HRP20191680T1 - Neljudske životinje koje izražavaju antitijela sa zajedničkim lakim lancem - Google Patents

Neljudske životinje koje izražavaju antitijela sa zajedničkim lakim lancem Download PDF

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HRP20191680T1
HRP20191680T1 HRP20191680T HRP20191680T1 HR P20191680 T1 HRP20191680 T1 HR P20191680T1 HR P20191680 T HRP20191680 T HR P20191680T HR P20191680 T1 HRP20191680 T1 HR P20191680T1
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mouse
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John Mcwhirter
Lynn Macdonald
Sean Stevens
Samuel Davis
David R Buckler
Karolina A Hosiawa
Andrew J Murphy
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Regeneron Pharma
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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
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    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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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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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • 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
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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
    • 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
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • 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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    • 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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    • C07—ORGANIC CHEMISTRY
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
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    • C07—ORGANIC CHEMISTRY
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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    • C12N2800/00—Nucleic acids vectors
    • C12N2800/20—Pseudochromosomes, minichrosomosomes
    • C12N2800/204—Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC

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Claims (20)

1. Genetski modificirani miš koji obuhvaća B stanicu koja izražava varijabilnu (VL) domenu humanog lakog lanca izvedenu iz preuređene humane sekvence Vκ1-39/Jκ koja je prisutna u zametnoj liniji miša, naznačeno time, što miš ne posjeduje nepreuređeni endogeni humani imunoglobulinski segment gena Vκ i nepreuređeni endogeni imunoglobulinski segment gena Jκ; i naznačeno time, što je humana VL domena(e) povezana s humanom varijabilnom domenom (VH) teškog lanca izvedenom iz preuređene humane regije VH/DH/JH odabrane iz 2-5/3-22/1, 3-13/6-6/5, 3-23/2-8/4, 3-23/6-6/4, 3-23/7-27/4, 3-30/1-1/4, 3-30/3-3/4, 3-30/5-5/2, 3-30/7-27/6, 1-69/6-6/5 ili 1-69/6-13/4.
2. Miš prema patentnom zahtjevu 1, naznačen time, što: (a) humana sekvenca Vκ1-39/Jκ je operativno povezana sa sekvencom mišje regije Cκ; (b) sekvenca koja šifrira humanu domenu VH je operativno povezana sa sekvencom koja šifrira sekvencu konstantne (CH) regije mišjeg teškog lanca odabranu iz CH1, spojne regije, CH2, CH3 ili njihove kombinacije; ili (c) humana domena VH se izražava iz endogenog lokusa imunoglobulinskog teškog lanca.
3. Miš prema patentnom zahtjevu 1, naznačen time, što su svi ili praktično svi mišji segmenti gena Vκ i Jκ zamijenjeni preuređenom humanom sekvencom Vκ1-39/Jκ.
4. Miš prema patentnom zahtjevu 1, naznačen time, što je preuređena humana sekvenca Vκ1-39/Jκ operativno povezana sa sekvencom konstantne regije imunoglobulinskog lakog lanca odabranom iz mišje, štakorske ili humane sekvence.
5. Genetski modificirani miš koji obuhvaća B stanicu koja izražava varijabilnu (VL) domenu humanog lakog lanca izvedenu iz preuređene humane sekvence Vκ3-20/Jκ koja je prisutna u zametnoj liniji miša, naznačeno time, što miš ne posjeduje nepreuređeni endogeni humani imunoglobulinski segment gena Vκ i nepreuređeni endogeni imunoglobulinski segment gena Jκ; i naznačeno time, što je humana VL domena(e) povezana s humanom varijabilnom domenom (VH) teškog lanca izvedenom iz preuređene humane regije VH/DH/JH odabrane iz 3-30/3-3/3, 3-33/1-7/4, 3-33/2-15/4 ili 3-53/1-1/4.
6. Miš prema patentnom zahtjevu 5, naznačen time, što: (a) humana sekvenca Vκ3-20/Jκ je operativno povezana sa sekvencom mišje regije Cκ; (b) sekvenca koja šifrira humanu domenu VH je operativno povezana sa sekvencom koja šifrira sekvencu mišje regije CH odabranu iz CH1, spojne regije, CH2, CH3 ili njihove kombinacije; ili (c) humana domena VH se izražava iz endogenog lokusa imunoglobulinskog teškog lanca.
7. Miš prema patentnom zahtjevu 5, naznačen time, što su svi ili praktično svi mišji segmenti gena Vκ i Jκ zamijenjeni preuređenom humanom sekvencom Vκ3-20/Jκ.
8. Miš prema patentnom zahtjevu 5, naznačen time, što je preuređena humana sekvenca Vκ3-20/Jκ operativno povezana sa sekvencom konstantne regije imunoglobulinskog lakog lanca odabranom iz mišje, štakorske ili humane sekvence.
9. Miš prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, što miš obuhvaća nefunkcionalni lokus imunoglobulinskog lambda (λ) lakog lanca.
10. Upotreba miša prema bilo kojem patentnom zahtjevu od 1 do 4 u proizvodnji antitijela koje obuhvaća varijabilnu (VH) domenu humanog lakog lanca izvedenu iz preuređene humane regije VH/DH/JH odabrane iz 2-5/3-22/1, 3-13/6-6/5, 3-23/2-8/4, 3-23/6-6/4, 3-23/7-27/4, 3-30/1-1/4, 3-30/3-3/4, 3-30/5-5/2, 3-30/7-27/6, 1-69/6-6/5 ili 1-69/6-13/4 povezane s varijabilnom regijom humanog lakog lanca izvedenom iz preuređene humane sekvence Vκ1-39/Jκ.
11. Upotreba prema patentnom zahtjevu 10, naznačena time, što je antitijelo bispecifično antitijelo.
12. Upotreba miša prema bilo kojem patentnom zahtjevu od 5 do 8 u proizvodnji antitijela koje obuhvaća varijabilnu (VH) domenu humanog teškog lanca izvedenu iz preuređene humane regije VH/DH/JH odabrane iz 3-30/3-3/3, 3-33/1-7/4, 3-33/2-15/4 ili 3-53/1-1/4 povezane s varijabilnom regijom humanog lakog lanca izvedenom iz preuređene humane sekvence Vκ3-20/Jκ.
13. Upotreba prema patentnom zahtjevu 12, naznačena time, što je antitijelo bispecifično antitijelo.
14. Upotreba prema patentnom zahtjevu 11 ili 13, naznačena time, što se proizvodnja vrši pomoću metode koja se sastoji od koraka izražavanja varijabilnih domena humanog teškog lanca u jednoj stanici.
15. Upotreba prema bilo kojem patentnom zahtjevu od 10 do 14, naznačena time, što su teški lanci antitijela u potpunosti humani.
16. Upotreba prema patentnom zahtjevu 10 ili 11, naznačena time, što teški lanci obuhvaćaju par varijabilnih domena humanog teškog lanca dok laki lanac obuhvaća humanu domenu VL izvedenu iz preuređene humane sekvence Vκ1-39/Jκ.
17. Upotreba prema patentnom zahtjevu 12 ili 13, naznačena time, što teški lanci obuhvaćaju par varijabilnih domena humanog teškog lanca dok laki lanac obuhvaća humanu domenu VL izvedenu iz preuređene humane sekvence Vκ3-20/Jκ.
18. Upotreba prema bilo kojem patentnom zahtjevu od 10 do 17, naznačena time, što su varijabilne domene humanog teškog lanca odabrane imunizacijom miša pomoću interesnog antigena, utvrđivanjem sekvenci varijabilnih domena humanog teškog lanca koje miš izražava i izražavanjem sekvenci u stanici.
19. Metoda za proizvodnju antitijela za interesni antigen koje obuhvaća varijabilnu domenu humanog teškog lanca izvedenu iz preuređene humane regije VH/DH/JH odabrane iz 2-5/3-22/1, 3-13/6-6/5, 3-23/2-8/4, 3-23/6-6/4, 3-23/7-27/4, 3-30/1-1/4, 3-30/3-3/4, 3-30/5-5/2, 3-30/7-27/6, 1-69/6-6/5 ili 1-69/6-13/4 povezane s varijabilnom regijom humanog lakog lanca izvedenom iz preuređene humane sekvence Vκ1-39/Jκ, pri čemu metoda obuhvaća: (a) imunizaciju miša prema bilo kojem patentnom zahtjevu od 1 do 4 pomoću interesnog antigena; (b) dobivanja iz miša varijabilne domene humanog teškog lanca izvedenog iz preuređene humane regije VH/DH/JH odabrane iz 2-5/3-22/1, 3-13/6-6/5, 3-23/2-8/4, 3-23/6-6/4, 3-23/7-27/4, 3-30/1-1/4, 3-30/3-3/4, 3-30/5-5/2, 3-30/7-27/6, 1-69/6-6/5 ili 1-69/6-13/4; i (c) korištenja sekvence varijabilne regije imunoglobulina dobivene u koraku (b) povezane sa spomenutom varijabilnom regijom humanog lakog lanac u antitijelu koje se specifično vezuje za interesni antigen.
20. Metoda za proizvodnju antitijela za interesni antigen koje obuhvaća varijabilnu domenu humanog teškog lanca izvedenu iz preuređene humane regije VH/DH/JH odabrane iz 3-30/3-3/3, 3-33/1-7/4, 3-33/2-15/4 ili 3-53/1-1/4 povezane s varijabilnom regijom humanog lakog lanca izvedenom iz preuređene humane sekvence Vκ3-20/Jκ, pri čemu metoda obuhvaća: (a) imunizaciju miša prema bilo kojem patentnom zahtjevu od 5 do 8 pomoću interesnog antigena; (b) dobivanja iz miša varijabilne domene humanog teškog lanca izvedenog iz preuređene humane regije VH/DH/JH odabrane iz 3-30/3-3/3, 3-33/1-7/4, 3-33/2-15/4 ili 3-53/1-1/4; i (c) korištenja sekvence varijabilne regije imunoglobulina dobivene u koraku (b) povezane sa spomenutom varijabilnom regijom humanog lakog lanac u antitijelu koje se specifično vezuje za interesni antigen.
HRP20191680 2011-04-25 2019-09-17 Neljudske životinje koje izražavaju antitijela sa zajedničkim lakim lancem HRP20191680T1 (hr)

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Application Number Priority Date Filing Date Title
US13/093,156 US20120021409A1 (en) 2010-02-08 2011-04-25 Common Light Chain Mouse
EP15186515.1A EP2989893B1 (en) 2011-04-25 2012-04-24 Non-human animals expressing antibodies having a common light chain

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HRP20191680T1 true HRP20191680T1 (hr) 2019-12-13

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HRP20160484TT HRP20160484T4 (hr) 2011-04-25 2016-05-06 Životinje koje izražavaju antitijela sa zajedničkim lakim lancem
HRP20191680 HRP20191680T1 (hr) 2011-04-25 2019-09-17 Neljudske životinje koje izražavaju antitijela sa zajedničkim lakim lancem

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US (2) US20120021409A1 (hr)
EP (2) EP2989893B1 (hr)
JP (2) JP6393613B2 (hr)
KR (1) KR101995753B1 (hr)
CN (2) CN103596424B (hr)
AU (3) AU2012249953B2 (hr)
BR (1) BR112013027420A2 (hr)
CA (1) CA2846806A1 (hr)
CY (2) CY1117606T1 (hr)
DK (2) DK2701499T4 (hr)
ES (2) ES2743681T3 (hr)
HK (2) HK1193718A1 (hr)
HR (2) HRP20160484T4 (hr)
HU (2) HUE045401T2 (hr)
IL (1) IL228929A0 (hr)
LT (1) LT2989893T (hr)
MX (1) MX353609B (hr)
PL (2) PL2701499T5 (hr)
PT (1) PT2989893T (hr)
RS (2) RS59331B1 (hr)
RU (2) RU2017108634A (hr)
SG (1) SG194466A1 (hr)
SI (2) SI2989893T1 (hr)
SM (1) SMT201600133B (hr)
WO (1) WO2012148873A2 (hr)

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US6596541B2 (en) * 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
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