AU760854B2 - Use of bi-specific antibodies for pre-targeting diagnosis and therapy - Google Patents
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- AU760854B2 AU760854B2 AU45792/99A AU4579299A AU760854B2 AU 760854 B2 AU760854 B2 AU 760854B2 AU 45792/99 A AU45792/99 A AU 45792/99A AU 4579299 A AU4579299 A AU 4579299A AU 760854 B2 AU760854 B2 AU 760854B2
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- 238000013519 translation Methods 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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Landscapes
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Applications Claiming Priority (5)
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| US9014298P | 1998-06-22 | 1998-06-22 | |
| US60/090142 | 1998-06-22 | ||
| US10415698P | 1998-10-14 | 1998-10-14 | |
| US60/104156 | 1998-10-14 | ||
| PCT/US1999/013879 WO1999066951A2 (en) | 1998-06-22 | 1999-06-22 | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
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| AU4579299A AU4579299A (en) | 2000-01-10 |
| AU760854B2 true AU760854B2 (en) | 2003-05-22 |
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| AU45792/99A Ceased AU760854B2 (en) | 1998-06-22 | 1999-06-22 | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
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| DE (1) | DE69942148D1 (enExample) |
| WO (1) | WO1999066951A2 (enExample) |
Cited By (1)
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| AU2005211754B2 (en) * | 2004-02-11 | 2010-11-11 | Immunomedics, Inc. | Therapeutic and diagnostic conjugates for use with multispecific antibodies |
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| US7138103B2 (en) * | 1998-06-22 | 2006-11-21 | Immunomedics, Inc. | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
| US7387772B1 (en) * | 1999-06-22 | 2008-06-17 | Immunimedics, Inc. | Chimeric, human and humanized anti-CSAP monoclonal antibodies |
| US6962702B2 (en) * | 1998-06-22 | 2005-11-08 | Immunomedics Inc. | Production and use of novel peptide-based agents for use with bi-specific antibodies |
| WO1999066951A2 (en) | 1998-06-22 | 1999-12-29 | Immunomedics, Inc. | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
| US7052872B1 (en) | 1999-06-22 | 2006-05-30 | Immunomedics, Inc. | Bi-specific antibodies for pre-targeting diagnosis and therapy |
| US7833528B2 (en) * | 1998-06-22 | 2010-11-16 | Immunomedics, Inc. | Use of multispecific, non-covalent complexes for targeted delivery of therapeutics |
| US6361774B1 (en) | 1999-09-17 | 2002-03-26 | Immunomedics, Inc. | Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug |
| CA2344440A1 (en) * | 1998-09-18 | 2000-03-30 | Immunomedics, Inc. | Antibody directed enzyme prodrug therapy (edept) with glucoronidase |
| US6897044B1 (en) | 1999-01-28 | 2005-05-24 | Biogen Idec, Inc. | Production of tetravalent antibodies |
| NZ521182A (en) | 2000-03-03 | 2004-11-26 | Cambridge Antibody Tech | Human antibodies against eotaxin comprising VH adn VL domains and their use |
| WO2002008293A2 (en) * | 2000-07-25 | 2002-01-31 | Immunomedics Inc. | Multivalent target binding protein |
| IL160126A0 (en) * | 2001-07-31 | 2004-06-20 | Immunomedics Inc | A kit for targeting a target site containing a polymer conjugate |
| JP4443923B2 (ja) * | 2001-10-15 | 2010-03-31 | イミューノメディクス、インコーポレイテッド | 親和性向上剤 |
| IL162732A0 (en) * | 2001-12-26 | 2005-11-20 | Immunomedics Inc | Methods of generating multispecific, multivalent agents from hv and vl domains |
| DE60325184D1 (de) * | 2002-03-01 | 2009-01-22 | Immunomedics Inc | Rs7 antikörper |
| AU2003209446B2 (en) * | 2002-03-01 | 2008-09-25 | Immunomedics, Inc. | Bispecific antibody point mutations for enhancing rate of clearance |
| WO2003101495A1 (en) * | 2002-05-29 | 2003-12-11 | Immunomedics, Inc. | Methods and compositions for radioimmunotherapy of brain and cns tumors |
| US20040022726A1 (en) * | 2002-06-03 | 2004-02-05 | Goldenberg David M. | Methods and compositions for intravesical therapy of bladder cancer |
| US7601351B1 (en) | 2002-06-26 | 2009-10-13 | Human Genome Sciences, Inc. | Antibodies against protective antigen |
| US20060034767A1 (en) * | 2002-07-05 | 2006-02-16 | Roger Williams Medical Center | Targeting and tracking of cells to specific organs and tissues in vivo |
| JP4790413B2 (ja) * | 2002-10-08 | 2011-10-12 | イミューノメディクス、インコーポレイテッド | 抗体療法 |
| WO2004045642A1 (en) * | 2002-11-15 | 2004-06-03 | Immunomedics, Inc. | Use of multi-specific, non-covalent complexes for targeted delivery of therapeutics |
| US7528235B2 (en) * | 2003-01-23 | 2009-05-05 | The Regents Of The Univarsity Of California | Multi-functional antibodies |
| US7820787B2 (en) * | 2003-01-23 | 2010-10-26 | The Regents Of The University Of California | Multi-functional antibodies |
| JP4874090B2 (ja) * | 2003-01-31 | 2012-02-08 | イミューノメディクス、インコーポレイテッド | 治療薬および診断薬を投与するための方法および組成物 |
| EP1638510B1 (en) | 2003-07-01 | 2015-09-02 | Immunomedics, Inc. | Multivalent carriers of bi-specific antibodies |
| WO2005069994A2 (en) * | 2004-01-22 | 2005-08-04 | Immunomedics, Inc. | Folate conjugates and complexes |
| MXPA06014684A (es) | 2004-06-18 | 2007-02-12 | Ambrx Inc | Novedosos polipeptidos de enlace antigeno y sus usos. |
| EP3332808B1 (en) | 2005-03-03 | 2020-09-09 | Immunomedics Inc. | Humanized l243 antibodies |
| WO2006114115A1 (de) | 2005-04-26 | 2006-11-02 | Trion Pharma Gmbh | Kombination von antikörpern mit glukokortikoiden zur behandlung von krebs |
| US20090035257A1 (en) * | 2005-08-25 | 2009-02-05 | Repair Technologies, Inc. | Devices, compositions and methods for the protection and repair of cells and tissues |
| GB2431352B (en) * | 2005-09-12 | 2011-03-16 | Essential Nutrition Ltd | Device |
| US8741260B2 (en) | 2005-10-07 | 2014-06-03 | Armagen Technologies, Inc. | Fusion proteins for delivery of GDNF to the CNS |
| JP5231231B2 (ja) * | 2005-10-19 | 2013-07-10 | アイビーシー・ファーマシューティカルズ・インコーポレーテッド | 複雑性が増大した生理活性アセンブリーを生成するための方法および組成物ならびに使用 |
| EP2418223A3 (en) * | 2006-06-12 | 2013-01-16 | Emergent Product Development Seattle, LLC | Single-chain multivalent binding proteins with effector function |
| WO2008009115A1 (en) * | 2006-07-18 | 2008-01-24 | Ottawa Health Research Institute | Disparate suicide carrier cells for tumor targeting of promiscuous oncolytic viruses |
| WO2008022349A2 (en) * | 2006-08-18 | 2008-02-21 | Armagen Technologies, Inc. | Agents for blood-brain barrier delivery |
| EP2997976A1 (en) | 2007-07-27 | 2016-03-23 | Armagen Technologies, Inc. | Methods and compositions for increasing alpha-l-iduronidase activity in the cns |
| JP2009051784A (ja) * | 2007-08-28 | 2009-03-12 | Inst Nuclear Energy Research Rocaec | 癌を抑制する放射性物質及びその調整方法 |
| CA2700714C (en) | 2007-09-26 | 2018-09-11 | Ucb Pharma S.A. | Dual specificity antibody fusions |
| US8450106B2 (en) * | 2007-10-17 | 2013-05-28 | The Ohio State University Research Foundation | Oncolytic virus |
| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| US9266967B2 (en) | 2007-12-21 | 2016-02-23 | Hoffmann-La Roche, Inc. | Bivalent, bispecific antibodies |
| PT2334705T (pt) * | 2008-09-26 | 2017-03-22 | Ucb Biopharma Sprl | Produtos biológicos |
| US20160095939A1 (en) | 2014-10-07 | 2016-04-07 | Immunomedics, Inc. | Neoadjuvant use of antibody-drug conjugates |
| CN102369215B (zh) | 2009-04-02 | 2015-01-21 | 罗切格利卡特公司 | 包含全长抗体和单链Fab片段的多特异性抗体 |
| DK2417156T3 (en) * | 2009-04-07 | 2015-03-02 | Roche Glycart Ag | Trivalent, bispecific antibodies |
| JP5497887B2 (ja) * | 2009-04-07 | 2014-05-21 | ロシュ グリクアート アクチェンゲゼルシャフト | 二重特異性抗ErbB−2/抗c−Met抗体 |
| RU2570633C2 (ru) * | 2009-05-27 | 2015-12-10 | Ф.Хоффманн-Ля Рош Аг | Три- или тетраспецифические антитела |
| US9676845B2 (en) * | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| US8703132B2 (en) * | 2009-06-18 | 2014-04-22 | Hoffmann-La Roche, Inc. | Bispecific, tetravalent antigen binding proteins |
| US9050375B2 (en) | 2009-07-06 | 2015-06-09 | Hoffmann-La Roche, Inc. | Bi-specific digoxigenin binding antibodies |
| IN2012DN00551A (enExample) | 2009-07-22 | 2015-06-12 | Actinium Pharmaceuticals Inc | |
| US9493578B2 (en) * | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
| CN102482701B (zh) | 2009-09-16 | 2015-05-13 | 免疫医疗公司 | I类抗-cea抗体及其使用 |
| JP6091894B2 (ja) | 2009-09-16 | 2017-03-15 | ジェネンテック, インコーポレイテッド | コイルドコイルおよび/またはテザー含有タンパク質複合体およびその使用 |
| EP2485761B1 (en) | 2009-10-09 | 2019-02-27 | Armagen, Inc. | Methods and compositions for increasing iduronate 2-sulfatase activity in the cns |
| CA2782194C (en) | 2009-12-02 | 2018-01-16 | Immunomedics, Inc. | Combination of radiolabelled antibodies (rait) and antibody-drug conjugates (adc) for treatment of pancreatic cancer |
| CN102770456B (zh) | 2009-12-04 | 2018-04-06 | 弗·哈夫曼-拉罗切有限公司 | 多特异性抗体、抗体类似物、组合物和方法 |
| TW201138821A (en) | 2010-03-26 | 2011-11-16 | Roche Glycart Ag | Bispecific antibodies |
| EP3029066B1 (en) | 2010-07-29 | 2019-02-20 | Xencor, Inc. | Antibodies with modified isoelectric points |
| WO2012025530A1 (en) | 2010-08-24 | 2012-03-01 | F. Hoffmann-La Roche Ag | Bispecific antibodies comprising a disulfide stabilized - fv fragment |
| CN103328514B (zh) * | 2010-11-09 | 2015-12-02 | 阿尔蒂单抗治疗公司 | 用于抗原结合的蛋白复合物及其使用方法 |
| US20130273055A1 (en) * | 2010-11-16 | 2013-10-17 | Eric Borges | Agents and methods for treating diseases that correlate with bcma expression |
| CA2820619C (en) | 2010-11-24 | 2020-01-07 | Litron Laboratories, Ltd. | Rapid in vivo gene mutation assay based on the pig-a gene |
| EP2655413B1 (en) | 2010-12-23 | 2019-01-16 | F.Hoffmann-La Roche Ag | Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery |
| BR112013019975A2 (pt) | 2011-02-28 | 2017-08-01 | Hoffmann La Roche | proteínas de ligação de antígeno, composição farmacêutica, uso de uma proteína de ligação de antígeno, método para o tratamento de um paciente e método para a preparação de uma proteína de ligação de antígeno, ácido nucleico, vetor e célula hospedeira" |
| CN103403025B (zh) | 2011-02-28 | 2016-10-12 | 弗·哈夫曼-拉罗切有限公司 | 单价抗原结合蛋白 |
| JP6024025B2 (ja) | 2011-05-02 | 2016-11-09 | イミューノメディクス、インコーポレイテッドImmunomedics, Inc. | 少容量投与用のアロタイプ選択抗体の限外濾過濃縮 |
| US12466897B2 (en) | 2011-10-10 | 2025-11-11 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| US10851178B2 (en) | 2011-10-10 | 2020-12-01 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| TWI679212B (zh) | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對bcma之e3以及cd3的結合分子 |
| EP2785378B1 (en) | 2011-12-02 | 2020-05-13 | Armagen, Inc. | Methods and compositions for increasing arylsulfatase a activity in the cns |
| JP6486686B2 (ja) | 2012-02-10 | 2019-03-20 | ジェネンテック, インコーポレイテッド | 単鎖抗体及び他のヘテロ多量体 |
| CN104395339A (zh) | 2012-06-27 | 2015-03-04 | 弗·哈夫曼-拉罗切有限公司 | 用于选择并产生含有至少两种不同结合实体的定制高度选择性和多特异性靶向实体的方法及其用途 |
| MX2014014804A (es) | 2012-06-27 | 2015-02-12 | Hoffmann La Roche | Metodo para la elaboracion de conjugados de la region fc de anticuerpos que comprenden por lo menos una entidad de union que se une especificamente a un objetivo y usos del mismo. |
| US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
| US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
| US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
| CA2898100C (en) | 2013-01-14 | 2023-10-10 | Xencor, Inc. | Novel heterodimeric proteins |
| US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
| US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
| US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
| WO2014113510A1 (en) | 2013-01-15 | 2014-07-24 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
| EP3421495A3 (en) | 2013-03-15 | 2019-05-15 | Xencor, Inc. | Modulation of t cells with bispecific antibodies and fc fusions |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
| US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
| JP6422956B2 (ja) | 2013-10-11 | 2018-11-14 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 多重特異性ドメイン交換共通可変軽鎖抗体 |
| EP3110445A4 (en) | 2014-02-25 | 2017-09-27 | Immunomedics, Inc. | Humanized rfb4 anti-cd22 antibody |
| MX385936B (es) | 2014-03-28 | 2025-03-11 | Xencor Inc | Anticuerpos biespecíficos que se unen a cd38 y cd3. |
| HRP20211273T1 (hr) | 2014-11-26 | 2021-11-12 | Xencor, Inc. | Heterodimerna protutijela koja vežu cd3 i cd20 |
| MX2017006918A (es) | 2014-11-26 | 2018-01-25 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y cd38. |
| US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
| PL3227332T3 (pl) | 2014-12-03 | 2020-06-15 | F. Hoffmann-La Roche Ag | Wielospecyficzne przeciwciała |
| EP3237449A2 (en) | 2014-12-22 | 2017-11-01 | Xencor, Inc. | Trispecific antibodies |
| US10538589B2 (en) | 2015-01-14 | 2020-01-21 | Armagen Inc. | Methods and compositions for increasing N-acetylglucosaminidase (NAGLU) activity in the CNS using a fusion antibody comprising an anti-human insulin receptor antibody and NAGLU |
| WO2016141387A1 (en) | 2015-03-05 | 2016-09-09 | Xencor, Inc. | Modulation of t cells with bispecific antibodies and fc fusions |
| EP3286224A4 (en) | 2015-04-22 | 2018-11-14 | Immunomedics, Inc. | Isolation, detection, diagnosis and/or characterization of circulating trop-2-positive cancer cells |
| JP6872181B2 (ja) | 2015-05-20 | 2021-05-19 | 国立大学法人 鹿児島大学 | IgG結合ペプチドによる抗体の特異的修飾 |
| EP3316885B1 (en) | 2015-07-01 | 2021-06-23 | Immunomedics, Inc. | Antibody-sn-38 immunoconjugates with a cl2a linker |
| UA126278C2 (uk) | 2015-09-21 | 2022-09-14 | Аптево Рісьорч Енд Девелопмент Ллс | Поліпептиди, які зв'язують cd3 |
| JP7058219B2 (ja) | 2015-12-07 | 2022-04-21 | ゼンコア インコーポレイテッド | Cd3及びpsmaに結合するヘテロ二量体抗体 |
| PL3470418T3 (pl) | 2016-06-13 | 2024-12-16 | Kagoshima University | Przeciwciało znakowane izotopem promieniotwórczym specyficzne dla danego miejsca wykorzystujące peptyd wiążący IgG |
| FI3468586T3 (fi) | 2016-06-14 | 2024-10-29 | Xencor Inc | Bispesifisiä immuuniaktivaatiota vapauttavia vasta-aineita |
| EP3475304B1 (en) | 2016-06-28 | 2022-03-23 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
| US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| CA3040504A1 (en) | 2016-10-14 | 2018-04-19 | Xencor, Inc. | Il15/il15ra heterodimeric fc-fusion proteins |
| MA49517A (fr) | 2017-06-30 | 2020-05-06 | Xencor Inc | Protéines de fusion fc hétérodimères ciblées contenant il-15/il-15ra et domaines de liaison à l'antigène |
| WO2019094637A1 (en) | 2017-11-08 | 2019-05-16 | Xencor, Inc. | Bispecific and monospecific antibodies using novel anti-pd-1 sequences |
| US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| KR102722731B1 (ko) | 2017-12-19 | 2024-10-25 | 젠코어 인코포레이티드 | 조작된 il-2 fc 융합 단백질 |
| CN112469477A (zh) | 2018-04-04 | 2021-03-09 | Xencor股份有限公司 | 与成纤维细胞活化蛋白结合的异源二聚体抗体 |
| CA3097741A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains |
| JP2021521784A (ja) | 2018-04-18 | 2021-08-30 | ゼンコア インコーポレイテッド | IL−15/IL−15RaFc融合タンパク質とPD−1抗原結合ドメインを含むPD−1標的化ヘテロダイマー融合タンパク質およびそれらの使用 |
| SG11202103192RA (en) | 2018-10-03 | 2021-04-29 | Xencor Inc | Il-12 heterodimeric fc-fusion proteins |
| MX2021010390A (es) | 2019-03-01 | 2021-11-17 | Xencor Inc | Anticuerpos heterodimericos que se unen a enpp3 y cd3. |
| WO2021231976A1 (en) | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3 |
| WO2022040482A1 (en) | 2020-08-19 | 2022-02-24 | Xencor, Inc. | Anti-cd28 and/or anti-b7h3 compositions |
| CN117157319A (zh) | 2021-03-09 | 2023-12-01 | Xencor股份有限公司 | 结合cd3和cldn6的异二聚抗体 |
| KR20230154311A (ko) | 2021-03-10 | 2023-11-07 | 젠코어 인코포레이티드 | Cd3 및 gpc3에 결합하는 이종이량체 항체 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0419387A1 (fr) * | 1989-09-21 | 1991-03-27 | IMMUNOTECH PARTNERS: Société en Commandite par Actions dite | Nouveaux dérivés hydrophiles, application au diagnostic et à la thérapeutique, kits diagnostiques ou thérapeutiques et réactifs immunologiques |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4863713A (en) * | 1986-06-23 | 1989-09-05 | The Board Of Trustees Of Leland Stanford Jr. Univ. | Method and system for administering therapeutic and diagnostic agents |
| FR2604092B1 (fr) | 1986-09-19 | 1990-04-13 | Immunotech Sa | Immunoreactifs destines a cibler les cellules animales pour leur visualisation ou leur destruction in vivo |
| US5851527A (en) * | 1988-04-18 | 1998-12-22 | Immunomedics, Inc. | Method for antibody targeting of therapeutic agents |
| US5632990A (en) * | 1988-04-22 | 1997-05-27 | Cancer Research Campaign Tech. Ltd. | Treatment for tumors comprising conjugated antibody A5B7 and a prodrug |
| CA2047717C (en) * | 1989-03-14 | 2000-08-01 | Fred W. Wagner | Monoclonal antibodies for small moieties, methods therefor |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| AU665758B2 (en) | 1991-04-26 | 1996-01-18 | Surface Active Limited | Novel antibodies, and methods for their use |
| DE69334255D1 (de) * | 1992-02-06 | 2009-02-12 | Novartis Vaccines & Diagnostic | Marker für Krebs und biosynthetisches Bindeprotein dafür |
| US6096289A (en) | 1992-05-06 | 2000-08-01 | Immunomedics, Inc. | Intraoperative, intravascular, and endoscopic tumor and lesion detection, biopsy and therapy |
| ZA938243B (en) * | 1992-11-12 | 1995-05-04 | Hybritech Inc | Altered affinity polypeptides of metal chelate binding antibodies |
| US5502037A (en) * | 1993-07-09 | 1996-03-26 | Neuromed Technologies, Inc. | Pro-cytotoxic drug conjugates for anticancer therapy |
| US5686578A (en) | 1994-08-05 | 1997-11-11 | Immunomedics, Inc. | Polyspecific immunoconjugates and antibody composites for targeting the multidrug resistant phenotype |
| AU4119397A (en) * | 1996-08-28 | 1998-03-19 | Viva Diagnostika Diagnostische Produkte Gmbh | Novel combination preparations and their use in immunodiagnosis and immunotherapy |
| JP3992923B2 (ja) * | 1997-09-03 | 2007-10-17 | イムノメディクス, インコーポレイテッド | F−18陽電子放出トモグラフィー用のタン白及びペプチドのフッ素化方法 |
| WO1999066951A2 (en) | 1998-06-22 | 1999-12-29 | Immunomedics, Inc. | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
-
1999
- 1999-06-22 WO PCT/US1999/013879 patent/WO1999066951A2/en not_active Ceased
- 1999-06-22 US US09/337,756 patent/US7074405B1/en not_active Expired - Fee Related
- 1999-06-22 EP EP99928808A patent/EP1089766B1/en not_active Expired - Lifetime
- 1999-06-22 AT AT99928808T patent/ATE460946T1/de not_active IP Right Cessation
- 1999-06-22 CA CA2335364A patent/CA2335364C/en not_active Expired - Fee Related
- 1999-06-22 CA CA2690395A patent/CA2690395C/en not_active Expired - Fee Related
- 1999-06-22 JP JP2000555637A patent/JP4113670B2/ja not_active Expired - Fee Related
- 1999-06-22 DE DE69942148T patent/DE69942148D1/de not_active Expired - Lifetime
- 1999-06-22 AU AU45792/99A patent/AU760854B2/en not_active Ceased
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0419387A1 (fr) * | 1989-09-21 | 1991-03-27 | IMMUNOTECH PARTNERS: Société en Commandite par Actions dite | Nouveaux dérivés hydrophiles, application au diagnostic et à la thérapeutique, kits diagnostiques ou thérapeutiques et réactifs immunologiques |
Non-Patent Citations (2)
| Title |
|---|
| BOSSLET, K. ET AL. INT. J. CANCER (1991)63 PP681-686 * |
| KRANENBORG, MHGC ET AL. CANCER RESEARCH (SUPPL)55 P5864S-67S * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2005211754B2 (en) * | 2004-02-11 | 2010-11-11 | Immunomedics, Inc. | Therapeutic and diagnostic conjugates for use with multispecific antibodies |
| AU2010249265B2 (en) * | 2004-02-11 | 2012-12-13 | Immunomedics, Inc. | Therapeutic and diagnostic conjugates for use with multispecific antibodies |
| AU2010249265C1 (en) * | 2004-02-11 | 2013-06-27 | Immunomedics, Inc. | Therapeutic and diagnostic conjugates for use with multispecific antibodies |
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| JP2002518460A (ja) | 2002-06-25 |
| CA2690395C (en) | 2013-11-05 |
| WO1999066951A3 (en) | 2000-06-15 |
| ATE460946T1 (de) | 2010-04-15 |
| WO1999066951A2 (en) | 1999-12-29 |
| CA2335364A1 (en) | 1999-12-29 |
| CA2335364C (en) | 2010-05-04 |
| DE69942148D1 (de) | 2010-04-29 |
| US7074405B1 (en) | 2006-07-11 |
| CA2690395A1 (en) | 1999-12-29 |
| AU4579299A (en) | 2000-01-10 |
| JP4113670B2 (ja) | 2008-07-09 |
| EP1089766A2 (en) | 2001-04-11 |
| EP1089766B1 (en) | 2010-03-17 |
| WO1999066951A8 (en) | 2001-02-01 |
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