CN105340834B - 动物模型及治疗分子 - Google Patents
动物模型及治疗分子 Download PDFInfo
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| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| ES2547142T5 (es) | 2010-02-08 | 2021-12-09 | Regeneron Pharma | Cadena ligera común de ratón |
| KR20210010942A (ko) | 2010-03-31 | 2021-01-28 | 아블렉시스, 엘엘씨 | 키메라 항체의 제조를 위한 비-인간 동물의 유전적 조작 |
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| US9043996B2 (en) | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| KR101926442B1 (ko) | 2011-10-28 | 2018-12-12 | 리제너론 파아마슈티컬스, 인크. | 키메라 주요 조직적합성 복합체 (mhc) ii 분자들을 발현하는 유전자 변형된 마우스 |
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| DK2770821T3 (da) * | 2011-10-28 | 2017-11-27 | Regeneron Pharma | Genetisk modificerede major histocompatibility-kompleks-mus |
| SMT202100243T1 (it) | 2011-10-28 | 2021-05-07 | Regeneron Pharma | Topi con recettori delle cellule t geneticamente modificati |
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| RU2664473C2 (ru) | 2012-03-16 | 2018-08-17 | Регенерон Фармасьютикалз, Инк. | ОТЛИЧНЫЕ ОТ ЧЕЛОВЕКА ЖИВОТНЫЕ, ЭКСПРЕССИРУЮЩИЕ ЧУВСТВИТЕЛЬНЫЕ К pН ПОСЛЕДОВАТЕЛЬНОСТИ ИММУНОГЛОБУЛИНОВ |
| US20140013456A1 (en) | 2012-03-16 | 2014-01-09 | Regeneron Pharmaceuticals, Inc. | Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same |
| EP2825036B1 (en) | 2012-03-16 | 2018-05-02 | Regeneron Pharmaceuticals, Inc. | Histidine engineered light chain antibodies and genetically modified rodents for generating the same |
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| US10251377B2 (en) | 2012-03-28 | 2019-04-09 | Kymab Limited | Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies |
| GB2502127A (en) * | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
| PT3597037T (pt) * | 2012-06-12 | 2021-06-01 | Regeneron Pharma | Animais não humanos humanizados com lócus de cadeia pesada de imunoglobulina restrito |
| EP2880055B1 (en) | 2012-08-03 | 2017-06-28 | Sab, Llc | Complex chromosome engineering for production of human antibodies in transgenic animals |
| PL3653049T3 (pl) * | 2012-12-14 | 2024-02-26 | Omniab, Inc. | Polinukleotydy kodujące przeciwciała gryzoni z ludzkimi idiotypami i zwierzęta je zawierające |
| WO2014124156A1 (en) * | 2013-02-06 | 2014-08-14 | Regeneron Pharmaceuticals, Inc. | B cell lineage based immunogen design with humanized animals |
| LT2958938T (lt) | 2013-02-20 | 2019-07-25 | Regeneron Pharmaceuticals, Inc. | Pelės, ekspresuojančios humanizuotus t ląstelių koreceptorius |
| SMT201800435T1 (it) | 2013-02-20 | 2018-09-13 | Regeneron Pharma | Animali non umani con sequenze della catena pesante dell’immunoglobulina modificate riferimento incrociato a domande correlate |
| US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
| EP2958937B1 (en) | 2013-02-22 | 2018-08-15 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized major histocompatibility complex |
| US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
| US9783618B2 (en) | 2013-05-01 | 2017-10-10 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
| US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
| ES2844174T3 (es) * | 2013-09-18 | 2021-07-21 | Kymab Ltd | Métodos, células y organismos |
| ES2993142T3 (en) | 2013-10-01 | 2024-12-23 | Kymab Ltd | Animal models and therapeutic molecules |
| JP6174811B2 (ja) | 2013-12-11 | 2017-08-02 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | ゲノムの標的改変のための方法及び組成物 |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| BR112016021572A2 (pt) | 2014-03-21 | 2017-10-03 | Regeneron Pharma | Métodos para preparar um animal não humano geneticamente modificado e para produzir proteínas de ligação, hibridoma, ácido nucleico, célula, e, proteína de ligação |
| ES2762640T3 (es) | 2014-03-21 | 2020-05-25 | Regeneron Pharma | Proteínas VL de unión a antígeno que exhiben diferentes características de unión |
| MX385689B (es) * | 2014-06-06 | 2025-03-18 | Regeneron Pharma | Métodos y composiciones para modificar un locus dirigido. |
| EA039787B1 (ru) * | 2014-07-14 | 2022-03-14 | Вашингтон Стейт Юниверсити | Сельскохозяйственное животное с абляцией клеток зародышевой линии и способы его получения |
| RU2017113134A (ru) | 2014-09-19 | 2018-10-19 | Регенерон Фармасьютикалз, Инк. | Химерные антигенные рецепторы |
| GB201418713D0 (en) | 2014-10-21 | 2014-12-03 | Kymab Ltd | Bindings Proteins |
| WO2016080399A1 (ja) * | 2014-11-20 | 2016-05-26 | 国立大学法人京都大学 | 哺乳動物の標的ゲノム領域にdnaをノックインする方法及び細胞 |
| FI3265123T3 (fi) | 2015-03-03 | 2023-01-31 | Vasta-aineita, käyttöjä & menetelmiä | |
| EP3271403A1 (en) | 2015-03-19 | 2018-01-24 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
| KR20240132525A (ko) | 2015-04-06 | 2024-09-03 | 리제너론 파아마슈티컬스, 인크. | 비인간 동물에서의 인간화 t 세포 매개 면역반응 |
| TWI752920B (zh) | 2015-10-12 | 2022-01-21 | 美商再生元醫藥公司 | 活化瘦素受體的抗原結合蛋白 |
| EP3384030A4 (en) | 2015-12-03 | 2019-07-03 | Trianni, Inc. | IMPROVED IMMUNOGLULINIVITY |
| WO2017136734A1 (en) | 2016-02-04 | 2017-08-10 | Trianni, Inc. | Enhanced production of immunoglobulins |
| PL3426271T3 (pl) | 2016-03-10 | 2025-11-24 | Cg Oncology, Inc. | Sposoby leczenia guzów litych terapią skojarzoną |
| US11066464B2 (en) | 2016-03-21 | 2021-07-20 | Kymab Limited | Anti-malarial antibodies that bind circumsporozoite protein |
| WO2017163049A1 (en) | 2016-03-21 | 2017-09-28 | Kymab Limited | Anti-malarial antibodies that bind circumsporozoite protein |
| GB2550114A (en) | 2016-05-03 | 2017-11-15 | Kymab Ltd | Methods, regimens, combinations & antagonists |
| MX2018014172A (es) | 2016-05-20 | 2019-08-22 | Regeneron Pharma | Métodos para romper la tolerancia inmunológica usando múltiples arn guías. |
| CN109640644B (zh) | 2016-06-03 | 2021-10-26 | 瑞泽恩制药公司 | 表达外源末端脱氧核苷酸转移酶的非人动物 |
| US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
| WO2018029474A2 (en) | 2016-08-09 | 2018-02-15 | Kymab Limited | Anti-icos antibodies |
| JP7461741B2 (ja) | 2016-06-20 | 2024-04-04 | カイマブ・リミテッド | 抗pd-l1およびil-2サイトカイン |
| JP7198752B2 (ja) | 2016-08-09 | 2023-01-04 | カイマブ・リミテッド | 抗icos抗体 |
| WO2018065552A1 (en) | 2016-10-06 | 2018-04-12 | Innate Pharma | Anti-cd39 antibodies |
| EP3534947A1 (en) | 2016-11-03 | 2019-09-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
| CA3038720A1 (en) | 2016-11-04 | 2018-07-12 | Regeneron Pharmaceuticals, Inc. | Non-human animals having an engineered immunoglobulin lambda light chain locus |
| AU2017382850B2 (en) * | 2016-12-21 | 2024-11-21 | Cephalon Llc | Antibodies that specifically bind to human IL-15 and uses thereof |
| CN118140872A (zh) | 2017-01-19 | 2024-06-07 | 欧莫诺艾比公司 | 来自具有多个重链免疫球蛋白基因座的转基因啮齿类动物的人抗体 |
| WO2018138297A1 (en) | 2017-01-27 | 2018-08-02 | Kymab Limited | Anti-opg antibodies |
| FI3583120T3 (fi) | 2017-02-17 | 2023-01-13 | Muunneltuja transferriinireseptoria sitovia polypeptidejä | |
| WO2018152285A1 (en) | 2017-02-17 | 2018-08-23 | Denali Therapeutics Inc. | Transferrin receptor transgenic models |
| US10457717B2 (en) | 2017-02-17 | 2019-10-29 | Denali Therapeutics Inc. | Engineered polypeptides |
| US10143187B2 (en) | 2017-02-17 | 2018-12-04 | Denali Therapeutics Inc. | Transferrin receptor transgenic models |
| GB2561352B (en) * | 2017-04-10 | 2023-01-18 | Genome Res Ltd | Animal models and therapeutic molecules |
| JP2020516590A (ja) | 2017-04-14 | 2020-06-11 | コールド ジェネシス, インコーポレイテッド | 膀胱癌の治療方法 |
| GB201709808D0 (en) | 2017-06-20 | 2017-08-02 | Kymab Ltd | Antibodies |
| GB201709970D0 (en) | 2017-06-22 | 2017-08-09 | Kymab Ltd | Bispecific antigen-binding molecules |
| CN111246882A (zh) * | 2017-08-01 | 2020-06-05 | 希望之城 | 抗il1rap抗体 |
| JP7383607B2 (ja) | 2017-10-20 | 2023-11-20 | フレッド ハッチンソン キャンサー センター | 選択された抗体を発現するように遺伝子改変されたb細胞を産生するシステム及び方法 |
| SG11202003044SA (en) | 2017-12-05 | 2020-04-29 | Regeneron Pharma | Non-human animals having an engineered immunoglobulin lambda light chain and uses thereof |
| GB201721338D0 (en) | 2017-12-19 | 2018-01-31 | Kymab Ltd | Anti-icos Antibodies |
| US11629189B2 (en) | 2017-12-19 | 2023-04-18 | Kymab Limited | Bispecific antibody for ICOS and PD-L1 |
| US20210051929A1 (en) | 2018-03-24 | 2021-02-25 | Regeneron Pharmaceuticals, Inc. | Genetically modified non-human animals for generating therapeutic antibodies against peptide-mhc complexes, methods of making and uses thereof |
| CA3093850A1 (en) | 2018-03-26 | 2019-10-03 | Regeneron Pharmaceuticals, Inc. | Humanized rodents for testing therapeutic agents |
| CN108486125B (zh) * | 2018-03-27 | 2024-01-05 | 重庆金迈博生物科技有限公司 | 一种核酸分子及其在制备人源单域抗体中的应用 |
| CN108486126A (zh) | 2018-03-27 | 2018-09-04 | 重庆金迈博生物科技有限公司 | 一种核酸分子及其在人源化抗体中的应用 |
| CA3094400A1 (en) | 2018-04-06 | 2019-10-10 | Regeneron Pharmaceuticals, Inc. | A leptin receptor agonist antibody for use in treating a metabolic dysfunction or hypoleptinemia |
| IL318469A (en) | 2018-06-14 | 2025-03-01 | Regeneron Pharma | Non-human animals capable of reorganizing transgenic DH-DH, and their uses |
| GB2576914A (en) * | 2018-09-06 | 2020-03-11 | Kymab Ltd | Antigen-binding molecules comprising unpaired variable domains produced in mammals |
| GB201815629D0 (en) | 2018-09-25 | 2018-11-07 | Kymab Ltd | Antagonists |
| GB201820687D0 (en) | 2018-12-19 | 2019-01-30 | Kymab Ltd | Antagonists |
| EP3927832A4 (en) * | 2019-02-18 | 2022-11-30 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | GENETICALLY MODIFIED NON-HUMAN ANIMALS WITH HUMANIZED IMMUNOGLOBULIN LOCUS |
| BR112021019128A2 (pt) | 2019-04-09 | 2022-01-04 | Abcuro Inc | Anticorpos de depleção de membro 1 da subfamília g do receptor tipo lectina de célula assassina (klrg1) |
| SG11202111258TA (en) * | 2019-06-05 | 2021-11-29 | Regeneron Pharma | Non-human animals having a limited lambda light chain repertoire expressed from the kappa locus and uses thereof |
| IL293314A (en) | 2019-11-29 | 2022-07-01 | Kymab Ltd | Treatment for physiological iron overload |
| CN114901678A (zh) | 2019-12-02 | 2022-08-12 | 瑞泽恩制药公司 | 肽-mhc ii蛋白构建体及其用途 |
| IL298632A (en) | 2020-06-02 | 2023-01-01 | Biocytogen Pharmaceuticals Beijing Co Ltd | Non-human animals genetically modified with a common light chain immunoglobulin locus |
| KR20230024822A (ko) * | 2020-06-25 | 2023-02-21 | 주식회사 휴맵 | 이형접합성 형질전환 동물 |
| TW202229328A (zh) | 2020-09-11 | 2022-08-01 | 美商再生元醫藥公司 | 抗原特異性抗體之鑑定及產生 |
| EP4248743A1 (en) | 2020-10-08 | 2023-09-27 | Humab Co. Ltd. | Method for preparing transgenic non-human animal having genome including humanized immunoglobulin gene locus |
| KR20230150779A (ko) * | 2020-12-09 | 2023-10-31 | 트리아니, 인코포레이티드 | 중쇄-단독 항체 |
| JP2024500399A (ja) | 2020-12-16 | 2024-01-09 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | ヒト化Fcアルファ受容体を発現するマウス |
| IL303868A (en) | 2020-12-23 | 2023-08-01 | Regeneron Pharma | Nucleic acids encoding anchor-modified antibodies and uses thereof |
| CN118511853A (zh) | 2021-03-31 | 2024-08-20 | 瑞泽恩制药公司 | 包含具有改善的tcrb组库多样性的人源化细胞免疫系统组分的基因修饰的小鼠 |
| EP4377346A1 (en) | 2021-07-26 | 2024-06-05 | Abcuro, Inc. | Killer cell lectin-like receptor subfamily g member 1 (klrg1) depleting antibodies |
| WO2023097236A1 (en) * | 2021-11-24 | 2023-06-01 | The Rockefeller University | Compositions and methods for generating immunoglobulin knock-in mice |
| GB202216503D0 (en) | 2022-11-05 | 2022-12-21 | Quadrucept Bio Ltd | Non-human vertebrates & cells |
| CN120813375A (zh) | 2023-01-30 | 2025-10-17 | 凯玛布有限公司 | 抗体 |
| EP4512243A1 (en) | 2023-08-21 | 2025-02-26 | Kymab Limited | Binding molecules |
| EP4548758A4 (en) * | 2023-09-15 | 2025-11-19 | Cyagen Biosciences Suzhou Inc | Genetically modified mice for antibody preparation and the method of preparation |
| WO2025147544A1 (en) | 2024-01-02 | 2025-07-10 | Abcuro, Inc. | Methods of treating inclusion body myositis (ibm) |
| WO2025166904A1 (zh) * | 2024-02-07 | 2025-08-14 | 赛业(苏州)生物科技有限公司 | 用于制备抗体的基因修饰小鼠及其制备方法 |
Family Cites Families (192)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US114985A (en) * | 1871-05-16 | Improvement in apparatus for cooling and preserving milk and other liquids | ||
| US5807715A (en) * | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| US5169939A (en) | 1985-05-21 | 1992-12-08 | Massachusetts Institute Of Technology & Pres. & Fellows Of Harvard College | Chimeric antibodies |
| US4720449A (en) | 1985-06-03 | 1988-01-19 | Polaroid Corporation | Thermal imaging method |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| WO1991000906A1 (en) | 1989-07-12 | 1991-01-24 | Genetics Institute, Inc. | Chimeric and transgenic animals capable of producing human antibodies |
| US6657103B1 (en) | 1990-01-12 | 2003-12-02 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6713610B1 (en) | 1990-01-12 | 2004-03-30 | Raju Kucherlapati | Human antibodies derived from immunized xenomice |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| ATE139258T1 (de) | 1990-01-12 | 1996-06-15 | Cell Genesys Inc | Erzeugung xenogener antikörper |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| AU8507191A (en) | 1990-08-29 | 1992-03-30 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US7041871B1 (en) | 1995-10-10 | 2006-05-09 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US7084260B1 (en) | 1996-10-10 | 2006-08-01 | Genpharm International, Inc. | High affinity human antibodies and human antibodies against human antigens |
| US6255458B1 (en) * | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
| AU2515992A (en) * | 1991-08-20 | 1993-03-16 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| EP0746609A4 (en) | 1991-12-17 | 1997-12-17 | Genpharm Int | NON-HUMAN TRANSGENIC ANIMALS CAPABLE OF PRODUCING HETEROLOGOUS ANTIBODIES |
| US5859307A (en) | 1992-02-04 | 1999-01-12 | Massachusetts Institute Of Technology | Mutant RAG-1 deficient animals having no mature B and T lymphocytes |
| NZ255101A (en) | 1992-07-24 | 1997-08-22 | Cell Genesys Inc | A yeast artificial chromosome (yac) vector containing an hprt minigene expressible in murine stem cells and genetically modified rodent therefor |
| DE4228162C1 (de) | 1992-08-25 | 1994-01-13 | Rajewsky Klaus Dr | Verfahren zum Ersetzen homologer Genabschnitte aus Säugern in der Keimbahn von nicht-menschlichen Säugern |
| JP4242447B2 (ja) | 1993-01-22 | 2009-03-25 | イミュネックス・コーポレーション | Cd40リガンド遺伝子の突然変異の検出および治療 |
| JPH08509612A (ja) | 1993-04-26 | 1996-10-15 | ジェンファーム インターナショナル インコーポレイテッド | 異種抗体を産生することができるトランスジェニック非ヒト動物 |
| DE4331162A1 (de) | 1993-09-14 | 1995-03-16 | Bayer Ag | Verfahren zur Herstellung von Cyaninfarbstoffen |
| US7119248B1 (en) | 1994-04-12 | 2006-10-10 | Miltenyi Biotec Gmbh | Antibodies against epitopes with homology to self antigens, methods of preparation and applications thereof |
| US6130364A (en) | 1995-03-29 | 2000-10-10 | Abgenix, Inc. | Production of antibodies using Cre-mediated site-specific recombination |
| AU3507297A (en) | 1996-06-26 | 1998-01-14 | Baylor College Of Medicine | Chromosomal rearrangement by insertion of two recombination substrates |
| ES2294799T3 (es) | 1996-06-27 | 2008-04-01 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw. | Moleculas de anticuerpos que interactuan especificamente con el sitio activo o hendidura de una molecula diana. |
| EP1500329B1 (en) | 1996-12-03 | 2012-03-21 | Amgen Fremont Inc. | Human antibodies that specifically bind human TNF alpha |
| US6319906B1 (en) | 1996-12-31 | 2001-11-20 | Isis Pharmaceuticals | Oligonucleotide compositions and methods for the modulation of the expression of B7 protein |
| AU751659B2 (en) | 1997-05-02 | 2002-08-22 | Genentech Inc. | A method for making multispecific antibodies having heteromultimeric and common components |
| US20020088019A1 (en) | 1997-09-02 | 2002-07-04 | Oron Yacoby-Zeevi | Methods of and pharmaceutical compositions for improving implantation of embryos |
| CA2306184C (en) | 1997-11-18 | 2007-05-15 | Pioneer Hi-Bred International, Inc. | Compositions and methods for genetic modification of plants |
| ES2337027T3 (es) | 1997-12-05 | 2010-04-20 | Europaisches Laboratorium Fur Molekularbiologie (Embl) | Nuevo metodo de clonacion de dna basado en el sistema de recombinacion rece-rect de e. coli. |
| EP0939120A1 (en) | 1998-02-27 | 1999-09-01 | Gesellschaft für biotechnologische Forschung mbH (GBF) | Method for marker-free repetitive DNA expression cassette exchange in the genome of cells or parts of cells |
| NZ525513A (en) | 1998-08-07 | 2004-09-24 | Pont Pharmaceuticals Du | Succinoylamino lactams as inhibitors of Abeta protein production |
| GB9823930D0 (en) | 1998-11-03 | 1998-12-30 | Babraham Inst | Murine expression of human ig\ locus |
| US6914128B1 (en) | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
| EP1173485A1 (en) | 1999-05-03 | 2002-01-23 | Medarex, Inc. | Human antibodies to staphylococcus aureus |
| US6833268B1 (en) | 1999-06-10 | 2004-12-21 | Abgenix, Inc. | Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions |
| US6355412B1 (en) | 1999-07-09 | 2002-03-12 | The European Molecular Biology Laboratory | Methods and compositions for directed cloning and subcloning using homologous recombination |
| US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
| CA2307503A1 (en) * | 2000-05-02 | 2001-11-02 | Carlos F. Barbas Iii | Peptides for use as a vaccine or treatment for hiv infection |
| IL154063A0 (en) * | 2000-07-21 | 2003-07-31 | Us Agriculture | Methods for the replacement, translocation and stacking of dna in eukaryotic genomes |
| US7105348B2 (en) | 2000-10-31 | 2006-09-12 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| 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 |
| AU2002219841A1 (en) * | 2000-11-16 | 2002-05-27 | Cornell Research Foundation Inc. | Vectors for conditional gene inactivation |
| ATE503012T1 (de) | 2000-11-17 | 2011-04-15 | Kyowa Hakko Kirin Co Ltd | Expression von xenogenen (humanen) immunglobulinen in klonierten, transgenen huftieren |
| ES2405944T3 (es) | 2000-11-30 | 2013-06-04 | Medarex, Inc. | Ácidos nucleicos que codifican las secuencias de inmunoglobulina humana reorganizadas a partir de ratones transcromoscómicos transgénicos zadas |
| EP1409646B1 (en) * | 2000-12-19 | 2012-06-13 | Altor BioScience Corporation | Transgenic animals comprising a humanized immune system |
| UY27087A1 (es) | 2001-01-05 | 2002-06-20 | Pfizer | Anticuerpos contra el receptor del factor de crecimiento similar a insulina |
| AUPR446701A0 (en) | 2001-04-18 | 2001-05-17 | Gene Stream Pty Ltd | Transgenic mammals for pharmacological and toxicological studies |
| JP2003000243A (ja) | 2001-06-25 | 2003-01-07 | Takachika Azuma | 変異体の製造法 |
| FR2827302B1 (fr) * | 2001-07-13 | 2003-10-10 | Genoway | Cellule et animal transgenique modelisant la presentation antigenique humaine et leurs utilisations |
| WO2003017336A2 (en) | 2001-08-13 | 2003-02-27 | Amberwave Systems Corporation | Dram trench capacitor and method of making the same |
| US20060199204A1 (en) | 2001-10-05 | 2006-09-07 | U.S. Epa | Genetic testing for male factor infertility |
| US20030108925A1 (en) | 2001-10-05 | 2003-06-12 | U.S. Epa | Genetic testing for male factor infertility |
| EP1461442B1 (en) * | 2001-11-30 | 2017-09-06 | Amgen Fremont Inc. | Transgenic animals bearing human ig lambda light chain genes |
| AU2003214842A1 (en) | 2002-01-17 | 2003-09-02 | Albert Einstein College Of Medicine Of Yeshiva University | Mutations caused by activation-induced cytidine deaminase |
| US8877901B2 (en) | 2002-12-13 | 2014-11-04 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
| AU2003250074B2 (en) | 2002-07-18 | 2010-09-09 | Merus N.V. | Recombinant production of mixtures of antibodies |
| EP1539946A4 (en) | 2002-09-09 | 2006-03-15 | California Inst Of Techn | METHOD AND COMPOSITIONS FOR PRODUCING HUMANIZED MICE |
| AU2003277075B2 (en) | 2002-10-01 | 2009-12-17 | Mitos Pharmaceuticals, Inc. | Nitroxide radioprotector formulations and methods of use |
| US7700356B2 (en) | 2002-11-08 | 2010-04-20 | The United States Of America As Represented By The Secretary Of Agriculture | System for gene targeting and producing stable genomic transgene insertions |
| DE10251918A1 (de) * | 2002-11-08 | 2004-05-19 | Horn, Carsten, Dipl.-Biochem. Dr. | Systeme zur Erzeugung stabiler genomischer Transgen-Insertionen |
| AR042145A1 (es) | 2002-11-27 | 2005-06-08 | Dow Agrociences Llc | Produccion de inmunoglobulinas en plantas con una fucocilacion reducida |
| GB2398784B (en) | 2003-02-26 | 2005-07-27 | Babraham Inst | Removal and modification of the immunoglobulin constant region gene cluster of a non-human mammal |
| CN1326878C (zh) * | 2003-04-29 | 2007-07-18 | 中国抗体制药有限公司 | 抗人非何杰金淋巴瘤嵌合抗体及其衍生物与应用 |
| US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| EP2395017A3 (en) | 2003-05-30 | 2012-12-19 | Merus B.V. | Design and use of paired variable regions of specific binding molecules |
| US7205148B2 (en) | 2003-06-11 | 2007-04-17 | Regeneron Pharmaceuticals, Inc. | Genome mutation by intron insertion into an embryonic stem cell genome |
| GB2403475B (en) | 2003-07-01 | 2008-02-06 | Oxitec Ltd | Stable integrands |
| MXPA06000562A (es) | 2003-07-15 | 2006-03-30 | Therapeutic Human Polyclonals | Loci de inmunoglobulina humanizada. |
| US7663017B2 (en) * | 2003-07-30 | 2010-02-16 | Institut Pasteur | Transgenic mice having a human major histocompatability complex (MHC) phenotype, experimental uses and applications |
| WO2005019463A1 (en) | 2003-08-11 | 2005-03-03 | Therapeutic Human Polyclonals, Inc. | Improved transgenesis with humanized immunoglobulin loci |
| US7604994B2 (en) | 2003-09-03 | 2009-10-20 | Morphotek, Inc. | Genetically altered antibody-producing cell lines with improved antibody characteristics |
| CA2445602C (en) | 2003-10-20 | 2014-01-14 | Campusgen Gmbh | Nucleotide sequence for creatinine deiminase and method of use |
| US20050191293A1 (en) | 2003-12-10 | 2005-09-01 | Shrikant Deshpande | IP-10 antibodies and their uses |
| US7625549B2 (en) | 2004-03-19 | 2009-12-01 | Amgen Fremont Inc. | Determining the risk of human anti-human antibodies in transgenic mice |
| MXPA06010673A (es) | 2004-03-19 | 2007-06-20 | Amgen Inc | Reduccion del riesgo de anticuerpos humanos anti-humano a traves de manipulacion del gen v. |
| CA2580336C (en) | 2004-07-22 | 2016-07-19 | Roger Kingdon Craig | Vh heavy chain only antibodies, and vh heavy chain only dimer compounds and uses thereof |
| FR2875239B1 (fr) | 2004-09-10 | 2007-07-20 | Inst Necker Ass Loi De 1901 | Procede pour l'acceleration des mutations somatiques et son application en proteomique |
| WO2006029459A1 (en) | 2004-09-13 | 2006-03-23 | Evogenix, Inc | Antibodies specific for hepatocellular carcinoma and other carcinomas and uses thereof |
| WO2006044492A2 (en) | 2004-10-14 | 2006-04-27 | Ingenious Targeting Laboratory, Inc. | Methods for generating rat embryo-derived cell lines and genetic modification of rat genome |
| PL2767161T3 (pl) | 2004-10-19 | 2018-09-28 | Regeneron Pharmaceuticals, Inc. | Sposób wytwarzania zwierzęcia homozygotycznego pod względem modyfikacji genetycznej |
| US20060117398A1 (en) | 2004-10-22 | 2006-06-01 | Roland Buelow | Suppression of endogenous immunoglobulin expression |
| WO2006055704A2 (en) | 2004-11-17 | 2006-05-26 | Curagen Corporation | Antibodies directed to ten-m proteins and uses thereof |
| KR101017301B1 (ko) | 2004-12-21 | 2011-02-28 | 메드임뮨 리미티드 | 앤지오포이에틴-2에 대한 항체 및 그의 용도 |
| WO2006117699A2 (en) | 2005-04-29 | 2006-11-09 | Innate Pharma | Transgenic animals and methods of making recombinant antibodies |
| WO2006122442A1 (en) * | 2005-05-14 | 2006-11-23 | Fudan University | Piggybac as a tool for genetic manipulation and analysis in vertebrates |
| EP1780272A1 (en) | 2005-10-27 | 2007-05-02 | GSF-Forschungszentrum für Umwelt und Gesundheit GmbH | Method for enhancing somatic hypermutation, gene conversion and class switch recombination |
| GB0601513D0 (en) | 2006-01-25 | 2006-03-08 | Univ Erasmus Medical Ct | Binding molecules 3 |
| SG169348A1 (en) * | 2006-01-25 | 2011-03-30 | Univ Erasmus Medical Ct | Generation of heavy-chain only antibodies in transgenic animals |
| US7462759B2 (en) | 2006-02-03 | 2008-12-09 | Pioneer Hi-Bred International, Inc. | Brittle stalk 2 gene family and related methods and uses |
| WO2007117410A2 (en) | 2006-03-31 | 2007-10-18 | Medarex, Inc. | Transgenic animals expressing chimeric antibodies for use in preparing human antibodies |
| US7846724B2 (en) | 2006-04-11 | 2010-12-07 | Hoffmann-La Roche Inc. | Method for selecting CHO cell for production of glycosylated antibodies |
| PL2374818T3 (pl) | 2006-06-02 | 2013-05-31 | Regeneron Pharma | Przeciwciała o wysokim powinowactwie przeciw ludzkiemu receptorowi IL 6 |
| CA2655344C (en) | 2006-06-27 | 2016-09-13 | Vaxdesign Corporation | Models for vaccine assessment |
| EP1878342A1 (en) | 2006-07-13 | 2008-01-16 | Institut Pasteur | Immunodeficient mice transgenic for HLA class I and HLA class II molecules and their uses |
| CN101501073A (zh) | 2006-08-22 | 2009-08-05 | G2英弗勒美欣私人有限公司 | 抗体制备方法 |
| US7778624B2 (en) * | 2006-09-01 | 2010-08-17 | Wanda Ying Li | Outdoor umbrella with audio system |
| CN101522716B (zh) | 2006-10-02 | 2013-03-20 | 瑞泽恩制药公司 | 抗人il-4受体的高亲和力人抗体 |
| US7732195B2 (en) * | 2006-11-01 | 2010-06-08 | Facet Biotech Corporation | Tethered vectors for cell surface immunoglobulin display |
| NO347649B1 (no) * | 2006-12-14 | 2024-02-12 | Regeneron Pharma | Humant antistoff eller antistoff fragment som spesifikt binder human deltaliknende ligand 4 (hDII4), nukleinsyremolekyl som koder for slike og vektor og vert-vektorsystemer, samt fremgangsmåte for fremstilling, sammensetning og anvendelse. |
| GB0700194D0 (en) | 2007-01-05 | 2007-02-14 | Univ Edinburgh | Humanisation of animals |
| JP5675109B2 (ja) | 2007-02-20 | 2015-02-25 | アナプティスバイオ インコーポレイティッド | ライブラリーの生成方法及びその使用 |
| CA2678888C (en) | 2007-02-21 | 2015-04-14 | University Of Massachusetts | Human antibodies against hepatitis c virus (hcv) and uses thereof |
| JP5779350B2 (ja) | 2007-03-27 | 2015-09-16 | シー レーン バイオテクノロジーズ, エルエルシー | 抗体代替軽鎖配列を含む構築物およびライブラリー |
| GB0706628D0 (en) | 2007-04-04 | 2007-05-16 | Univ Erasmus | Germ-line manipulation 1 |
| SG182144A1 (en) | 2007-06-01 | 2012-07-30 | Omt Inc | Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies |
| WO2009013620A2 (en) | 2007-06-11 | 2009-01-29 | Erasmus University Medical Center Rotterdam | Homologous recombination |
| AU2008282152B2 (en) | 2007-07-31 | 2013-12-19 | Regeneron Pharmaceuticals, Inc. | Human antibodies to human CD20 and method of using thereof |
| JP5588866B2 (ja) | 2007-08-10 | 2014-09-10 | メダレックス エル.エル.シー. | Hco32およびhco27、ならびに関連実施例 |
| US7988967B2 (en) | 2007-08-10 | 2011-08-02 | Regeneron Pharmaceuticals, Inc. | High affinity human antibodies to human nerve growth factor |
| SI2592148T1 (sl) * | 2007-10-12 | 2018-12-31 | F. Hoffmann-La Roche Ag | Izražanje beljakovin iz več nukleinskih kislin |
| WO2009076464A2 (en) * | 2007-12-10 | 2009-06-18 | Aliva Biopharmaceuticals, Inc. | Methods for sequential replacement of targeted region by homologous recombination |
| US8227577B2 (en) * | 2007-12-21 | 2012-07-24 | Hoffman-La Roche Inc. | Bivalent, bispecific antibodies |
| WO2009094178A2 (en) | 2008-01-25 | 2009-07-30 | Cabot Corporation | Method of preparing modified colored pigments |
| KR101409375B1 (ko) | 2008-01-31 | 2014-06-18 | 삼성전자주식회사 | 반도체 메모리장치의 블록 디코딩 회로 |
| EP2271207A2 (en) | 2008-03-26 | 2011-01-12 | ITI Scotland Limited | Efficient insertion of dna into embryonic stem cells |
| CA2721231C (en) | 2008-04-14 | 2015-10-06 | Innovative Targeting Solutions Inc. | Sequence diversity generation in immunoglobulins |
| EP2669298A3 (en) * | 2008-05-23 | 2014-02-26 | Ablexis, LLC | Single variable immunoglobulin domain comprising VL-DH-JL |
| ES2445193T3 (es) | 2008-06-27 | 2014-02-28 | Merus B.V. | Mamíferos no humanos productores de anticuerpos |
| WO2010039900A2 (en) * | 2008-09-30 | 2010-04-08 | Aliva Biopharmaceuticals, Inc. | Non-human mammals for the production of chimeric antibodies |
| JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
| KR101711222B1 (ko) | 2008-12-18 | 2017-02-28 | 에라스무스 유니버시티 메디컬 센터 로테르담 | 인간화 항체들을 발현하는 비-인간 유전자이식 동물들 및 그의 이용 |
| CA2983133A1 (en) | 2009-02-04 | 2010-08-12 | Molecular Innovations | Methods for screening candidate agents for modulating prorenin and renin, assays for detecting prorenin, and antibodies used therein |
| JP2012518398A (ja) | 2009-02-24 | 2012-08-16 | グラクソ グループ リミテッド | 抗原結合性構築物 |
| GB0905023D0 (en) | 2009-03-24 | 2009-05-06 | Univ Erasmus Medical Ct | Binding molecules |
| RU2537264C2 (ru) | 2009-04-03 | 2014-12-27 | Медикал Рисерч Каунсил | Мутанты индуцируемой активацией цитидиндеаминазы (aid) и способы их применения |
| EP3205723A1 (en) | 2009-06-26 | 2017-08-16 | i2 Pharmaceuticals, Inc. | Expression of surrogate light chains |
| GB0911846D0 (en) | 2009-07-08 | 2009-08-19 | Genome Res Ltd | Animal models and therapeutic molecules |
| ES2948572T3 (es) * | 2009-07-08 | 2023-09-14 | Kymab Ltd | Modelos de roedores y moléculas terapéuticas |
| GB0913102D0 (en) | 2009-07-28 | 2009-09-02 | Genome Res Ltd | Animal models and therapeutic molesules |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| AU2010271583B2 (en) | 2009-07-15 | 2015-02-12 | Kling Biotherapeutics B.V. | Means and methods for producing high affinity antibodies |
| JO3182B1 (ar) | 2009-07-29 | 2018-03-08 | Regeneron Pharma | مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2 |
| AU2010282508B2 (en) | 2009-08-13 | 2015-05-28 | Crystal Bioscience Inc. | Transgenic animal for production of antibodies having minimal CDRs |
| JP2013509878A (ja) | 2009-11-05 | 2013-03-21 | アナプティスバイオ インコーポレイティッド | 鎖シャフリングおよび任意に体細胞超変異を用いる、改善された抗原結合物質の生成方法 |
| WO2011062207A1 (ja) | 2009-11-17 | 2011-05-26 | 協和発酵キリン株式会社 | ヒト人工染色体ベクター |
| US20120269830A1 (en) | 2009-12-07 | 2012-10-25 | Lawrence Horowitz | Conjugates with improved pharmacokinetic properties |
| MY172472A (en) | 2009-12-10 | 2019-11-26 | Regeneron Pharma | Mice that make heavy chain antibodies |
| US20120021409A1 (en) | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| ES2547142T5 (es) | 2010-02-08 | 2021-12-09 | Regeneron Pharma | Cadena ligera común de ratón |
| CN103025344B (zh) | 2010-05-17 | 2016-06-29 | 桑格摩生物科学股份有限公司 | 新型dna-结合蛋白及其用途 |
| CA2802591A1 (en) | 2010-06-17 | 2011-12-22 | Kymab Limited | Animal models and therapeutic molecules |
| MY195217A (en) | 2010-06-22 | 2023-01-11 | Regeneron Pharma | MICE Expressing An Immunoglobulin Hybrid Light Chain |
| IL315833A (en) | 2010-08-02 | 2024-11-01 | Regeneron Pharma | Mice producing binding proteins containing VL regions |
| JP5997154B2 (ja) | 2010-08-16 | 2016-09-28 | ノビミューン エスアー | 多重特異性多価抗体の生成方法 |
| JO3375B1 (ar) | 2010-11-08 | 2019-03-13 | Regeneron Pharma | أجسام مضادة بشرية للجين a1 الشبيه بعامل النخر الورمي (tl1a) |
| SG191219A1 (en) | 2010-12-22 | 2013-07-31 | Genentech Inc | Anti-pcsk9 antibodies and methods of use |
| HUE024534T2 (hu) | 2011-02-25 | 2016-01-28 | Regeneron Pharma | ADAM6 egerek |
| IL273982B2 (en) | 2011-08-05 | 2023-03-01 | Regeneron Pharma | Humanized mice possess a universal light chain |
| EP2757875B2 (en) | 2011-09-19 | 2023-03-22 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| WO2013041845A2 (en) | 2011-09-19 | 2013-03-28 | Kymab Limited | Animals, repertoires & methods |
| WO2013045916A1 (en) | 2011-09-26 | 2013-04-04 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| US10246509B2 (en) | 2011-10-17 | 2019-04-02 | Regeneron Pharmaceuticals, Inc. | Restricted immunoglobulin heavy chain mice |
| US20130102031A1 (en) | 2011-10-25 | 2013-04-25 | Anaptysbio, Inc. | Use of somatic hypermutation to create insertion and deletion mutations in vitro |
| GB2496375A (en) | 2011-10-28 | 2013-05-15 | Kymab Ltd | A non-human assay vertebrate comprising human antibody loci and human epitope knock-in, and uses thereof |
| US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| GB201122047D0 (en) | 2011-12-21 | 2012-02-01 | Kymab Ltd | Transgenic animals |
| US20180295821A1 (en) | 2011-12-02 | 2018-10-18 | Kymab Limited | Transgenic Animals |
| SG11201403326VA (en) | 2011-12-20 | 2014-07-30 | Regeneron Pharma | Humanized light chain mice |
| WO2013116609A1 (en) | 2012-02-01 | 2013-08-08 | Regeneron Pharmaceuticals, Inc. | Humanized rodents that express heavy chains containing vl domains |
| WO2013130981A1 (en) | 2012-03-02 | 2013-09-06 | Regeneron Pharmaceuticals, Inc. | Human antibodies to clostridium difficile toxins |
| EP3165086A1 (en) | 2012-03-06 | 2017-05-10 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
| AU2013204581B2 (en) | 2012-03-16 | 2015-06-25 | Regeneron Pharmaceuticals, Inc. | Non-human animals expressing pH-sensitive immunoglobulin sequences |
| GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
| WO2013144567A1 (en) | 2012-03-28 | 2013-10-03 | Kymab Limited | Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies |
| US10251377B2 (en) | 2012-03-28 | 2019-04-09 | Kymab Limited | Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies |
| JO3820B1 (ar) | 2012-05-03 | 2021-01-31 | Regeneron Pharma | أجسام مضادة بشرية لـ fel d1وطرق لاستخدامها |
| SI3401400T1 (sl) | 2012-05-25 | 2019-10-30 | Univ California | Postopki in sestavki za RNA usmerjeno modifikacijo tarčne DNA in za RNA usmerjeno modulacijo prepisovanja |
| US8518765B1 (en) | 2012-06-05 | 2013-08-27 | Intermolecular, Inc. | Aqua regia and hydrogen peroxide HCl combination to remove Ni and NiPt residues |
| PT3597037T (pt) | 2012-06-12 | 2021-06-01 | Regeneron Pharma | Animais não humanos humanizados com lócus de cadeia pesada de imunoglobulina restrito |
| US8962913B2 (en) * | 2012-06-18 | 2015-02-24 | Regeneron Pharmaceuticals, Inc. | Humanized IL-7 rodents |
| ES2913136T3 (es) | 2012-11-09 | 2022-05-31 | Shenzhen Inst Of Molecular Crop Design | Gen de fertilidad y usos del mismo |
| BR112015013784A2 (pt) | 2012-12-12 | 2017-07-11 | Massachusetts Inst Technology | aplicação, manipulação e otimização de sistemas, métodos e composições para manipulação de sequência e aplicações terapêuticas |
| SMT201800435T1 (it) | 2013-02-20 | 2018-09-13 | Regeneron Pharma | Animali non umani con sequenze della catena pesante dell’immunoglobulina modificate riferimento incrociato a domande correlate |
| US10993420B2 (en) | 2013-03-15 | 2021-05-04 | Erasmus University Medical Center | Production of heavy chain only antibodies in transgenic mammals |
| US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
| US9783618B2 (en) * | 2013-05-01 | 2017-10-10 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| US20150033372A1 (en) | 2013-05-01 | 2015-01-29 | Kymab Limited | Human VpreB & Chimaeric Surrogate Light Chains in Transgenic Non-Human Vertebrates |
| US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
| US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
| US20140331339A1 (en) | 2013-05-03 | 2014-11-06 | Kymab Limited | Transgenic Non-Human Assay Vertebrates, Assays and Kits |
| US20140331344A1 (en) | 2013-05-03 | 2014-11-06 | Kymab Ltd. | Transgenic Animals |
| ES2993142T3 (en) | 2013-10-01 | 2024-12-23 | Kymab Ltd | Animal models and therapeutic molecules |
| GB201710984D0 (en) | 2017-07-07 | 2017-08-23 | Kymab Ltd | Cells, vertebrates, populations & methods |
| JP7087648B2 (ja) * | 2018-05-08 | 2022-06-21 | トヨタ自動車株式会社 | 電池パック |
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- 2020-05-08 US US16/870,365 patent/US20200352144A1/en not_active Abandoned
- 2020-05-08 US US16/870,413 patent/US20200375158A1/en not_active Abandoned
- 2020-06-15 JP JP2020102978A patent/JP6876854B2/ja active Active
- 2020-06-15 JP JP2020102977A patent/JP7141427B2/ja active Active
- 2020-06-15 JP JP2020102976A patent/JP6876853B2/ja active Active
- 2020-06-18 US US16/905,537 patent/US20200337280A1/en active Pending
- 2020-06-18 US US16/905,557 patent/US20200352145A1/en not_active Abandoned
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2021
- 2021-01-07 AU AU2021200079A patent/AU2021200079B2/en active Active
- 2021-08-04 HR HRP20211253TT patent/HRP20211253T1/hr unknown
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2022
- 2022-09-13 US US17/943,533 patent/US20240057572A1/en not_active Abandoned
- 2022-11-29 US US18/059,809 patent/US20230270088A1/en not_active Abandoned
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2023
- 2023-01-31 US US18/162,043 patent/US20230225302A1/en active Pending
- 2023-02-09 US US18/166,813 patent/US20230263143A1/en not_active Abandoned
- 2023-07-05 CY CY20231100315T patent/CY1126083T1/el unknown
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