JP5746137B2 - アルギナーゼの部位指定的ペグ化並びにその抗がん剤及び抗ウイルス剤としての使用 - Google Patents
アルギナーゼの部位指定的ペグ化並びにその抗がん剤及び抗ウイルス剤としての使用 Download PDFInfo
- Publication number
- JP5746137B2 JP5746137B2 JP2012501126A JP2012501126A JP5746137B2 JP 5746137 B2 JP5746137 B2 JP 5746137B2 JP 2012501126 A JP2012501126 A JP 2012501126A JP 2012501126 A JP2012501126 A JP 2012501126A JP 5746137 B2 JP5746137 B2 JP 5746137B2
- Authority
- JP
- Japan
- Prior art keywords
- arginase
- peg
- bacillus
- cys
- arginine
- 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 description 180
- 102000004452 Arginase Human genes 0.000 title claims description 175
- 230000006320 pegylation Effects 0.000 title description 15
- 230000001093 anti-cancer Effects 0.000 title description 8
- 239000003443 antiviral agent Substances 0.000 title description 4
- 239000002246 antineoplastic agent Substances 0.000 title description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 89
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 72
- 239000004475 Arginine Substances 0.000 claims description 56
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 56
- 201000011510 cancer Diseases 0.000 claims description 45
- 229920001223 polyethylene glycol Polymers 0.000 claims description 24
- 239000002202 Polyethylene glycol Substances 0.000 claims description 10
- 241000700605 Viruses Species 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 7
- 230000001419 dependent effect Effects 0.000 claims description 6
- 230000005847 immunogenicity Effects 0.000 claims description 6
- 210000002966 serum Anatomy 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 238000012239 gene modification Methods 0.000 claims description 4
- 230000005017 genetic modification Effects 0.000 claims description 4
- 235000013617 genetically modified food Nutrition 0.000 claims description 4
- 125000003275 alpha amino acid group Chemical group 0.000 claims 8
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- 230000002068 genetic effect Effects 0.000 claims 2
- 101000792852 Bacillus caldovelox Arginase Proteins 0.000 claims 1
- 241000711549 Hepacivirus C Species 0.000 claims 1
- 241000700721 Hepatitis B virus Species 0.000 claims 1
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002452 interceptive effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 160
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 76
- 101000752037 Homo sapiens Arginase-1 Proteins 0.000 description 73
- 102000053089 human ARG1 Human genes 0.000 description 72
- 238000011282 treatment Methods 0.000 description 36
- 238000000855 fermentation Methods 0.000 description 34
- 230000004151 fermentation Effects 0.000 description 34
- 108090000623 proteins and genes Proteins 0.000 description 34
- 108010082340 Arginine deiminase Proteins 0.000 description 31
- 239000003814 drug Substances 0.000 description 30
- 102000053640 Argininosuccinate synthases Human genes 0.000 description 29
- 108700024106 Argininosuccinate synthases Proteins 0.000 description 29
- 229940079593 drug Drugs 0.000 description 29
- 241000725303 Human immunodeficiency virus Species 0.000 description 27
- 101710191958 Amino-acid acetyltransferase Proteins 0.000 description 21
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 21
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 21
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 21
- 229960003104 ornithine Drugs 0.000 description 21
- 102000004169 proteins and genes Human genes 0.000 description 21
- 102000009042 Argininosuccinate Lyase Human genes 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 19
- 230000000694 effects Effects 0.000 description 18
- 238000000034 method Methods 0.000 description 18
- 150000001413 amino acids Chemical class 0.000 description 16
- 102000004190 Enzymes Human genes 0.000 description 15
- 108090000790 Enzymes Proteins 0.000 description 15
- ASUGWWOMVNVWAW-UHFFFAOYSA-N 1-(2-methoxyethyl)pyrrole-2,5-dione Chemical compound COCCN1C(=O)C=CC1=O ASUGWWOMVNVWAW-UHFFFAOYSA-N 0.000 description 13
- 230000037396 body weight Effects 0.000 description 13
- 230000014509 gene expression Effects 0.000 description 13
- 102220565736 Acid-sensing ion channel 4_V20P_mutation Human genes 0.000 description 12
- 239000011572 manganese Substances 0.000 description 12
- 206010006187 Breast cancer Diseases 0.000 description 11
- 208000026310 Breast neoplasm Diseases 0.000 description 11
- 230000002401 inhibitory effect Effects 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 208000014018 liver neoplasm Diseases 0.000 description 10
- 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 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 230000000120 cytopathologic effect Effects 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 201000007270 liver cancer Diseases 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 239000001301 oxygen Substances 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 241000588724 Escherichia coli Species 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 201000001441 melanoma Diseases 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 7
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 7
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000021615 conjugation Effects 0.000 description 7
- 229960002949 fluorouracil Drugs 0.000 description 7
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- 201000002528 pancreatic cancer Diseases 0.000 description 7
- 208000008443 pancreatic carcinoma Diseases 0.000 description 7
- 230000010076 replication Effects 0.000 description 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
- 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
- 235000001014 amino acid Nutrition 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000007795 chemical reaction product Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 238000003757 reverse transcription PCR Methods 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 230000003833 cell viability Effects 0.000 description 5
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 5
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 5
- 230000005917 in vivo anti-tumor Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 208000020816 lung neoplasm Diseases 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
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000003104 tissue culture media Substances 0.000 description 5
- 238000007492 two-way ANOVA Methods 0.000 description 5
- 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 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-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
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 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
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 4
- 229920002684 Sepharose Polymers 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
- 210000001099 axilla Anatomy 0.000 description 4
- 235000013477 citrulline Nutrition 0.000 description 4
- 229960002173 citrulline Drugs 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000002054 inoculum Substances 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 4
- 230000003285 pharmacodynamic effect Effects 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
- 230000004614 tumor growth Effects 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- 230000029812 viral genome replication Effects 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
- 239000006145 Eagle's minimal essential medium Substances 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
- 208000000389 T-cell leukemia Diseases 0.000 description 3
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction 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
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000000593 degrading effect Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000013613 expression plasmid Substances 0.000 description 3
- 201000006585 gastric adenocarcinoma 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
- 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 3
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- 230000004143 urea cycle Effects 0.000 description 3
- 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 3
- 239000013598 vector Substances 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- 229960002555 zidovudine Drugs 0.000 description 3
- 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 2
- 108010075480 ADI PEG20 Proteins 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 102100031650 C-X-C chemokine receptor type 4 Human genes 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
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 2
- 231100000002 MTT assay Toxicity 0.000 description 2
- 238000000134 MTT assay Methods 0.000 description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 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
- -1 activated hydroxide ions Chemical class 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000005907 cancer growth Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 201000010881 cervical cancer Diseases 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
- 230000006378 damage Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 239000000890 drug combination Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 229910052748 manganese Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 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
- 230000035772 mutation Effects 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
- 229910052759 nickel Inorganic materials 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 238000010152 Bonferroni least significant difference Methods 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
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 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
- 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
- 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
- 102100034343 Integrase Human genes 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical group [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 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
- 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
- 210000001744 T-lymphocyte Anatomy 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
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000005804 alkylation reaction 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
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 230000003796 beauty Effects 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
- 210000000481 breast Anatomy 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 230000004611 cancer cell death 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
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000001268 conjugating effect Effects 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
- 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
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000001962 electrophoresis Methods 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
- 239000012634 fragment Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000009950 gastric cancer growth 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
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000028993 immune response 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
- 238000010348 incorporation Methods 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
- 230000002147 killing effect Effects 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 239000013642 negative control Substances 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
- 230000037361 pathway Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 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
- 238000004064 recycling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000002441 reversible effect Effects 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
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 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
- 210000001519 tissue Anatomy 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
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005760 tumorsuppression Effects 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
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (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 (3)
| Publication Number | Publication Date |
|---|---|
| JP2012521201A JP2012521201A (ja) | 2012-09-13 |
| JP2012521201A5 JP2012521201A5 (cg-RX-API-DMAC7.html) | 2013-05-09 |
| JP5746137B2 true JP5746137B2 (ja) | 2015-07-08 |
Family
ID=42784510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012501126A Active JP5746137B2 (ja) | 2009-03-26 | 2010-03-26 | アルギナーゼの部位指定的ペグ化並びにその抗がん剤及び抗ウイルス剤としての使用 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8507245B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2411040B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP5746137B2 (cg-RX-API-DMAC7.html) |
| CN (1) | CN102481345B (cg-RX-API-DMAC7.html) |
| AU (1) | AU2010242422B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2756442C (cg-RX-API-DMAC7.html) |
| WO (1) | WO2010124547A1 (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023522888A (ja) * | 2020-04-17 | 2023-06-01 | バイオ－キャンサー・トリートメント・インターナショナル・リミテッド | アルギナーゼを使用してウイルス感染症を処置する方法 |
Families Citing this family (20)
| 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 |
| WO2011008495A2 (en) * | 2009-06-29 | 2011-01-20 | The Board Of Regents Of The University Of Texas System | Arginase formulations and methods |
| US9682132B2 (en) | 2010-01-26 | 2017-06-20 | Banyan Biomarkers, Inc | Compositions and methods relating to argininosucccinate synthetase |
| WO2012085793A1 (en) * | 2010-12-21 | 2012-06-28 | Ning Man Cheng | Use of pegylated recombinant human arginase for treatment of leukemia |
| CN103184209B (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 |
| WO2014003850A2 (en) | 2012-06-26 | 2014-01-03 | Timothy Paul Foster | Methods for treatment of ocular diseases |
| GB2535937B (en) * | 2014-04-29 | 2017-05-31 | Bio-Cancer Treat Int Ltd | Arginase I for treating rheumatoid arthritis |
| 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 |
| CN112513099A (zh) * | 2018-05-31 | 2021-03-16 | 香港理工大学 | 用于癌症、肥胖症、代谢紊乱和相关并发症及合并症的精氨酸耗竭剂的组合物和应用 |
| KR20210095141A (ko) | 2018-10-19 | 2021-07-30 | 에어레이즈, 인크. | 지에이엠티 결핍 치료를 위한 아르기닌 결핍 요법 |
| 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 |
| KR20220082813A (ko) | 2019-08-30 | 2022-06-17 | 아이글레아 바이오테라퓨틱스, 인크. | 인간 재조합 아르기나아제 1의 제조 방법 및 이의 사용 |
| WO2021110071A1 (en) * | 2019-12-02 | 2021-06-10 | The Hong Kong Polytechnic University | Methods for inducing intermittent fasting and modulating autophagy |
| CN115843267A (zh) * | 2020-05-14 | 2023-03-24 | 克云生物科技股份公司 | 呼吸道病毒感染的治疗 |
| WO2022063178A1 (en) * | 2020-09-23 | 2022-03-31 | 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 |
| EP1499342A2 (en) * | 2002-01-25 | 2005-01-26 | Cancer Treatments International | Therapeutic composition for treatment of cancer by arginine depletion |
| EP1908478B1 (en) | 2002-06-20 | 2010-03-24 | 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 |
| JP2006501820A (ja) * | 2002-09-06 | 2006-01-19 | バイエル・フアーマシユーチカルズ・コーポレーシヨン | 修飾ｇｌｐ−１受容体アゴニストおよびそれらの薬理学的使用法 |
| 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 |
| WO2011008495A2 (en) * | 2009-06-29 | 2011-01-20 | The Board Of Regents Of The University Of Texas System | Arginase formulations and methods |
-
2010
- 2010-03-26 JP JP2012501126A patent/JP5746137B2/ja active Active
- 2010-03-26 EP EP10769236.0A patent/EP2411040B1/en active Active
- 2010-03-26 US US12/732,188 patent/US8507245B2/en active Active
- 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 AU AU2010242422A patent/AU2010242422B2/en active Active
- 2010-03-26 CA CA2756442A patent/CA2756442C/en active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023522888A (ja) * | 2020-04-17 | 2023-06-01 | バイオ－キャンサー・トリートメント・インターナショナル・リミテッド | アルギナーゼを使用してウイルス感染症を処置する方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102481345A (zh) | 2012-05-30 |
| EP2411040B1 (en) | 2015-09-23 |
| WO2010124547A1 (en) | 2010-11-04 |
| CA2756442A1 (en) | 2010-11-04 |
| US8507245B2 (en) | 2013-08-13 |
| AU2010242422B2 (en) | 2014-12-04 |
| EP2411040A4 (en) | 2012-09-12 |
| CN102481345B (zh) | 2015-04-22 |
| JP2012521201A (ja) | 2012-09-13 |
| AU2010242422A1 (en) | 2011-10-27 |
| US20100247508A1 (en) | 2010-09-30 |
| CA2756442C (en) | 2016-03-29 |
| EP2411040A1 (en) | 2012-02-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5746137B2 (ja) | アルギナーゼの部位指定的ペグ化並びにその抗がん剤及び抗ウイルス剤としての使用 | |
| US9382525B2 (en) | Site-directed pegylation of arginases and the use thereof as anti-cancer and anti-viral agents | |
| KR102442231B1 (ko) | 종양 치료를 위한 키누레닌 고갈 효소의 투여 | |
| EP2964761B1 (en) | Pharmaceutical composition comprising albumin-binding arginine deiminase for cancer targeting treatment | |
| JP2024069234A (ja) | アスパラギナーゼを用いた治療法 | |
| 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 | |
| CN105531371A (zh) | 用于治疗目的的工程改造的灵长类动物l-甲硫氨酸酶 | |
| TWI827593B (zh) | 人類犬尿胺酸酶及其用途 | |
| KR20190026813A (ko) | 시스틴의 인간-효소 매개된 고갈 | |
| EP2721057B1 (en) | Polypeptides isolated from brevibacterium aurantiacum and their use for the treatment of cancer | |
| EP2196477B1 (en) | Modified recombinant human endostatin and its application | |
| CN102131844B (zh) | 肽-聚合物缀合物 | |
| CN102724980B (zh) | 蛋白-聚合物偶联物的治疗用途 | |
| WO2024020366A1 (en) | Broad spectrum nanozymes | |
| HK1176015B (en) | Therapeutic use of protein-polymer conjugates |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130325 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130325 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140808 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141106 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150409 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150507 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5746137 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |