RU2664185C2 - Гуманизированные грызуны, которые экспрессируют тяжелые цепи, содержащие домены vl - Google Patents
Гуманизированные грызуны, которые экспрессируют тяжелые цепи, содержащие домены vl Download PDFInfo
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009143472A2 (en) * | 2008-05-23 | 2009-11-26 | Aliva Biopharmaceuticals, Inc. | Method of generating single vl domain antibodies in transgenic animals |
| RU2425880C2 (ru) * | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
| WO2011158009A1 (en) * | 2010-06-17 | 2011-12-22 | Kymab Limited | Animal models and therapeutic molecules |
Family Cites Families (28)
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| WO2002012437A2 (en) * | 2000-08-03 | 2002-02-14 | Schooten Wim Van | Production of humanized antibodies in transgenic animals |
| US6596541B2 (en) * | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US7105348B2 (en) | 2000-10-31 | 2006-09-12 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| CN101016543A (zh) * | 2000-11-17 | 2007-08-15 | 罗切斯特大学 | 筛选编码抗原特异性免疫球蛋白分子或其抗原特异性片段的多核苷酸的方法 |
| US7473557B2 (en) | 2001-06-06 | 2009-01-06 | Regeneron Pharmaceuticals, Inc. | Method for targeting transcriptionally active loci |
| CN100526455C (zh) * | 2001-12-21 | 2009-08-12 | 斯路姆-X股份有限公司 | 用于体外分离和培养具有种系传递能力的胚胎干细胞(es)细胞系的组合物 |
| US20050246782A1 (en) * | 2002-03-22 | 2005-11-03 | Origen Therapeutics | Transgenic aves producing human polyclonal antibodies |
| CN1852925A (zh) * | 2003-07-15 | 2006-10-25 | 人类多克隆治疗公司 | 人源化免疫球蛋白基因座 |
| PT1802193E (pt) | 2004-10-19 | 2014-06-23 | Regeneron Pharma | Método para gerar um murganho homozigótico para uma modificação genética |
| WO2006047367A2 (en) * | 2004-10-22 | 2006-05-04 | Therapeutic Human Polyclonals, Inc. | Suppression of endogenous immunoglubolin expression in non-human transgenic animals |
| WO2007117410A2 (en) * | 2006-03-31 | 2007-10-18 | Medarex, Inc. | Transgenic animals expressing chimeric antibodies for use in preparing human antibodies |
| EP2064325B1 (en) * | 2006-09-01 | 2011-12-07 | Therapeutic Human Polyclonals, Inc. | Enhanced expression of human or humanized immunoglobulin in non-human transgenic animals |
| CA2697448C (en) * | 2007-08-30 | 2019-06-11 | The Burnet Institute | Dendritic cell marker and uses thereof |
| TWI563002B (en) * | 2007-09-26 | 2016-12-21 | Chugai Pharmaceutical Co Ltd | Antibody constant region mutant |
| US7659842B2 (en) | 2007-10-24 | 2010-02-09 | Infineon Technologies Ag | Quantization error reduction in PWM full-MASH converters |
| CA2729095C (en) * | 2008-06-27 | 2018-12-04 | Merus B.V. | Method for producing a transgenic murine mammal |
| US20100069262A1 (en) * | 2008-08-29 | 2010-03-18 | Symphogen A/S | Method for Cloning Avian-Derived Antibodies |
| EP2394159B1 (en) * | 2009-02-04 | 2018-09-26 | Molecular Innovations | Assays for detecting prorenin, and antibodies used therein |
| CN102638971B (zh) * | 2009-07-08 | 2015-10-07 | 科马布有限公司 | 动物模型及治疗分子 |
| IL315833A (en) * | 2010-08-02 | 2024-11-01 | Regeneron Pharma | Mice producing binding proteins containing VL regions |
| MX375115B (es) * | 2011-02-25 | 2025-03-06 | Regeneron Pharma | Ratones de una desintegrina y metaloproteasa 6 (adam6). |
| CN107602696B (zh) * | 2011-08-05 | 2022-05-13 | 瑞泽恩制药公司 | 人源化的通用轻链小鼠 |
| SI2793567T1 (sl) * | 2011-12-20 | 2019-05-31 | Regeneron Pharmaceuticals, Inc. | Humanizirane lahkoverižne miši |
| EP3912465A1 (en) * | 2012-02-01 | 2021-11-24 | Regeneron Pharmaceuticals, Inc. | Humanized rodents that express heavy chains containing vl domains |
| EP3912464A1 (en) * | 2012-06-12 | 2021-11-24 | Regeneron Pharmaceuticals, Inc. | Humanized non-human animals with restricted immunoglobulin heavy chain loci |
| PL4082334T3 (pl) * | 2016-11-04 | 2025-08-11 | Regeneron Pharmaceuticals, Inc. | Zwierzęta inne niż człowiek posiadające zmodyfikowane locus łańcucha lekkiego lambda immunoglobuliny |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009143472A2 (en) * | 2008-05-23 | 2009-11-26 | Aliva Biopharmaceuticals, Inc. | Method of generating single vl domain antibodies in transgenic animals |
| RU2425880C2 (ru) * | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
| WO2011158009A1 (en) * | 2010-06-17 | 2011-12-22 | Kymab Limited | Animal models and therapeutic molecules |
Non-Patent Citations (1)
| Title |
|---|
| HAN C. et al., Comprehensive analysis of reproductive ADAMs: relationship of ADAM4 and ADAM6 with an ADAM complex required for fertilization in mice, Biol Reprod., 2009, Vol.80, N.5, pp.1001-1008. * |
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