ES2986443T3 - Células, vertebrados, poblaciones y métodos - Google Patents
Células, vertebrados, poblaciones y métodos Download PDFInfo
- Publication number
- ES2986443T3 ES2986443T3 ES18743421T ES18743421T ES2986443T3 ES 2986443 T3 ES2986443 T3 ES 2986443T3 ES 18743421 T ES18743421 T ES 18743421T ES 18743421 T ES18743421 T ES 18743421T ES 2986443 T3 ES2986443 T3 ES 2986443T3
- Authority
- ES
- Spain
- Prior art keywords
- cell
- antibody
- domain
- locus
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title claims description 78
- 241000251539 Vertebrata <Metazoa> Species 0.000 title claims description 28
- 241000282414 Homo sapiens Species 0.000 claims abstract description 128
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 210000004027 cell Anatomy 0.000 claims description 259
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 131
- 239000000427 antigen Substances 0.000 claims description 105
- 108091007433 antigens Proteins 0.000 claims description 104
- 102000036639 antigens Human genes 0.000 claims description 104
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 72
- 230000027455 binding Effects 0.000 claims description 70
- 241000699670 Mus sp. Species 0.000 claims description 57
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 44
- 241000283984 Rodentia Species 0.000 claims description 31
- 239000002773 nucleotide Substances 0.000 claims description 29
- 125000003729 nucleotide group Chemical group 0.000 claims description 29
- 210000002459 blastocyst Anatomy 0.000 claims description 28
- 239000003623 enhancer Substances 0.000 claims description 28
- 108090000623 proteins and genes Proteins 0.000 claims description 23
- 108700028369 Alleles Proteins 0.000 claims description 22
- 230000014509 gene expression Effects 0.000 claims description 22
- 108020004414 DNA Proteins 0.000 claims description 19
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 17
- 238000003780 insertion Methods 0.000 claims description 17
- 230000037431 insertion Effects 0.000 claims description 17
- 230000003053 immunization Effects 0.000 claims description 13
- 239000013598 vector Substances 0.000 claims description 12
- 241000700159 Rattus Species 0.000 claims description 9
- 210000004602 germ cell Anatomy 0.000 claims description 9
- 230000035772 mutation Effects 0.000 claims description 9
- 241000894007 species Species 0.000 claims description 8
- 108700019146 Transgenes Proteins 0.000 claims description 7
- 101001005365 Homo sapiens Immunoglobulin lambda variable 3-21 Proteins 0.000 claims description 6
- 102100025934 Immunoglobulin lambda variable 3-21 Human genes 0.000 claims description 6
- 210000001161 mammalian embryo Anatomy 0.000 claims description 6
- 108020004707 nucleic acids Proteins 0.000 claims description 6
- 102000039446 nucleic acids Human genes 0.000 claims description 6
- 150000007523 nucleic acids Chemical class 0.000 claims description 6
- 210000004989 spleen cell Anatomy 0.000 claims description 6
- 230000001413 cellular effect Effects 0.000 claims description 5
- 239000013604 expression vector Substances 0.000 claims description 5
- 230000009261 transgenic effect Effects 0.000 claims description 5
- 210000004899 c-terminal region Anatomy 0.000 claims description 4
- 230000004186 co-expression Effects 0.000 claims description 4
- 230000006798 recombination Effects 0.000 claims description 4
- 238000005215 recombination Methods 0.000 claims description 4
- 101000998952 Homo sapiens Immunoglobulin heavy variable 1-3 Proteins 0.000 claims description 3
- 101000998947 Homo sapiens Immunoglobulin heavy variable 1-46 Proteins 0.000 claims description 3
- 101000998951 Homo sapiens Immunoglobulin heavy variable 1-8 Proteins 0.000 claims description 3
- 101001037138 Homo sapiens Immunoglobulin heavy variable 3-11 Proteins 0.000 claims description 3
- 101001037136 Homo sapiens Immunoglobulin heavy variable 3-15 Proteins 0.000 claims description 3
- 101001037141 Homo sapiens Immunoglobulin heavy variable 3-21 Proteins 0.000 claims description 3
- 101001037140 Homo sapiens Immunoglobulin heavy variable 3-23 Proteins 0.000 claims description 3
- 101001037139 Homo sapiens Immunoglobulin heavy variable 3-30 Proteins 0.000 claims description 3
- 101001037143 Homo sapiens Immunoglobulin heavy variable 3-33 Proteins 0.000 claims description 3
- 101000839662 Homo sapiens Immunoglobulin heavy variable 3-48 Proteins 0.000 claims description 3
- 101000839660 Homo sapiens Immunoglobulin heavy variable 3-53 Proteins 0.000 claims description 3
- 101001037153 Homo sapiens Immunoglobulin heavy variable 3-7 Proteins 0.000 claims description 3
- 101001037144 Homo sapiens Immunoglobulin heavy variable 3-9 Proteins 0.000 claims description 3
- 101000839684 Homo sapiens Immunoglobulin heavy variable 4-31 Proteins 0.000 claims description 3
- 101000839686 Homo sapiens Immunoglobulin heavy variable 4-4 Proteins 0.000 claims description 3
- 101000839781 Homo sapiens Immunoglobulin heavy variable 4-59 Proteins 0.000 claims description 3
- 101000989076 Homo sapiens Immunoglobulin heavy variable 4-61 Proteins 0.000 claims description 3
- 101000989062 Homo sapiens Immunoglobulin heavy variable 5-51 Proteins 0.000 claims description 3
- 101000989060 Homo sapiens Immunoglobulin heavy variable 6-1 Proteins 0.000 claims description 3
- 101000989065 Homo sapiens Immunoglobulin heavy variable 7-4-1 Proteins 0.000 claims description 3
- 102100036886 Immunoglobulin heavy variable 1-3 Human genes 0.000 claims description 3
- 102100036888 Immunoglobulin heavy variable 1-46 Human genes 0.000 claims description 3
- 102100036885 Immunoglobulin heavy variable 1-8 Human genes 0.000 claims description 3
- 102100040222 Immunoglobulin heavy variable 3-11 Human genes 0.000 claims description 3
- 102100040224 Immunoglobulin heavy variable 3-15 Human genes 0.000 claims description 3
- 102100040217 Immunoglobulin heavy variable 3-21 Human genes 0.000 claims description 3
- 102100040220 Immunoglobulin heavy variable 3-23 Human genes 0.000 claims description 3
- 102100040219 Immunoglobulin heavy variable 3-30 Human genes 0.000 claims description 3
- 102100040236 Immunoglobulin heavy variable 3-33 Human genes 0.000 claims description 3
- 102100028320 Immunoglobulin heavy variable 3-48 Human genes 0.000 claims description 3
- 102100028317 Immunoglobulin heavy variable 3-53 Human genes 0.000 claims description 3
- 102100040231 Immunoglobulin heavy variable 3-7 Human genes 0.000 claims description 3
- 102100040234 Immunoglobulin heavy variable 3-9 Human genes 0.000 claims description 3
- 102100028310 Immunoglobulin heavy variable 4-31 Human genes 0.000 claims description 3
- 102100028308 Immunoglobulin heavy variable 4-4 Human genes 0.000 claims description 3
- 102100028405 Immunoglobulin heavy variable 4-59 Human genes 0.000 claims description 3
- 102100029419 Immunoglobulin heavy variable 4-61 Human genes 0.000 claims description 3
- 102100029414 Immunoglobulin heavy variable 5-51 Human genes 0.000 claims description 3
- 102100029416 Immunoglobulin heavy variable 6-1 Human genes 0.000 claims description 3
- 102100029420 Immunoglobulin heavy variable 7-4-1 Human genes 0.000 claims description 3
- 210000004408 hybridoma Anatomy 0.000 claims description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 2
- 101000839682 Homo sapiens Immunoglobulin heavy variable 4-34 Proteins 0.000 claims description 2
- 102100028306 Immunoglobulin heavy variable 4-34 Human genes 0.000 claims description 2
- 230000008707 rearrangement Effects 0.000 claims description 2
- 238000011830 transgenic mouse model Methods 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 3
- 101000998950 Homo sapiens Immunoglobulin heavy variable 1-18 Proteins 0.000 claims 2
- 101001037142 Homo sapiens Immunoglobulin heavy variable 3-20 Proteins 0.000 claims 2
- 101000839679 Homo sapiens Immunoglobulin heavy variable 4-39 Proteins 0.000 claims 2
- 101000854886 Homo sapiens Immunoglobulin iota chain Proteins 0.000 claims 2
- 101001091242 Homo sapiens Immunoglobulin kappa joining 1 Proteins 0.000 claims 2
- 102100036884 Immunoglobulin heavy variable 1-18 Human genes 0.000 claims 2
- 102100040218 Immunoglobulin heavy variable 3-20 Human genes 0.000 claims 2
- 102100028312 Immunoglobulin heavy variable 4-39 Human genes 0.000 claims 2
- 102100020744 Immunoglobulin iota chain Human genes 0.000 claims 2
- 102100034892 Immunoglobulin kappa joining 1 Human genes 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 101001138089 Homo sapiens Immunoglobulin kappa variable 1-39 Proteins 0.000 claims 1
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 claims 1
- 102100020910 Immunoglobulin kappa variable 1-39 Human genes 0.000 claims 1
- 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 claims 1
- 210000000628 antibody-producing cell Anatomy 0.000 claims 1
- 230000000890 antigenic effect Effects 0.000 claims 1
- 210000000601 blood cell Anatomy 0.000 claims 1
- 210000002798 bone marrow cell Anatomy 0.000 claims 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims 1
- 239000013611 chromosomal DNA Substances 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 230000006801 homologous recombination Effects 0.000 claims 1
- 238000002744 homologous recombination Methods 0.000 claims 1
- 238000013518 transcription Methods 0.000 claims 1
- 230000035897 transcription Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract description 4
- 238000003745 diagnosis Methods 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 description 36
- 239000002609 medium Substances 0.000 description 24
- 241000288906 Primates Species 0.000 description 23
- 239000000872 buffer Substances 0.000 description 18
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 18
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 14
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 14
- 230000002950 deficient Effects 0.000 description 13
- 238000004520 electroporation Methods 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 210000000952 spleen Anatomy 0.000 description 13
- 230000008685 targeting Effects 0.000 description 13
- 239000006285 cell suspension Substances 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 238000002649 immunization Methods 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000005516 engineering process Methods 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
- 230000003393 splenic effect Effects 0.000 description 10
- 238000001890 transfection Methods 0.000 description 10
- 108090000631 Trypsin Proteins 0.000 description 9
- 102000004142 Trypsin Human genes 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000012588 trypsin Substances 0.000 description 9
- 238000010494 dissociation reaction Methods 0.000 description 8
- 230000005593 dissociations Effects 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 238000007481 next generation sequencing Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000003550 marker Substances 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 101000889461 Mus musculus Trefoil factor 2 Proteins 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 238000007857 nested PCR Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000004458 analytical method Methods 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
- 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
- 150000001413 amino acids Chemical group 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000008014 freezing Effects 0.000 description 4
- 238000007710 freezing Methods 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 101710145634 Antigen 1 Proteins 0.000 description 3
- 241000282693 Cercopithecidae Species 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
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 3
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 3
- 239000012515 MabSelect SuRe Substances 0.000 description 3
- 229940037003 alum Drugs 0.000 description 3
- 239000002299 complementary DNA Substances 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
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 238000011813 knockout mouse model Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000000520 microinjection Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000012146 running buffer Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000000392 somatic effect Effects 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 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
- 239000004471 Glycine Substances 0.000 description 2
- 239000012124 Opti-MEM Substances 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 239000002671 adjuvant 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
- 238000003766 bioinformatics method Methods 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 239000003085 diluting agent 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
- 210000002257 embryonic structure Anatomy 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000008569 process Effects 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
- 239000000725 suspension Substances 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 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 1
- 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
- CGTRVJQMKJCCRF-UHFFFAOYSA-N 3-(3-carbazol-9-ylphenyl)-9-[3-[3-(3-carbazol-9-ylphenyl)carbazol-9-yl]phenyl]carbazole Chemical compound C12=CC=CC=C2C2=CC(C=3C=CC=C(C=3)N3C4=CC=CC=C4C4=CC=CC=C43)=CC=C2N1C1=CC=CC(N2C3=CC=C(C=C3C3=CC=CC=C32)C=2C=C(C=CC=2)N2C3=CC=CC=C3C3=CC=CC=C32)=C1 CGTRVJQMKJCCRF-UHFFFAOYSA-N 0.000 description 1
- 241000700114 Chinchillidae Species 0.000 description 1
- 241000699800 Cricetinae Species 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
- 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
- 241001272567 Hominoidea Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 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
- 241001465754 Metazoa Species 0.000 description 1
- 241000699729 Muridae Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000282520 Papio Species 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
- 102000001183 RAG-1 Human genes 0.000 description 1
- 108060006897 RAG1 Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 235000011449 Rosa Nutrition 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 108010032099 V(D)J recombination activating protein 2 Proteins 0.000 description 1
- 102100029591 V(D)J recombination-activating protein 2 Human genes 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000010420 art technique Methods 0.000 description 1
- 229960003008 blinatumomab Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 229960000419 catumaxomab Drugs 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying 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
- 238000000605 extraction Methods 0.000 description 1
- 239000012595 freezing medium Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- 102000054584 human Y acceptor Human genes 0.000 description 1
- 108700023876 human Y acceptor Proteins 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000003519 mature b lymphocyte Anatomy 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
- 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
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001105 regulatory 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
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000012536 storage buffer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 238000011144 upstream manufacturing Methods 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 |
|---|---|---|---|
| GBGB1710984.4A GB201710984D0 (en) | 2017-07-07 | 2017-07-07 | Cells, vertebrates, populations & methods |
| PCT/EP2018/068309 WO2019008123A2 (en) | 2017-07-07 | 2018-07-05 | CELLS, VERTEBRATES, POPULATIONS AND METHODS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2986443T3 true ES2986443T3 (es) | 2024-11-11 |
Family
ID=59676641
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18743421T Active ES2986443T3 (es) | 2017-07-07 | 2018-07-05 | Células, vertebrados, poblaciones y métodos |
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 |
Family Cites Families (13)
| 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 |
| RU2559524C2 (ru) * | 2008-06-27 | 2015-08-10 | Мерюс Б.В. | Продуцирующие антитела млекопитающие, не являющиеся человеком |
| 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 |
| US9253965B2 (en) * | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| 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
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 |
| EP3648587B1 (en) | 2024-05-29 |
| TWI820030B (zh) | 2023-11-01 |
| 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 |
|---|---|---|
| ES2986443T3 (es) | Células, vertebrados, poblaciones y métodos | |
| JP6960005B2 (ja) | 共通の軽鎖のマウス | |
| JP7010902B2 (ja) | 限られた免疫グロブリン軽鎖レパートリーを発現するマウス | |
| ES2849349T3 (es) | Anticuerpos de cadena ligera modificados mediante ingeniería con histidina y roedores modificados genéticamente para la generación de los mismos | |
| US10966412B2 (en) | Animal models and therapeutic molecules | |
| JP6574811B2 (ja) | ｐＨ感受性免疫グロブリン配列を発現する非ヒト動物 | |
| ES2573828T5 (es) | Animales no humanos que expresan anticuerpos con una cadena ligera común | |
| CN104244709B (zh) | 共同轻链小鼠 | |
| CN104582476B (zh) | 使用共同轻链制备完全人双特异性抗体的方法 | |
| ES2962489T3 (es) | Anticuerpos de cadena ligera diseñados genéticamente con histidina y animales no humanos modificados genéticamente para generar los mismos | |
| JP2021118746A (ja) | ヒト化ユニバーサル軽鎖マウス | |
| WO2013144566A2 (en) | Animal models and therapeutic molecules | |
| GB2496375A (en) | A non-human assay vertebrate comprising human antibody loci and human epitope knock-in, and uses thereof | |
| HK40114663A (en) | Cells, vertebrates, populations & methods | |
| HK40026551A (en) | Cells, vertebrates, populations & methods | |
| HK40026551B (en) | Cells, vertebrates, populations & methods | |
| RU2812814C2 (ru) | Мыши, экспрессирующие ограниченный репертуар легких цепей иммуноглобулина | |
| CN120712013A (zh) | 表达共同轻链的啮齿动物 |