HRP20220205T1 - Transgena mišja životinja koja proizvodi antitijela - Google Patents
Transgena mišja životinja koja proizvodi antitijela Download PDFInfo
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- HRP20220205T1 HRP20220205T1 HRP20220205TT HRP20220205T HRP20220205T1 HR P20220205 T1 HRP20220205 T1 HR P20220205T1 HR P20220205T T HRP20220205T T HR P20220205TT HR P20220205 T HRP20220205 T HR P20220205T HR P20220205 T1 HRP20220205 T1 HR P20220205T1
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- Prior art keywords
- host according
- light chain
- transgenic host
- transgenic
- nucleic acid
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Links
- 230000009261 transgenic effect Effects 0.000 title claims 16
- 241001529936 Murinae Species 0.000 title 1
- 108020004707 nucleic acids Proteins 0.000 claims 8
- 150000007523 nucleic acids Chemical class 0.000 claims 8
- 102000039446 nucleic acids Human genes 0.000 claims 8
- 210000004602 germ cell Anatomy 0.000 claims 6
- 239000000427 antigen Substances 0.000 claims 4
- 108091007433 antigens Proteins 0.000 claims 4
- 102000036639 antigens Human genes 0.000 claims 4
- 230000005875 antibody response Effects 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 210000003719 b-lymphocyte Anatomy 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 230000010354 integration Effects 0.000 claims 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims 1
- 101001091242 Homo sapiens Immunoglobulin kappa joining 1 Proteins 0.000 claims 1
- 101001138089 Homo sapiens Immunoglobulin kappa variable 1-39 Proteins 0.000 claims 1
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 102100034892 Immunoglobulin kappa joining 1 Human genes 0.000 claims 1
- 102100020910 Immunoglobulin kappa variable 1-39 Human genes 0.000 claims 1
- 101150008942 J gene Proteins 0.000 claims 1
- 241001465754 Metazoa Species 0.000 claims 1
- 101100351020 Mus musculus Pax5 gene Proteins 0.000 claims 1
- 101100370002 Mus musculus Tnfsf14 gene Proteins 0.000 claims 1
- 102100037504 Paired box protein Pax-5 Human genes 0.000 claims 1
- 101710149067 Paired box protein Pax-5 Proteins 0.000 claims 1
- 101100351021 Xenopus laevis pax5 gene Proteins 0.000 claims 1
- 230000011712 cell development Effects 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 230000030279 gene silencing Effects 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
- 229940072221 immunoglobulins Drugs 0.000 claims 1
- 230000008707 rearrangement Effects 0.000 claims 1
- 230000000717 retained effect Effects 0.000 claims 1
- 238000011830 transgenic mouse model Methods 0.000 claims 1
Classifications
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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
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified 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; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0276—Knock-out vertebrates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
- A01K2217/052—Animals comprising random inserted nucleic acids (transgenic) inducing gain of function
-
- 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
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/15—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
- A01K2267/00—Animals characterised by purpose
- A01K2267/01—Animal expressing industrially exogenous proteins
-
- 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
- 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
- C12N2800/00—Nucleic acids vectors
- C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Environmental Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Animal Husbandry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (19)
1. Transgeni mišji domaćin koji je u stanju da proizvodi imunoglobuline koji sadrže ljudsku VL regiju, pri čemu navedeni mišji domaćin sadrži integriranu u svojoj germinativnoj liniji preuređenu nukleinsku kiselinu koja sadrži jedan ljudske germinativne linije V i jedan ljudske germinativne linije J genski segment koji kodira preuređenu ljudsku VL regiju i konstantnu regiju lakog lanca bilo koje životinjske vrste, pri čemu je navedena varijabilna regija lakog lanca u stanju da se upari sa najmanje dva različita teška lanca kodirana od strane domaćina, tako da se raznolikost u specifičnosti antitijela koja sadrže navedenu ljudsku VL regiju zadržava kroz preuređivanja i hipermutacije u teškim lancima.
2. Transgeni domaćin prema patentnom zahtjevu 1, pri čemu je domaćin miš.
3. Transgeni domaćin prema patentnom zahtjevu 1 ili 2, pri čemu navedena konstantna regija lakog lanca je mišja konstantna regija lakog lanca.
4. Transgeni domaćin prema bilo kojem od patentnih zahtjeva 1-3, pri čemu je integracija u lokusu koji je otporan na utišavanje.
5. Transgeni domaćin prema bilo kojem od patentnih zahtjeva 1-3, pri čemu je integracija u Rosa-lokusu.
6. Transgeni domaćin prema bilo kojem od patentnih zahtjeva 1-5, pri čemu je varijabilna regija lakog lanca koja kodira nukleinsku kiselinu osigurana sredstvom koje omogućava eksprimiranje spomenute nukleinske kiseline suštinski ograničeno na stanice B stanične loze.
7. Transgeni domaćin prema patentnom zahtjevu 6, pri čemu je varijabilna regija lakog lanca koja kodira nukleinsku kiselinu osigurana sredstvom koje omogućava eksprimiranje varijabilne regije lakog lanca koja kodira nukleinsku kiselinu pretežno tokom određene faze razvoja B stanica.
8. Transgeni domaćin prema patentnom zahtjevu 7, pri čemu navedeno sredstvo sadrži promoter odabran iz grupe CD19, CD20, µHC, VpreB1, VpreB2, VpreB3, λ5, Igα, Igβ, κLC, λLC, i BSAP (Pax5).
9. Transgeni domaćin prema patentnom zahtjevu 7 ili 8, pri čemu navedeno sredstvo sadrži cre-lox sustav.
10. Transgeni domaćin prema bilo kojem od patentnih zahtjeva 1-9, pri čemu je navedena varijabilna regija lakog lanca sposobna za uparivanje sa najmanje dva teška lanca domaćina.
11. Transgeni domaćin prema bilo kojem od patentnih zahtjeva 1-9, pri čemu je navedena varijabilna regija lakog lanca sposobna za uparivanje sa najmanje dva ljudska teška lanca.
12. Transgeni domaćin prema bilo kojem od patentnih zahtjeva 1-11, pri čemu je najmanje jedan od endogenih lokusa koji kodira endogeni laki lanac funkcionalno utišan.
13. Transgeni domaćin prema bilo kojem od patentnih zahtjeva 1-12, pri čemu je lokus endogenog κ lakog lanca funkcionalno utišan.
14. Transgeni domaćin prema bilo kojem od patentnih zahtjeva 1-13, pri čemu sekvenca varijabilne regije lakog lanca koja kodira nukleinsku kiselinu je sekvenca vκ ljudske germinativne linije.
15. Transgeni domaćin prema patentnom zahtjevu 14, pri čemu sekvenca vκ germinativne linije je na bazi 012.
16. Transgeni domaćin prema patentnom zahtjevu 15, pri čemu sekvenca vκ germinativne linije je IGKV1-39*01 / IGKJ1*01.
17. Postupak za proizvodnju željenog antitijela koji obuhvaća izlaganje domaćina prema bilo kojem od patentnih zahtjeva 1-16 antigenu tako da je odgovor antitijela induciran i izoliranje antitijela specifičnih za antigen.
18. Postupak za proizvodnju željenog antitijela koji obuhvaća izlaganje domaćina prema bilo kojem od patentnih zahtjeva 1-16 antigenu tako da je odgovor antitijela induciran i izoliranje stanica koje proizvode takva antitijela, kultivaciju i prikupljanje spomenutih antitijela.
19. Postupak za proizvodnju željenog antitijela koji obuhvaća izlaganje domaćina prema bilo kojem od patentnih zahtjeva 1-16 antigenu tako da je odgovor antitijela induciran i izoliranje nukleinske kiseline koja kodira najmanje dio takvog antitijela, umetanje navedene nukleinske kiseline ili kopije ili derivata iste u ekspresijsku kasetu i eksprimiranje navedenog antitijela u stanici domaćina.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NL2008050430 | 2008-06-27 | ||
EP18183980.4A EP3456190B1 (en) | 2008-06-27 | 2009-06-29 | Antibody producing transgenic murine animal |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20220205T1 true HRP20220205T1 (hr) | 2022-05-27 |
Family
ID=41280336
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20220205TT HRP20220205T1 (hr) | 2008-06-27 | 2009-06-29 | Transgena mišja životinja koja proizvodi antitijela |
HRP20140139AT HRP20140139T1 (hr) | 2008-06-27 | 2014-02-13 | Protutijela koja proizvode nehumani sisavci |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20140139AT HRP20140139T1 (hr) | 2008-06-27 | 2014-02-13 | Protutijela koja proizvode nehumani sisavci |
Country Status (23)
Country | Link |
---|---|
EP (6) | EP3456191A1 (hr) |
JP (6) | JP5749161B2 (hr) |
KR (5) | KR20110029156A (hr) |
CN (3) | CN102123582B (hr) |
AU (1) | AU2009263082C1 (hr) |
CA (1) | CA2729095C (hr) |
CY (2) | CY1114830T1 (hr) |
DK (3) | DK2147594T3 (hr) |
ES (3) | ES2906344T3 (hr) |
HK (1) | HK1154463A1 (hr) |
HR (2) | HRP20220205T1 (hr) |
HU (1) | HUE057994T2 (hr) |
LT (1) | LT3456190T (hr) |
MX (1) | MX2010014542A (hr) |
NZ (1) | NZ590118A (hr) |
PL (2) | PL2147594T3 (hr) |
PT (3) | PT2147594E (hr) |
RS (2) | RS53146B (hr) |
RU (2) | RU2731084C2 (hr) |
SG (3) | SG10201408500RA (hr) |
SI (2) | SI2147594T1 (hr) |
WO (1) | WO2009157771A2 (hr) |
ZA (1) | ZA201009312B (hr) |
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USRE47770E1 (en) | 2002-07-18 | 2019-12-17 | Merus N.V. | Recombinant production of mixtures of antibodies |
US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
EP2395016A3 (en) | 2003-05-30 | 2012-12-19 | Merus B.V. | Design and use of paired variable regions of specific binding molecules |
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ES2906344T3 (es) * | 2008-06-27 | 2022-04-18 | Merus Nv | Animal murino transgénico productor de anticuerpos |
LT2346994T (lt) | 2008-09-30 | 2022-03-10 | Ablexis, Llc | Knock-in pelė, skirta chimerinių antikūnų gamybai |
CN102638971B (zh) | 2009-07-08 | 2015-10-07 | 科马布有限公司 | 动物模型及治疗分子 |
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US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
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US9580491B2 (en) | 2010-03-31 | 2017-02-28 | Ablexis, Llc | Genetic engineering of non-human animals for the production of chimeric antibodies |
CN103228130B (zh) * | 2010-06-17 | 2016-03-16 | 科马布有限公司 | 动物模型及治疗分子 |
CA2806233C (en) | 2010-07-26 | 2021-12-07 | Trianni, Inc. | Transgenic animals and methods of use |
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US10793829B2 (en) | 2010-07-26 | 2020-10-06 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
NZ606824A (en) * | 2010-08-02 | 2015-05-29 | Regeneron Pharma | Mice that make binding proteins comprising vl domains |
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JP2014533930A (ja) * | 2011-09-19 | 2014-12-18 | カイマブ・リミテッド | 免疫グロブリン遺伝子多様性の操作およびマルチ抗体治療薬 |
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EP3816284A1 (en) | 2011-12-22 | 2021-05-05 | F. Hoffmann-La Roche AG | Expression vector for antibody production in eukaryotic cells |
PL2809150T3 (pl) * | 2012-02-01 | 2020-04-30 | Regeneron Pharmaceuticals, Inc. | Humanizowane myszy wykazujące ekspresję łańcuchów ciężkich zawierających domeny VL |
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