CN114502728A - 改进的尿酸酶及其用于治疗高尿酸血症的方法 - Google Patents
改进的尿酸酶及其用于治疗高尿酸血症的方法 Download PDFInfo
- Publication number
- CN114502728A CN114502728A CN202080070950.5A CN202080070950A CN114502728A CN 114502728 A CN114502728 A CN 114502728A CN 202080070950 A CN202080070950 A CN 202080070950A CN 114502728 A CN114502728 A CN 114502728A
- Authority
- CN
- China
- Prior art keywords
- seq
- amino acid
- uricase
- variant
- sequence
- 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
- 108010092464 Urate Oxidase Proteins 0.000 title claims abstract description 233
- 201000001431 Hyperuricemia Diseases 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 title abstract description 29
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- 125000000539 amino acid group Chemical group 0.000 claims description 89
- 150000001413 amino acids Chemical group 0.000 claims description 86
- 235000001014 amino acid Nutrition 0.000 claims description 80
- 229940024606 amino acid Drugs 0.000 claims description 77
- 229920001223 polyethylene glycol Polymers 0.000 claims description 58
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims description 38
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims description 37
- 229940116269 uric acid Drugs 0.000 claims description 37
- 239000002202 Polyethylene glycol Substances 0.000 claims description 35
- 230000035772 mutation Effects 0.000 claims description 32
- 235000018417 cysteine Nutrition 0.000 claims description 28
- 238000006467 substitution reaction Methods 0.000 claims description 26
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 23
- 229920000642 polymer Polymers 0.000 claims description 22
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 10
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 230000002255 enzymatic effect Effects 0.000 claims description 8
- 239000012634 fragment Substances 0.000 claims description 8
- 235000013922 glutamic acid Nutrition 0.000 claims description 8
- 239000004220 glutamic acid Substances 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 6
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 6
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 6
- 235000004554 glutamine Nutrition 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 5
- 235000004279 alanine Nutrition 0.000 claims description 5
- 210000001124 body fluid Anatomy 0.000 claims description 5
- 229930182817 methionine Natural products 0.000 claims description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004473 Threonine Substances 0.000 claims description 4
- 235000003704 aspartic acid Nutrition 0.000 claims description 4
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 4
- 238000012217 deletion Methods 0.000 claims description 4
- 230000037430 deletion Effects 0.000 claims description 4
- 235000008521 threonine Nutrition 0.000 claims description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 3
- 239000010839 body fluid Substances 0.000 claims description 3
- 210000004899 c-terminal region Anatomy 0.000 claims description 3
- 150000001720 carbohydrates Chemical class 0.000 claims description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 3
- 229960000310 isoleucine Drugs 0.000 claims description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 3
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 claims description 3
- 229950004354 phosphorylcholine Drugs 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000004474 valine Substances 0.000 claims description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 2
- 235000009582 asparagine Nutrition 0.000 claims description 2
- 229960001230 asparagine Drugs 0.000 claims description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 2
- 235000002374 tyrosine Nutrition 0.000 claims description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 1
- 229920001059 synthetic polymer Polymers 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 abstract description 40
- 230000000694 effects Effects 0.000 description 30
- 102000004190 Enzymes Human genes 0.000 description 25
- 108090000790 Enzymes Proteins 0.000 description 25
- 229940088598 enzyme Drugs 0.000 description 25
- 108090000623 proteins and genes Proteins 0.000 description 25
- 235000018102 proteins Nutrition 0.000 description 24
- 102000004169 proteins and genes Human genes 0.000 description 24
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 21
- 108010068701 Pegloticase Proteins 0.000 description 21
- -1 about 1 Chemical class 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 14
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 201000005569 Gout Diseases 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 230000005847 immunogenicity Effects 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 241000192041 Micrococcus Species 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 238000000465 moulding Methods 0.000 description 6
- 230000006320 pegylation Effects 0.000 description 6
- 239000013615 primer Substances 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 238000001712 DNA sequencing Methods 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000007853 buffer solution Substances 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 102220096711 rs876659744 Human genes 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 5
- 229910001868 water Inorganic materials 0.000 description 5
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 206010045170 Tumour lysis syndrome Diseases 0.000 description 4
- 229960000458 allantoin Drugs 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229940053603 elitek Drugs 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 108010084837 rasburicase Proteins 0.000 description 4
- 208000010380 tumor lysis syndrome Diseases 0.000 description 4
- 108020004705 Codon Proteins 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 3
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000001851 biosynthetic effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 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 3
- 239000013604 expression vector Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229960005356 urokinase Drugs 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 102000004400 Aminopeptidases Human genes 0.000 description 2
- 108090000915 Aminopeptidases Proteins 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000036783 anaphylactic response Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229940050526 hydroxyethylstarch Drugs 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 229940120535 krystexxa Drugs 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000008176 lyophilized powder Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- 229940005267 urate oxidase Drugs 0.000 description 2
- MFAONEQLPARJAO-UHFFFAOYSA-N (2,5-dioxoimidazol-4-yl)urea Chemical compound NC(=O)NC1=NC(=O)NC1=O MFAONEQLPARJAO-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- POJWUDADGALRAB-SFOWXEAESA-N (S)-(+)-allantoin Chemical compound NC(=O)N[C@H]1NC(=O)NC1=O POJWUDADGALRAB-SFOWXEAESA-N 0.000 description 1
- WHKYNCPIXMNTRQ-RXMQYKEDSA-N 2-Oxo-4-hydroxy-4-carboxy-5-ureidoimidazole Natural products O=C(NC=1[C@@](O)(C(=O)O)NC(=O)N=1)N WHKYNCPIXMNTRQ-RXMQYKEDSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- 101710102541 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase Proteins 0.000 description 1
- PBVAJRFEEOIAGW-UHFFFAOYSA-N 3-[bis(2-carboxyethyl)phosphanyl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)CCP(CCC(O)=O)CCC(O)=O PBVAJRFEEOIAGW-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- WHKYNCPIXMNTRQ-UHFFFAOYSA-N 5-hydroxy-2-oxo-4-ureido-2,5-dihydro-1H-imidazole-5-carboxylic acid Chemical compound NC(=O)NC1=NC(=O)NC1(O)C(O)=O WHKYNCPIXMNTRQ-UHFFFAOYSA-N 0.000 description 1
- 101710163573 5-hydroxyisourate hydrolase Proteins 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- 101000767281 Aspergillus flavus Uricase Proteins 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 208000002682 Hyperkalemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000013038 Hypocalcemia Diseases 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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 240000000220 Panda oleosa Species 0.000 description 1
- 235000016496 Panda oleosa Nutrition 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100020935 Putative 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase Human genes 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- 101710137769 Uricase Proteins 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 208000026816 acute arthritis Diseases 0.000 description 1
- 230000010398 acute inflammatory response Effects 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000011443 conventional therapy Methods 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
- 230000009089 cytolysis Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 201000005991 hyperphosphatemia Diseases 0.000 description 1
- 230000000705 hypocalcaemia Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229920001427 mPEG Polymers 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000002715 modification method Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000037434 nonsense mutation Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000011330 nucleic acid test Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 102220195105 rs868208063 Human genes 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000013097 stability assessment Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- 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
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
- C12N9/0044—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on other nitrogen compounds as donors (1.7)
- C12N9/0046—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on other nitrogen compounds as donors (1.7) with oxygen as acceptor (1.7.3)
- C12N9/0048—Uricase (1.7.3.3)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y107/00—Oxidoreductases acting on other nitrogenous compounds as donors (1.7)
- C12Y107/03—Oxidoreductases acting on other nitrogenous compounds as donors (1.7) with oxygen as acceptor (1.7.3)
- C12Y107/03003—Factor-independent urate hydroxylase (1.7.3.3), i.e. uricase
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
提供了改进的尿酸酶及其治疗高尿酸血症的方法以及包含该尿酸酶的药物组合物。该改进的尿酸酶包含与SEQ ID NO:1具有至少约90%的一致性的氨基酸序列,且所述序列不是SEQ ID NO:1。
Description
PCT国内申请,说明书已公开。
Claims (15)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2019109643254 | 2019-10-11 | ||
CN201910964325.4A CN112646790A (zh) | 2019-10-11 | 2019-10-11 | 改进的尿酸酶及其用于治疗高尿酸血症的方法 |
PCT/CN2020/120133 WO2021068925A1 (zh) | 2019-10-11 | 2020-10-10 | 改进的尿酸酶及其用于治疗高尿酸血症的方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114502728A true CN114502728A (zh) | 2022-05-13 |
Family
ID=75342725
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910964325.4A Pending CN112646790A (zh) | 2019-10-11 | 2019-10-11 | 改进的尿酸酶及其用于治疗高尿酸血症的方法 |
CN202080070950.5A Pending CN114502728A (zh) | 2019-10-11 | 2020-10-10 | 改进的尿酸酶及其用于治疗高尿酸血症的方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910964325.4A Pending CN112646790A (zh) | 2019-10-11 | 2019-10-11 | 改进的尿酸酶及其用于治疗高尿酸血症的方法 |
Country Status (9)
Country | Link |
---|---|
US (1) | US20230073183A1 (zh) |
EP (1) | EP4043559A1 (zh) |
JP (1) | JP2022553648A (zh) |
KR (1) | KR20220078647A (zh) |
CN (2) | CN112646790A (zh) |
AU (1) | AU2020362820A1 (zh) |
BR (1) | BR112022005757A2 (zh) |
CA (1) | CA3153029A1 (zh) |
WO (1) | WO2021068925A1 (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112646790A (zh) * | 2019-10-11 | 2021-04-13 | 上海君实生物医药科技股份有限公司 | 改进的尿酸酶及其用于治疗高尿酸血症的方法 |
CN115197922B (zh) * | 2021-04-09 | 2024-05-14 | 派格生物医药(苏州)股份有限公司 | 尿酸酶或其同功异型物及其制备方法 |
WO2022214086A1 (zh) * | 2021-04-09 | 2022-10-13 | 上海君实生物医药科技股份有限公司 | 尿酸酶、其药物组合物及其用途 |
WO2023064732A1 (en) * | 2021-10-15 | 2023-04-20 | Georgia State University Research Foundation, Inc. | Delivery of therapeutic recombinant uricase using nanoparticles |
CN117230034A (zh) * | 2023-10-16 | 2023-12-15 | 临沂大学 | 一种高稳定性哺乳动物尿酸氧化酶突变体 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060188971A1 (en) * | 1998-08-06 | 2006-08-24 | Duke University | Urate oxidase |
CN101875922A (zh) * | 2009-04-30 | 2010-11-03 | 重庆医科大学 | 来自苛求芽孢杆菌的两种尿酸酶和其突变体及它们的聚乙二醇修饰与应用 |
CN105543187A (zh) * | 2016-02-18 | 2016-05-04 | 重庆医科大学 | 苛求芽孢杆菌尿酸酶突变体v145a |
KR101637010B1 (ko) * | 2015-04-24 | 2016-07-07 | 광주과학기술원 | 위치 특이적으로 알부민이 연결된 요산 산화효소 및 단백질에 위치 특이적으로 알부민을 연결하는 방법 |
CN107614007A (zh) * | 2015-05-15 | 2018-01-19 | 免疫医疗有限责任公司 | 改进的尿酸酶序列和治疗方法 |
US20180282707A1 (en) * | 2015-09-29 | 2018-10-04 | Shanghai Institute Of Biological Products Co., Ltd. | Mutant-type uricase, peg modified mutant-type uricase, and application thereof |
US20200071681A1 (en) * | 2017-07-07 | 2020-03-05 | Allena Pharmaceuticals, Inc. | Recombinant uricase enzyme |
CN112646790A (zh) * | 2019-10-11 | 2021-04-13 | 上海君实生物医药科技股份有限公司 | 改进的尿酸酶及其用于治疗高尿酸血症的方法 |
CN115197923A (zh) * | 2021-04-09 | 2022-10-18 | 上海君实生物医药科技股份有限公司 | 尿酸酶、其药物组合物及其用途 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69942834D1 (de) * | 1998-08-06 | 2010-11-18 | Univ Duke | Harnsäureoxidase |
HUE052976T2 (hu) * | 2005-04-11 | 2021-06-28 | Horizon Pharma Rheumatology Llc | Urát-oxidáz variáns formái és azok alkalmazása |
-
2019
- 2019-10-11 CN CN201910964325.4A patent/CN112646790A/zh active Pending
-
2020
- 2020-10-10 EP EP20874785.7A patent/EP4043559A1/en active Pending
- 2020-10-10 US US17/767,718 patent/US20230073183A1/en active Pending
- 2020-10-10 BR BR112022005757A patent/BR112022005757A2/pt unknown
- 2020-10-10 JP JP2022521317A patent/JP2022553648A/ja active Pending
- 2020-10-10 AU AU2020362820A patent/AU2020362820A1/en active Pending
- 2020-10-10 WO PCT/CN2020/120133 patent/WO2021068925A1/zh unknown
- 2020-10-10 CN CN202080070950.5A patent/CN114502728A/zh active Pending
- 2020-10-10 CA CA3153029A patent/CA3153029A1/en active Pending
- 2020-10-10 KR KR1020227015028A patent/KR20220078647A/ko active Search and Examination
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060188971A1 (en) * | 1998-08-06 | 2006-08-24 | Duke University | Urate oxidase |
CN101875922A (zh) * | 2009-04-30 | 2010-11-03 | 重庆医科大学 | 来自苛求芽孢杆菌的两种尿酸酶和其突变体及它们的聚乙二醇修饰与应用 |
KR101637010B1 (ko) * | 2015-04-24 | 2016-07-07 | 광주과학기술원 | 위치 특이적으로 알부민이 연결된 요산 산화효소 및 단백질에 위치 특이적으로 알부민을 연결하는 방법 |
CN107614007A (zh) * | 2015-05-15 | 2018-01-19 | 免疫医疗有限责任公司 | 改进的尿酸酶序列和治疗方法 |
US20180282707A1 (en) * | 2015-09-29 | 2018-10-04 | Shanghai Institute Of Biological Products Co., Ltd. | Mutant-type uricase, peg modified mutant-type uricase, and application thereof |
CN105543187A (zh) * | 2016-02-18 | 2016-05-04 | 重庆医科大学 | 苛求芽孢杆菌尿酸酶突变体v145a |
US20200071681A1 (en) * | 2017-07-07 | 2020-03-05 | Allena Pharmaceuticals, Inc. | Recombinant uricase enzyme |
CN112646790A (zh) * | 2019-10-11 | 2021-04-13 | 上海君实生物医药科技股份有限公司 | 改进的尿酸酶及其用于治疗高尿酸血症的方法 |
CN115197923A (zh) * | 2021-04-09 | 2022-10-18 | 上海君实生物医药科技股份有限公司 | 尿酸酶、其药物组合物及其用途 |
Non-Patent Citations (7)
Title |
---|
ANDREW C. NYBORG 等: "A Therapeutic Uricase with Reduced Immunogenicity Risk and Improved Development Properties", PLOS ONE, vol. 11, no. 12, 21 December 2016 (2016-12-21), pages 1 - 23, XP055880050, DOI: 10.1371/journal.pone.0167935 * |
ELLA CZARINA MAGAT JUAN 等: "Structures of Arthrobacter globiformis urate oxidase–ligand complexes", BIOLOGICAL, vol. 64, no. 8, pages 815 - 822, XP009540260, DOI: 10.1107/S0907444908013590 * |
HOSSAIN, M.T.: "Chain A, Revision History:~JUN 28 5 Initial Entry", GENBANK DATABASE, pages 1 * |
JUAN, E.C.: "RecName: Full=Uricase; AltName: Full=Urate oxidase; Short=AgUOX", GENBANK DATABASE, 24 June 2015 (2015-06-24), pages 0 * |
YI SHI 等: "Structure-based design of a hyperthermostable AgUricase for hyperuricemia and gout therapy", ACTA PHARMACOL SIN, vol. 40, no. 10, 28 June 2019 (2019-06-28), pages 1364 - 1372, XP036895200, DOI: 10.1038/s41401-019-0269-x * |
YI-CHIH CHIU 等: "Structures of Arthrobacter globiformis urate oxidase–ligand complexes", BIOLOGICAL, vol. 188, 21 September 2009 (2009-09-21), pages 815 - 822 * |
李想: "苛求芽孢杆菌尿酸酶的重组表达及其N端序列与功能关系的初步探讨", 中国优秀硕士学位论文全文数据库(电子期刊), no. 3, pages 1 - 52 * |
Also Published As
Publication number | Publication date |
---|---|
EP4043559A1 (en) | 2022-08-17 |
CN112646790A (zh) | 2021-04-13 |
KR20220078647A (ko) | 2022-06-10 |
JP2022553648A (ja) | 2022-12-26 |
BR112022005757A2 (pt) | 2022-06-21 |
WO2021068925A1 (zh) | 2021-04-15 |
US20230073183A1 (en) | 2023-03-09 |
AU2020362820A1 (en) | 2022-05-05 |
CA3153029A1 (en) | 2021-04-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN114502728A (zh) | 改进的尿酸酶及其用于治疗高尿酸血症的方法 | |
US20240026327A1 (en) | Ph20 polypeptide variants, formulations and uses thereof | |
US11584949B2 (en) | Engineered enzymes with methionine-gamma-lyase enzymes and pharmacological preparations thereof | |
KR102076348B1 (ko) | 사람 아르기나제 및 부위-지향성 페길화된 사람 아르기나제 및 그의 용도 | |
KR102244750B1 (ko) | 치료적 목적을 위한 조작된 영장류 l-메티오니나제 | |
US20150010529A1 (en) | Thermally stable ph20 hyaluronidase variants and uses thereof | |
KR102269209B1 (ko) | 항신생물제로서 조작된 영장류 시스틴/시스테인 분해 효소 | |
US20190048327A1 (en) | Uricase sequences and methods of treatment | |
US20210386838A1 (en) | Human-enzyme mediated depletion of homocysteine for treating patients with hyperhomocysteinemia and homocystinuria | |
KR20190026813A (ko) | 시스틴의 인간-효소 매개된 고갈 | |
JP2017205120A (ja) | コリンエステラーゼ部分とポリマーとのコンジュゲート | |
CN106554948A (zh) | 突变型尿酸酶、peg修饰的突变型尿酸酶及其应用 | |
WO2022214086A1 (zh) | 尿酸酶、其药物组合物及其用途 | |
CN109652400A (zh) | 抗癌药物精氨酸脱亚胺酶半衰期的分子改造方法及突变株 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |