RU2290441C2 - Способ генетической модификации интересующего эндогенного гена или хромосомного локуса (варианты) и его использование - Google Patents

Способ генетической модификации интересующего эндогенного гена или хромосомного локуса (варианты) и его использование Download PDF

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RU2290441C2
RU2290441C2 RU2003116125/13A RU2003116125A RU2290441C2 RU 2290441 C2 RU2290441 C2 RU 2290441C2 RU 2003116125/13 A RU2003116125/13 A RU 2003116125/13A RU 2003116125 A RU2003116125 A RU 2003116125A RU 2290441 C2 RU2290441 C2 RU 2290441C2
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cells
gene
chromosomal locus
endogenous gene
genetically modified
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RU2003116125A (ru
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Арис Н. ЭКОНОМИДИС (US)
Арис Н. ЭКОНОМИДИС
Эндрю Дж. МЕРФИ (US)
Эндрю Дж. МЕРФИ
Дэвид М. ВАЛЕНСУЭЛА (US)
Дэвид М. ВАЛЕНСУЭЛА
Дэвид ФРЕНДЬЮЭЙ (US)
Дэвид ФРЕНДЬЮЭЙ
Джордж Д. ЯНКОПУЛОС (US)
Джордж Д. Янкопулос
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Ридженерон Фармасьютикалз, Инк.
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
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    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/87Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90Stable introduction of foreign DNA into chromosome
    • C12N15/902Stable introduction of foreign DNA into chromosome using homologous recombination
    • C12N15/907Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/05Animals comprising random inserted nucleic acids (transgenic)
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00Animals characterised by species
    • A01K2227/10Mammal
    • A01K2227/105Murine

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RU2003116125/13A 2000-10-31 2001-10-31 Способ генетической модификации интересующего эндогенного гена или хромосомного локуса (варианты) и его использование RU2290441C2 (ru)

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US24466500P 2000-10-31 2000-10-31
US60/244,665 2000-10-31
US09/732,234 US6586251B2 (en) 2000-10-31 2000-12-07 Methods of modifying eukaryotic cells
US09/732,234 2000-12-07

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RU2003116125A RU2003116125A (ru) 2005-01-20
RU2290441C2 true RU2290441C2 (ru) 2006-12-27

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US (1) US6586251B2 (OSRAM)
EP (1) EP1399575B1 (OSRAM)
JP (7) JP5339566B2 (OSRAM)
KR (1) KR100833136B1 (OSRAM)
CN (1) CN100497642C (OSRAM)
AT (1) ATE332388T1 (OSRAM)
AU (2) AU2004802A (OSRAM)
BR (1) BRPI0115096B1 (OSRAM)
CA (1) CA2426398C (OSRAM)
CZ (1) CZ304856B6 (OSRAM)
DE (1) DE60121372T2 (OSRAM)
HU (1) HU227639B1 (OSRAM)
MX (1) MXPA03003797A (OSRAM)
NO (1) NO332300B1 (OSRAM)
NZ (1) NZ525511A (OSRAM)
PL (1) PL204759B1 (OSRAM)
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2514672C2 (ru) * 2008-06-27 2014-04-27 Эвоник Рем ГмбХ Рекомбинантная клетка, продуцирующая 2-гидроксиизомасляную кислоту
RU2656159C2 (ru) * 2012-09-07 2018-05-31 ДАУ АГРОСАЙЕНСИЗ ЭлЭлСи Локусы функциональности fad2 и соответствующие специфичные к участку-мишени связывающие белки, способные индуцировать направленные разрывы
RU2676708C2 (ru) * 2013-04-16 2019-01-10 Регенерон Фармасьютикалс, Инк. Направленная модификация генома крысы
RU2685914C1 (ru) * 2013-12-11 2019-04-23 Регенерон Фармасьютикалс, Инк. Способы и композиции для направленной модификации генома
RU2734770C2 (ru) * 2014-11-21 2020-10-23 Регенерон Фармасьютикалз, Инк. Способы и композиции для нацеленной генетической модификации с использованием парных гидовых рнк
RU2749717C2 (ru) * 2015-11-24 2021-06-16 Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед Способ временной трансфекции для продуцирования ретровируса
RU2751237C1 (ru) * 2020-06-10 2021-07-12 Регенерон Фармасьютикалс, Инк. Способы и композиции для направленной модификации генома
RU2752498C2 (ru) * 2015-11-24 2021-07-28 Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед Стабильные клеточные линии для продуцирования ретровирусов

Families Citing this family (207)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6908744B1 (en) * 2000-03-14 2005-06-21 Regeneron Pharmaceuticals, Inc. Methods of stimulating cartilage formation
DK1311661T3 (da) * 2000-08-14 2012-11-26 Us Gov Health & Human Serv Forøget homolog rekombination medieret ved lambda-rekombinationsproteiner
US6586251B2 (en) * 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
GB0110029D0 (en) 2001-04-24 2001-06-13 Grosveld Frank Transgenic animal
EP2361966A1 (en) 2002-05-17 2011-08-31 Mount Sinai School of Medicine of New York University Mesoderm and definitive endoderm cell populations
USRE47770E1 (en) 2002-07-18 2019-12-17 Merus N.V. Recombinant production of mixtures of antibodies
SI1523496T1 (sl) 2002-07-18 2011-11-30 Merus B V Rekombinantno proizvajanje zmesi protiteles
JP2005537805A (ja) * 2002-09-09 2005-12-15 カリフォルニア インスティチュート オブ テクノロジー ヒト化マウスを作成するための方法および組成物
WO2004067725A2 (en) * 2003-01-30 2004-08-12 Regeneron Pharmaceuticals, Inc. Methods of identifying modulators of nmur2-mediated activity
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
PT2767161T (pt) 2004-10-19 2018-04-20 Regeneron Pharma Método para gerar um animal homozigótico para uma modificação genética
US20060117396A1 (en) * 2004-11-30 2006-06-01 Murphy Andrew J Assay methods for identifying modulators of OPSDL3 and transgenic knockouts
HUE041818T2 (hu) 2007-03-22 2019-05-28 Biogen Ma Inc Kötõ proteinek, beleértve az antitesteket, CD154-et specifikusan kötõ antitest származékokat és antitest fragmenseket is, és alkalmazásaik
PT2336329E (pt) 2007-06-01 2012-12-24 Omt Inc Composições e métodos para inibição de genes de imunoglobulina endógena e produção de anticorpos transgénicos humanos idiotípicos
US20110119779A1 (en) * 2007-12-10 2011-05-19 Aliva Biopharmaceuticals, Inc. Methods for sequential replacement of targeted region by homologous recombination
AU2009238629C1 (en) * 2008-04-14 2015-04-30 Sangamo Therapeutics, Inc. Linear donor constructs for targeted integration
US20090328240A1 (en) * 2008-06-24 2009-12-31 Sing George L Genetically modified mice as predictors of immune response
KR101987351B1 (ko) 2008-09-30 2019-06-10 아블렉시스, 엘엘씨 키메라 항체의 제조를 위한 인간 이외의 포유동물
PT2564695E (pt) 2009-07-08 2015-06-03 Kymab Ltd Modelos animais e moléculas terapêuticas
US9445581B2 (en) 2012-03-28 2016-09-20 Kymab Limited Animal models and therapeutic molecules
ES2700852T3 (es) 2009-10-06 2019-02-19 Regeneron Pharma Ratones modificados genéticamente e injerto
AU2010319894B2 (en) 2009-10-29 2015-03-05 Regeneron Pharmaceuticals, Inc. Multifunctional alleles
CN104131035A (zh) 2009-12-10 2014-11-05 瑞泽恩制药公司 生产重链抗体的小鼠
SG181690A1 (en) 2009-12-21 2012-07-30 Regeneron Pharma Humanized fcy r mice
US20130045492A1 (en) 2010-02-08 2013-02-21 Regeneron Pharmaceuticals, Inc. Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
DK2505654T4 (da) 2010-02-08 2020-07-27 Regeneron Pharma Mus med fælles letkæde
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
PL2553100T3 (pl) 2010-03-31 2018-03-30 Ablexis, Llc Inżynieria genetyczna zwierząt nie będących ludźmi w celu wytworzenia przeciwciał chimerycznych
WO2011159847A2 (en) 2010-06-15 2011-12-22 The Regents Of The University Of California Receptor tyrosine kinase-like orphan receptor 1 (ror1) single chain fv antibody fragment conjugates and methods of use thereof
RU2601297C2 (ru) 2010-06-22 2016-10-27 Ридженерон Фармасьютикалз, Инк. Мыши, экспрессирующие гибридную легкую цепь иммуноглобулина
US10793829B2 (en) 2010-07-26 2020-10-06 Trianni, Inc. Transgenic mammals and methods of use thereof
US10662256B2 (en) 2010-07-26 2020-05-26 Trianni, Inc. Transgenic mammals and methods of use thereof
AU2011286185B2 (en) 2010-07-26 2014-08-14 Trianni, Inc. Transgenic animals and methods of use
CA3250882A1 (en) 2010-08-02 2025-11-29 Regeneron Pharamaceuticals, Inc. Mice that Make Binding Proteins Comprising VL Domains
WO2012063048A1 (en) 2010-11-08 2012-05-18 Kymab Limited Cells & vertebrates for enhanced somatic hypermutation and class switch recombination
WO2012097313A2 (en) 2011-01-14 2012-07-19 The Regents Of The University Of California Therapeutic antibodies against ror-1 protein and methods for use of same
DK3375284T3 (da) 2011-02-15 2023-06-12 Univ Yale Humaniserede M-CSF-mus og anvendelser deraf
US10920242B2 (en) 2011-02-25 2021-02-16 Recombinetics, Inc. Non-meiotic allele introgression
SI2738258T2 (sl) 2011-02-25 2023-05-31 Regeneron Pharmaceuticals, Inc. Miši ADAM6
DK2527842T3 (da) 2011-05-12 2013-09-08 Regeneron Pharma Neuropeptidfrisætningsanalyse til natriumkanaler
MY172718A (en) * 2011-08-05 2019-12-11 Regeneron Pharma Humanized universal light chain mice
EP3741862A1 (en) 2011-09-19 2020-11-25 Kymab Limited Animals, repertoires & methods for the production of human antibodies
WO2013041844A2 (en) 2011-09-19 2013-03-28 Kymab Limited Antibodies, variable domains & chains tailored for human use
WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
MY172946A (en) 2011-10-17 2019-12-16 Regeneron Pharma Restricted immunoglobulin heavy chain mice
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
SMT202200205T1 (it) 2011-10-28 2022-07-21 Regeneron Pharma Topi geneticamente modificati che esprimono molecole chimeriche del complesso maggiore di istocompatibilità (mhc) ii
AU2012324016C1 (en) 2011-10-28 2018-02-15 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex mice
US9591835B2 (en) 2011-10-28 2017-03-14 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex animals
ES2858978T3 (es) 2011-10-28 2021-09-30 Regeneron Pharma Ratones con receptores de linfocitos T genéticamente modificados
US9043996B2 (en) 2011-10-28 2015-06-02 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex animals
JP2014532655A (ja) 2011-10-31 2014-12-08 メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. ナノ懸濁過程
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
KR102081657B1 (ko) 2011-12-20 2020-02-26 리제너론 파마슈티칼스 인코포레이티드 인간화 경쇄 마우스
EP3597038B1 (en) 2012-02-01 2021-04-21 Regeneron Pharmaceuticals, Inc. Humanized rodents that express heavy chains containing vl domains
JP2015509380A (ja) 2012-03-06 2015-03-30 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. 共通の軽鎖のマウス
NZ730271A (en) 2012-03-16 2022-09-30 Regeneron Pharma Non-human animals expressing ph-sensitive immunoglobulin sequences
CN104302170B (zh) 2012-03-16 2016-09-28 瑞泽恩制药公司 生产具有ph依赖性结合特性的抗原结合蛋白的小鼠
ES2665793T3 (es) 2012-03-16 2018-04-27 Regeneron Pharmaceuticals, Inc. Anticuerpos de cadena ligera modificada mediante ingeniería genética con histidina y roedores modificados genéticamente para la generación de los mismos
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
GB2502127A (en) 2012-05-17 2013-11-20 Kymab Ltd Multivalent antibodies and in vivo methods for their production
EP2831245A1 (en) 2012-03-28 2015-02-04 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
KR101904508B1 (ko) 2012-04-25 2018-10-04 리제너론 파마슈티칼스 인코포레이티드 큰 표적화 벡터를 사용한 뉴클레아제-중재된 표적화
HUE055617T2 (hu) 2012-06-12 2021-12-28 Regeneron Pharma Korlátozott immunglobulin nehézlánc lókuszokkal rendelkezõ, humanizált, nem humán élõlények
AR091482A1 (es) * 2012-06-21 2015-02-04 Recombinetics Inc Celulas modificadas geneticamente y metodos par su obtencion
AR092219A1 (es) 2012-08-23 2015-04-08 Seattle Genetics Inc Conjugados anticuerpo-farmaco (adc) que se unen a proteinas 158p1d7
KR101935088B1 (ko) 2012-08-24 2019-01-04 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 Ror1 암을 치료하고 전이를 저해하는데 이용을 위한 항체와 백신
EP4193834B1 (en) 2012-09-07 2025-05-14 Yale University Methods of using genetically modified mice
KR102402806B1 (ko) 2012-11-05 2022-05-30 리제너론 파마슈티칼스 인코포레이티드 유전자 변형된 비-인간 동물 및 그것의 사용 방법
CA2900832A1 (en) 2013-02-20 2014-08-28 Regeneron Pharmaceuticals, Inc. Mice expressing humanized t-cell co-receptors
EP2958990B1 (en) 2013-02-20 2019-10-16 Regeneron Pharmaceuticals, Inc. Genetic modification of rats
ES2678221T3 (es) * 2013-02-20 2018-08-09 Regeneron Pharmaceuticals, Inc. Animales no humanos con secuencias de cadena pesada de inmunoglobulina modificadas
WO2014130667A1 (en) 2013-02-22 2014-08-28 Regeneron Pharmaceuticals, Inc. Mice expressing humanized major histocompatibility complex
US20150342163A1 (en) 2013-02-22 2015-12-03 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex mice
AU2014249150B2 (en) 2013-03-11 2020-04-02 Regeneron Pharmaceuticals, Inc. Transgenic mice expressing chimeric major histocompatibility complex (MHC) class I molecules
CA2903025C (en) 2013-03-11 2025-10-07 Regeneron Pharmaceuticals, Inc. TRANSGENIC MICE EXPRESSING CHIMERIC MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS II MOLECULES
EP2970437A1 (en) 2013-03-13 2016-01-20 Regeneron Pharmaceuticals, Inc. Common light chain mouse
LT3501272T (lt) 2013-03-13 2023-03-27 Regeneron Pharmaceuticals, Inc. Pelės, vykdančios imunoglobulino lengvosios grandinės riboto rinkinio raišką
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
JP6510518B2 (ja) 2013-08-01 2019-05-08 アジェンシス,インコーポレイテッド Cd37タンパク質に結合する抗体薬物結合体(adc)
SG11201600036QA (en) 2013-08-07 2016-02-26 Regeneron Pharma Lincrna-deficient non-human animals
SG10201810825YA (en) 2013-09-18 2019-01-30 Regeneron Pharma Histidine engineered light chain antibodies and genetically modified non-human animals for generating the same
LT3175706T (lt) 2013-09-23 2019-02-25 Regeneron Pharmaceuticals, Inc. Gyvūnai, išskyrus žmogų, turintys humanizuotą signalą reguliuojančio baltymo geną
NL2013554B1 (en) 2013-10-01 2016-01-08 Kymab Ltd Animal models and therapeutic molecules.
US20150143559A1 (en) 2013-11-19 2015-05-21 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized a proliferation-inducing ligand gene
WO2015077071A1 (en) 2013-11-19 2015-05-28 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized b-cell activating factor gene
ES2700596T3 (es) 2013-12-11 2019-02-18 Regeneron Pharma Métodos y composiciones para la modificación dirigida de un genoma
JP6593595B2 (ja) 2014-01-15 2019-10-23 正道 山本 Atp可視化動物およびその用途
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
BR112016021679A2 (pt) 2014-03-21 2018-12-04 Regeneron Pharmaceuticals, Inc. proteína de ligação ao antígeno, métodos de produção de uma proteína de ligação ao antígeno e de identificação de uma ou mais proteínas de ligação ao antígeno, hibridoma, ácido nucleico, célula, e, animal não humano geneticamente modificado.
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
RU2711744C1 (ru) 2014-05-19 2020-01-21 Ридженерон Фармасьютикалз, Инк. Генетически модифицированные животные, отличные от человека, экспрессирующие epo человека
EP3381279B1 (en) 2014-05-30 2021-04-14 Regeneron Pharmaceuticals, Inc. Humanized dipeptidyl peptidase iv (dpp4) animals
JP6688231B2 (ja) 2014-06-06 2020-04-28 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. 標的遺伝子座を修飾するための方法及び組成物
RS60097B1 (sr) 2014-06-19 2020-05-29 Regeneron Pharma Ne-humane životinje koje imaju humanizovani gen za programiranu ćelijsku smrt 1
DK3354732T3 (da) 2014-06-23 2020-04-06 Regeneron Pharma Nukleasemedieret dna-samling
EP3161128B1 (en) 2014-06-26 2018-09-26 Regeneron Pharmaceuticals, Inc. Methods and compositions for targeted genetic modifications and methods of use
RU2017113134A (ru) 2014-09-19 2018-10-19 Регенерон Фармасьютикалз, Инк. Химерные антигенные рецепторы
KR20170070136A (ko) 2014-10-15 2017-06-21 리제너론 파마슈티칼스 인코포레이티드 만능성 세포를 생성하거나 유지하는 방법 및 조성물
CA2967823A1 (en) 2014-11-24 2016-06-02 Regeneron Pharmaceuticals, Inc. Non-human animals expressing humanized cd3 complex
SMT201900178T1 (it) 2014-12-05 2019-05-10 Regeneron Pharma Animali diversi dall’uomo aventi un gruppo umanizzato del gene 47 di differenziazione
IL282649B (en) 2014-12-09 2022-07-01 Regeneron Pharma Non-human animals with a humanized gene for differentiation cluster 274
EP3653048B9 (en) 2014-12-19 2023-10-04 Regeneron Pharmaceuticals, Inc. Methods and compositions for targeted genetic modification through single-step multiple targeting
CN107614010A (zh) 2015-03-09 2018-01-19 艾更斯司股份有限公司 结合至flt3蛋白的抗体药物偶联物(adc)
ES2955841T3 (es) 2015-03-16 2023-12-07 Regeneron Pharma Célula de un roedor que presenta función de la neurona motora superior e inferior y percepción sensorial disminuidas
CA2979702A1 (en) 2015-03-19 2016-09-22 Regeneron Pharmaceuticals, Inc. Non-human animals that select for light chain variable regions that bind antigen
RS64540B1 (sr) 2015-04-06 2023-09-29 Regeneron Pharma Imunski odgovori posredovani humanizovanim t ćelijama kod ne-humanih životinja
WO2016168212A1 (en) 2015-04-13 2016-10-20 Regeneron Pharmaceuticals, Inc. Humanized sirpa-il15 knockin mice and methods of use thereof
US10395759B2 (en) 2015-05-18 2019-08-27 Regeneron Pharmaceuticals, Inc. Methods and systems for copy number variant detection
EP3297663B1 (en) 2015-05-18 2025-11-12 Agensys, Inc. Antibodies that bind to axl proteins
WO2016187354A1 (en) 2015-05-18 2016-11-24 Agensys, Inc. Antibodies that bind to axl proteins
US10285388B2 (en) * 2015-05-29 2019-05-14 Regeneron Pharmaceuticals, Inc. Non-human animals having a disruption in a C9ORF72 locus
US10412939B2 (en) 2015-09-02 2019-09-17 Regeneron Pharmaceuticals, Inc. Rodent model of prostate cancer
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
PL3376857T3 (pl) * 2015-11-20 2021-09-13 Regeneron Pharmaceuticals, Inc. Zwierzęta inne niż człowiek posiadające humanizowany gen aktywacji limfocytów 3
WO2017095939A1 (en) 2015-12-03 2017-06-08 Trianni, Inc. Enhanced immunoglobulin diversity
SG10201914034WA (en) 2016-01-13 2020-03-30 Regeneron Pharma Rodents having an engineered heavy chain diversity region
US20170218398A1 (en) * 2016-01-30 2017-08-03 Markus Alexander Brown Method to selectively target cancerous cells for genetic manipulation
CN108779159B (zh) * 2016-02-04 2022-12-30 瑞泽恩制药公司 具有经改造的angptl8基因的非人动物
US11053288B2 (en) 2016-02-04 2021-07-06 Trianni, Inc. Enhanced production of immunoglobulins
US12071669B2 (en) 2016-02-12 2024-08-27 Regeneron Pharmaceuticals, Inc. Methods and systems for detection of abnormal karyotypes
US20170247436A1 (en) 2016-02-16 2017-08-31 Regeneron Pharmaceuticals, Inc. Non-human animals having a mutant kynureninase gene
EP3422845B1 (en) 2016-02-29 2021-06-02 Regeneron Pharmaceuticals, Inc. Rodents having a humanized tmprss gene
WO2017172958A1 (en) 2016-03-29 2017-10-05 Regeneron Pharmaceuticals, Inc. Genetic variant-phenotype analysis system and methods of use
JP7324583B2 (ja) 2016-05-20 2023-08-10 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 複数のガイドrnaを使用して免疫寛容を破綻させるための方法
PT3462853T (pt) 2016-06-03 2023-04-21 Regeneron Pharma Animais não humanos que expressam desoxinucleotidiltransferase terminal exógena
IL299099B2 (en) 2016-06-27 2025-07-01 Univ California Cancer treatment combinations
DK3476865T5 (da) 2016-06-28 2024-09-09 Biocytogen Pharmaceuticals Beijing Co Ltd Fremgangsmåde til konstruktion af pd-1-gen-modificeret humaniseret dyremodel og anvendelse deraf
CN109803530A (zh) 2016-07-29 2019-05-24 瑞泽恩制药公司 包含引起c-截短的原纤维蛋白-1表达的突变的小鼠
EP3518667B1 (en) * 2016-09-30 2024-10-30 Regeneron Pharmaceuticals, Inc. Rodents having a hexanucleotide repeat expansion in a c9orf72 locus
DK3766343T3 (da) 2016-11-04 2022-06-20 Regeneron Pharma Ikke-humane dyr med et manipuleret immunoglobulin-lambda-letkædelocus
JP2020505037A (ja) 2017-01-19 2020-02-20 オープン モノクローナル テクノロジー,インコーポレイテッド 複数の重鎖免疫グロブリン遺伝子座を有するトランスジェニックげっ歯類由来のヒト抗体
WO2018157058A1 (en) 2017-02-27 2018-08-30 Regeneron Pharmaceuticals, Inc. Non-human animal models of retinoschisis
CA3067872A1 (en) 2017-07-31 2019-02-07 Regeneron Pharmaceuticals, Inc. Cas-transgenic mouse embryonic stem cells and mice and uses thereof
EP3585160A2 (en) 2017-07-31 2020-01-01 Regeneron Pharmaceuticals, Inc. Crispr reporter non-human animals and uses thereof
DK3687287T5 (da) 2017-09-29 2024-08-26 Regeneron Pharma Gnavere, udtrykkende humaniseret c1q-kompleks
BR112020003609A2 (pt) 2017-09-29 2020-09-01 Regeneron Pharmaceuticals, Inc. sistema e método para formar uma emulsão
WO2019072241A1 (en) * 2017-10-13 2019-04-18 Beijing Biocytogen Co., Ltd NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC
CN109666701B (zh) * 2017-10-13 2021-08-24 百奥赛图(北京)医药科技股份有限公司 一种pd-1基因修饰人源化动物模型的构建方法及其应用
CN116064611A (zh) 2017-11-30 2023-05-05 瑞泽恩制药公司 包含人源化trkb基因座的非人动物
CN116058333A (zh) 2017-12-05 2023-05-05 瑞泽恩制药公司 具有经工程改造的免疫球蛋白λ轻链的非人动物以及所述非人动物的用途
EP3592140A1 (en) 2018-03-19 2020-01-15 Regeneron Pharmaceuticals, Inc. Transcription modulation in animals using crispr/cas systems
CN116420679B (zh) 2018-03-26 2025-10-03 瑞泽恩制药公司 用于测试治疗剂的人源化啮齿动物
HRP20250986T1 (hr) 2018-04-06 2025-10-24 Regeneron Pharmaceuticals, Inc. Antitijelo agonista leptinskog receptora za upotrebu u povećanju koštane mase kod osobe koja pati od metaboličke disfunkcije ili hipoleptinemije
CN112639980A (zh) 2018-06-01 2021-04-09 瑞泽恩制药公司 用于基于稀疏向量的矩阵变换的方法和系统
IL318469A (en) 2018-06-14 2025-03-01 Regeneron Pharma Non-human animals capable of reorganizing transgenic DH-DH, and their uses
WO2020018511A1 (en) 2018-07-16 2020-01-23 Regeneron Pharmaceuticals, Inc. Non-human animal models of ditra disease and uses thereof
CN109504708A (zh) * 2018-12-03 2019-03-22 江苏集萃药康生物科技有限公司 一种筛选标记自我删除的基因打靶载体及方法
IL301193A (en) 2018-12-20 2023-05-01 Regeneron Pharma Nuclease-mediated repeat expansion
US20220104468A1 (en) 2019-01-22 2022-04-07 St. Jude Children's Research Hospital Modulation of lc3-associated endocytosis pathway and genetically modified non-human animals as a model of neuroinflammation and neurodegeneration
KR20210133234A (ko) * 2019-02-18 2021-11-05 바이오사이토젠 파마슈티컬스 (베이징) 컴퍼니 리미티드 인간화 면역글로불린 유전자좌를 갖는 유전적으로 변형된 비-인간 동물
CA3127153A1 (en) 2019-02-22 2020-08-27 Regeneron Pharmaceuticals, Inc. Rodents having genetically modified sodium channels and methods of use thereof
KR102487901B1 (ko) 2019-04-04 2023-01-12 리제너론 파마슈티칼스 인코포레이티드 표적화된 변형의 표적화 벡터로의 무흔적 도입을 위한 방법
AU2020253532B2 (en) 2019-04-04 2024-06-20 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized coagulation factor 12 locus
JP2022529943A (ja) 2019-04-15 2022-06-27 クウィクセル セラピューティクス リミテッド ライアビリティ カンパニー がんの処置における使用のための、標的指向性のマスクされたi型インターフェロン(ifnaおよびifnb)と腫瘍抗原に対する抗体とを含む融合タンパク質組成物
CN113874510A (zh) 2019-06-04 2021-12-31 瑞泽恩制药公司 包括具有β滑移突变的人源化TTR基因座的非人动物和使用方法
KR20220016880A (ko) 2019-06-05 2022-02-10 리제너론 파마슈티칼스 인코포레이티드 카파 유전자좌에서 발현된 제한적 람다 경쇄 레퍼토리를 갖는 비-인간 동물 및 이의 용도
US11622547B2 (en) 2019-06-07 2023-04-11 Regeneran Pharmaceuticals, Inc. Genetically modified mouse that expresses human albumin
KR20220024134A (ko) 2019-06-27 2022-03-03 리제너론 파마슈티칼스 인코포레이티드 Tdp-43 단백질이상질환 모델링
CA3145453A1 (en) 2019-07-01 2021-01-07 Tonix Pharma Limited Anti-cd154 antibodies and uses thereof
MX2022003935A (es) 2019-10-04 2022-04-25 Tae Life Sciences Llc Composiciones de anticuerpo que comprenden mutaciones fc y propiedades de conjugacion especificas del sitio.
WO2021108363A1 (en) 2019-11-25 2021-06-03 Regeneron Pharmaceuticals, Inc. Crispr/cas-mediated upregulation of humanized ttr allele
EP4096396A1 (en) 2020-01-28 2022-12-07 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized pnpla3 locus and methods of use
US20230081547A1 (en) 2020-02-07 2023-03-16 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized klkb1 locus and methods of use
EP4125348A1 (en) 2020-03-23 2023-02-08 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus comprising a v30m mutation and methods of use
KR20230004472A (ko) 2020-04-21 2023-01-06 리제너론 파마슈티칼스 인코포레이티드 인간화 cxcl13 유전자를 갖는 비인간 동물
AU2021283564B2 (en) 2020-06-02 2025-05-29 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animals with common light chain immunoglobulin locus
AU2020454777A1 (en) 2020-06-25 2023-02-02 Humab Co., Ltd. Heterozygous transgenic animal
IL301137A (en) 2020-09-11 2023-05-01 Regeneron Pharma Identification and production of antigen-specific antibodies
WO2022072671A1 (en) 2020-10-01 2022-04-07 Regeneron Pharmaceuticals, Inc. Rodent animals expressing human cr1
US12012441B2 (en) 2020-10-26 2024-06-18 Neptune Biosciences Llc Engineered human IL-21 cytokines and methods for using the same
WO2022132943A1 (en) 2020-12-16 2022-06-23 Regeneron Pharmaceuticals, Inc. Mice expressing humanized fc alpha receptors
CN116802200A (zh) 2020-12-21 2023-09-22 瑞泽恩制药公司 具有人源化tslp基因、人源化tslp受体基因和/或人源化il7ra基因的非人动物
CA3165366A1 (en) 2020-12-23 2022-06-30 Regeneron Pharmaceuticals, Inc. Nucleic acids encoding anchor modified antibodies and uses thereof
JP2024503625A (ja) 2021-01-06 2024-01-26 トニックス ファーマ リミテッド 改変された抗cd154抗体により免疫寛容を誘導する方法
JP2024512702A (ja) 2021-03-31 2024-03-19 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 Tcrβレパートリーの改善された多様性を伴うヒト化細胞免疫系の構成要素を含む、遺伝的に改変されたマウス
WO2022220603A1 (ko) 2021-04-16 2022-10-20 고려대학교 산학협력단 코로나-19 바이러스 표적 인간 항체
US20250325634A1 (en) 2021-06-18 2025-10-23 Nammi Therapeutics, Inc. Fusion Protein Composition(s) Comprising Masked Type I Interferons (IFNa and IFNb) For Use in the Treatment of Cancer and Methods Thereof
US20240415980A1 (en) 2021-10-28 2024-12-19 Regeneron Pharmaceuticals, Inc. Crispr/cas-related methods and compositions for knocking out c5
IL312971A (en) 2021-12-08 2024-07-01 Regeneron Pharma Mutant myocilin disease model and uses thereof
EP4451863A1 (en) 2021-12-20 2024-10-30 Regeneron Pharmaceuticals, Inc. Non-human animals comprising humanized ace2 and tmprss loci
WO2023150798A1 (en) 2022-02-07 2023-08-10 Regeneron Pharmaceuticals, Inc. Compositions and methods for defining optimal treatment timeframes in lysosomal disease
EP4476245A1 (en) 2022-02-11 2024-12-18 Regeneron Pharmaceuticals, Inc. Compositions and methods for screening 4r tau targeting agents
EP4514125A1 (en) 2022-04-26 2025-03-05 Regeneron Pharmaceuticals, Inc. A rodent model of fibrodysplasia ossificans progressiva
WO2023235677A1 (en) 2022-05-31 2023-12-07 Regeneron Pharmaceuticals, Inc. Animal model of tdp-43 proteinopathy
WO2023235725A2 (en) 2022-05-31 2023-12-07 Regeneron Pharmaceuticals, Inc. Crispr-based therapeutics for c9orf72 repeat expansion disease
US20230417899A1 (en) 2022-06-27 2023-12-28 Oshkosh Corporation Position tracking for a lift device
CN119654068A (zh) 2022-07-19 2025-03-18 瑞泽恩制药公司 转基因动物模型及其模拟人类免疫系统的用途
CA3265746A1 (en) 2022-09-22 2024-03-28 Regeneron Pharmaceuticals, Inc. GENETICALLY MODIFIED MICE EXPRESSING COMPONENTS OF A HUMAN CELLULAR IMMUNE SYSTEM
US20240224964A9 (en) 2022-09-29 2024-07-11 Regeneron Pharmaceuticals, Inc. Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes
AU2024214456A1 (en) 2023-02-01 2025-07-03 Regeneron Pharmaceuticals, Inc. Animals comprising a modified klhdc7b locus
WO2024258743A1 (en) 2023-06-13 2024-12-19 Adcentrx Therapeutics, Inc. Methods and compositions related to antibodies and antibody drug conjugates (adcs) that bind nectin-4 proteins
AU2024304358A1 (en) 2023-06-16 2025-11-06 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
WO2025122669A1 (en) 2023-12-05 2025-06-12 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized complement factor b gene
WO2025171307A1 (en) 2024-02-08 2025-08-14 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
WO2025212991A1 (en) 2024-04-05 2025-10-09 Regeneron Pharmaceuticals, Inc. Rodent models of disease
WO2025235388A1 (en) 2024-05-06 2025-11-13 Regeneron Pharmaceuticals, Inc. Transgene genomic identification by nuclease-mediated long read sequencing
WO2025250495A1 (en) 2024-05-28 2025-12-04 Regeneron Pharmaceuticals, Inc. Acceleration of human hepatocyte engraftment in humanized liver animals by supplementing paracrine ligands or agonists that activate human liver regeneration signals

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5770429A (en) * 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1993004169A1 (en) 1991-08-20 1993-03-04 Genpharm International, Inc. Gene targeting in animal cells using isogenic dna constructs
SG48760A1 (en) * 1992-07-24 2003-03-18 Abgenix Inc Generation of xenogenetic antibodies
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
US5436149A (en) 1993-02-19 1995-07-25 Barnes; Wayne M. Thermostable DNA polymerase with enhanced thermostability and enhanced length and efficiency of primer extension
AU6819494A (en) * 1993-04-26 1994-11-21 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO2000046251A2 (en) * 1999-02-05 2000-08-10 Buelow Jens Ulrich Human polyclonal antibodies from transgenic nonhuman animals
US6586251B2 (en) * 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YANG X.W. et al., "Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome", Nat Biotechnol. 1997 Sep; 15(9):859-65. *

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2514672C2 (ru) * 2008-06-27 2014-04-27 Эвоник Рем ГмбХ Рекомбинантная клетка, продуцирующая 2-гидроксиизомасляную кислоту
RU2514672C9 (ru) * 2008-06-27 2014-10-20 Эвоник Рем ГмбХ Рекомбинантная клетка, продуцирующая 2-гидроксиизомасляную кислоту
RU2656159C2 (ru) * 2012-09-07 2018-05-31 ДАУ АГРОСАЙЕНСИЗ ЭлЭлСи Локусы функциональности fad2 и соответствующие специфичные к участку-мишени связывающие белки, способные индуцировать направленные разрывы
RU2656158C2 (ru) * 2012-09-07 2018-05-31 ДАУ АГРОСАЙЕНСИЗ ЭлЭлСи Функциональные локусы fad2 и соответствующие специфичные для сайта-мишени связывающиеся белки, способные индуцировать направленные разрывы
RU2676708C2 (ru) * 2013-04-16 2019-01-10 Регенерон Фармасьютикалс, Инк. Направленная модификация генома крысы
RU2685914C1 (ru) * 2013-12-11 2019-04-23 Регенерон Фармасьютикалс, Инк. Способы и композиции для направленной модификации генома
RU2725520C2 (ru) * 2013-12-11 2020-07-02 Регенерон Фармасьютикалс, Инк. Способы и композиции для направленной модификации генома
RU2734770C2 (ru) * 2014-11-21 2020-10-23 Регенерон Фармасьютикалз, Инк. Способы и композиции для нацеленной генетической модификации с использованием парных гидовых рнк
RU2749717C2 (ru) * 2015-11-24 2021-06-16 Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед Способ временной трансфекции для продуцирования ретровируса
RU2752498C2 (ru) * 2015-11-24 2021-07-28 Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед Стабильные клеточные линии для продуцирования ретровирусов
RU2751237C1 (ru) * 2020-06-10 2021-07-12 Регенерон Фармасьютикалс, Инк. Способы и композиции для направленной модификации генома

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