HRP20192218T1 - Humanizirani miševi koji izražavaju teške lance koji sadrže vl domene - Google Patents
Humanizirani miševi koji izražavaju teške lance koji sadrže vl domene Download PDFInfo
- Publication number
- HRP20192218T1 HRP20192218T1 HRP20192218TT HRP20192218T HRP20192218T1 HR P20192218 T1 HRP20192218 T1 HR P20192218T1 HR P20192218T T HRP20192218T T HR P20192218TT HR P20192218 T HRP20192218 T HR P20192218T HR P20192218 T1 HRP20192218 T1 HR P20192218T1
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- Prior art keywords
- human
- gene
- segments
- mouse
- light chain
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- 238000011577 humanized mouse model Methods 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 claims 38
- 241001529936 Murinae Species 0.000 claims 9
- 150000007523 nucleic acids Chemical group 0.000 claims 9
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims 7
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims 7
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 5
- 239000000427 antigen Substances 0.000 claims 5
- 102000036639 antigens Human genes 0.000 claims 5
- 108091007433 antigens Proteins 0.000 claims 5
- 239000012634 fragment Substances 0.000 claims 5
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims 4
- 210000003719 b-lymphocyte Anatomy 0.000 claims 4
- 102000004169 proteins and genes Human genes 0.000 claims 4
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 229920001184 polypeptide Polymers 0.000 claims 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 claims 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 claims 1
- 108090000143 Mouse Proteins Proteins 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 238000012217 deletion Methods 0.000 claims 1
- 230000037430 deletion Effects 0.000 claims 1
- 210000004408 hybridoma Anatomy 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 230000008707 rearrangement Effects 0.000 claims 1
- 238000011144 upstream manufacturing Methods 0.000 claims 1
Classifications
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6489—Metalloendopeptidases (3.4.24)
-
- 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
- A01K2217/15—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
- 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
- C07K2317/24—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
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2318/00—Antibody mimetics or scaffolds
- C07K2318/10—Immunoglobulin or domain(s) thereof as scaffolds for inserted non-Ig peptide sequences, e.g. for vaccination purposes
-
- 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
- C12N2800/20—Pseudochromosomes, minichrosomosomes
- C12N2800/204—Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/24—Metalloendopeptidases (3.4.24)
- C12Y304/24046—Adamalysin (3.4.24.46)
Claims (14)
1. Miš čiji genom sadrži:
(a) umetanje jednog ili više humanih segmenata gena VL i jednog ili više humanih segmenata gena JL iznad gena konstantne regije mišjeg imunoglobulinskog lakog lanca, naznačeno time, što su jedan ili više humanih segmenata gena VL i jedan ili više humanih segmenata gena JL operativno povezani s genom konstantne regije mišjeg imunoglobulinskog lakog lanca;
(b) umetanje jednog ili više humanih segmenata gena VL i jednog ili više humanih segmenata gena JL iznad gena konstantne regije mišjeg imunoglobulinskog teškog lanca, naznačeno time, što su jedan ili više humanih segmenata gena VL i jedan ili više humanih segmenata gena JL operativno povezani s genom konstantne regije mišjeg imunoglobulinskog teškog lanca; i
(c) ektopijsku sekvencu nukleinske kiseline koja šifrira mišji protein ADAM6a ili njegov funkcionalni fragment i ektopijsku sekvencu nukleinske kiseline koja šifrira mišji protein ADAM6b ili njegov funkcionalni fragment, naznačeno time, što se mišji proteini ADAM6a i ADAM6b ili njihovi funkcionalni fragmenti izražavaju iz ektopijskih sekvenci nukleinske kiseline,
naznačen time, što miš izražava antitijelo koje sadrži (i) polipeptid koji sadrži varijabilnu domenu humanog lakog lanca povezanu s konstantnom domenom mišjeg teškog lanca; i (ii) polipeptid koji sadrži varijabilnu domenu humanog lakog lanca povezanu s konstantnom domenom mišjeg lakog lanca.
2. Miš prema patentnom zahtjevu 1, naznačen time, što je gen konstantne regije mišjeg imunoglobulinskog lakog lanca mišji Cκ.
3. Miš prema patentnom zahtjevu 1 ili 2, naznačen time, što jedan ili više humanih segmenata gena VL i jedan ili više humanih segmenata gena JL iznad gena konstantne regije mišjeg imunoglobulinskog lakog lanca jesu jedan ili više humanih segmenata gena Vκ i jedan ili više humanih segmenata gena Jκ.
4. Miš prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, što jedan ili više humanih segmenata gena VL i jedan ili više humanih segmenata gena JL iznad gena konstantne regije mišjeg imunoglobulinskog teškog lanca jesu jedan ili više humanih segmenata gena Vκ i jedan ili više humanih segmenata gena Jκ.
5. Miš prema bilo kojem patentnom zahtjevu od 1 do 4, naznačen time, što su ektopijske sekvence nukleinske kiseline prisutne između dva od umetnutog jednog ili više humanih segmenata gena VL i jednog ili više humanih segmenata gena JL navedenih u (b).
6. Miš prema patentnom zahtjevu 5, naznačen time, što umetnuti jedan ili više humanih segmenata gena VL i jedan ili više humanih segment gena JL jesu humani segmenti gena lakog lanca κ ili humani segmenti gena lakog lanca λ.
7. Miš prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, što umetnuti jedan ili više humanih segmenata gena VL uključuje Vκ5-2 i Vκ4-1, a ektopijske sekvence nukleinske kiseline koje šifriraju mišje proteine ADAM6a i ADAM6b ili njihove funkcionalne fragmente su prisutne između Vκ5-2 i Vκ4-1.
8. Miš prema bilo kojem patentnom zahtjevu od 1 do 6, naznačen time, što umetnuti jedan ili više humanih segmenata gena VL uključuje Vκ4-1 i umetnuti jedan ili više humanih segmenata gena JL uključuje Jκ1, a ektopijske sekvence nukleinske kiseline koje šifriraju mišje proteine ADAM6a i ADAM6b ili njihove funkcionalne fragmente su prisutne između Vκ4-1 i Jκ1.
9. Miš prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, što miš sadrži jedan ili više endogenih segmenata gena VL i/ili jedan ili više endogenih segmenata gena JL koji nisu sposobni za vršenje preuređenja kako bi formirali varijabilnu sekvencu imunoglobulinskog lakog lanca u mišu.
10. Miš prema bilo kojem od prethodnih zahtjeva, naznačen time, što miš sadrži deleciju ili zamjenu jedne ili više endogenih sekvenci gena imunoglobulinskog teškog lanca.
11. Stanica dobivena iz miša prema patentnom zahtjevu 1.
12. Stanica prema patentnom zahtjevu 11, naznačena time, što stanica jest B stanica.
13. Hibridom dobiven iz B stanice prema patentnom zahtjevu 12.
14. Metoda za dobivanje antitijela koje se vezuje za interesni antigen, naznačena time, što se sastoji od
(a) izlaganja miša iz patentnog zahtjeva 1 interesnom antigenu;
(b) izoliranja jedne ili više B stanica miša, naznačeno time, što jedna ili više B stanica izražavaju antitijelo koje se vezuje za interesni antigen;
(c) identifikacije sekvence nukleinske kiseline koja šifrira jednu od varijabilnih domena lakog lanca antitijela koje se vezuje za dani interesni antigen, naznačeno time, što antitijelo sadrži varijabilnu domenu humanog imunoglobulinskog lakog lanca κ povezanu s konstantnom domenom mišjeg lakog lanca i varijabilnu domenu humanog imunoglobulinskog lakog lanca κ povezanu s konstantnom domenom mišjeg teškog lanca; i
(d) primjene sekvence nukleinske kiseline iz (c) sa sekvencom nukleinske kiseline konstantne regije humanog imunoglobulina radi dobivanja humanog antitijela koje se vezuje za interesni antigen.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261593463P | 2012-02-01 | 2012-02-01 | |
US201261677538P | 2012-07-31 | 2012-07-31 | |
EP13704329.5A EP2809150B1 (en) | 2012-02-01 | 2013-02-01 | Humanized mice that express heavy chains containing vl domains |
PCT/US2013/024295 WO2013116609A1 (en) | 2012-02-01 | 2013-02-01 | Humanized rodents that express heavy chains containing vl domains |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20192218T1 true HRP20192218T1 (hr) | 2020-03-06 |
Family
ID=47714588
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20192218TT HRP20192218T1 (hr) | 2012-02-01 | 2019-12-10 | Humanizirani miševi koji izražavaju teške lance koji sadrže vl domene |
HRP20210987TT HRP20210987T1 (hr) | 2012-02-01 | 2021-06-23 | Humanizirani glodavci koji eksprimiraju teške lance koji sadrže vl domene |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
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HRP20210987TT HRP20210987T1 (hr) | 2012-02-01 | 2021-06-23 | Humanizirani glodavci koji eksprimiraju teške lance koji sadrže vl domene |
Country Status (26)
Country | Link |
---|---|
US (3) | US20130212719A1 (hr) |
EP (3) | EP3912465A1 (hr) |
JP (6) | JP2015505477A (hr) |
KR (2) | KR20140123983A (hr) |
CN (2) | CN106117364B (hr) |
AU (3) | AU2013204758B2 (hr) |
BR (1) | BR112014018843B1 (hr) |
CA (1) | CA2863175A1 (hr) |
CY (2) | CY1122419T1 (hr) |
DK (2) | DK2809150T3 (hr) |
ES (2) | ES2753774T3 (hr) |
HK (1) | HK1202771A1 (hr) |
HR (2) | HRP20192218T1 (hr) |
HU (2) | HUE055610T2 (hr) |
IL (3) | IL233827A0 (hr) |
LT (2) | LT2809150T (hr) |
ME (1) | ME03611B (hr) |
MX (2) | MX2020003491A (hr) |
NZ (3) | NZ627977A (hr) |
PL (2) | PL2809150T3 (hr) |
PT (2) | PT3597038T (hr) |
RS (2) | RS59699B1 (hr) |
RU (2) | RU2664185C2 (hr) |
SG (3) | SG10201913428QA (hr) |
SI (2) | SI2809150T1 (hr) |
WO (1) | WO2013116609A1 (hr) |
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ES2436044T3 (es) * | 2008-05-23 | 2013-12-26 | Ablexis, Llc | Procedimiento de generación de anticuerpos de dominio VL individual en animales transgénicos |
US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
US20120204278A1 (en) | 2009-07-08 | 2012-08-09 | Kymab Limited | Animal models and therapeutic molecules |
ES2965212T3 (es) | 2009-07-08 | 2024-04-11 | Kymab Ltd | Modelos de animales y moléculas terapéuticas |
NZ707327A (en) | 2010-08-02 | 2017-01-27 | Regeneron Pharma | Mice that make binding proteins comprising vl domains |
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 |
GB201122047D0 (en) * | 2011-12-21 | 2012-02-01 | Kymab Ltd | Transgenic animals |
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 |
US10251377B2 (en) | 2012-03-28 | 2019-04-09 | 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 |
LT3597037T (lt) | 2012-06-12 | 2021-06-10 | Regeneron Pharmaceuticals, Inc. | Humanizuoti gyvūnai, išskyrus žmones, su apribotu imunoglobulino sunkiosios grandinės lokusu |
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 |
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US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
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 |
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 |
AU2016232715A1 (en) * | 2015-03-19 | 2017-09-28 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
ES2959608T3 (es) * | 2015-04-03 | 2024-02-27 | Dana Farber Cancer Inst Inc | Composición y métodos de edición del genoma de células B |
KR20240016444A (ko) | 2016-05-20 | 2024-02-06 | 리제너론 파마슈티칼스 인코포레이티드 | 다중 가이드 RNAs를 이용한 면역학적 내성 파괴 방법 |
CN110719732B (zh) * | 2017-03-30 | 2022-11-18 | 犹他州立大学 | 表达蜘蛛丝的转基因蚕 |
HUE060608T2 (hu) * | 2017-12-05 | 2023-03-28 | Regeneron Pharma | Genetikailag módosított immunglobulin lambda könnyûlánccal rendelkezõ egerek és azok alkalmazása |
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