CN109071633B - 基于使用表达增强性基因座来制备抗体的组合物和方法 - Google Patents

基于使用表达增强性基因座来制备抗体的组合物和方法 Download PDF

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CN109071633B
CN109071633B CN201780024560.2A CN201780024560A CN109071633B CN 109071633 B CN109071633 B CN 109071633B CN 201780024560 A CN201780024560 A CN 201780024560A CN 109071633 B CN109071633 B CN 109071633B
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nucleic acid
hcf
rrs
nucleotide sequence
sequence encoding
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CN109071633A (zh
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R·巴布
D·布拉科夫
陈刚
J·P·梵迪
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Regeneron Pharmaceuticals Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • C12N15/65—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression using markers
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6897—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/526—CH3 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2510/00—Genetically modified cells
    • C12N2510/02—Cells for production

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CN201780024560.2A 2016-04-20 2017-04-20 基于使用表达增强性基因座来制备抗体的组合物和方法 Active CN109071633B (zh)

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US201662325385P 2016-04-20 2016-04-20
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Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG10202010156XA (en) 2016-04-20 2020-11-27 Regeneron Pharma Compositions and methods for making antibodies based on use of an expression-enhancing locus
IL275462B2 (en) * 2017-12-22 2026-01-01 Genentech Inc Targeted integration of nucleic acids
WO2020034097A1 (en) 2018-08-14 2020-02-20 Wuxi Biologics (Shanghai) Co., Ltd. Transcriptional regulatory element and its use in enhancing the expression of exogenous protein
KR102559149B1 (ko) 2018-10-26 2023-07-24 에프. 호프만-라 로슈 아게 재조합효소 매개 카세트 교환을 이용한 다중특이적 항체 스크리닝 방법
CN113631711B (zh) * 2018-12-21 2025-03-04 豪夫迈·罗氏有限公司 核酸的靶向整合
KR20210134932A (ko) * 2019-03-29 2021-11-11 에프. 호프만-라 로슈 아게 정의된 조직에서 다중 발현 카세트의 표적화된 통합에 의해 FcRn 발현 세포를 생성하는 방법
EP3950938A4 (en) 2019-04-02 2023-01-18 Chugai Seiyaku Kabushiki Kaisha PROCEDURE FOR INTRODUCING A TARGET-SPECIFIC ALIEN
BR112021025425A2 (pt) * 2019-06-19 2022-02-01 Hoffmann La Roche Método para produzir uma célula de mamífero recombinante e uso de mrna de recombinase cre
CA3140323A1 (en) * 2019-06-19 2020-12-24 Johannes Auer Method for the generation of a multivalent, bispecific antibody expressing cell by targeted integration of multiple expression cassettes in a defined organization
MX2021015648A (es) 2019-06-19 2022-02-03 Hoffmann La Roche Metodo para la generacion de una celula que expresa un anticuerpo multiespecifico multivalente mediante integracion dirigida de multiples casetes de expresion en una organizacion definida.
KR20220010019A (ko) * 2019-06-19 2022-01-25 에프. 호프만-라 로슈 아게 정의된 조직에서 다중 발현 카세트의 표적화된 통합에 의해 2가 이중특이성 항체 발현 세포를 생성하는 방법
CA3140287A1 (en) * 2019-06-19 2020-12-24 Johannes Auer Method for the generation of a trivalent antibody expressing cell by targeted integration of multiple expression cassettes in a defined organization
AU2020308002A1 (en) * 2019-06-26 2022-01-20 Genentech, Inc. Randomized configuration targeted integration of nucleic acids
CN115335517A (zh) * 2020-01-10 2022-11-11 豪夫迈·罗氏有限公司 用于从短片段组装大核酸的方法
EP4453227A1 (en) * 2021-12-22 2024-10-30 Genentech, Inc. Multi-vector recombinase mediated cassette exchange
CN121794393A (zh) 2023-09-07 2026-04-03 里珍纳龙药品有限公司 经共价表面修饰的腺相关病毒的生产和纯化
CN119955730A (zh) * 2023-11-08 2025-05-09 深圳太力生物技术有限责任公司 一种细胞株及其制备方法与应用
TW202540433A (zh) 2023-11-21 2025-10-16 美商再生元醫藥公司 藉由活體外接合產生共價表面修飾之腺相關病毒及共價表面修飾的腺相關病毒之純化

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107109434A (zh) * 2014-10-23 2017-08-29 瑞泽恩制药公司 新颖cho整合位点和其用途

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4634665A (en) 1980-02-25 1987-01-06 The Trustees Of Columbia University In The City Of New York Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4656134A (en) 1982-01-11 1987-04-07 Board Of Trustees Of Leland Stanford Jr. University Gene amplification in eukaryotic cells
US20020062010A1 (en) 1997-05-02 2002-05-23 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
US6800457B2 (en) 1998-09-22 2004-10-05 Bristol-Myers Squibb Company Expression vectors containing hot spot for increased recombinant protein expression in transfected cells
KR100781481B1 (ko) 2000-08-07 2007-12-03 세로노 제네틱스 인스티튜트 에스.에이. 정신분열증 관련된 유전자와 단백질
GB0209884D0 (en) 2002-04-30 2002-06-05 Ares Trading Sa Proteins
AU2003237259B2 (en) 2002-05-29 2008-01-24 Regeneron Pharmaceuticals, Inc. Inducible eukaryotic expression system
CA2504595A1 (en) 2002-11-14 2004-06-03 Lynne Krummen Intron fusion construct and method of using for selecting high-expressing production cell lines
CN101198698B (zh) 2005-03-31 2014-03-19 中外制药株式会社 通过调节多肽缔合制备多肽的方法
WO2007110205A2 (en) 2006-03-24 2007-10-04 Merck Patent Gmbh Engineered heterodimeric protein domains
NZ587107A (en) 2006-06-02 2012-05-25 Regeneron Pharma High affinity antibodies to human il-6 receptor
WO2008079943A2 (en) 2006-12-21 2008-07-03 Smithkline Beecham Corporation Novel methods
US20080216185A1 (en) 2007-01-19 2008-09-04 Invitrogen Corporation Compositions and Methods for Genetic Manipulation and Monitoring of Cell Lines
CN104497143B (zh) 2007-03-29 2020-08-25 健玛保 双特异性抗体及其制造方法
WO2008151219A1 (en) * 2007-06-04 2008-12-11 Regeneron Pharmaceuticals, Inc. Enhanced expression and stability regions
EP3663318A1 (en) 2008-01-07 2020-06-10 Amgen Inc. Method for making antibody fc-heterodimeric molecules using electrostatic steering effects
US8409838B2 (en) 2009-06-02 2013-04-02 Regeneron Pharmaceuticals, Inc. Fucosylation-deficient cells
LT2975051T (lt) 2009-06-26 2021-07-12 Regeneron Pharmaceuticals, Inc. Lengvai išskiriami bispecifiniai antikūnai su natyvios formos imunoglobulinu
MX2012003396A (es) 2009-09-16 2012-04-10 Genentech Inc Complejos de proteina conteniendo helice super-enrollada y/o enlazador tether y usos de los mismos.
JP6040148B2 (ja) 2010-04-20 2016-12-07 ゲンマブ エー／エス ヘテロ二量体抗体Ｆｃ含有タンパク質およびその産生方法
AU2011290480B2 (en) 2010-08-16 2015-07-30 Novimmune S.A. Methods for the generation of multispecific and multivalent antibodies
PT3865581T (pt) 2011-08-05 2024-10-04 Regeneron Pharma Murganhos da cadeia leve universal humanizada
TWI641687B (zh) 2012-05-29 2018-11-21 美商再生元醫藥公司 生產細胞株增強子
EP2711428A1 (en) 2012-09-21 2014-03-26 Lonza Biologics plc. Site-specific integration
JOP20200236A1 (ar) 2012-09-21 2017-06-16 Regeneron Pharma الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها
TW202423993A (zh) 2012-11-14 2024-06-16 美商再生元醫藥公司 重組細胞表面捕捉蛋白質
TWI682941B (zh) 2013-02-01 2020-01-21 美商再生元醫藥公司 含嵌合恆定區之抗體
US20140308285A1 (en) 2013-03-15 2014-10-16 Amgen Inc. Heterodimeric bispecific antibodies
TWI670283B (zh) 2013-12-23 2019-09-01 美商建南德克公司 抗體及使用方法
TWI754319B (zh) 2014-03-19 2022-02-01 美商再生元醫藥公司 用於腫瘤治療之方法及抗體組成物
KR102777500B1 (ko) 2015-09-23 2025-03-11 리제너론 파아마슈티컬스, 인크. 최적화된 항-cd3 이중특이적 항체 및 이의 용도
SG10202010156XA (en) 2016-04-20 2020-11-27 Regeneron Pharma Compositions and methods for making antibodies based on use of an expression-enhancing locus

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107109434A (zh) * 2014-10-23 2017-08-29 瑞泽恩制药公司 新颖cho整合位点和其用途

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EP3445780A1 (en) 2019-02-27
US20230322956A1 (en) 2023-10-12
TW201803981A (zh) 2018-02-01
SG10202010156XA (en) 2020-11-27
JP7789143B2 (ja) 2025-12-19
AU2017253240A1 (en) 2018-09-20
US12503520B2 (en) 2025-12-23
AU2024220126A1 (en) 2024-10-17
IL309065A (en) 2024-02-01
IL262268B2 (en) 2024-05-01
CN109071633A (zh) 2018-12-21
SG11201807881VA (en) 2018-10-30
IL262268A (en) 2018-11-29
JP2019514358A (ja) 2019-06-06
AR108295A1 (es) 2018-08-08
JP7134868B2 (ja) 2022-09-12
IL262268B1 (en) 2024-01-01
JP2024164196A (ja) 2024-11-26
KR20210135340A (ko) 2021-11-12
KR102474757B1 (ko) 2022-12-07
WO2017184831A1 (en) 2017-10-26
US11530277B2 (en) 2022-12-20
KR20180134894A (ko) 2018-12-19
IL309065B1 (en) 2026-03-01
EA201892137A1 (ru) 2019-03-29
AU2017253240B2 (en) 2024-07-04
JP7546015B2 (ja) 2024-09-05
CA3015371A1 (en) 2017-10-26
JP2022164824A (ja) 2022-10-27
BR112018071285A2 (pt) 2019-02-12
CN116004544A (zh) 2023-04-25
US20190263937A1 (en) 2019-08-29
MX2018012866A (es) 2019-03-11

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