GB2502127A - Multivalent antibodies and in vivo methods for their production - Google Patents

Multivalent antibodies and in vivo methods for their production Download PDF

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Publication number
GB2502127A
GB2502127A GB1208708.6A GB201208708A GB2502127A GB 2502127 A GB2502127 A GB 2502127A GB 201208708 A GB201208708 A GB 201208708A GB 2502127 A GB2502127 A GB 2502127A
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GB
United Kingdom
Prior art keywords
vertebrate
antibody
cell
domain
epitope binding
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
GB1208708.6A
Other languages
English (en)
Other versions
GB201208708D0 (en
Inventor
E-Chiang Lee
Volker Germaschewski
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kymab Ltd
Original Assignee
Kymab Ltd
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.)
Filing date
Publication date
Application filed by Kymab Ltd filed Critical Kymab Ltd
Priority to GB1208708.6A priority Critical patent/GB2502127A/en
Publication of GB201208708D0 publication Critical patent/GB201208708D0/en
Priority to JP2015502440A priority patent/JP2015512635A/ja
Priority to SG11201405059XA priority patent/SG11201405059XA/en
Priority to PCT/GB2013/050683 priority patent/WO2013144567A1/en
Priority to EP13711120.9A priority patent/EP2831245A1/en
Priority to EP13723933.1A priority patent/EP2852672A2/en
Priority to SG11201406947RA priority patent/SG11201406947RA/en
Priority to EP22173215.9A priority patent/EP4116427A1/en
Priority to PCT/GB2013/051280 priority patent/WO2013171505A2/en
Priority to JP2015512133A priority patent/JP2015519055A/ja
Priority to CN201380038167.0A priority patent/CN104508135B/zh
Publication of GB2502127A publication Critical patent/GB2502127A/en
Priority to US14/498,685 priority patent/US10251377B2/en
Priority to US14/543,359 priority patent/US10667501B2/en
Priority to US16/353,870 priority patent/US11297811B2/en
Priority to US16/869,416 priority patent/US20200267952A1/en
Priority to US17/707,060 priority patent/US20220295765A1/en
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
    • C07K16/462—Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
    • 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
    • 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
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. 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
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • 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
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
    • 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
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • 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
    • A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
    • 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
    • A01K2217/20—Animal model comprising regulated expression system
    • A01K2217/206—Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
    • 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
    • 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
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/01—Animal expressing industrially exogenous proteins
    • 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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35—Valency
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • 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
    • 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
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • C12N2015/8518—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/90—Vectors containing a transposable element

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Animal Husbandry (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
GB1208708.6A 2012-03-28 2012-05-17 Multivalent antibodies and in vivo methods for their production Withdrawn GB2502127A (en)

Priority Applications (16)

Application Number Priority Date Filing Date Title
GB1208708.6A GB2502127A (en) 2012-05-17 2012-05-17 Multivalent antibodies and in vivo methods for their production
JP2015502440A JP2015512635A (ja) 2012-03-28 2013-03-18 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
SG11201405059XA SG11201405059XA (en) 2012-03-28 2013-03-18 Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies
PCT/GB2013/050683 WO2013144567A1 (en) 2012-03-28 2013-03-18 Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies
EP13711120.9A EP2831245A1 (en) 2012-03-28 2013-03-18 Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies
CN201380038167.0A CN104508135B (zh) 2012-05-17 2013-05-17 用于在体内产生双重特异性免疫球蛋白或者仅高变重链免疫球蛋白的转基因非人脊椎动物
PCT/GB2013/051280 WO2013171505A2 (en) 2012-05-17 2013-05-17 In vivo guided selection & antibodies
SG11201406947RA SG11201406947RA (en) 2012-05-17 2013-05-17 Transgenic non-human vertebrate for the in vivo production of dual specificity|immunoglobulins or hypermutated heavy chain only immunoglobulins
EP22173215.9A EP4116427A1 (en) 2012-05-17 2013-05-17 In vivo guided selection & antibodies
EP13723933.1A EP2852672A2 (en) 2012-05-17 2013-05-17 In vivo guided selection&antibodies
JP2015512133A JP2015519055A (ja) 2012-05-17 2013-05-17 二重特異性免疫グロブリンまたは超変異重鎖のみの免疫グロブリンのinvivoでの生成のためのトランスジェニック非ヒト脊椎動物
US14/498,685 US10251377B2 (en) 2012-03-28 2014-09-26 Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies
US14/543,359 US10667501B2 (en) 2012-05-17 2014-11-17 Transgenic non-human vertebrate for the in vivo production of dual specificity immunoglobulins or hypermutated heavy chain only immunoglobulins
US16/353,870 US11297811B2 (en) 2012-03-28 2019-03-14 Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies
US16/869,416 US20200267952A1 (en) 2012-05-17 2020-05-07 Transgenic non-human vertebrate for the in vivo production of dual specificity immunoglobulins or hypermutated heavy chain only immunoglobulins
US17/707,060 US20220295765A1 (en) 2012-03-28 2022-03-29 Transgenic Non-Human Vertebrate for the Expression of Class-Switched, Fully Human, Antibodies

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB1208708.6A GB2502127A (en) 2012-05-17 2012-05-17 Multivalent antibodies and in vivo methods for their production

Publications (2)

Publication Number Publication Date
GB201208708D0 GB201208708D0 (en) 2012-07-04
GB2502127A true GB2502127A (en) 2013-11-20

Family

ID=46546244

Family Applications (1)

Application Number Title Priority Date Filing Date
GB1208708.6A Withdrawn GB2502127A (en) 2012-03-28 2012-05-17 Multivalent antibodies and in vivo methods for their production

Country Status (7)

Country Link
US (2) US10667501B2 (enExample)
EP (2) EP4116427A1 (enExample)
JP (1) JP2015519055A (enExample)
CN (1) CN104508135B (enExample)
GB (1) GB2502127A (enExample)
SG (1) SG11201406947RA (enExample)
WO (1) WO2013171505A2 (enExample)

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GB2584219A (en) * 2014-10-22 2020-11-25 Crescendo Biologics Ltd Transgenic mice
GB2547587B (en) * 2014-10-22 2020-12-09 Crescendo Biologics Ltd Transgenic mice

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US10662256B2 (en) 2010-07-26 2020-05-26 Trianni, Inc. Transgenic mammals and methods of use thereof
CN103025884B (zh) 2010-07-26 2015-11-25 特里安尼公司 转基因动物和使用方法
US10793829B2 (en) 2010-07-26 2020-10-06 Trianni, Inc. Transgenic mammals and methods of use thereof
EP2601298B1 (en) 2010-08-02 2016-11-30 Regeneron Pharmaceuticals, Inc. Mice that make binding proteins comprising vl domains
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WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
EP4074833A1 (en) 2011-10-17 2022-10-19 Regeneron Pharmaceuticals, Inc. Restricted immunoglobulin heavy chain mice
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
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
NZ703689A (en) 2012-06-12 2016-05-27 Regeneron Pharma Humanized non-human animals with restricted immunoglobulin heavy chain loci
RS57582B1 (sr) 2013-02-20 2018-11-30 Regeneron Pharma Nehumane životinje sa modifikovanim sekvencama imunoglobulinskog teškog lanca
US10993420B2 (en) 2013-03-15 2021-05-04 Erasmus University Medical Center Production of heavy chain only antibodies in transgenic mammals
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
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
WO2015049517A2 (en) 2013-10-01 2015-04-09 Kymab Limited Animal models and therapeutic molecules
AU2015230938C1 (en) 2014-03-21 2021-10-14 Regeneron Pharmaceuticals, Inc. Non-human animals that make single domain binding proteins
SG10201808083VA (en) 2014-03-21 2018-10-30 Regeneron Pharma Vl antigen binding proteins exhibiting distinct binding characteristics
CN107438622A (zh) * 2015-03-19 2017-12-05 瑞泽恩制药公司 选择结合抗原的轻链可变区的非人动物
JP2018524373A (ja) 2015-07-15 2018-08-30 ザイムワークス,インコーポレイテッド 薬物がコンジュゲートされた二重特異性抗原結合コンストラクト
WO2017035252A1 (en) * 2015-08-24 2017-03-02 Trianni, Inc. Enhanced production of immunoglobulins
EP3384030A4 (en) 2015-12-03 2019-07-03 Trianni, Inc. IMPROVED IMMUNOGLULINIVITY
EP4414484A3 (en) 2016-02-04 2025-01-15 Trianni, Inc. Enhanced production of immunoglobulins
US20190112380A1 (en) * 2016-03-29 2019-04-18 University Of Southern California Chimeric antigen receptors targeting cancer
JP7722629B2 (ja) 2017-07-04 2025-08-13 キュアバック エスイー 新規核酸分子
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BR112020004351A2 (pt) 2017-10-19 2020-09-08 Curevac Ag moléculas de ácido nucleico artificial
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EP4534560A3 (en) * 2018-03-24 2025-06-11 Regeneron Pharmaceuticals, Inc. Genetically modified non-human animals for generating therapeutic antibodies against peptide-mhc complexes, methods of making and uses thereof
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CN108486126A (zh) * 2018-03-27 2018-09-04 重庆金迈博生物科技有限公司 一种核酸分子及其在人源化抗体中的应用
GB2576914A (en) 2018-09-06 2020-03-11 Kymab Ltd Antigen-binding molecules comprising unpaired variable domains produced in mammals
TW202039534A (zh) 2018-12-14 2020-11-01 美商美國禮來大藥廠 KRAS變體mRNA分子
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CN113661173B (zh) 2019-03-29 2024-10-01 豪夫迈·罗氏有限公司 通过以限定的组织形式靶向整合多个表达盒来产生表达FcRn的细胞的方法
KR20220024637A (ko) * 2019-06-19 2022-03-03 에프. 호프만-라 로슈 아게 정의된 조직의 다수 발현 카세트들의 표적화 통합에 의한 3가 항체 발현 세포의 생성 방법
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WO2021154993A1 (en) * 2020-01-28 2021-08-05 University Of Southern California Genome engineering the human immunoglobulin locus to express recombinant binding domain molecules
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US20220090060A1 (en) 2020-09-11 2022-03-24 Regeneron Pharmaceuticals, Inc. Identification and production of antigen-specific antibodies
EP4262373A1 (en) 2020-12-16 2023-10-25 Regeneron Pharmaceuticals, Inc. Mice expressing humanized fc alpha receptors
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