2008-06-12 | Jennings Philip A | Chimeric antibodies |
| US20080260738A1 (en) | 2007-04-18 | 2008-10-23 | Moore Margaret D | Single chain fc, methods of making and methods of treatment |
| DE112008003232T5 (de) | 2007-11-30 | 2011-02-24 | Glaxo Group Limited, Greenford | Antigen-Bindungskonstrukte |
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2007
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- 2007-02-01 MX MX2008009792A patent/MX2008009792A/es active IP Right Grant
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- 2007-02-01 WO PCT/AU2007/000085 patent/WO2007087673A1/en not_active Ceased
- 2007-02-01 KR KR1020087021381A patent/KR20090039666A/ko not_active Ceased
- 2007-02-01 EP EP07701418A patent/EP1987064A4/en not_active Withdrawn
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- 2007-02-01 JP JP2008552642A patent/JP5259423B2/ja not_active Expired - Fee Related
- 2007-02-01 CN CN2007800083708A patent/CN101400703B/zh not_active Expired - Fee Related
- 2007-02-01 CN CN2013100625658A patent/CN103232540A/zh active Pending
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2010
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5892019A (en) * | 1987-07-15 | 1999-04-06 | The United States Of America, As Represented By The Department Of Health And Human Services | Production of a single-gene-encoded immunoglobulin |
| WO1989001974A1 (en) * | 1987-09-04 | 1989-03-09 | Celltech Limited | Recombinant antibody |
| WO1989007142A1 (en) * | 1988-02-05 | 1989-08-10 | Morrison Sherie L | Domain-modified constant region antibodies |
| US20030232971A1 (en) * | 1989-08-07 | 2003-12-18 | Rathjen Deborah Ann | Tumour necrosis factor binding ligands |
| WO2002077029A2 (en) * | 2000-11-07 | 2002-10-03 | City Of Hope | Cd19-specific redirected immune cells |
| US20030215427A1 (en) * | 2001-04-11 | 2003-11-20 | Michael Jensen | CE7-specific redirected immune cells |
Non-Patent Citations (2)
| Title |
|---|
| GenBank accession AAB37424 & Qi and Xiang (1995), "A genetically engineered single-gene-encoded anti-TAG72 chimeric antibody secreted from myeloma cells" Hum. Antibodies Hybridomas 6(4): 161-166 * |
| Muñoz E. et al. (1998), "The C1 domain of IgG is not essential for C3 covalent binding: importance of the other constant domains as targets for C3" International Immunology 10(2): 97-106, Fig. 1 and 2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20090039666A (ko) | 2009-04-22 |
| US20110044979A1 (en) | 2011-02-24 |
| EP1987064A1 (en) | 2008-11-05 |
| CA2640661A1 (en) | 2007-08-09 |
| CN101400703B (zh) | 2013-05-08 |
| JP2009525031A (ja) | 2009-07-09 |
| US20070202105A1 (en) | 2007-08-30 |
| AU2007211829B2 (en) | 2012-11-08 |
| CN103232540A (zh) | 2013-08-07 |
| CN101400703A (zh) | 2009-04-01 |
| AU2007211829A1 (en) | 2007-08-09 |
| US7846439B2 (en) | 2010-12-07 |
| AU2007211829C1 (en) | 2013-05-23 |
| WO2007087673A1 (en) | 2007-08-09 |
| JP5259423B2 (ja) | 2013-08-07 |
| BRPI0707425A2 (pt) | 2011-05-03 |
| EA200870208A1 (ru) | 2009-02-27 |
| NZ569988A (en) | 2011-09-30 |
| EP1987064A4 (en) | 2010-04-07 |
| MX2008009792A (es) | 2008-09-01 |
| AU2007211829C9 (en) | 2013-07-11 |
| AU2007211829C8 (en) | 2013-06-27 |
| JP2013059338A (ja) | 2013-04-04 |
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