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Withdrawn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 PCT/GB2013/050683 priority patent/WO2013144567A1/en
Priority to EP13711120.9A priority patent/EP2831245A1/en
Priority to SG11201405059XA priority patent/SG11201405059XA/en
Priority to EP13723933.1A priority patent/EP2852672A2/en
Priority to JP2015512133A priority patent/JP2015519055A/ja
Priority to EP22173215.9A priority patent/EP4116427A1/en
Priority to CN201380038167.0A priority patent/CN104508135B/zh
Priority to SG11201406947RA priority patent/SG11201406947RA/en
Priority to PCT/GB2013/051280 priority patent/WO2013171505A2/en
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)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Animal Husbandry (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (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
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
SG11201405059XA SG11201405059XA (en) 2012-03-28 2013-03-18 Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies
PCT/GB2013/051280 WO2013171505A2 (en) 2012-05-17 2013-05-17 In vivo guided selection & 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
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
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
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
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) EP2852672A2 (enExample)
JP (1) JP2015519055A (enExample)
CN (1) CN104508135B (enExample)
GB (1) GB2502127A (enExample)
SG (1) SG11201406947RA (enExample)
WO (1) WO2013171505A2 (enExample)

Cited By (2)

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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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US10793829B2 (en) 2010-07-26 2020-10-06 Trianni, Inc. Transgenic mammals and methods of use thereof
US10662256B2 (en) 2010-07-26 2020-05-26 Trianni, Inc. Transgenic mammals and methods of use thereof
RU2580017C2 (ru) 2010-07-26 2016-04-10 Трианни, Инк. Трансгенные животные и способы применения
KR102306967B1 (ko) 2010-08-02 2021-10-01 리제너론 파아마슈티컬스, 인크. Ｖｌ 도메인을 포함하는 결합 단백질을 생성하는 마우스
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WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
KR20140082824A (ko) 2011-10-17 2014-07-02 리제너론 파아마슈티컬스, 인크. 제한된 면역글로불린 중쇄 마우스
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
US10251377B2 (en) 2012-03-28 2019-04-09 Kymab Limited Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies
GB2502127A (en) 2012-05-17 2013-11-20 Kymab Ltd Multivalent antibodies and in vivo methods for their production
EP3912464A1 (en) 2012-06-12 2021-11-24 Regeneron Pharmaceuticals, Inc. Humanized non-human animals with restricted immunoglobulin heavy chain loci
MY185881A (en) 2013-02-20 2021-06-14 Regeneron Pharma Non-human animals with modified immunoglobulin heavy chain sequences
WO2014141192A1 (en) * 2013-03-15 2014-09-18 Erasmus University Medical Center Generation of heavy chain-only antibodies
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
US11707056B2 (en) 2013-05-02 2023-07-25 Kymab Limited Animals, repertoires and methods
US9783593B2 (en) 2013-05-02 2017-10-10 Kymab Limited Antibodies, variable domains and chains tailored for human use
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CN106164092A (zh) 2014-03-21 2016-11-23 瑞泽恩制药公司 表现不同结合特征的vl抗原结合蛋白
CN106255410B (zh) 2014-03-21 2020-01-10 瑞泽恩制药公司 产生单结构域结合蛋白的非人动物
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IL257411B2 (en) * 2015-08-24 2024-05-01 Trianni Inc Enhanced production of immunoglobulins
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AU2017213633B2 (en) 2016-02-04 2023-08-03 Trianni, Inc. Enhanced production of immunoglobulins
WO2017172981A2 (en) * 2016-03-29 2017-10-05 University Of Southern California Chimeric antigen receptors targeting cancer
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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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JP7648654B2 (ja) * 2020-05-05 2025-03-18 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 Ｃｄ２８ゼータ及びｃｄ３ゼータを含むｃａｒ
KR20230018439A (ko) 2020-06-02 2023-02-07 바이오사이토젠 파마슈티컬스 (베이징) 컴퍼니 리미티드 공동 경쇄 면역글로불린 좌위를 갖는 유전자 변형 비인간 동물
KR20230066386A (ko) 2020-09-11 2023-05-15 리제너론 파마슈티칼스 인코포레이티드 항원 특이적 항체의 확인 및 제조
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