CA2756442C - Site-directed pegylation of arginases and the use thereof as anti-cancer and anti-viral agents - Google Patents
Site-directed pegylation of arginases and the use thereof as anti-cancer and anti-viral agents Download PDFInfo
- Publication number
- CA2756442C CA2756442C CA2756442A CA2756442A CA2756442C CA 2756442 C CA2756442 C CA 2756442C CA 2756442 A CA2756442 A CA 2756442A CA 2756442 A CA2756442 A CA 2756442A CA 2756442 C CA2756442 C CA 2756442C
- Authority
- CA
- Canada
- Prior art keywords
- arginase
- peg
- arginine
- pegylated
- human
- 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.)
- Active
Links
- 108700024123 Arginases Proteins 0.000 title claims abstract description 125
- 102000004452 Arginase Human genes 0.000 title claims abstract description 122
- 230000006320 pegylation Effects 0.000 title description 16
- 230000001093 anti-cancer Effects 0.000 title description 9
- 239000003443 antiviral agent Substances 0.000 title description 5
- 239000002246 antineoplastic agent Substances 0.000 title description 3
- 101000792852 Bacillus caldovelox Arginase Proteins 0.000 claims abstract description 117
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 101
- 101000752037 Homo sapiens Arginase-1 Proteins 0.000 claims abstract description 97
- 102000053089 human ARG1 Human genes 0.000 claims abstract description 96
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 25
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 17
- 201000011510 cancer Diseases 0.000 claims description 58
- 239000004475 Arginine Substances 0.000 claims description 53
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 53
- 230000000694 effects Effects 0.000 claims description 23
- 241000700605 Viruses Species 0.000 claims description 12
- 230000001419 dependent effect Effects 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 230000005847 immunogenicity Effects 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 210000002966 serum Anatomy 0.000 claims description 6
- 238000012239 gene modification Methods 0.000 claims description 3
- 230000005017 genetic modification Effects 0.000 claims description 3
- 235000013617 genetically modified food Nutrition 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 241000711549 Hepacivirus C Species 0.000 claims 2
- 241000700721 Hepatitis B virus Species 0.000 claims 2
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 claims 2
- 239000012752 auxiliary agent Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 abstract description 36
- 102000004190 Enzymes Human genes 0.000 abstract description 19
- 108090000790 Enzymes Proteins 0.000 abstract description 19
- 238000000034 method Methods 0.000 abstract description 19
- 208000036142 Viral infection Diseases 0.000 abstract description 4
- 230000009385 viral infection Effects 0.000 abstract description 4
- 125000000539 amino acid group Chemical group 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 239000000562 conjugate Substances 0.000 abstract 3
- 210000004027 cell Anatomy 0.000 description 169
- 239000003814 drug Substances 0.000 description 38
- 229940079593 drug Drugs 0.000 description 36
- 108010082340 Arginine deiminase Proteins 0.000 description 35
- 238000011282 treatment Methods 0.000 description 35
- 238000000855 fermentation Methods 0.000 description 33
- 230000004151 fermentation Effects 0.000 description 33
- 102000053640 Argininosuccinate synthases Human genes 0.000 description 32
- 108700024106 Argininosuccinate synthases Proteins 0.000 description 32
- 241000725303 Human immunodeficiency virus Species 0.000 description 32
- 101710191958 Amino-acid acetyltransferase Proteins 0.000 description 27
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 25
- 102000009042 Argininosuccinate Lyase Human genes 0.000 description 24
- 102000004169 proteins and genes Human genes 0.000 description 23
- 241000699670 Mus sp. Species 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 20
- 239000002609 medium Substances 0.000 description 18
- 238000001727 in vivo Methods 0.000 description 17
- 150000001413 amino acids Chemical class 0.000 description 16
- 238000007912 intraperitoneal administration Methods 0.000 description 16
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 14
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 14
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 14
- 229960003104 ornithine Drugs 0.000 description 14
- ASUGWWOMVNVWAW-UHFFFAOYSA-N 1-(2-methoxyethyl)pyrrole-2,5-dione Chemical compound COCCN1C(=O)C=CC1=O ASUGWWOMVNVWAW-UHFFFAOYSA-N 0.000 description 13
- 102000007981 Ornithine carbamoyltransferase Human genes 0.000 description 13
- 101710198224 Ornithine carbamoyltransferase, mitochondrial Proteins 0.000 description 13
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical group SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 12
- 230000037396 body weight Effects 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 12
- 231100000135 cytotoxicity Toxicity 0.000 description 11
- 230000003013 cytotoxicity Effects 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 201000001441 melanoma Diseases 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 206010006187 Breast cancer Diseases 0.000 description 9
- 208000026310 Breast neoplasm Diseases 0.000 description 9
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000000120 cytopathologic effect Effects 0.000 description 9
- 208000032839 leukemia Diseases 0.000 description 9
- 201000007270 liver cancer Diseases 0.000 description 9
- 208000014018 liver neoplasm Diseases 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 238000011725 BALB/c mouse Methods 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 230000010261 cell growth Effects 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 208000008443 pancreatic carcinoma Diseases 0.000 description 8
- 230000010076 replication Effects 0.000 description 8
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 8
- 241000193830 Bacillus <bacterium> Species 0.000 description 7
- 108020004705 Codon Proteins 0.000 description 7
- 239000011572 manganese Substances 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- 229960002555 zidovudine Drugs 0.000 description 7
- 238000011729 BALB/c nude mouse Methods 0.000 description 6
- 206010009944 Colon cancer Diseases 0.000 description 6
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 230000003833 cell viability Effects 0.000 description 6
- 239000007795 chemical reaction product Substances 0.000 description 6
- 230000021615 conjugation Effects 0.000 description 6
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000002054 inoculum Substances 0.000 description 6
- 238000003757 reverse transcription PCR Methods 0.000 description 6
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 108091006629 SLC13A2 Proteins 0.000 description 5
- 241001468254 [Bacillus] caldovelox Species 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
- 229960002949 fluorouracil Drugs 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 238000003752 polymerase chain reaction Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000003104 tissue culture media Substances 0.000 description 5
- 230000035899 viability Effects 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 4
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 4
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- 229920002684 Sepharose Polymers 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 210000001099 axilla Anatomy 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 229960002173 citrulline Drugs 0.000 description 4
- 235000013477 citrulline Nutrition 0.000 description 4
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 4
- 201000006585 gastric adenocarcinoma Diseases 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
- 229910052748 manganese Inorganic materials 0.000 description 4
- 201000002528 pancreatic cancer Diseases 0.000 description 4
- 230000003285 pharmacodynamic effect Effects 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 239000001488 sodium phosphate Substances 0.000 description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 3
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 206010027458 Metastases to lung Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 229910017052 cobalt Inorganic materials 0.000 description 3
- 239000010941 cobalt Substances 0.000 description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 239000013613 expression plasmid Substances 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
- 230000005917 in vivo anti-tumor Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 3
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 201000011549 stomach cancer Diseases 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 238000007492 two-way ANOVA Methods 0.000 description 3
- 230000004143 urea cycle Effects 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- 108010075480 ADI PEG20 Proteins 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 238000012365 batch cultivation Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000001268 conjugating effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 239000000890 drug combination Substances 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- ZGMLACURZVGTPK-UHFFFAOYSA-N 5-fluoranyl-1h-pyrimidine-2,4-dione Chemical compound OC1=NC=C(F)C(O)=N1.FC1=CNC(=O)NC1=O ZGMLACURZVGTPK-UHFFFAOYSA-N 0.000 description 1
- 102220565736 Acid-sensing ion channel 4_V20P_mutation Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000511343 Chondrostoma nasus Species 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 210000000712 G cell Anatomy 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001138285 Homo sapiens Adenylosuccinate lyase Proteins 0.000 description 1
- 101000685154 Homo sapiens Argininosuccinate lyase Proteins 0.000 description 1
- 101001066129 Homo sapiens Glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 101000986595 Homo sapiens Ornithine transcarbamylase, mitochondrial Proteins 0.000 description 1
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108091006006 PEGylated Proteins Proteins 0.000 description 1
- 241001662443 Phemeranthus parviflorus Species 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 125000003277 amino group Chemical group 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
- 230000003698 anagen phase Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000002001 anti-metastasis Effects 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 230000004611 cancer cell death Effects 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- KTVIXTQDYHMGHF-UHFFFAOYSA-L cobalt(2+) sulfate Chemical compound [Co+2].[O-]S([O-])(=O)=O KTVIXTQDYHMGHF-UHFFFAOYSA-L 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000013267 controlled drug release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000009295 crossflow filtration Methods 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 102000047486 human GAPDH Human genes 0.000 description 1
- 102000053926 human OTC Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical class [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 1
- 229910000357 manganese(II) sulfate Inorganic materials 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 229910001453 nickel ion Inorganic materials 0.000 description 1
- 230000024121 nodulation Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- -1 ornithineõ Chemical class 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000012536 storage buffer Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
-
- 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
-
- 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
-
- 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
- A61P31/12—Antivirals
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
- C12Y305/03—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in linear amidines (3.5.3)
- C12Y305/03001—Arginase (3.5.3.1)
-
- 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)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Genetics & Genomics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16386309P | 2009-03-26 | 2009-03-26 | |
| US61/163,863 | 2009-03-26 | ||
| PCT/CN2010/071357 WO2010124547A1 (en) | 2009-03-26 | 2010-03-26 | Site-directed pegylation of arginases and the use thereof as anti-cancer and anti-viral agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2756442A1 CA2756442A1 (en) | 2010-11-04 |
| CA2756442C true CA2756442C (en) | 2016-03-29 |
Family
ID=42784510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2756442A Active CA2756442C (en) | 2009-03-26 | 2010-03-26 | Site-directed pegylation of arginases and the use thereof as anti-cancer and anti-viral agents |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8507245B2 (enExample) |
| EP (1) | EP2411040B1 (enExample) |
| JP (1) | JP5746137B2 (enExample) |
| CN (1) | CN102481345B (enExample) |
| AU (1) | AU2010242422B2 (enExample) |
| CA (1) | CA2756442C (enExample) |
| WO (1) | WO2010124547A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9382525B2 (en) * | 2009-03-26 | 2016-07-05 | The Hong Kong Polytechnic University | Site-directed pegylation of arginases and the use thereof as anti-cancer and anti-viral agents |
| US8679479B2 (en) * | 2009-06-29 | 2014-03-25 | Aerase, Inc. | Methods for purifying pegylated arginase |
| ES2735530T3 (es) | 2010-01-26 | 2019-12-19 | Bioregency Inc | Composiciones y métodos relacionados con la argininosuccinato sintetasa |
| US20130295073A1 (en) * | 2010-12-21 | 2013-11-07 | Bio-Cancer Treatment International Ltd. | Use of pegylated recombinant human arginase for treatment of leukemia |
| CN103184208B (zh) | 2011-12-27 | 2015-09-16 | 拜奥生物科技（上海）有限公司 | 人精氨酸酶和定点聚乙二醇化人精氨酸酶及其应用 |
| US9011845B2 (en) | 2012-06-26 | 2015-04-21 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Methods for treatment of inflammatory and infectious viral diseases |
| US8877183B2 (en) | 2012-06-26 | 2014-11-04 | National Institutes Of Health (Nih) | Methods for treatment of ocular diseases |
| CA2944554A1 (en) | 2014-04-29 | 2015-11-05 | Bio-Cancer Treatment International Limited | Methods and compositions for modulating the immune system with arginase i |
| CN105112391B (zh) * | 2015-09-22 | 2018-07-06 | 浙江道尔生物科技有限公司 | 一种人源精氨酸酶突变体及其制备方法和用途 |
| CN106692961B (zh) * | 2015-11-17 | 2020-12-11 | 长春市福迪奥美科技有限公司 | 精氨酸酶组合物、精氨酸酶激活剂及其应用 |
| CN106434710A (zh) * | 2016-10-14 | 2017-02-22 | 江南大学 | 一种耐热精氨酸酶的基因表达序列和应用 |
| CN108265044B (zh) * | 2016-12-31 | 2021-05-11 | 江苏众红生物工程创药研究院有限公司 | 聚乙二醇定点修饰的精氨酸脱亚胺酶及其制备方法与应用 |
| TW201910513A (zh) * | 2017-08-16 | 2019-03-16 | 香港商鎧耀波麗堂（香港）有限公司 | 胺基酸耗竭治療的組合物及方法 |
| EP3802621B8 (en) | 2018-05-31 | 2025-10-15 | The Chinese University of Hong Kong | Composition and application of arginine-depleting agents for cancer, obesity, metabolic disorders, and related complications and comorbidities |
| CA3116736A1 (en) | 2018-10-19 | 2020-04-23 | Aerase, Inc. | Arginine depletion therapy for treatment of gamt deficiency |
| CN109793917B (zh) * | 2019-02-11 | 2020-10-09 | 海南建科药业有限公司 | 一种预防结直肠手术后吻合口瘘的凝胶的制备方法 |
| CA3149592A1 (en) | 2019-08-30 | 2021-03-04 | Scott W. Rowlinson | Methods for production of human recombinant arginase 1 and uses thereof |
| EP4069280A4 (en) * | 2019-12-02 | 2024-01-03 | The Hong Kong Polytechnic University | METHODS FOR INDUCING INTERMITTENT FASTING AND MODULATING AUTOPHAGY |
| CN116056720A (zh) * | 2020-04-17 | 2023-05-02 | 香港商康达医药科技有限公司 | 使用精胺酸酶治疗病毒感染的方法 |
| WO2021228875A1 (en) * | 2020-05-14 | 2021-11-18 | Kyon Biotech Ag | Treatment of respiratory viral infections |
| US20230348884A1 (en) * | 2020-09-23 | 2023-11-02 | The Hong Kong Polytechnic University | Fluorescent Biosensor for Rapid Determination of L-arginine |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5766897A (en) * | 1990-06-21 | 1998-06-16 | Incyte Pharmaceuticals, Inc. | Cysteine-pegylated proteins |
| AU2003216109A1 (en) * | 2002-01-25 | 2003-09-02 | Cancer Treatments International | Therapeutic composition for treatment of cancer by arginine depletion |
| AU2003250371B2 (en) | 2002-06-20 | 2009-01-29 | Bio-Cancer Treatment International Limited | Pharmaceutical preparation and method of treatment of human malignancies with arginine deprivation |
| HK1053577A2 (en) * | 2002-06-20 | 2003-10-10 | Bio-Cancer Treatment International Limited | Pharmaceutical composition and method of treatment of human malignanices with arginine deprivation |
| EP1539210A4 (en) | 2002-09-06 | 2006-06-07 | Bayer Pharmaceuticals Corp | GLP-1 RECEPTOR MODIFIED AGONISTS AND THEIR PHARMACOLOGICAL METHODS OF USE |
| CN1745847A (zh) | 2004-09-08 | 2006-03-15 | 康达医药科技有限公司 | 用精氨酸酶治疗肝炎的药物组合物和方法 |
| WO2006058486A1 (en) | 2004-12-03 | 2006-06-08 | Bio-Cancer Treatment International Limited | Use of arginase in combination with 5fu and other compounds for treatment of human malignancies |
| US8679479B2 (en) * | 2009-06-29 | 2014-03-25 | Aerase, Inc. | Methods for purifying pegylated arginase |
-
2010
- 2010-03-26 WO PCT/CN2010/071357 patent/WO2010124547A1/en not_active Ceased
- 2010-03-26 CN CN201080023256.4A patent/CN102481345B/zh active Active
- 2010-03-26 EP EP10769236.0A patent/EP2411040B1/en active Active
- 2010-03-26 CA CA2756442A patent/CA2756442C/en active Active
- 2010-03-26 AU AU2010242422A patent/AU2010242422B2/en active Active
- 2010-03-26 JP JP2012501126A patent/JP5746137B2/ja active Active
- 2010-03-26 US US12/732,188 patent/US8507245B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2010242422B2 (en) | 2014-12-04 |
| CA2756442A1 (en) | 2010-11-04 |
| EP2411040A1 (en) | 2012-02-01 |
| US20100247508A1 (en) | 2010-09-30 |
| EP2411040B1 (en) | 2015-09-23 |
| US8507245B2 (en) | 2013-08-13 |
| WO2010124547A1 (en) | 2010-11-04 |
| JP2012521201A (ja) | 2012-09-13 |
| CN102481345B (zh) | 2015-04-22 |
| JP5746137B2 (ja) | 2015-07-08 |
| AU2010242422A1 (en) | 2011-10-27 |
| CN102481345A (zh) | 2012-05-30 |
| EP2411040A4 (en) | 2012-09-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2756442C (en) | Site-directed pegylation of arginases and the use thereof as anti-cancer and anti-viral agents | |
| US9382525B2 (en) | Site-directed pegylation of arginases and the use thereof as anti-cancer and anti-viral agents | |
| CN105722522B (zh) | 用于肿瘤疗法的犬尿氨酸耗竭酶的施用 | |
| CA2922550C (en) | Engineered primate l-methioninase for therapeutic purposes | |
| EP3030244B1 (en) | Polyconjugates for delivery of rnai triggers to tumor cells in vivo | |
| CN105612252B (zh) | 作为抗新生剂的工程改造的灵长类动物胱氨酸/半胱氨酸降解酶 | |
| JP2012531893A (ja) | アルギナーゼ製剤および方法 | |
| ES2987380T3 (es) | Administración de enzimas de depleción de la quinurenina para la terapia tumoral | |
| US12144828B2 (en) | Human Kynureninase enzymes and uses thereof | |
| JP7744621B2 (ja) | 切断されたモルモットｌ－アスパラギナーゼバリアントおよび使用の方法 | |
| EP2721057B1 (en) | Polypeptides isolated from brevibacterium aurantiacum and their use for the treatment of cancer | |
| EP2196477B1 (en) | Modified recombinant human endostatin and its application | |
| CN106692961B (zh) | 精氨酸酶组合物、精氨酸酶激活剂及其应用 | |
| WO2024020366A1 (en) | Broad spectrum nanozymes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20150224 |