TWI820030B - 細胞、脊椎動物、群體及方法 - Google Patents
細胞、脊椎動物、群體及方法 Download PDFInfo
- Publication number
- TWI820030B TWI820030B TW107123525A TW107123525A TWI820030B TW I820030 B TWI820030 B TW I820030B TW 107123525 A TW107123525 A TW 107123525A TW 107123525 A TW107123525 A TW 107123525A TW I820030 B TWI820030 B TW I820030B
- Authority
- TW
- Taiwan
- Prior art keywords
- antibody
- cell
- domain
- light chain
- heavy chain
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 176
- 241000251539 Vertebrata <Metazoa> Species 0.000 title claims description 71
- 241000282414 Homo sapiens Species 0.000 claims abstract description 306
- 210000004027 cell Anatomy 0.000 claims description 636
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 210
- 239000000427 antigen Substances 0.000 claims description 205
- 108091007433 antigens Proteins 0.000 claims description 204
- 102000036639 antigens Human genes 0.000 claims description 204
- 239000003623 enhancer Substances 0.000 claims description 146
- 230000027455 binding Effects 0.000 claims description 136
- 239000002773 nucleotide Substances 0.000 claims description 109
- 125000003729 nucleotide group Chemical group 0.000 claims description 109
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 73
- 241000700159 Rattus Species 0.000 claims description 66
- 108090000623 proteins and genes Proteins 0.000 claims description 65
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 63
- 241000283984 Rodentia Species 0.000 claims description 31
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 29
- 150000007523 nucleic acids Chemical group 0.000 claims description 29
- 241000894007 species Species 0.000 claims description 29
- 108020004707 nucleic acids Proteins 0.000 claims description 27
- 102000039446 nucleic acids Human genes 0.000 claims description 27
- 108020004414 DNA Proteins 0.000 claims description 22
- 108700019146 Transgenes Proteins 0.000 claims description 21
- 210000004602 germ cell Anatomy 0.000 claims description 21
- 239000013598 vector Substances 0.000 claims description 20
- 238000004519 manufacturing process Methods 0.000 claims description 18
- 230000035772 mutation Effects 0.000 claims description 18
- 230000006798 recombination Effects 0.000 claims description 18
- 238000005215 recombination Methods 0.000 claims description 18
- 210000004899 c-terminal region Anatomy 0.000 claims description 17
- 206010028980 Neoplasm Diseases 0.000 claims description 16
- 239000013604 expression vector Substances 0.000 claims description 16
- 239000004570 mortar (masonry) Substances 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 14
- 210000000952 spleen Anatomy 0.000 claims description 14
- 238000003780 insertion Methods 0.000 claims description 13
- 230000037431 insertion Effects 0.000 claims description 13
- 230000004927 fusion Effects 0.000 claims description 12
- 101000998950 Homo sapiens Immunoglobulin heavy variable 1-18 Proteins 0.000 claims description 11
- 101000998952 Homo sapiens Immunoglobulin heavy variable 1-3 Proteins 0.000 claims description 11
- 101000998947 Homo sapiens Immunoglobulin heavy variable 1-46 Proteins 0.000 claims description 11
- 101001037138 Homo sapiens Immunoglobulin heavy variable 3-11 Proteins 0.000 claims description 11
- 101001037136 Homo sapiens Immunoglobulin heavy variable 3-15 Proteins 0.000 claims description 11
- 101001037140 Homo sapiens Immunoglobulin heavy variable 3-23 Proteins 0.000 claims description 11
- 101001037139 Homo sapiens Immunoglobulin heavy variable 3-30 Proteins 0.000 claims description 11
- 101001037143 Homo sapiens Immunoglobulin heavy variable 3-33 Proteins 0.000 claims description 11
- 101000839662 Homo sapiens Immunoglobulin heavy variable 3-48 Proteins 0.000 claims description 11
- 101000839660 Homo sapiens Immunoglobulin heavy variable 3-53 Proteins 0.000 claims description 11
- 101001037153 Homo sapiens Immunoglobulin heavy variable 3-7 Proteins 0.000 claims description 11
- 101001037144 Homo sapiens Immunoglobulin heavy variable 3-9 Proteins 0.000 claims description 11
- 101000839682 Homo sapiens Immunoglobulin heavy variable 4-34 Proteins 0.000 claims description 11
- 101000839679 Homo sapiens Immunoglobulin heavy variable 4-39 Proteins 0.000 claims description 11
- 101000989076 Homo sapiens Immunoglobulin heavy variable 4-61 Proteins 0.000 claims description 11
- 101000989060 Homo sapiens Immunoglobulin heavy variable 6-1 Proteins 0.000 claims description 11
- 101001005365 Homo sapiens Immunoglobulin lambda variable 3-21 Proteins 0.000 claims description 11
- 102100036884 Immunoglobulin heavy variable 1-18 Human genes 0.000 claims description 11
- 102100036886 Immunoglobulin heavy variable 1-3 Human genes 0.000 claims description 11
- 102100036888 Immunoglobulin heavy variable 1-46 Human genes 0.000 claims description 11
- 102100040222 Immunoglobulin heavy variable 3-11 Human genes 0.000 claims description 11
- 102100040224 Immunoglobulin heavy variable 3-15 Human genes 0.000 claims description 11
- 102100040220 Immunoglobulin heavy variable 3-23 Human genes 0.000 claims description 11
- 102100040219 Immunoglobulin heavy variable 3-30 Human genes 0.000 claims description 11
- 102100040236 Immunoglobulin heavy variable 3-33 Human genes 0.000 claims description 11
- 102100028320 Immunoglobulin heavy variable 3-48 Human genes 0.000 claims description 11
- 102100028317 Immunoglobulin heavy variable 3-53 Human genes 0.000 claims description 11
- 102100040231 Immunoglobulin heavy variable 3-7 Human genes 0.000 claims description 11
- 102100040234 Immunoglobulin heavy variable 3-9 Human genes 0.000 claims description 11
- 102100028306 Immunoglobulin heavy variable 4-34 Human genes 0.000 claims description 11
- 102100028312 Immunoglobulin heavy variable 4-39 Human genes 0.000 claims description 11
- 102100029419 Immunoglobulin heavy variable 4-61 Human genes 0.000 claims description 11
- 102100029416 Immunoglobulin heavy variable 6-1 Human genes 0.000 claims description 11
- 102100025934 Immunoglobulin lambda variable 3-21 Human genes 0.000 claims description 11
- 238000012258 culturing Methods 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 101000998951 Homo sapiens Immunoglobulin heavy variable 1-8 Proteins 0.000 claims description 10
- 101001037141 Homo sapiens Immunoglobulin heavy variable 3-21 Proteins 0.000 claims description 10
- 101000839684 Homo sapiens Immunoglobulin heavy variable 4-31 Proteins 0.000 claims description 10
- 101000839686 Homo sapiens Immunoglobulin heavy variable 4-4 Proteins 0.000 claims description 10
- 101000989065 Homo sapiens Immunoglobulin heavy variable 7-4-1 Proteins 0.000 claims description 10
- 102100036885 Immunoglobulin heavy variable 1-8 Human genes 0.000 claims description 10
- 102100040217 Immunoglobulin heavy variable 3-21 Human genes 0.000 claims description 10
- 102100028310 Immunoglobulin heavy variable 4-31 Human genes 0.000 claims description 10
- 102100028308 Immunoglobulin heavy variable 4-4 Human genes 0.000 claims description 10
- 102100029420 Immunoglobulin heavy variable 7-4-1 Human genes 0.000 claims description 10
- 101001037142 Homo sapiens Immunoglobulin heavy variable 3-20 Proteins 0.000 claims description 9
- 101000839781 Homo sapiens Immunoglobulin heavy variable 4-59 Proteins 0.000 claims description 9
- 101000989062 Homo sapiens Immunoglobulin heavy variable 5-51 Proteins 0.000 claims description 9
- 102100040218 Immunoglobulin heavy variable 3-20 Human genes 0.000 claims description 9
- 102100028405 Immunoglobulin heavy variable 4-59 Human genes 0.000 claims description 9
- 102100029414 Immunoglobulin heavy variable 5-51 Human genes 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 210000001185 bone marrow Anatomy 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 210000000601 blood cell Anatomy 0.000 claims description 7
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 7
- 230000006801 homologous recombination Effects 0.000 claims description 7
- 238000002744 homologous recombination Methods 0.000 claims description 7
- 101001091242 Homo sapiens Immunoglobulin kappa joining 1 Proteins 0.000 claims description 6
- 102100034892 Immunoglobulin kappa joining 1 Human genes 0.000 claims description 6
- 101000854886 Homo sapiens Immunoglobulin iota chain Proteins 0.000 claims description 5
- 102100020744 Immunoglobulin iota chain Human genes 0.000 claims description 5
- 230000001413 cellular effect Effects 0.000 claims description 5
- 230000008707 rearrangement Effects 0.000 claims description 5
- 238000013518 transcription Methods 0.000 claims description 5
- 230000035897 transcription Effects 0.000 claims description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 4
- 108700028146 Genetic Enhancer Elements Proteins 0.000 claims description 4
- 210000000628 antibody-producing cell Anatomy 0.000 claims description 4
- 239000013611 chromosomal DNA Substances 0.000 claims description 4
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 claims description 3
- 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 claims description 3
- 210000004881 tumor cell Anatomy 0.000 claims description 3
- 101001138089 Homo sapiens Immunoglobulin kappa variable 1-39 Proteins 0.000 claims description 2
- -1 IGHV3 -20 Proteins 0.000 claims description 2
- 102100020910 Immunoglobulin kappa variable 1-39 Human genes 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 230000009977 dual effect Effects 0.000 claims 1
- 230000003362 replicative effect Effects 0.000 claims 1
- 238000003745 diagnosis Methods 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 79
- 239000000203 mixture Substances 0.000 description 46
- 239000002609 medium Substances 0.000 description 24
- 108700028369 Alleles Proteins 0.000 description 20
- 210000000472 morula Anatomy 0.000 description 19
- 239000000872 buffer Substances 0.000 description 18
- 239000012634 fragment Substances 0.000 description 18
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 18
- 210000002459 blastocyst Anatomy 0.000 description 16
- 230000008685 targeting Effects 0.000 description 16
- 230000014509 gene expression Effects 0.000 description 15
- 230000003393 splenic effect Effects 0.000 description 15
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 14
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 14
- 150000001413 amino acids Chemical group 0.000 description 14
- 230000003053 immunization Effects 0.000 description 14
- 238000004520 electroporation Methods 0.000 description 13
- 230000009261 transgenic effect Effects 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 12
- 241000288906 Primates Species 0.000 description 11
- 108090000631 Trypsin Proteins 0.000 description 11
- 102000004142 Trypsin Human genes 0.000 description 11
- 238000002649 immunization Methods 0.000 description 11
- 238000007481 next generation sequencing Methods 0.000 description 11
- 239000012588 trypsin Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000006285 cell suspension Substances 0.000 description 10
- 238000012217 deletion Methods 0.000 description 10
- 230000037430 deletion Effects 0.000 description 10
- 210000001161 mammalian embryo Anatomy 0.000 description 10
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 10
- 238000001890 transfection Methods 0.000 description 10
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- 238000010494 dissociation reaction Methods 0.000 description 7
- 230000005593 dissociations Effects 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 230000001588 bifunctional effect Effects 0.000 description 6
- 238000000520 microinjection Methods 0.000 description 6
- 238000007857 nested PCR Methods 0.000 description 6
- 210000002706 plastid Anatomy 0.000 description 6
- 230000037452 priming Effects 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 238000011740 C57BL/6 mouse Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 210000001109 blastomere Anatomy 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 229950010131 puromycin Drugs 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- BDEDPKFUFGCVCJ-UHFFFAOYSA-N 3,6-dihydroxy-8,8-dimethyl-1-oxo-3,4,7,9-tetrahydrocyclopenta[h]isochromene-5-carbaldehyde Chemical compound O=C1OC(O)CC(C(C=O)=C2O)=C1C1=C2CC(C)(C)C1 BDEDPKFUFGCVCJ-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000002308 embryonic cell Anatomy 0.000 description 4
- 210000002257 embryonic structure Anatomy 0.000 description 4
- 230000008014 freezing Effects 0.000 description 4
- 238000007710 freezing Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 210000004989 spleen cell Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000012515 MabSelect SuRe Substances 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102000001183 RAG-1 Human genes 0.000 description 3
- 108060006897 RAG1 Proteins 0.000 description 3
- 108010032099 V(D)J recombination activating protein 2 Proteins 0.000 description 3
- 102100029591 V(D)J recombination-activating protein 2 Human genes 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000012146 running buffer Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 235000012431 wafers Nutrition 0.000 description 3
- 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 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 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
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=C(N)C=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 2
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 101100476210 Caenorhabditis elegans rnt-1 gene Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 241001272567 Hominoidea Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 235000011449 Rosa Nutrition 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 108010068991 arginyl-threonyl-prolyl-prolyl-prolyl-seryl-glycine Proteins 0.000 description 2
- 238000003766 bioinformatics method Methods 0.000 description 2
- 201000000053 blastoma Diseases 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000000375 direct analysis in real time Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000012063 dual-affinity re-targeting Methods 0.000 description 2
- 201000008184 embryoma Diseases 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 238000007480 sanger sequencing Methods 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 210000004988 splenocyte Anatomy 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 102000006822 Agouti Signaling Protein Human genes 0.000 description 1
- 108010072151 Agouti Signaling Protein Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000700114 Chinchillidae Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000484025 Cuniculus Species 0.000 description 1
- 101150097493 D gene Proteins 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 241001481760 Erethizon dorsatum Species 0.000 description 1
- 241001302160 Escherichia coli str. K-12 substr. DH10B Species 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- 241000282575 Gorilla Species 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
- 101001138544 Homo sapiens UMP-CMP kinase Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 101150008942 J gene Proteins 0.000 description 1
- 241000288903 Lemuridae Species 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 240000008821 Menyanthes trifoliata Species 0.000 description 1
- 235000011779 Menyanthes trifoliata Nutrition 0.000 description 1
- 241000699729 Muridae Species 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- 239000012570 Opti-MEM I medium Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000282520 Papio Species 0.000 description 1
- 101800005164 Peptide V Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000282405 Pongo abelii Species 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960003008 blinatumomab Drugs 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 229960000419 catumaxomab Drugs 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 230000009483 enzymatic pathway Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000012595 freezing medium Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000003519 mature b lymphocyte Anatomy 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000012536 storage buffer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 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
- 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
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0276—Knock-out vertebrates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- 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
-
- 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
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/01—Animal expressing industrially exogenous proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—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
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—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
- C07K2317/515—Complete light chain, i.e. VL + CL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- 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
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Environmental Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1710984.4 | 2017-07-07 | ||
| GBGB1710984.4A GB201710984D0 (en) | 2017-07-07 | 2017-07-07 | Cells, vertebrates, populations & methods |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201907010A TW201907010A (zh) | 2019-02-16 |
| TWI820030B true TWI820030B (zh) | 2023-11-01 |
Family
ID=59676641
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW107123525A TWI820030B (zh) | 2017-07-07 | 2018-07-06 | 細胞、脊椎動物、群體及方法 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20200214274A1 (enExample) |
| EP (2) | EP3648587B8 (enExample) |
| JP (1) | JP7288892B2 (enExample) |
| ES (1) | ES2986443T3 (enExample) |
| GB (1) | GB201710984D0 (enExample) |
| HU (1) | HUE068193T2 (enExample) |
| PL (1) | PL3648587T3 (enExample) |
| TW (1) | TWI820030B (enExample) |
| WO (1) | WO2019008123A2 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3028565B1 (en) | 2009-07-08 | 2017-09-27 | Kymab Limited | Animal models and therapeutic molecules |
| EP2757875B2 (en) | 2011-09-19 | 2023-03-22 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| US10251377B2 (en) | 2012-03-28 | 2019-04-09 | Kymab Limited | Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies |
| GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
| US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
| 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 |
| WO2015049517A2 (en) | 2013-10-01 | 2015-04-09 | Kymab Limited | Animal models and therapeutic molecules |
| PL3720279T3 (pl) * | 2017-12-05 | 2023-01-16 | Regeneron Pharmaceuticals, Inc. | Myszy posiadające zmodyfikowany sposobami inżynierii łańcuch lekki lambda immunoglobuliny oraz ich zastosowania |
| AU2020226445B2 (en) | 2019-02-18 | 2025-05-29 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animals with humanized immunoglobulin locus |
| JP2022532388A (ja) * | 2019-05-15 | 2022-07-14 | カイマブ・リミテッド | 改善されたラムダ抗体 |
| GB2590642B (en) * | 2019-12-20 | 2024-02-14 | Kymab Ltd | Improved lambda antibodies |
| CA3136478A1 (en) * | 2019-06-05 | 2020-12-10 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a limited lambda light chain repertoire expressed from the kappa locus and uses thereof |
| AU2021283564B2 (en) * | 2020-06-02 | 2025-05-29 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animals with common light chain immunoglobulin locus |
| EP4211155A1 (en) | 2020-09-11 | 2023-07-19 | Regeneron Pharmaceuticals, Inc. | Identification and production of antigen-specific antibodies |
| EP4262373A1 (en) | 2020-12-16 | 2023-10-25 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized fc alpha receptors |
| GB202107372D0 (en) | 2021-05-24 | 2021-07-07 | Petmedix Ltd | Animal models and therapeutics molecules |
| GB202209247D0 (en) | 2022-06-23 | 2022-08-10 | Petmedix Ltd | Animal models and therapeutic molecules |
| GB202216503D0 (en) | 2022-11-05 | 2022-12-21 | Quadrucept Bio Ltd | Non-human vertebrates & cells |
| GB202217978D0 (en) | 2022-11-30 | 2023-01-11 | Petmedix Ltd | Rodents expressing a common light chain |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102123582A (zh) * | 2008-06-27 | 2011-07-13 | 莫鲁斯有限公司 | 产生抗体的非人哺乳动物 |
| CN104334732A (zh) * | 2012-03-28 | 2015-02-04 | 科马布有限公司 | 表达人λ免疫球蛋白轻链可变结构域的动物 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7041871B1 (en) * | 1995-10-10 | 2006-05-09 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| EP0979281B1 (en) | 1997-05-02 | 2005-07-20 | Genentech, Inc. | A method for making multispecific antibodies having heteromultimeric and common components |
| SI1523496T1 (sl) * | 2002-07-18 | 2011-11-30 | Merus B V | Rekombinantno proizvajanje zmesi protiteles |
| EP2395017A3 (en) | 2003-05-30 | 2012-12-19 | Merus B.V. | Design and use of paired variable regions of specific binding molecules |
| WO2006117699A2 (en) * | 2005-04-29 | 2006-11-09 | Innate Pharma | Transgenic animals and methods of making recombinant antibodies |
| US20120021409A1 (en) * | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| SMT201900372T1 (it) * | 2010-02-08 | 2019-09-09 | Regeneron Pharma | Topo con catena leggera comune |
| RS57582B1 (sr) * | 2013-02-20 | 2018-11-30 | Regeneron Pharma | Nehumane životinje sa modifikovanim sekvencama imunoglobulinskog teškog lanca |
| RU2015143108A (ru) | 2013-03-13 | 2017-04-20 | Регенерон Фарматютикалз, Инк. | Мышь с общей легкой цепью |
| GB201316644D0 (en) | 2013-09-19 | 2013-11-06 | Kymab Ltd | Expression vector production & High-Throughput cell screening |
-
2017
- 2017-07-07 GB GBGB1710984.4A patent/GB201710984D0/en not_active Ceased
-
2018
- 2018-07-05 EP EP18743421.2A patent/EP3648587B8/en active Active
- 2018-07-05 JP JP2020500127A patent/JP7288892B2/ja active Active
- 2018-07-05 WO PCT/EP2018/068309 patent/WO2019008123A2/en not_active Ceased
- 2018-07-05 PL PL18743421.2T patent/PL3648587T3/pl unknown
- 2018-07-05 HU HUE18743421A patent/HUE068193T2/hu unknown
- 2018-07-05 ES ES18743421T patent/ES2986443T3/es active Active
- 2018-07-05 EP EP24178098.0A patent/EP4410986A3/en active Pending
- 2018-07-06 TW TW107123525A patent/TWI820030B/zh active
-
2019
- 2019-12-19 US US16/721,326 patent/US20200214274A1/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102123582A (zh) * | 2008-06-27 | 2011-07-13 | 莫鲁斯有限公司 | 产生抗体的非人哺乳动物 |
| CN104334732A (zh) * | 2012-03-28 | 2015-02-04 | 科马布有限公司 | 表达人λ免疫球蛋白轻链可变结构域的动物 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019008123A2 (en) | 2019-01-10 |
| US20200214274A1 (en) | 2020-07-09 |
| GB201710984D0 (en) | 2017-08-23 |
| WO2019008123A3 (en) | 2019-02-14 |
| ES2986443T3 (es) | 2024-11-11 |
| EP3648587B1 (en) | 2024-05-29 |
| EP4410986A2 (en) | 2024-08-07 |
| EP3648587A2 (en) | 2020-05-13 |
| EP3648587C0 (en) | 2024-05-29 |
| JP2020530760A (ja) | 2020-10-29 |
| TW201907010A (zh) | 2019-02-16 |
| EP3648587B8 (en) | 2024-10-16 |
| EP4410986A3 (en) | 2024-12-18 |
| JP7288892B2 (ja) | 2023-06-08 |
| HUE068193T2 (hu) | 2024-12-28 |
| PL3648587T3 (pl) | 2025-03-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI820030B (zh) | 細胞、脊椎動物、群體及方法 | |
| US11224207B2 (en) | Non-human animals expressing pH-sensitive immunoglobulin sequences | |
| JP2024091957A (ja) | 改変された重鎖のみの抗体を産生するトランスジェニック非ヒト動物 | |
| AU2013204579B2 (en) | Histidine engineered light chain antibodies and genetically modified non-human animals for generating the same | |
| CN108611369B (zh) | 表达限制的免疫球蛋白轻链库的小鼠 | |
| CN105722387B (zh) | 组氨酸工程改造的轻链抗体和用于生成所述抗体的经基因修饰的非人动物 | |
| US20190029237A1 (en) | Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same | |
| KR20150023535A (ko) | 공통 경쇄를 사용하여 완전한 인간 이중 특이적 항체를 만드는 방법 | |
| WO2018011573A1 (en) | Animals, cells, ligands, polypeptides & methods | |
| HK40114663A (en) | Cells, vertebrates, populations & methods | |
| HK40026551A (en) | Cells, vertebrates, populations & methods | |
| HK40026551B (en) | Cells, vertebrates, populations & methods | |
| US12495776B2 (en) | Transgenic non-human animals producing modified heavy chain-only antibodies | |
| CN120712013A (zh) | 表达共同轻链的啮齿动物 |