BR112013002695B1 - Métodos para preparação de um camundongo geneticamente modificado, proteína de ligação ao antígeno, uso de um camundongo preparado pelo método e vetor de direcionamento - Google Patents
Métodos para preparação de um camundongo geneticamente modificado, proteína de ligação ao antígeno, uso de um camundongo preparado pelo método e vetor de direcionamento Download PDFInfo
- Publication number
- BR112013002695B1 BR112013002695B1 BR112013002695-2A BR112013002695A BR112013002695B1 BR 112013002695 B1 BR112013002695 B1 BR 112013002695B1 BR 112013002695 A BR112013002695 A BR 112013002695A BR 112013002695 B1 BR112013002695 B1 BR 112013002695B1
- Authority
- BR
- Brazil
- Prior art keywords
- mouse
- human
- gene
- endogenous
- heavy chain
- Prior art date
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 347
- 239000013598 vector Substances 0.000 title claims abstract description 49
- 238000000034 method Methods 0.000 title claims abstract description 47
- 230000008685 targeting Effects 0.000 title claims description 68
- 102000004169 proteins and genes Human genes 0.000 title abstract description 13
- 108091008324 binding proteins Proteins 0.000 claims abstract description 126
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims abstract description 35
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims abstract description 33
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims abstract description 26
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims abstract description 26
- 210000004027 cell Anatomy 0.000 claims description 137
- 229920001184 polypeptide Polymers 0.000 claims description 106
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 106
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 106
- 239000000427 antigen Substances 0.000 claims description 64
- 108060003951 Immunoglobulin Proteins 0.000 claims description 63
- 102000018358 immunoglobulin Human genes 0.000 claims description 63
- 150000007523 nucleic acids Chemical group 0.000 claims description 60
- 108091007433 antigens Proteins 0.000 claims description 57
- 102000036639 antigens Human genes 0.000 claims description 57
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 44
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 36
- 230000006798 recombination Effects 0.000 claims description 36
- 238000005215 recombination Methods 0.000 claims description 36
- 210000004602 germ cell Anatomy 0.000 claims description 33
- 239000002773 nucleotide Substances 0.000 claims description 19
- 125000003729 nucleotide group Chemical group 0.000 claims description 19
- 239000000539 dimer Substances 0.000 claims description 14
- 101150042441 K gene Proteins 0.000 claims description 8
- 102000025171 antigen binding proteins Human genes 0.000 claims description 7
- 108091000831 antigen binding proteins Proteins 0.000 claims description 7
- 230000006801 homologous recombination Effects 0.000 claims description 7
- 238000002744 homologous recombination Methods 0.000 claims description 7
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 6
- 101100370002 Mus musculus Tnfsf14 gene Proteins 0.000 claims description 5
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 4
- 108700005091 Immunoglobulin Genes Proteins 0.000 claims description 3
- 230000028993 immune response Effects 0.000 claims description 2
- 102000023732 binding proteins Human genes 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 102000014914 Carrier Proteins Human genes 0.000 abstract description 126
- 241000699670 Mus sp. Species 0.000 abstract description 73
- 101150008942 J gene Proteins 0.000 abstract description 18
- 101150117115 V gene Proteins 0.000 abstract description 14
- 101150097493 D gene Proteins 0.000 abstract description 5
- 210000002257 embryonic structure Anatomy 0.000 abstract description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 329
- 230000002068 genetic effect Effects 0.000 description 73
- 238000011144 upstream manufacturing Methods 0.000 description 54
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 47
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 38
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 38
- 125000006850 spacer group Chemical group 0.000 description 36
- 102000018120 Recombinases Human genes 0.000 description 32
- 108010091086 Recombinases Proteins 0.000 description 32
- 230000000392 somatic effect Effects 0.000 description 28
- 210000001185 bone marrow Anatomy 0.000 description 26
- 239000012634 fragment Substances 0.000 description 25
- 230000004048 modification Effects 0.000 description 25
- 238000012986 modification Methods 0.000 description 25
- 238000007792 addition Methods 0.000 description 24
- 108020004707 nucleic acids Proteins 0.000 description 24
- 102000039446 nucleic acids Human genes 0.000 description 24
- 150000001413 amino acids Chemical class 0.000 description 20
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 17
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 16
- 229930193140 Neomycin Natural products 0.000 description 15
- 229960004927 neomycin Drugs 0.000 description 15
- 210000000952 spleen Anatomy 0.000 description 15
- 238000004519 manufacturing process Methods 0.000 description 14
- 210000004988 splenocyte Anatomy 0.000 description 14
- 125000003275 alpha amino acid group Chemical group 0.000 description 13
- 238000003780 insertion Methods 0.000 description 13
- 230000037431 insertion Effects 0.000 description 13
- 210000001161 mammalian embryo Anatomy 0.000 description 13
- 108020004414 DNA Proteins 0.000 description 12
- 101000662009 Homo sapiens UDP-N-acetylglucosamine pyrophosphorylase Proteins 0.000 description 12
- 102100037921 UDP-N-acetylglucosamine pyrophosphorylase Human genes 0.000 description 12
- 238000006467 substitution reaction Methods 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 11
- 210000003519 mature b lymphocyte Anatomy 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 238000012217 deletion Methods 0.000 description 8
- 230000037430 deletion Effects 0.000 description 8
- 210000004408 hybridoma Anatomy 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 7
- 108010002162 IgK Proteins 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000003297 immature b lymphocyte Anatomy 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 210000004698 lymphocyte Anatomy 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- 108700028369 Alleles Proteins 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 6
- 230000000750 progressive effect Effects 0.000 description 6
- 230000003393 splenic effect Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 101000608935 Homo sapiens Leukosialin Proteins 0.000 description 5
- 102100039564 Leukosialin Human genes 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 238000011577 humanized mouse model Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000008707 rearrangement Effects 0.000 description 5
- 230000002207 retinal effect Effects 0.000 description 5
- 238000003757 reverse transcription PCR Methods 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 210000000689 upper leg Anatomy 0.000 description 5
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 4
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 101150076489 B gene Proteins 0.000 description 3
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 3
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 3
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 3
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 3
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 description 3
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 3
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 3
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 239000012979 RPMI medium Substances 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 108700005077 Viral Genes Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000011712 cell development Effects 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000012239 gene modification Methods 0.000 description 3
- 230000005017 genetic modification Effects 0.000 description 3
- 235000013617 genetically modified food Nutrition 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000008521 reorganization Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- 206010069754 Acquired gene mutation Diseases 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 101001073212 Arabidopsis thaliana Peroxidase 33 Proteins 0.000 description 2
- 101150111062 C gene Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 2
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 2
- 101001123325 Homo sapiens Peroxisome proliferator-activated receptor gamma coactivator 1-beta Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- 108091092724 Noncoding DNA Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 102100028961 Peroxisome proliferator-activated receptor gamma coactivator 1-beta Human genes 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 108010052160 Site-specific recombinase Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108700019146 Transgenes Proteins 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 210000002459 blastocyst Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 102000054766 genetic haplotypes Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000008105 immune reaction Effects 0.000 description 2
- 229940027941 immunoglobulin g Drugs 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000013011 mating Effects 0.000 description 2
- 239000011325 microbead Substances 0.000 description 2
- 108700039855 mouse a Proteins 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 230000037439 somatic mutation Effects 0.000 description 2
- 238000001847 surface plasmon resonance imaging Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 210000003501 vero cell Anatomy 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 102000019260 B-Cell Antigen Receptors Human genes 0.000 description 1
- 108010012919 B-Cell Antigen Receptors Proteins 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000251729 Elasmobranchii Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000777314 Homo sapiens Choline kinase alpha Proteins 0.000 description 1
- 101000777313 Homo sapiens Choline/ethanolamine kinase Proteins 0.000 description 1
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 1
- 101001138544 Homo sapiens UMP-CMP kinase Proteins 0.000 description 1
- 241000235789 Hyperoartia Species 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 description 1
- 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 description 1
- 108091029795 Intergenic region Proteins 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241001452677 Ogataea methanolica Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108091008109 Pseudogenes Proteins 0.000 description 1
- 102000057361 Pseudogenes Human genes 0.000 description 1
- 241000382353 Pupa Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 208000035199 Tetraploidy Diseases 0.000 description 1
- 241000255993 Trichoplusia ni Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000007503 antigenic stimulation Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 102000053391 human F Human genes 0.000 description 1
- 108700031895 human F Proteins 0.000 description 1
- 229940096329 human immunoglobulin a Drugs 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- AEMBWNDIEFEPTH-UHFFFAOYSA-N n-tert-butyl-n-ethylnitrous amide Chemical compound CCN(N=O)C(C)(C)C AEMBWNDIEFEPTH-UHFFFAOYSA-N 0.000 description 1
- 108091014756 nucleotide binding proteins Proteins 0.000 description 1
- 230000005257 nucleotidylation Effects 0.000 description 1
- 238000010397 one-hybrid screening Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013595 supernatant sample Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
-
- 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
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/081—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from DNA viruses
- C07K16/082—Hepadnaviridae, e.g. hepatitis B virus
-
- 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
-
- 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
-
- 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
- A01K2217/07—Animals genetically altered by homologous recombination
-
- 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
- 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
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
- C12N2015/8518—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Environmental Sciences (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Husbandry (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36990910P | 2010-08-02 | 2010-08-02 | |
| US61/369,909 | 2010-08-02 | ||
| PCT/US2011/046196 WO2012018764A1 (en) | 2010-08-02 | 2011-08-02 | Mice that make binding proteins comprising vl domains |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR112013002695A2 BR112013002695A2 (pt) | 2017-03-01 |
| BR112013002695B1 true BR112013002695B1 (pt) | 2023-01-24 |
Family
ID=44543797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112013002695-2A BR112013002695B1 (pt) | 2010-08-02 | 2011-08-02 | Métodos para preparação de um camundongo geneticamente modificado, proteína de ligação ao antígeno, uso de um camundongo preparado pelo método e vetor de direcionamento |
Country Status (27)
| Country | Link |
|---|---|
| US (7) | US9516868B2 (enExample) |
| EP (3) | EP2947151A1 (enExample) |
| JP (6) | JP6146913B2 (enExample) |
| KR (4) | KR102008655B1 (enExample) |
| CN (4) | CN118791596A (enExample) |
| AU (1) | AU2011285919C1 (enExample) |
| BR (1) | BR112013002695B1 (enExample) |
| CA (2) | CA3250882A1 (enExample) |
| CY (1) | CY1118562T1 (enExample) |
| DK (1) | DK2601298T3 (enExample) |
| ES (1) | ES2612459T3 (enExample) |
| HK (1) | HK1217511A1 (enExample) |
| HR (1) | HRP20170322T1 (enExample) |
| HU (1) | HUE031903T2 (enExample) |
| IL (4) | IL315833A (enExample) |
| LT (1) | LT2601298T (enExample) |
| MX (5) | MX363084B (enExample) |
| MY (1) | MY172618A (enExample) |
| NZ (2) | NZ707327A (enExample) |
| PL (1) | PL2601298T3 (enExample) |
| PT (1) | PT2601298T (enExample) |
| RS (1) | RS55495B1 (enExample) |
| RU (2) | RU2612903C2 (enExample) |
| SG (3) | SG10201912639SA (enExample) |
| SI (1) | SI2601298T1 (enExample) |
| SM (2) | SMT201700023T1 (enExample) |
| WO (1) | WO2012018764A1 (enExample) |
Families Citing this family (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2669298A3 (en) * | 2008-05-23 | 2014-02-26 | Ablexis, LLC | Single variable immunoglobulin domain comprising VL-DH-JL |
| ES2948572T3 (es) | 2009-07-08 | 2023-09-14 | Kymab Ltd | Modelos de roedores y moléculas terapéuticas |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| ES2547142T5 (es) | 2010-02-08 | 2021-12-09 | Regeneron Pharma | Cadena ligera común de ratón |
| US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| US10662256B2 (en) | 2010-07-26 | 2020-05-26 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| US10793829B2 (en) | 2010-07-26 | 2020-10-06 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| EP2597945B1 (en) | 2010-07-26 | 2020-07-22 | Trianni, Inc. | Transgenic animals and methods of use |
| IL315833A (en) | 2010-08-02 | 2024-11-01 | Regeneron Pharma | Mice producing binding proteins containing VL regions |
| IL273982B2 (en) | 2011-08-05 | 2023-03-01 | Regeneron Pharma | Humanized mice possess a universal light chain |
| EP2757875B2 (en) | 2011-09-19 | 2023-03-22 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| WO2013041845A2 (en) | 2011-09-19 | 2013-03-28 | Kymab Limited | Animals, repertoires & methods |
| WO2013045916A1 (en) | 2011-09-26 | 2013-04-04 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| US10246509B2 (en) | 2011-10-17 | 2019-04-02 | Regeneron Pharmaceuticals, Inc. | Restricted immunoglobulin heavy chain mice |
| US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| SG11201403326VA (en) | 2011-12-20 | 2014-07-30 | Regeneron Pharma | Humanized light chain mice |
| WO2013116609A1 (en) * | 2012-02-01 | 2013-08-08 | Regeneron Pharmaceuticals, Inc. | Humanized rodents that express heavy chains containing vl domains |
| EP2839009B1 (en) * | 2012-03-14 | 2019-08-21 | Innovative Targeting Solutions Inc. | Generating targeted sequence diversity in proteins |
| EP2825653A4 (en) | 2012-03-14 | 2016-01-20 | Innovative Targeting Solutions Inc | PRODUCTION OF TARGETED SEQUENCE DIVERSITY IN FUSION PROTEINS |
| 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 |
| PT3597037T (pt) | 2012-06-12 | 2021-06-01 | Regeneron Pharma | Animais não humanos humanizados com lócus de cadeia pesada de imunoglobulina restrito |
| US20150203591A1 (en) | 2012-08-02 | 2015-07-23 | Regeneron Pharmaceuticals, Inc. | Mutivalent antigen-binding proteins |
| SMT201800435T1 (it) | 2013-02-20 | 2018-09-13 | Regeneron Pharma | Animali non umani con sequenze della catena pesante dell’immunoglobulina modificate riferimento incrociato a domande correlate |
| AU2014244020B2 (en) * | 2013-03-13 | 2020-06-04 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| EA038512B1 (ru) | 2013-03-15 | 2021-09-08 | Регенерон Фармасьютикалз, Инк. | Конъюгаты майтанзиноидов и их терапевтическое применение |
| 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 |
| US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
| US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
| CA2921412C (en) | 2013-08-26 | 2024-05-28 | Regeneron Pharmaceuticals, Inc. | Pharmaceutical compositions comprising macrolide diastereomers, methods of their synthesis and therapeutic uses |
| FR3011249A1 (enExample) * | 2013-10-01 | 2015-04-03 | Kymab Ltd | |
| ES2993142T3 (en) | 2013-10-01 | 2024-12-23 | Kymab Ltd | Animal models and therapeutic molecules |
| ES2762640T3 (es) | 2014-03-21 | 2020-05-25 | Regeneron Pharma | Proteínas VL de unión a antígeno que exhiben diferentes características de unión |
| BR112016021572A2 (pt) * | 2014-03-21 | 2017-10-03 | Regeneron Pharma | Métodos para preparar um animal não humano geneticamente modificado e para produzir proteínas de ligação, hibridoma, ácido nucleico, célula, e, proteína de ligação |
| EP3271403A1 (en) * | 2015-03-19 | 2018-01-24 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
| WO2016160615A1 (en) | 2015-03-27 | 2016-10-06 | Regeneron Pharmaceuticals, Inc. | Maytansinoid derivatives, conjugates thereof, and methods of use |
| PL3303386T3 (pl) | 2015-06-05 | 2025-03-03 | Genentech, Inc. | Przeciwciała anty-tau i sposoby zastosowania |
| EP3384030A4 (en) | 2015-12-03 | 2019-07-03 | Trianni, Inc. | IMPROVED IMMUNOGLULINIVITY |
| MX390630B (es) | 2016-01-25 | 2025-03-21 | Regeneron Pharma | Derivados de maitansinoide, conjugados de los mismos y metodos de uso. |
| WO2017136734A1 (en) | 2016-02-04 | 2017-08-10 | Trianni, Inc. | Enhanced production of immunoglobulins |
| MX2018014172A (es) | 2016-05-20 | 2019-08-22 | Regeneron Pharma | Métodos para romper la tolerancia inmunológica usando múltiples arn guías. |
| CN109640644B (zh) | 2016-06-03 | 2021-10-26 | 瑞泽恩制药公司 | 表达外源末端脱氧核苷酸转移酶的非人动物 |
| MY199937A (en) | 2016-11-08 | 2023-11-29 | Regeneron Pharma | Steroids and protein-conjugates thereof |
| TWI787219B (zh) | 2016-12-07 | 2022-12-21 | 美商建南德克公司 | 抗-tau抗體及使用方法 |
| CA3045294A1 (en) | 2016-12-07 | 2018-06-14 | Genentech, Inc. | Anti-tau antibodies and methods of use |
| CN118140872A (zh) | 2017-01-19 | 2024-06-07 | 欧莫诺艾比公司 | 来自具有多个重链免疫球蛋白基因座的转基因啮齿类动物的人抗体 |
| KR20200007905A (ko) | 2017-05-18 | 2020-01-22 | 리제너론 파마슈티칼스 인코포레이티드 | 사이클로덱스트린 단백질 약물 접합체 |
| KR20200045520A (ko) | 2017-09-07 | 2020-05-04 | 오거스타 유니버시티 리서치 인스티튜트, 인크. | 프로그래밍된 세포사 단백질 1에 대한 항체 |
| CN111601619A (zh) | 2017-11-07 | 2020-08-28 | 里珍纳龙药品有限公司 | 用于抗体药物偶联物的亲水性连接体 |
| US12070506B2 (en) | 2018-01-08 | 2024-08-27 | Regeneron Pharmaceuticals, Inc. | Steroids and antibody-conjugates thereof |
| US20210051929A1 (en) | 2018-03-24 | 2021-02-25 | Regeneron Pharmaceuticals, Inc. | Genetically modified non-human animals for generating therapeutic antibodies against peptide-mhc complexes, methods of making and uses thereof |
| CA3093850A1 (en) | 2018-03-26 | 2019-10-03 | Regeneron Pharmaceuticals, Inc. | Humanized rodents for testing therapeutic agents |
| AU2019265703A1 (en) | 2018-05-09 | 2020-11-19 | Regeneron Pharmaceuticals, Inc. | Anti-MSR1 antibodies and methods of use thereof |
| IL318469A (en) | 2018-06-14 | 2025-03-01 | Regeneron Pharma | Non-human animals capable of reorganizing transgenic DH-DH, and their uses |
| JP2020146299A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146301A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146300A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146314A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146306A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146309A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146307A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146316A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146318A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146304A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146298A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146315A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146313A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146312A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146310A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146317A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146303A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146302A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146297A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146308A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| JP2020146305A (ja) * | 2019-03-14 | 2020-09-17 | 株式会社三洋物産 | 遊技機 |
| KR20230004651A (ko) | 2020-04-16 | 2023-01-06 | 리제너론 파마슈티칼스 인코포레이티드 | 딜스-알더 접합 방법 |
| BR112023000489A2 (pt) | 2020-07-13 | 2023-03-28 | Regeneron Pharma | Análogos de camptotecina conjugados a um resíduo de glutamina em uma proteína, e seu uso |
| TW202229328A (zh) | 2020-09-11 | 2022-08-01 | 美商再生元醫藥公司 | 抗原特異性抗體之鑑定及產生 |
| US12280124B2 (en) | 2020-09-14 | 2025-04-22 | Regeneron Pharmaceuticals, Inc. | Antibody-drug conjugates comprising GLP1 peptidomimetics and uses thereof |
| JP2024500399A (ja) | 2020-12-16 | 2024-01-09 | 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 | ヒト化Fcアルファ受容体を発現するマウス |
| IL303868A (en) | 2020-12-23 | 2023-08-01 | Regeneron Pharma | Nucleic acids encoding anchor-modified antibodies and uses thereof |
| US20230287138A1 (en) | 2022-01-12 | 2023-09-14 | Regneron Pharmaceuticals, Inc. | Protein-drug conjugates comprising camptothecin analogs and methods of use thereof |
| CN118984837A (zh) | 2022-01-28 | 2024-11-19 | 乔治穆内公司 | 作为pd-1激动剂的程序性细胞死亡蛋白1的抗体 |
| KR20250133813A (ko) | 2022-12-21 | 2025-09-08 | 리제너론 파마슈티칼스 인코포레이티드 | Adc 접합을 위한 토포이소머라아제 i 억제제의 전구약물 및 이의 사용 방법 |
| US20250171516A1 (en) | 2023-11-03 | 2025-05-29 | Regeneron Pharmaceuticals, Inc. | Peptide acids as a glp1r agonist and antibody-drug conjugates thereof |
Family Cites Families (135)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4977081A (en) | 1987-05-04 | 1990-12-11 | Adi Diagnostics, Inc. | Stable rabbit-mouse hybridomas and secretion products thereof |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5075181A (en) | 1989-05-05 | 1991-12-24 | Kennametal Inc. | High hardness/high compressive stress multilayer coated tool |
| WO1991000906A1 (en) | 1989-07-12 | 1991-01-24 | Genetics Institute, Inc. | Chimeric and transgenic animals capable of producing human antibodies |
| ATE139258T1 (de) | 1990-01-12 | 1996-06-15 | Cell Genesys Inc | Erzeugung xenogener antikörper |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US6657103B1 (en) | 1990-01-12 | 2003-12-02 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| CA2066433A1 (en) | 1990-07-10 | 1992-01-11 | Haruo Matsuda | Chicken-specific immunoglobulin g-producing hybridoma |
| US7041871B1 (en) | 1995-10-10 | 2006-05-09 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| JP2835787B2 (ja) | 1991-03-22 | 1998-12-14 | キヤノン株式会社 | 強誘電性液晶素子 |
| CA2078539C (en) * | 1991-09-18 | 2005-08-02 | Kenya Shitara | Process for producing humanized chimera antibody |
| US5150584A (en) | 1991-09-26 | 1992-09-29 | General Motors Corporation | Method and apparatus for detecting low refrigerant charge |
| NZ255101A (en) | 1992-07-24 | 1997-08-22 | Cell Genesys Inc | A yeast artificial chromosome (yac) vector containing an hprt minigene expressible in murine stem cells and genetically modified rodent therefor |
| EP0583980A1 (en) | 1992-08-20 | 1994-02-23 | Eli Lilly And Company | Method for generating monoclonal antibodies from rabbits |
| DE69330523D1 (de) | 1992-08-21 | 2001-09-06 | Vrije Universiteit Brussel Bru | Immunoglobuline ohne leichte ketten |
| US6005079A (en) | 1992-08-21 | 1999-12-21 | Vrije Universiteit Brussels | Immunoglobulins devoid of light chains |
| US6765087B1 (en) | 1992-08-21 | 2004-07-20 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
| WO1994012215A1 (en) | 1992-12-01 | 1994-06-09 | Protein Design Labs, Inc. | Humanized antibodies reactive with l-selectin |
| DE4309308C1 (de) | 1993-03-23 | 1994-04-14 | Siemens Nixdorf Inf Syst | Belüftungssystem für Schränke mit stark wärmeerzeugenden elektronischen Funktionseinheiten |
| IL109168A0 (en) * | 1993-04-01 | 1994-06-24 | Univ Columbia | A retroviral vector capable of transducing the aldehyde dehydrogenase-1 gene and making cells resistant to the chemotherapeutic agent cyclophosphamide and its derivatives and analogs |
| JPH08509612A (ja) | 1993-04-26 | 1996-10-15 | ジェンファーム インターナショナル インコーポレイテッド | 異種抗体を産生することができるトランスジェニック非ヒト動物 |
| US5523226A (en) | 1993-05-14 | 1996-06-04 | Biotechnology Research And Development Corp. | Transgenic swine compositions and methods |
| EP0739981A1 (en) | 1995-04-25 | 1996-10-30 | Vrije Universiteit Brussel | Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes |
| US6632976B1 (en) | 1995-08-29 | 2003-10-14 | Kirin Beer Kabushiki Kaisha | Chimeric mice that are produced by microcell mediated chromosome transfer and that retain a human antibody gene |
| WO1997016537A1 (en) | 1995-10-30 | 1997-05-09 | Spectral Diagnostics, Inc. | Stable chicken b-cell line and method of use thereof |
| AU3507297A (en) | 1996-06-26 | 1998-01-14 | Baylor College Of Medicine | Chromosomal rearrangement by insertion of two recombination substrates |
| EP1500329B1 (en) | 1996-12-03 | 2012-03-21 | Amgen Fremont Inc. | Human antibodies that specifically bind human TNF alpha |
| CN1203922A (zh) | 1997-03-21 | 1999-01-06 | 三共株式会社 | 人源化抗人fas抗体 |
| US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| US6774279B2 (en) | 1997-05-30 | 2004-08-10 | Carnegie Institution Of Washington | Use of FLP recombinase in mice |
| GB9823930D0 (en) | 1998-11-03 | 1998-12-30 | Babraham Inst | Murine expression of human ig\ locus |
| EP1183344A4 (en) | 1999-05-27 | 2003-06-25 | Human Genome Sciences Inc | ADAM POLYNUCLEOTIDES AND POLYPEPTIDES |
| GB0001448D0 (en) | 2000-01-21 | 2000-03-08 | Novartis Ag | Organic compounds |
| AU8470301A (en) * | 2000-08-03 | 2002-02-18 | Wim-Van Schooten | Production of humanized antibodies in transgenic animals |
| US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US7105348B2 (en) | 2000-10-31 | 2006-09-12 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| PE20020574A1 (es) | 2000-12-06 | 2002-07-02 | Wyeth Corp | Anticuerpos humanizados que reconocen el peptido amiloideo beta |
| GB0110029D0 (en) | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
| US7034134B2 (en) | 2001-04-26 | 2006-04-25 | Bristol-Myers Squibb Company | Polynucleotide encoding a novel metalloprotease highly expressed in the testis, MMP-29 |
| EP1970448A1 (en) | 2001-05-11 | 2008-09-17 | Kirin Pharma Kabushiki Kaisha | Human artificial chromosome containting human antibody lambda light chain and non-human animal containting the human artificial chromosome capable of genetic transmission |
| GB0115256D0 (en) | 2001-06-21 | 2001-08-15 | Babraham Inst | Mouse light chain locus |
| WO2003002609A2 (en) | 2001-06-28 | 2003-01-09 | Domantis Limited | Dual-specific ligand and its use |
| FR2827302B1 (fr) * | 2001-07-13 | 2003-10-10 | Genoway | Cellule et animal transgenique modelisant la presentation antigenique humaine et leurs utilisations |
| US20060199204A1 (en) | 2001-10-05 | 2006-09-07 | U.S. Epa | Genetic testing for male factor infertility |
| US20030108925A1 (en) | 2001-10-05 | 2003-06-12 | U.S. Epa | Genetic testing for male factor infertility |
| EP1461442B1 (en) | 2001-11-30 | 2017-09-06 | Amgen Fremont Inc. | Transgenic animals bearing human ig lambda light chain genes |
| ATE395413T1 (de) | 2001-12-03 | 2008-05-15 | Amgen Fremont Inc | Antikörperkategorisierung auf der grundlage von bindungseigenschaften |
| US20030182675A1 (en) | 2002-03-22 | 2003-09-25 | Origen Therapeutics | Functional disruption of avian immunoglobulin genes |
| AU2003230741A1 (en) | 2002-03-22 | 2003-10-13 | Origen Therapeutics | Transgenic aves producing human polyclonal antibodies |
| AU2003244817B2 (en) | 2002-06-28 | 2010-08-26 | Domantis Limited | Antigen-binding immunoglobulin single variable domains and dual-specific constructs |
| FI117110B (fi) | 2002-07-05 | 2006-06-15 | Outokumpu Oy | Anodin syöttö sulatusreaktoriin |
| AU2003250074B2 (en) | 2002-07-18 | 2010-09-09 | Merus N.V. | Recombinant production of mixtures of antibodies |
| US20040101920A1 (en) | 2002-11-01 | 2004-05-27 | Czeslaw Radziejewski | Modification assisted profiling (MAP) methodology |
| GB0228210D0 (en) * | 2002-12-03 | 2003-01-08 | Babraham Inst | Single chain antibodies |
| GB0230203D0 (en) | 2002-12-27 | 2003-02-05 | Domantis Ltd | Fc fusion |
| AU2003290330A1 (en) | 2002-12-27 | 2004-07-22 | Domantis Limited | Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand |
| GB0230201D0 (en) | 2002-12-27 | 2003-02-05 | Domantis Ltd | Retargeting |
| GB2398784B (en) | 2003-02-26 | 2005-07-27 | Babraham Inst | Removal and modification of the immunoglobulin constant region gene cluster of a non-human mammal |
| US20100069614A1 (en) * | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| EP2395017A3 (en) * | 2003-05-30 | 2012-12-19 | Merus B.V. | Design and use of paired variable regions of specific binding molecules |
| US7205148B2 (en) | 2003-06-11 | 2007-04-17 | Regeneron Pharmaceuticals, Inc. | Genome mutation by intron insertion into an embryonic stem cell genome |
| MXPA06000562A (es) | 2003-07-15 | 2006-03-30 | Therapeutic Human Polyclonals | Loci de inmunoglobulina humanizada. |
| WO2005019463A1 (en) | 2003-08-11 | 2005-03-03 | Therapeutic Human Polyclonals, Inc. | Improved transgenesis with humanized immunoglobulin loci |
| RU2251699C1 (ru) | 2003-09-25 | 2005-05-10 | Киселев Всеволод Иванович | Способ ранней и доклинической диагностики цервикального рака |
| WO2005038001A2 (en) | 2003-10-14 | 2005-04-28 | Therapeutic Human Polyclonals, Inc. | Improved transgenesis by sperm-mediated gene transfer |
| FR2861255B1 (fr) | 2003-10-24 | 2006-02-17 | Centre Nat Rech Scient | Mammifere non-humain transgenique pour la region constante de la chaine lourde des immunoglobulines humaines de classe a et ses applications. |
| US8911234B2 (en) | 2004-02-20 | 2014-12-16 | Woodwelding Ag | Implant that can be implanted in osseous tissue, method for producing said implant and corresponding implant |
| CA2580336C (en) * | 2004-07-22 | 2016-07-19 | Roger Kingdon Craig | Vh heavy chain only antibodies, and vh heavy chain only dimer compounds and uses thereof |
| PL2767161T3 (pl) | 2004-10-19 | 2018-09-28 | Regeneron Pharmaceuticals, Inc. | Sposób wytwarzania zwierzęcia homozygotycznego pod względem modyfikacji genetycznej |
| US20060117398A1 (en) | 2004-10-22 | 2006-06-01 | Roland Buelow | Suppression of endogenous immunoglobulin expression |
| SG169348A1 (en) | 2006-01-25 | 2011-03-30 | Univ Erasmus Medical Ct | Generation of heavy-chain only antibodies in transgenic animals |
| GB0618345D0 (en) * | 2006-09-18 | 2006-10-25 | Univ Erasmus | Binding molecules |
| WO2007117410A2 (en) | 2006-03-31 | 2007-10-18 | Medarex, Inc. | Transgenic animals expressing chimeric antibodies for use in preparing human antibodies |
| PL2374818T3 (pl) | 2006-06-02 | 2013-05-31 | Regeneron Pharma | Przeciwciała o wysokim powinowactwie przeciw ludzkiemu receptorowi IL 6 |
| CA2661848C (en) | 2006-09-01 | 2015-02-03 | Therapeutic Human Polyclonals, Inc. | Enhanced expression of human or humanized immunoglobulin in non-human transgenic animals |
| CN101522716B (zh) * | 2006-10-02 | 2013-03-20 | 瑞泽恩制药公司 | 抗人il-4受体的高亲和力人抗体 |
| NO347649B1 (no) | 2006-12-14 | 2024-02-12 | Regeneron Pharma | Humant antistoff eller antistoff fragment som spesifikt binder human deltaliknende ligand 4 (hDII4), nukleinsyremolekyl som koder for slike og vektor og vert-vektorsystemer, samt fremgangsmåte for fremstilling, sammensetning og anvendelse. |
| SG182144A1 (en) | 2007-06-01 | 2012-07-30 | Omt Inc | Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies |
| WO2009013620A2 (en) | 2007-06-11 | 2009-01-29 | Erasmus University Medical Center Rotterdam | Homologous recombination |
| ITMI20071522A1 (it) | 2007-07-27 | 2009-01-28 | Areta Internat S R L | Vaccino idiotipico |
| CN101952312A (zh) * | 2007-07-31 | 2011-01-19 | 米迪缪尼有限公司 | 多特异性表位结合蛋白及其应用 |
| JP5588866B2 (ja) | 2007-08-10 | 2014-09-10 | メダレックス エル.エル.シー. | Hco32およびhco27、ならびに関連実施例 |
| WO2009026660A1 (en) | 2007-08-30 | 2009-03-05 | Walter And Eliza Hall Institute Of Medical Research | Dendritic cell marker and uses thereof |
| KR102339457B1 (ko) | 2007-09-26 | 2021-12-14 | 추가이 세이야쿠 가부시키가이샤 | 항체 정상영역 개변체 |
| EP2050764A1 (en) * | 2007-10-15 | 2009-04-22 | sanofi-aventis | Novel polyvalent bispecific antibody format and uses thereof |
| CA2721231C (en) | 2008-04-14 | 2015-10-06 | Innovative Targeting Solutions Inc. | Sequence diversity generation in immunoglobulins |
| EP2669298A3 (en) * | 2008-05-23 | 2014-02-26 | Ablexis, LLC | Single variable immunoglobulin domain comprising VL-DH-JL |
| US20100122358A1 (en) | 2008-06-06 | 2010-05-13 | Crescendo Biologics Limited | H-Chain-only antibodies |
| ES2445193T3 (es) | 2008-06-27 | 2014-02-28 | Merus B.V. | Mamíferos no humanos productores de anticuerpos |
| WO2010039900A2 (en) | 2008-09-30 | 2010-04-08 | Aliva Biopharmaceuticals, Inc. | Non-human mammals for the production of chimeric antibodies |
| KR101711222B1 (ko) | 2008-12-18 | 2017-02-28 | 에라스무스 유니버시티 메디컬 센터 로테르담 | 인간화 항체들을 발현하는 비-인간 유전자이식 동물들 및 그의 이용 |
| CA2983133A1 (en) | 2009-02-04 | 2010-08-12 | Molecular Innovations | Methods for screening candidate agents for modulating prorenin and renin, assays for detecting prorenin, and antibodies used therein |
| GB0905023D0 (en) | 2009-03-24 | 2009-05-06 | Univ Erasmus Medical Ct | Binding molecules |
| JP5497887B2 (ja) * | 2009-04-07 | 2014-05-21 | ロシュ グリクアート アクチェンゲゼルシャフト | 二重特異性抗ErbB−2/抗c−Met抗体 |
| MX368932B (es) | 2009-06-26 | 2019-10-22 | Regeneron Pharma | Anticuerpos biespecificos facilmente aislados con formato de inmunoglobulina original. |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| ES2948572T3 (es) | 2009-07-08 | 2023-09-14 | Kymab Ltd | Modelos de roedores y moléculas terapéuticas |
| RU2425880C2 (ru) | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
| CN101620635A (zh) * | 2009-08-07 | 2010-01-06 | 中兴通讯股份有限公司 | 页面数据获取方法及服务器、页面更新方法及服务器 |
| MY172472A (en) | 2009-12-10 | 2019-11-26 | Regeneron Pharma | Mice that make heavy chain antibodies |
| US20120021409A1 (en) | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| ES2547142T5 (es) | 2010-02-08 | 2021-12-09 | Regeneron Pharma | Cadena ligera común de ratón |
| US20130185821A1 (en) | 2010-02-08 | 2013-07-18 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| CA2802591A1 (en) * | 2010-06-17 | 2011-12-22 | Kymab Limited | Animal models and therapeutic molecules |
| MY195217A (en) | 2010-06-22 | 2023-01-11 | Regeneron Pharma | MICE Expressing An Immunoglobulin Hybrid Light Chain |
| IL315833A (en) | 2010-08-02 | 2024-11-01 | Regeneron Pharma | Mice producing binding proteins containing VL regions |
| EP2638155A1 (en) | 2010-11-08 | 2013-09-18 | Kymab Limited | Cells & vertebrates for enhanced somatic hypermutation and class switch recombination |
| HUE024534T2 (hu) | 2011-02-25 | 2016-01-28 | Regeneron Pharma | ADAM6 egerek |
| CN103403025B (zh) | 2011-02-28 | 2016-10-12 | 弗·哈夫曼-拉罗切有限公司 | 单价抗原结合蛋白 |
| BR112013019975A2 (pt) | 2011-02-28 | 2017-08-01 | Hoffmann La Roche | proteínas de ligação de antígeno, composição farmacêutica, uso de uma proteína de ligação de antígeno, método para o tratamento de um paciente e método para a preparação de uma proteína de ligação de antígeno, ácido nucleico, vetor e célula hospedeira" |
| US20120310284A1 (en) | 2011-06-03 | 2012-12-06 | Royal Oak Industries | Polyaxial pedicle screw |
| IL273982B2 (en) | 2011-08-05 | 2023-03-01 | Regeneron Pharma | Humanized mice possess a universal light chain |
| EP2757875B2 (en) | 2011-09-19 | 2023-03-22 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| WO2013041845A2 (en) | 2011-09-19 | 2013-03-28 | Kymab Limited | Animals, repertoires & methods |
| WO2013045916A1 (en) | 2011-09-26 | 2013-04-04 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| US10246509B2 (en) | 2011-10-17 | 2019-04-02 | Regeneron Pharmaceuticals, Inc. | Restricted immunoglobulin heavy chain mice |
| GB2496375A (en) | 2011-10-28 | 2013-05-15 | Kymab Ltd | A non-human assay vertebrate comprising human antibody loci and human epitope knock-in, and uses thereof |
| US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| GB201122047D0 (en) | 2011-12-21 | 2012-02-01 | Kymab Ltd | Transgenic animals |
| SG11201403326VA (en) | 2011-12-20 | 2014-07-30 | Regeneron Pharma | Humanized light chain mice |
| WO2013116609A1 (en) | 2012-02-01 | 2013-08-08 | Regeneron Pharmaceuticals, Inc. | Humanized rodents that express heavy chains containing vl domains |
| GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
| TWI682941B (zh) | 2013-02-01 | 2020-01-21 | 美商再生元醫藥公司 | 含嵌合恆定區之抗體 |
| US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
| SG10201808935WA (en) | 2013-04-16 | 2018-11-29 | Regeneron Pharma | Targeted modification of rat genome |
| ES2762640T3 (es) | 2014-03-21 | 2020-05-25 | Regeneron Pharma | Proteínas VL de unión a antígeno que exhiben diferentes características de unión |
| BR112016021572A2 (pt) | 2014-03-21 | 2017-10-03 | Regeneron Pharma | Métodos para preparar um animal não humano geneticamente modificado e para produzir proteínas de ligação, hibridoma, ácido nucleico, célula, e, proteína de ligação |
| EP3271403A1 (en) | 2015-03-19 | 2018-01-24 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
-
2011
- 2011-08-02 IL IL315833A patent/IL315833A/en unknown
- 2011-08-02 NZ NZ707327A patent/NZ707327A/en unknown
- 2011-08-02 KR KR1020137004960A patent/KR102008655B1/ko active Active
- 2011-08-02 EP EP15173007.4A patent/EP2947151A1/en not_active Ceased
- 2011-08-02 CA CA3250882A patent/CA3250882A1/en active Pending
- 2011-08-02 SG SG10201912639SA patent/SG10201912639SA/en unknown
- 2011-08-02 ES ES11741730.3T patent/ES2612459T3/es active Active
- 2011-08-02 EP EP11741730.3A patent/EP2601298B1/en active Active
- 2011-08-02 US US13/195,951 patent/US9516868B2/en active Active
- 2011-08-02 WO PCT/US2011/046196 patent/WO2012018764A1/en not_active Ceased
- 2011-08-02 JP JP2013523258A patent/JP6146913B2/ja active Active
- 2011-08-02 MY MYPI2013000340A patent/MY172618A/en unknown
- 2011-08-02 KR KR1020207027965A patent/KR102306967B1/ko active Active
- 2011-08-02 RU RU2013109068A patent/RU2612903C2/ru active
- 2011-08-02 RU RU2017106292A patent/RU2750219C2/ru active
- 2011-08-02 MX MX2017006698A patent/MX363084B/es unknown
- 2011-08-02 IL IL271804A patent/IL271804B2/en unknown
- 2011-08-02 CN CN202410984383.4A patent/CN118791596A/zh active Pending
- 2011-08-02 KR KR1020197022706A patent/KR102163138B1/ko active Active
- 2011-08-02 SM SM20170023T patent/SMT201700023T1/it unknown
- 2011-08-02 PT PT117417303T patent/PT2601298T/pt unknown
- 2011-08-02 CA CA2807282A patent/CA2807282A1/en active Pending
- 2011-08-02 MX MX2013001360A patent/MX345251B/es active IP Right Grant
- 2011-08-02 DK DK11741730.3T patent/DK2601298T3/en active
- 2011-08-02 MX MX2018014787A patent/MX2018014787A/es unknown
- 2011-08-02 SG SG10201504971QA patent/SG10201504971QA/en unknown
- 2011-08-02 CN CN202110412459.2A patent/CN113150121B9/zh active Active
- 2011-08-02 HR HRP20170322TT patent/HRP20170322T1/hr unknown
- 2011-08-02 LT LTEP11741730.3T patent/LT2601298T/lt unknown
- 2011-08-02 BR BR112013002695-2A patent/BR112013002695B1/pt active IP Right Grant
- 2011-08-02 SG SG2013007893A patent/SG187673A1/en unknown
- 2011-08-02 EP EP21174332.3A patent/EP3960865A1/en active Pending
- 2011-08-02 RS RS20161086A patent/RS55495B1/sr unknown
- 2011-08-02 CN CN201610124564.5A patent/CN105753979B/zh active Active
- 2011-08-02 MX MX2016014021A patent/MX350591B/es unknown
- 2011-08-02 SI SI201131072A patent/SI2601298T1/sl unknown
- 2011-08-02 KR KR1020217030387A patent/KR102434557B1/ko active Active
- 2011-08-02 HU HUE11741730A patent/HUE031903T2/en unknown
- 2011-08-02 CN CN201180045609.5A patent/CN103154255B/zh active Active
- 2011-08-02 PL PL11741730T patent/PL2601298T3/pl unknown
- 2011-08-02 NZ NZ606824A patent/NZ606824A/en unknown
- 2011-08-02 AU AU2011285919A patent/AU2011285919C1/en active Active
-
2013
- 2013-01-31 IL IL224523A patent/IL224523B/en active IP Right Grant
- 2013-02-01 MX MX2023001793A patent/MX2023001793A/es unknown
- 2013-12-19 US US14/135,510 patent/US9686970B2/en active Active
- 2013-12-19 US US14/135,518 patent/US20140130194A1/en not_active Abandoned
-
2016
- 2016-01-21 JP JP2016009916A patent/JP2016054746A/ja not_active Withdrawn
- 2016-05-10 HK HK16105319.5A patent/HK1217511A1/en unknown
-
2017
- 2017-01-04 CY CY20171100009T patent/CY1118562T1/el unknown
- 2017-01-16 SM SM201700023T patent/SMT201700023B/it unknown
- 2017-04-25 US US15/497,075 patent/US10954310B2/en active Active
- 2017-04-25 US US15/497,043 patent/US20170226231A1/en not_active Abandoned
-
2018
- 2018-01-04 JP JP2018000123A patent/JP7078400B2/ja active Active
- 2018-03-25 IL IL258338A patent/IL258338B/en active IP Right Grant
- 2018-11-12 JP JP2018212094A patent/JP6759303B2/ja active Active
-
2020
- 2020-02-14 JP JP2020023076A patent/JP7110257B2/ja active Active
-
2021
- 2021-02-05 US US17/168,708 patent/US20210163628A1/en active Pending
- 2021-05-19 JP JP2021084769A patent/JP2021119792A/ja active Pending
- 2021-12-14 US US17/550,839 patent/US12486335B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7110257B2 (ja) | Vlドメインを含む結合タンパク質を作製するマウス | |
| AU2017219079B9 (en) | Mice that make binding proteins comprising vl domains | |
| HK40069751A (en) | Mice that make binding proteins comprising vl domains | |
| HK1181810B (en) | Mice that make binding proteins comprising vl domains | |
| NZ724003B2 (en) | Mice that make binding proteins comprising vl domains |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B06F | Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette] | ||
| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] | ||
| B07G | Grant request does not fulfill article 229-c lpi (prior consent of anvisa) [chapter 7.7 patent gazette] | ||
| B06U | Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette] | ||
| B07A | Application suspended after technical examination (opinion) [chapter 7.1 patent gazette] | ||
| B09A | Decision: intention to grant [chapter 9.1 patent gazette] | ||
| B09X | Republication of the decision to grant [chapter 9.1.3 patent gazette] | ||
| B16A | Patent or certificate of addition of invention granted [chapter 16.1 patent gazette] |
Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 02/08/2011, OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF, QUE DETERMINA A ALTERACAO DO PRAZO DE CONCESSAO. |