HRP20190897T1 - Laki lanac humaniziranih miševa - Google Patents

Laki lanac humaniziranih miševa Download PDF

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Publication number
HRP20190897T1
HRP20190897T1 HRP20190897TT HRP20190897T HRP20190897T1 HR P20190897 T1 HRP20190897 T1 HR P20190897T1 HR P20190897T T HRP20190897T T HR P20190897TT HR P20190897 T HRP20190897 T HR P20190897T HR P20190897 T1 HRP20190897 T1 HR P20190897T1
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Croatia
Prior art keywords
human
mouse
light chain
gene
nucleic acid
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Application number
HRP20190897TT
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English (en)
Inventor
Lynn Macdonald
Cagan Gurer
Karolina A. Hosiawa
Sean Stevens
Andrew J. Murphy
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Regeneron Pharmaceuticals, Inc.
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Application filed by Regeneron Pharmaceuticals, Inc. filed Critical Regeneron Pharmaceuticals, Inc.
Publication of HRP20190897T1 publication Critical patent/HRP20190897T1/hr

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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027New breeds of vertebrates
    • A01K67/0275Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278Humanized animals, e.g. knockin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46Hybrid immunoglobulins
    • C07K16/461Igs containing Ig-regions, -domains or -residues form different species
    • C07K16/462Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • 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
    • 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
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/15Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00Animals characterised by species
    • A01K2227/10Mammal
    • A01K2227/105Murine
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00Animals characterised by purpose
    • A01K2267/01Animal expressing industrially exogenous proteins
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00Nucleic acids vectors
    • C12N2800/20Pseudochromosomes, minichrosomosomes
    • C12N2800/204Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00Nucleic acids vectors
    • C12N2800/30Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT

Claims (12)

1. Miš koji sadrži: (a) jedan ili više nepreuređenih humanih genskih segmenata Vλ i jedan ili više nepreuređenih humanih genskih segmenata Jλ na lokusu endogenog imunoglobulinskog lakog lanca kapa miša, naznačen time, što imunoglobulinski lokus lakog lanca kapa sadrži mišju Cκ regiju; (b) jedan ili više humanih genskih segmenata VH, jedan ili više humanih genskih segmenata DH i jedan ili više humanih genskih segmenata JH na lokusu endogenog imunoglobulinskog teškog lanca miša; i (c) modifikaciju lokusa imunoglobulinskog teškog lanca, naznačenu time, što modifikacija eliminira endogenu ADAM6 funkciju, koja je povezana sa smanjenjem plodnosti kod mužjaka miševa, pri čemu miš dodatno sadrži sekvencu nukleinske kiseline koja šifrira mišji ADAM6a protein ili njegov ortolog ili homolog ili funkcionalni fragment, pri čemu je svaki funkcionalan radi poboljšanja ili obnavljanja spomenutog smanjenja plodnosti kod mužjaka miševa, i sekvencu nukleinske kiseline koja šifrira mišji ADAM6b protein ili njegov ortolog ili homolog ili funkcionalni fragment, pri čemu je svaki funkcionalan radi poboljšanja ili obnavljanja spomenutog smanjenja plodnosti kod mužjaka miševa, naznačeno time, što su sekvence nukleinske kiseline koje šifriraju ADAM6 proteine, njegove ortologe, homologe ili funkcionalne fragmente prisutne unutar genskih segmenata humanog teškog lanca.
2. Miš prema prethodnom patentnom zahtjevu, naznačen time, što miš sadrži od 12 do 40 humanih genskih segmenata Vλ i najmanje jedan humani genski segment Jλ.
3. Miš prema patentnom zahtjevu 2, naznačen time, što: (a) miš sadrži 12 humanih genskih segmenata Vλ i najmanje jedan humani genski segment Jλ; (b) miš sadrži 28 humanih genskih segmenata Vλ i najmanje jedan humani genski segment Vλ; ili (c) miš sadrži 40 humanih genskih segmenata Vλ i najmanje jedan humani genski segment Jλ.
4. Miš prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, što: (a) najmanje jedan humani genski segment Jλ je odabran iz Jλ1, Jλ2, Jλ3, Jλ7 i njihove kombinacije; i/ili (b) miš sadrži najmanje četiri humana genska segmenta Jλ.
5. Miš prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, što miš ne posjeduje varijabilnu regiju endogenog lakog lanca kapa na lokusu endogenog imunoglobulinskog lakog lanca kapa.
6. Miš prema bilo kojem od prethodnih patentnih zahtjeva, koji dodatno sadrži humanu međugensku regiju Vκ-Jκ iz lokusa humanog lakog lanca κ, naznačen time, što se humana međugenska regija Vκ-Jκ graniči s jednim ili više nepreuređenih genskih segmenata Vλ i s jednim ili više nepreuređenih genskih segmenata Jλ, poželjno pri čemu se humana međugenska regija Vκ-Jκ nalazi između genskog segmenta Vλ i genskog segmenta Jλ, i naznačena time, što humana međugenska regija Vκ-Jκ sadrži SEQ ID NO. 158.
7. Miš prema bilo kojem od prethodnih patentnih zahtjeva, koji je mužjak miša.
8. Izolirana stanica ili tkivo iz miša prema bilo kojem od prethodnih patentnih zahtjeva.
9. Primjena miša prema bilo kojem patentnom zahtjevu od 1 do 7, za dobivanje: (i) reverznog kimernog antitijela; (ii) potpunog humanog antitijela; (iii) potpuno humanog Fab fragmenta; ili (iv) potpuno humanog F(ab)2 fragmenta.
10. Metoda za dobivanje antitijela, pri čemu se metoda sastoji od: (a) izlaganja miša prema bilo kojem patentnom zahtjevu od 1 do 7 antigenu; (b) dozvoljavanja mišu da razvije imunološki odgovor na antigen; i (c) izoliranja iz miša iz (b) antitijela koje specifično prepoznaje antigen, naznačeno time, što antitijelo sadrži laki lanac dobiven iz hVλ, hJλ i mišje Cκ regije, ili izoliranja iz miša iz (b) stanice koja sadrži imunoglobulinsku domenu koja specifično prepoznaje antigen, ili identifikacije u mišu iz (b) sekvence nukleinske kiseline koja šifrira varijabilnu domenu teškog i/ili lakog lanca koja vezuje antigen.
11. Metoda za dobivanje humanog antitijela, pri čemu se metoda sastoji od izlaganja miša prema bilo kojem patentnom zahtjevu od 1 do 7 antigenu, dozvoljavanja mišu da ispolji imunološki odgovor koji se sastoji od stvaranja antitijela koje se specifično vezuje za antigen, identificiranja u B stanici iz miša preuređene sekvence nukleinske kiseline koja šifrira varijabilnu domenu humanog teškog lanca i preuređenu sekvencu nukleinske kiseline i preuređene sekvence nukleinske kiseline koja šifrira srodnu sekvencu varijabilne domene humanog lakog lanca, naznačena time, što se antitijelo specifično vezuje za antigen, i korištenja sekvenci nukleinske kiseline koje šifriraju varijabilnu domenu humanog teškog lanca odnosno varijabilnu domenu humanog lakog lanca za sekvencu nukleinske kiseline koja šifrira konstantnu domenu humanog teškog lanca odnosno sekvencu nukleinske kiseline koja šifrira konstantnu domenu humanog lakog lanca, kako bi se dobilo željeno antitijelo.
12. Metoda za dobivanje sekvence nukleinske kiseline koja šifrira varijabilnu domenu teškog i/ili lakog lanca koja se sastoji od: (a) izlaganja miša prema bilo kojem patentnom zahtjevu od 1 do 7 antigenu; (b) identifikacije u B stanici iz miša: (i) gena imunoglobulina preuređenog lakog lanca, naznačeno time, što gen imunoglobulina preuređenog lakog lanca sadrži najmanje jedan genski segment varijabilne regije humanog lakog lanca λ povezan za mišju Cκ regiju; ili (ii) gena imunoglobulina preuređenog lakog lanca iz (b)(i) i gena imunoglobulina preuređenog teškog lanca, naznačeno time, što gen imunoglobulina preuređenog teškog lanca šifrira teški lanac koji se uparuje s lakim lancem šifriranim genom imunoglobulina preuređenog lakog lanca iz (b)(i); i (c) kloniranja sekvence nukleinske kiseline koja šifrira varijabilnu domenu teškog i/ili lakog lanca iz B stanice miša, naznačeno time, što je varijabilna domena teškog i/ili lakog lanca iz antitijela koje sadrži humani Vλ i mišji Cκ.
HRP20190897TT 2011-12-20 2019-05-15 Laki lanac humaniziranih miševa HRP20190897T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161578097P 2011-12-20 2011-12-20
EP12809955.3A EP2793567B1 (en) 2011-12-20 2012-12-17 Humanized light chain mice
PCT/US2012/069981 WO2013096142A1 (en) 2011-12-20 2012-12-17 Humanized light chain mice

Publications (1)

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HRP20190897T1 true HRP20190897T1 (hr) 2019-09-20

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US (6) US9706759B2 (hr)
EP (2) EP3527070A1 (hr)
JP (5) JP6327750B2 (hr)
KR (5) KR101924805B1 (hr)
CN (1) CN104159444B (hr)
AU (5) AU2012323987B2 (hr)
BR (2) BR122021007339B1 (hr)
CA (1) CA2859408C (hr)
CY (1) CY1121638T1 (hr)
DK (1) DK2793567T3 (hr)
ES (1) ES2720186T3 (hr)
HK (1) HK1202772A1 (hr)
HR (1) HRP20190897T1 (hr)
HU (1) HUE044266T2 (hr)
IL (3) IL233153B (hr)
IN (1) IN2014DN06094A (hr)
LT (1) LT2793567T (hr)
ME (1) ME03477B (hr)
MX (2) MX356429B (hr)
MY (1) MY173936A (hr)
PL (1) PL2793567T3 (hr)
PT (1) PT2793567T (hr)
RS (1) RS58761B1 (hr)
RU (2) RU2664181C2 (hr)
SG (3) SG10201913164YA (hr)
SI (1) SI2793567T1 (hr)
TR (1) TR201903439T4 (hr)
WO (1) WO2013096142A1 (hr)

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