CA2283740C - Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same - Google Patents
Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same Download PDFInfo
- Publication number
- CA2283740C CA2283740C CA002283740A CA2283740A CA2283740C CA 2283740 C CA2283740 C CA 2283740C CA 002283740 A CA002283740 A CA 002283740A CA 2283740 A CA2283740 A CA 2283740A CA 2283740 C CA2283740 C CA 2283740C
- Authority
- CA
- Canada
- Prior art keywords
- dna
- plasmid
- selectable marker
- protein
- homologous recombination
- 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.)
- Expired - Fee Related
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 151
- 239000013598 vector Substances 0.000 title claims abstract description 84
- 238000002744 homologous recombination Methods 0.000 title claims abstract description 65
- 230000006801 homologous recombination Effects 0.000 title claims abstract description 65
- 210000004962 mammalian cell Anatomy 0.000 title claims abstract description 65
- 238000000034 method Methods 0.000 title claims abstract description 65
- 239000003550 marker Substances 0.000 claims abstract description 145
- 239000013612 plasmid Substances 0.000 claims abstract description 122
- 210000004027 cell Anatomy 0.000 claims abstract description 116
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 75
- 230000010354 integration Effects 0.000 claims abstract description 41
- 108060003951 Immunoglobulin Proteins 0.000 claims abstract description 16
- 102000018358 immunoglobulin Human genes 0.000 claims abstract description 16
- 108020004414 DNA Proteins 0.000 claims description 183
- 230000014509 gene expression Effects 0.000 claims description 73
- 239000012634 fragment Substances 0.000 claims description 47
- 230000008685 targeting Effects 0.000 claims description 37
- SHXWCVYOXRDMCX-UHFFFAOYSA-N 3,4-methylenedioxymethamphetamine Chemical compound CNC(C)CC1=CC=C2OCOC2=C1 SHXWCVYOXRDMCX-UHFFFAOYSA-N 0.000 claims description 29
- 108700024394 Exon Proteins 0.000 claims description 29
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 29
- 230000003321 amplification Effects 0.000 claims description 27
- 241000110847 Kochia Species 0.000 claims description 25
- 108010022394 Threonine synthase Proteins 0.000 claims description 23
- 102000004419 dihydrofolate reductase Human genes 0.000 claims description 22
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims description 18
- 239000002773 nucleotide Substances 0.000 claims description 13
- 125000003729 nucleotide group Chemical group 0.000 claims description 13
- 108010025815 Kanamycin Kinase Proteins 0.000 claims description 11
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 7
- 241000699802 Cricetulus griseus Species 0.000 claims description 6
- 238000003780 insertion Methods 0.000 claims description 6
- 230000037431 insertion Effects 0.000 claims description 6
- 108010085336 phosphoribosyl-AMP cyclohydrolase Proteins 0.000 claims description 6
- 238000012216 screening Methods 0.000 claims description 6
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 claims description 5
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 claims description 5
- 241000700584 Simplexvirus Species 0.000 claims description 5
- 108020004440 Thymidine kinase Proteins 0.000 claims description 5
- 108020002326 glutamine synthetase Proteins 0.000 claims description 5
- 108010002685 hygromycin-B kinase Proteins 0.000 claims description 5
- 210000001672 ovary Anatomy 0.000 claims description 5
- 229920001184 polypeptide Polymers 0.000 claims description 5
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 4
- 230000001131 transforming effect Effects 0.000 claims description 4
- 241000699800 Cricetinae Species 0.000 claims description 3
- 108091008146 restriction endonucleases Proteins 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 2
- 102000055025 Adenosine deaminases Human genes 0.000 claims 4
- 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 claims 4
- 102000006601 Thymidine Kinase Human genes 0.000 claims 4
- 102000005396 glutamine synthetase Human genes 0.000 claims 4
- 108020000946 Bacterial DNA Proteins 0.000 claims 2
- 241000238631 Hexapoda Species 0.000 claims 2
- 108020005202 Viral DNA Proteins 0.000 claims 2
- 210000003292 kidney cell Anatomy 0.000 claims 2
- 229940072221 immunoglobulins Drugs 0.000 abstract description 9
- 238000010367 cloning Methods 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 241001045988 Neogene Species 0.000 description 17
- 101150091879 neo gene Proteins 0.000 description 17
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 229960000485 methotrexate Drugs 0.000 description 14
- 108091029865 Exogenous DNA Proteins 0.000 description 13
- 238000004520 electroporation Methods 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- 230000004544 DNA amplification Effects 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 7
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 7
- 238000010363 gene targeting Methods 0.000 description 7
- 230000001771 impaired effect Effects 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 6
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 6
- 229940045513 CTLA4 antagonist Drugs 0.000 description 6
- 101150074155 DHFR gene Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000010276 construction Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000003248 secreting effect Effects 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 5
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000006798 recombination Effects 0.000 description 5
- 238000005215 recombination Methods 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 4
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 4
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 4
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 4
- 108020005067 RNA Splice Sites Proteins 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000002759 chromosomal effect Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 230000008488 polyadenylation Effects 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 2
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- ZQISRDCJNBUVMM-UHFFFAOYSA-N L-Histidinol Natural products OCC(N)CC1=CN=CN1 ZQISRDCJNBUVMM-UHFFFAOYSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- ZQISRDCJNBUVMM-YFKPBYRVSA-N L-histidinol Chemical compound OC[C@@H](N)CC1=CNC=N1 ZQISRDCJNBUVMM-YFKPBYRVSA-N 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 230000003466 anti-cipated effect Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000644 propagated effect Effects 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 108010051219 Cre recombinase Proteins 0.000 description 1
- 238000007399 DNA isolation Methods 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000702191 Escherichia virus P1 Species 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 108010073816 IgE Receptors Proteins 0.000 description 1
- 102000009438 IgE Receptors Human genes 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 241000254158 Lampyridae Species 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 241000950638 Symphysodon discus Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000013493 large scale plasmid preparation Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229940070376 protein Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2851—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the lectin superfamily, e.g. CD23, CD72
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- 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
- C12N2800/10—Plasmid DNA
- C12N2800/108—Plasmid DNA episomal vectors
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/42—Vector systems having a special element relevant for transcription being an intron or intervening sequence for splicing and/or stability of RNA
-
- 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
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
-
- 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
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/44—Vectors comprising a special translation-regulating system being a specific part of the splice mechanism, e.g. donor, acceptor
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Mycology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/819,866 | 1997-03-14 | ||
| US08/819,866 US5830698A (en) | 1997-03-14 | 1997-03-14 | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
| US09/023,715 | 1998-02-13 | ||
| US09/023,715 US5998144A (en) | 1997-03-14 | 1998-02-13 | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
| PCT/US1998/003935 WO1998041645A1 (en) | 1997-03-14 | 1998-03-09 | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2283740A1 CA2283740A1 (en) | 1998-09-24 |
| CA2283740C true CA2283740C (en) | 2006-06-27 |
Family
ID=26697516
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002283740A Expired - Fee Related CA2283740C (en) | 1997-03-14 | 1998-03-09 | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
Country Status (21)
| Country | Link |
|---|---|
| US (3) | US6413777B1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP0981637B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP4128227B2 (cg-RX-API-DMAC7.html) |
| CN (1) | CN1175111C (cg-RX-API-DMAC7.html) |
| AT (1) | ATE296356T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU737155B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BR9808584A (cg-RX-API-DMAC7.html) |
| CA (1) | CA2283740C (cg-RX-API-DMAC7.html) |
| CZ (1) | CZ293355B6 (cg-RX-API-DMAC7.html) |
| DE (1) | DE69830312T2 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2242997T3 (cg-RX-API-DMAC7.html) |
| ID (1) | ID24565A (cg-RX-API-DMAC7.html) |
| IL (1) | IL131746A0 (cg-RX-API-DMAC7.html) |
| IN (1) | IN189732B (cg-RX-API-DMAC7.html) |
| NO (1) | NO994397L (cg-RX-API-DMAC7.html) |
| PL (1) | PL191251B1 (cg-RX-API-DMAC7.html) |
| PT (1) | PT981637E (cg-RX-API-DMAC7.html) |
| RO (1) | RO120148B1 (cg-RX-API-DMAC7.html) |
| RU (1) | RU2004107694A (cg-RX-API-DMAC7.html) |
| TW (1) | TWI232239B (cg-RX-API-DMAC7.html) |
| WO (1) | WO1998041645A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (108)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5830698A (en) * | 1997-03-14 | 1998-11-03 | Idec Pharmaceuticals Corporation | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
| RO120148B1 (ro) * | 1997-03-14 | 2005-09-30 | Idec Pharmaceuticals Corporation | Sistem vector şi procedeu de inserţie a unui fragment adn, în genomul celulelor de mamifere |
| WO1999029902A1 (en) | 1997-12-08 | 1999-06-17 | California Institute Of Technology | Method for creating polynucleotide and polypeptide sequences |
| CA2360347C (en) | 1998-12-31 | 2013-05-07 | Chiron Corporation | Improved expression of hiv polypeptides and production of virus-like particles |
| WO2000039304A2 (en) | 1998-12-31 | 2000-07-06 | Chiron Corporation | Polynucleotides encoding antigenic hiv type c polypeptides, polypeptides and uses thereof |
| GB9912965D0 (en) * | 1999-06-03 | 1999-08-04 | Oxford Biomedica Ltd | In vivo selection method |
| US6316253B1 (en) | 1999-11-01 | 2001-11-13 | Chiron Corporation | Expression vectors, transfection systems, and method of use thereof |
| DK1297170T3 (en) * | 2000-06-23 | 2016-03-14 | Novozymes As | A process for stable chromosomal integration of multiple copies of the genes |
| EP2412242A3 (en) | 2001-07-05 | 2012-06-13 | Novartis Vaccines and Diagnostics, Inc. | Polynucleotides encoding antigenic HIV Type C polypeptides, polypeptides and uses thereof |
| US20030170614A1 (en) | 2001-08-31 | 2003-09-11 | Megede Jan Zur | Polynucleotides encoding antigenic HIV type B polypeptides, polypeptides and uses thereof |
| HUP0402164A3 (en) | 2001-11-16 | 2010-01-28 | Biogen Idec Inc | Polycistronic expression of antibodies |
| US7164056B2 (en) * | 2002-05-03 | 2007-01-16 | Pioneer Hi-Bred International, Inc. | Gene targeting using replicating DNA molecules |
| PT1523496E (pt) | 2002-07-18 | 2011-09-29 | Merus B V | Produção de misturas de anticorpos de forma recombinante |
| USRE47770E1 (en) | 2002-07-18 | 2019-12-17 | Merus N.V. | Recombinant production of mixtures of antibodies |
| US20040170614A1 (en) * | 2002-10-30 | 2004-09-02 | Gail Bishop | Somatic cell gene targeting vectors and methods of use thereof |
| EA013225B1 (ru) * | 2003-01-07 | 2010-04-30 | Симфоген А/С | Способ получения линии клеток, продуцирующей рекомбинантный поликлональный белок, способ получения поликлонального белка, линия клеток, продуцирующая рекомбинантный поликлональный белок, библиотека векторов, популяция клеток |
| DE10303937A1 (de) * | 2003-01-31 | 2004-08-12 | Icon Genetics Ag | Pflanzentransformation mit Assemblierung einer gewünschten Sequenz in Vivo |
| ATE426672T1 (de) * | 2003-01-31 | 2009-04-15 | Icon Genetics Gmbh | Pflanzentransformation mit in-vivo-zusammenbau einer eigenschaft |
| WO2004085648A2 (en) | 2003-03-19 | 2004-10-07 | Biogen Idec Ma Inc. | Nogo receptor binding protein |
| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| JP5416338B2 (ja) * | 2003-05-09 | 2014-02-12 | デューク ユニバーシティ | Ｃｄ２０特異的抗体およびその使用方法 |
| US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| EP1639009B1 (en) | 2003-05-30 | 2013-02-27 | Merus B.V. | Fab library for the preparation of a mixture of antibodies |
| AU2004252170B2 (en) * | 2003-06-27 | 2011-01-27 | Biogen Ma Inc. | Use of hydrophobic-interaction-chromatography or hinge-region modifications for the production of homogeneous antibody-solutions |
| ES2374526T3 (es) | 2003-09-04 | 2012-02-17 | Medarex, Inc. | Vector de expresión. |
| US8030833B2 (en) * | 2003-09-19 | 2011-10-04 | The Board Of Trustees Of The University Of Illinois | Electron emission device incorporating free standing monocrystalline nanowires |
| US7344753B2 (en) * | 2003-09-19 | 2008-03-18 | The Board Of Trustees Of The University Of Illinois | Nanostructures including a metal |
| US7935862B2 (en) * | 2003-12-02 | 2011-05-03 | Syngenta Participations Ag | Targeted integration and stacking of DNA through homologous recombination |
| CA2554054C (en) | 2004-01-20 | 2013-06-04 | Merus B.V. | Mixtures of binding proteins |
| BRPI0512500A (pt) | 2004-06-24 | 2008-03-11 | Biogen Idec Inc | tratamento ou condições envolvendo desmielinação |
| EP2053408B1 (en) | 2004-07-20 | 2012-03-07 | Symphogen A/S | A procedure for structural characterization of a recombinant polyclonal protein or a polyclonal cell line |
| EP2329714A1 (en) | 2004-08-03 | 2011-06-08 | Biogen Idec MA Inc. | Influence of TAJ in the neuronal functions |
| FR2879204B1 (fr) | 2004-12-15 | 2007-02-16 | Lab Francais Du Fractionnement | Anticorps cytotoxique dirige contre les proliferations hematopoietiques lymphoides de type b. |
| KR20070100346A (ko) | 2005-01-05 | 2007-10-10 | 바이오겐 아이덱 엠에이 인코포레이티드 | 크립토 결합 분자 |
| CN100381573C (zh) * | 2005-04-14 | 2008-04-16 | 北京天广实生物技术有限公司 | 快速构建目标基因高表达的哺乳动物细胞株的体系和方法 |
| RS53058B (sr) | 2005-07-08 | 2014-04-30 | Biogen Idec Ma Inc. | Sp35 antitela i njihova primena |
| NZ565711A (en) * | 2005-08-09 | 2011-10-28 | Revivicor Inc | Transgenic ungulates expressing a porcine CTLA4 peptide fused to an immunoglobulin |
| JP2009517340A (ja) | 2005-11-04 | 2009-04-30 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | ドーパミン作動性ニューロンの神経突起成長および生存を促進するための方法 |
| NZ569428A (en) | 2005-12-02 | 2012-11-30 | Biogen Idec Inc | Treatment of conditions involving demyelination with a Sp35 antagonist |
| US20070136826A1 (en) * | 2005-12-02 | 2007-06-14 | Biogen Idec Inc. | Anti-mouse CD20 antibodies and uses thereof |
| CN103215293B (zh) | 2006-01-27 | 2015-10-28 | 比奥根Ma公司 | Nogo受体拮抗剂 |
| SI2436696T1 (sl) | 2007-01-05 | 2017-10-30 | University Of Zurich | Anti-beta-amiloidno protitelo in načini njegove uporabe |
| CA2674603C (en) | 2007-01-09 | 2016-03-29 | Biogen Idec Ma Inc. | Sp35 antibodies and uses thereof |
| US8128926B2 (en) | 2007-01-09 | 2012-03-06 | Biogen Idec Ma Inc. | Sp35 antibodies and uses thereof |
| EA017403B1 (ru) | 2007-02-02 | 2012-12-28 | Байоджен Айдек Эмэй Инк. | Использование семафорина 6а в качестве промотора миелинизации и дифференцировки олигодендроцитов |
| CA2701189C (en) * | 2007-10-11 | 2017-05-16 | Biogen Idec Ma Inc. | Methods for treating pressure induced optic neuropathy, preventing neuronal degeneration and promoting neuronal cell survival via administration of lingo-1 antagonists and trkb agonists |
| WO2009061500A1 (en) * | 2007-11-08 | 2009-05-14 | Biogen Idec Ma Inc. | Use of lingo-4 antagonists in the treatment of conditions involving demyelination |
| CA2708776A1 (en) * | 2007-12-10 | 2009-06-18 | Aliva Biopharmaceuticals, Inc. | Methods for sequential replacement of targeted region by homologous recombination |
| DK2982695T3 (da) | 2008-07-09 | 2019-05-13 | Biogen Ma Inc | Sammensætninger, der omfatter antistoffer mod lingo eller fragmenter deraf |
| KR102362774B1 (ko) | 2008-09-30 | 2022-02-15 | 아블렉시스, 엘엘씨 | 키메라 항체의 제조를 위한 인간 이외의 포유동물 |
| EA030826B1 (ru) | 2008-12-19 | 2018-10-31 | Панима Фармасьютикалз Аг | ЧЕЛОВЕЧЕСКИЕ АУТОАНТИТЕЛА ПРОТИВ α-СИНУКЛЕИНА |
| EP2382238A1 (en) | 2008-12-31 | 2011-11-02 | Biogen Idec MA Inc. | Anti-lymphotoxin antibodies |
| CA2756186A1 (en) | 2009-03-24 | 2010-09-30 | Teva Biopharmaceuticals Usa, Inc. | Humanized antibodies against light and uses thereof |
| JP4998814B2 (ja) | 2009-10-01 | 2012-08-15 | Ｔｏｔｏ株式会社 | Ｄｎａ構築物およびそれを用いた組み換えｃｈｏ細胞の製造方法 |
| ES2641920T3 (es) | 2010-03-31 | 2017-11-14 | Ablexis, Llc | Ingeniería genética de animales no humanos para la producción de anticuerpos quiméricos |
| SG184903A1 (en) * | 2010-04-30 | 2012-11-29 | Temasek Life Sciences Lab Ltd | Fragment switch: a reverse genetic approach |
| EA201291482A1 (ru) | 2010-07-09 | 2013-10-30 | Байоджен Айдек Хемофилия Инк. | Химерные факторы коагуляции |
| PT2627672T (pt) | 2010-10-11 | 2018-11-16 | Univ Zuerich | Anticorpos anti-tau humanos |
| DK2640743T3 (en) | 2010-11-16 | 2017-01-23 | Excelimmune Inc | PROCEDURES FOR THE PREPARATION OF RECOMBINANT PROTEINS |
| JP5209693B2 (ja) * | 2010-12-10 | 2013-06-12 | ロンザ・バイオロジクス・ピーエルシー | Ｃｈｏ細胞において組換えタンパク質を発現する方法 |
| JP6067575B2 (ja) | 2010-12-17 | 2017-01-25 | ニューリミューン ホールディング エイジー | ヒト抗ｓｏｄ１抗体 |
| ES2699801T3 (es) | 2011-06-23 | 2019-02-12 | Biogen Int Neuroscience Gmbh | Moléculas de unión anti-alfa sinucleína |
| US9738707B2 (en) | 2011-07-15 | 2017-08-22 | Biogen Ma Inc. | Heterodimeric Fc regions, binding molecules comprising same, and methods relating thereto |
| US9175072B2 (en) | 2011-12-22 | 2015-11-03 | Elwha Llc | Compositions and methods including recombinant B lymphocyte cell line including an exogenously incorporated nucleic acid expressing an exogenous membrane immunoglobulin reactive to a first antigen and including an endogenous gene expressing an endogenous secreted immunoglobulin reactive to a second antigen |
| US10745468B2 (en) | 2011-12-22 | 2020-08-18 | Kota Biotherapeutics, Llc | Compositions and methods for modified B cells expressing reassigned biological agents |
| US8962315B2 (en) | 2011-12-22 | 2015-02-24 | Elwha Llc | Compositions and methods including recombinant B lymphocyte cell line including at least one endogenous gene expressing at least one endogenous membrane immunoglobulin reactive to a first antigen and including at least one exogenously incorporated nucleic acid expressing at least one exogenous secreted immunoglobulin reactive to a second antigen |
| US10233424B2 (en) | 2011-12-22 | 2019-03-19 | Elwha Llc | Compositions and methods including cytotoxic B lymphocyte cell line expressing exogenous membrane immunoglobulin different from secreted immunoglobulin |
| ES2740749T3 (es) | 2012-04-20 | 2020-02-06 | Merus Nv | Métodos y medios para la producción de moléculas heterodiméricas similares a Ig |
| KR101904508B1 (ko) | 2012-04-25 | 2018-10-04 | 리제너론 파마슈티칼스 인코포레이티드 | 큰 표적화 벡터를 사용한 뉴클레아제-중재된 표적화 |
| US10174331B2 (en) | 2012-05-07 | 2019-01-08 | Sangamo Therapeutics, Inc. | Methods and compositions for nuclease-mediated targeted integration of transgenes |
| EP2849787A4 (en) | 2012-05-14 | 2016-06-15 | Biogen Ma Inc | LINGO-2 ANTAGONISTS FOR THE TREATMENT OF DISEASES INVOLVING ENGINE NEURONS |
| JP2015525222A (ja) | 2012-06-08 | 2015-09-03 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | キメラ性凝固因子 |
| MX2015004436A (es) | 2012-10-09 | 2015-06-24 | Biogen Idec Inc | Tratamientos conjuntos y usos para tratar trastornos desmielinizantes. |
| AU2013361107B2 (en) | 2012-12-21 | 2018-08-23 | Biogen International Neuroscience Gmbh | Human anti-tau antibodies |
| US9771413B2 (en) | 2012-12-31 | 2017-09-26 | Neurimmune Holding Ag | Recombinant human antibodies for therapy and prevention of polyomavirus-related diseases |
| PL2956477T5 (pl) | 2013-02-15 | 2024-05-27 | Bioverativ Therapeutics Inc. | Zoptymalizowany gen czynnika viii |
| SG10201707600XA (en) | 2013-03-15 | 2017-11-29 | Biogen Ma Inc | Factor ix polypeptide formulations |
| US11008561B2 (en) | 2014-06-30 | 2021-05-18 | Bioverativ Therapeutics Inc. | Optimized factor IX gene |
| CN107074937B (zh) | 2014-07-29 | 2021-07-27 | 神经免疫控股公司 | 人源抗亨廷顿蛋白(htt)抗体及其用途 |
| AU2015326911C1 (en) | 2014-09-30 | 2025-12-18 | Neurimmune Holding Ag | Human-derived anti-dipeptide repeats (DPRs) antibody |
| MA40835A (fr) | 2014-10-23 | 2017-08-29 | Biogen Ma Inc | Anticorps anti-gpiib/iiia et leurs utilisations |
| MA40861A (fr) | 2014-10-31 | 2017-09-05 | Biogen Ma Inc | Anticorps anti-glycoprotéines iib/iiia |
| MX2017009038A (es) | 2015-01-08 | 2017-10-25 | Biogen Ma Inc | Antagonistas de proteina 1 de interacción con el receptor de nogo que contiene el dominio de inmunoglobulina y repeticiones ricas en leucina (lingo-1) y usos para el tratamiento de trastornos desmielinizantes. |
| CN106191040B (zh) * | 2015-04-30 | 2021-09-14 | 杭州菁因康生物科技有限公司 | 基因打靶方法 |
| IL257231B (en) | 2015-08-03 | 2022-09-01 | Bioverativ Therapeutics Inc | Factor ix fusion proteins and methods of making and using same |
| RS63548B1 (sr) | 2016-02-01 | 2022-09-30 | Bioverativ Therapeutics Inc | Optimizovani geni faktora viii |
| WO2017214376A1 (en) | 2016-06-10 | 2017-12-14 | Elwha Llc | Compositions and methods including b lymphocyte cell line expressing membrane immunoglobulin different from secreted immunoglobulin and cytolytic function |
| JP2018035137A (ja) | 2016-07-13 | 2018-03-08 | マブイミューン ダイアグノスティックス エイジーＭａｂｉｍｍｕｎｅ Ｄｉａｇｎｏｓｔｉｃｓ Ａｇ | 新規な抗線維芽細胞活性化タンパク質（ｆａｐ）結合薬剤およびその使用 |
| MA45668A (fr) | 2016-07-13 | 2019-05-22 | Biogen Ma Inc | Schémas posologiques d'antagonistes de lingo-1 et leurs utilisations pour le traitement de troubles de démyélinisation |
| CA3044838A1 (en) | 2016-12-02 | 2018-06-07 | Bioverativ Therapeutics Inc. | Methods of inducing immune tolerance to clotting factors |
| CN110520150A (zh) | 2016-12-02 | 2019-11-29 | 比奥维拉迪维治疗股份有限公司 | 使用嵌合凝血因子治疗血友病性关节病的方法 |
| EA201991768A1 (ru) | 2017-01-31 | 2020-01-22 | Байоверетив Терапьютикс Инк. | Слитые белки на основе фактора ix и способы их получения и пути применения |
| KR20250040746A (ko) | 2017-08-09 | 2025-03-24 | 바이오버라티브 테라퓨틱스 인크. | 핵산 분자 및 이의 용도 |
| BR112020018709A2 (pt) | 2018-03-28 | 2021-01-05 | Bristol-Myers Squibb Company | Proteínas de fusão do receptor alfa de interleucina-2/interleucina-2 e métodos de uso |
| WO2019210054A1 (en) | 2018-04-27 | 2019-10-31 | Biogen Ma Inc. | Human-derived anti-(poly-ga) dipeptide repeat (dpr) antibody |
| LT3793588T (lt) | 2018-05-18 | 2025-06-25 | Bioverativ Therapeutics Inc. | Hemofilijos a gydymo būdai |
| KR102848349B1 (ko) | 2018-06-04 | 2025-08-21 | 바이오젠 엠에이 인코포레이티드 | 감소된 효과기 기능을 갖는 항-ｖｌａ-4 항체 |
| CN110607326B (zh) * | 2018-06-15 | 2022-11-29 | 江苏省农业科学院 | 非强启动式的外源基因表达法及其在具有毒性的目标蛋白表达中的应用 |
| JP7602454B2 (ja) | 2018-08-09 | 2024-12-18 | バイオベラティブ セラピューティクス インコーポレイテッド | 核酸分子及び非ウイルス遺伝子治療のためのそれらの使用 |
| JP7549582B2 (ja) * | 2018-10-01 | 2024-09-11 | ロンザ リミテッド | 予測可能かつ安定な導入遺伝子発現を有するｓｓｉ細胞および形成の方法 |
| SG11202108560RA (en) | 2019-02-13 | 2021-09-29 | Brigham & Womens Hospital Inc | Anti-peripheral lymph node addressin antibodies and uses thereof |
| US12403164B2 (en) | 2019-09-30 | 2025-09-02 | Bioverativ Therapeutics Inc. | Lentiviral vector formulations |
| JP2023516028A (ja) | 2020-02-28 | 2023-04-17 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッド | 多重特異性抗体を介したトランスフォーミング増殖因子ベータスーパーファミリーシグナル伝達の選択的調節 |
| BR112022026127A2 (pt) | 2020-06-24 | 2023-01-17 | Bioverativ Therapeutics Inc | Métodos para remoção de fator viii livre de preparações de vetores lentivirais modificados para expressar referida proteína |
| WO2023028455A1 (en) | 2021-08-23 | 2023-03-02 | Bioverativ Therapeutics Inc. | Closed-end dna production with inverted terminal repeat sequences |
| TW202323274A (zh) | 2021-08-23 | 2023-06-16 | 美商百歐維拉提夫治療公司 | 優化因子viii基因 |
| AU2022355088A1 (en) | 2021-09-30 | 2024-05-16 | Bioverativ Therapeutics Inc. | Nucleic acids encoding factor viii polypeptides with reduced immunogenicity |
| WO2025104243A1 (en) | 2023-11-15 | 2025-05-22 | Neurimmune Ag | Anti-transthyretin antibody, compositions comprising said antibody and methods for treating or preventing transthyretin-mediated amyloidosis |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5202238A (en) | 1987-10-27 | 1993-04-13 | Oncogen | Production of chimeric antibodies by homologous recombination |
| FR2646438B1 (fr) | 1989-03-20 | 2007-11-02 | Pasteur Institut | Procede de remplacement specifique d'une copie d'un gene present dans le genome receveur par l'integration d'un gene different de celui ou se fait l'integration |
| US5464764A (en) * | 1989-08-22 | 1995-11-07 | University Of Utah Research Foundation | Positive-negative selection methods and vectors |
| WO1991006667A1 (en) | 1989-11-06 | 1991-05-16 | Cell Genesys, Inc. | Production of proteins using homologous recombination |
| PT101031B (pt) | 1991-11-05 | 2002-07-31 | Transkaryotic Therapies Inc | Processo para o fornecimento de proteinas por terapia genetica |
| AU4401993A (en) * | 1992-06-04 | 1993-12-30 | Exemplar Corporation | Insertion of heterologous dna outside of known chromosomal genes |
| MX9305183A (es) * | 1992-08-27 | 1994-05-31 | Us Agriculture | Intron portatil, molecula de adn genomico viral, virus vivo y vacuna que los contiene y metodo para su obtencion. |
| US5648267A (en) * | 1992-11-13 | 1997-07-15 | Idec Pharmaceuticals Corporation | Impaired dominant selectable marker sequence and intronic insertion strategies for enhancement of expression of gene product and expression vector systems comprising same |
| US5830698A (en) * | 1997-03-14 | 1998-11-03 | Idec Pharmaceuticals Corporation | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
| RO120148B1 (ro) * | 1997-03-14 | 2005-09-30 | Idec Pharmaceuticals Corporation | Sistem vector şi procedeu de inserţie a unui fragment adn, în genomul celulelor de mamifere |
-
1998
- 1998-03-09 RO RO99-00972A patent/RO120148B1/ro unknown
- 1998-03-09 AT AT98910109T patent/ATE296356T1/de not_active IP Right Cessation
- 1998-03-09 AU AU64435/98A patent/AU737155B2/en not_active Ceased
- 1998-03-09 CA CA002283740A patent/CA2283740C/en not_active Expired - Fee Related
- 1998-03-09 EP EP98910109A patent/EP0981637B1/en not_active Revoked
- 1998-03-09 CN CNB988049880A patent/CN1175111C/zh not_active Expired - Fee Related
- 1998-03-09 JP JP54053998A patent/JP4128227B2/ja not_active Expired - Fee Related
- 1998-03-09 DE DE69830312T patent/DE69830312T2/de not_active Revoked
- 1998-03-09 ES ES98910109T patent/ES2242997T3/es not_active Expired - Lifetime
- 1998-03-09 CZ CZ19993162A patent/CZ293355B6/cs not_active IP Right Cessation
- 1998-03-09 BR BR9808584-0A patent/BR9808584A/pt not_active Application Discontinuation
- 1998-03-09 IL IL13174698A patent/IL131746A0/xx not_active IP Right Cessation
- 1998-03-09 PT PT98910109T patent/PT981637E/pt unknown
- 1998-03-09 WO PCT/US1998/003935 patent/WO1998041645A1/en not_active Ceased
- 1998-03-09 ID IDW991196A patent/ID24565A/id unknown
- 1998-03-09 PL PL335695A patent/PL191251B1/pl not_active IP Right Cessation
- 1998-03-10 IN IN616DE1998 patent/IN189732B/en unknown
- 1998-03-13 TW TW087103778A patent/TWI232239B/zh not_active IP Right Cessation
-
1999
- 1999-06-30 US US09/343,485 patent/US6413777B1/en not_active Expired - Fee Related
- 1999-09-10 NO NO994397A patent/NO994397L/no not_active Application Discontinuation
-
2002
- 2002-04-01 US US10/109,853 patent/US6841383B2/en not_active Expired - Fee Related
-
2004
- 2004-03-15 RU RU2004107694/13A patent/RU2004107694A/ru not_active Application Discontinuation
- 2004-04-06 US US10/817,950 patent/US7235360B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1175111C (zh) | 2004-11-10 |
| NO994397L (no) | 1999-11-09 |
| ID24565A (id) | 2000-07-27 |
| EP0981637A1 (en) | 2000-03-01 |
| US7235360B2 (en) | 2007-06-26 |
| US6841383B2 (en) | 2005-01-11 |
| US20040166528A1 (en) | 2004-08-26 |
| IL131746A0 (en) | 2001-03-19 |
| AU737155B2 (en) | 2001-08-09 |
| BR9808584A (pt) | 2000-05-23 |
| JP2001516221A (ja) | 2001-09-25 |
| NO994397D0 (no) | 1999-09-10 |
| CZ293355B6 (cs) | 2004-04-14 |
| RU2004107694A (ru) | 2005-08-27 |
| TWI232239B (en) | 2005-05-11 |
| US20020192820A1 (en) | 2002-12-19 |
| AU6443598A (en) | 1998-10-12 |
| DE69830312T2 (de) | 2006-02-02 |
| ES2242997T3 (es) | 2005-11-16 |
| EP0981637B1 (en) | 2005-05-25 |
| WO1998041645A1 (en) | 1998-09-24 |
| CZ316299A3 (cs) | 2000-02-16 |
| US6413777B1 (en) | 2002-07-02 |
| CA2283740A1 (en) | 1998-09-24 |
| PL335695A1 (en) | 2000-05-08 |
| ATE296356T1 (de) | 2005-06-15 |
| IN189732B (cg-RX-API-DMAC7.html) | 2003-04-19 |
| CN1255166A (zh) | 2000-05-31 |
| RO120148B1 (ro) | 2005-09-30 |
| DE69830312D1 (de) | 2005-06-30 |
| PT981637E (pt) | 2005-09-30 |
| JP4128227B2 (ja) | 2008-07-30 |
| PL191251B1 (pl) | 2006-04-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2283740C (en) | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same | |
| US5998144A (en) | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same | |
| WO1998041645A9 (en) | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same | |
| KR100479146B1 (ko) | 큰게놈dna결실유발법 | |
| US5578461A (en) | Gene manipulation and expression using genomic elements | |
| USRE49347E1 (en) | Mammalian expression vector | |
| US7968341B2 (en) | Sequence specific DNA recombination in eukaryotic cells | |
| HK1086298A (en) | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same | |
| HK1086299A (en) | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same | |
| MXPA99008363A (en) | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same | |
| HUP0002320A2 (hu) | Eljárás gének helyspecifikus integrálására emlős sejtekbe homológ rekombinációval és az eljárás végrehajtására alkalmas vektorok | |
| US6884622B1 (en) | Method for preparing a mammalian cell deficient in HPRT | |
| Wurm | 1.4 Aspects of Gene Transfer and Gene Amplification | |
| HK1026000B (en) | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |