GB2460810A - Transgenic non-human mammal with homodimeric vh binding complex - Google Patents

Transgenic non-human mammal with homodimeric vh binding complex Download PDF

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Publication number
GB2460810A
GB2460810A GB0918846A GB0918846A GB2460810A GB 2460810 A GB2460810 A GB 2460810A GB 0918846 A GB0918846 A GB 0918846A GB 0918846 A GB0918846 A GB 0918846A GB 2460810 A GB2460810 A GB 2460810A
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United Kingdom
Prior art keywords
homodimeric
transgenic non
binding
encodes
gene segments
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Withdrawn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
GB0918846A
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GB0918846D0 (en
Inventor
Frank Grosveld
Rick Janssens
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Erasmus University Medical Center
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Erasmus University Medical Center
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Publication date
Application filed by Erasmus University Medical Center filed Critical Erasmus University Medical Center
Publication of GB0918846D0 publication Critical patent/GB0918846D0/en
Publication of GB2460810A publication Critical patent/GB2460810A/en
Withdrawn legal-status Critical Current

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    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • 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
    • 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
    • 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
    • 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
    • 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
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/22—Immunoglobulins specific features characterized by taxonomic origin from camelids, e.g. camel, llama or dromedary
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Environmental Sciences (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The present invention relates to methods for the manufacture in transgenic non-human mammals of a diverse repertoire of functional, affinity-matured homodimeric VHbinding complexes in response to antigen challenge and uses thereof, especially the derivation of antigen specific VH binding domains. In particular the methods of the present invention involve the step of providing one or more heterologous VH binding complex loci in transgenic non-human mammal, wherein each VH binding complex locus is defined by the formula 5'-A-B-C-D-3' wherein: A comprises one or more V gene segments, one or more D gene segments and one or more J gene segments; B is optional and encodes one or more characterised binding domains of known specificity; C encodes a CH2-CH3 dimerisation domain; and D encodes one or more characterised binding domains of known specificity. The homodimeric VH binding complexes are minimally tetravalent and bispecific but may also be multivalent and bispecific or multivalent and multispecific.
GB0918846A 2007-04-04 2009-10-27 Transgenic non-human mammal with homodimeric vh binding complex Withdrawn GB2460810A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0706628.5A GB0706628D0 (en) 2007-04-04 2007-04-04 Germ-line manipulation 1
PCT/IB2008/000953 WO2008122886A2 (en) 2007-04-04 2008-04-04 Transgenic non-human mammal with homodimeric vh binding complex

Publications (2)

Publication Number Publication Date
GB0918846D0 GB0918846D0 (en) 2009-12-09
GB2460810A true GB2460810A (en) 2009-12-16

Family

ID=38090889

Family Applications (2)

Application Number Title Priority Date Filing Date
GBGB0706628.5A Ceased GB0706628D0 (en) 2007-04-04 2007-04-04 Germ-line manipulation 1
GB0918846A Withdrawn GB2460810A (en) 2007-04-04 2009-10-27 Transgenic non-human mammal with homodimeric vh binding complex

Family Applications Before (1)

Application Number Title Priority Date Filing Date
GBGB0706628.5A Ceased GB0706628D0 (en) 2007-04-04 2007-04-04 Germ-line manipulation 1

Country Status (3)

Country Link
GB (2) GB0706628D0 (en)
TW (1) TW200846468A (en)
WO (1) WO2008122886A2 (en)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009013620A2 (en) * 2007-06-11 2009-01-29 Erasmus University Medical Center Rotterdam Homologous recombination
DK3028564T5 (en) 2009-07-08 2024-04-29 Kymab Ltd ANIMAL MODELS AND THERAPEUTIC MOLECULES
US20120204278A1 (en) 2009-07-08 2012-08-09 Kymab Limited Animal models and therapeutic molecules
US9445581B2 (en) 2012-03-28 2016-09-20 Kymab Limited Animal models and therapeutic molecules
EP2509409B1 (en) 2009-12-10 2016-07-27 Regeneron Pharmaceuticals, Inc. Mice that make heavy chain antibodies
EP3865581A1 (en) 2011-08-05 2021-08-18 Regeneron Pharmaceuticals, Inc. Humanized universal light chain mice
DK2757875T3 (en) 2011-09-19 2018-01-08 Kymab Ltd MANIPULATION OF IMMUNOGLOBULIN GENE DIVERSITY AND MULTI-ANTIBODY THERAPEUTICS
EP2761008A1 (en) 2011-09-26 2014-08-06 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
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
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
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
EP3794941A1 (en) 2013-10-01 2021-03-24 Kymab Limited Animal models and therapeutic molecules
EP3119194B1 (en) 2014-03-21 2021-04-28 Regeneron Pharmaceuticals, Inc. Non-human animals that make single domain binding proteins
WO2017058944A1 (en) 2015-09-29 2017-04-06 Amgen Inc. Asgr inhibitors
EP3980464A1 (en) 2019-06-07 2022-04-13 Amgen Inc. Bispecific binding constructs with selectively cleavable linkers
CA3184351A1 (en) 2020-06-04 2021-12-09 Amgen Inc. Bispecific binding constructs
AU2021393456A1 (en) 2020-12-03 2023-06-29 Amgen Inc. Immunoglobuline constructs with multiple binding domains

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002085945A2 (en) * 2001-04-24 2002-10-31 Erasmus Universiteit Rotterdam Vhh single heavy chain antibody and a method for its preparation in a mammal
WO2004049794A2 (en) * 2002-12-03 2004-06-17 The Babraham Institute Single chain antibodies produced in a transgenic mouse
WO2006008548A2 (en) * 2004-07-22 2006-01-26 Erasmus University Medical Centre Rotterdam Binding molecules

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002085945A2 (en) * 2001-04-24 2002-10-31 Erasmus Universiteit Rotterdam Vhh single heavy chain antibody and a method for its preparation in a mammal
WO2002085944A2 (en) * 2001-04-24 2002-10-31 Erasmus Universiteit Rotterdam Single chain camelid vhh antibodies, method for their production in a mammal and their uses
WO2004049794A2 (en) * 2002-12-03 2004-06-17 The Babraham Institute Single chain antibodies produced in a transgenic mouse
WO2006008548A2 (en) * 2004-07-22 2006-01-26 Erasmus University Medical Centre Rotterdam Binding molecules

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
J. Immunol. Methods, Vol.316, 2006, Iglesias-Ussel, M. D. et al., "Forced expression of AID...", pp.59-66 *
Prco. Natl. Conf. Electron Probe Anal., Vol.28, 1998, Jendreyko, N. et al., "Genetic origin of IgG antibodies...", pp.4236-4247 *
Proc. Natl. Acad. Sci. USA, Vol.103, 2006, Janssens, R. et al., "Generation of heavy-chain-only...", pp.15130-15135 *

Also Published As

Publication number Publication date
TW200846468A (en) 2008-12-01
GB0918846D0 (en) 2009-12-09
WO2008122886A3 (en) 2009-02-05
WO2008122886A2 (en) 2008-10-16
GB0706628D0 (en) 2007-05-16

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