AU2012328917B2 - Bispecific immunobinders directed against TNF and IL-17 - Google Patents
Bispecific immunobinders directed against TNF and IL-17 Download PDFInfo
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- AU2012328917B2 AU2012328917B2 AU2012328917A AU2012328917A AU2012328917B2 AU 2012328917 B2 AU2012328917 B2 AU 2012328917B2 AU 2012328917 A AU2012328917 A AU 2012328917A AU 2012328917 A AU2012328917 A AU 2012328917A AU 2012328917 B2 AU2012328917 B2 AU 2012328917B2
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| ES2877548T3 (es) | 2016-06-02 | 2021-11-17 | Abbvie Inc | Agonista del receptor de glucocorticoides e inmunoconjugados del mismo |
| EP3538141A4 (en) | 2016-11-10 | 2020-07-15 | Merck Sharp & Dohme Corp. | LIGAND ILT3 |
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| CN120025437A (zh) | 2019-01-31 | 2025-05-23 | 努玛治疗有限公司 | 对TNFα和IL-17A具有特异性的多特异性抗体、靶向IL-17A的抗体及其使用方法 |
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| EP3980448A4 (en) * | 2019-06-04 | 2023-06-28 | Academia Sinica | Ligands targed to epidermal growth factor receptors and compositions for use in treating tumors |
| US11179473B2 (en) | 2020-02-21 | 2021-11-23 | Silverback Therapeutics, Inc. | Nectin-4 antibody conjugates and uses thereof |
| KR20230012539A (ko) | 2020-05-13 | 2023-01-26 | 디스크 메디슨, 인크. | 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체 |
| CN116209678A (zh) | 2020-07-01 | 2023-06-02 | 安尔士制药公司 | 抗asgr1抗体缀合物及其用途 |
| CN112375149B (zh) * | 2020-10-30 | 2023-04-18 | 沣潮医药科技（上海）有限公司 | Ace2免疫融合蛋白及其应用 |
| CA3235096A1 (en) | 2021-11-17 | 2023-05-25 | Disc Medicine, Inc. | Methods for treating anemia of kidney disease |
| AR133647A1 (es) | 2023-08-25 | 2025-10-22 | Proteologix Us Inc | Constructos de anticuerpos multiespecíficos anti-il-13 y usos de los mismos |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090311253A1 (en) * | 2008-06-03 | 2009-12-17 | Abbott Laboratories | Dual Variable Domain Immunoglobulins and Uses Thereof |
| US20100266531A1 (en) * | 2009-03-05 | 2010-10-21 | Abbott Laboratories | Il-17 binding proteins |
| US20110250130A1 (en) * | 2010-04-07 | 2011-10-13 | Lorenzo Benatuil | Tnf-alpha binding proteins |
Family Cites Families (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4554101A (en) | 1981-01-09 | 1985-11-19 | New York Blood Center, Inc. | Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity |
| US4980286A (en) | 1985-07-05 | 1990-12-25 | Whitehead Institute For Biomedical Research | In vivo introduction and expression of foreign genetic material in epithelial cells |
| DE3631229A1 (de) * | 1986-09-13 | 1988-03-24 | Basf Ag | Monoklonale antikoerper gegen humanen tumornekrosefaktor (tnf) und deren verwendung |
| AU600575B2 (en) | 1987-03-18 | 1990-08-16 | Sb2, Inc. | Altered antibodies |
| US5006309A (en) | 1988-04-22 | 1991-04-09 | Abbott Laboratories | Immunoassay device with liquid transfer between wells by washing |
| US5089424A (en) | 1988-06-14 | 1992-02-18 | Abbott Laboratories | Method and apparatus for heterogeneous chemiluminescence assay |
| SE462454B (sv) | 1988-11-10 | 1990-06-25 | Pharmacia Ab | Maetyta foer anvaendning i biosensorer |
| 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 |
| US5063081A (en) | 1988-11-14 | 1991-11-05 | I-Stat Corporation | Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor |
| CA2048302A1 (en) | 1990-08-15 | 1992-02-16 | Victoria P. Meucci | Solubilization reagent for biological test samples |
| US5135875A (en) | 1990-08-15 | 1992-08-04 | Abbott Laboratories | Protein precipitation reagent |
| CA2069530A1 (en) | 1991-06-03 | 1992-12-04 | Cass J. Grandone | Reagent pack for immunoassays |
| WO1993020442A1 (en) | 1992-03-30 | 1993-10-14 | Abbott Laboratories | Reagents and methods for the detection and quantification of thyroxine in fluid samples |
| US6309636B1 (en) * | 1995-09-14 | 2001-10-30 | Cancer Research Institute Of Contra Costa | Recombinant peptides derived from the Mc3 anti-BA46 antibody, methods of use thereof, and methods of humanizing antibody peptides |
| US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
| US6019968A (en) | 1995-04-14 | 2000-02-01 | Inhale Therapeutic Systems, Inc. | Dispersible antibody compositions and methods for their preparation and use |
| US6127977A (en) | 1996-11-08 | 2000-10-03 | Cohen; Nathan | Microstrip patch antenna with fractal structure |
| DE69721548T2 (de) | 1996-02-09 | 2004-04-01 | Abbott Laboratories(Bermuda)Ltd. | HUMANE ANTIKÖRPER WELCHE AN HUMANEN TNFalpha BINDEN |
| NZ516848A (en) | 1997-06-20 | 2004-03-26 | Ciphergen Biosystems Inc | Retentate chromatography apparatus with applications in biology and medicine |
| CA2323638A1 (en) | 1998-04-03 | 1999-10-14 | Phylos, Inc. | Addressable protein arrays |
| US6406921B1 (en) | 1998-07-14 | 2002-06-18 | Zyomyx, Incorporated | Protein arrays for high-throughput screening |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| AU4025300A (en) | 1999-03-24 | 2000-10-09 | Packard Bioscience Company | Continuous porous matrix arrays |
| US6914128B1 (en) | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
| DK1272647T3 (en) | 2000-04-11 | 2014-12-15 | Genentech Inc | Multivalent antibodies and uses thereof |
| EP2386575A3 (en) | 2000-06-29 | 2011-11-30 | Abbott Laboratories | Dual specificity antibodies and methods of making and using |
| US7419821B2 (en) | 2002-03-05 | 2008-09-02 | I-Stat Corporation | Apparatus and methods for analyte measurement and immunoassay |
| SI1523496T1 (sl) | 2002-07-18 | 2011-11-30 | Merus B V | Rekombinantno proizvajanje zmesi protiteles |
| US20040018577A1 (en) | 2002-07-29 | 2004-01-29 | Emerson Campbell John Lewis | Multiple hybrid immunoassay |
| JP4754219B2 (ja) | 2002-12-02 | 2011-08-24 | アムジエン・フレモント・インコーポレイテツド | 腫瘍壊死因子を対象とする抗体、およびそれらの使用 |
| CA2517145C (en) | 2003-03-05 | 2017-08-01 | Halozyme, Inc. | Soluble hyaluronidase glycoprotein (shasegp), process for preparing the same, uses and pharmaceutical compositions comprising thereof |
| US20060104968A1 (en) | 2003-03-05 | 2006-05-18 | Halozyme, Inc. | Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases |
| NZ544618A (en) | 2003-06-16 | 2009-02-28 | Celltech R & D Inc | Antibodies specific for sclerostin and methods for increasing bone mineralization |
| AU2004280333A1 (en) | 2003-08-22 | 2005-04-21 | Medimmune, Llc | Humanization of antibodies |
| US7723099B2 (en) | 2003-09-10 | 2010-05-25 | Abbott Point Of Care Inc. | Immunoassay device with immuno-reference electrode |
| US7682833B2 (en) | 2003-09-10 | 2010-03-23 | Abbott Point Of Care Inc. | Immunoassay device with improved sample closure |
| 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 |
| US7592429B2 (en) | 2005-05-03 | 2009-09-22 | Ucb Sa | Sclerostin-binding antibody |
| US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
| US7883855B2 (en) | 2006-07-21 | 2011-02-08 | Abbott Laboratories | Immunosuppressant drug extraction reagent for immunoassays |
| EP2460828A3 (en) | 2006-11-10 | 2012-08-08 | UCB Pharma, S.A. | Antibodies and diagnostics |
| US20100036091A1 (en) | 2006-11-10 | 2010-02-11 | Amgen Inc. | Antibody-based diagnostics and therapeutics |
| MY149129A (en) | 2007-03-20 | 2013-07-15 | Lilly Co Eli | Anti-sclerostin antibodies |
| US7906293B2 (en) | 2007-04-09 | 2011-03-15 | Abbott Laboratories | Acridinium phenyl esters useful in the analysis of biological |
| TWI489993B (zh) | 2007-10-12 | 2015-07-01 | Novartis Ag | 骨硬化素（ｓｃｌｅｒｏｓｔｉｎ）抗體組合物及使用方法 |
| EP2240581B1 (en) | 2008-01-15 | 2016-05-11 | AbbVie Inc. | Improved mammalian expression vectors and uses thereof |
| UY32979A (es) | 2009-10-28 | 2011-02-28 | Abbott Lab | Inmunoglobulinas con dominio variable dual y usos de las mismas |
| TW201206473A (en) | 2010-08-03 | 2012-02-16 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
| AR084210A1 (es) | 2010-12-08 | 2013-05-02 | Abbott Lab | PROTEINAS DE UNION AL TNF-a |
| JP2014533659A (ja) | 2011-10-24 | 2014-12-15 | アッヴィ・インコーポレイテッド | スクレロスチンに対するイムノバインダー |
| CN104093739A (zh) | 2011-10-24 | 2014-10-08 | 艾伯维公司 | 针对tnf的免疫结合剂 |
-
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- 2012-10-24 WO PCT/US2012/061686 patent/WO2013063110A1/en not_active Ceased
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- 2013-11-18 US US14/082,502 patent/US20140079705A1/en not_active Abandoned
-
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- 2014-04-23 IL IL232207A patent/IL232207A0/en unknown
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- 2014-05-19 EC ECIEPI20141260A patent/ECSP14001260A/es unknown
- 2014-05-22 CO CO14110752A patent/CO7020874A2/es unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090311253A1 (en) * | 2008-06-03 | 2009-12-17 | Abbott Laboratories | Dual Variable Domain Immunoglobulins and Uses Thereof |
| US20100266531A1 (en) * | 2009-03-05 | 2010-10-21 | Abbott Laboratories | Il-17 binding proteins |
| US20110250130A1 (en) * | 2010-04-07 | 2011-10-13 | Lorenzo Benatuil | Tnf-alpha binding proteins |
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| US20140079705A1 (en) | 2014-03-20 |
| RS20140202A1 (sr) | 2014-10-31 |
| SG11201401796SA (en) | 2014-10-30 |
| WO2013063110A1 (en) | 2013-05-02 |
| PE20142245A1 (es) | 2015-01-22 |
| JP2015502145A (ja) | 2015-01-22 |
| PH12014500903A1 (en) | 2014-06-09 |
| GT201400077A (es) | 2014-12-23 |
| US9655964B2 (en) | 2017-05-23 |
| JP6121432B2 (ja) | 2017-04-26 |
| CN104185641A (zh) | 2014-12-03 |
| EP2771361A1 (en) | 2014-09-03 |
| AU2012328917A1 (en) | 2014-05-22 |
| CR20140224A (es) | 2014-09-03 |
| TW201323441A (zh) | 2013-06-16 |
| CL2014001055A1 (es) | 2014-08-18 |
| DOP2014000084A (es) | 2014-09-15 |
| ECSP14001260A (es) | 2015-07-31 |
| CA2853114A1 (en) | 2013-05-02 |
| MX2014004980A (es) | 2014-09-11 |
| BR112014009810A2 (pt) | 2017-04-25 |
| IL232207A0 (en) | 2014-06-30 |
| KR20140084254A (ko) | 2014-07-04 |
| HK1200321A1 (en) | 2015-08-07 |
| US20140161804A1 (en) | 2014-06-12 |
| UY34410A (es) | 2013-05-31 |
| RU2014121043A (ru) | 2015-12-10 |
| CO7020874A2 (es) | 2014-08-11 |
| AR088514A1 (es) | 2014-06-18 |
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