DK2825036T3 - Histidinmanipulerede letkædeantistoffer og genetisk modificerede gnavere til generering heraf - Google Patents
Histidinmanipulerede letkædeantistoffer og genetisk modificerede gnavere til generering heraf Download PDFInfo
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- DK2825036T3 DK2825036T3 DK13713652.9T DK13713652T DK2825036T3 DK 2825036 T3 DK2825036 T3 DK 2825036T3 DK 13713652 T DK13713652 T DK 13713652T DK 2825036 T3 DK2825036 T3 DK 2825036T3
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- histidine
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Claims (20)
1. Genetisk modificeret gnaver, der i sin kimbane ved et endogent immunoglobulin-letkædelocus omfatter et immunoglobulin-letkædelocus, der omfatter en enkelt omarrangeret human immunoglobulin-letkæde-variabel-gensekvens afledt af en omarrangeret Vk1-39/Jk- eller VK3-20/JK-sekvens, hvor den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens er operativt bundet til en immunoglobulin-letkæde-konstant-region-gensekvens, og hvor (i) den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens omfatter VK1-39/Ji<-gensekvensen, der omfatter en udskiftning af mindst én ikke-histidinkodon med en histidinkodon designet til at udtrykke et histidin (a) ved en position udvalgt fra 105,106,108,111 og en kombination deraf; (b) ved positionerne 105,106,108 og 111 eller (c) ved positionerne 106,108 og 111; eller (ii) den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens omfatter Vk3-20/Jk omfattende en udskiftning af mindst én ikke-histidinkodon med en histidinkodon designet til at udtrykke et histidin (a) ved en position udvalgt fra 105,106,107,109 og en kombination deraf; (b) ved positionerne 105,106,107 og 109 eller (c) ved positionerne 105,106 og 109; hvor positionerne er i henhold til IMGT-nummerering.
2. Gnaver ifølge krav 1, hvor: immunoglobulin-letkæde-konstant-region-gensekvensen er en gnaver-immunoglobulin-letkæde-konstant-region-gensekvens, såsom en endogen gnaver-immunoglobulin-letkæde-konstant-region-gensekvens.
3. Gnaver ifølge et hvilket som helst af de foregående krav, hvor: gnaveren endvidere i sin kimbane omfatter en ikke-omarrangeret immunoglobulin-tungkæde-variabel-region-gensekvens, der omfatter humane Vh-, Dh- og JH-segmenter operativt bundet til en immunoglobulin-tungkæde-konstant-region-gensekvens, eventuelt hvor immunoglobulin-tungkæde-konstant-region-gensekvensen er en gnaver-immunoglobulin-tungkæde-konstant-region- gensekvens, såsom en endogen gnaver-immunoglobulin-konstant-region- gensekvens, eventuelt ved et endogent gnaver-immunoglobulin-tungkædelocus.
4. Gnaver ifølge et hvilket som helst af de foregående krav, hvor gnaveren mangler en funktionel ikke-omarrangeret immunoglobulin-letkæde-variabel-region.
5. Gnaver ifølge et hvilket som helst af de foregående krav, hvor den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens er afledt af en omarrangeret Vk1-39/Jk5- eller Vk3-20/Jk1-gensekvens.
6. Gnaver ifølge et hvilket som helst af de foregående krav, hvor gnaveren omfatter en population af antigenspecifikke antistoffer, der sammenlignet med en population af antigenspecifikke antistoffer genereret hos gnavere, som ikke omfatter en substitueret histidinkodon i en immunoglobulin-letkæde-variabel-region, er beriget med antigenspecifikke antistoffer, der udviser et fald i dissociativ halveringstid (ti/2) ved et surt pH sammenlignet med neutralt pH på mindst ca. 2-fold, mindst ca. 3-fold, mindst ca. 4-fold, mindst ca. 5-fold, mindst ca. 10-fold, mindst ca. 15-fold, mindst ca. 20-fold, mindst ca. 25-fold, mindst ca. 30-fold eller eventuelt ca. 30-fold eller mere.
7. Gnaver ifølge et hvilket som helst af de foregående krav, hvor gnaveren udtrykker et antistof, der omfatter et humant immunoglobulin-letkæde-variabelt-domæne med en substitution af mindst én ikke-histidinrest med et histidin ved en aminosyreposition kodet for af den mindst ene kodon, der er substitueret i immunoglobulin-letkæde-variabel-region-gensekvensen.
8. Gnaver ifølge et hvilket som helst af de foregående krav, hvor gnaveren er en rotte.
9. Gnaver ifølge et hvilket som helst af kravene 1 -7, hvor gnaveren er en mus.
10. Gnaver ifølge et hvilket som helst af kravene 8-9, hvor immunoglobulin-letkæde-konstant-region-gensekvensen er udvalgt fra en rotte- eller en muse- immunoglobulin-letkæde-konstant-region-gensekvens, eventuelt ved henholdsvis et endogent rotte-letkædelocus eller et endogent muse-letkædelocus; og hvor gnaveren eventuelt endvidere i sin kimbane omfatter en ikke-omarrangeret immunoglobulin-tungkæde-variabel-region-sekvens, der omfatter humane Vh-, Dh- og JH-segmenter operativt bundet til en immunoglobulin-tungkæde-konstant-region-gensekvens udvalgt fra en rotte- eller en muse-tungkæde-konstant-region-gensekvens; eventuelt henholdsvis ved et endogent rotte-tungkædelocus eller ved et endogent muse-immunoglobulin-tungkædelocus.
11. Gnaver ifølge krav 10, hvor gnaveren udtrykker en population af antigenspecifikke antistoffer som reaktion på et antigen af interesse, hvor samtlige antistoffer fra populationen omfatter: variable immunoglobulin-letkædedomæner afledt af den samme enkelte omarrangerede humane tungkæde-variabel-region-gensekvens, der omfatter en substitution af mindst én ikke-histidinkodon med en histidinkodon, og immunoglobulin-tungkæder, der omfatter humane tungkæde-variable-domæner afledt af et repertoire af humane tungkæde-V-, D- og J-segmenter.
12. Fremgangsmåde til frembringelse af gnaveren ifølge et hvilket som helst af de foregående krav, hvor fremgangsmåde omfatter udskiftning af samtlige funktionelle immunoglobulin-letkæde-variabel-region-gensekvenser ved et endogent immunoglobulin-letkædelocus hos gnaveren med den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens, hvor den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens er operativt bundet til en immunoglobulin-letkæde-konstant-region-gensekvens, såsom en endogen gnaver-letkæde-konstant-region-gensekvens ved det endogene gnaver-immunoglobulin-letkædelocus.
13. Fremgangsmåde til generering af et antistof, der har pH-afhængig binding til et antigen af interesse, hvilken fremgangsmåde omfatter: immunisering af en gnaver ifølge et hvilket som helst af kravene 1 til 11, eller en gnaver frembragt ved hjælp af fremgangsmåden ifølge krav 12 med et antigen af interesse; og opnåelse af en B-celle, der udtrykker et antistof, der binder til antigenet af interesse med en ønsket affinitet ved et neutralt pH, mens der udvises reduceret binding til antigenet af interesse ved et surt pH, og eventuelt (a) anvendelse af B-cellen til at frembringe et hybridom eller (b) isolering af DNA, der koder for antistoffet, fra B-cellen eller hybridomet og udskiftning af DNA’et i ekspressionsvektorer og transfektion af vektorerne ind i en værtscelle.
14. Fremgangsmåde ifølge krav 13, hvor antistoffet udviser en dissociativ halveringstid (ti/2) ved surt pH og 37 °C på ca. 2 minutter eller mindre.
15. Fremgangsmåde ifølge krav 13 eller 14, hvor fremgangsmåden er til frembringelse af et bispecifikt antistof, der har pH-afhængig binding til et eller flere antigener.
16. Fremgangsmåde ifølge krav 15, hvor fremgangsmåden omfatter: (a) identificering af en B-celle, der koder for et første tungkæde-variabelt-domæne, der binder en første epitop af interesse og udtrykker et antistof, der udviser pH-afhængig antigenbinding, og isolering af en første nukleinsyre, der koder for den variable tungkæderegion; og (b) identificering af en B-celle, der koder for et andet tungkæde-variabel-region-domæne, der binder en anden epitop af interesse og udtrykker et antistof, der udviser pH-afhængig antigenbinding, og isolering af en anden nukleinsyre, der koder for den anden tungkæde-variable-region; (c) udvælgelse af en tredje nukleinsyresekvens afledt af den enkelte omarrangerede humane immunoglobulin-letkæde-variabel-region-sekvens; og (d) ekspression af den første, anden og tredje nukleinsyresekvens, der udtrykker den første, anden og tredje nukleinsyresekvens for at danne det bispecifikke antistof.
17. Gnavercelle isoleret fra en gnaver ifølge et hvilket som helst af kravene 1 til 11, eller isoleret fra en gnaver frembragt ved fremgangsmåden ifølge krav 12, hvor cellen omfatter en enkelt omarrangeret human immunoglobulin-letkæde-variabel-gensekvens, der er operativt bundet til en immunoglobulin-letkæde-konstant-region-gensekvens og er afledt af en omarrangeret Vk1-39/Jk- eller Vk3-20/JK-sekvens, og hvor (i) den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens omfatter VKl-39/J«-gensekvensen, der omfatter en udskiftning af mindst én ikke-histidinkodon med en histidinkodon designet til at udtrykke et histidin (a) ved en position udvalgt fra 105, 106, 108, 111 og en kombination deraf (b) ved positionerne 105, 106, 108 og 111 eller (c) ved positionerne 106, 108 og 111; eller (ii) den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens omfatter Vk3-20/Jk omfattende en udskiftning af mindst én ikke-histidinkodon med en histidinkodon designet til at udtrykke et histidin (a) ved en position udvalgt fra 105,106,107, 109 og en kombination deraf; (b) ved positionerne 105, 106, 107, og 109, eller (c) ved positionerne 105, 106, og 109; hvor positionerne er i henhold til IMGT-nummerering.
18. Gnavercelle ifølge krav 17 hvor cellen er en B-celle.
19. Hybridom frembragt fra en B-celle isoleret fra gnaveren ifølge et hvilket som helst af kravene 1 til 11, eller en gnaver frembragt ved hjælp af fremgangsmåden ifølge krav 12, hvor hybridomet omfatter et immunoglobulin-letkædelocus, der omfatter en enkelt omarrangeret human immunoglobulin-letkæde-variabel-region-gensekvens, der er operativt bundet til en immunoglobulin-letkæde-konstant-region-gensekvens og er afledt af en omarrangeret Vk1-39/Jk-eller VK3-20/JK-sekvens, og hvor (i) den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens omfatter VKl-39/J«-gensekvensen, der omfatter en udskiftning af mindst én ikke-histidinkodon med en histidinkodon designet til at udtrykke et histidin (a) ved en position udvalgt fra 105, 106, 108, 111 og en kombination deraf (b) ved positionerne 105, 106, 108 og 111 eller (c) ved positionerne 106, 108 og 111; eller (ii) den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens omfatter Vk3-20/Jk omfattende en udskiftning af mindst én ikke-histidinkodon med en histidinkodon designet til at udtrykke et histidin (a) ved en position udvalgt fra 105,106,107,109 og en kombination deraf; (b) ved positionerne 105, 106, 107 og 109 eller (c) ved positionerne 105, 106 og 109; hvor positionerne er i henhold til IMGT-nummerering.
20. Gnavercelle, der omfatter et immunoglobulin-letkædelocus, der omfatter ved et endogent immunoglobulin-letkædelocus en enkelt omarrangeret human immunoglobulin-letkæde-variabel-gensekvens operativt bundet til en immunoglobulin-letkæde-konstant-region-sekvens og afledt af en omarrangeret Vk1-39/Jk- eller VK3-20/J«-sekvens, og hvor (i) den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens omfatter VKl-39/J«-gensekvensen, der omfatter en udskiftning af mindst én ikke-histidinkodon med en histidinkodon designet til at udtrykke et histidin (a) ved en position udvalgt fra 105, 106, 108, 111 og en kombination deraf (b) ved positionerne 105, 106, 108 og 111 eller (c) ved positionerne 106, 108 og 111; eller (ii) den enkelte omarrangerede humane immunoglobulin-letkæde-region-gensekvens omfatter Vk3-20/Jk omfattende en udskiftning af mindst én ikke-histidinkodon med en histidinkodon designet til at udtrykke et histidin (a) ved en position udvalgt fra 105,106,107, 109 og en kombination deraf; (b) ved positionerne 105, 106, 107 og 109, eller (c) ved positionerne 105, 106 og 109; hvor positionerne er i henhold til IMGT-nummerering.
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Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4001409A1 (en) | 2006-03-31 | 2022-05-25 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
| DK2202245T3 (da) | 2007-09-26 | 2016-11-21 | Chugai Pharmaceutical Co Ltd | Fremgangsmåde til modificering af et antistofs isoelektriske punkt via aminosyresubstitution i cdr |
| EP3521311A1 (en) | 2008-04-11 | 2019-08-07 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
| CA2819356C (en) | 2010-11-30 | 2023-01-24 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly |
| SG10201609665PA (en) | 2011-02-25 | 2017-01-27 | Chugai Pharmaceutical Co Ltd | FcɣRIIb-SPECIFIC Fc ANTIBODY |
| WO2013047748A1 (ja) | 2011-09-30 | 2013-04-04 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
| PL2627773T3 (pl) | 2011-10-17 | 2017-11-30 | Regeneron Pharmaceuticals, Inc. | Ograniczony łańcuch ciężki immonoglobuliny pochodzącej od myszy |
| CA2857159C (en) | 2011-11-30 | 2024-05-07 | Chugai Seiyaku Kabushiki Kaisha | Drug containing carrier into cell for forming immune complex |
| 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 |
| BR112014022855A2 (pt) | 2012-03-16 | 2017-07-18 | Regeneron Pharma | animal não humano geneticamente modificado, mamífero geneticamente modificado, e, método para fabricar um animal não humano |
| ME03551B (me) | 2012-06-12 | 2020-07-20 | Regeneron Pharma | Humanizovane nehumane živoтinje sa ograničenim lokusima imunoglobulinskog тeškog lanca |
| KR20230110836A (ko) | 2012-08-24 | 2023-07-25 | 추가이 세이야쿠 가부시키가이샤 | ＦｃγＲＩＩｂ 특이적 Ｆｃ영역 개변체 |
| US11236168B2 (en) | 2012-08-24 | 2022-02-01 | Chugai Seiyaku Kabushiki Kaisha | Mouse FcγammaRII-specific Fc antibody |
| DK2940135T5 (da) | 2012-12-27 | 2021-09-20 | Chugai Pharmaceutical Co Ltd | Heterodimeriseret polypeptid |
| WO2014130690A1 (en) | 2013-02-20 | 2014-08-28 | Regeneron Pharmaceuticals, Inc. | Non-human animals with modified immunoglobulin heavy chain sequences |
| EP2982689B1 (en) | 2013-04-02 | 2020-08-26 | Chugai Seiyaku Kabushiki Kaisha | Fc region variant |
| WO2014177460A1 (en) | 2013-04-29 | 2014-11-06 | F. Hoffmann-La Roche Ag | Human fcrn-binding modified antibodies and methods of use |
| EP3842455A1 (en) | 2014-01-15 | 2021-06-30 | F. Hoffmann-La Roche AG | Fc-region variants with improved protein a-binding |
| TWI681969B (zh) * | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對ｐｄ-１的人類抗體 |
| TWI680138B (zh) | 2014-01-23 | 2019-12-21 | 美商再生元醫藥公司 | 抗ｐｄ-ｌ１之人類抗體 |
| US10183994B2 (en) | 2014-06-30 | 2019-01-22 | Merck Patent Gmbh | Anti-TNFα antibodies with pH-dependent antigen binding for improved target clearence |
| ES2899894T3 (es) * | 2014-12-19 | 2022-03-15 | Chugai Pharmaceutical Co Ltd | Anticuerpos anti-C5 y métodos de uso |
| NZ730607A (en) | 2014-12-19 | 2022-07-01 | Chugai Pharmaceutical Co Ltd | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
| CN107428823B (zh) * | 2015-01-22 | 2021-10-26 | 中外制药株式会社 | 两种以上抗-c5抗体的组合与使用方法 |
| EA201791754A1 (ru) | 2015-02-05 | 2019-01-31 | Чугаи Сейяку Кабусики Кайся | АНТИТЕЛА, СОДЕРЖАЩИЕ ЗАВИСЯЩИЙ ОТ КОНЦЕНТРАЦИИ ИОНОВ АНТИГЕНСВЯЗЫВАЮЩИЙ ДОМЕН, ВАРИАНТЫ Fc-ОБЛАСТИ, IL-8-СВЯЗЫВАЮЩИЕ АНТИТЕЛА И ИХ ПРИМЕНЕНИЯ |
| CA2979702A1 (en) | 2015-03-19 | 2016-09-22 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
| EP3302553A4 (en) * | 2015-05-28 | 2019-03-06 | Bio-rad Laboratories, Inc. | AFFINITY LIGANDS AND ASSOCIATED METHODS |
| SG10201707267RA (en) * | 2015-12-18 | 2017-10-30 | Chugai Pharmaceutical Co Ltd | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
| RU2742606C2 (ru) * | 2015-12-18 | 2021-02-09 | Чугаи Сейяку Кабусики Кайся | Антитела к с5 и способы их применения |
| JP7141336B2 (ja) | 2015-12-25 | 2022-09-22 | 中外製薬株式会社 | 抗ミオスタチン抗体および使用方法 |
| RU2745563C2 (ru) | 2016-05-20 | 2021-03-29 | Регенерон Фармасьютикалс, Инк. | Способы преодоления иммунологической толерантности с использованием множества направляющих рнк |
| SI3462853T1 (sl) | 2016-06-03 | 2023-05-31 | Regeneron Pharmaceuticals, Inc. | Glodavci, ki izražajo eksogeno terminalno deoksinukleotidiltransferazo |
| CN109689099B (zh) | 2016-08-05 | 2023-02-28 | 中外制药株式会社 | 用于预防或治疗il-8相关疾病的组合物 |
| GB201707484D0 (en) * | 2017-05-10 | 2017-06-21 | Argenx Bvba | Method of preparing ph-dependent antibodies |
| CN111801351A (zh) * | 2018-03-14 | 2020-10-20 | 豪夫迈·罗氏有限公司 | 抗体亲和力成熟的方法 |
| CN112040769B (zh) * | 2018-03-24 | 2023-05-16 | 瑞泽恩制药公司 | 用于产生针对肽-mhc复合物的治疗抗体的经过基因修饰的非人动物、制造方法和用途 |
| CA3093850A1 (en) | 2018-03-26 | 2019-10-03 | Regeneron Pharmaceuticals, Inc. | Humanized rodents for testing therapeutic agents |
| KR102444180B1 (ko) | 2018-06-14 | 2022-09-16 | 리제너론 파마슈티칼스 인코포레이티드 | 면역글로불린 중쇄 암호화 서열에서 dh-dh 재배열 가능한 비인간 동물 |
| JP6935383B2 (ja) * | 2018-09-27 | 2021-09-15 | 公益財団法人実験動物中央研究所 | 免疫不全マウス |
| WO2020204040A1 (ja) | 2019-04-04 | 2020-10-08 | 日精エー・エス・ビー機械株式会社 | 樹脂製容器の製造方法、射出コア型、射出成形用金型および樹脂製容器の製造装置 |
| TW202110323A (zh) | 2019-06-05 | 2021-03-16 | 美商再生元醫藥公司 | 具有表現自κ 基因座的有限λ 輕鏈組庫的非人類動物及其用途 |
| AU2020374878A1 (en) * | 2019-10-28 | 2022-04-28 | Regeneron Pharmaceuticals, Inc. | Anti-hemagglutinin antibodies and methods of use thereof |
| IL300176A (en) * | 2020-08-04 | 2023-03-01 | Seagen Inc | Anti-CD228 antibodies and antibody-drug conjugates |
| CN116194142A (zh) | 2020-09-03 | 2023-05-30 | 瑞泽恩制药公司 | 通过施用pd-1抑制剂治疗癌症疼痛的方法 |
| CA3187680A1 (en) | 2020-09-11 | 2022-03-17 | Yashu Liu | Identification and production of antigen-specific antibodies |
| IL303626A (en) | 2020-12-16 | 2023-08-01 | Regeneron Pharma | Mice expressing human FC alpha receptors |
| TW202241934A (zh) | 2020-12-23 | 2022-11-01 | 美商再生元醫藥公司 | 編碼錨定修飾抗體之核酸及其用途 |
Family Cites Families (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| CA2075927A1 (en) | 1990-02-16 | 1991-08-17 | Victor A. Raso | Hybrid reagents capable of selectively releasing molecules into cells |
| US7041871B1 (en) | 1995-10-10 | 2006-05-09 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5545806A (en) * | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| DK0546073T3 (da) * | 1990-08-29 | 1998-02-02 | Genpharm Int | Frembringelse og anvendelse af transgene, ikke-humane dyr, der er i stand til at danne heterologe antistoffer |
| US7067284B1 (en) | 1992-01-27 | 2006-06-27 | The Scripps Research Institute | Methods for producing antibody libraries using universal or randomized immunoglobulin light chains |
| US5667988A (en) | 1992-01-27 | 1997-09-16 | The Scripps Research Institute | Methods for producing antibody libraries using universal or randomized immunoglobulin light chains |
| WO1994002602A1 (en) | 1992-07-24 | 1994-02-03 | Cell Genesys, Inc. | Generation of xenogeneic antibodies |
| US5999908A (en) | 1992-08-06 | 1999-12-07 | Abelow; Daniel H. | Customer-based product design module |
| AU2466895A (en) | 1995-04-28 | 1996-11-18 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| CA2230759C (en) | 1995-08-29 | 2012-02-21 | Kirin Beer Kabushiki Kaisha | Chimeric animal and method for producing the same |
| TR199902553T2 (xx) | 1997-04-14 | 2000-03-21 | Micromet Gesellschaft F�R Biomedizinische Forschung Mbh | �nsan v�cuduna kar�� antijen resept�rlerinin �retimi i�in yeni metod ve kullan�mlar�. |
| ES2246069T3 (es) | 1997-05-02 | 2006-02-01 | Genentech, Inc. | Procedimiento de preparacion de anticuerpos multiespecificos que tienen componentes comunes y multimericos. |
| US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| US6774279B2 (en) | 1997-05-30 | 2004-08-10 | Carnegie Institution Of Washington | Use of FLP recombinase in mice |
| EP1020522B1 (en) | 1997-10-03 | 2007-09-19 | Chugai Seiyaku Kabushiki Kaisha | Natural human antibody |
| GB9823930D0 (en) | 1998-11-03 | 1998-12-30 | Babraham Inst | Murine expression of human ig\ locus |
| AU9096001A (en) | 2000-09-08 | 2002-03-22 | Amgen Inc | G-csf analog compositions and methods |
| 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 |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US20030108925A1 (en) | 2001-10-05 | 2003-06-12 | U.S. Epa | Genetic testing for male factor infertility |
| US20060199204A1 (en) | 2001-10-05 | 2006-09-07 | U.S. Epa | Genetic testing for male factor infertility |
| US7435871B2 (en) | 2001-11-30 | 2008-10-14 | Amgen Fremont Inc. | Transgenic animals bearing human Igλ light chain genes |
| EP1511861A4 (en) | 2002-06-12 | 2007-12-05 | Genencor Int | METHODS AND BINDING COMPOSITIONS DEPENDENT FROM THE MEDIUM OF A TARGET AGENT TO A TARGET |
| US20060088838A1 (en) | 2002-06-12 | 2006-04-27 | Murray Christopher J | Methods for improving a binding characteristic of a molecule |
| DK2314629T4 (da) | 2002-07-18 | 2023-02-06 | Merus Nv | Rekombinant produktion af blandinger af antistoffer |
| EP1439234A1 (en) | 2003-01-08 | 2004-07-21 | ARTEMIS Pharmaceuticals GmbH | Targeted transgenesis using the rosa26 locus |
| WO2004065611A1 (ja) | 2003-01-21 | 2004-08-05 | Chugai Seiyaku Kabushiki Kaisha | 抗体の軽鎖スクリーニング方法 |
| US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| AU2004242614B2 (en) | 2003-05-30 | 2011-09-22 | Merus N.V. | Fab library for the preparation of anti vegf and anti rabies virus fabs |
| CA2532117C (en) | 2003-07-15 | 2012-07-10 | Therapeutic Human Polyclonals, Inc. | Humanized immunoglobulin loci |
| CN1560081A (zh) | 2004-02-17 | 2005-01-05 | 大连帝恩生物工程有限公司 | 用能产生人IgGl重链－κ轻链小鼠作为制备人源化单克隆抗体和应用 |
| WO2005092925A2 (en) | 2004-03-24 | 2005-10-06 | Xencor, Inc. | Immunoglobulin variants outside the fc region |
| US20050260711A1 (en) | 2004-03-30 | 2005-11-24 | Deepshikha Datta | Modulating pH-sensitive binding using non-natural amino acids |
| ES2667169T3 (es) | 2004-10-19 | 2018-05-09 | Regeneron Pharmaceuticals, Inc. | Método para generar un animal no humano homocigótico para una modificación genética |
| CA2585043A1 (en) | 2004-10-22 | 2007-01-04 | Medimmune, Inc. | High affinity antibodies against hmgb1 and methods of use thereof |
| EP1874817A2 (en) | 2005-04-29 | 2008-01-09 | Innate Pharma | Transgenic animals and methods of making recombinant antibodies |
| EP1966241A2 (en) | 2005-12-05 | 2008-09-10 | Symphogen A/S | Anti-orthopoxvirus recombinant polyclonal antibody |
| AU2007235496B2 (en) | 2006-03-31 | 2013-11-21 | E. R. Squibb & Sons, L.L.C. | Transgenic animals expressing chimeric antibodies for use in preparing human antibodies |
| MY159787A (en) | 2006-06-02 | 2017-01-31 | Regeneron Pharma | High affinity antibodies to human il-6 receptor |
| PL2769992T3 (pl) | 2006-10-02 | 2021-08-02 | Regeneron Pharmaceuticals, Inc. | Przeciwciała ludzkie o wysokim powinowactwie względem ludzkiego receptora IL-4 |
| US7608693B2 (en) | 2006-10-02 | 2009-10-27 | Regeneron Pharmaceuticals, Inc. | High affinity human antibodies to human IL-4 receptor |
| US20100034194A1 (en) | 2006-10-11 | 2010-02-11 | Siemens Communications Inc. | Eliminating unreachable subscribers in voice-over-ip networks |
| RU2448979C2 (ru) | 2006-12-14 | 2012-04-27 | Ридженерон Фармасьютикалз, Инк. | Антитела человека к дельта-подобному лиганду-4 человека |
| JP2010521170A (ja) | 2007-03-13 | 2010-06-24 | ナショナル ジューイッシュ ヘルス | 抗体の生成方法 |
| ITMI20071522A1 (it) | 2007-07-27 | 2009-01-28 | Areta Internat S R L | Vaccino idiotipico |
| CA2697193C (en) | 2007-09-14 | 2017-06-06 | Adimab, Inc. | Rationally designed, synthetic antibody libraries and uses therefor |
| DK2202245T3 (da) | 2007-09-26 | 2016-11-21 | Chugai Pharmaceutical Co Ltd | Fremgangsmåde til modificering af et antistofs isoelektriske punkt via aminosyresubstitution i cdr |
| DK2222706T4 (da) | 2007-12-14 | 2016-11-21 | Novo Nordisk As | Antistoffer der binder til NKG2D og brugen heraf |
| EP3521311A1 (en) * | 2008-04-11 | 2019-08-07 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
| WO2009139822A1 (en) * | 2008-05-01 | 2009-11-19 | Amgen Inc. | Anti-hepcidin antibodies and methods of use |
| KR102261586B1 (ko) | 2008-06-27 | 2021-06-08 | 메뤼스 엔.페. | 항체 생산 비-인간 포유동물 |
| TWI516501B (zh) | 2008-09-12 | 2016-01-11 | 禮納特神經系統科學公司 | Ｐｃｓｋ９拮抗劑類 |
| TWI440469B (zh) | 2008-09-26 | 2014-06-11 | Chugai Pharmaceutical Co Ltd | Improved antibody molecules |
| KR102362774B1 (ko) | 2008-09-30 | 2022-02-15 | 아블렉시스, 엘엘씨 | 키메라 항체의 제조를 위한 인간 이외의 포유동물 |
| 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). |
| MX2011007660A (es) | 2008-12-18 | 2011-08-17 | Kingdon Craig R | Animales transgenicos no humanos que expresan anticuerpos humanizados y usos de los mismos. |
| KR20140056401A (ko) | 2009-05-07 | 2014-05-12 | 볼보 컨스트럭션 이큅먼트 에이비 | 작업 기계 및 작업 기계를 작동하기 위한 방법 |
| JP5804521B2 (ja) | 2009-05-29 | 2015-11-04 | モルフォシス・アー・ゲー | コレクション及びその使用方法 |
| CN103833855A (zh) | 2009-06-26 | 2014-06-04 | 瑞泽恩制药公司 | 容易地分离的具有天然免疫球蛋白形式的双特异性抗体 |
| DK3622813T3 (da) | 2009-07-08 | 2021-05-03 | Kymab Ltd | Dyremodeller og terapeutiske molekyler |
| US20120204278A1 (en) | 2009-07-08 | 2012-08-09 | Kymab Limited | Animal models and therapeutic molecules |
| MX2012000731A (es) | 2009-07-16 | 2012-05-08 | Univ Wageningen | Regulacion de deficiencia y tolerancia de zinc en plantas. |
| GB2472108B (en) | 2009-08-27 | 2011-07-13 | Budha Singh Dhinjan | Wall bead |
| DK2954779T3 (da) | 2009-12-10 | 2019-05-13 | Regeneron Pharma | Mus, der frembringer tungkædeantistoffer |
| US10143186B2 (en) * | 2010-02-08 | 2018-12-04 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| US20120021409A1 (en) | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| US20130185821A1 (en) | 2010-02-08 | 2013-07-18 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| BR112012022917A2 (pt) * | 2010-03-11 | 2017-01-10 | Pfizer | anticorpos com ligação a antígeno dependente de ph |
| TWI667257B (zh) | 2010-03-30 | 2019-08-01 | 中外製藥股份有限公司 | 促進抗原消失之具有經修飾的ＦｃＲｎ親和力之抗體 |
| CN105695415A (zh) | 2010-06-17 | 2016-06-22 | 科马布有限公司 | 动物模型及治疗分子 |
| KR20220150430A (ko) | 2010-06-22 | 2022-11-10 | 리제너론 파아마슈티컬스, 인크. | 사람 람다 가변 영역 및 마우스 불변 영역을 갖는 경쇄를 발현하는 마우스 |
| DE12192727T1 (de) | 2011-02-25 | 2013-07-11 | Regeneron Pharmaceuticals, Inc. | ADAM6 Mäuse |
| PT3572517T (pt) | 2011-08-05 | 2021-06-23 | Regeneron Pharma | Murganhos da cadeia leve universal humanizada |
| EP3778889A1 (en) | 2011-09-30 | 2021-02-17 | Chugai Seiyaku Kabushiki Kaisha | Ion concentration-dependent binding molecule library |
| GB201122047D0 (en) | 2011-12-21 | 2012-02-01 | Kymab Ltd | Transgenic animals |
| MX353278B (es) | 2012-03-06 | 2018-01-05 | Regeneron Pharma | Raton con cadena ligera comun. |
| BR112014022855A2 (pt) | 2012-03-16 | 2017-07-18 | Regeneron Pharma | animal não humano geneticamente modificado, mamífero geneticamente modificado, e, método para fabricar um animal não humano |
| 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 |
| CN104582476B (zh) | 2012-06-05 | 2017-03-08 | 瑞泽恩制药公司 | 使用共同轻链制备完全人双特异性抗体的方法 |
| WO2014130690A1 (en) | 2013-02-20 | 2014-08-28 | Regeneron Pharmaceuticals, Inc. | Non-human animals with modified immunoglobulin heavy chain sequences |
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