DE14154918T1 - ADAM6 Mäuse - Google Patents

ADAM6 Mäuse Download PDF

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DE14154918T1
DE14154918T1 DE14154918.8T DE14154918T DE14154918T1 DE 14154918 T1 DE14154918 T1 DE 14154918T1 DE 14154918 T DE14154918 T DE 14154918T DE 14154918 T1 DE14154918 T1 DE 14154918T1
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mouse
human
gene
gene segments
heavy chain
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Sean Stevens
Andrew J. Murphy
Lynn Macdonald
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Regeneron Pharmaceuticals Inc
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Regeneron Pharmaceuticals Inc
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    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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    • B60H1/3228Cooling devices using compression characterised by refrigerant circuit configurations
    • B60H1/32281Cooling devices using compression characterised by refrigerant circuit configurations comprising a single secondary circuit, e.g. at evaporator or condenser side
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    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
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    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6489Metalloendopeptidases (3.4.24)
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01K2207/00Modified animals
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    • AHUMAN NECESSITIES
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    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/07Animals genetically altered by homologous recombination
    • A01K2217/072Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
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    • A01K2217/00Genetically modified animals
    • A01K2217/15Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
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    • A01K2227/10Mammal
    • A01K2227/105Murine
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    • B60H1/00642Control systems or circuits; Control members or indication devices for heating, cooling or ventilating devices
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    • B60VEHICLES IN GENERAL
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    • B60H1/00Heating, cooling or ventilating [HVAC] devices
    • B60H1/00007Combined heating, ventilating, or cooling devices
    • B60H1/00021Air flow details of HVAC devices
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Abstract

Eine genetisch modifizierte Maus, deren Genom umfasst: (a) eine ektopische Nukleinsäuresequenz umfassend einer Sequenz, die ein Maus-Adam6a-Protein oder ein Ortholog oder Homolog oder Fragment davon kodiert, das in einer männlichen Maus funktionell ist, und ein Maus-Adam6b-Protein oder ein Ortholog oder Homolog oder Fragment davon kodiert, das in einer männlichen Maus funktionell ist; und (b) einen humanisierten Locus der variablen Region der schweren Immunglobulin-Kette.

Claims (19)

  1. Eine genetisch modifizierte Maus, deren Genom umfasst: (a) eine ektopische Nukleinsäuresequenz umfassend einer Sequenz, die ein Maus-Adam6a-Protein oder ein Ortholog oder Homolog oder Fragment davon kodiert, das in einer männlichen Maus funktionell ist, und ein Maus-Adam6b-Protein oder ein Ortholog oder Homolog oder Fragment davon kodiert, das in einer männlichen Maus funktionell ist; und (b) einen humanisierten Locus der variablen Region der schweren Immunglobulin-Kette.
  2. Die Maus vom Anspruch 1, wobei die ektopische Nukleinsäuresequenz am humanisierten Locus der variablen Region der schweren Immunglobulin-Kette vorliegt.
  3. Die Maus von Anspruch 2, wobei die ektopische Nukleinsäuresequenz innerhalb einer Sequenz der humanen schweren Kette des humanisierten Locus der variablen Region der schweren Kette liegt.
  4. Die Maus von Anspruch 1, wobei die ektopische Nukleinsäuresequenz an einer anderen Position als dem humanisierten Genlocus der variable-Region der schweren Kette vorhanden ist.
  5. Die Maus irgendeines der vorhergehenden Ansprüche, wobei der humanisierte Locus der variablen Region der schweren Immunglobulin-Kette eine Insertion eines oder mehrerer humanen/r VH-Gensegments/e, eines oder mehrerer humanen/r DH-Gensegments/e und eines oder mehrerer humanen/r JH-Gensegments/e umfasst.
  6. Maus von Anspruch 5, wobei der humanisierte Locus der variablen Region der schweren Immunglobulin-Kette umfasst: a) mindestens 18 humane VH-Gensegmente, 27 humane DH-Gensegmente und sechs humane JH-Gensegmente; b) mindestens 39 humane VH-Gensegmente, 27 humane DH-Gensegmente und sechs humane JH-Gensegmente; oder c) 80 humane VH-Gensegmente, 27 humane DH-Gensegmente und sechs humane JH-Gensegmente, wobei die humanen VH, DH und JH-Gensegmente funktionsfähig mit einem nicht-humanen Gen der konstanten Region verknüpft sind.
  7. Die Maus von Anspruch 6, wobei das nicht-humane Gen der konstanten Region ein Nagetier-Gen der konstanten Region ist.
  8. Die Maus von Anspruch 7, wobei das Nagetier-Gen der konstanten Region eine Maus-Gensequenz der konstanten Region umfasst, ausgewählt aus einer CH1, einer Gelenk, einer CH2, einer CH3, einer CH4 und eine Kombination davon.
  9. Die Maus irgendeines der vorhergehenden Ansprüche, weiter umfassend ein oder mehrere humane/s Vκ-Gensegment/e und ein oder mehrere humane/s Jκ-Gensegment/e.
  10. Die Maus von Anspruch 9, wobei das eine oder die mehreren humane/n Vκ-Gensegment/e und das eine oder die mehreren humane/n Jκ-Gensegment/e an einem endogenen Locus der leichten Immunglobulin-κ-Kette vorliegen.
  11. Die Maus von Anspruch 9 oder 10, wobei die Maus umfasst: a) mindestens 16 humane Vκ- und fünf humane Jκ-Gensegmente; b) mindestens 30 humane Vκ- und fünf humane Jκ-Gensegmente; oder c) mindestens 40 humane Vκ- und fünf humane Jκ-Gensegmente.
  12. Die Maus irgendeines der vorhergehenden Ansprüche, wobei der Maus endogene VH-, DH- und JH-Gensegmente fehlen.
  13. Die Maus irgendeines der vorhergehenden Ansprüche, wobei der Maus endogene Vκ-, und Jκ-Gensegmente fehlen.
  14. Eine isolierte Mauszelle, deren Genom umfasst: (a) eine ektopische Nukleinsäuresequenz, umfassend einer Sequenz, die ein Maus-Adam6a-Protein oder ein Ortholog oder Homolog oder Fragment davon kodiert, das in einer männlichen Maus funktionell ist, und ein Maus-Adam6b-Protein oder ein Ortholog oder Homolog oder Fragment davon kodiert, das in einer männlichen Maus funktionell ist; und b) ein humanisierter Locus der variablen Region der schweren Immunglobulin-Kette.
  15. Die isolierte Zelle gemäß Anspruch 14, wobei die Zelle eine B-Zelle ist.
  16. Ein Hybridom, das aus der B-Zelle von Anspruch 15 hergestellt wurde.
  17. Eine immortalisierte Zelle, die aus der isolierten Zelle von Anspruch 14 hergestellt wurde.
  18. Die isolierte Zelle gemäß Anspruch 14, wobei die Zelle eine embryonale Maus-Stammzelle ist.
  19. Ein Maus-Embryo, dessen Genom umfasst: (a) eine ektopische Nukleinsäuresequenz, umfassend einer Sequenz, die ein Maus-Adam6a-Protein oder ein Ortholog oder Homolog oder Fragment davon kodiert, das in einer männlichen Maus funktionell ist, und ein Maus-Adam6b-Protein oder ein Ortholog oder Homolog oder Fragment davon kodiert, das in einer männlichen Maus funktionell ist; und b) ein humanisierter Locus der variablen Region der schweren Immunglobulin-Kette.
DE14154918.8T 2011-02-25 2012-02-24 ADAM6 Mäuse Pending DE14154918T1 (de)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201161446895P 2011-02-25 2011-02-25
US201161446895P 2011-02-25
US201161497650P 2011-06-16 2011-06-16
US201161497650P 2011-06-16
US201261595200P 2012-02-06 2012-02-06
US201261595200P 2012-02-06
EP14154918.8A EP2738258B2 (de) 2011-02-25 2012-02-24 ADAM6 Mäuse

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