CA2867530A1 - Animal models and therapeutic molecules - Google Patents
Animal models and therapeutic molecules Download PDFInfo
- Publication number
- CA2867530A1 CA2867530A1 CA2867530A CA2867530A CA2867530A1 CA 2867530 A1 CA2867530 A1 CA 2867530A1 CA 2867530 A CA2867530 A CA 2867530A CA 2867530 A CA2867530 A CA 2867530A CA 2867530 A1 CA2867530 A1 CA 2867530A1
- Authority
- CA
- Canada
- Prior art keywords
- human
- lambda
- vertebrate
- cell
- kappa
- 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.)
- Abandoned
Links
- 230000001225 therapeutic effect Effects 0.000 title description 6
- 238000010171 animal model Methods 0.000 title description 3
- 241000282414 Homo sapiens Species 0.000 claims abstract description 1856
- 238000000034 method Methods 0.000 claims abstract description 245
- 210000004027 cell Anatomy 0.000 claims description 691
- 108090000623 proteins and genes Proteins 0.000 claims description 489
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims description 486
- 238000003780 insertion Methods 0.000 claims description 290
- 230000037431 insertion Effects 0.000 claims description 290
- 238000011144 upstream manufacturing Methods 0.000 claims description 175
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 158
- 108091007433 antigens Proteins 0.000 claims description 150
- 102000036639 antigens Human genes 0.000 claims description 150
- 239000000427 antigen Substances 0.000 claims description 149
- 230000014509 gene expression Effects 0.000 claims description 149
- 210000002966 serum Anatomy 0.000 claims description 121
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims description 98
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims description 98
- 239000003623 enhancer Substances 0.000 claims description 92
- 230000006798 recombination Effects 0.000 claims description 89
- 238000005215 recombination Methods 0.000 claims description 89
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 79
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 79
- 230000003393 splenic effect Effects 0.000 claims description 79
- 108700028369 Alleles Proteins 0.000 claims description 56
- 108060003951 Immunoglobulin Proteins 0.000 claims description 55
- 102000018358 immunoglobulin Human genes 0.000 claims description 55
- 101150008942 J gene Proteins 0.000 claims description 46
- 238000004519 manufacturing process Methods 0.000 claims description 41
- 101150117115 V gene Proteins 0.000 claims description 26
- 108020004707 nucleic acids Proteins 0.000 claims description 24
- 102000039446 nucleic acids Human genes 0.000 claims description 24
- 150000007523 nucleic acids Chemical class 0.000 claims description 24
- 210000001185 bone marrow Anatomy 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 17
- 230000003053 immunization Effects 0.000 claims description 17
- 230000000415 inactivating effect Effects 0.000 claims description 14
- 210000000130 stem cell Anatomy 0.000 claims description 13
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 12
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 12
- 238000011534 incubation Methods 0.000 claims description 12
- 238000011002 quantification Methods 0.000 claims description 12
- 108700028146 Genetic Enhancer Elements Proteins 0.000 claims description 11
- 101150111062 C gene Proteins 0.000 claims description 5
- 210000003519 mature b lymphocyte Anatomy 0.000 claims description 5
- 241000701959 Escherichia virus Lambda Species 0.000 claims 9
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 claims 5
- 239000013598 vector Substances 0.000 abstract description 57
- 239000000203 mixture Substances 0.000 abstract description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 692
- 108020004414 DNA Proteins 0.000 description 238
- 241000700159 Rattus Species 0.000 description 177
- 241000124008 Mammalia Species 0.000 description 105
- 210000000349 chromosome Anatomy 0.000 description 96
- 239000002773 nucleotide Substances 0.000 description 81
- 125000003729 nucleotide group Chemical group 0.000 description 81
- 239000012634 fragment Substances 0.000 description 74
- 210000004602 germ cell Anatomy 0.000 description 59
- 230000009261 transgenic effect Effects 0.000 description 54
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 50
- 239000003550 marker Substances 0.000 description 38
- 210000003917 human chromosome Anatomy 0.000 description 29
- 210000004408 hybridoma Anatomy 0.000 description 29
- 210000001519 tissue Anatomy 0.000 description 29
- 108091028043 Nucleic acid sequence Proteins 0.000 description 28
- 238000011161 development Methods 0.000 description 27
- 230000018109 developmental process Effects 0.000 description 27
- 108091092195 Intron Proteins 0.000 description 26
- 230000002779 inactivation Effects 0.000 description 24
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 23
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 23
- 108091026890 Coding region Proteins 0.000 description 22
- 241000699670 Mus sp. Species 0.000 description 21
- 230000000977 initiatory effect Effects 0.000 description 21
- 241001465754 Metazoa Species 0.000 description 20
- 238000001727 in vivo Methods 0.000 description 20
- 230000002103 transcriptional effect Effects 0.000 description 19
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 18
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 18
- 210000000952 spleen Anatomy 0.000 description 18
- 108010091086 Recombinases Proteins 0.000 description 17
- 102000018120 Recombinases Human genes 0.000 description 17
- 238000002744 homologous recombination Methods 0.000 description 17
- 230000006801 homologous recombination Effects 0.000 description 17
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 17
- 101150097493 D gene Proteins 0.000 description 16
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
- 239000000523 sample Substances 0.000 description 16
- 241000894007 species Species 0.000 description 16
- 230000008707 rearrangement Effects 0.000 description 14
- 230000035772 mutation Effects 0.000 description 12
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 108700024394 Exon Proteins 0.000 description 10
- 239000008194 pharmaceutical composition Substances 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 239000003085 diluting agent Substances 0.000 description 9
- 239000003937 drug carrier Substances 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- 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 8
- 241000282412 Homo Species 0.000 description 8
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 8
- 238000012217 deletion Methods 0.000 description 8
- 230000037430 deletion Effects 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 108091008109 Pseudogenes Proteins 0.000 description 7
- 102000057361 Pseudogenes Human genes 0.000 description 7
- 108700019146 Transgenes Proteins 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 108010004020 Immunoglobulin lambda-Chains Proteins 0.000 description 6
- 206010035226 Plasma cell myeloma Diseases 0.000 description 6
- 238000009395 breeding Methods 0.000 description 6
- 230000001488 breeding effect Effects 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 210000004962 mammalian cell Anatomy 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 201000000050 myeloid neoplasm Diseases 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 108091008875 B cell receptors Proteins 0.000 description 5
- 101100322565 Mus musculus Adam3 gene Proteins 0.000 description 5
- 241000283984 Rodentia Species 0.000 description 5
- 108050000761 Serpin Proteins 0.000 description 5
- 102000008847 Serpin Human genes 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 5
- 108091033319 polynucleotide Proteins 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 239000003001 serine protease inhibitor Substances 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 4
- 238000011740 C57BL/6 mouse Methods 0.000 description 4
- 102100029567 Immunoglobulin kappa light chain Human genes 0.000 description 4
- 101710189008 Immunoglobulin kappa light chain Proteins 0.000 description 4
- 241000288906 Primates Species 0.000 description 4
- 230000009824 affinity maturation Effects 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229940124691 antibody therapeutics Drugs 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000002759 chromosomal effect Effects 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 210000003918 fraction a Anatomy 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 4
- 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 4
- 230000011664 signaling Effects 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 210000001541 thymus gland Anatomy 0.000 description 4
- 229960005486 vaccine Drugs 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 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 3
- 101710081722 Antitrypsin Proteins 0.000 description 3
- 101100384798 Lupinus albus Cgamma gene Proteins 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 101100166834 Mus musculus Cp gene Proteins 0.000 description 3
- 108010052160 Site-specific recombinase Proteins 0.000 description 3
- 108010020764 Transposases Proteins 0.000 description 3
- 102000008579 Transposases Human genes 0.000 description 3
- 230000007720 allelic exclusion Effects 0.000 description 3
- 230000001475 anti-trypsic effect Effects 0.000 description 3
- 239000004019 antithrombin Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000011830 transgenic mouse model Methods 0.000 description 3
- 239000002753 trypsin inhibitor Substances 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
- 108091022885 ADAM Proteins 0.000 description 2
- 102000029791 ADAM Human genes 0.000 description 2
- 101150023103 CHI gene Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 208000035473 Communicable disease Diseases 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
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 2
- 102100029620 Immunoglobulin lambda constant 2 Human genes 0.000 description 2
- 101000777315 Mus musculus Choline kinase alpha Proteins 0.000 description 2
- 101000777310 Mus musculus Choline/ethanolamine kinase Proteins 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- 241000577979 Peromyscus spicilegus Species 0.000 description 2
- 102100028087 Protein-tyrosine sulfotransferase 2 Human genes 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000002459 blastocyst Anatomy 0.000 description 2
- 230000011712 cell development Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 101150076615 ck gene Proteins 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- 230000004720 fertilization Effects 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000012804 iterative process Methods 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 229940092253 ovalbumin Drugs 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 108020005065 3' Flanking Region Proteins 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- 108020005029 5' Flanking Region Proteins 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- ORILYTVJVMAKLC-UHFFFAOYSA-N Adamantane Natural products C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 101150061009 C1 gene Proteins 0.000 description 1
- 238000011814 C57BL/6N mouse Methods 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 208000037051 Chromosomal Instability Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 241000699662 Cricetomys gambianus Species 0.000 description 1
- 101100193633 Danio rerio rag2 gene Proteins 0.000 description 1
- 235000017274 Diospyros sandwicensis Nutrition 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 108010046276 FLP recombinase Proteins 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010069446 Fertilins Proteins 0.000 description 1
- 102000001133 Fertilins Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000856199 Homo sapiens Chymotrypsin-like protease CTRL-1 Proteins 0.000 description 1
- 101000649077 Homo sapiens Protein-tyrosine sulfotransferase 2 Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 208000007466 Male Infertility Diseases 0.000 description 1
- 101100058506 Mus musculus Bloc1s5 gene Proteins 0.000 description 1
- 101100193635 Mus musculus Rag2 gene Proteins 0.000 description 1
- 101100370002 Mus musculus Tnfsf14 gene Proteins 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710162468 Protein-tyrosine sulfotransferase 2 Proteins 0.000 description 1
- 102000001183 RAG-1 Human genes 0.000 description 1
- 108060006897 RAG1 Proteins 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 101150045960 TPST2 gene Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 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
- 241001416177 Vicugna pacos Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000000991 chicken egg Anatomy 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 230000002888 effect on disease Effects 0.000 description 1
- 101150097231 eg gene Proteins 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 201000010063 epididymitis Diseases 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000011331 genomic analysis Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 208000021267 infertility disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 210000001778 pluripotent stem cell Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 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
- 238000004321 preservation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 230000010010 testicular gene expression Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000013715 transcription antitermination Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- 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
-
- 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
-
- 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
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
- C07K16/1239—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Vibrionaceae (G)
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
- C07K16/462—Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/15—Humanized animals
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/01—Animal expressing industrially exogenous proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- 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
- C07K2317/35—Valency
-
- 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
- C07K2317/56—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
- C07K2317/50—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
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/80—Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Environmental Sciences (AREA)
- Veterinary Medicine (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/433,084 US9445581B2 (en) | 2012-03-28 | 2012-03-28 | Animal models and therapeutic molecules |
| US13/433,084 | 2012-03-28 | ||
| US13/434,361 | 2012-03-29 | ||
| US13/434,361 US9253965B2 (en) | 2012-03-28 | 2012-03-29 | Animal models and therapeutic molecules |
| PCT/GB2013/050682 WO2013144566A2 (en) | 2012-03-28 | 2013-03-18 | Animal models and therapeutic molecules |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2867530A1 true CA2867530A1 (en) | 2013-10-03 |
Family
ID=47913490
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2867530A Abandoned CA2867530A1 (en) | 2012-03-28 | 2013-03-18 | Animal models and therapeutic molecules |
Country Status (12)
| Country | Link |
|---|---|
| US (7) | US9253965B2 (OSRAM) |
| EP (3) | EP2785845A2 (OSRAM) |
| JP (4) | JP6336435B2 (OSRAM) |
| CN (1) | CN104334732B (OSRAM) |
| AU (1) | AU2013239501B2 (OSRAM) |
| CA (1) | CA2867530A1 (OSRAM) |
| DK (1) | DK2831244T3 (OSRAM) |
| ES (1) | ES2979344T3 (OSRAM) |
| IN (1) | IN2014MN01879A (OSRAM) |
| NZ (1) | NZ629202A (OSRAM) |
| SG (1) | SG11201405058WA (OSRAM) |
| WO (2) | WO2013061098A2 (OSRAM) |
Families Citing this family (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG174053A1 (en) | 2006-09-01 | 2011-09-29 | Therapeutic Human Polyclonals Inc | Enhanced expression of human or humanized immunoglobulin in non-human transgenic animals |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| PL2517556T3 (pl) | 2009-07-08 | 2016-03-31 | Kymab Ltd | Sposób miejscowo specyficznej rekombinacji, gryzonie i komórki gryzonia zdolne do ekspresji chimerycznych przeciwciał lub łańcuchów |
| US10793829B2 (en) | 2010-07-26 | 2020-10-06 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| JP6482757B2 (ja) | 2010-07-26 | 2019-03-13 | トリアンニ インコーポレイテッドＴｒｉａｎｎｉ，Ｉｎｃ． | トランスジェニック動物および使用方法 |
| US10662256B2 (en) | 2010-07-26 | 2020-05-26 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| CA2807282A1 (en) | 2010-08-02 | 2012-02-09 | Regeneron Pharamaceuticals, Inc. | Mice that make binding proteins comprising vl domains |
| ME02106B (me) | 2011-02-25 | 2015-10-20 | Regeneron Pharma | Miševi sa adam6 |
| RU2664232C2 (ru) | 2011-08-05 | 2018-08-15 | Регенерон Фармасьютикалз, Инк. | Мыши с гуманизированной универсальной легкой цепью |
| CA2846319A1 (en) | 2011-09-19 | 2013-03-28 | Kymab Limited | Antibodies, variable domains & chains tailored for human use |
| EP2761008A1 (en) | 2011-09-26 | 2014-08-06 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| ES2640139T3 (es) | 2011-10-17 | 2017-10-31 | Regeneron Pharmaceuticals, Inc. | Ratones de cadena pesada de inmunoglobulina restringida |
| US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| JP6327750B2 (ja) | 2011-12-20 | 2018-05-23 | 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | ヒト化軽鎖マウス |
| 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 |
| SG11201407789RA (en) | 2012-06-12 | 2014-12-30 | Regeneron Pharma | Humanized non-human animals with restricted immunoglobulin heavy chain loci |
| RU2017114166A (ru) | 2013-02-20 | 2019-01-29 | Регенерон Фармасьютикалс, Инк. | Не являющиеся человеком животные с модифицированными последовательностями тяжелых цепей иммуноглобулинов |
| 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 |
| DE112014004537T5 (de) | 2013-10-01 | 2016-07-21 | Kymab Limited | Tiermodelle und therapeutische Moleküle |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| CN106164092A (zh) | 2014-03-21 | 2016-11-23 | 瑞泽恩制药公司 | 表现不同结合特征的vl抗原结合蛋白 |
| JP6636498B2 (ja) | 2014-03-21 | 2020-01-29 | 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | 単一ドメイン結合タンパク質を作る非ヒト動物 |
| WO2015153912A1 (en) | 2014-04-03 | 2015-10-08 | Igm Biosciences, Inc. | Modified j-chain |
| CN115093479A (zh) | 2015-03-04 | 2022-09-23 | Igm生物科学股份有限公司 | Cd20结合分子及其用途 |
| JP2018508224A (ja) | 2015-03-19 | 2018-03-29 | 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | 抗原を結合する軽鎖可変領域を選択する非ヒト動物 |
| WO2017059387A1 (en) | 2015-09-30 | 2017-04-06 | Igm Biosciences, Inc. | Binding molecules with modified j-chain |
| US10618978B2 (en) | 2015-09-30 | 2020-04-14 | Igm Biosciences, Inc. | Binding molecules with modified J-chain |
| WO2017095939A1 (en) | 2015-12-03 | 2017-06-08 | Trianni, Inc. | Enhanced immunoglobulin diversity |
| US11098310B2 (en) | 2016-01-27 | 2021-08-24 | Just-Evotec Biologics, Inc. | Expression from transposon-based vectors and uses |
| US11261462B2 (en) | 2016-01-27 | 2022-03-01 | Just-Evotec Biologics, Inc. | Inducible expression from transposon-based vectors and uses |
| JP6937309B2 (ja) | 2016-01-27 | 2021-09-22 | ジャスト−エヴォテック バイオロジックス、インコーポレイテッド | ハイブリッドプロモーターおよびその使用 |
| JP6929877B2 (ja) | 2016-02-04 | 2021-09-01 | トリアニ・インコーポレイテッドＴｒｉａｎｎｉ， Ｉｎｃ． | 免疫グロブリン産生の増強 |
| GB2550114A (en) | 2016-05-03 | 2017-11-15 | Kymab Ltd | Methods, regimens, combinations & antagonists |
| IL263834B2 (en) | 2016-06-20 | 2024-01-01 | Kymab Ltd | Anti-pd-l1 antibodies |
| WO2018029474A2 (en) | 2016-08-09 | 2018-02-15 | Kymab Limited | Anti-icos antibodies |
| US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
| US11858996B2 (en) | 2016-08-09 | 2024-01-02 | Kymab Limited | Anti-ICOS antibodies |
| EP3534947A1 (en) | 2016-11-03 | 2019-09-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
| SI3766343T1 (sl) * | 2016-11-04 | 2022-06-30 | Regeneron Pharmaceuticals, Inc. | Nehumane živali z modificiranim lokusom lahke verige lambda imunoglobulina |
| CN109906030B (zh) * | 2016-11-04 | 2022-03-18 | 安健基因公司 | 用于产生仅重链抗体的经基因修饰的非人动物和方法 |
| US11793833B2 (en) | 2016-12-02 | 2023-10-24 | Juno Therapeutics, Inc. | Engineered B cells and related compositions and methods |
| EP3574017A1 (en) | 2017-01-27 | 2019-12-04 | Kymab Limited | Anti-opg antibodies |
| GB201709808D0 (en) | 2017-06-20 | 2017-08-02 | Kymab Ltd | Antibodies |
| GB201709970D0 (en) | 2017-06-22 | 2017-08-09 | Kymab Ltd | Bispecific antigen-binding molecules |
| GB201710984D0 (en) * | 2017-07-07 | 2017-08-23 | Kymab Ltd | Cells, vertebrates, populations & methods |
| AU2018302668B2 (en) * | 2017-07-21 | 2024-11-07 | I'rom Group Co., Ltd. | Polynucleotide for modifying target sequence and use thereof |
| WO2019037099A1 (en) * | 2017-08-25 | 2019-02-28 | Wenning Qin | LARGE SCALE MODIFICATION OF GENOME EUCARYOTE |
| SI3720279T1 (sl) * | 2017-12-05 | 2022-11-30 | Regeneron Pharmaceuticals, Inc. | Miši, ki imajo spremenjeno lahko verigo imunoglobulina lambda in njihova uporaba |
| US11629189B2 (en) | 2017-12-19 | 2023-04-18 | Kymab Limited | Bispecific antibody for ICOS and PD-L1 |
| GB201721338D0 (en) | 2017-12-19 | 2018-01-31 | Kymab Ltd | Anti-icos Antibodies |
| CN108486126A (zh) * | 2018-03-27 | 2018-09-04 | 重庆金迈博生物科技有限公司 | 一种核酸分子及其在人源化抗体中的应用 |
| GB201815629D0 (en) | 2018-09-25 | 2018-11-07 | Kymab Ltd | Antagonists |
| US12331320B2 (en) | 2018-10-10 | 2025-06-17 | The Research Foundation For The State University Of New York | Genome edited cancer cell vaccines |
| CN117099741A (zh) | 2019-02-18 | 2023-11-24 | 百奥赛图(北京)医药科技股份有限公司 | 具有人源化免疫球蛋白基因座的经遗传修饰的非人动物 |
| SG11202110610VA (en) | 2019-04-09 | 2021-10-28 | Abcuro Inc | Killer cell lectin-like receptor subfamily g member 1 (klrg1) depleting antibodies |
| US20210000087A1 (en) * | 2019-07-01 | 2021-01-07 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| EP4065607A1 (en) | 2019-11-29 | 2022-10-05 | Kymab Limited | Treatment for physiological iron overload |
| CN115667532A (zh) | 2020-06-02 | 2023-01-31 | 百奥赛图(北京)医药科技股份有限公司 | 具有共有轻链免疫球蛋白基因座的经遗传修饰的非人动物 |
| CN115988960A (zh) | 2020-06-25 | 2023-04-18 | 株式会社湖美宝 | 杂合转基因动物 |
| WO2022026775A1 (en) * | 2020-07-30 | 2022-02-03 | Prellis Biologics, Inc | Compositions and methods for targeting coronavirus |
| EP4211155A1 (en) | 2020-09-11 | 2023-07-19 | Regeneron Pharmaceuticals, Inc. | Identification and production of antigen-specific antibodies |
| US20240065239A1 (en) | 2020-12-16 | 2024-02-29 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized fc alpha receptors |
| AU2022320627A1 (en) | 2021-07-26 | 2024-02-08 | Abcuro, Inc. | Killer cell lectin-like receptor subfamily g member 1 (klrg1) depleting antibodies |
| US20240260553A1 (en) * | 2023-01-18 | 2024-08-08 | Gilead Sciences, Inc. | Chimeric transgenic immunoglobulin mice with an altered heavy chain locus and methods of making and using same |
| TW202444754A (zh) | 2023-01-30 | 2024-11-16 | 英商凱麥博有限公司 | 抗體 |
| WO2025067231A1 (en) * | 2023-09-26 | 2025-04-03 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animals with humanized immunoglobulin locus |
| WO2025147544A1 (en) | 2024-01-02 | 2025-07-10 | Abcuro, Inc. | Methods of treating inclusion body myositis (ibm) |
Family Cites Families (162)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| US5169939A (en) | 1985-05-21 | 1992-12-08 | Massachusetts Institute Of Technology & Pres. & Fellows Of Harvard College | Chimeric antibodies |
| US4720449A (en) | 1985-06-03 | 1988-01-19 | Polaroid Corporation | Thermal imaging method |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| WO1991000906A1 (en) | 1989-07-12 | 1991-01-24 | Genetics Institute, Inc. | Chimeric and transgenic animals capable of producing human antibodies |
| US6713610B1 (en) | 1990-01-12 | 2004-03-30 | Raju Kucherlapati | Human antibodies derived from immunized xenomice |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| CA2050918A1 (en) | 1990-01-12 | 1991-07-13 | Raju Kucherlapati | Generation of xenogeneic antibodies |
| US7084260B1 (en) | 1996-10-10 | 2006-08-01 | Genpharm International, Inc. | High affinity human antibodies and human antibodies against human antigens |
| JP2938569B2 (ja) | 1990-08-29 | 1999-08-23 | ジェンファーム インターナショナル，インコーポレイティド | 異種免疫グロブリンを作る方法及びトランスジェニックマウス |
| WO1993012227A1 (en) | 1991-12-17 | 1993-06-24 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US7041871B1 (en) | 1995-10-10 | 2006-05-09 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | 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 |
| US5770429A (en) * | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| AU2515992A (en) | 1991-08-20 | 1993-03-16 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| US5859307A (en) | 1992-02-04 | 1999-01-12 | Massachusetts Institute Of Technology | Mutant RAG-1 deficient animals having no mature B and T lymphocytes |
| SG48760A1 (en) | 1992-07-24 | 2003-03-18 | Abgenix Inc | Generation of xenogenetic antibodies |
| DE4228162C1 (de) | 1992-08-25 | 1994-01-13 | Rajewsky Klaus Dr | Verfahren zum Ersetzen homologer Genabschnitte aus Säugern in der Keimbahn von nicht-menschlichen Säugern |
| US5565321A (en) | 1993-01-22 | 1996-10-15 | Immunex Corporation | Detection of mutations in a CD40 ligand gene |
| EP0754225A4 (en) | 1993-04-26 | 2001-01-31 | Genpharm Int | HETEROLOGIC ANTIBODY-PRODUCING TRANSGENIC NON-HUMAN ANIMALS |
| DE4331162A1 (de) | 1993-09-14 | 1995-03-16 | Bayer Ag | Verfahren zur Herstellung von Cyaninfarbstoffen |
| US7119248B1 (en) | 1994-04-12 | 2006-10-10 | Miltenyi Biotec Gmbh | Antibodies against epitopes with homology to self antigens, methods of preparation and applications thereof |
| US6130364A (en) | 1995-03-29 | 2000-10-10 | Abgenix, Inc. | Production of antibodies using Cre-mediated site-specific recombination |
| US6077667A (en) | 1996-06-26 | 2000-06-20 | Bradley; Allan | Method for chromosomal rearrangement by consecutive gene targeting of two recombination substrates to the deletion endpoints |
| CA2258518C (en) | 1996-06-27 | 2011-11-22 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw | Recognition molecules interacting specifically with the active site or cleft of a target molecule |
| AU5702298A (en) | 1996-12-03 | 1998-06-29 | Abgenix, Inc. | Transgenic mammals having human Ig loci including plural VH and VK regions nd antibodies produced therefrom |
| US6319906B1 (en) | 1996-12-31 | 2001-11-20 | Isis Pharmaceuticals | Oligonucleotide compositions and methods for the modulation of the expression of B7 protein |
| ES2308327T3 (es) | 1997-11-18 | 2008-12-01 | Pioneer Hi-Bred International, Inc. | Composiciones y metodos para modificacion genetica de plantas. |
| ATE449844T1 (de) | 1997-12-05 | 2009-12-15 | Europ Lab Molekularbiolog | Neue methode zur klonierung dns unter anwendung des e. coli rece/rect rekombinationssystems |
| EP0939120A1 (en) | 1998-02-27 | 1999-09-01 | Gesellschaft für biotechnologische Forschung mbH (GBF) | Method for marker-free repetitive DNA expression cassette exchange in the genome of cells or parts of cells |
| GB9823930D0 (en) | 1998-11-03 | 1998-12-30 | Babraham Inst | Murine expression of human ig\ locus |
| US6914128B1 (en) | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
| US6833268B1 (en) | 1999-06-10 | 2004-12-21 | Abgenix, Inc. | Transgenic animals for producing specific isotypes of human antibodies via non-cognate switch regions |
| US6355412B1 (en) | 1999-07-09 | 2002-03-12 | The European Molecular Biology Laboratory | Methods and compositions for directed cloning and subcloning using homologous recombination |
| US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
| CA2307503A1 (en) | 2000-05-02 | 2001-11-02 | Carlos F. Barbas Iii | Peptides for use as a vaccine or treatment for hiv infection |
| MXPA03000634A (es) | 2000-07-21 | 2004-12-03 | Us Agriculture | Metodos para el reemplazo, el desplazamiento y acumulacion de adn en genomas eucarioticos. |
| US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US7105348B2 (en) | 2000-10-31 | 2006-09-12 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| EP1343880B1 (en) | 2000-11-17 | 2009-05-27 | Kyowa Hakko Kirin Co., Ltd. | Expression of xenogenous (human) immunoglobulins in cloned, transgenic bovine |
| KR100857943B1 (ko) | 2000-11-30 | 2008-09-09 | 메다렉스, 인코포레이티드 | 인간 항체의 제조를 위한 형질전환 트랜스염색체 설치류 |
| EP1409646B1 (en) | 2000-12-19 | 2012-06-13 | Altor BioScience Corporation | Transgenic animals comprising a humanized immune system |
| PL224873B1 (pl) | 2001-01-05 | 2017-02-28 | Amgen Fremont Inc | Przeciwciało przeciwko receptorowi insulinopodobnego czynnika wzrostu I, zawierająca go kompozycja farmaceutyczna, sposób jego wytwarzania, zastosowania, linia komórkowa, wyizolowana cząsteczka kwasu nukleinowego, wektor, komórka gospodarza oraz zwierzę transgeniczne |
| FR2827302B1 (fr) | 2001-07-13 | 2003-10-10 | Genoway | Cellule et animal transgenique modelisant la presentation antigenique humaine et leurs utilisations |
| US20030108925A1 (en) | 2001-10-05 | 2003-06-12 | U.S. Epa | Genetic testing for male factor infertility |
| US20060199204A1 (en) | 2001-10-05 | 2006-09-07 | U.S. Epa | Genetic testing for male factor infertility |
| CA2468565C (en) | 2001-11-30 | 2014-06-03 | Abgenix, Inc. | Transgenic animals bearing human iglambda light chain genes |
| WO2003061363A2 (en) | 2002-01-17 | 2003-07-31 | Albert Einstein College Of Medicine Of Yeshiva University | Mutations caused by activation-induced cytidine deaminase |
| US8877901B2 (en) | 2002-12-13 | 2014-11-04 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
| AU2003278790A1 (en) | 2002-09-09 | 2004-03-29 | California Institute Of Technology | Methods and compositions for the generation of humanized mice |
| DE10251918A1 (de) | 2002-11-08 | 2004-05-19 | Horn, Carsten, Dipl.-Biochem. Dr. | Systeme zur Erzeugung stabiler genomischer Transgen-Insertionen |
| US7700356B2 (en) | 2002-11-08 | 2010-04-20 | The United States Of America As Represented By The Secretary Of Agriculture | System for gene targeting and producing stable genomic transgene insertions |
| AR042145A1 (es) | 2002-11-27 | 2005-06-08 | Dow Agrociences Llc | Produccion de inmunoglobulinas en plantas con una fucocilacion reducida |
| 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 |
| US7205148B2 (en) | 2003-06-11 | 2007-04-17 | Regeneron Pharmaceuticals, Inc. | Genome mutation by intron insertion into an embryonic stem cell genome |
| GB2403475B (en) | 2003-07-01 | 2008-02-06 | Oxitec Ltd | Stable integrands |
| JP2005042792A (ja) | 2003-07-28 | 2005-02-17 | Nsk Ltd | ローラクラッチ及びローラクラッチ内蔵型プーリ装置 |
| US7663017B2 (en) | 2003-07-30 | 2010-02-16 | Institut Pasteur | Transgenic mice having a human major histocompatability complex (MHC) phenotype, experimental uses and applications |
| WO2005019463A1 (en) | 2003-08-11 | 2005-03-03 | Therapeutic Human Polyclonals, Inc. | Improved transgenesis with humanized immunoglobulin loci |
| US7604994B2 (en) | 2003-09-03 | 2009-10-20 | Morphotek, Inc. | Genetically altered antibody-producing cell lines with improved antibody characteristics |
| CA2445602C (en) | 2003-10-20 | 2014-01-14 | Campusgen Gmbh | Nucleotide sequence for creatinine deiminase and method of use |
| ZA200604620B (en) | 2003-12-10 | 2007-10-31 | Medarex Inc | IP-10 antibodies and their uses |
| EP2418224A3 (en) | 2004-03-19 | 2013-07-24 | Amgen Inc. | Reducing the risk of human and anti-human antibodies through V gene manipulation |
| US7625549B2 (en) | 2004-03-19 | 2009-12-01 | Amgen Fremont Inc. | Determining the risk of human anti-human antibodies in transgenic mice |
| US20090285805A1 (en) | 2004-07-22 | 2009-11-19 | Erasmus University Medical Centre Rotterdam Depart Ment Of Cell Biology And Genetics | Binding molecules |
| FR2875239B1 (fr) | 2004-09-10 | 2007-07-20 | Inst Necker Ass Loi De 1901 | Procede pour l'acceleration des mutations somatiques et son application en proteomique |
| WO2006044492A2 (en) | 2004-10-14 | 2006-04-27 | Ingenious Targeting Laboratory, Inc. | Methods for generating rat embryo-derived cell lines and genetic modification of rat genome |
| PT1802193E (pt) | 2004-10-19 | 2014-06-23 | Regeneron Pharma | Método para gerar um murganho homozigótico para uma modificação genética |
| WO2006055704A2 (en) | 2004-11-17 | 2006-05-26 | Curagen Corporation | Antibodies directed to ten-m proteins and uses thereof |
| BRPI0519596B1 (pt) | 2004-12-21 | 2022-01-18 | Astrazeneca Ab | Agente de ligação alvejado, anticorpo monoclonal que se liga a angiopoietina-2, molécula de ácido nucleico, vetor, e, uso do agente de ligação alvejado |
| MX2007014139A (es) | 2005-05-14 | 2008-10-09 | Univ Fudan | Piggybac como una herramienta para manipulacion genetica y analisis en vertebrados. |
| EP1780272A1 (en) | 2005-10-27 | 2007-05-02 | GSF-Forschungszentrum für Umwelt und Gesundheit GmbH | Method for enhancing somatic hypermutation, gene conversion and class switch recombination |
| GB0601513D0 (en) | 2006-01-25 | 2006-03-08 | Univ Erasmus Medical Ct | Binding molecules 3 |
| SG169348A1 (en) | 2006-01-25 | 2011-03-30 | Univ Erasmus Medical Ct | Generation of heavy-chain only antibodies in transgenic animals |
| US7462759B2 (en) | 2006-02-03 | 2008-12-09 | Pioneer Hi-Bred International, Inc. | Brittle stalk 2 gene family and related methods and uses |
| AU2007235496B2 (en) | 2006-03-31 | 2013-11-21 | E. R. Squibb & Sons, L.L.C. | Transgenic animals expressing chimeric antibodies for use in preparing human antibodies |
| PT2041177E (pt) | 2006-06-02 | 2012-03-05 | Regeneron Pharma | Anticorpos com elevada afinidade para o receptor il-6 humano |
| US7709257B2 (en) | 2006-06-27 | 2010-05-04 | Vax Design Corp. | Models for vaccine assessment |
| EP1878342A1 (en) | 2006-07-13 | 2008-01-16 | Institut Pasteur | Immunodeficient mice transgenic for HLA class I and HLA class II molecules and their uses |
| JP2010501165A (ja) | 2006-08-22 | 2010-01-21 | ジーツー インフラメイション プロプライエタリー リミテッド | 抗体の作製方法 |
| EP3845563A3 (en) | 2006-10-02 | 2021-11-24 | Regeneron Pharmaceuticals, Inc. | High affinity human antibodies to human il-4 receptor |
| US7732195B2 (en) | 2006-11-01 | 2010-06-08 | Facet Biotech Corporation | Tethered vectors for cell surface immunoglobulin display |
| 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. |
| GB0700194D0 (en) | 2007-01-05 | 2007-02-14 | Univ Edinburgh | Humanisation of animals |
| JP2010520748A (ja) | 2007-02-20 | 2010-06-17 | アナプティスバイオ インコーポレイティッド | 体細胞超変異系 |
| JP5779350B2 (ja) | 2007-03-27 | 2015-09-16 | シー レーン バイオテクノロジーズ， エルエルシー | 抗体代替軽鎖配列を含む構築物およびライブラリー |
| GB0706628D0 (en) | 2007-04-04 | 2007-05-16 | Univ Erasmus | Germ-line manipulation 1 |
| ES2664218T3 (es) | 2007-06-01 | 2018-04-18 | Open Monoclonal Technology, Inc | Composiciones y procedimientos de inhibición de genes de inmunoglobulinas endógenas y de producción de anticuerpos idiotípicos humanos transgénicos |
| WO2009013620A2 (en) | 2007-06-11 | 2009-01-29 | Erasmus University Medical Center Rotterdam | Homologous recombination |
| CA2695199C (en) | 2007-07-31 | 2016-07-19 | Regeneron Pharmaceuticals, Inc. | Human antibodies to human cd20 and method of using thereof |
| KR101709488B1 (ko) | 2007-08-10 | 2017-02-24 | 리제너론 파아마슈티컬스, 인크. | 인간 신경성장인자에 대한 고친화성 인간 항체 |
| US9693539B2 (en) | 2007-08-10 | 2017-07-04 | E. R. Squibb & Sons, L.L.C. | HCO32 and HCO27 and related examples |
| JP2009122383A (ja) * | 2007-11-14 | 2009-06-04 | Canon Inc | 揺動体装置の製造方法、該製造方法により製造された揺動体装置によって構成される光偏向器及び光学機器 |
| NZ586149A (en) | 2007-12-10 | 2012-05-25 | Ablexis Llc | Methods for sequential replacement of targeted region by homologous recombination |
| US8227577B2 (en) | 2007-12-21 | 2012-07-24 | Hoffman-La Roche Inc. | Bivalent, bispecific antibodies |
| JP2011510155A (ja) | 2008-01-25 | 2011-03-31 | キャボット コーポレイション | 改質された着色顔料の調製方法 |
| KR101409375B1 (ko) | 2008-01-31 | 2014-06-18 | 삼성전자주식회사 | 반도체 메모리장치의 블록 디코딩 회로 |
| JP2011515098A (ja) | 2008-03-26 | 2011-05-19 | アイティーアイ・スコットランド・リミテッド | 胚性幹細胞へのｄｎａの効率的な挿入 |
| CA2721231C (en) | 2008-04-14 | 2015-10-06 | Innovative Targeting Solutions Inc. | Sequence diversity generation in immunoglobulins |
| DK2288623T3 (da) | 2008-05-23 | 2014-01-27 | Ablexis Llc | Fremgangsmåde til frembringelse af enkelt-vl-domæne-antistoffer hos transgene dyr |
| PT3456190T (pt) | 2008-06-27 | 2022-02-15 | Merus Nv | Animal murino transgénico produtor de anticorpo |
| AU2009298458B2 (en) | 2008-09-30 | 2015-10-08 | Ablexis, Llc | Non-human mammals for the production of chimeric antibodies |
| JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
| MX2011007660A (es) | 2008-12-18 | 2011-08-17 | Kingdon Craig R | Animales transgenicos no humanos que expresan anticuerpos humanizados y usos de los mismos. |
| CA2750520C (en) | 2009-02-04 | 2017-12-05 | Molecular Innovations | Methods for screening candidate agents for modulating prorenin and renin, assays for detecting prorenin, and antibodies used therein |
| CA2753287A1 (en) | 2009-02-24 | 2010-09-02 | Glaxo Group Limited | Antigen-binding constructs |
| GB0905023D0 (en) | 2009-03-24 | 2009-05-06 | Univ Erasmus Medical Ct | Binding molecules |
| JP5683566B2 (ja) | 2009-04-03 | 2015-03-11 | メディカル リサーチ カウンシル | 活性化誘導シチジンデアミナーゼ（ａｉｄ）の変異体及び使用方法 |
| AU2010265949B2 (en) | 2009-06-26 | 2016-05-05 | I2 Pharmaceuticals, Inc. | Expression of surrogate light chains |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| PL2517556T3 (pl) | 2009-07-08 | 2016-03-31 | Kymab Ltd | Sposób miejscowo specyficznej rekombinacji, gryzonie i komórki gryzonia zdolne do ekspresji chimerycznych przeciwciał lub łańcuchów |
| EP2454283B1 (en) | 2009-07-15 | 2018-03-14 | AIMM Therapeutics B.V. | Means and methods for producing high affinity antibodies |
| JO3182B1 (ar) | 2009-07-29 | 2018-03-08 | Regeneron Pharma | مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2 |
| JP5756802B2 (ja) | 2009-08-13 | 2015-07-29 | クリスタル バイオサイエンス インク．Ｃｒｙｓｔａｌ Ｂｉｏｓｃｉｅｎｃｅ Ｉｎｃ． | 最小ｃｄｒを有する抗体を産生するトランスジェニック動物 |
| WO2011056864A1 (en) | 2009-11-05 | 2011-05-12 | Anaptysbio, Inc. | Methods of generating improved antigen-binding agents using chain shuffling and optionally somatic hypermutation |
| EP2502993B1 (en) | 2009-11-17 | 2017-07-26 | Sanford Applied Biosciences L.L.C. | Human artificial chromosome vector |
| US20120269830A1 (en) | 2009-12-07 | 2012-10-25 | Lawrence Horowitz | Conjugates with improved pharmacokinetic properties |
| ES2724975T3 (es) | 2009-12-10 | 2019-09-18 | Regeneron Pharma | Ratones que producen anticuerpos de cadena pesada |
| US20120021409A1 (en) | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| ES2728942T3 (es) | 2010-02-08 | 2019-10-29 | Regeneron Pharma | Cadena ligera común de ratón |
| EP2571512B1 (en) | 2010-05-17 | 2017-08-23 | Sangamo BioSciences, Inc. | Novel dna-binding proteins and uses thereof |
| NZ605966A (en) | 2010-06-17 | 2015-04-24 | Kymab Ltd | Animal models and therapeutic molecules |
| ME02902B (me) | 2010-06-22 | 2018-04-20 | Regeneron Pharma | Transgeni miševi sa modifikovanim lokusom endogenog lambda imunoglobulina |
| CA2807282A1 (en) | 2010-08-02 | 2012-02-09 | Regeneron Pharamaceuticals, Inc. | Mice that make binding proteins comprising vl domains |
| CN103261220B (zh) | 2010-08-16 | 2016-06-15 | 诺夫免疫股份有限公司 | 用于生成多特异性和多价抗体的方法 |
| JO3375B1 (ar) | 2010-11-08 | 2019-03-13 | Regeneron Pharma | أجسام مضادة بشرية للجين a1 الشبيه بعامل النخر الورمي (tl1a) |
| AR084456A1 (es) | 2010-12-22 | 2013-05-15 | Genentech Inc | Anticuerpo anti-pcsk9 y metodos de uso |
| ME02106B (me) | 2011-02-25 | 2015-10-20 | Regeneron Pharma | Miševi sa adam6 |
| RU2664232C2 (ru) | 2011-08-05 | 2018-08-15 | Регенерон Фармасьютикалз, Инк. | Мыши с гуманизированной универсальной легкой цепью |
| CA2846319A1 (en) | 2011-09-19 | 2013-03-28 | Kymab Limited | Antibodies, variable domains & chains tailored for human use |
| WO2013041845A2 (en) | 2011-09-19 | 2013-03-28 | Kymab Limited | Animals, repertoires & methods |
| EP2761008A1 (en) | 2011-09-26 | 2014-08-06 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| ES2640139T3 (es) | 2011-10-17 | 2017-10-31 | Regeneron Pharmaceuticals, Inc. | Ratones de cadena pesada de inmunoglobulina restringida |
| US20130102031A1 (en) | 2011-10-25 | 2013-04-25 | Anaptysbio, Inc. | Use of somatic hypermutation to create insertion and deletion mutations in vitro |
| 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 |
| JP6327750B2 (ja) | 2011-12-20 | 2018-05-23 | 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | ヒト化軽鎖マウス |
| ES2870703T3 (es) | 2012-02-01 | 2021-10-27 | Regeneron Pharma | Roedores humanizados que expresan cadenas pesadas que contienen dominios VL |
| AR090219A1 (es) | 2012-03-02 | 2014-10-29 | Regeneron Pharma | Anticuerpos humanos frente a toxinas de clostridium difficile |
| KR20140136462A (ko) | 2012-03-06 | 2014-11-28 | 리제너론 파마슈티칼스 인코포레이티드 | 공통 경쇄 마우스 |
| JP2015512245A (ja) | 2012-03-16 | 2015-04-27 | 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | ｐＨ依存性の結合特徴を有する抗原結合タンパク質を産生するマウス |
| 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 |
| JO3820B1 (ar) | 2012-05-03 | 2021-01-31 | Regeneron Pharma | أجسام مضادة بشرية لـ fel d1وطرق لاستخدامها |
| MY184753A (en) | 2012-05-25 | 2021-04-20 | Univ California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation transcription |
| SG11201407789RA (en) | 2012-06-12 | 2014-12-30 | Regeneron Pharma | Humanized non-human animals with restricted immunoglobulin heavy chain loci |
| ES2658401T3 (es) | 2012-12-12 | 2018-03-09 | The Broad Institute, Inc. | Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas |
| RU2017114166A (ru) | 2013-02-20 | 2019-01-29 | Регенерон Фармасьютикалс, Инк. | Не являющиеся человеком животные с модифицированными последовательностями тяжелых цепей иммуноглобулинов |
| US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
| US20150033372A1 (en) | 2013-05-01 | 2015-01-29 | Kymab Limited | Human VpreB & Chimaeric Surrogate Light Chains in Transgenic Non-Human Vertebrates |
| US9783618B2 (en) | 2013-05-01 | 2017-10-10 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
| US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
| US20140331339A1 (en) | 2013-05-03 | 2014-11-06 | Kymab Limited | Transgenic Non-Human Assay Vertebrates, Assays and Kits |
| US20140331344A1 (en) | 2013-05-03 | 2014-11-06 | Kymab Ltd. | Transgenic Animals |
| DE112014004537T5 (de) | 2013-10-01 | 2016-07-21 | Kymab Limited | Tiermodelle und therapeutische Moleküle |
-
2012
- 2012-03-29 US US13/434,361 patent/US9253965B2/en active Active
- 2012-11-30 WO PCT/GB2012/052960 patent/WO2013061098A2/en active Application Filing
- 2012-11-30 EP EP12795841.1A patent/EP2785845A2/en not_active Withdrawn
-
2013
- 2013-03-18 JP JP2015502439A patent/JP6336435B2/ja active Active
- 2013-03-18 ES ES18153171T patent/ES2979344T3/es active Active
- 2013-03-18 IN IN1879MUN2014 patent/IN2014MN01879A/en unknown
- 2013-03-18 WO PCT/GB2013/050682 patent/WO2013144566A2/en active Application Filing
- 2013-03-18 EP EP13711119.1A patent/EP2831244B1/en active Active
- 2013-03-18 NZ NZ629202A patent/NZ629202A/en not_active IP Right Cessation
- 2013-03-18 CN CN201380027944.1A patent/CN104334732B/zh active Active
- 2013-03-18 EP EP18153171.6A patent/EP3366126B1/en active Active
- 2013-03-18 DK DK13711119.1T patent/DK2831244T3/en active
- 2013-03-18 AU AU2013239501A patent/AU2013239501B2/en not_active Expired - Fee Related
- 2013-03-18 SG SG11201405058WA patent/SG11201405058WA/en unknown
- 2013-03-18 CA CA2867530A patent/CA2867530A1/en not_active Abandoned
-
2016
- 2016-02-08 US US15/018,670 patent/US9924705B2/en active Active
- 2016-12-19 US US15/383,196 patent/US9938357B2/en active Active
- 2016-12-19 US US15/383,202 patent/US9938358B2/en active Active
-
2018
- 2018-04-09 US US15/948,709 patent/US10774155B2/en active Active
- 2018-05-02 JP JP2018088749A patent/JP2018119012A/ja active Pending
-
2020
- 2020-07-30 JP JP2020129123A patent/JP2020176140A/ja active Pending
- 2020-09-15 US US17/020,997 patent/US20210079118A1/en not_active Abandoned
-
2022
- 2022-09-19 US US17/947,884 patent/US20230159660A1/en active Pending
- 2022-11-04 JP JP2022177513A patent/JP7475415B2/ja active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7475415B2 (ja) | 動物モデルおよび治療用分子 | |
| US20220287283A1 (en) | Animal models and therapeutic molecules | |
| US20240057572A1 (en) | Animal Models and Therapeutic Molecules | |
| US9896516B2 (en) | Animal models and therapeutic molecules | |
| HK1200872B (en) | Transgenic mice expressing human lambda and kappa immunoglobulin light chain variable domains |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20180227 |
|
| FZDE | Discontinued |
Effective date: 20200831 |