HRP20130253T1 - Životinjski modeli i terapijske molekule - Google Patents

Životinjski modeli i terapijske molekule Download PDF

Info

Publication number
HRP20130253T1
HRP20130253T1 HRP20130253AT HRP20130253T HRP20130253T1 HR P20130253 T1 HRP20130253 T1 HR P20130253T1 HR P20130253A T HRP20130253A T HR P20130253AT HR P20130253 T HRP20130253 T HR P20130253T HR P20130253 T1 HRP20130253 T1 HR P20130253T1
Authority
HR
Croatia
Prior art keywords
human
regions
cell
mammal
constant region
Prior art date
Application number
HRP20130253AT
Other languages
English (en)
Inventor
Allan Bradley
E-Chiang Lee
Qi LIANG
Wei Wang
Original Assignee
Kymab Limited
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=46318717&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HRP20130253(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from GBGB0911846.4A external-priority patent/GB0911846D0/en
Priority claimed from GB0913102A external-priority patent/GB0913102D0/en
Priority claimed from PCT/GB2010/051122 external-priority patent/WO2011004192A1/en
Application filed by Kymab Limited filed Critical Kymab Limited
Publication of HRP20130253T1 publication Critical patent/HRP20130253T1/hr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027—New breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Humanized animals, e.g. knockin
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027—New breeds of vertebrates
    • A01K67/0271—Chimeric animals, e.g. comprising exogenous cells
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027—New breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027—New breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0276—Knockout animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/107—Vibrio
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/35—Allergens
    • 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
    • C07K16/12—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • 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)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C07K16/462—Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
    • 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
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/567—Framework region [FR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • 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
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • 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
    • C12N2015/8518—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles

Claims (15)

1. Sisavac različit od čovjek a čiji genom obuhvaća: a) množinu ljudskih IgH V regija, jednu ili više ljudskih D regija i jednu ili više ljudskih J regija uzvodno od konstantne regije sisavca domaćina različitog od čovjeka; i b) neobavezno jednu ili više kappa V regija lakog lanca ljudskog Ig i jednu ili više kappa J regija lakog lanca ljudskog Ig uzvodno od konstantne kappa regije sisavca domaćina različitog od čovjeka i/ili jednu ili više lambda V regija lakog lanca ljudskog Ig i jednu ili više lambda J regija lakog lanca ljudskog Ig uzvodno od konstantne lambda regije sisavca domaćina različitog od čovjeka pri čemu je sisavac različit od čovjeka u mogućnosti stvoriti repertoar kimeričnih protutijela, ili kimeričnih teških lanaca i neobavezno kimerične lake lance, koji imaju konstantnu regiju sisavca različitog od čovjeka i ljudsku varijabilnu regiju; pri čemu neljudski genom sisavca u koji je umetnuta DNA obuhvaća endogene V(D)J regije koje nisu izbrisane, pri čemu je sisavac različit od čovjeka glodavac, i pri čemu je umetanje DNA ljudskog teškog lanca učinjeno između neljudske konstantne regije sisavca i zadnje, 3' J regije siavca različitog od čovjeka. Ili sisavac različit od čovjeka čiji genom obuhvaća: a) množinu kappa V regija lakog lanca ljudskog Ig i jednu ili više kappa J regija lakog lanca ljudskog Ig uzvodno od konstantne kappa regije sisavca domaćina različitog od čovjeka i/ili množinu lambda V regija lakog lanca ljudskog Ig i jednu ili više lambda J regija lakog lanca ljudskog Ig uzvodno od konstantne lambda regije sisavca domaćina različitog od čovjeka; i b) neobavezno jednu ili više ljudskih IgH V regija, jednu ili više ljudskih D regija i jednu ili više ljudskih J regija uzvodno od konstantne regije sisavca domaćina različitog od čovjeka; pri čemu je sisavac različit od čovjeka u mogućnosti stvoriti repertoar kimeričnih protutijela, ili kimeričnih lakih lanaca i neobavezno kimerične teške lance, koji imaju konstantnu regiju sisavca različitog od čovjeka i ljudsku varijabilnu regiju pri čemu neljudski genom sisavca u koji je umetnuta DNA obuhvaća endogene V(D)J regije koje nisu izbrisane pri čemu je sisavac različit od čovjeka glodavac, i pri čemu je umetanje DNA ljudskog kappa ili lambda lanca učinjeno između neljudske konstantne regije sisavca i zadnje, 3' J regije siavca različitog od čovjeka.
2. Stanica sisavca različitog od čovjek a čiji genom obuhvaća: a) množinu ljudskih IgH V regija, jednu ili više ljudskih D regija i jednu ili više ljudskih J regija uzvodno od konstantne regije sisavca domaćina različitog od čovjeka i b) neobavezno jednu ili više kappa V regija lakog lanca ljudskog Ig i jednu ili više kappa J regija lakog lanca ljudskog Ig uzvodno od konstantne kappa regije sisavca domaćina različitog od čovjeka i/ili jednu ili više lambda V regija lakog lanca ljudskog Ig i jednu ili više lambda J regija lakog lanca ljudskog Ig uzvodno od konstantne lambda regije sisavca domaćina različitog od čovjeka pri čemu neljudski genom sisavca u koji je umetnuta DNA obuhvaća endogene V(D)J regije koje nisu obrisane, pri čemu je sisavac različit od čovjeka glodavac, i pri čemu je umetanje DNA ljudskog teškog lanca učinjeno između neljudske konstantne regije sisavca i zadnje, 3' J regije siavca različitog od čovjeka ili stanica sisavca različitog od čovjek a čiji genom obuhvaća a) množinu kappa V regija lakog lanca ljudskog Ig i jednu ili više kappa J regija lakog lanca ljudskog Ig uzvodno od konstantne kappa regije sisavca domaćina različitog od čovjeka i/ili množinu lambda V regija lakog lanca ljudskog Ig i jednu ili više lambda J regija lakog lanca ljudskog Ig uzvodno od konstantne lambda regije sisavca domaćina različitog od čovjeka; i b) neobavezno jednu ili više ljudskih IgH V regija, jednu ili više ljudskih D regija i jednu ili više ljudskih J regija uzvodno od konstantne regije sisavca domaćina različitog od čovjeka; pri čemu neljudski genom sisavca u koji je umetnuta DNA obuhvaća endogene V(D)J regije koje nisu izbrisane, pri čemu je sisavac različit od čovjeka glodavac, i pri čemu je umetanje DNA ljudskog kappa ili lambda lanca učinjeno između neljudske konstantne regije sisavca i zadnje, 3' J regije siavca različitog od čovjeka
3. Sisavac ili stanica u skladu s patentnim zahtjevom 1 ili 2 čiji genom obuhvaća umetnutu DNA ljudske varijabilne regije iz ljudskog teškog i ljudskog lakog lanca, pri čemu su, a) množina ljudskih IgH V regija, jedna ili više ljudskih D regija i jedna ili više ljudskih J regija uzvodno od konstantne regije sisavca domaćina različitog od čovjeka i pri čemu je umetanje DNA ljudskog lakog lanca uzvodno od neljudske konstantne regije lakog lanca sisavca, tako da u stanici može nastati kimerični laki lanac.
4. Stanica ili sisavac različit od čovjeka u skladu s patentnim zahtjevima 1-3 pri čemu je sisavac miš ili je stanica mišja stanica i pri čemu je umetanje DNA ljudskog teškog lanca učinjeno u mišjem genomu između koordinata 114,667,091 i 114,665,190 mišjeg kromosoma 12 (koordinate se odnose na NCBI m37, travanj 2007 ENSEMBL izdanje 55.37h za soj miševa C57BL/6J).
5. Stanica ili sisavac različit od čovjeka u skladu s patentnim zahtjevima 1-3 pri čemu je genom stanice ili sisavca promijenjen zbog sprječavanja ili smanjenja ekspresije protutijela potpuno specifičnih za vrstu domaćina, neobavezno pri čemu je genom sisavca različitog od čovjeka preuređen inverzijom cijelog ili dijela VDJ regije ili VJ regije sisavca različitog od čovjeka.
6. Stanica u skladu s bilo kojim od patentnih zahtjeva 2-5 koja je ES stanica, hematopoetska matična stanica ili iPS stanica sposobna za razvoj u sisavca različitog od čovjeka, ili sposobna za doprinos tkivima i organima sisavca različitog od čovjeka, sisavac je u mogućnosti stvoriti repertoar protutijela ili lanaca protutijela koji su kimerični, navedena kimerična protutijela ili lanci imaju neljudsku konstantnu regiju sisavca i ljudsku varijabilnu regiju.
7. Stanica u skladu s bilo kojim od patentnih zahtjeva 2-5 koja je stanica koja stvara protutijelo.
8. Stanica ili sisavac u skladu s bilo kojim od prethodnih patentnih zahtjeva obuhvaća umetnutu DNA ljudske varijabilne regije najmanje od ljudskog teškog i ljudskog lakog lanca.
9. Stanica ili sisavac u skladu s bilo kojim od prethodnih patentnih zahtjeva pri čemu genom stanice ne obuhvaća DNA konstantne regije druge stanice ili organizma.
10. Stanica ili sisavac u skladu s bilo kojim od prethodnih patentnih zahtjeva obuhvaća spojni slijed štakora.
11. Stanica u skladu s bilo kojim od patentnih zahtjeva 2-10 koj je besmrtna.
12. Stanica u skladu spatentnim zahtjevom 11 koja je stanica koja stvara protutijelo učinjena besmrtnom ili spajanjem s tumorskom stanicom zbog dobivanja stanice i stanične linije koja stvara protutijelo, ili učinjena izravnim obesmrćivanjem stanice.
13. Metoda za stvaranje protutijela ili teškog ili lakog lanca protutijela specifičnog za željeni antigen, metoda obuhvaća imuniziranje sisavca različitog od čovjeka prema bilo kojem od prethodnih patentnih zahtjeva sa željenim antigenom i stjecanje protutijela ili lanaca protutijela ili stjecanje stanica koje stvaraju protutijela ili teški ili laki lanac.
14. Sisavac različit od čovjeka, stanica, ili metoda u skladu s bilo kojim od patentnih zahtjeva 1-3 ili 5-13 pri čemu sisavac različit od čovjeka ili stanica jesu redom miš ili mišja stanica.
15. Metoda za stvaranje potpuno humaniziranih protutijela ili lanca protutijela obuhvaća imunizaciju sisavca različitog od čovjeka prema bilo kojem od patentnih zahtjeva 1, 3-5, 8-10 i 14, i zatim zamjenu konstantne regije protutijela sisavca različitog od čovjeka ili kimeričnog lanaca protutijela specifično reaktivnog s antigenom s ljudskom konstantnom regijom, neobavezno preuređivanjem nukleinskih kiselina koje kodiraju protutijelo ili lanac kimeričnog protutijela.
HRP20130253AT 2009-07-08 2013-03-21 Životinjski modeli i terapijske molekule HRP20130253T1 (hr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US22396009P 2009-07-08 2009-07-08
GBGB0911846.4A GB0911846D0 (en) 2009-07-08 2009-07-08 Animal models and therapeutic molecules
GB0913102A GB0913102D0 (en) 2009-07-28 2009-07-28 Animal models and therapeutic molesules
US35566610P 2010-06-17 2010-06-17
PCT/GB2010/051122 WO2011004192A1 (en) 2009-07-08 2010-07-07 Animal models and therapeutic molecules

Publications (1)

Publication Number Publication Date
HRP20130253T1 true HRP20130253T1 (hr) 2013-05-31

Family

ID=46318717

Family Applications (2)

Application Number Title Priority Date Filing Date
HRP20130253AT HRP20130253T1 (hr) 2009-07-08 2013-03-21 Životinjski modeli i terapijske molekule
HRP20211253TT HRP20211253T1 (hr) 2009-07-08 2021-08-04 Životinjski modeli i terapijske molekule

Family Applications After (1)

Application Number Title Priority Date Filing Date
HRP20211253TT HRP20211253T1 (hr) 2009-07-08 2021-08-04 Životinjski modeli i terapijske molekule

Country Status (5)

Country Link
US (27) US20120204278A1 (hr)
JP (6) JP6088562B2 (hr)
HK (5) HK1172207A1 (hr)
HR (2) HRP20130253T1 (hr)
SM (1) SMT201300046B (hr)

Families Citing this family (64)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2965212T3 (es) 2009-07-08 2024-04-11 Kymab Ltd Modelos de animales y moléculas terapéuticas
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
TR201906650T4 (tr) 2010-02-08 2019-05-21 Regeneron Pharma Ortak hafif zincirli fare.
US9796788B2 (en) 2010-02-08 2017-10-24 Regeneron Pharmaceuticals, Inc. Mice expressing a limited immunoglobulin light chain repertoire
US20130045492A1 (en) 2010-02-08 2013-02-21 Regeneron Pharmaceuticals, Inc. Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain
NZ707327A (en) 2010-08-02 2017-01-27 Regeneron Pharma Mice that make binding proteins comprising vl domains
DK2550363T3 (en) * 2011-02-25 2015-03-23 Regeneron Pharma ADAM6 mice
AU2012279018B2 (en) 2011-07-05 2017-06-08 Children's Medical Center Corporation N-terminal deleted GP120 immunogens
ES2872081T3 (es) 2011-08-05 2021-11-02 Regeneron Pharma Ratones con cadena ligera universal humanizada
CA2846322A1 (en) 2011-09-19 2013-03-28 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
WO2013052095A2 (en) 2011-10-03 2013-04-11 Duke University Vaccine
RU2603090C2 (ru) 2011-10-17 2016-11-20 Регенерон Фармасьютикалс, Инк. Мыши с ограниченной тяжелой цепью иммуноглобулина
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
MX356429B (es) * 2011-12-20 2018-05-29 Regeneron Pharma Ratones con cadena ligera humanizada.
DK2809150T3 (da) * 2012-02-01 2019-12-09 Regeneron Pharma Humaniserede mus, der udtrykker tungkæder indeholdende VL-domæner
US20140013456A1 (en) 2012-03-16 2014-01-09 Regeneron Pharmaceuticals, Inc. Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same
LT2825036T (lt) 2012-03-16 2018-07-10 Regeneron Pharmaceuticals, Inc. Histidino pakeitimus lengvoje grandinėje turintys antikūnai ir genetiškai modifikuoti graužikai, išvesti ju gamybai
RS59076B1 (sr) 2012-03-16 2019-09-30 Regeneron Pharma Glodari koji eksprimiraju imunoglobulinske sekvence senzitivne na ph
AU2013204581B2 (en) 2012-03-16 2015-06-25 Regeneron Pharmaceuticals, Inc. Non-human animals expressing pH-sensitive immunoglobulin sequences
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
LT3597037T (lt) * 2012-06-12 2021-06-10 Regeneron Pharmaceuticals, Inc. Humanizuoti gyvūnai, išskyrus žmones, su apribotu imunoglobulino sunkiosios grandinės lokusu
AU2013296182B2 (en) 2012-08-03 2018-03-08 Sab, Llc Complex chromosome engineering for production of human antibodies in transgenic animals
LT2931030T (lt) 2012-12-14 2020-11-10 Open Monoclonal Technology, Inc. Polinukleotidai, koduojantys graužikų antikūnus su žmogaus idiotipais, ir juos apimantys gyvūnai
MX357061B (es) * 2013-02-06 2018-06-25 Regeneron Pharma Diseño de inmunogenos a base de linaje de celulas b con animales humanizados.
RS57582B1 (sr) 2013-02-20 2018-11-30 Regeneron Pharma Nehumane životinje sa modifikovanim sekvencama imunoglobulinskog teškog lanca
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
ES2844174T3 (es) 2013-09-18 2021-07-21 Kymab Ltd Métodos, células y organismos
JP7133902B2 (ja) 2013-10-01 2022-09-09 カイマブ・リミテッド 動物モデル及び治療用分子
RU2685914C1 (ru) 2013-12-11 2019-04-23 Регенерон Фармасьютикалс, Инк. Способы и композиции для направленной модификации генома
JP2017510273A (ja) 2014-03-21 2017-04-13 リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 異なる結合特性を示すｖｌ抗原結合タンパク質
KR20210088756A (ko) 2014-03-21 2021-07-14 리제너론 파마슈티칼스 인코포레이티드 단일 도메인 결합 단백질을 생산하는 비-인간 동물
WO2016044745A1 (en) 2014-09-19 2016-03-24 Regeneron Pharmaceuticals, Inc. Chimeric antigen receptors
AU2016232715A1 (en) 2015-03-19 2017-09-28 Regeneron Pharmaceuticals, Inc. Non-human animals that select for light chain variable regions that bind antigen
JP7053499B2 (ja) 2016-06-03 2022-04-12 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 外因性ターミナルデオキシヌクレオチジルトランスフェラーゼを発現する非ヒト動物
LT3407709T (lt) * 2016-11-04 2020-10-12 Regeneron Pharmaceuticals, Inc. Gyvūnai, išskyrus žmogų, turintys sukonstruotą imunoglobulino lambda lengvosios grandinės lokusą
AR110414A1 (es) * 2016-12-21 2019-03-27 Cephalon Inc Anticuerpos que se unen específicamente a il-15 humana y usos de estos
SG11201907419PA (en) 2017-02-17 2019-09-27 Denali Therapeutics Inc Transferrin receptor transgenic models
US10457717B2 (en) 2017-02-17 2019-10-29 Denali Therapeutics Inc. Engineered polypeptides
US10143187B2 (en) 2017-02-17 2018-12-04 Denali Therapeutics Inc. Transferrin receptor transgenic models
AU2018221731C1 (en) 2017-02-17 2021-11-18 Denali Therapeutics Inc. Engineered transferrin receptor binding polypeptides
GB2561352B (en) 2017-04-10 2023-01-18 Genome Res Ltd Animal models and therapeutic molecules
JP2020533960A (ja) 2017-08-01 2020-11-26 シティ・オブ・ホープＣｉｔｙ ｏｆ Ｈｏｐｅ 抗ｉｌ１ｒａｐ抗体
MX2020004063A (es) 2017-10-20 2020-10-05 Hutchinson Fred Cancer Res Sistemas y metodos para producir celulas b modificadas geneticamente para expresar anticuerpos seleccionados.
RU2020131383A (ru) 2018-03-24 2022-04-26 Ридженерон Фармасьютикалз, Инк. Генетически модифицированные животные, отличные от человека, для выработки терапевтических антител против комплексов пептид-mhc, способы их получения и варианты применения
MA52177A (fr) 2018-03-26 2021-02-17 Regeneron Pharma Rongeurs humanisés pour tester des agents thérapeutiques
CN108486125B (zh) * 2018-03-27 2024-01-05 重庆金迈博生物科技有限公司 一种核酸分子及其在制备人源单域抗体中的应用
CN108486126A (zh) * 2018-03-27 2018-09-04 重庆金迈博生物科技有限公司 一种核酸分子及其在人源化抗体中的应用
SG11202012084WA (en) 2018-06-14 2021-01-28 Regeneron Pharma Non-human animals capable of dh-dh rearrangement in the immunoglobulin heavy chain coding sequences
KR20210133234A (ko) 2019-02-18 2021-11-05 바이오사이토젠 파마슈티컬스 (베이징) 컴퍼니 리미티드 인간화 면역글로불린 유전자좌를 갖는 유전적으로 변형된 비-인간 동물
CN114040800A (zh) 2019-04-09 2022-02-11 阿波科有限责任公司 杀伤细胞凝集素样受体亚家族g成员1(klrg1)耗竭抗体
EP4069722A1 (en) 2019-12-02 2022-10-12 Regeneron Pharmaceuticals, Inc. Peptide-mhc ii protein constructs and uses thereof
KR20230024822A (ko) 2020-06-25 2023-02-21 주식회사 휴맵 이형접합성 형질전환 동물
US20220090060A1 (en) 2020-09-11 2022-03-24 Regeneron Pharmaceuticals, Inc. Identification and production of antigen-specific antibodies
KR20230084157A (ko) 2020-10-08 2023-06-12 주식회사 휴맵 인간화 면역글로불린 유전자좌를 포함하는 게놈을 가지는 형질전환 비인간-동물 제조방법
EP4262373A1 (en) 2020-12-16 2023-10-25 Regeneron Pharmaceuticals, Inc. Mice expressing humanized fc alpha receptors
KR20230125236A (ko) 2020-12-23 2023-08-29 리제너론 파마슈티칼스 인코포레이티드 앵커 변형된 항체를 암호화하는 핵산 및 이의 사용
AU2022320627A1 (en) 2021-07-26 2024-02-08 Abcuro, Inc. Killer cell lectin-like receptor subfamily g member 1 (klrg1) depleting antibodies
WO2023097236A1 (en) * 2021-11-24 2023-06-01 The Rockefeller University Compositions and methods for generating immunoglobulin knock-in mice

Family Cites Families (184)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US114985A (en) * 1871-05-16 Improvement in apparatus for cooling and preserving milk and other liquids
US5807715A (en) * 1984-08-27 1998-09-15 The Board Of Trustees Of The Leland Stanford Junior University Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin
US5169939A (en) 1985-05-21 1992-12-08 Massachusetts Institute Of Technology & Pres. & Fellows Of Harvard College Chimeric antibodies
US4720449A (en) 1985-06-03 1988-01-19 Polaroid Corporation Thermal imaging method
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
WO1991000906A1 (en) 1989-07-12 1991-01-24 Genetics Institute, Inc. Chimeric and transgenic animals capable of producing human antibodies
US6713610B1 (en) 1990-01-12 2004-03-30 Raju Kucherlapati Human antibodies derived from immunized xenomice
WO1991010741A1 (en) 1990-01-12 1991-07-25 Cell Genesys, Inc. Generation of xenogeneic antibodies
US6673986B1 (en) 1990-01-12 2004-01-06 Abgenix, Inc. Generation of xenogeneic antibodies
US6657103B1 (en) 1990-01-12 2003-12-02 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US6255458B1 (en) 1990-08-29 2001-07-03 Genpharm International High affinity human antibodies and human antibodies against digoxin
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US7084260B1 (en) 1996-10-10 2006-08-01 Genpharm International, Inc. High affinity human antibodies and human antibodies against human antigens
ES2108048T3 (es) 1990-08-29 1997-12-16 Genpharm Int Produccion y utilizacion de animales inferiores transgenicos capaces de producir anticuerpos heterologos.
US6300129B1 (en) 1990-08-29 2001-10-09 Genpharm International Transgenic non-human animals for producing heterologous antibodies
US7041871B1 (en) 1995-10-10 2006-05-09 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1993004169A1 (en) 1991-08-20 1993-03-04 Genpharm International, Inc. Gene targeting in animal cells using isogenic dna constructs
CA2124967C (en) 1991-12-17 2008-04-08 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
CA2140638C (en) 1992-07-24 2010-05-04 Raju Kucherlapati Generation of xenogeneic antibodies
DE4228162C1 (de) 1992-08-25 1994-01-13 Rajewsky Klaus Dr Verfahren zum Ersetzen homologer Genabschnitte aus Säugern in der Keimbahn von nicht-menschlichen Säugern
JP4242447B2 (ja) 1993-01-22 2009-03-25 イミュネックス・コーポレーション Ｃｄ４０リガンド遺伝子の突然変異の検出および治療
CA2161351C (en) 1993-04-26 2010-12-21 Nils Lonberg Transgenic non-human animals capable of producing heterologous antibodies
DE4331162A1 (de) 1993-09-14 1995-03-16 Bayer Ag Verfahren zur Herstellung von Cyaninfarbstoffen
US7119248B1 (en) 1994-04-12 2006-10-10 Miltenyi Biotec Gmbh Antibodies against epitopes with homology to self antigens, methods of preparation and applications thereof
US6130364A (en) 1995-03-29 2000-10-10 Abgenix, Inc. Production of antibodies using Cre-mediated site-specific recombination
US6077667A (en) 1996-06-26 2000-06-20 Bradley; Allan Method for chromosomal rearrangement by consecutive gene targeting of two recombination substrates to the deletion endpoints
ATE374248T1 (de) 1996-06-27 2007-10-15 Vlaams Interuniv Inst Biotech Antikörpermoleküle, die spezifisch mit dem aktiven zentrum oder dem aktiven spalt eines zielmoleküls interagieren
EP1500329B1 (en) 1996-12-03 2012-03-21 Amgen Fremont Inc. Human antibodies that specifically bind human TNF alpha
US6319906B1 (en) 1996-12-31 2001-11-20 Isis Pharmaceuticals Oligonucleotide compositions and methods for the modulation of the expression of B7 protein
AU751659B2 (en) 1997-05-02 2002-08-22 Genentech Inc. A method for making multispecific antibodies having heteromultimeric and common components
US20020088019A1 (en) 1997-09-02 2002-07-04 Oron Yacoby-Zeevi Methods of and pharmaceutical compositions for improving implantation of embryos
EP1034262B1 (en) 1997-11-18 2005-08-17 Pioneer Hi-Bred International, Inc. Compositions and methods for genetic modification of plants
EP0939120A1 (en) 1998-02-27 1999-09-01 Gesellschaft für biotechnologische Forschung mbH (GBF) Method for marker-free repetitive DNA expression cassette exchange in the genome of cells or parts of cells
GB9823930D0 (en) 1998-11-03 1998-12-30 Babraham Inst Murine expression of human ig\ locus
US6914128B1 (en) 1999-03-25 2005-07-05 Abbott Gmbh & Co. Kg Human antibodies that bind human IL-12 and methods for producing
CA2373221A1 (en) 1999-05-03 2000-11-30 Yashwant M. Deo Human antibodies to staphylococcus aureus
US6833268B1 (en) 1999-06-10 2004-12-21 Abgenix, Inc. Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions
US7605238B2 (en) 1999-08-24 2009-10-20 Medarex, Inc. Human CTLA-4 antibodies and their uses
CA2307503A1 (en) 2000-05-02 2001-11-02 Carlos F. Barbas Iii Peptides for use as a vaccine or treatment for hiv infection
EP1309709A2 (en) 2000-07-21 2003-05-14 The United States of America, represented by The Secretary of Agriculture Methods for the replacement, translocation and stacking of dna in eukaryotic genomes
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US7105348B2 (en) 2000-10-31 2006-09-12 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
KR100882029B1 (ko) 2000-11-17 2009-02-09 교와 핫꼬 기린 가부시키가이샤 클로닝된 트랜스제닉 유제류에서 이종 (사람)면역글로블린의 발현
ATE378403T1 (de) 2000-11-30 2007-11-15 Medarex Inc Transchromosomale transgen-nagetiere zur herstellung von humänen antikörpern
DK1409646T3 (da) 2000-12-19 2012-08-06 Altor Bioscience Corp Transgene dyr omfattende et humaniseret immunsystem
HUP0302525A2 (hu) 2001-01-05 2003-10-28 Abgenix, Inc. Az inzulinszerű növekedési faktor I receptor elleni ellenanyagok
AUPR446701A0 (en) 2001-04-18 2001-05-17 Gene Stream Pty Ltd Transgenic mammals for pharmacological and toxicological studies
JP2003000243A (ja) 2001-06-25 2003-01-07 Takachika Azuma 変異体の製造法
FR2827302B1 (fr) 2001-07-13 2003-10-10 Genoway Cellule et animal transgenique modelisant la presentation antigenique humaine et leurs utilisations
US20060199204A1 (en) 2001-10-05 2006-09-07 U.S. Epa Genetic testing for male factor infertility
WO2003031656A1 (en) 2001-10-05 2003-04-17 United States Environmental Protection Agency Genetic testing for male factor infertility
DK2319301T3 (en) 2001-11-30 2017-12-04 Amgen Fremont Inc Transgenic animals with human Ig lambda light chain genes
WO2003061363A2 (en) 2002-01-17 2003-07-31 Albert Einstein College Of Medicine Of Yeshiva University Mutations caused by activation-induced cytidine deaminase
US8877901B2 (en) 2002-12-13 2014-11-04 Immunomedics, Inc. Camptothecin-binding moiety conjugates
ES2442615T5 (es) 2002-07-18 2023-03-16 Merus Nv Producción recombinante de mezclas de anticuerpos
WO2004022738A1 (en) 2002-09-09 2004-03-18 California Institute Of Technology Methods and compositions for the generation of humanized mice
EP1553945A4 (en) 2002-10-01 2008-11-05 Mitos Pharmaceuticals Inc NITROXIDE RADIATION PROTECTION AND APPLICATION METHOD
US7700356B2 (en) 2002-11-08 2010-04-20 The United States Of America As Represented By The Secretary Of Agriculture System for gene targeting and producing stable genomic transgene insertions
DE10251918A1 (de) 2002-11-08 2004-05-19 Horn, Carsten, Dipl.-Biochem. Dr. Systeme zur Erzeugung stabiler genomischer Transgen-Insertionen
CL2003002461A1 (es) 2002-11-27 2005-01-07 Dow Chemical Company Agroscien Inmunoglobulina que comprende al menos un glicano afucosilado, composicion que la contiene, secuencia nucleotidica y vector que la comprende, procedimiento para producir dicha inmunoglobulina en plantas.
GB2398784B (en) 2003-02-26 2005-07-27 Babraham Inst Removal and modification of the immunoglobulin constant region gene cluster of a non-human mammal
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
EP1639009B1 (en) 2003-05-30 2013-02-27 Merus B.V. Fab library for the preparation of a mixture of antibodies
US7205148B2 (en) 2003-06-11 2007-04-17 Regeneron Pharmaceuticals, Inc. Genome mutation by intron insertion into an embryonic stem cell genome
GB2403475B (en) 2003-07-01 2008-02-06 Oxitec Ltd Stable integrands
MXPA06000562A (es) 2003-07-15 2006-03-30 Therapeutic Human Polyclonals Loci de inmunoglobulina humanizada.
US7663017B2 (en) 2003-07-30 2010-02-16 Institut Pasteur Transgenic mice having a human major histocompatability complex (MHC) phenotype, experimental uses and applications
WO2005019463A1 (en) 2003-08-11 2005-03-03 Therapeutic Human Polyclonals, Inc. Improved transgenesis with humanized immunoglobulin loci
US7604994B2 (en) 2003-09-03 2009-10-20 Morphotek, Inc. Genetically altered antibody-producing cell lines with improved antibody characteristics
CA2445602C (en) 2003-10-20 2014-01-14 Campusgen Gmbh Nucleotide sequence for creatinine deiminase and method of use
US20050191293A1 (en) 2003-12-10 2005-09-01 Shrikant Deshpande IP-10 antibodies and their uses
WO2005092926A2 (en) 2004-03-19 2005-10-06 Amgen Inc. Reducing the risk of human and anti-human antibodies through v gene manipulation
US7625549B2 (en) 2004-03-19 2009-12-01 Amgen Fremont Inc. Determining the risk of human anti-human antibodies in transgenic mice
SI2311874T1 (sl) 2004-07-22 2017-12-29 Erasmus University Medical Center Rotterdam Department of Cell Biology and Genetics Vezavne molekule
FR2875239B1 (fr) 2004-09-10 2007-07-20 Inst Necker Ass Loi De 1901 Procede pour l'acceleration des mutations somatiques et son application en proteomique
CN101076542A (zh) 2004-09-13 2007-11-21 伊沃詹尼克斯有限公司 特异性针对肝细胞癌和其他癌的抗体及其用途
WO2006044492A2 (en) 2004-10-14 2006-04-27 Ingenious Targeting Laboratory, Inc. Methods for generating rat embryo-derived cell lines and genetic modification of rat genome
WO2006044962A1 (en) 2004-10-19 2006-04-27 Regeneron Pharmaceuticals, Inc. Method for generating an animal homozygous for a genetic modification
US20080184380A1 (en) 2004-10-22 2008-07-31 Therapeutic Human Polyclonals Inc. Suppression of Endogenous Immunoglobulin Expression in Non-Human Transgenic Animals
WO2006055704A2 (en) 2004-11-17 2006-05-26 Curagen Corporation Antibodies directed to ten-m proteins and uses thereof
EP2284194A1 (en) 2004-12-21 2011-02-16 AstraZeneca AB Antibodies directed to angiopoietin-2 and uses thereof
CA2604440A1 (en) 2005-04-29 2006-11-09 Inserm (Institut De La Sante Et De La Recherche Medicale) Transgenic animals and methods of making recombinant antibodies
JP2008545375A (ja) 2005-05-14 2008-12-18 フダン ユニバーシテイ 脊椎動物の遺伝子操作および解析のための手段としてのｐｉｇｇｙＢａｃ
EP1780272A1 (en) 2005-10-27 2007-05-02 GSF-Forschungszentrum für Umwelt und Gesundheit GmbH Method for enhancing somatic hypermutation, gene conversion and class switch recombination
GB0601513D0 (en) 2006-01-25 2006-03-08 Univ Erasmus Medical Ct Binding molecules 3
WO2007096779A2 (en) * 2006-01-25 2007-08-30 Erasmus University Medical Center Rotterdam Generation of heavy-chain only antibodies in transgenic animals
US7462759B2 (en) 2006-02-03 2008-12-09 Pioneer Hi-Bred International, Inc. Brittle stalk 2 gene family and related methods and uses
JP5514539B2 (ja) 2006-03-31 2014-06-04 メダレックス・リミテッド・ライアビリティ・カンパニー ヒト抗体の調製に用いるためのキメラ抗体を発現するトランスジェニック動物
US7846724B2 (en) * 2006-04-11 2010-12-07 Hoffmann-La Roche Inc. Method for selecting CHO cell for production of glycosylated antibodies
RS52643B (en) 2006-06-02 2013-06-28 Regeneron Pharmaceuticals Inc. HIGH AFINITY ANTIBODIES TO THE HUMAN IL-6 RECEPTOR
EP2409714A1 (en) 2006-06-27 2012-01-25 Sanofi Pasteur VaxDesign Corporation Models for vaccine assessment
EP1878342A1 (en) 2006-07-13 2008-01-16 Institut Pasteur Immunodeficient mice transgenic for HLA class I and HLA class II molecules and their uses
US8084024B2 (en) 2006-08-22 2011-12-27 G2 Inflammation Pty Ltd Method for producing antibodies
US7778624B2 (en) * 2006-09-01 2010-08-17 Wanda Ying Li Outdoor umbrella with audio system
RU2445318C2 (ru) 2006-10-02 2012-03-20 Ридженерон Фармасьютикалз, Инк. Высокоаффинные антитела человека к рецептору il-4 человека
WO2008070367A2 (en) 2006-11-01 2008-06-12 Facet Biotech Corporation Mammalian cell-based immunoglobulin display libraries
RU2448979C2 (ru) 2006-12-14 2012-04-27 Ридженерон Фармасьютикалз, Инк. Антитела человека к дельта-подобному лиганду-4 человека
GB0700194D0 (en) 2007-01-05 2007-02-14 Univ Edinburgh Humanisation of animals
US8603950B2 (en) 2007-02-20 2013-12-10 Anaptysbio, Inc. Methods of generating libraries and uses thereof
RS53258B (en) 2007-02-21 2014-08-29 University Of Massachusetts HUMAN ANTIBODIES AGAINST HEPATITIS C (HCV) VIRUS AND USE
MX2009009912A (es) 2007-03-27 2010-01-18 Sea Lane Biotechnologies Llc Constructos y colecciones que comprenden secuencias de cadena ligera sustitutas de anticuerpos.
GB0706628D0 (en) 2007-04-04 2007-05-16 Univ Erasmus Germ-line manipulation 1
KR101886610B1 (ko) 2007-06-01 2018-08-09 오픈 모노클로날 테크놀로지, 인코포레이티드 내생적 면역글로불린 유전자를 억제하고 트랜스제닉 인간 이디오타입 항체를 생산하기 위한 방법 및 조성물
WO2009013620A2 (en) 2007-06-11 2009-01-29 Erasmus University Medical Center Rotterdam Homologous recombination
DK2178916T3 (en) 2007-07-31 2015-01-12 Regeneron Pharma Human antibodies to human cd20 and method thereof for use
EP3255144A1 (en) 2007-08-10 2017-12-13 E. R. Squibb & Sons, L.L.C. Recombineering construct for preparing transgenic mice capable of producing human immunoglobulin
PT2187964E (pt) 2007-08-10 2015-01-14 Regeneron Pharma Anticorpos humanos de elevada afinidade para o factor de crescimento neural humano
AU2008309934B2 (en) * 2007-10-12 2014-03-06 F. Hoffmann-La Roche Ag Protein expression from multiple nucleic acids
US20110119779A1 (en) 2007-12-10 2011-05-19 Aliva Biopharmaceuticals, Inc. Methods for sequential replacement of targeted region by homologous recombination
US8227577B2 (en) 2007-12-21 2012-07-24 Hoffman-La Roche Inc. Bivalent, bispecific antibodies
JP2011510155A (ja) 2008-01-25 2011-03-31 キャボット コーポレイション 改質された着色顔料の調製方法
KR101409375B1 (ko) 2008-01-31 2014-06-18 삼성전자주식회사 반도체 메모리장치의 블록 디코딩 회로
WO2009118524A2 (en) 2008-03-26 2009-10-01 Iti Scotland Limited Efficient insertion of dna into embryonic stem cells
WO2009129247A2 (en) 2008-04-14 2009-10-22 Innovative Targeting Solutions Inc. Sequence diversity generation in immunoglobulins
ES2436044T3 (es) 2008-05-23 2013-12-26 Ablexis, Llc Procedimiento de generación de anticuerpos de dominio VL individual en animales transgénicos
EP2556747B1 (en) 2008-06-27 2020-12-02 Merus N.V. Antibody producing transgenic mice
KR101987351B1 (ko) * 2008-09-30 2019-06-10 아블렉시스, 엘엘씨 키메라 항체의 제조를 위한 인간 이외의 포유동물
JO3672B1 (ar) 2008-12-15 2020-08-27 Regeneron Pharma أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9).
SG172176A1 (en) 2008-12-18 2011-07-28 Univ Erasmus Medical Ct Non-human transgenic animals expressing humanised antibodies and use therof
US9085795B2 (en) 2009-02-04 2015-07-21 Molecular Innovations, Inc. Methods for screening candidate agents for modulating prorenin and renin, assays for detecting prorenin and antibodies
JP2012518398A (ja) 2009-02-24 2012-08-16 グラクソ グループ リミテッド 抗原結合性構築物
GB0905023D0 (en) 2009-03-24 2009-05-06 Univ Erasmus Medical Ct Binding molecules
WO2010113039A1 (en) 2009-04-03 2010-10-07 Medical Research Council Mutants of activation-induced cytidine deaminase (aid) and methods of use
US8969082B2 (en) 2009-06-26 2015-03-03 Sea Lane Biotechnologies, Llc Expression of surrogate light chains
ES2965212T3 (es) 2009-07-08 2024-04-11 Kymab Ltd Modelos de animales y moléculas terapéuticas
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
DK2454283T3 (en) 2009-07-15 2018-05-07 Aimm Therapeutics Bv METHODS AND PROCEDURES FOR MANUFACTURING HIGH EFFICIENCY ANTIBODIES
JO3182B1 (ar) 2009-07-29 2018-03-08 Regeneron Pharma مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2
WO2011019844A1 (en) 2009-08-13 2011-02-17 Crystal Bioscience Inc. Transgenic animal for production of antibodies having minimal cdrs
US20120251552A1 (en) 2009-11-05 2012-10-04 Anaptysbio, Inc. Methods of generating improved antigen-binding agents using chain shuffling and optionally somatic hypermutation
CN102741404B (zh) 2009-11-17 2017-03-08 Sab有限责任公司 人类人工染色体载体
WO2011071957A1 (en) 2009-12-07 2011-06-16 Sea Lane Biotechnologies, Llc Conjugates comprising an antibody surrogate scaffold with improved pharmacokinetic properties
LT2954779T (lt) 2009-12-10 2019-05-27 Regeneron Pharmaceuticals, Inc. Pelės, gaminančios sunkiosios grandinės antikūnus
US20120021409A1 (en) 2010-02-08 2012-01-26 Regeneron Pharmaceuticals, Inc. Common Light Chain Mouse
TR201906650T4 (tr) 2010-02-08 2019-05-21 Regeneron Pharma Ortak hafif zincirli fare.
EP2571512B1 (en) 2010-05-17 2017-08-23 Sangamo BioSciences, Inc. Novel dna-binding proteins and uses thereof
EP2582230A1 (en) 2010-06-17 2013-04-24 Kymab Limited Animal models and therapeutic molecules
RS58736B1 (sr) 2010-06-22 2019-06-28 Regeneron Pharma Miševi koji ispoljavaju imunoglobinski hibrid lakog lanca sa ljudskom varijabilnom regijom
NZ707327A (en) 2010-08-02 2017-01-27 Regeneron Pharma Mice that make binding proteins comprising vl domains
RU2608640C2 (ru) 2010-08-16 2017-01-23 Новиммун С.А. Способы получения мультиспецифичных и мультивалентных антител
JO3375B1 (ar) 2010-11-08 2019-03-13 Regeneron Pharma أجسام مضادة بشرية للجين a1 الشبيه بعامل النخر الورمي (tl1a)
EA201390929A1 (ru) 2010-12-22 2013-12-30 Дженентек, Инк. Антитела к pcsk9 и способы их применения
DK2550363T3 (en) 2011-02-25 2015-03-23 Regeneron Pharma ADAM6 mice
ES2872081T3 (es) 2011-08-05 2021-11-02 Regeneron Pharma Ratones con cadena ligera universal humanizada
EP3741862A1 (en) 2011-09-19 2020-11-25 Kymab Limited Animals, repertoires & methods for the production of human antibodies
CA2846322A1 (en) 2011-09-19 2013-03-28 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
WO2013045916A1 (en) 2011-09-26 2013-04-04 Kymab Limited Chimaeric surrogate light chains (slc) comprising human vpreb
RU2603090C2 (ru) 2011-10-17 2016-11-20 Регенерон Фармасьютикалс, Инк. Мыши с ограниченной тяжелой цепью иммуноглобулина
US20130102031A1 (en) 2011-10-25 2013-04-25 Anaptysbio, Inc. Use of somatic hypermutation to create insertion and deletion mutations in vitro
GB2496375A (en) 2011-10-28 2013-05-15 Kymab Ltd A non-human assay vertebrate comprising human antibody loci and human epitope knock-in, and uses thereof
US9253965B2 (en) 2012-03-28 2016-02-09 Kymab Limited Animal models and therapeutic molecules
GB201122047D0 (en) 2011-12-21 2012-02-01 Kymab Ltd Transgenic animals
US20180295821A1 (en) 2011-12-02 2018-10-18 Kymab Limited Transgenic Animals
MX356429B (es) 2011-12-20 2018-05-29 Regeneron Pharma Ratones con cadena ligera humanizada.
DK2809150T3 (da) 2012-02-01 2019-12-09 Regeneron Pharma Humaniserede mus, der udtrykker tungkæder indeholdende VL-domæner
AR090219A1 (es) 2012-03-02 2014-10-29 Regeneron Pharma Anticuerpos humanos frente a toxinas de clostridium difficile
AU2013204140B2 (en) 2012-03-06 2016-01-28 Regeneron Pharmaceuticals, Inc. Common light chain mouse
AU2013204581B2 (en) 2012-03-16 2015-06-25 Regeneron Pharmaceuticals, Inc. Non-human animals expressing pH-sensitive immunoglobulin sequences
WO2013144567A1 (en) 2012-03-28 2013-10-03 Kymab Limited Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies
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
JO3820B1 (ar) 2012-05-03 2021-01-31 Regeneron Pharma أجسام مضادة بشرية لـ fel d1وطرق لاستخدامها
LT3401400T (lt) 2012-05-25 2019-06-10 The Regents Of The University Of California Būdai ir kompozicijos, skirtos rnr molekulės nukreipiamai tikslinės dnr modifikacijai ir rnr molekulės nukreipiamam transkripcijos moduliavimui
US8518765B1 (en) 2012-06-05 2013-08-27 Intermolecular, Inc. Aqua regia and hydrogen peroxide HCl combination to remove Ni and NiPt residues
LT3597037T (lt) 2012-06-12 2021-06-10 Regeneron Pharmaceuticals, Inc. Humanizuoti gyvūnai, išskyrus žmones, su apribotu imunoglobulino sunkiosios grandinės lokusu
US8962913B2 (en) * 2012-06-18 2015-02-24 Regeneron Pharmaceuticals, Inc. Humanized IL-7 rodents
CN105602952B (zh) 2012-11-09 2019-11-19 深圳市作物分子设计育种研究院 一种育性基因及其应用
ES2658401T3 (es) 2012-12-12 2018-03-09 The Broad Institute, Inc. Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas
RS57582B1 (sr) 2013-02-20 2018-11-30 Regeneron Pharma Nehumane životinje sa modifikovanim sekvencama imunoglobulinskog teškog lanca
US10993420B2 (en) 2013-03-15 2021-05-04 Erasmus University Medical Center Production of heavy chain only antibodies in transgenic mammals
US9788534B2 (en) 2013-03-18 2017-10-17 Kymab Limited Animal models and therapeutic molecules
US20150033372A1 (en) 2013-05-01 2015-01-29 Kymab Limited Human VpreB & Chimaeric Surrogate Light Chains in Transgenic Non-Human Vertebrates
US9783618B2 (en) * 2013-05-01 2017-10-10 Kymab Limited Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics
US9783593B2 (en) 2013-05-02 2017-10-10 Kymab Limited Antibodies, variable domains and chains tailored for human use
US11707056B2 (en) 2013-05-02 2023-07-25 Kymab Limited Animals, repertoires and methods
US20140331339A1 (en) 2013-05-03 2014-11-06 Kymab Limited Transgenic Non-Human Assay Vertebrates, Assays and Kits
US20140331344A1 (en) 2013-05-03 2014-11-06 Kymab Ltd. Transgenic Animals
JP7133902B2 (ja) 2013-10-01 2022-09-09 カイマブ・リミテッド 動物モデル及び治療用分子
GB201710984D0 (en) 2017-07-07 2017-08-23 Kymab Ltd Cells, vertebrates, populations & methods
JP7087648B2 (ja) * 2018-05-08 2022-06-21 トヨタ自動車株式会社 電池パック

Also Published As

Publication number Publication date
JP2015126736A (ja) 2015-07-09
US20130042331A2 (en) 2013-02-14
JP2020028296A (ja) 2020-02-27
JP6876854B2 (ja) 2021-05-26
US20130318643A1 (en) 2013-11-28
HK1172207A1 (zh) 2013-04-19
US20170101482A1 (en) 2017-04-13
US20160345551A1 (en) 2016-12-01
US20170071174A1 (en) 2017-03-16
US9505827B2 (en) 2016-11-29
JP6612275B2 (ja) 2019-11-27
US10064398B2 (en) 2018-09-04
US20120204278A1 (en) 2012-08-09
HK1180535A1 (en) 2013-10-25
US20140182003A1 (en) 2014-06-26
US20140150125A1 (en) 2014-05-29
US20170105396A1 (en) 2017-04-20
JP7141427B2 (ja) 2022-09-22
US20140120582A1 (en) 2014-05-01
US20140150126A1 (en) 2014-05-29
US20160044900A1 (en) 2016-02-18
US20170051045A1 (en) 2017-02-23
US20200352144A1 (en) 2020-11-12
JP6876853B2 (ja) 2021-05-26
US20140201856A1 (en) 2014-07-17
US9447177B2 (en) 2016-09-20
US20160345552A1 (en) 2016-12-01
JP2020150951A (ja) 2020-09-24
US20150040250A1 (en) 2015-02-05
US20170099816A1 (en) 2017-04-13
HK1202373A1 (en) 2015-10-02
JP6088562B2 (ja) 2017-03-01
US20140201854A1 (en) 2014-07-17
JP2017086084A (ja) 2017-05-25
US20170099817A1 (en) 2017-04-13
JP2020156503A (ja) 2020-10-01
US11812731B2 (en) 2023-11-14
US20150113669A1 (en) 2015-04-23
HK1162119A1 (en) 2012-08-24
SMT201300046B (it) 2013-07-09
US20120167237A1 (en) 2012-06-28
JP6930695B2 (ja) 2021-09-01
US20200337280A1 (en) 2020-10-29
US9434782B2 (en) 2016-09-06
HRP20211253T1 (hr) 2021-11-12
US11606941B2 (en) 2023-03-21
US20170094956A1 (en) 2017-04-06
US20170099815A1 (en) 2017-04-13
US20200352145A1 (en) 2020-11-12
US20140134156A1 (en) 2014-05-15
HK1201026A1 (en) 2015-08-21
US10165763B2 (en) 2019-01-01
JP2020156502A (ja) 2020-10-01
US20200375158A1 (en) 2020-12-03

Similar Documents

Publication Publication Date Title
HRP20130253T1 (hr) Životinjski modeli i terapijske molekule
JP2012532598A5 (hr)
JP6479024B2 (ja) 抗体親和性の最適化のための高スループットマウスモデル
ES2665793T3 (es) Anticuerpos de cadena ligera modificada mediante ingeniería genética con histidina y roedores modificados genéticamente para la generación de los mismos
ES2770424T3 (es) Ratones ADAM6
JP2015502149A5 (hr)
PT2421357E (pt) Modelos animais e moléculas terapêuticas
ES2712207T3 (es) Ratones que expresan un repertorio limitado de cadenas ligeras de inmunoglobulina
HRP20200613T1 (hr) Neljudske životinje koje imaju humanizirani gen 1 za programiranu staničnu smrt
ES2738679T3 (es) Anticuerpos de cadena ligera diseñados genéticamente con histidina y animales no humanos modificados genéticamente para generar los mismos
HRP20160484T4 (hr) Životinje koje izražavaju antitijela sa zajedničkim lakim lancem
SG10201408500RA (en) Antibody producing non-human mammals
JP2020530760A5 (hr)
Laffleur et al. Production of human or humanized antibodies in mice
HRP20160158T4 (hr) Topiva protutijela koja sadrže samo teške lance
Shi et al. Dynamics of planar cell polarity protein Vangl2 in the mouse oviduct epithelium
Hasegawa et al. Generation of CRISPR/Cas9-mediated bicistronic knock-in ins1-cre driver mice
Fatema et al. Gamete nuclear migration in animals and plants
BR112021023683A2 (pt) Roedor e camundongo geneticamente modificado, embrião de roedor, célula b do roedor ou camundongo geneticamente modificado, hibridoma, população de células b, célula-tronco embrionária, célula de mamífero, métodos de produção de um anticorpo, de uma cadeia pesada, de um domínio variável, de uma coleção de domínios variáveis, de uma cadeia leve, de uma sequência nucleotídica, de um roedor geneticamente modificado e de células es, de geração de um domínio variável e in vitro para gerar uma célula recombinante de roedor, e, vetor de direcionamento
CN110438160A (zh) 一种Cd2ap基因敲除动物的构建方法及应用
Iwata et al. Bacillus subtilis genome vector-based complete manipulation and reconstruction of genomic DNA for mouse transgenesis
Makino et al. Generation of a dual-color reporter mouse line to monitor spermatogenesis in vivo
WO2022248445A1 (en) Animal models and therapeutic molecules
Meng et al. Generation and identification of endothelial-specific Hrh2 knockout mice
KR102131883B1 (ko) Cre 재조합효소 의존적으로 TREK-1 발현이 억제되는 항우울 동물모델 및 이의 제조방법