JP2013515474A - 組換え体ｈ因子ならびにそのバリアントおよびコンジュゲート - Google Patents
組換え体ｈ因子ならびにそのバリアントおよびコンジュゲート Download PDFInfo
- Publication number
- JP2013515474A JP2013515474A JP2012545436A JP2012545436A JP2013515474A JP 2013515474 A JP2013515474 A JP 2013515474A JP 2012545436 A JP2012545436 A JP 2012545436A JP 2012545436 A JP2012545436 A JP 2012545436A JP 2013515474 A JP2013515474 A JP 2013515474A
- Authority
- JP
- Japan
- Prior art keywords
- sequence
- amino acid
- variant
- protein
- mammalian
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108010053085 Complement Factor H Proteins 0.000 title abstract description 166
- 102000016550 Complement Factor H Human genes 0.000 title abstract description 164
- 238000000034 method Methods 0.000 claims abstract description 30
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 239000000126 substance Substances 0.000 claims abstract description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 61
- 239000013598 vector Substances 0.000 claims description 59
- 102000004169 proteins and genes Human genes 0.000 claims description 53
- 235000018102 proteins Nutrition 0.000 claims description 46
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 40
- 241000235058 Komagataella pastoris Species 0.000 claims description 36
- 125000000539 amino acid group Chemical group 0.000 claims description 34
- 230000014509 gene expression Effects 0.000 claims description 34
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 32
- 229920001184 polypeptide Polymers 0.000 claims description 31
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 27
- 150000007523 nucleic acids Chemical group 0.000 claims description 26
- 238000006467 substitution reaction Methods 0.000 claims description 26
- 101100335629 Homo sapiens FH gene Proteins 0.000 claims description 19
- 229920001223 polyethylene glycol Polymers 0.000 claims description 18
- 238000000746 purification Methods 0.000 claims description 18
- 235000001014 amino acid Nutrition 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 16
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 14
- 150000001413 amino acids Chemical class 0.000 claims description 14
- 230000013595 glycosylation Effects 0.000 claims description 14
- 238000006206 glycosylation reaction Methods 0.000 claims description 14
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 13
- 238000004587 chromatography analysis Methods 0.000 claims description 11
- 208000004451 Membranoproliferative Glomerulonephritis Diseases 0.000 claims description 10
- 230000004048 modification Effects 0.000 claims description 10
- 238000012986 modification Methods 0.000 claims description 10
- 230000035772 mutation Effects 0.000 claims description 10
- 208000022401 dense deposit disease Diseases 0.000 claims description 9
- 208000035913 Atypical hemolytic uremic syndrome Diseases 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 230000003248 secreting effect Effects 0.000 claims description 8
- 238000012217 deletion Methods 0.000 claims description 7
- 230000037430 deletion Effects 0.000 claims description 7
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 6
- 230000037361 pathway Effects 0.000 claims description 6
- 102000054765 polymorphisms of proteins Human genes 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 229920002307 Dextran Polymers 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 230000001965 increasing effect Effects 0.000 claims description 5
- 239000002773 nucleotide Substances 0.000 claims description 5
- 125000003729 nucleotide group Chemical group 0.000 claims description 5
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 4
- 241001494479 Pecora Species 0.000 claims description 4
- 230000004071 biological effect Effects 0.000 claims description 4
- 230000002068 genetic effect Effects 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 229920005615 natural polymer Polymers 0.000 claims description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 2
- DSLBDPPHINVUID-REOHCLBHSA-N (2s)-2-aminobutanediamide Chemical compound NC(=O)[C@@H](N)CC(N)=O DSLBDPPHINVUID-REOHCLBHSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- 241000283690 Bos taurus Species 0.000 claims description 2
- 241000282836 Camelus dromedarius Species 0.000 claims description 2
- 241000700199 Cavia porcellus Species 0.000 claims description 2
- 229920001661 Chitosan Polymers 0.000 claims description 2
- 241000699800 Cricetinae Species 0.000 claims description 2
- 241000283073 Equus caballus Species 0.000 claims description 2
- 241000282326 Felis catus Species 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 2
- 241000009328 Perro Species 0.000 claims description 2
- 229920002873 Polyethylenimine Polymers 0.000 claims description 2
- 239000004721 Polyphenylene oxide Substances 0.000 claims description 2
- 241000288906 Primates Species 0.000 claims description 2
- 241000700159 Rattus Species 0.000 claims description 2
- 241000282898 Sus scrofa Species 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 230000004927 fusion Effects 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 229960003160 hyaluronic acid Drugs 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 229920000729 poly(L-lysine) polymer Polymers 0.000 claims description 2
- 229920000962 poly(amidoamine) Polymers 0.000 claims description 2
- 229920000570 polyether Polymers 0.000 claims description 2
- 229920002643 polyglutamic acid Polymers 0.000 claims description 2
- 229920005862 polyol Polymers 0.000 claims description 2
- 150000003077 polyols Chemical class 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 229920001059 synthetic polymer Polymers 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 11
- 210000004027 cell Anatomy 0.000 description 35
- 108020004705 Codon Proteins 0.000 description 26
- 108020004414 DNA Proteins 0.000 description 19
- 102000053602 DNA Human genes 0.000 description 19
- 230000027455 binding Effects 0.000 description 19
- 101100335631 Mus musculus Fh gene Proteins 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 230000028327 secretion Effects 0.000 description 14
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 13
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 13
- 230000000295 complement effect Effects 0.000 description 13
- 208000002780 macular degeneration Diseases 0.000 description 13
- 238000005457 optimization Methods 0.000 description 11
- 101000737574 Homo sapiens Complement factor H Proteins 0.000 description 10
- 102000045512 human CFH Human genes 0.000 description 10
- 230000006320 pegylation Effects 0.000 description 10
- 229960000074 biopharmaceutical Drugs 0.000 description 8
- 229920000669 heparin Polymers 0.000 description 8
- 229960002897 heparin Drugs 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 208000024172 Cardiovascular disease Diseases 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 6
- 230000004988 N-glycosylation Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003623 enhancer Substances 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 102000054766 genetic haplotypes Human genes 0.000 description 6
- 108010049041 glutamylalanine Proteins 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000005847 immunogenicity Effects 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 4
- 108700010070 Codon Usage Proteins 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 238000001042 affinity chromatography Methods 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- -1 cationic lipid Chemical class 0.000 description 4
- 230000024203 complement activation Effects 0.000 description 4
- 230000021615 conjugation Effects 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- 238000010348 incorporation Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 230000017854 proteolysis Effects 0.000 description 4
- 230000002797 proteolythic effect Effects 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 230000002207 retinal effect Effects 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 101150063409 Fh gene Proteins 0.000 description 3
- JZDHUJAFXGNDSB-WHFBIAKZSA-N Glu-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O JZDHUJAFXGNDSB-WHFBIAKZSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108020005038 Terminator Codon Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000005349 anion exchange Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 125000001165 hydrophobic group Chemical group 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 241000701447 unidentified baculovirus Species 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 206010000234 Abortion spontaneous Diseases 0.000 description 2
- 101710194180 Alcohol oxidase 1 Proteins 0.000 description 2
- 102000052866 Amino Acyl-tRNA Synthetases Human genes 0.000 description 2
- 108700028939 Amino Acyl-tRNA Synthetases Proteins 0.000 description 2
- 101001007681 Candida albicans (strain WO-1) Kexin Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 101710184994 Complement control protein Proteins 0.000 description 2
- 102000003712 Complement factor B Human genes 0.000 description 2
- 108090000056 Complement factor B Proteins 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 2
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000000751 azo group Chemical group [*]N=N[*] 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 102000006834 complement receptors Human genes 0.000 description 2
- 108010047295 complement receptors Proteins 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000006167 equilibration buffer Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 208000015994 miscarriage Diseases 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 238000012261 overproduction Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 230000006267 polysialylation Effects 0.000 description 2
- 201000011461 pre-eclampsia Diseases 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 208000000995 spontaneous abortion Diseases 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- SBKVPJHMSUXZTA-MEJXFZFPSA-N (2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-5-amino-2-[[2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 SBKVPJHMSUXZTA-MEJXFZFPSA-N 0.000 description 1
- FQVLRGLGWNWPSS-BXBUPLCLSA-N (4r,7s,10s,13s,16r)-16-acetamido-13-(1h-imidazol-5-ylmethyl)-10-methyl-6,9,12,15-tetraoxo-7-propan-2-yl-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carboxamide Chemical compound N1C(=O)[C@@H](NC(C)=O)CSSC[C@@H](C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@@H]1CC1=CN=CN1 FQVLRGLGWNWPSS-BXBUPLCLSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
- 101150006240 AOX2 gene Proteins 0.000 description 1
- CXISPYVYMQWFLE-VKHMYHEASA-N Ala-Gly Chemical compound C[C@H]([NH3+])C(=O)NCC([O-])=O CXISPYVYMQWFLE-VKHMYHEASA-N 0.000 description 1
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 1
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 1
- 102100034035 Alcohol dehydrogenase 1A Human genes 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 108010003529 Alternative Pathway Complement C3 Convertase Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102000005427 Asialoglycoprotein Receptor Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010009575 CD55 Antigens Proteins 0.000 description 1
- 101100327917 Caenorhabditis elegans chup-1 gene Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 102000015612 Complement 3b Receptors Human genes 0.000 description 1
- 108010024114 Complement 3b Receptors Proteins 0.000 description 1
- 108010078015 Complement C3b Proteins 0.000 description 1
- 108700017374 Complement Factor H Deficiency Proteins 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 238000011537 Coomassie blue staining Methods 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 101150067325 DAS1 gene Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101100223032 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) dapB gene Proteins 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 108050001049 Extracellular proteins Proteins 0.000 description 1
- 108010067193 Formaldehyde transketolase Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 101000892220 Geobacillus thermodenitrificans (strain NG80-2) Long-chain-alcohol dehydrogenase 1 Proteins 0.000 description 1
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 1
- 206010018370 Glomerulonephritis membranoproliferative Diseases 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 1
- 101000780443 Homo sapiens Alcohol dehydrogenase 1A Proteins 0.000 description 1
- 101000961414 Homo sapiens Membrane cofactor protein Proteins 0.000 description 1
- 101000579123 Homo sapiens Phosphoglycerate kinase 1 Proteins 0.000 description 1
- 101001079065 Homo sapiens Ras-related protein Rab-1A Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 241001138401 Kluyveromyces lactis Species 0.000 description 1
- 101100502336 Komagataella pastoris FLD1 gene Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 125000000769 L-threonyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](O[H])(C([H])([H])[H])[H] 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 108010038049 Mating Factor Proteins 0.000 description 1
- 108091027974 Mature messenger RNA Proteins 0.000 description 1
- 102000050019 Membrane Cofactor Human genes 0.000 description 1
- 102100039373 Membrane cofactor protein Human genes 0.000 description 1
- 101710146216 Membrane cofactor protein Proteins 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000969137 Mus musculus Metallothionein-1 Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 101150005314 PEX8 gene Proteins 0.000 description 1
- KJWZYMMLVHIVSU-IYCNHOCDSA-N PGK1 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](CCCCCCC(O)=O)C(=O)CC1=O KJWZYMMLVHIVSU-IYCNHOCDSA-N 0.000 description 1
- 241000577979 Peromyscus spicilegus Species 0.000 description 1
- 102100028251 Phosphoglycerate kinase 1 Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 102100028191 Ras-related protein Rab-1A Human genes 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 101100516268 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) NDT80 gene Proteins 0.000 description 1
- 101100421128 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SEI1 gene Proteins 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 101100277719 Schizosaccharomyces pombe (strain 972 / ATCC 24843) ste13 gene Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 241000256248 Spodoptera Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241000701093 Suid alphaherpesvirus 1 Species 0.000 description 1
- 101100335632 Sus scrofa FH gene Proteins 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 108010084455 Zeocin Proteins 0.000 description 1
- 208000035472 Zoonoses Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 108010047495 alanylglycine Proteins 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 108010059803 amino acyl tRNA-protein transferase Proteins 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 108010006523 asialoglycoprotein receptor Proteins 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 238000011281 clinical therapy Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 108010052926 complement C3d,g Proteins 0.000 description 1
- 208000003576 complement factor H deficiency Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000022811 deglycosylation Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 201000000523 end stage renal failure Diseases 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 238000012215 gene cloning Methods 0.000 description 1
- 238000003208 gene overexpression Methods 0.000 description 1
- 230000001434 glomerular 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
- 108010051015 glutathione-independent formaldehyde dehydrogenase Proteins 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 101150109249 lacI gene Proteins 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 238000010202 multivariate logistic regression analysis Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 230000005408 paramagnetism Effects 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 108091005611 polysialylated proteins Proteins 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 230000029983 protein stabilization Effects 0.000 description 1
- 230000012743 protein tagging Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000004286 retinal pathology Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 239000007320 rich medium Substances 0.000 description 1
- 102200031793 rs800292 Human genes 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000009962 secretion pathway Effects 0.000 description 1
- 238000012206 semi-quantitative assay Methods 0.000 description 1
- 238000011896 sensitive detection Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 125000005629 sialic acid group Chemical group 0.000 description 1
- 230000009450 sialylation Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 238000012868 site-directed mutagenesis technique Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 206010048282 zoonosis Diseases 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/88—Lyases (4.)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07K14/4702—Regulators; Modulating activity
-
- 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
- C12Y—ENZYMES
- C12Y402/00—Carbon-oxygen lyases (4.2)
- C12Y402/01—Hydro-lyases (4.2.1)
- C12Y402/01002—Fumarate hydratase (4.2.1.2)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Urology & Nephrology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Communicable Diseases (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Cardiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0922659.8A GB0922659D0 (en) | 2009-12-24 | 2009-12-24 | Factor H |
| GB0922659.8 | 2009-12-24 | ||
| PCT/GB2010/002334 WO2011077102A1 (en) | 2009-12-24 | 2010-12-23 | Recombinant factor h and variants and conjugates thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2013515474A true JP2013515474A (ja) | 2013-05-09 |
| JP2013515474A5 JP2013515474A5 (enExample) | 2014-02-20 |
Family
ID=41716988
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012545436A Abandoned JP2013515474A (ja) | 2009-12-24 | 2010-12-23 | 組換え体ｈ因子ならびにそのバリアントおよびコンジュゲート |
Country Status (5)
| Country | Link |
|---|---|
| US (3) | US8889374B2 (enExample) |
| EP (1) | EP2516464B1 (enExample) |
| JP (1) | JP2013515474A (enExample) |
| GB (1) | GB0922659D0 (enExample) |
| WO (1) | WO2011077102A1 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017500049A (ja) * | 2013-12-20 | 2017-01-05 | ラボラトワール・フランセ・デュ・フラクシオンマン・エ・デ・ビョテクノロジーＬａｂｏｒａｔｏｉｒｅ Ｆｒａｎｃａｉｓ Ｄｕ Ｆｒａｃｔｉｏｎｎｅｍｅｎｔ Ｅｔ Ｄｅｓ Ｂｉｏｔｅｃｈｎｏｌｏｇｉｅｓ | Ｈ因子活性を有する組換えタンパク質 |
| KR20180055872A (ko) * | 2015-09-24 | 2018-05-25 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 보체 매개 질환 치료용 조성물 및 방법 |
| JP2022500047A (ja) * | 2018-09-13 | 2022-01-04 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | Ｃ３糸球体症のモデルとしての補体因子ｈ遺伝子ノックアウトラット |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0922659D0 (en) | 2009-12-24 | 2010-02-10 | Univ Edinburgh | Factor H |
| FR2981661B1 (fr) * | 2011-10-25 | 2015-06-19 | Lfb Biotechnologies | Procede de preparation du facteur h humain |
| FR3038517B1 (fr) | 2015-07-06 | 2020-02-28 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Utilisation de fragments fc modifies en immunotherapie |
| WO2017075189A1 (en) * | 2015-10-27 | 2017-05-04 | University Of Massachusetts | Factor h-fc immunotherapy |
| GB201706808D0 (en) | 2017-04-28 | 2017-06-14 | Univ Newcastle | Modified complement proteins and uses thereof |
| GB201800620D0 (en) | 2018-01-15 | 2018-02-28 | Univ Manchester | C3b Binding Polypeptide |
| EP3824095A4 (en) * | 2018-07-20 | 2022-04-20 | University of Utah Research Foundation | GENE THERAPY FOR MACULATE GENERATION |
| IL299048A (en) | 2020-06-14 | 2023-02-01 | Vertex Pharma | Variants of complement factor - 1 fusion structures and preparations containing them and their uses |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7037504B2 (en) | 2001-10-23 | 2006-05-02 | Waratah Pharmaceuticals, Inc. | Epidermal growth factor protein and gene, and methods of use therefor |
| EP1336618A1 (en) | 2002-02-15 | 2003-08-20 | HANS-KNÖLL-INSTITUT FÜR NATURSTOFF-FORSCHUNG e.V. | Porcine complement regulator factor H and its use |
| EP2357257B1 (en) | 2005-02-14 | 2019-07-31 | University of Iowa Research Foundation | Methods and reagents for treatment and diagnosis of age-related macular degeneration |
| WO2007038995A1 (en) | 2005-09-19 | 2007-04-12 | Csl Behring Gmbh | Factor h for the treatment of chronic nephropathies and production thereof |
| AU2007261315B2 (en) * | 2006-06-21 | 2012-10-25 | Musc Foundation For Research Development | Targeting complement factor H for treatment of diseases |
| EP2208737B1 (en) | 2007-05-03 | 2017-07-05 | Lysomab GmbH | Complement factor H-derived short consensus repeat-antibody constructs |
| WO2008139496A1 (en) | 2007-05-16 | 2008-11-20 | Bigtec Private Limited | Recombinant human insulin and a method thereof |
| GB0922659D0 (en) | 2009-12-24 | 2010-02-10 | Univ Edinburgh | Factor H |
| EP2533797A1 (en) | 2010-02-12 | 2012-12-19 | CeMM Forschungszentrum für Molekulare Medizin GmbH | Complement factor h for oxidative stress disease conditions |
| WO2013142362A1 (en) | 2012-03-19 | 2013-09-26 | The Trustees Of The University Of Pennsylvania | Regulator of complement activation and uses thereof |
-
2009
- 2009-12-24 GB GBGB0922659.8A patent/GB0922659D0/en not_active Ceased
-
2010
- 2010-12-23 US US13/518,614 patent/US8889374B2/en active Active
- 2010-12-23 EP EP10803266.5A patent/EP2516464B1/en not_active Not-in-force
- 2010-12-23 JP JP2012545436A patent/JP2013515474A/ja not_active Abandoned
- 2010-12-23 WO PCT/GB2010/002334 patent/WO2011077102A1/en not_active Ceased
-
2014
- 2014-11-14 US US14/541,834 patent/US20150139975A1/en not_active Abandoned
-
2017
- 2017-04-10 US US15/483,814 patent/US10378005B2/en not_active Expired - Fee Related
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017500049A (ja) * | 2013-12-20 | 2017-01-05 | ラボラトワール・フランセ・デュ・フラクシオンマン・エ・デ・ビョテクノロジーＬａｂｏｒａｔｏｉｒｅ Ｆｒａｎｃａｉｓ Ｄｕ Ｆｒａｃｔｉｏｎｎｅｍｅｎｔ Ｅｔ Ｄｅｓ Ｂｉｏｔｅｃｈｎｏｌｏｇｉｅｓ | Ｈ因子活性を有する組換えタンパク質 |
| JP2020014468A (ja) * | 2013-12-20 | 2020-01-30 | ラボラトワール・フランセ・デュ・フラクシオンマン・エ・デ・ビョテクノロジーＬａｂｏｒａｔｏｉｒｅ Ｆｒａｎｃａｉｓ Ｄｕ Ｆｒａｃｔｉｏｎｎｅｍｅｎｔ Ｅｔ Ｄｅｓ Ｂｉｏｔｅｃｈｎｏｌｏｇｉｅｓ | Ｈ因子活性を有する組換えタンパク質 |
| KR20180055872A (ko) * | 2015-09-24 | 2018-05-25 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 보체 매개 질환 치료용 조성물 및 방법 |
| JP2018527941A (ja) * | 2015-09-24 | 2018-09-27 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 補体媒介性疾患を処置するための組成物及び方法 |
| JP2022000017A (ja) * | 2015-09-24 | 2022-01-04 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 補体媒介性疾患を処置するための組成物及び方法 |
| JP7261583B2 (ja) | 2015-09-24 | 2023-04-20 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 補体媒介性疾患を処置するための組成物及び方法 |
| JP7324253B2 (ja) | 2015-09-24 | 2023-08-09 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 補体媒介性疾患を処置するための組成物及び方法 |
| JP2023139256A (ja) * | 2015-09-24 | 2023-10-03 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 補体媒介性疾患を処置するための組成物及び方法 |
| KR102773865B1 (ko) * | 2015-09-24 | 2025-03-04 | 더 트러스티스 오브 더 유니버시티 오브 펜실베니아 | 보체 매개 질환 치료용 조성물 및 방법 |
| JP2025029082A (ja) * | 2015-09-24 | 2025-03-05 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 補体媒介性疾患を処置するための組成物及び方法 |
| JP2022500047A (ja) * | 2018-09-13 | 2022-01-04 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | Ｃ３糸球体症のモデルとしての補体因子ｈ遺伝子ノックアウトラット |
| JP7222075B2 (ja) | 2018-09-13 | 2023-02-14 | 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 | Ｃ３糸球体症のモデルとしての補体因子ｈ遺伝子ノックアウトラット |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0922659D0 (en) | 2010-02-10 |
| US20130225795A1 (en) | 2013-08-29 |
| US8889374B2 (en) | 2014-11-18 |
| US10378005B2 (en) | 2019-08-13 |
| WO2011077102A1 (en) | 2011-06-30 |
| EP2516464A1 (en) | 2012-10-31 |
| US20170335310A1 (en) | 2017-11-23 |
| EP2516464B1 (en) | 2018-11-28 |
| US20150139975A1 (en) | 2015-05-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10378005B2 (en) | Recombinant factor H and variants and conjugates thereof | |
| US10898545B2 (en) | Tear lipocalin muteins binding IL-4 r alpha | |
| HK1258140A1 (zh) | 经修饰松弛素多肽及其用途 | |
| CN107056929A (zh) | 经过修饰的猪促生长素多肽和其用途 | |
| CN107674121A (zh) | 经过修饰的牛促生长素多肽和其用途 | |
| US20170334971A1 (en) | Alpha-1-Antitrypsin (A1AT) Fusion Proteins and Uses Thereof | |
| US11840703B2 (en) | Recombinant versican isoforms and related compositions and methods | |
| WO1999057147A1 (fr) | Mutants de la thrombopoietine humaine | |
| WO2024046280A1 (zh) | 一种聚乙二醇修饰的il-21衍生物及其应用 | |
| HK1232549B (zh) | 结合IL-4受体α的泪脂质运载蛋白突变蛋白 | |
| HK1232549A1 (en) | Tear lipocalin muteins binding il-4 r alpha | |
| WO2013028527A1 (en) | Compositions and methods for treating cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131224 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20131224 |
|
| A762 | Written abandonment of application |
Free format text: JAPANESE INTERMEDIATE CODE: A762 Effective date: 20141014 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141114 |