HRP20190897T1 - Laki lanac humaniziranih miševa - Google Patents
Laki lanac humaniziranih miševa Download PDFInfo
- Publication number
- HRP20190897T1 HRP20190897T1 HRP20190897TT HRP20190897T HRP20190897T1 HR P20190897 T1 HRP20190897 T1 HR P20190897T1 HR P20190897T T HRP20190897T T HR P20190897TT HR P20190897 T HRP20190897 T HR P20190897T HR P20190897 T1 HRP20190897 T1 HR P20190897T1
- Authority
- HR
- Croatia
- Prior art keywords
- human
- mouse
- light chain
- gene
- nucleic acid
- Prior art date
Links
- 241000699670 Mus sp. Species 0.000 title claims 4
- 241000699666 Mus <mouse, genus> Species 0.000 claims 31
- 108090000623 proteins and genes Proteins 0.000 claims 23
- 150000007523 nucleic acids Chemical group 0.000 claims 12
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 10
- 239000000427 antigen Substances 0.000 claims 9
- 108091007433 antigens Proteins 0.000 claims 9
- 102000036639 antigens Human genes 0.000 claims 9
- 108700005091 Immunoglobulin Genes Proteins 0.000 claims 6
- 238000000034 method Methods 0.000 claims 5
- 108091029795 Intergenic region Proteins 0.000 claims 4
- 241001529936 Murinae Species 0.000 claims 4
- 239000012634 fragment Substances 0.000 claims 4
- 210000003719 b-lymphocyte Anatomy 0.000 claims 3
- 231100000502 fertility decrease Toxicity 0.000 claims 3
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims 2
- 102000012960 Immunoglobulin kappa-Chains Human genes 0.000 claims 2
- 108010090227 Immunoglobulin kappa-Chains Proteins 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 230000028993 immune response Effects 0.000 claims 2
- 230000004048 modification Effects 0.000 claims 2
- 238000012986 modification Methods 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims 1
- 102100029567 Immunoglobulin kappa light chain Human genes 0.000 claims 1
- 101710189008 Immunoglobulin kappa light chain Proteins 0.000 claims 1
- 101100060131 Mus musculus Cdk5rap2 gene Proteins 0.000 claims 1
- 238000010367 cloning Methods 0.000 claims 1
- 102000053391 human F Human genes 0.000 claims 1
- 108700031895 human F Proteins 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
- 108700031127 mouse Adam6a Proteins 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
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- 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
- 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
- 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
-
- 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
Claims (12)
1. Miš koji sadrži:
(a) jedan ili više nepreuređenih humanih genskih segmenata Vλ i jedan ili više nepreuređenih humanih genskih segmenata Jλ na lokusu endogenog imunoglobulinskog lakog lanca kapa miša, naznačen time, što imunoglobulinski lokus lakog lanca kapa sadrži mišju Cκ regiju;
(b) jedan ili više humanih genskih segmenata VH, jedan ili više humanih genskih segmenata DH i jedan ili više humanih genskih segmenata JH na lokusu endogenog imunoglobulinskog teškog lanca miša; i
(c) modifikaciju lokusa imunoglobulinskog teškog lanca, naznačenu time, što modifikacija eliminira endogenu ADAM6 funkciju, koja je povezana sa smanjenjem plodnosti kod mužjaka miševa, pri čemu miš dodatno sadrži sekvencu nukleinske kiseline koja šifrira mišji ADAM6a protein ili njegov ortolog ili homolog ili funkcionalni fragment, pri čemu je svaki funkcionalan radi poboljšanja ili obnavljanja spomenutog smanjenja plodnosti kod mužjaka miševa, i sekvencu nukleinske kiseline koja šifrira mišji ADAM6b protein ili njegov ortolog ili homolog ili funkcionalni fragment, pri čemu je svaki funkcionalan radi poboljšanja ili obnavljanja spomenutog smanjenja plodnosti kod mužjaka miševa, naznačeno time, što su sekvence nukleinske kiseline koje šifriraju ADAM6 proteine, njegove ortologe, homologe ili funkcionalne fragmente prisutne unutar genskih segmenata humanog teškog lanca.
2. Miš prema prethodnom patentnom zahtjevu, naznačen time, što miš sadrži od 12 do 40 humanih genskih segmenata Vλ i najmanje jedan humani genski segment Jλ.
3. Miš prema patentnom zahtjevu 2, naznačen time, što:
(a) miš sadrži 12 humanih genskih segmenata Vλ i najmanje jedan humani genski segment Jλ;
(b) miš sadrži 28 humanih genskih segmenata Vλ i najmanje jedan humani genski segment Vλ; ili
(c) miš sadrži 40 humanih genskih segmenata Vλ i najmanje jedan humani genski segment Jλ.
4. Miš prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, što:
(a) najmanje jedan humani genski segment Jλ je odabran iz Jλ1, Jλ2, Jλ3, Jλ7 i njihove kombinacije; i/ili
(b) miš sadrži najmanje četiri humana genska segmenta Jλ.
5. Miš prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, što miš ne posjeduje varijabilnu regiju endogenog lakog lanca kapa na lokusu endogenog imunoglobulinskog lakog lanca kapa.
6. Miš prema bilo kojem od prethodnih patentnih zahtjeva, koji dodatno sadrži humanu međugensku regiju Vκ-Jκ iz lokusa humanog lakog lanca κ, naznačen time, što se humana međugenska regija Vκ-Jκ graniči s jednim ili više nepreuređenih genskih segmenata Vλ i s jednim ili više nepreuređenih genskih segmenata Jλ, poželjno pri čemu se humana međugenska regija Vκ-Jκ nalazi između genskog segmenta Vλ i genskog segmenta Jλ, i naznačena time, što humana međugenska regija Vκ-Jκ sadrži SEQ ID NO. 158.
7. Miš prema bilo kojem od prethodnih patentnih zahtjeva, koji je mužjak miša.
8. Izolirana stanica ili tkivo iz miša prema bilo kojem od prethodnih patentnih zahtjeva.
9. Primjena miša prema bilo kojem patentnom zahtjevu od 1 do 7, za dobivanje:
(i) reverznog kimernog antitijela;
(ii) potpunog humanog antitijela;
(iii) potpuno humanog Fab fragmenta; ili
(iv) potpuno humanog F(ab)2 fragmenta.
10. Metoda za dobivanje antitijela, pri čemu se metoda sastoji od:
(a) izlaganja miša prema bilo kojem patentnom zahtjevu od 1 do 7 antigenu;
(b) dozvoljavanja mišu da razvije imunološki odgovor na antigen; i
(c) izoliranja iz miša iz (b) antitijela koje specifično prepoznaje antigen, naznačeno time, što antitijelo sadrži laki lanac dobiven iz hVλ, hJλ i mišje Cκ regije, ili izoliranja iz miša iz (b) stanice koja sadrži imunoglobulinsku domenu koja specifično prepoznaje antigen, ili identifikacije u mišu iz (b) sekvence nukleinske kiseline koja šifrira varijabilnu domenu teškog i/ili lakog lanca koja vezuje antigen.
11. Metoda za dobivanje humanog antitijela, pri čemu se metoda sastoji od izlaganja miša prema bilo kojem patentnom zahtjevu od 1 do 7 antigenu, dozvoljavanja mišu da ispolji imunološki odgovor koji se sastoji od stvaranja antitijela koje se specifično vezuje za antigen, identificiranja u B stanici iz miša preuređene sekvence nukleinske kiseline koja šifrira varijabilnu domenu humanog teškog lanca i preuređenu sekvencu nukleinske kiseline i preuređene sekvence nukleinske kiseline koja šifrira srodnu sekvencu varijabilne domene humanog lakog lanca, naznačena time, što se antitijelo specifično vezuje za antigen, i korištenja sekvenci nukleinske kiseline koje šifriraju varijabilnu domenu humanog teškog lanca odnosno varijabilnu domenu humanog lakog lanca za sekvencu nukleinske kiseline koja šifrira konstantnu domenu humanog teškog lanca odnosno sekvencu nukleinske kiseline koja šifrira konstantnu domenu humanog lakog lanca, kako bi se dobilo željeno antitijelo.
12. Metoda za dobivanje sekvence nukleinske kiseline koja šifrira varijabilnu domenu teškog i/ili lakog lanca koja se sastoji od:
(a) izlaganja miša prema bilo kojem patentnom zahtjevu od 1 do 7 antigenu;
(b) identifikacije u B stanici iz miša:
(i) gena imunoglobulina preuređenog lakog lanca, naznačeno time, što gen imunoglobulina preuređenog lakog lanca sadrži najmanje jedan genski segment varijabilne regije humanog lakog lanca λ povezan za mišju Cκ regiju; ili
(ii) gena imunoglobulina preuređenog lakog lanca iz (b)(i) i gena imunoglobulina preuređenog teškog lanca, naznačeno time, što gen imunoglobulina preuređenog teškog lanca šifrira teški lanac koji se uparuje s lakim lancem šifriranim genom imunoglobulina preuređenog lakog lanca iz (b)(i); i
(c) kloniranja sekvence nukleinske kiseline koja šifrira varijabilnu domenu teškog i/ili lakog lanca iz B stanice miša, naznačeno time, što je varijabilna domena teškog i/ili lakog lanca iz antitijela koje sadrži humani Vλ i mišji Cκ.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161578097P | 2011-12-20 | 2011-12-20 | |
EP12809955.3A EP2793567B1 (en) | 2011-12-20 | 2012-12-17 | Humanized light chain mice |
PCT/US2012/069981 WO2013096142A1 (en) | 2011-12-20 | 2012-12-17 | Humanized light chain mice |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20190897T1 true HRP20190897T1 (hr) | 2019-09-20 |
Family
ID=47501484
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20190897TT HRP20190897T1 (hr) | 2011-12-20 | 2019-05-15 | Laki lanac humaniziranih miševa |
Country Status (28)
Country | Link |
---|---|
US (6) | US9706759B2 (hr) |
EP (2) | EP3527070A1 (hr) |
JP (5) | JP6327750B2 (hr) |
KR (5) | KR101924805B1 (hr) |
CN (1) | CN104159444B (hr) |
AU (5) | AU2012323987B2 (hr) |
BR (2) | BR122021007339B1 (hr) |
CA (1) | CA2859408C (hr) |
CY (1) | CY1121638T1 (hr) |
DK (1) | DK2793567T3 (hr) |
ES (1) | ES2720186T3 (hr) |
HK (1) | HK1202772A1 (hr) |
HR (1) | HRP20190897T1 (hr) |
HU (1) | HUE044266T2 (hr) |
IL (3) | IL233153B (hr) |
IN (1) | IN2014DN06094A (hr) |
LT (1) | LT2793567T (hr) |
ME (1) | ME03477B (hr) |
MX (2) | MX356429B (hr) |
MY (1) | MY173936A (hr) |
PL (1) | PL2793567T3 (hr) |
PT (1) | PT2793567T (hr) |
RS (1) | RS58761B1 (hr) |
RU (2) | RU2664181C2 (hr) |
SG (3) | SG10201913164YA (hr) |
SI (1) | SI2793567T1 (hr) |
TR (1) | TR201903439T4 (hr) |
WO (1) | WO2013096142A1 (hr) |
Families Citing this family (67)
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US20120204278A1 (en) | 2009-07-08 | 2012-08-09 | Kymab Limited | Animal models and therapeutic molecules |
EP2564695B1 (en) | 2009-07-08 | 2015-04-15 | Kymab Limited | Animal models and therapeutic molecules |
US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
NZ707327A (en) | 2010-08-02 | 2017-01-27 | Regeneron Pharma | Mice that make binding proteins comprising vl domains |
ES2758974T5 (es) | 2011-02-25 | 2023-06-08 | Regeneron Pharma | Ratones ADAM6 |
MY172718A (en) | 2011-08-05 | 2019-12-11 | Regeneron Pharma | Humanized universal light chain mice |
JP2014531452A (ja) | 2011-09-19 | 2014-11-27 | カイマブ・リミテッド | 動物、レパートリーおよび方法 |
WO2013041844A2 (en) | 2011-09-19 | 2013-03-28 | Kymab Limited | Antibodies, variable domains & chains tailored for human use |
WO2013045916A1 (en) | 2011-09-26 | 2013-04-04 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
ES2906462T3 (es) * | 2011-10-17 | 2022-04-18 | Regeneron Pharma | Ratones de cadena pesada de inmunoglobulina restringida |
US20180295821A1 (en) * | 2011-12-02 | 2018-10-18 | Kymab Limited | Transgenic Animals |
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 |
KR101924805B1 (ko) | 2011-12-20 | 2018-12-04 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 경쇄 마우스 |
DK3597038T3 (da) * | 2012-02-01 | 2021-06-28 | Regeneron Pharma | Humaniserede gnavere, der udtrykker tungkæder indeholdende VL-domæner |
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 |
KR102381716B1 (ko) | 2012-06-12 | 2022-04-01 | 리제너론 파마슈티칼스 인코포레이티드 | 제한된 면역글로불린 중쇄 유전자좌를 가지는 인간화된 비-인간 동물 |
WO2014130690A1 (en) | 2013-02-20 | 2014-08-28 | Regeneron Pharmaceuticals, Inc. | Non-human animals with modified immunoglobulin heavy chain sequences |
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 |
DE112014004537T5 (de) | 2013-10-01 | 2016-07-21 | Kymab Limited | Tiermodelle und therapeutische Moleküle |
SG11201607203XA (en) | 2014-03-21 | 2016-09-29 | Regeneron Pharma | Non-human animals that make single domain binding proteins |
SG11201607015VA (en) | 2014-03-21 | 2016-09-29 | Regeneron Pharma | V<sb>L</sb> ANTIGEN BINDING PROTEINS EXHIBITING DISTINCT BINDING CHARACTERISTICS |
CA2979702A1 (en) | 2015-03-19 | 2016-09-22 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
WO2017035252A1 (en) * | 2015-08-24 | 2017-03-02 | Trianni, Inc. | Enhanced production of immunoglobulins |
WO2017095939A1 (en) | 2015-12-03 | 2017-06-08 | Trianni, Inc. | Enhanced immunoglobulin diversity |
EP3457840B1 (en) | 2016-05-20 | 2024-04-10 | Regeneron Pharmaceuticals, Inc. | Methods for breaking immunological tolerance using multiple guide rnas |
WO2017214089A1 (en) * | 2016-06-06 | 2017-12-14 | Regeneron Pharmaceuticals, Inc. | Non-human animals expressing antibodies with human lambda light chains |
EP4082334A1 (en) * | 2016-11-04 | 2022-11-02 | Regeneron Pharmaceuticals, Inc. | Non-human animals having an engineered immunoglobulin lambda light chain locus |
SG11201906540WA (en) * | 2017-01-19 | 2019-08-27 | Open Monoclonal Tech Inc | Human antibodies from transgenic rodents with multiple heavy chain immunoglobulin loci |
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TW202003564A (zh) * | 2018-03-24 | 2020-01-16 | 美商再生元醫藥公司 | 用於產生抗肽-mhc複合物之治療性抗體的經基因修飾的非人類動物、其製法與用途 |
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