HRP20190634T1 - Životinje koje nisu ljudi, koje imaju humanizirani gen 47 iz razlikovnog grozda - Google Patents
Životinje koje nisu ljudi, koje imaju humanizirani gen 47 iz razlikovnog grozda Download PDFInfo
- Publication number
- HRP20190634T1 HRP20190634T1 HRP20190634TT HRP20190634T HRP20190634T1 HR P20190634 T1 HRP20190634 T1 HR P20190634T1 HR P20190634T T HRP20190634T T HR P20190634TT HR P20190634 T HRP20190634 T HR P20190634T HR P20190634 T1 HRP20190634 T1 HR P20190634T1
- Authority
- HR
- Croatia
- Prior art keywords
- rodent
- gene
- endogenous
- humanized
- human
- Prior art date
Links
- 101150095412 47 gene Proteins 0.000 title 1
- 241001465754 Metazoa Species 0.000 title 1
- 230000004069 differentiation Effects 0.000 title 1
- 241000283984 Rodentia Species 0.000 claims 37
- 101150084532 CD47 gene Proteins 0.000 claims 17
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 claims 13
- 238000000034 method Methods 0.000 claims 11
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 claims 10
- 108700024394 Exon Proteins 0.000 claims 9
- 101000863873 Homo sapiens Tyrosine-protein phosphatase non-receptor type substrate 1 Proteins 0.000 claims 8
- 229920001184 polypeptide Polymers 0.000 claims 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims 8
- 210000001671 embryonic stem cell Anatomy 0.000 claims 7
- 210000004027 cell Anatomy 0.000 claims 6
- 210000005260 human cell Anatomy 0.000 claims 6
- 101100059527 Homo sapiens CD47 gene Proteins 0.000 claims 4
- 102100029948 Tyrosine-protein phosphatase non-receptor type substrate 1 Human genes 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 3
- 210000003743 erythrocyte Anatomy 0.000 claims 3
- 230000004520 agglutination Effects 0.000 claims 2
- 239000012634 fragment Substances 0.000 claims 2
- 230000003834 intracellular effect Effects 0.000 claims 2
- 230000001225 therapeutic effect Effects 0.000 claims 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims 1
- 102000044459 human CD47 Human genes 0.000 claims 1
- 210000001161 mammalian embryo Anatomy 0.000 claims 1
- 238000012544 monitoring process Methods 0.000 claims 1
Classifications
-
- 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
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
- A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4703—Inhibitors; Suppressors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
-
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5014—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing toxicity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
- G01N33/5047—Cells of the immune system
- G01N33/5055—Cells of the immune system involving macrophages
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/12—Animals modified by administration of exogenous cells
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/15—Humanized animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (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
- A01K2267/03—Animal model, e.g. for test or diseases
-
- 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
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0331—Animal model for proliferative diseases
-
- 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
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0381—Animal model for diseases of the hematopoietic system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Veterinary Medicine (AREA)
- Environmental Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Public Health (AREA)
- Plant Pathology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
Claims (12)
1. Glodavac čiji genom sadrži humanizirani gen CD47, naznačen time što humanizirani gen CD47 sadrži egzon 1 iz endogenog glodavačkog gena CD47, egzone 2-7 iz ljudskog gena CD47, te egzone nizvodno od egzona 7 iz endogenog glodavačkog gena CD47, gdje je humanizirani gen CD47 operabilno spojen s promotorom endogenog glodavčkog CD47.
2. Glodavac u skladu s patentnim zahtjevom 1, naznačen time što glodavac dodatno sadrži gen SIRPα, koji kodira polipeptid SIRPα, koji sadrži izvanstaničnu domenu ljudskog polipeptida SIRPα i unutarstaničnu domenu endogenog glodavačkog polipeptida SIRPα, gdje polipeptid SIRPα međudjeluje s CD47, te gdje gen SIRPα može sadržavati egzone 1, 5, 6, 7 i 8 iz endogenog glodavačkog gena SIRPα i egzone 2-4 iz ljudskog gena SIRPα.
3. Glodavac u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2, naznačen time što je glodavac štakor ili miš.
4. Izolirana glodavačka stanica ili tkivo čiji genom sadrži humanizirani gen CD47, naznačeni time što humanizirani gen CD47 sadrži egzon 1 iz endogenog glodavačkog gena CD47, egzone 2-7 iz ljudskog gena CD47, te egzone nizvodno od egzona 7 iz endogenog glodavačkog gena CD47, gdje je humanizirani gen CD47 operabilno spojen s promotorom endogenog glodavčkog CD47, te gdje glodavačka stanica ili tkivo mogu biti mišja stanica ili mišje tkivo, ili štakorska stanica ili štakorsko tkivo.
5. Glodavačka stanica u skladu s patentnim zahtjevom 4, naznačena time što je navedena stanica glodavačka embrionska matična stanica, gdje glodavačka embrionska matična stanica može biti mišja ili štakorska embrionska matična stanica.
6. Glodavački embrij, naznačen time što se dobiva iz embrionske matične stanice u skladu s patentnim zahtjevom 5.
7. Postupak osiguravanja glodavca čiji genom sadrži gen CD47, koji kodira izvanstanični dio ljudskog polipeptida CD47 spojen s unutarstaničnim dijelom endogenog polipeptida CD47, naznačen time što se postupak sastoji u modificiranju genoma glodavca tako da sadrži humanizirani gen CD47, gdje humanizirani gen CD47 sadrži egzon 1 iz endogenog glodavačkog gena CD47, egzone 2-7 iz ljudskog gena CD47, te egzone nizvodno od egzona 7 iz endogenog glodavačkog gena CD47, gdje je humanizirani gen CD47 operabilno spojen s promotorom endogenog glodavčkog CD47, čime se osigurava navedeni glodavac.
8. Postupak dobivanja glodavca koji eksprimira polipeptid CD47 iz lokusa endogenog CD47, gdje polipeptid CD47 sadrži ljudski slijed, naznačen time što se postupak sastoji u:
(a) umetanju genomskog fragmenta u lokus endogenog glodavčkog CD47 u glodavačkoj embrionskoj matičnoj stanici, gdje navedeni genomski fragment sadrži egzone 2-7 iz ljudskog gena CD47, čime se dobije humanizirani gen CD47 na lokusu endogenog glodavčkog CD47;
(b) dobivanju glodavačke embrionske matične stanice koja sadrži humanizirani gen CD47 iz (a); i
(c) dobivanju glodavca iz glodavačke embrionske matične stanice iz (b).
9. Postupak u skladu s patentnim zahtjevom 7 ili patentnim zahtjevom 8, naznačen time što je glodavac miš ili štakor.
10. Postupak procjenjivanja usađenosti ljudskih stanica, naznačen time što se navedeni postupak sastoji u procjenjivanju usađenosti ljudskih stanica u glodavca u skladu s bilo kojim od patentnih zahtjeva 1-3, gdje ljudske stanice mogu biti krvotvorne matične stanice.
11. Postupak procjenjivanja terapijske djelotvornosti lijeka koji cilja na ljudske stanice, naznačen time što se postupak sastoji u:
primjeni kandidatnog lijeka na glodavcu u skladu s bilo kojim od patentnih zahtjeva 1-3, u kojeg je presađena jedna ili više ljudskih stanica; i
praćenju ljudskih stanica u glodavcu kako bi se odredilo terapijsku djelotvornost kandidatnog lijeka.
12. Postupak procjenjivanja potiče li kandidatni modulator ljudskog proteina CD47 aglutiniranje eritrocita, naznačen time što se navedeni postupak sastoji u:
inkubiranju eritrocita izoliranih iz glodavca u skladu s bilo kojim od patentnih zahtjeva 1-3 u prisutnosti kandidatnog modulatora; i
procjenjivanju potiče li kandidatni modulator aglutiniranje eritrocita.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462087992P | 2014-12-05 | 2014-12-05 | |
PCT/US2015/062614 WO2016089692A1 (en) | 2014-12-05 | 2015-11-25 | Non-human animals having a humanized cluster of differentiation 47 gene |
EP15813960.0A EP3086637B1 (en) | 2014-12-05 | 2015-11-25 | Non-human animals having a humanized cluster of differentiation 47 gene |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20190634T1 true HRP20190634T1 (hr) | 2019-08-09 |
Family
ID=54979926
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20231707TT HRP20231707T1 (hr) | 2014-12-05 | 2015-11-25 | Životinje koje nisu ljudi, koje sadrže humanizirani gen iz diferencijacijske skupine 47 |
HRP20190634TT HRP20190634T1 (hr) | 2014-12-05 | 2019-04-02 | Životinje koje nisu ljudi, koje imaju humanizirani gen 47 iz razlikovnog grozda |
HRP20210662TT HRP20210662T1 (hr) | 2014-12-05 | 2021-04-27 | Neljudske životinje koje imaju humanizirani gen za diferencijacijski biljeg 47 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20231707TT HRP20231707T1 (hr) | 2014-12-05 | 2015-11-25 | Životinje koje nisu ljudi, koje sadrže humanizirani gen iz diferencijacijske skupine 47 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20210662TT HRP20210662T1 (hr) | 2014-12-05 | 2021-04-27 | Neljudske životinje koje imaju humanizirani gen za diferencijacijski biljeg 47 |
Country Status (29)
Country | Link |
---|---|
US (5) | US20160345549A1 (hr) |
EP (4) | EP3086637B1 (hr) |
JP (2) | JP6730277B2 (hr) |
KR (3) | KR102617691B1 (hr) |
CN (2) | CN107205368B (hr) |
AR (1) | AR102888A1 (hr) |
AU (2) | AU2015355328B2 (hr) |
BR (1) | BR112017010490A2 (hr) |
CA (1) | CA2967834C (hr) |
CY (2) | CY1121547T1 (hr) |
DK (3) | DK3466255T3 (hr) |
ES (3) | ES2870462T3 (hr) |
FI (1) | FI3850946T3 (hr) |
HK (1) | HK1225912A1 (hr) |
HR (3) | HRP20231707T1 (hr) |
HU (3) | HUE043132T2 (hr) |
IL (2) | IL286403B2 (hr) |
LT (3) | LT3850946T (hr) |
MX (1) | MX2017007293A (hr) |
NZ (1) | NZ731471A (hr) |
PL (3) | PL3086637T3 (hr) |
PT (3) | PT3086637T (hr) |
RS (3) | RS58536B1 (hr) |
RU (1) | RU2728412C2 (hr) |
SG (2) | SG10202103050YA (hr) |
SI (3) | SI3466255T1 (hr) |
TR (1) | TR201903891T4 (hr) |
TW (1) | TWI681053B (hr) |
WO (1) | WO2016089692A1 (hr) |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102617691B1 (ko) | 2014-12-05 | 2023-12-27 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 분화 클러스터 47 유전자를 가진 비인간 동물 |
SI3808775T1 (sl) | 2014-12-09 | 2024-08-30 | Regeneron Pharmaceuticals, Inc. | Nehumane živali s humaniziranim genom označevalca pripadnosti 274 |
WO2016154299A1 (en) * | 2015-03-24 | 2016-09-29 | The Trustees Of Columbia University In The City Of New York | Genetic modification of pigs for xenotransplantation |
US10285388B2 (en) | 2015-05-29 | 2019-05-14 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a disruption in a C9ORF72 locus |
BR112018010158A2 (pt) | 2015-11-20 | 2018-11-21 | Regeneron Pharma | roedor, polipeptídeo lag-3 humanizado, célula ou tecido, célula-tronco embrionária e embrião de roedor, métodos para produzir um roedor, para avaliar a eficácia antitumoral e as propriedades farmacocinéticas de uma droga |
CN108779159B (zh) | 2016-02-04 | 2022-12-30 | 瑞泽恩制药公司 | 具有经改造的angptl8基因的非人动物 |
RU2749715C2 (ru) | 2016-02-29 | 2021-06-16 | Регенерон Фармасьютикалз, Инк. | Грызуны, характеризующиеся гуманизированным геном tmprss |
SG10202101133SA (en) * | 2016-08-11 | 2021-03-30 | Jackson Lab | Methods and compositions relating to improved human red blood cell survival in genetically modified immunodeficient non-human animals |
WO2018041119A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric ox40 |
CN107815468B (zh) | 2016-08-31 | 2021-03-16 | 百奥赛图(北京)医药科技股份有限公司 | 人源化基因改造动物模型的制备方法及应用 |
WO2018041121A1 (en) | 2016-08-31 | 2018-03-08 | Beijing Biocytogen Co., Ltd | Genetically modified non-human animal with human or chimeric ctla-4 |
CN107815465B (zh) | 2016-08-31 | 2021-03-16 | 百奥赛图(北京)医药科技股份有限公司 | 人源化基因改造动物模型的制备方法及应用 |
WO2018064600A1 (en) * | 2016-09-30 | 2018-04-05 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a hexanucleotide repeat expansion in a c9orf72 locus |
CN108588126B (zh) | 2017-03-31 | 2020-04-10 | 北京百奥赛图基因生物技术有限公司 | Cd47基因人源化改造动物模型的制备方法及应用 |
WO2018177441A1 (en) | 2017-03-31 | 2018-10-04 | Beijing Biocytogen Co., Ltd | GENETICALLY MODIFIED NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC SIRPα |
GB2588249B (en) * | 2017-06-12 | 2023-01-04 | Sinai Health Sys | Allograft tolerance without the need for systemic immune suppression |
US11401329B2 (en) | 2017-08-02 | 2022-08-02 | Phanes Therapeutics, Inc. | Anti-CD47 antibodies and uses thereof |
IL274740B2 (en) * | 2017-11-30 | 2024-06-01 | Regeneron Pharma | Non-human animals containing a human TRKB locus |
IL314733A (en) | 2018-03-26 | 2024-10-01 | Regeneron Pharma | Humanized rodents for testing therapeutic agents |
SG11202011284RA (en) | 2018-07-16 | 2020-12-30 | Regeneron Pharma | Non-human animal models of ditra disease and uses thereof |
WO2020131632A1 (en) | 2018-12-20 | 2020-06-25 | Regeneron Pharmaceuticals, Inc. | Nuclease-mediated repeat expansion |
WO2020147829A1 (zh) * | 2019-01-17 | 2020-07-23 | 北京百奥赛图基因生物技术有限公司 | 人源化转基因动物 |
WO2021027737A1 (en) * | 2019-08-09 | 2021-02-18 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animal with human or chimeric il2ra |
WO2021136537A1 (en) * | 2019-12-31 | 2021-07-08 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | GENETICALLY MODIFIED IMMUNODEFICIENT NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC SIRPα/CD47 |
CN112080522A (zh) * | 2020-09-15 | 2020-12-15 | 广东药康生物科技有限公司 | 一种cd47人源化小鼠模型的构建方法 |
CN112725379B (zh) * | 2021-01-27 | 2024-08-13 | 上海南方模式生物科技股份有限公司 | 人源化cd40基因改造动物模型的构建方法及应用 |
WO2023046061A1 (en) * | 2021-09-24 | 2023-03-30 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animal with human or chimeric trop2 |
WO2024020057A1 (en) | 2022-07-19 | 2024-01-25 | Regeneron Pharmaceuticals, Inc. | Genetically modified animal model and its use to model the human immune system |
Family Cites Families (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5670356A (en) | 1994-12-12 | 1997-09-23 | Promega Corporation | Modified luciferase |
US5874304A (en) | 1996-01-18 | 1999-02-23 | University Of Florida Research Foundation, Inc. | Humanized green fluorescent protein genes and methods |
US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
EP1693385A4 (en) * | 2003-11-11 | 2009-11-04 | Chugai Pharmaceutical Co Ltd | ANTI-CD47 ANTIBODIES HUMANIZED |
PL1802193T3 (pl) | 2004-10-19 | 2014-09-30 | Regeneron Pharma | Sposób wytwarzania myszy homozygotycznej pod względem modyfikacji genetycznej |
WO2007033221A2 (en) * | 2005-09-13 | 2007-03-22 | The General Hospital Corporation | Methods and compositions for inhibition of immune responses |
CA2661848C (en) * | 2006-09-01 | 2015-02-03 | Therapeutic Human Polyclonals, Inc. | Enhanced expression of human or humanized immunoglobulin in non-human transgenic animals |
WO2009039244A2 (en) * | 2007-09-18 | 2009-03-26 | Genizon Biosciences Inc. | Genemap of the human genes associated with crohn's disease |
CN101668387A (zh) | 2008-09-02 | 2010-03-10 | 鸿富锦精密工业(深圳)有限公司 | 印刷电路板 |
WO2010082385A1 (ja) * | 2009-01-16 | 2010-07-22 | 財団法人実験動物中央研究所 | ヒト肝細胞が移植されたマウス |
RU2425880C2 (ru) * | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
WO2011020014A1 (en) | 2009-08-14 | 2011-02-17 | Regeneron Pharmaceuticals, Inc. | Promoter-regulated differentiation-dependent self-deleting cassette |
WO2011034969A1 (en) * | 2009-09-15 | 2011-03-24 | The Board Of Trustees Of The Leland Stanford Junior University | Synergistic anti-cd47 therapy for hematologic cancers |
DK3417701T3 (da) | 2009-10-06 | 2022-03-14 | Regeneron Pharma | Genmodificerede mus og indpodning |
EP4233537A3 (en) | 2011-02-15 | 2023-09-13 | Regeneron Pharmaceuticals, Inc. | Humanized m-csf mice and uses thereof |
US20140242095A1 (en) * | 2011-10-19 | 2014-08-28 | University Health Network | Antibodies and antibody fragments targeting sirp-alpha and their use in treating hematologic cancers |
MY164836A (en) | 2011-10-28 | 2018-01-30 | Regeneron Pharma | Genetically modified major histocompatibility complex mice |
CN108866101A (zh) | 2011-10-28 | 2018-11-23 | 瑞泽恩制药公司 | 人源化il-6和il-6受体 |
PT2770822T (pt) | 2011-10-28 | 2017-09-18 | Regeneron Pharma | Ratinhos geneticamente modificados que expressam moléculas quiméricas de complexo principal de histocompatibilidade (mhc) ii |
EP2644027A1 (en) * | 2012-03-26 | 2013-10-02 | Institut Pasteur | Transgenic immunodefficient mouse expressing human SIRPalpha. |
US8962913B2 (en) | 2012-06-18 | 2015-02-24 | Regeneron Pharmaceuticals, Inc. | Humanized IL-7 rodents |
JP6283031B2 (ja) | 2012-09-07 | 2018-02-21 | イエール ユニバーシティ | 遺伝学的に修飾された非ヒト動物およびその使用法 |
RU2673156C2 (ru) | 2012-11-05 | 2018-11-22 | Ридженерон Фармасьютикалз, Инк. | Генетически модифицированные не относящиеся к человеческому роду животные и способы их применения |
ES2786083T3 (es) * | 2012-12-12 | 2020-10-08 | Arch Oncology Inc | Anticuerpos terapéuticos CD47 |
SI2958938T1 (sl) | 2013-02-20 | 2019-08-30 | Regeneron Pharmaceuticals, Inc. | Miši, ki izražajo humanizirane koreceptorje za celice T |
US10154658B2 (en) | 2013-02-22 | 2018-12-18 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
ES2959333T3 (es) | 2013-09-23 | 2024-02-23 | Regeneron Pharma | Animales no humanos que tienen un gen humanizado de la proteína reguladora de señales |
DK3138397T3 (en) | 2013-10-15 | 2019-04-15 | Regeneron Pharma | Humanized IL-15 animals |
KR102173260B1 (ko) | 2013-11-19 | 2020-11-03 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화된 b-세포 활성화 인자 유전자를 가지고 있는 비-인간 동물 |
WO2015077072A1 (en) | 2013-11-19 | 2015-05-28 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized a proliferation-inducing ligand gene |
PT3129400T (pt) | 2014-04-08 | 2020-05-27 | Regeneron Pharma | Animais não humanos que possuem recetores fc-gamma humanizados |
NO2785538T3 (hr) | 2014-05-07 | 2018-08-04 | ||
AU2015264427B2 (en) | 2014-05-19 | 2021-09-23 | Institute For Research In Biomedicine (Irb) | Genetically modified non-human animals expressing human EPO |
KR102482295B1 (ko) | 2014-06-19 | 2022-12-30 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 프로그램화 세포 사멸 1 유전자를 가지는 비인간 동물 |
DK3223605T3 (da) | 2014-11-24 | 2020-11-16 | Regeneron Pharma | Ikke-humane dyr, der eksprimerer humaniseret cd3-kompleks |
KR102617691B1 (ko) | 2014-12-05 | 2023-12-27 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 분화 클러스터 47 유전자를 가진 비인간 동물 |
-
2015
- 2015-11-25 KR KR1020237007814A patent/KR102617691B1/ko active IP Right Grant
- 2015-11-25 RS RS20190370A patent/RS58536B1/sr unknown
- 2015-11-25 ES ES18207075T patent/ES2870462T3/es active Active
- 2015-11-25 HU HUE15813960A patent/HUE043132T2/hu unknown
- 2015-11-25 SI SI201531599T patent/SI3466255T1/sl unknown
- 2015-11-25 AU AU2015355328A patent/AU2015355328B2/en active Active
- 2015-11-25 RU RU2017123357A patent/RU2728412C2/ru active
- 2015-11-25 HR HRP20231707TT patent/HRP20231707T1/hr unknown
- 2015-11-25 EP EP15813960.0A patent/EP3086637B1/en active Active
- 2015-11-25 BR BR112017010490A patent/BR112017010490A2/pt not_active Application Discontinuation
- 2015-11-25 NZ NZ731471A patent/NZ731471A/en unknown
- 2015-11-25 SI SI201530659T patent/SI3086637T1/sl unknown
- 2015-11-25 CN CN201580066047.0A patent/CN107205368B/zh active Active
- 2015-11-25 RS RS20231251A patent/RS64989B1/sr unknown
- 2015-11-25 IL IL286403A patent/IL286403B2/en unknown
- 2015-11-25 WO PCT/US2015/062614 patent/WO2016089692A1/en active Application Filing
- 2015-11-25 DK DK18207075.5T patent/DK3466255T3/da active
- 2015-11-25 ES ES15813960T patent/ES2716735T3/es active Active
- 2015-11-25 MX MX2017007293A patent/MX2017007293A/es unknown
- 2015-11-25 EP EP20215046.2A patent/EP3850946B1/en active Active
- 2015-11-25 US US14/951,825 patent/US20160345549A1/en not_active Abandoned
- 2015-11-25 KR KR1020217032415A patent/KR102508175B1/ko active IP Right Grant
- 2015-11-25 KR KR1020177013948A patent/KR102313073B1/ko active IP Right Grant
- 2015-11-25 PL PL15813960T patent/PL3086637T3/pl unknown
- 2015-11-25 CN CN202011160730.XA patent/CN112342197A/zh active Pending
- 2015-11-25 DK DK15813960.0T patent/DK3086637T3/en active
- 2015-11-25 EP EP18207075.5A patent/EP3466255B1/en active Active
- 2015-11-25 PT PT15813960T patent/PT3086637T/pt unknown
- 2015-11-25 DK DK20215046.2T patent/DK3850946T5/da active
- 2015-11-25 SG SG10202103050YA patent/SG10202103050YA/en unknown
- 2015-11-25 JP JP2017526681A patent/JP6730277B2/ja active Active
- 2015-11-25 RS RS20210547A patent/RS61774B1/sr unknown
- 2015-11-25 ES ES20215046T patent/ES2969389T3/es active Active
- 2015-11-25 PL PL18207075T patent/PL3466255T3/pl unknown
- 2015-11-25 HU HUE18207075A patent/HUE054661T2/hu unknown
- 2015-11-25 LT LTEP20215046.2T patent/LT3850946T/lt unknown
- 2015-11-25 PT PT182070755T patent/PT3466255T/pt unknown
- 2015-11-25 LT LTEP15813960.0T patent/LT3086637T/lt unknown
- 2015-11-25 SI SI201531982T patent/SI3850946T1/sl unknown
- 2015-11-25 EP EP23192469.7A patent/EP4296278A3/en active Pending
- 2015-11-25 FI FIEP20215046.2T patent/FI3850946T3/fi active
- 2015-11-25 PL PL20215046.2T patent/PL3850946T3/pl unknown
- 2015-11-25 LT LTEP18207075.5T patent/LT3466255T/lt unknown
- 2015-11-25 PT PT202150462T patent/PT3850946T/pt unknown
- 2015-11-25 HU HUE20215046A patent/HUE064960T2/hu unknown
- 2015-11-25 CA CA2967834A patent/CA2967834C/en active Active
- 2015-11-25 SG SG11201703463WA patent/SG11201703463WA/en unknown
- 2015-11-25 TR TR2019/03891T patent/TR201903891T4/tr unknown
- 2015-12-03 TW TW104140456A patent/TWI681053B/zh active
- 2015-12-03 AR ARP150103952A patent/AR102888A1/es unknown
-
2016
- 2016-01-19 US US15/000,751 patent/US10015953B2/en active Active
- 2016-12-15 HK HK16114307A patent/HK1225912A1/zh unknown
-
2017
- 2017-04-30 IL IL252019A patent/IL252019B/en unknown
-
2018
- 2018-05-17 US US15/982,174 patent/US10939673B2/en active Active
-
2019
- 2019-03-21 CY CY20191100334T patent/CY1121547T1/el unknown
- 2019-04-02 HR HRP20190634TT patent/HRP20190634T1/hr unknown
-
2020
- 2020-07-02 JP JP2020114628A patent/JP7089554B2/ja active Active
-
2021
- 2021-01-29 US US17/161,801 patent/US11910788B2/en active Active
- 2021-04-27 HR HRP20210662TT patent/HRP20210662T1/hr unknown
- 2021-05-06 CY CY20211100382T patent/CY1124089T1/el unknown
-
2022
- 2022-06-02 AU AU2022203787A patent/AU2022203787A1/en active Pending
-
2024
- 2024-01-16 US US18/413,219 patent/US20240138384A1/en active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HRP20190634T1 (hr) | Životinje koje nisu ljudi, koje imaju humanizirani gen 47 iz razlikovnog grozda | |
HRP20190227T1 (hr) | Životinje koje nisu ljudi, koje imaju humanizirani gen za protein za reguliranje signala | |
Jacobsen et al. | Diverse cellular architecture of atherosclerotic plaque derives from clonal expansion of a few medial SMCs | |
HRP20202034T1 (hr) | Neljudske životinje s genom za humanizirani diferencijacijski biljeg cd274 | |
HRP20200613T1 (hr) | Neljudske životinje koje imaju humanizirani gen 1 za programiranu staničnu smrt | |
Gancz et al. | Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration | |
Pichol-Thievend et al. | A blood capillary plexus-derived population of progenitor cells contributes to genesis of the dermal lymphatic vasculature during embryonic development | |
Volz et al. | Pericytes are progenitors for coronary artery smooth muscle | |
Morris et al. | Single‐cell transcriptomics of suprachiasmatic nuclei reveal a Prokineticin‐driven circadian network | |
Ramsbottom et al. | Vangl2-regulated polarisation of second heart field-derived cells is required for outflow tract lengthening during cardiac development | |
Yamada et al. | Promoter decommissioning by the NuRD chromatin remodeling complex triggers synaptic connectivity in the mammalian brain | |
Fre et al. | Notch lineages and activity in intestinal stem cells determined by a new set of knock-in mice | |
Sun et al. | Mosaic mutant analysis identifies PDGFRα/PDGFRβ as negative regulators of adipogenesis | |
RU2020103811A (ru) | Гуманизированные животные по с5 и с3 | |
HRP20210824T1 (hr) | Neljudske životinje koje imaju humanizirani gen 3 za aktiviranje limfocita | |
Hua et al. | Frizzled3 controls axonal development in distinct populations of cranial and spinal motor neurons | |
Yu et al. | VGLL4 plays a critical role in heart valve development and homeostasis | |
CN104450602B (zh) | 非人哺乳动物神经精神疾病动物模型及其制备方法和用途 | |
SI3027015T1 (en) | HUMANIZED IL-4 AND IL-4R ALPHA ANIMALS | |
Bruyère et al. | Presynaptic APP levels and synaptic homeostasis are regulated by Akt phosphorylation of huntingtin | |
RU2016123708A (ru) | Отличные от человека животные, содержащие гуманизированный ген фактора активации в-клеток | |
JP2019506897A5 (hr) | ||
Ridge et al. | Non-muscle myosin IIB (Myh10) is required for epicardial function and coronary vessel formation during mammalian development | |
RU2013123512A (ru) | Муриновая модель воспаления с делецией il33 n-концевого домена | |
Uchtmann et al. | Homozygous loss of mouse tetraspanin CD82 enhances integrin αIIbβ3 expression and clot retraction in platelets |