DK2831244T3 - Transgene mus, der udtrykker human lambda og kappa immunoglobulin-letkæde variable domæner - Google Patents

Transgene mus, der udtrykker human lambda og kappa immunoglobulin-letkæde variable domæner Download PDF

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DK2831244T3
DK2831244T3 DK13711119.1T DK13711119T DK2831244T3 DK 2831244 T3 DK2831244 T3 DK 2831244T3 DK 13711119 T DK13711119 T DK 13711119T DK 2831244 T3 DK2831244 T3 DK 2831244T3
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human
mouse
endogenous
region
antibody
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DK13711119.1T
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Allan Bradley
E-Chiang Lee
Qi Liang
Wei Wang
Dominik Spensberger
Hui Liu
Jasper Clube
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Kymab Ltd
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    • 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
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    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
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    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
    • C07K16/1239—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Vibrionaceae (G)
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    • C07K16/00—Immunoglobulins [IGs], 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
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K2207/00—Modified animals
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    • 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
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    • 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
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    • 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
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    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
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    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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    • C07K2317/35—Valency
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    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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Claims (3)

  1. I. Anvendelse af en mus til fremstilling af immunoglobulin (Ig)-letkæder i Exceller, der har en normal andel af modne milt-B-celler, hvor musen udtrykker Ig-letkæder, der bærer humane lambda variable regioner og immunoglobulin-letkæder, der bærer humane kappa variable regioner, hvor mere end 30 % af letkæderne udtrykt af musen omfatter lambda variable regioner, hvor musegenomet omfatter et Ig-gensegment-repertoire fremstillet ved målrettet indsættelse af humane Ig-gensegmenter, genomet omfattende humane VA- og JA-gensegmenter tilvejebragt ved indsættelse i et endogen kappa-letkæde-locus af musen, mellem det 3' mest endogene Jk og muse-CK, opstrøms af nævnte konstant region, hvor den humane VA- og JA-indsættelse omfatter i det mindste humane V-gensegmenter VA3-27, VA3-25, VA2-23, VA3-22, VA3-21, VA3-19, VA2-18, VA3-16, VA2-14, VA3-12, VA2- II, VA3-10, VA3-9, VA2-8, VA4-3 og VA3-1, humane J- og C-gensegmenter JAl-CAl, JA2-CA2, JA3-CA3, JA6-CA6 og JA7-CA7 og en human Ελ-fremmer, hvor de humane V-gensegmenter er 5' af de humane J-gensegmenter, genomet omfattende humane Vk- og JK-gensegmenter tilvejebragt ved indsættelse i det andet endogene kappa-letkæde-locus af musen, mellem det 3' mest endogene Jk og muse-CK, opstrøms af nævnte kappa konstant region, hvor den humane Vk- og JK-indsættelse omfatter i det mindste humane V-gensegmenter Vk2-40, Vk1-39, Vk1-33, Vk2-30, Vk2-29, Vk2-28, Vk1-27, Vk2-24, Vk3-20, Vk1-17, Vk1-16, Vk3-15, Vk1-13, Vk1-12, Vk3-11, Vk1-9, Vk1-8, Vk1-6, Vk1-5, Vk5-2 og Vk4-1 og humane J-gensegmenter JkI, Jk2, Jk3, Jk4 og Jk5, hvor de humane V-gensegmenter er 5' af de humane J-gensegmenter, hvor det endogene kappa VJ er blevet inaktiveret og de endogene lambda loci er intakte, hvor de endogene kappa-fremmere ϊΕκ og 3Έκ er bevaret og hvor i det mindste 50 % af totale milt-B-celler fremstillet af musen er modne B-celler.
  2. 2. Anvendelse ifølge krav 1, hvor de humane VA- og JA-gensegmenter er indsat inden for 100 kb afen endogen muse-letkæde-fremmer.
  3. 3. Anvendelse ifølge krav 2, hvor fremmeren er muse-ϊΕκ eller -3Έκ.
DK13711119.1T 2012-03-28 2013-03-18 Transgene mus, der udtrykker human lambda og kappa immunoglobulin-letkæde variable domæner DK2831244T3 (da)

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Application Number Priority Date Filing Date Title
US13/433,084 US9445581B2 (en) 2012-03-28 2012-03-28 Animal models and therapeutic molecules
US13/434,361 US9253965B2 (en) 2012-03-28 2012-03-29 Animal models and therapeutic molecules
PCT/GB2013/050682 WO2013144566A2 (en) 2012-03-28 2013-03-18 Animal models and therapeutic molecules

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US (7) US9253965B2 (da)
EP (3) EP2785845A2 (da)
JP (4) JP6336435B2 (da)
CN (1) CN104334732B (da)
AU (1) AU2013239501B2 (da)
CA (1) CA2867530A1 (da)
DK (1) DK2831244T3 (da)
ES (1) ES2979344T3 (da)
HK (1) HK1200872A1 (da)
IN (1) IN2014MN01879A (da)
NZ (1) NZ629202A (da)
SG (1) SG11201405058WA (da)
WO (2) WO2013061098A2 (da)

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