CA3225091A1 - Humanized c5 and c3 animals - Google Patents
Humanized c5 and c3 animals Download PDFInfo
- Publication number
- CA3225091A1 CA3225091A1 CA3225091A CA3225091A CA3225091A1 CA 3225091 A1 CA3225091 A1 CA 3225091A1 CA 3225091 A CA3225091 A CA 3225091A CA 3225091 A CA3225091 A CA 3225091A CA 3225091 A1 CA3225091 A1 CA 3225091A1
- Authority
- CA
- Canada
- Prior art keywords
- rodent
- human
- mouse
- protein
- gene
- 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.)
- Pending
Links
- 241001465754 Metazoa Species 0.000 title abstract description 28
- 241000283984 Rodentia Species 0.000 claims abstract description 327
- 101100440311 Homo sapiens C5 gene Proteins 0.000 claims abstract description 85
- 238000000034 method Methods 0.000 claims abstract description 68
- 230000001105 regulatory effect Effects 0.000 claims abstract description 64
- 101000901154 Homo sapiens Complement C3 Proteins 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 52
- 102000057770 human C3 Human genes 0.000 claims abstract description 42
- 101150069146 C5 gene Proteins 0.000 claims abstract description 36
- 101150071258 C3 gene Proteins 0.000 claims abstract description 32
- 150000007523 nucleic acids Chemical group 0.000 claims abstract description 24
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 302
- 102000004169 proteins and genes Human genes 0.000 claims description 145
- 210000002966 serum Anatomy 0.000 claims description 93
- 230000024203 complement activation Effects 0.000 claims description 75
- 108700024394 Exon Proteins 0.000 claims description 57
- 230000000295 complement effect Effects 0.000 claims description 52
- 101100328540 Homo sapiens C3 gene Proteins 0.000 claims description 47
- 101100328542 Mus musculus C3 gene Proteins 0.000 claims description 44
- 238000003556 assay Methods 0.000 claims description 31
- 101100440312 Mus musculus C5 gene Proteins 0.000 claims description 30
- 101710131943 40S ribosomal protein S3a Proteins 0.000 claims description 29
- 230000014509 gene expression Effects 0.000 claims description 23
- 108020004707 nucleic acids Proteins 0.000 claims description 15
- 102000039446 nucleic acids Human genes 0.000 claims description 15
- -1 small molecule chemical compound Chemical class 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 230000003247 decreasing effect Effects 0.000 claims description 4
- 238000011577 humanized mouse model Methods 0.000 claims description 4
- 238000007423 screening assay Methods 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 abstract description 66
- 241000700159 Rattus Species 0.000 abstract description 59
- 230000004154 complement system Effects 0.000 abstract description 22
- 241000699666 Mus <mouse, genus> Species 0.000 description 195
- 235000018102 proteins Nutrition 0.000 description 132
- 210000004027 cell Anatomy 0.000 description 54
- 230000002949 hemolytic effect Effects 0.000 description 39
- 108090000765 processed proteins & peptides Proteins 0.000 description 30
- 102000004196 processed proteins & peptides Human genes 0.000 description 30
- 235000001014 amino acid Nutrition 0.000 description 29
- 229920001184 polypeptide Polymers 0.000 description 26
- 230000001225 therapeutic effect Effects 0.000 description 24
- 108700028369 Alleles Proteins 0.000 description 22
- 150000001413 amino acids Chemical class 0.000 description 21
- 239000000523 sample Substances 0.000 description 21
- 241001529936 Murinae Species 0.000 description 19
- 241000894007 species Species 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 18
- 102000000989 Complement System Proteins Human genes 0.000 description 17
- 108010069112 Complement System Proteins Proteins 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- 108091034117 Oligonucleotide Proteins 0.000 description 16
- 230000006870 function Effects 0.000 description 16
- 238000011144 upstream manufacturing Methods 0.000 description 16
- 239000002773 nucleotide Substances 0.000 description 15
- 125000003729 nucleotide group Chemical group 0.000 description 15
- 108700019146 Transgenes Proteins 0.000 description 14
- 230000003285 pharmacodynamic effect Effects 0.000 description 13
- 230000002441 reversible effect Effects 0.000 description 13
- 239000012634 fragment Substances 0.000 description 12
- 210000001161 mammalian embryo Anatomy 0.000 description 12
- 150000003384 small molecules Chemical class 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 206010018910 Haemolysis Diseases 0.000 description 10
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 10
- 125000003275 alpha amino acid group Chemical group 0.000 description 10
- 239000005557 antagonist Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 230000037361 pathway Effects 0.000 description 10
- 108091026890 Coding region Proteins 0.000 description 9
- 102100022133 Complement C3 Human genes 0.000 description 9
- 102100031506 Complement C5 Human genes 0.000 description 9
- 230000004913 activation Effects 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000008588 hemolysis Effects 0.000 description 9
- 238000011813 knockout mouse model Methods 0.000 description 9
- 241000124008 Mammalia Species 0.000 description 8
- 108091036066 Three prime untranslated region Proteins 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 238000011529 RT qPCR Methods 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 210000004602 germ cell Anatomy 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000000349 chromosome Anatomy 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 239000007790 solid phase Substances 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 230000009261 transgenic effect Effects 0.000 description 6
- 206010063837 Reperfusion injury Diseases 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 238000001212 derivatisation Methods 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- 238000006352 cycloaddition reaction Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000012239 gene modification Methods 0.000 description 4
- 230000005017 genetic modification Effects 0.000 description 4
- 235000013617 genetically modified food Nutrition 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 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 3
- 238000011740 C57BL/6 mouse Methods 0.000 description 3
- 108010028773 Complement C5 Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 3
- 206010064930 age-related macular degeneration Diseases 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 210000002257 embryonic structure Anatomy 0.000 description 3
- 238000003205 genotyping method Methods 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 208000002780 macular degeneration Diseases 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002207 retinal effect Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- RFLVMTUMFYRZCB-UHFFFAOYSA-N 1-methylguanine Chemical compound O=C1N(C)C(N)=NC2=C1N=CN2 RFLVMTUMFYRZCB-UHFFFAOYSA-N 0.000 description 2
- YSAJFXWTVFGPAX-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetic acid Chemical compound OC(=O)COC1=CNC(=O)NC1=O YSAJFXWTVFGPAX-UHFFFAOYSA-N 0.000 description 2
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
- XDNDSAQVXNZKGP-UHFFFAOYSA-N 3-(1h-pyrrol-2-yl)propanoic acid Chemical compound OC(=O)CCC1=CC=CN1 XDNDSAQVXNZKGP-UHFFFAOYSA-N 0.000 description 2
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 2
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
- ZLAQATDNGLKIEV-UHFFFAOYSA-N 5-methyl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CC1=CNC(=S)NC1=O ZLAQATDNGLKIEV-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 102400000069 Activation peptide Human genes 0.000 description 2
- 101800001401 Activation peptide Proteins 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 2
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 108010028780 Complement C3 Proteins 0.000 description 2
- 108010034753 Complement Membrane Attack Complex Proteins 0.000 description 2
- 241000252212 Danio rerio Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 2
- 229930010555 Inosine Natural products 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- HYVABZIGRDEKCD-UHFFFAOYSA-N N(6)-dimethylallyladenine Chemical compound CC(C)=CCNC1=NC=NC2=C1N=CN2 HYVABZIGRDEKCD-UHFFFAOYSA-N 0.000 description 2
- 108091092724 Noncoding DNA Proteins 0.000 description 2
- 206010030043 Ocular hypertension Diseases 0.000 description 2
- 208000030768 Optic nerve injury Diseases 0.000 description 2
- 241000282577 Pan troglodytes Species 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 206010038997 Retroviral infections Diseases 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 210000002459 blastocyst Anatomy 0.000 description 2
- 210000001109 blastomere Anatomy 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical class SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 208000004264 complement component 5 deficiency Diseases 0.000 description 2
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229960003786 inosine Drugs 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- DRAVOWXCEBXPTN-UHFFFAOYSA-N isoguanine Chemical compound NC1=NC(=O)NC2=C1NC=N2 DRAVOWXCEBXPTN-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000003016 pheromone Substances 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 229940076372 protein antagonist Drugs 0.000 description 2
- 150000007660 quinolones Chemical class 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 150000003548 thiazolidines Chemical class 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- CADQNXRGRFJSQY-UOWFLXDJSA-N (2r,3r,4r)-2-fluoro-2,3,4,5-tetrahydroxypentanal Chemical compound OC[C@@H](O)[C@@H](O)[C@@](O)(F)C=O CADQNXRGRFJSQY-UOWFLXDJSA-N 0.000 description 1
- WJNGQIYEQLPJMN-IOSLPCCCSA-N 1-methylinosine Chemical compound C1=NC=2C(=O)N(C)C=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O WJNGQIYEQLPJMN-IOSLPCCCSA-N 0.000 description 1
- 238000011714 129 mouse Methods 0.000 description 1
- HLYBTPMYFWWNJN-UHFFFAOYSA-N 2-(2,4-dioxo-1h-pyrimidin-5-yl)-2-hydroxyacetic acid Chemical compound OC(=O)C(O)C1=CNC(=O)NC1=O HLYBTPMYFWWNJN-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- ZUYKJZQOPXDNOK-UHFFFAOYSA-N 2-(ethylamino)-2-thiophen-2-ylcyclohexan-1-one;hydrochloride Chemical class Cl.C=1C=CSC=1C1(NCC)CCCCC1=O ZUYKJZQOPXDNOK-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- SGAKLDIYNFXTCK-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)methylamino]acetic acid Chemical compound OC(=O)CNCC1=CNC(=O)NC1=O SGAKLDIYNFXTCK-UHFFFAOYSA-N 0.000 description 1
- XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical compound NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 description 1
- XMSMHKMPBNTBOD-UHFFFAOYSA-N 2-dimethylamino-6-hydroxypurine Chemical compound N1C(N(C)C)=NC(=O)C2=C1N=CN2 XMSMHKMPBNTBOD-UHFFFAOYSA-N 0.000 description 1
- SMADWRYCYBUIKH-UHFFFAOYSA-N 2-methyl-7h-purin-6-amine Chemical compound CC1=NC(N)=C2NC=NC2=N1 SMADWRYCYBUIKH-UHFFFAOYSA-N 0.000 description 1
- KOLPWZCZXAMXKS-UHFFFAOYSA-N 3-methylcytosine Chemical compound CN1C(N)=CC=NC1=O KOLPWZCZXAMXKS-UHFFFAOYSA-N 0.000 description 1
- GJAKJCICANKRFD-UHFFFAOYSA-N 4-acetyl-4-amino-1,3-dihydropyrimidin-2-one Chemical compound CC(=O)C1(N)NC(=O)NC=C1 GJAKJCICANKRFD-UHFFFAOYSA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 1
- VKLFQTYNHLDMDP-PNHWDRBUSA-N 5-carboxymethylaminomethyl-2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C(CNCC(O)=O)=C1 VKLFQTYNHLDMDP-PNHWDRBUSA-N 0.000 description 1
- ZFTBZKVVGZNMJR-UHFFFAOYSA-N 5-chlorouracil Chemical compound ClC1=CNC(=O)NC1=O ZFTBZKVVGZNMJR-UHFFFAOYSA-N 0.000 description 1
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 1
- KELXHQACBIUYSE-UHFFFAOYSA-N 5-methoxy-1h-pyrimidine-2,4-dione Chemical compound COC1=CNC(=O)NC1=O KELXHQACBIUYSE-UHFFFAOYSA-N 0.000 description 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
- DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 description 1
- XTPUXCVIDQFHIT-UHFFFAOYSA-N 8-(3-methylbut-3-enyl)-2-methylsulfanyl-7h-purin-6-amine Chemical compound CSC1=NC(N)=C2NC(CCC(C)=C)=NC2=N1 XTPUXCVIDQFHIT-UHFFFAOYSA-N 0.000 description 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
- 206010060931 Adenovirus infection Diseases 0.000 description 1
- 206010052613 Allergic bronchitis Diseases 0.000 description 1
- 102000013918 Apolipoproteins E Human genes 0.000 description 1
- 108010025628 Apolipoproteins E Proteins 0.000 description 1
- 206010003557 Asthma exercise induced Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000219495 Betulaceae Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006474 Bronchopulmonary aspergillosis allergic Diseases 0.000 description 1
- 101150114997 CD59 gene Proteins 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000016918 Complement C3 Human genes 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000191823 Cynomys Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- ZAQJHHRNXZUBTE-WUJLRWPWSA-N D-xylulose Chemical compound OC[C@@H](O)[C@H](O)C(=O)CO ZAQJHHRNXZUBTE-WUJLRWPWSA-N 0.000 description 1
- 238000011765 DBA/2 mouse Methods 0.000 description 1
- 238000011767 DBA/2J (JAX™ mouse strain) Methods 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 102100023387 Endoribonuclease Dicer Human genes 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 241001481760 Erethizon dorsatum Species 0.000 description 1
- 208000004657 Exercise-Induced Asthma Diseases 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 238000007341 Heck reaction Methods 0.000 description 1
- 108010006464 Hemolysin Proteins Proteins 0.000 description 1
- 238000006842 Henry reaction Methods 0.000 description 1
- 101000882982 Homo sapiens CDK5 regulatory subunit-associated protein 3 Proteins 0.000 description 1
- 101000907904 Homo sapiens Endoribonuclease Dicer Proteins 0.000 description 1
- 101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- 206010048643 Hypereosinophilic syndrome Diseases 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
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 206010022680 Intestinal ischaemia Diseases 0.000 description 1
- 206010022822 Intravascular haemolysis Diseases 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- 101150088352 MDM1 gene Proteins 0.000 description 1
- 208000004451 Membranoproliferative Glomerulonephritis Diseases 0.000 description 1
- 235000011779 Menyanthes trifoliata Nutrition 0.000 description 1
- 240000008821 Menyanthes trifoliata Species 0.000 description 1
- 238000006957 Michael reaction Methods 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- SGSSKEDGVONRGC-UHFFFAOYSA-N N(2)-methylguanine Chemical compound O=C1NC(NC)=NC2=C1N=CN2 SGSSKEDGVONRGC-UHFFFAOYSA-N 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 208000016999 Parasitic Lung disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000035415 Reinfection Diseases 0.000 description 1
- 206010061481 Renal injury Diseases 0.000 description 1
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 0.000 description 1
- 241000555745 Sciuridae Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- 238000006281 Stork reaction Methods 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 208000011589 adenoviridae infectious disease Diseases 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000010085 airway hyperresponsiveness Effects 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 238000005882 aldol condensation reaction Methods 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000006778 allergic bronchopulmonary aspergillosis Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 150000008378 aryl ethers Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 125000005228 aryl sulfonate group Chemical group 0.000 description 1
- 150000001541 aziridines Chemical class 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 238000007193 benzoin condensation reaction Methods 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical class C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000007675 cardiac surgery Methods 0.000 description 1
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 201000004897 cough variant asthma Diseases 0.000 description 1
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 208000022401 dense deposit disease Diseases 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 238000007878 drug screening assay Methods 0.000 description 1
- 208000011325 dry age related macular degeneration Diseases 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000007337 electrophilic addition reaction Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 201000009580 eosinophilic pneumonia Diseases 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 208000024695 exercise-induced bronchoconstriction Diseases 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 201000001505 hemoglobinuria Diseases 0.000 description 1
- 239000003228 hemolysin Substances 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 102000049790 human CDK5RAP3 Human genes 0.000 description 1
- 150000001469 hydantoins Chemical class 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002547 isoxazolines Chemical class 0.000 description 1
- 208000037806 kidney injury Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- IZAGSTRIDUNNOY-UHFFFAOYSA-N methyl 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetate Chemical compound COC(=O)COC1=CNC(=O)NC1=O IZAGSTRIDUNNOY-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 208000007892 occupational asthma Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 150000002917 oxazolidines Chemical class 0.000 description 1
- 150000002918 oxazolines Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- UKIUSKWWNRYHOO-UHFFFAOYSA-N pent-1-yn-1-ol Chemical compound CCCC#CO UKIUSKWWNRYHOO-UHFFFAOYSA-N 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 238000002732 pharmacokinetic assay Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 230000008832 photodamage Effects 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000036273 reactive airway disease Diseases 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 150000007659 semicarbazones Chemical class 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 101150062190 sod1 gene Proteins 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 150000003549 thiazolines Chemical class 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 150000003606 tin compounds Chemical class 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 230000009452 underexpressoin Effects 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- WCNMEQDMUYVWMJ-JPZHCBQBSA-N wybutoxosine Chemical compound C1=NC=2C(=O)N3C(CC([C@H](NC(=O)OC)C(=O)OC)OO)=C(C)N=C3N(C)C=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O WCNMEQDMUYVWMJ-JPZHCBQBSA-N 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 210000004340 zona pellucida Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
- A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/472—Complement proteins, e.g. anaphylatoxin, C3a, C5a
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- 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
- 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
- A01K2267/03—Animal model, e.g. for test or diseases
-
- 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
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0368—Animal model for inflammation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4716—Complement proteins, e.g. anaphylatoxin, C3a, C5a
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Environmental Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Organic Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Pathology (AREA)
- Molecular Biology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Husbandry (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Plant Pathology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Food Science & Technology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461988581P | 2014-05-05 | 2014-05-05 | |
| US61/988,581 | 2014-05-05 | ||
| US201462067836P | 2014-10-23 | 2014-10-23 | |
| US62/067,836 | 2014-10-23 | ||
| CA2946412A CA2946412C (en) | 2014-05-05 | 2015-05-04 | Humanized c5 and c3 animals |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2946412A Division CA2946412C (en) | 2014-05-05 | 2015-05-04 | Humanized c5 and c3 animals |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3225091A1 true CA3225091A1 (en) | 2015-11-12 |
Family
ID=53177902
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3225091A Pending CA3225091A1 (en) | 2014-05-05 | 2015-05-04 | Humanized c5 and c3 animals |
| CA2946412A Active CA2946412C (en) | 2014-05-05 | 2015-05-04 | Humanized c5 and c3 animals |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2946412A Active CA2946412C (en) | 2014-05-05 | 2015-05-04 | Humanized c5 and c3 animals |
Country Status (15)
| Country | Link |
|---|---|
| US (5) | US9795121B2 (enExample) |
| EP (3) | EP4317445A3 (enExample) |
| JP (1) | JP6598798B2 (enExample) |
| KR (1) | KR102461511B1 (enExample) |
| CN (1) | CN106659146B (enExample) |
| AU (1) | AU2015256299C1 (enExample) |
| BR (1) | BR112016025751A2 (enExample) |
| CA (2) | CA3225091A1 (enExample) |
| ES (2) | ES2968749T3 (enExample) |
| IL (1) | IL248481B (enExample) |
| MA (1) | MA51519A (enExample) |
| MX (2) | MX2016014504A (enExample) |
| RU (2) | RU2713327C2 (enExample) |
| SG (2) | SG11201608696RA (enExample) |
| WO (1) | WO2015171523A1 (enExample) |
Families Citing this family (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR095196A1 (es) | 2013-03-15 | 2015-09-30 | Regeneron Pharma | Medio de cultivo celular libre de suero |
| CA3225091A1 (en) * | 2014-05-05 | 2015-11-12 | Regeneron Pharmaceuticals, Inc. | Humanized c5 and c3 animals |
| NO2785538T3 (enExample) | 2014-05-07 | 2018-08-04 | ||
| TWI797060B (zh) | 2015-08-04 | 2023-04-01 | 美商再生元醫藥公司 | 補充牛磺酸之細胞培養基及用法 |
| WO2017132155A1 (en) * | 2016-01-25 | 2017-08-03 | President And Fellows Of Harvard College | Methods and compositions for detecting and treating schizophrenia |
| US10633434B2 (en) | 2016-06-14 | 2020-04-28 | Regeneron Pharmaceuticals, Inc. | Anti-C5 antibodies |
| WO2018039499A1 (en) | 2016-08-24 | 2018-03-01 | Regeneron Pharmaceuticals, Inc. | Host cell protein modification |
| JP7169979B2 (ja) * | 2017-02-27 | 2022-11-11 | 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 | 補体関連腎症および肝線維症の候補治療剤の治療有効性を評価する方法 |
| TW202526028A (zh) | 2017-07-06 | 2025-07-01 | 美商雷傑納榮製藥公司 | 供製備糖蛋白之細胞培養方法 |
| CN107736281A (zh) * | 2017-09-29 | 2018-02-27 | 中国水产科学研究院珠江水产研究所 | 一种利用益生菌发酵酱油渣防治池塘养殖鳜鱼寄生虫的方法 |
| EP3585162B1 (en) * | 2017-09-29 | 2023-08-30 | Regeneron Pharmaceuticals, Inc. | Rodents comprising a humanized ttr locus and methods of use |
| AU2018341685A1 (en) * | 2017-09-29 | 2020-04-02 | Regeneron Pharmaceuticals, Inc. | Non-human animals expressing humanized C1q complex |
| CN120571008A (zh) | 2017-12-13 | 2025-09-02 | 瑞泽恩制药公司 | 抗c5抗体组合及其用途 |
| CN111479618B (zh) | 2017-12-22 | 2022-08-02 | 瑞泽恩制药公司 | 用于表征药物产品杂质的系统和方法 |
| MX2020008095A (es) | 2018-01-31 | 2020-09-24 | Regeneron Pharma | Sistemas y métodos para caracterizar variantes de tamaño y carga de impurezas de productos farmacológicos. |
| TW202311746A (zh) | 2018-02-02 | 2023-03-16 | 美商再生元醫藥公司 | 用於表徵蛋白質二聚合之系統及方法 |
| WO2019168774A1 (en) | 2018-02-28 | 2019-09-06 | Regeneron Pharmaceuticals, Inc. | Systems and methods for identifying viral contaminants |
| KR102503356B1 (ko) | 2018-03-19 | 2023-02-24 | 리제너론 파마슈티칼스 인코포레이티드 | 마이크로칩 모세관 전기영동 분석 및 시약 |
| US12259355B2 (en) | 2018-03-19 | 2025-03-25 | Regeneron Pharmaceuticals, Inc. | Microchip capillary electrophoresis assays and reagents |
| US12253490B2 (en) | 2018-03-19 | 2025-03-18 | Regeneron Pharmaceuticals, Inc. | Microchip capillary electrophoresis assays and reagents |
| CA3093356A1 (en) | 2018-04-03 | 2019-10-10 | Ngm Biopharmaceuticals, Inc. | C3-binding agents and methods of use thereof |
| TW202016125A (zh) | 2018-05-10 | 2020-05-01 | 美商再生元醫藥公司 | 用於定量及調節蛋白質黏度之系統與方法 |
| AU2019308205B2 (en) | 2018-07-16 | 2025-11-06 | Regeneron Pharmaceuticals, Inc. | Non-human animal models of DITRA disease and uses thereof |
| IL317123A (en) | 2018-08-27 | 2025-01-01 | Regeneron Pharma | Using Raman Spectroscopy for Downstream Purification |
| TWI866924B (zh) | 2018-08-30 | 2024-12-21 | 美商再生元醫藥公司 | 用於將蛋白質複合物定特徵之方法 |
| KR20210055742A (ko) | 2018-09-06 | 2021-05-17 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 인간화된 항-c5 항체 및 이의 용도 |
| EP3857237B1 (en) | 2019-01-16 | 2023-03-01 | Regeneron Pharmaceuticals, Inc. | Methods for characterizing disulfide bonds |
| ES2966625T3 (es) | 2019-04-04 | 2024-04-23 | Regeneron Pharma | Roedores que comprenden un locus del factor de coagulación 12 humanizado |
| EP3958901A4 (en) * | 2019-04-24 | 2023-07-19 | The Trustees of the University of Pennsylvania | BI-FUNCTIONAL HUMANIZED ANTI-C5 ANTIBODIES AND H-FACTOR FUSION PROTEINS AND THEIR USES |
| US20200363400A1 (en) | 2019-05-13 | 2020-11-19 | Regeneron Pharmaceuticals, Inc. | Competitive Ligand Binding Assays |
| JP7610339B2 (ja) | 2019-06-04 | 2025-01-08 | 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 | ベータスリップ変異を有するヒト化ｔｔｒ遺伝子座を含む非ヒト動物と使用方法 |
| CA3137764A1 (en) | 2019-06-07 | 2020-12-10 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized albumin locus |
| KR20220066393A (ko) | 2019-09-24 | 2022-05-24 | 리제너론 파아마슈티컬스, 인크. | 크로마토그래피의 사용 및 재생을 위한 시스템 및 방법 |
| US12297451B1 (en) | 2019-10-25 | 2025-05-13 | Regeneron Pharmaceuticals, Inc. | Cell culture medium |
| EP4065086B1 (en) | 2019-11-25 | 2026-01-28 | Regeneron Pharmaceuticals, Inc. | Sustained release formulations using non-aqueous emulsions |
| BR112022014212B1 (pt) | 2020-01-21 | 2024-01-23 | Regeneron Pharmaceuticals, Inc | Métodos de análise de uma amostra incluindo uma proteína de interesse |
| WO2022047108A1 (en) | 2020-08-31 | 2022-03-03 | Regeneron Pharmaceuticals, Inc. | Asparagine feed strategies to improve cell culture performance and mitigate asparagine sequence variants |
| JP2023544333A (ja) | 2020-10-01 | 2023-10-23 | 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 | ヒトｃｒ１を発現する齧歯類動物 |
| JP2023551446A (ja) | 2020-11-25 | 2023-12-08 | 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 | 非水膜乳化を使用した持続放出製剤 |
| KR20230121854A (ko) | 2020-12-17 | 2023-08-21 | 리제너론 파아마슈티컬스, 인크. | 단백질-캡슐화 마이크로겔의 제작 |
| CA3202197A1 (en) | 2021-01-20 | 2022-07-28 | Reginald Smith | Methods of improving protein titer in cell culture |
| WO2022187323A1 (en) | 2021-03-03 | 2022-09-09 | Regeneron Pharmaceuticals, Inc. | Systems and methods for quantifying and modifying protein viscosity |
| JP2024519407A (ja) | 2021-03-26 | 2024-05-13 | 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 | 混合プロトコルを作成するための方法およびシステム |
| AU2022286340A1 (en) | 2021-06-01 | 2024-01-04 | Regeneron Pharmaceuticals, Inc. | Microchip capillary electrophoresis assays and reagents |
| WO2023039457A1 (en) | 2021-09-08 | 2023-03-16 | Regeneron Pharmaceuticals, Inc. | A high-throughput and mass-spectrometry-based method for quantitating antibodies and other fc-containing proteins |
| CA3232463A1 (en) | 2021-09-20 | 2023-03-23 | Philip Mellors | Methods of controlling antibody heterogeneity |
| KR20240090311A (ko) | 2021-10-07 | 2024-06-21 | 리제너론 파아마슈티컬스, 인크. | pH 모델링 및 제어 시스템 및 방법 |
| US20230110811A1 (en) | 2021-10-07 | 2023-04-13 | Regeneron Pharmaceuticals, Inc. | pH METER CALIBRATION AND CORRECTION |
| MX2024005090A (es) | 2021-10-26 | 2024-07-19 | Regeneron Pharma | Sistemas y metodos para generar agua de laboratorio y distribuir agua de laboratorio a diferentes temperaturas. |
| EP4423271A2 (en) | 2021-10-28 | 2024-09-04 | Regeneron Pharmaceuticals, Inc. | Crispr/cas-related methods and compositions for knocking out c5 |
| CA3245647A1 (en) | 2022-03-18 | 2023-09-21 | Regeneron Pharmaceuticals, Inc. | METHODS AND SYSTEMS FOR ANALYZING POLYPEPTIDE VARIANTS |
| JP2026500269A (ja) | 2022-12-16 | 2026-01-06 | 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 | クロマトグラフィーカラムの完全性を評価するための方法及びシステム |
| WO2024158880A1 (en) | 2023-01-25 | 2024-08-02 | Regeneron Pharmaceuticals, Inc. | Methods of modeling liquid protein composition stability |
| WO2024158961A1 (en) | 2023-01-25 | 2024-08-02 | Regeneron Pharmaceuticals, Inc. | Mass spectrometry-based characterization of antibodies co-expressed in vivo |
| US20240280551A1 (en) | 2023-02-22 | 2024-08-22 | Regeneron Pharmaceuticals, Inc. | System suitability parameters and column aging |
| TW202508625A (zh) | 2023-05-01 | 2025-03-01 | 美商再生元醫藥公司 | 使用苯酚或苯甲醇之多劑量抗體藥物產品 |
| WO2025054406A1 (en) | 2023-09-08 | 2025-03-13 | Regeneron Pharmaceuticals, Inc. | Methods and systems for assessing chromatographic column integrity |
| US20250095773A1 (en) | 2023-09-18 | 2025-03-20 | Regeneron Pharmaceuticals, Inc. | Methods and systems for developing chromatography protocols |
| US20250109905A1 (en) | 2023-09-29 | 2025-04-03 | Regeneron Pharmaceuticals, Inc. | Lyophilization using controlled nucleation |
| WO2025085594A1 (en) | 2023-10-18 | 2025-04-24 | Regeneron Pharmaceuticals, Inc. | Rapid purification of monoclonal antibody from in-process upstream cell culture material |
| TW202535934A (zh) | 2023-11-02 | 2025-09-16 | 美商再生元醫藥公司 | 利用應力來降低脂酶活性的方法 |
| WO2025122669A1 (en) | 2023-12-05 | 2025-06-12 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized complement factor b gene |
| WO2025166281A1 (en) | 2024-02-01 | 2025-08-07 | Regeneron Pharmaceuticals, Inc. | Platform for charge-detection mass spectrometry analysis of aavs |
| WO2025175164A1 (en) | 2024-02-16 | 2025-08-21 | Regeneron Pharmaceuticals, Inc. | Methods of producing concentrated formulated drug substances comprising proteins, and concentrated formulated drug substance made by the methods |
| WO2025194043A1 (en) | 2024-03-15 | 2025-09-18 | Regeneron Pharmaceuticals, Inc. | Polysorbate and polyoxyethylene sorbitan as excipients for stable protein formulations |
| WO2025259840A1 (en) | 2024-06-13 | 2025-12-18 | Regeneron Pharmaceuticals, Inc. | Methods and systems for scaled chromatography |
| WO2026025028A1 (en) | 2024-07-26 | 2026-01-29 | Regeneron Pharmaceuticals, Inc. | Methods of making ultra-high concentrated protein formulations using lyophilization |
Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ207394A (en) | 1983-03-08 | 1987-03-06 | Commw Serum Lab Commission | Detecting or determining sequence of amino acids |
| EP0138854B1 (en) | 1983-03-08 | 1992-11-04 | Chiron Mimotopes Pty. Ltd. | Antigenically active amino acid sequences |
| WO1984003506A1 (en) | 1983-03-08 | 1984-09-13 | Commw Serum Lab Commission | Antigenically active amino acid sequences |
| US6492107B1 (en) | 1986-11-20 | 2002-12-10 | Stuart Kauffman | Process for obtaining DNA, RNA, peptides, polypeptides, or protein, by recombinant DNA technique |
| WO1986005803A1 (fr) | 1985-03-30 | 1986-10-09 | Marc Ballivet | Procede d'obtention d'adn, arn, peptides, polypeptides ou proteines, par une technique de recombinaison d'adn |
| NZ215865A (en) | 1985-04-22 | 1988-10-28 | Commw Serum Lab Commission | Method of determining the active site of a receptor-binding analogue |
| WO1988007089A1 (en) | 1987-03-18 | 1988-09-22 | Medical Research Council | Altered antibodies |
| US5266684A (en) | 1988-05-02 | 1993-11-30 | The Reagents Of The University Of California | Peptide mixtures |
| US5571689A (en) | 1988-06-16 | 1996-11-05 | Washington University | Method of N-acylating peptide and proteins with diheteroatom substituted analogs of myristic acid |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5663143A (en) | 1988-09-02 | 1997-09-02 | Dyax Corp. | Engineered human-derived kunitz domains that inhibit human neutrophil elastase |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| US5723286A (en) | 1990-06-20 | 1998-03-03 | Affymax Technologies N.V. | Peptide library and screening systems |
| US5698426A (en) | 1990-09-28 | 1997-12-16 | Ixsys, Incorporated | Surface expression libraries of heteromeric receptors |
| US5770434A (en) | 1990-09-28 | 1998-06-23 | Ixsys Incorporated | Soluble peptides having constrained, secondary conformation in solution and method of making same |
| ATE176239T1 (de) | 1990-11-21 | 1999-02-15 | Iterex Pharma Lp | Synthese äquimolarer mischungen vielzähliger oligomere, speziell oligopeptidmischungen |
| DE69129154T2 (de) | 1990-12-03 | 1998-08-20 | Genentech, Inc., South San Francisco, Calif. | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
| US5270170A (en) | 1991-10-16 | 1993-12-14 | Affymax Technologies N.V. | Peptide library and screening method |
| US5644048A (en) | 1992-01-10 | 1997-07-01 | Isis Pharmaceuticals, Inc. | Process for preparing phosphorothioate oligonucleotides |
| CA2163345A1 (en) | 1993-06-16 | 1994-12-22 | Susan Adrienne Morgan | Antibodies |
| US6074642A (en) | 1994-05-02 | 2000-06-13 | Alexion Pharmaceuticals, Inc. | Use of antibodies specific to human complement component C5 for the treatment of glomerulonephritis |
| US6166288A (en) * | 1995-09-27 | 2000-12-26 | Nextran Inc. | Method of producing transgenic animals for xenotransplantation expressing both an enzyme masking or reducing the level of the gal epitope and a complement inhibitor |
| GB9521943D0 (en) | 1995-10-26 | 1996-01-03 | Univ Hertfordshire | Coded particles for process sequence tracking in combinatorial compound library preparation |
| ATE375365T1 (de) | 1998-04-02 | 2007-10-15 | Genentech Inc | Antikörper varianten und fragmente davon |
| US6335155B1 (en) | 1998-06-26 | 2002-01-01 | Sunesis Pharmaceuticals, Inc. | Methods for rapidly identifying small organic molecule ligands for binding to biological target molecules |
| US6280946B2 (en) | 1998-08-07 | 2001-08-28 | Boston Probes, Inc. | PNA probes, probe sets, methods and kits pertaining to the universal detection of bacteria and eucarya |
| JP2002533726A (ja) | 1998-12-28 | 2002-10-08 | サネシス ファーマシューティカルス インコーポレイテッド | 結合のための小有機分子リガンドの同定 |
| EP1701611B1 (en) * | 2003-12-24 | 2011-05-18 | G2 Inflammation Pty Ltd | Transgenic non-human mammal comprising a polynucleotide encoding human or humanized c5ar |
| JP5137053B2 (ja) | 2004-02-10 | 2013-02-06 | ザ リージェンツ オブ ザ ユニバーシティ オブ コロラド，ア ボディー コーポレイト | 抗ｂ因子抗体もしくはその抗原結合性フラグメント、それを含む組成物、抗原結合性ポリペプチド、および治療薬 |
| DK1802193T3 (da) | 2004-10-19 | 2014-06-10 | Regeneron Pharma | Fremgangsmåde til frembringelse af en homozygot mus til genetisk modifikation |
| EP2384811A1 (en) | 2006-01-11 | 2011-11-09 | Novo Nordisk A/S | A spherical encoded bead with an ultrasonic identification chip |
| MX2010009190A (es) * | 2008-02-20 | 2010-09-10 | G2 Inflammation Pty Ltd | Anticuerpos anti-c5ar humanizados. |
| RU2425880C2 (ru) * | 2009-07-30 | 2011-08-10 | Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН | Способ получения трансгенных мышей |
| AU2010303737B2 (en) | 2009-10-06 | 2014-05-29 | Institute For Research In Biomedicine (Irb) | Genetically modified mice and engraftment |
| KR102256316B1 (ko) | 2011-02-15 | 2021-05-28 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화된 ｍ－ｃｓｆ 마우스 |
| RU2634417C2 (ru) | 2011-10-28 | 2017-10-26 | Регенерон Фармасьютикалс, Инк. | Гуманизированные il-6 и рецептор il-6 |
| RS56656B1 (sr) | 2011-10-28 | 2018-03-30 | Regeneron Pharma | Miševi sa genetski modifikovanim glavnim kompleksom gena tkivne podudarnosti |
| US8962913B2 (en) | 2012-06-18 | 2015-02-24 | Regeneron Pharmaceuticals, Inc. | Humanized IL-7 rodents |
| DK2892330T3 (da) | 2012-09-07 | 2023-01-30 | Univ Yale | Genetisk modificeret mus og fremgangsmåder til anvendelse deraf |
| EP3939423B1 (en) | 2012-11-05 | 2024-03-06 | Regeneron Pharmaceuticals, Inc. | Genetically modified non-human animals and methods of use thereof |
| CN110192541B (zh) | 2013-02-22 | 2022-02-18 | 瑞泽恩制药公司 | 表达人源化主要组织相容性复合物的小鼠 |
| RU2674910C2 (ru) | 2013-10-15 | 2018-12-13 | Регенерон Фармасьютикалс, Инк. | Животные с гуманизированным геном il-15 |
| KR102173297B1 (ko) | 2013-11-19 | 2020-11-03 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화된 증식-유도 리간드 유전자를 가지고 있는 비-인간 동물 |
| CA3225091A1 (en) | 2014-05-05 | 2015-11-12 | Regeneron Pharmaceuticals, Inc. | Humanized c5 and c3 animals |
-
2015
- 2015-05-04 CA CA3225091A patent/CA3225091A1/en active Pending
- 2015-05-04 EP EP23202404.2A patent/EP4317445A3/en not_active Withdrawn
- 2015-05-04 ES ES19211905T patent/ES2968749T3/es active Active
- 2015-05-04 MX MX2016014504A patent/MX2016014504A/es active IP Right Grant
- 2015-05-04 KR KR1020167032659A patent/KR102461511B1/ko active Active
- 2015-05-04 AU AU2015256299A patent/AU2015256299C1/en not_active Ceased
- 2015-05-04 WO PCT/US2015/029111 patent/WO2015171523A1/en not_active Ceased
- 2015-05-04 EP EP15722639.0A patent/EP3142483B1/en active Active
- 2015-05-04 US US14/703,818 patent/US9795121B2/en not_active Expired - Fee Related
- 2015-05-04 BR BR112016025751A patent/BR112016025751A2/pt not_active Application Discontinuation
- 2015-05-04 ES ES15722639T patent/ES2779070T3/es active Active
- 2015-05-04 RU RU2016146390A patent/RU2713327C2/ru active
- 2015-05-04 SG SG11201608696RA patent/SG11201608696RA/en unknown
- 2015-05-04 MX MX2019013850A patent/MX386644B/es unknown
- 2015-05-04 CN CN201580034127.8A patent/CN106659146B/zh active Active
- 2015-05-04 EP EP19211905.5A patent/EP3636073B1/en active Active
- 2015-05-04 CA CA2946412A patent/CA2946412C/en active Active
- 2015-05-04 SG SG10202003996YA patent/SG10202003996YA/en unknown
- 2015-05-04 MA MA051519A patent/MA51519A/fr unknown
- 2015-05-04 RU RU2020103811A patent/RU2020103811A/ru unknown
- 2015-05-04 JP JP2016566228A patent/JP6598798B2/ja active Active
-
2016
- 2016-10-25 IL IL248481A patent/IL248481B/en active IP Right Grant
-
2017
- 2017-07-26 US US15/660,833 patent/US10492477B2/en active Active
-
2018
- 2018-07-02 US US16/025,377 patent/US10524458B2/en active Active
-
2019
- 2019-10-21 US US16/658,541 patent/US11178860B2/en not_active Expired - Fee Related
-
2021
- 2021-10-20 US US17/505,834 patent/US20220132818A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11178860B2 (en) | Humanized C5 animals | |
| US10945418B2 (en) | Genetically modified non-human animal with human or chimeric PD-L1 | |
| US11317611B2 (en) | Genetically modified non-human animal with human or chimeric PD-L1 | |
| US11534502B2 (en) | Genetically modified non-human animal with human or chimeric TIGIT | |
| KR102602199B1 (ko) | 신장 및 간 장애의 인간화 모델 | |
| US20250134079A1 (en) | Genetically modified non-human animal with human or chimeric genes | |
| HK40104063A (en) | Humanized c5 and c3 animals | |
| HK40016898A (en) | Humanized c5 and c3 animals | |
| HK40016898B (en) | Humanized c5 and c3 animals | |
| HK1240031A1 (en) | Humanized c5 and c3 animals | |
| HK1240031B (en) | Humanized c5 and c3 animals |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20231228 |
|
| EEER | Examination request |
Effective date: 20231228 |
|
| EEER | Examination request |
Effective date: 20231228 |
|
| EEER | Examination request |
Effective date: 20231228 |