KR100833136B1 - 진핵세포의 변형 방법 - Google Patents
진핵세포의 변형 방법 Download PDFInfo
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- KR100833136B1 KR100833136B1 KR1020037005885A KR20037005885A KR100833136B1 KR 100833136 B1 KR100833136 B1 KR 100833136B1 KR 1020037005885 A KR1020037005885 A KR 1020037005885A KR 20037005885 A KR20037005885 A KR 20037005885A KR 100833136 B1 KR100833136 B1 KR 100833136B1
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Chemical & Material Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
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- Animal Husbandry (AREA)
- Cell Biology (AREA)
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 | ||
| PCT/US2001/045375 WO2002036789A2 (en) | 2000-10-31 | 2001-10-31 | Methods of modifying eukaryotic cells |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20030074614A KR20030074614A (ko) | 2003-09-19 |
| KR100833136B1 true KR100833136B1 (ko) | 2008-05-28 |
Family
ID=26936709
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020037005885A Expired - Lifetime KR100833136B1 (ko) | 2000-10-31 | 2001-10-31 | 진핵세포의 변형 방법 |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6586251B2 (https=) |
| EP (1) | EP1399575B1 (https=) |
| JP (7) | JP5339566B2 (https=) |
| KR (1) | KR100833136B1 (https=) |
| CN (1) | CN100497642C (https=) |
| AT (1) | ATE332388T1 (https=) |
| AU (2) | AU2004802A (https=) |
| BR (1) | BRPI0115096B1 (https=) |
| CA (1) | CA2426398C (https=) |
| CZ (1) | CZ304856B6 (https=) |
| DE (1) | DE60121372T2 (https=) |
| HU (1) | HU227639B1 (https=) |
| MX (1) | MXPA03003797A (https=) |
| NO (1) | NO332300B1 (https=) |
| NZ (1) | NZ525511A (https=) |
| PL (1) | PL204759B1 (https=) |
| RU (1) | RU2290441C2 (https=) |
| WO (1) | WO2002036789A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20150141987A (ko) * | 2013-04-16 | 2015-12-21 | 리제너론 파마슈티칼스 인코포레이티드 | 랫트 게놈의 표적화된 변형 |
Families Citing this family (218)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6908744B1 (en) * | 2000-03-14 | 2005-06-21 | Regeneron Pharmaceuticals, Inc. | Methods of stimulating cartilage formation |
| WO2002014495A2 (en) * | 2000-08-14 | 2002-02-21 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Enhanced homologous recombination mediated by lambda recombination proteins |
| 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 |
| US6586251B2 (en) * | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| GB0110029D0 (en) | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
| WO2004098490A2 (en) | 2002-05-17 | 2004-11-18 | 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 |
| NZ537277A (en) | 2002-07-18 | 2008-04-30 | Crucell Holland Bv | Recombinant production of mixtures of antibodies |
| CA2496233A1 (en) * | 2002-09-09 | 2004-03-18 | California Institute Of Technology | Methods and compositions for the generation of humanized mice |
| WO2004067725A2 (en) * | 2003-01-30 | 2004-08-12 | Regeneron Pharmaceuticals, Inc. | Methods of identifying modulators of nmur2-mediated activity |
| ES2408582T3 (es) | 2003-05-30 | 2013-06-21 | Merus B.V. | Biblioteca de Fab para la preparación de una mezcla de anticuerpos |
| US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| AU2005295269B2 (en) | 2004-10-19 | 2010-05-13 | Regeneron Pharmaceuticals, Inc. | Method for generating an animal homozygous for a genetic modification |
| US20060117396A1 (en) * | 2004-11-30 | 2006-06-01 | Murphy Andrew J | Assay methods for identifying modulators of OPSDL3 and transgenic knockouts |
| PT2125894T (pt) | 2007-03-22 | 2019-02-27 | Biogen Ma Inc | Proteínas de ligação incluindo anticorpos, derivados de anticorpos e fragmentos de anticorpos que se ligam especificamente ao cd154 e as suas utilizações |
| DK2602323T3 (en) | 2007-06-01 | 2018-04-16 | Open Monoclonal Tech Inc | Compositions and Methods for Inhibiting Endogenous Immunoglobin Genes and Producing Transgenic Human Idiotypic Antibodies |
| CA2708776A1 (en) * | 2007-12-10 | 2009-06-18 | Aliva Biopharmaceuticals, Inc. | Methods for sequential replacement of targeted region by homologous recombination |
| EP2281050B1 (en) * | 2008-04-14 | 2014-04-02 | Sangamo BioSciences, 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 |
| DE102008002715A1 (de) * | 2008-06-27 | 2009-12-31 | Evonik Röhm Gmbh | 2-Hydroxyisobuttersäure produzierende rekombinante Zelle |
| EP2346994B1 (en) | 2008-09-30 | 2022-02-16 | Ablexis, LLC | Knock-in mice for the production of chimeric antibodies |
| BR112012000536A2 (pt) | 2009-07-08 | 2020-08-11 | Kymab Limited | métodos para produção de anticorpo ou cadeia leve ou pesada de anticorpo específico para um antígeno desejado, para produção de anticorpo ou cadeia de anticorpo e seu uso, composição farmacêutica e derivado de anticorpo quimérico |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| PT2485583T (pt) | 2009-10-06 | 2016-09-22 | Univ Yale | Ratinhos geneticamente modificados e enxerto |
| EP2494047B1 (en) | 2009-10-29 | 2017-01-04 | Regeneron Pharmaceuticals, Inc. | Multifunctional alleles |
| US8754287B2 (en) | 2009-12-10 | 2014-06-17 | Regeneron Pharmaceuticals, Inc. | Mice that make heavy chain antibodies |
| PL3498730T3 (pl) | 2009-12-21 | 2026-04-07 | Regeneron Pharmaceuticals, Inc. | Humanizowane myszy fc gamma r |
| 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 |
| SI2501817T2 (sl) * | 2010-02-08 | 2021-09-30 | Regeneron Pharmaceuticals, Inc. | Miš z navadno lahko verigo |
| US20120021409A1 (en) | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| KR102203727B1 (ko) | 2010-03-31 | 2021-01-18 | 아블렉시스, 엘엘씨 | 키메라 항체의 제조를 위한 비-인간 동물의 유전적 조작 |
| US9242014B2 (en) | 2010-06-15 | 2016-01-26 | 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 |
| US9012717B2 (en) | 2010-06-22 | 2015-04-21 | Regeneron Pharmaceuticals, Inc. | Human lambda light chain mice |
| JP6482757B2 (ja) | 2010-07-26 | 2019-03-13 | トリアンニ インコーポレイテッドＴｒｉａｎｎｉ，Ｉｎｃ． | トランスジェニック動物および使用方法 |
| US10662256B2 (en) | 2010-07-26 | 2020-05-26 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| US10793829B2 (en) | 2010-07-26 | 2020-10-06 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| SG10201912639SA (en) | 2010-08-02 | 2020-02-27 | Regeneron Pharma | 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 |
| DK3252076T3 (da) | 2011-01-14 | 2019-12-02 | Univ California | Diagnostisk anvendelse af antistoffer mod ror-1-protein |
| MX350385B (es) | 2011-02-15 | 2017-09-04 | Regeneron Pharma | Ratones de m-csf humanizada. |
| US10920242B2 (en) | 2011-02-25 | 2021-02-16 | Recombinetics, Inc. | Non-meiotic allele introgression |
| RU2722373C2 (ru) | 2011-02-25 | 2020-05-29 | Редженерон Фармасьютикалс, Инк. | Мыши adam6 |
| PL2631654T3 (pl) | 2011-05-12 | 2015-09-30 | Regeneron Pharma | Oznaczenie uwalniania neuropeptydu dla kanałów sodowych |
| RS59728B1 (sr) | 2011-08-05 | 2020-02-28 | Regeneron Pharma | Humanizovani miševi univerzalnog lakog lanca |
| WO2013041845A2 (en) | 2011-09-19 | 2013-03-28 | Kymab Limited | Animals, repertoires & methods |
| BR112014006394A2 (pt) | 2011-09-19 | 2017-03-28 | Kymab Ltd | manipulação de diversidade genética de imunoglobulina e terapêuticos multi-anticorpos |
| WO2013045916A1 (en) | 2011-09-26 | 2013-04-04 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| KR20160098514A (ko) | 2011-10-17 | 2016-08-18 | 리제너론 파아마슈티컬스, 인크. | 제한된 면역글로불린 중쇄 마우스 |
| LT3424947T (lt) | 2011-10-28 | 2021-03-10 | Regeneron Pharmaceuticals, Inc. | Genetiškai modifikuotos t ląstelių receptorių pelės |
| US9043996B2 (en) | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| SI2770821T1 (en) | 2011-10-28 | 2018-01-31 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex of mice |
| US9591835B2 (en) | 2011-10-28 | 2017-03-14 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| 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 |
| DK3590332T3 (da) | 2011-10-28 | 2022-05-23 | Regeneron Pharma | Genmodificerede mus, der eksprimerer kimære major histokompatibilitetskompleks (MHC) II-molekyler |
| EP2773323A4 (en) | 2011-10-31 | 2015-04-22 | Merck Sharp & Dohme | NANO-SUSPENSION METHOD |
| GB201122047D0 (en) * | 2011-12-21 | 2012-02-01 | Kymab Ltd | Transgenic animals |
| US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| RU2664181C2 (ru) | 2011-12-20 | 2018-08-15 | Регенерон Фармасьютикалз, Инк. | Мыши с гуманизированной легкой цепью |
| RS62023B1 (sr) | 2012-02-01 | 2021-07-30 | Regeneron Pharma | Humanizovani glodari koji eksprimiraju teške lance koji sadrže vl domene |
| IN2014DN08163A (https=) | 2012-03-06 | 2015-05-01 | Regeneron Pharma | |
| MX2014011047A (es) | 2012-03-16 | 2015-04-08 | Regeneron Pharma | Ratones que producen proteinas de union a un antigeno con caracteristicas de union dependientes del ph. |
| 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 |
| KR102228296B1 (ko) | 2012-03-16 | 2021-03-17 | 리제너론 파마슈티칼스 인코포레이티드 | 히스티딘 공학처리된 경쇄 항체 및 그것을 생성하기 위한 유전자 변형된 비-사람 동물 |
| SG10201700360VA (en) | 2012-03-16 | 2017-03-30 | Regeneron Pharma | Non-human animals expressing ph-sensitive immunoglobulin sequences |
| JP2015512635A (ja) | 2012-03-28 | 2015-04-30 | カイマブ・リミテッド | クラススイッチした完全ヒト抗体の発現のためのトランスジェニック非−ヒト脊椎動物 |
| GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
| US10251377B2 (en) | 2012-03-28 | 2019-04-09 | Kymab Limited | Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies |
| IN2014DN09261A (https=) | 2012-04-25 | 2015-07-10 | Regeneron Pharma | |
| PT3597037T (pt) | 2012-06-12 | 2021-06-01 | Regeneron Pharma | Animais não humanos humanizados com lócus de cadeia pesada de imunoglobulina restrito |
| AR091482A1 (es) * | 2012-06-21 | 2015-02-04 | Recombinetics Inc | Celulas modificadas geneticamente y metodos par su obtencion |
| EP3494996B1 (en) | 2012-08-23 | 2026-04-15 | Agensys, Inc. | Antibody drug conjugates (adc) that bind to 158p1d7 proteins |
| PL3489261T3 (pl) | 2012-08-24 | 2021-08-16 | The Regents Of The University Of California | Przeciwciała i szczepionki do stosowania w leczeniu nowotworów z ekspresją ROR1 i w hamowaniu przerzutu |
| UA118090C2 (uk) * | 2012-09-07 | 2018-11-26 | ДАУ АГРОСАЙЄНСІЗ ЕлЕлСі | Спосіб інтегрування послідовності нуклеїнової кислоти, що представляє інтерес, у ген fad2 у клітині сої та специфічний для локусу fad2 білок, що зв'язується, здатний індукувати спрямований розрив |
| IN2015DN02032A (https=) | 2012-09-07 | 2015-08-14 | Univ Yale | |
| CA2887706C (en) | 2012-11-05 | 2022-08-02 | Regeneron Pharmaceuticals | Genetically modified non-human animals and methods of use thereof |
| MX2015010841A (es) | 2013-02-20 | 2016-05-09 | Regeneron Pharma | Modificacion genetica de ratas. |
| KR102714111B1 (ko) | 2013-02-20 | 2024-10-11 | 리제너론 파아마슈티컬스, 인크. | 사람화된 ｔ-세포 보조-수용체를 발현하는 마우스 |
| EP2840892B1 (en) | 2013-02-20 | 2018-04-18 | Regeneron Pharmaceuticals, Inc. | Non-human animals with modified immunoglobulin heavy chain sequences |
| US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
| PL2958937T3 (pl) | 2013-02-22 | 2019-01-31 | Regeneron Pharmaceuticals, Inc. | Myszy ekspresjonujące humanizowany główny układ zgodności tkankowej |
| JP6456351B2 (ja) | 2013-03-11 | 2019-01-23 | 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． | キメラ主要組織適合複合体（ｍｈｃ）クラスｉ分子を発現する遺伝子導入マウス |
| CA3249218A1 (en) | 2013-03-11 | 2026-03-02 | Regeneron Pharmaceuticals, Inc. | Transgenic mice expressing chimeric major histocompatibility complex (mhc) class ii molecules |
| CN105189545A (zh) | 2013-03-13 | 2015-12-23 | 瑞泽恩制药公司 | 常见轻链小鼠 |
| WO2014160202A1 (en) | 2013-03-13 | 2014-10-02 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| 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 |
| US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
| US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
| 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） |
| IL294443A (en) | 2013-08-07 | 2022-09-01 | Regeneron Pharma | Lincrna-deficient non-human animals |
| MY191512A (en) | 2013-09-18 | 2022-06-28 | Regeneron Pharma | Histidine engineered light chain antibodies and genetically modified non-human animals for generating the same |
| CN105592695B (zh) | 2013-09-23 | 2018-04-10 | 瑞泽恩制药公司 | 具有人源化信号调节蛋白基因的非人动物 |
| DE112014004537T5 (de) | 2013-10-01 | 2016-07-21 | Kymab Limited | Tiermodelle und therapeutische Moleküle |
| SG10201811701YA (en) | 2013-11-19 | 2019-01-30 | Regeneron Pharma | Non-human animals having a humanized a proliferation-inducing ligand gene |
| CA2929846C (en) | 2013-11-19 | 2020-09-15 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized b-cell activating factor gene |
| US9546384B2 (en) * | 2013-12-11 | 2017-01-17 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for the targeted modification of a mouse genome |
| SMT201800653T1 (it) | 2013-12-11 | 2019-01-11 | Regeneron Pharma | Metodi e composizioni per la modificazione indirizzata a bersaglio di un genoma |
| WO2015108102A1 (ja) | 2014-01-15 | 2015-07-23 | 国立大学法人 群馬大学 | 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 |
| KR102276752B1 (ko) | 2014-03-21 | 2021-07-13 | 리제너론 파마슈티칼스 인코포레이티드 | 단일 도메인 결합 단백질을 생산하는 비-인간 동물 |
| WO2015143406A2 (en) | 2014-03-21 | 2015-09-24 | Regeneron Pharmaceuticals, Inc. | Vl antigen binding proteins exhibiting distinct binding characteristics |
| SG10202002187WA (en) | 2014-05-19 | 2020-04-29 | Regeneron Pharma | Genetically modified non-human animals expressing human epo |
| US9497945B2 (en) | 2014-05-30 | 2016-11-22 | Regeneron Pharmaceuticals, Inc. | Humanized dipeptidyl peptidase IV (DPP4) animals |
| RS60359B1 (sr) | 2014-06-06 | 2020-07-31 | Regeneron Pharma | Postupci i kompozicije za modifikovanje ciljanog lokusa |
| ES2783424T3 (es) | 2014-06-19 | 2020-09-17 | Regeneron Pharma | Animales no humanos que tienen un gen de muerte celular programada 1 humanizado |
| HUE049405T2 (hu) | 2014-06-23 | 2020-09-28 | Regeneron Pharma | Nukleáz-közvetített DNS-összeállítás |
| KR102386101B1 (ko) | 2014-06-26 | 2022-04-14 | 리제너론 파마슈티칼스 인코포레이티드 | 표적화된 유전자 변형을 위한 방법 및 그 조성물, 및 사용 방법 |
| CA2959428A1 (en) | 2014-09-19 | 2016-03-24 | Regeneron Pharmaceuticals, Inc. | Chimeric antigen receptors |
| DK3207124T3 (da) | 2014-10-15 | 2019-08-12 | Regeneron Pharma | Fremgangsmåder og sammensætninger til generering eller bevaring af pluripotente celler |
| ES2731437T3 (es) * | 2014-11-21 | 2019-11-15 | Regeneron Pharma | Métodos y composiciones para la modificación genética dirigida mediante el uso de pares de ARN guías |
| RU2020122439A (ru) | 2014-11-24 | 2020-09-24 | Регенерон Фармасьютикалз, Инк. | Не относящиеся к человеку животные, экспрессирующие гуманизированный комплекс cd3 |
| SI3086637T1 (sl) | 2014-12-05 | 2019-04-30 | Regeneron Pharmaceuticals, Inc. | Nehumane živali s humaniziranim označevalcem diferenciacije gena CD47 |
| HUE052606T2 (hu) | 2014-12-09 | 2021-05-28 | Regeneron Pharma | Humanizált differenciációs klaszter 274 génnel rendelkezõ nem humán állatok |
| KR102530821B1 (ko) | 2014-12-19 | 2023-05-10 | 리제너론 파마슈티칼스 인코포레이티드 | 단일 단계 다중 표적화를 통한 표적화된 유전자 변형을 위한 방법 및 조성물 |
| ES2884844T3 (es) | 2015-03-09 | 2021-12-13 | Agensys Inc | Conjugados de anticuerpo fármaco (ADC) que se unen a proteínas FLT3 |
| IL274285B (en) | 2015-03-16 | 2022-07-01 | Regeneron Pharma | Non-human animals exhibiting reduced upper and lower motor neuron function and sensory perception |
| EP3271403A1 (en) | 2015-03-19 | 2018-01-24 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
| CN113349159B (zh) | 2015-04-06 | 2022-11-11 | 瑞泽恩制药公司 | 非人动物中的人源化t细胞介导的免疫应答 |
| KR102658190B1 (ko) | 2015-04-13 | 2024-04-17 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화된 sirpa-il15 녹인 마우스 및 이의 이용 방법 |
| WO2016187356A1 (en) | 2015-05-18 | 2016-11-24 | Agensys, Inc. | Antibodies that bind to axl proteins |
| WO2016187354A1 (en) | 2015-05-18 | 2016-11-24 | Agensys, Inc. | Antibodies that bind to axl proteins |
| US10395759B2 (en) | 2015-05-18 | 2019-08-27 | Regeneron Pharmaceuticals, Inc. | Methods and systems for copy number variant detection |
| JP6619822B2 (ja) | 2015-05-29 | 2019-12-11 | 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． | Ｃ９ｏｒｆ７２遺伝子座における破壊を有する非ヒト動物 |
| US10412939B2 (en) | 2015-09-02 | 2019-09-17 | Regeneron Pharmaceuticals, Inc. | Rodent model of prostate cancer |
| TW202417497A (zh) | 2015-10-12 | 2024-05-01 | 美商再生元醫藥公司 | 活化瘦素受體的抗原結合蛋白 |
| SG11201803409UA (en) | 2015-11-20 | 2018-05-30 | Regeneron Pharma | Non-human animals having a humanized lymphocyte-activation gene 3 |
| JP7110096B2 (ja) * | 2015-11-24 | 2022-08-01 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | レトロウイルス産生のための一時的トランスフェクション法 |
| EP3380604B1 (en) * | 2015-11-24 | 2022-12-28 | GlaxoSmithKline Intellectual Property Development Limited | Stable cell lines for retroviral production |
| EP3384030A4 (en) | 2015-12-03 | 2019-07-03 | Trianni, Inc. | IMPROVED IMMUNOGLULINIVITY |
| AU2017206785C1 (en) | 2016-01-13 | 2023-09-07 | Regeneron Pharmaceuticals, Inc. | 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 |
| AU2017213633B2 (en) | 2016-02-04 | 2023-08-03 | Trianni, Inc. | Enhanced production of immunoglobulins |
| MX2018009513A (es) * | 2016-02-04 | 2019-01-31 | Regeneron Pharma | Animales no humanos que tienen un gen angptl8 modificado genéticamente. |
| CA3014292A1 (en) | 2016-02-12 | 2017-08-17 | Regeneron Pharmaceuticals, Inc. | Methods and systems for detection of abnormal karyotypes |
| AU2017221425A1 (en) | 2016-02-16 | 2018-08-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a mutant kynureninase gene |
| CN109068621B (zh) | 2016-02-29 | 2021-07-20 | 再生元制药公司 | 具有人源化的tmprss基因的啮齿类动物 |
| US20170286594A1 (en) | 2016-03-29 | 2017-10-05 | Regeneron Pharmaceuticals, Inc. | Genetic Variant-Phenotype Analysis System And Methods Of Use |
| IL323024A (en) | 2016-05-20 | 2025-10-01 | Regeneron Pharma | Methods for breaking immunological tolerance using multiple guide RNAs |
| HUE061619T2 (hu) | 2016-06-03 | 2023-07-28 | Regeneron Pharma | Exogén terminális dezoxinukleotid-transzferázt expresszáló rágcsálók |
| IL299099B2 (en) | 2016-06-27 | 2025-07-01 | Univ California | Cancer treatment combinations |
| EP3476865B1 (en) | 2016-06-28 | 2023-09-13 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Method for constructing pd-1 gene-modified humanized animal model and use thereof |
| JP2019523009A (ja) | 2016-07-29 | 2019-08-22 | 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． | Ｃ末端切断型フィブリリン−１の発現をもたらす変異を有するマウス |
| JP7026678B2 (ja) * | 2016-09-30 | 2022-02-28 | 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 | Ｃ９ｏｒｆ７２座位中にヘキサヌクレオチドリピート伸長を有する非ヒト動物 |
| WO2018128691A1 (en) | 2016-11-04 | 2018-07-12 | Regeneron Pharmaceuticals, Inc. | Non-human animals having an engineered immunoglobulin lambda light chain locus |
| NZ755816A (en) | 2017-01-19 | 2026-03-27 | Omniab Inc | Human antibodies from transgenic rodents with multiple heavy chain immunoglobulin loci |
| AU2018224227A1 (en) | 2017-02-27 | 2019-08-29 | Regeneron Pharmaceuticals, Inc. | Non-human animal models of Retinoschisis |
| CN111182790A (zh) | 2017-07-31 | 2020-05-19 | 瑞泽恩制药公司 | Crispr报告体非人类动物及其用途 |
| WO2019028032A1 (en) | 2017-07-31 | 2019-02-07 | Regeneron Pharmaceuticals, Inc. | EMBRYONIC STEM CELLS OF TRANSGENIC MOUSE CASES AND MICE AND USES THEREOF |
| MX394999B (es) | 2017-09-29 | 2025-03-24 | Regeneron Pharma | Animales no humanos que comprenden un locus ttr humanizado y metodos de uso |
| PT3687287T (pt) | 2017-09-29 | 2023-11-03 | Regeneron Pharma | Roedores que expressam complexo c1q humanizado |
| 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 |
| IL310006A (en) | 2017-11-30 | 2024-03-01 | Regeneron Pharma | Non-human animals containing a humanized TRKB locus |
| DK4140297T3 (da) | 2017-12-05 | 2025-06-23 | Regeneron Pharma | Mus med en konstrueret immunglobulin-lambda-letkæde og anvendelser deraf |
| CN111885915B (zh) | 2018-03-19 | 2023-04-28 | 瑞泽恩制药公司 | 使用crispr/cas系统对动物进行转录调制 |
| KR20250121150A (ko) | 2018-03-26 | 2025-08-11 | 리제너론 파마슈티칼스 인코포레이티드 | 치료제를 시험하기 위한 인간화된 설치류 |
| DK3773713T3 (da) | 2018-04-06 | 2025-08-18 | Regeneron Pharma | Leptinreceptoragonistantistof til anvendelse i forøgelse af knoglemasse hos et individ, der lider af metabolisk dysfunktion eller hypoleptinæmI |
| 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 |
| IL278267B2 (en) | 2018-07-16 | 2025-02-01 | Regeneron Pharma | Non-human animal models of DITRA disease and their uses |
| 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 |
| CA3120799A1 (en) | 2018-12-20 | 2020-06-25 | Regeneron Pharmaceuticals, Inc. | 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 |
| EP3927832A4 (en) | 2019-02-18 | 2022-11-30 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | GENETICALLY MODIFIED NON-HUMAN ANIMALS WITH HUMANIZED IMMUNOGLOBULIN LOCUS |
| JP2022520819A (ja) | 2019-02-22 | 2022-04-01 | 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 | 遺伝子改変ナトリウムチャネルを有する齧歯類およびその使用方法 |
| WO2020206134A1 (en) | 2019-04-04 | 2020-10-08 | Regeneron Pharmaceuticals, Inc. | Methods for scarless introduction of targeted modifications into targeting vectors |
| ES2966625T3 (es) | 2019-04-04 | 2024-04-23 | Regeneron Pharma | Roedores que comprenden un locus del factor de coagulación 12 humanizado |
| WO2020214690A1 (en) | 2019-04-15 | 2020-10-22 | Qwixel Therapeutics | Fusion protein composition(s) comprising targeted masked type i interferons (ifna and ifnb) and an antibody against tumor antigen, for use in the treatment of cancer |
| US11891618B2 (en) | 2019-06-04 | 2024-02-06 | Regeneron Pharmaceuticals, Inc. | Mouse comprising a humanized TTR locus with a beta-slip mutation and methods of use |
| 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 |
| US11622547B2 (en) | 2019-06-07 | 2023-04-11 | Regeneran Pharmaceuticals, Inc. | Genetically modified mouse that expresses human albumin |
| CA3217237A1 (en) | 2019-06-27 | 2020-12-30 | Regeneration Pharmaceuticals, Inc. | Modeling tdp-43 proteinopathy |
| AU2020300002A1 (en) | 2019-07-01 | 2022-02-24 | Tonix Pharma Limited | Anti-CD154 antibodies and uses thereof |
| WO2021066869A1 (en) | 2019-10-04 | 2021-04-08 | TAE Life Sciences | Antibody compositions comprising fc mutations and site-specific conjugation properties |
| 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 |
| EP4099821A1 (en) | 2020-02-07 | 2022-12-14 | Regeneron Pharmaceuticals, Inc. | <smallcaps/>? ? ?klkb1? ? ? ? ?non-human animals comprising a humanizedlocus and methods of use |
| WO2021195079A1 (en) | 2020-03-23 | 2021-09-30 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized ttr locus comprising a v30m mutation and methods of use |
| WO2021216505A1 (en) | 2020-04-21 | 2021-10-28 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized cxcl13 gene |
| KR20230018439A (ko) | 2020-06-02 | 2023-02-07 | 바이오사이토젠 파마슈티컬스 (베이징) 컴퍼니 리미티드 | 공동 경쇄 면역글로불린 좌위를 갖는 유전자 변형 비인간 동물 |
| RU2751237C1 (ru) * | 2020-06-10 | 2021-07-12 | Регенерон Фармасьютикалс, Инк. | Способы и композиции для направленной модификации генома |
| KR20230024822A (ko) | 2020-06-25 | 2023-02-21 | 주식회사 휴맵 | 이형접합성 형질전환 동물 |
| CA3187680A1 (en) | 2020-09-11 | 2022-03-17 | Yashu Liu | Identification and production of antigen-specific antibodies |
| AU2021352420A1 (en) | 2020-10-01 | 2023-04-27 | 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 |
| KR20230124973A (ko) | 2020-12-21 | 2023-08-28 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 tslp 유전자, 인간화 tslp 수용체 유전자, 및/또는인간화 il7ra 유전자를 갖는 비인간 동물 |
| CA3165366A1 (en) | 2020-12-23 | 2022-06-30 | Regeneron Pharmaceuticals, Inc. | Nucleic acids encoding anchor modified antibodies and uses thereof |
| US20240059781A1 (en) | 2021-01-06 | 2024-02-22 | Tonix Pharma Limited | Methods of inducing immune tolerance with modified anti-cd154 antibodies |
| AU2022249328A1 (en) | 2021-03-31 | 2023-09-21 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice comprising humanized cellular immune system components with improved diversity of tcrβ repertoire |
| US20240199725A1 (en) | 2021-04-16 | 2024-06-20 | Korea University Research And Business Foundation | Human antibody targeting covid-19 virus |
| JP2024523290A (ja) | 2021-06-18 | 2024-06-28 | ナミ セラピューティクス， インコーポレイテッド | がんの処置およびその方法における使用のための、マスクされたＩ型インターフェロン（ＩＦＮαおよびＩＦＮβ）を含む融合タンパク質組成物 |
| EP4423271A2 (en) | 2021-10-28 | 2024-09-04 | Regeneron Pharmaceuticals, Inc. | Crispr/cas-related methods and compositions for knocking out c5 |
| CN118632622A (zh) | 2021-12-08 | 2024-09-10 | 瑞泽恩制药公司 | 突变型肌纤蛋白疾病模型及其用途 |
| WO2023122506A1 (en) | 2021-12-20 | 2023-06-29 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising humanized ace2 and tmprss loci |
| US20250194571A1 (en) | 2022-02-07 | 2025-06-19 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for defining optimal treatment timeframes in lysosomal disease |
| US20230257432A1 (en) | 2022-02-11 | 2023-08-17 | 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 |
| WO2023235725A2 (en) | 2022-05-31 | 2023-12-07 | Regeneron Pharmaceuticals, Inc. | Crispr-based therapeutics for c9orf72 repeat expansion disease |
| WO2023235677A1 (en) | 2022-05-31 | 2023-12-07 | Regeneron Pharmaceuticals, Inc. | Animal model of tdp-43 proteinopathy |
| US20230417899A1 (en) | 2022-06-27 | 2023-12-28 | Oshkosh Corporation | Position tracking for a lift device |
| IL318159A (en) | 2022-07-19 | 2025-03-01 | Regeneron Pharma | Genetically modified animal model and its use to model the human immune system |
| IL319406A (en) | 2022-09-22 | 2025-05-01 | Regeneron Pharma | Genetically modified mice expressing components of the human cellular immune system |
| WO2024073679A1 (en) | 2022-09-29 | 2024-04-04 | Regeneron Pharmaceuticals, Inc. | Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes |
| WO2024163650A1 (en) | 2023-02-01 | 2024-08-08 | Regeneron Pharmaceuticals, Inc. | Animals comprising a modified klhdc7b locus |
| EP4727971A1 (en) | 2023-06-13 | 2026-04-22 | Adcentrx Therapeutics Inc. | Methods and compositions related to antibodies and antibody drug conjugates (adcs) that bind nectin-4 proteins |
| US20240415103A1 (en) | 2023-06-16 | 2024-12-19 | 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 |
| US20250255282A1 (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 |
| WO2025264533A1 (en) | 2024-06-17 | 2025-12-26 | Adcentrx Therapeutics Inc. | Methods and compositions related to antibody drug conjugates (adcs) that bind steap-1 proteins |
| WO2026030428A2 (en) | 2024-08-01 | 2026-02-05 | Regeneron Pharmaceuticals, Inc. | Prostate-specific antigen peptides and uses thereof |
| WO2026035843A2 (en) | 2024-08-06 | 2026-02-12 | Regeneron Pharmaceuticals, Inc. | Non-human animals having modified immunoglobulin heavy chain constant region locus and uses thereof |
| WO2026039661A1 (en) | 2024-08-15 | 2026-02-19 | Regeneron Pharmaceuticals, Inc. | Non-human animals with humanized fc epsilon receptors that lack functional alpha-1, 3-galactosyltransferase (ggta1) |
Family Cites Families (8)
| 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 |
| 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 |
| 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 |
| CA2161351C (en) * | 1993-04-26 | 2010-12-21 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
| ATE307830T1 (de) * | 1999-02-05 | 2005-11-15 | Therapeutic Human Polyclonals | Aus nicht-menschlichen transgenen tieren gewonnene menschliche polyklonale antikörper |
| US6586251B2 (en) * | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
-
2000
- 2000-12-07 US US09/732,234 patent/US6586251B2/en not_active Expired - Lifetime
-
2001
- 2001-10-31 CN CNB018216609A patent/CN100497642C/zh not_active Expired - Lifetime
- 2001-10-31 RU RU2003116125/13A patent/RU2290441C2/ru active
- 2001-10-31 NZ NZ525511A patent/NZ525511A/en not_active IP Right Cessation
- 2001-10-31 CA CA2426398A patent/CA2426398C/en not_active Expired - Lifetime
- 2001-10-31 PL PL361927A patent/PL204759B1/pl unknown
- 2001-10-31 JP JP2002539535A patent/JP5339566B2/ja not_active Expired - Lifetime
- 2001-10-31 HU HU0301575A patent/HU227639B1/hu unknown
- 2001-10-31 AU AU2004802A patent/AU2004802A/xx active Pending
- 2001-10-31 AU AU2002220048A patent/AU2002220048B2/en not_active Expired
- 2001-10-31 KR KR1020037005885A patent/KR100833136B1/ko not_active Expired - Lifetime
- 2001-10-31 CZ CZ2003-1197A patent/CZ304856B6/cs not_active IP Right Cessation
- 2001-10-31 MX MXPA03003797A patent/MXPA03003797A/es active IP Right Grant
- 2001-10-31 WO PCT/US2001/045375 patent/WO2002036789A2/en not_active Ceased
- 2001-10-31 DE DE60121372T patent/DE60121372T2/de not_active Expired - Lifetime
- 2001-10-31 BR BRPI0115096A patent/BRPI0115096B1/pt active IP Right Grant
- 2001-10-31 AT AT01992495T patent/ATE332388T1/de not_active IP Right Cessation
- 2001-10-31 EP EP01992495A patent/EP1399575B1/en not_active Expired - Lifetime
-
2003
- 2003-04-28 NO NO20031897A patent/NO332300B1/no not_active IP Right Cessation
-
2010
- 2010-06-15 JP JP2010136321A patent/JP2010220628A/ja active Pending
-
2013
- 2013-05-23 JP JP2013108631A patent/JP5892975B2/ja not_active Expired - Lifetime
- 2013-11-29 JP JP2013247817A patent/JP5945263B2/ja not_active Expired - Lifetime
-
2014
- 2014-12-26 JP JP2014265082A patent/JP2015062432A/ja not_active Withdrawn
-
2017
- 2017-02-14 JP JP2017024803A patent/JP6486979B2/ja not_active Expired - Lifetime
- 2017-02-14 JP JP2017024802A patent/JP2017123855A/ja not_active Withdrawn
Non-Patent Citations (2)
| Title |
|---|
| Nature Biotech., vol.15(9):859-865 |
| Nucleic Acids Research, vol.27(17):e16 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20150141987A (ko) * | 2013-04-16 | 2015-12-21 | 리제너론 파마슈티칼스 인코포레이티드 | 랫트 게놈의 표적화된 변형 |
| KR102186281B1 (ko) * | 2013-04-16 | 2020-12-03 | 리제너론 파마슈티칼스 인코포레이티드 | 랫트 게놈의 표적화된 변형 |
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