MX2016008258A - Celulas eucariotas novedosas y metodos para la expresion recombinante de un producto de interes. - Google Patents

Celulas eucariotas novedosas y metodos para la expresion recombinante de un producto de interes.

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Publication number
MX2016008258A
MX2016008258A MX2016008258A MX2016008258A MX2016008258A MX 2016008258 A MX2016008258 A MX 2016008258A MX 2016008258 A MX2016008258 A MX 2016008258A MX 2016008258 A MX2016008258 A MX 2016008258A MX 2016008258 A MX2016008258 A MX 2016008258A
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MX
Mexico
Prior art keywords
interest
product
new
cells
eucariot
Prior art date
Application number
MX2016008258A
Other languages
English (en)
Other versions
MX373329B (es
Inventor
Jostock Thomas
Laux Holger
Ritter Anett
Original Assignee
Novartis Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=52278688&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=MX2016008258(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Novartis Ag filed Critical Novartis Ag
Publication of MX2016008258A publication Critical patent/MX2016008258A/es
Publication of MX373329B publication Critical patent/MX373329B/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702Regulators; Modulating activity
    • C07K14/4703Inhibitors; Suppressors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • 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
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00Preparation of peptides or proteins
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6888Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/14Type of nucleic acid interfering nucleic acids [NA]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2510/00Genetically modified cells
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    • C12N2511/00Cells for large scale production
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicinal Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Cell Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Mycology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La presente divulgación se refiere a nuevos derivados de célula huésped eucariota adecuado para la producción recombinante de un producto de interés, en el que el genoma de la célula hospedera se altera de manera que el efecto de la proteína FAM60A se altera en dicha célula, por ejemplo, reduciendo o eliminando la expresión funcional del gen FAM60A mejorando así las características de estabilidad. Además, la presente descripción proporciona tecnologías asociadas en el que dichas células hospederas que se utilizan en tecnologías recombinantes de producción.
MX2016008258A 2013-12-20 2014-12-18 Células eucariotas novedosas y métodos para la expresión recombinante de un producto de interés. MX373329B (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361919340P 2013-12-20 2013-12-20
PCT/IB2014/067076 WO2015092737A1 (en) 2013-12-20 2014-12-18 Novel eukaryotic cells and methods for recombinantly expressing a product of interest

Publications (2)

Publication Number Publication Date
MX2016008258A true MX2016008258A (es) 2016-09-29
MX373329B MX373329B (es) 2020-05-21

Family

ID=52278688

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2016008258A MX373329B (es) 2013-12-20 2014-12-18 Células eucariotas novedosas y métodos para la expresión recombinante de un producto de interés.

Country Status (18)

Country Link
US (2) US11242551B2 (es)
EP (2) EP3083677B1 (es)
JP (1) JP6709156B2 (es)
KR (1) KR102288232B1 (es)
CN (1) CN106029691B (es)
AU (1) AU2014369177B2 (es)
BR (1) BR112016013420A2 (es)
CA (1) CA2934412C (es)
DK (1) DK3083677T3 (es)
ES (1) ES2758505T3 (es)
IL (1) IL245856B (es)
LT (1) LT3083677T (es)
MX (1) MX373329B (es)
PL (1) PL3083677T3 (es)
PT (1) PT3083677T (es)
RU (1) RU2712507C2 (es)
SG (1) SG11201604218RA (es)
WO (1) WO2015092737A1 (es)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3604331A1 (en) 2013-12-20 2020-02-05 Novartis AG Novel eukaryotic cells and methods for recombinantly expressing a product of interest
EP3015475A1 (en) 2014-10-31 2016-05-04 Novartis AG Mammalian cells expressing cytomegalovirus antigens
EP3048114A1 (en) 2015-01-22 2016-07-27 Novartis AG Cytomegalovirus antigens and uses thereof
CN108018302A (zh) * 2016-10-31 2018-05-11 三生国健药业(上海)股份有限公司 一种高表达外源蛋白稳定细胞株的筛选方法
UY37758A (es) 2017-06-12 2019-01-31 Novartis Ag Método de fabricación de anticuerpos biespecíficos, anticuerpos biespecíficos y uso terapéutico de dichos anticuerpos
CN107723276B (zh) * 2017-11-02 2021-08-13 上海交通大学 一种稳定高表达目标产物的细胞株的构建方法和试剂盒
WO2019105770A1 (en) 2017-11-28 2019-06-06 Danmarks Tekniske Universitet Glycosylation of proteins
UY38299A (es) 2018-07-18 2020-02-28 Novartis Ag Apirasas solubilizadas, métodos y usos
WO2020084034A1 (en) 2018-10-26 2020-04-30 F. Hoffmann-La Roche Ag Multispecific antibody screening method using recombinase mediated cassette exchange
US20240409614A1 (en) 2021-11-09 2024-12-12 Danmarks Tekniske Universitet Variants of alpha-1-antitrypsin

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2585532B2 (ja) 1986-05-10 1997-02-26 三井東圧化学株式会社 動物細胞の形質転換体及びそれを得る方法並びにその形質転換体を用いてt−PAを生産する方法
DK0557459T3 (da) 1990-11-13 1997-12-15 Immunex Corp Bifunktionelle, selekterbare fusionsgener
ATE199023T1 (de) 1991-03-29 2001-02-15 Genentech Inc Methoden zur selektion von rekombinanten wirtszellen welche hohe mengen von einem gewünschten protein exprimieren
AU6953394A (en) 1993-05-21 1994-12-20 Targeted Genetics Corporation Bifunctional selectable fusion genes based on the cytosine deaminase (cd) gene
JP4031154B2 (ja) * 1999-07-30 2008-01-09 独立行政法人科学技術振興機構 遺伝子増幅細胞の迅速選択法
JP2004538002A (ja) 2001-08-02 2004-12-24 アルタナ ファルマ アクチエンゲゼルシャフト 停止コドン抑制による組み換え遺伝子発現の新規方法
US20050221325A1 (en) 2002-05-22 2005-10-06 Greg Thill Detection of secreted polypeptides
AU2003294217A1 (en) 2002-08-29 2004-05-04 Five Prime Therapeutics, Inc. Human polypeptides encoded by polynucleotides and methods of their use
PT1601776E (pt) 2003-03-11 2008-09-17 Serono Lab Vectores de expressão que compreendem o promotor ie2 do mcmv
GB0324044D0 (en) * 2003-10-14 2003-11-19 Astrazeneca Ab Protein
EP1716233B1 (en) 2004-01-30 2009-08-26 Maxygen Holdings Ltd. Regulated stop codon readthrough
US20050272061A1 (en) 2004-02-19 2005-12-08 Seattle Genetics, Inc. Expression profiling in non-small cell lung cancer
IL165484A0 (en) 2004-11-30 2006-01-15 Applied Research Systems Production of proteins
ES2573027T3 (es) 2006-05-17 2016-06-03 F. Hoffmann-La Roche Ag Células productoras de polipéptido
WO2008133711A2 (en) * 2006-10-30 2008-11-06 Functional Genetics, Inc. Random homozygous gene perturbation to enhance antibody production
WO2008064095A1 (en) 2006-11-17 2008-05-29 3M Innovative Properties Company Ribbon curling device
CA2677568A1 (en) 2007-02-15 2008-08-21 Dsm Ip Assets B.V. A recombinant host cell for the production of a compound of interest
BRPI0811843A2 (pt) * 2007-05-22 2014-10-07 Basf Plant Science Gmbh Métodos para a produção de uma planta transgênica, e para seleção de antagonistas, molécula, iniciador, mutante dominante negativo de um polipeptídeo, construto de ácido nucleico, vetor, célula de planta transgênica, planta ou uma parte da mesma, polipeptídeo isolado, anticorpo, tecido de planta, planta, material de planta colhido ou material de propagação de uma planta, processos para a produção de um polipeptídeo, e para a identificação de um composto, composição, e, uso da molécula de ácido nucleico, do construto de ácido nucleico e do vetor
US8697397B2 (en) 2007-08-07 2014-04-15 Chugai Seiyaku Kabushiki Kaisha Method of producing heterogeneous protein
PT2227549E (pt) 2007-12-21 2015-10-08 Novartis Ag Sistema de seleção para cultura de células eucarióticas com base num gene de recetor de folato ligado à membrana
KR101734585B1 (ko) 2008-08-28 2017-05-11 노파르티스 아게 정지 코돈 번역초과에 의한 폴리펩티드 이소형의 세포 표면 표시
PT2401377T (pt) 2009-02-27 2016-08-18 Novartis Ag Sistema de vectores de expressão compreendendo dois marcadores de selecção
CN102414320A (zh) 2009-05-15 2012-04-11 贝林格尔.英格海姆国际有限公司 具有降低的nocr表达的改良细胞系及其用途
EP3604331A1 (en) 2013-12-20 2020-02-05 Novartis AG Novel eukaryotic cells and methods for recombinantly expressing a product of interest
WO2019195274A2 (en) * 2018-04-02 2019-10-10 University Of Delaware Method to alter chinese hamster ovary cell line stability
CN114381433B (zh) * 2021-12-31 2024-05-10 浙江大学 Fam60a修饰的间充质干细胞及其制备方法和应用

Also Published As

Publication number Publication date
RU2712507C2 (ru) 2020-01-29
CN106029691A (zh) 2016-10-12
IL245856A0 (en) 2016-07-31
PT3083677T (pt) 2019-12-02
IL245856B (en) 2021-06-30
JP6709156B2 (ja) 2020-06-10
CA2934412A1 (en) 2015-06-25
US20170058307A1 (en) 2017-03-02
CA2934412C (en) 2024-02-20
US20220325310A1 (en) 2022-10-13
CN106029691B (zh) 2026-02-10
LT3083677T (lt) 2019-12-10
KR102288232B1 (ko) 2021-08-10
AU2014369177A1 (en) 2016-06-16
AU2014369177B2 (en) 2017-04-20
ES2758505T3 (es) 2020-05-05
WO2015092737A1 (en) 2015-06-25
KR20160099675A (ko) 2016-08-22
RU2016129278A (ru) 2018-01-25
JP2016540518A (ja) 2016-12-28
EP3083677A1 (en) 2016-10-26
US11242551B2 (en) 2022-02-08
EP3083677B1 (en) 2019-08-28
SG11201604218RA (en) 2016-07-28
PL3083677T3 (pl) 2020-03-31
MX373329B (es) 2020-05-21
DK3083677T3 (da) 2019-11-25
EP3604332A1 (en) 2020-02-05
BR112016013420A2 (pt) 2017-09-26

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