AU774989B2 - Methods and compositions for the prevention and treatment of anemia - Google Patents
Methods and compositions for the prevention and treatment of anemia Download PDFInfo
- Publication number
- AU774989B2 AU774989B2 AU11241/00A AU1124100A AU774989B2 AU 774989 B2 AU774989 B2 AU 774989B2 AU 11241/00 A AU11241/00 A AU 11241/00A AU 1124100 A AU1124100 A AU 1124100A AU 774989 B2 AU774989 B2 AU 774989B2
- Authority
- AU
- Australia
- Prior art keywords
- analog
- epo
- thr
- asn
- administered
- 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.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims description 48
- 208000007502 anemia Diseases 0.000 title claims description 32
- 239000000203 mixture Substances 0.000 title claims description 22
- 238000011282 treatment Methods 0.000 title description 13
- 230000002265 prevention Effects 0.000 title description 3
- 238000005534 hematocrit Methods 0.000 claims description 71
- 125000000837 carbohydrate group Chemical group 0.000 claims description 54
- 230000013595 glycosylation Effects 0.000 claims description 21
- 238000006206 glycosylation reaction Methods 0.000 claims description 21
- 108090000394 Erythropoietin Proteins 0.000 claims description 18
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 claims description 16
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 claims description 16
- 150000001413 amino acids Chemical class 0.000 claims description 16
- 102000044890 human EPO Human genes 0.000 claims description 15
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 14
- 102000003951 Erythropoietin Human genes 0.000 claims description 13
- 210000004369 blood Anatomy 0.000 claims description 13
- 239000008280 blood Substances 0.000 claims description 13
- 229940105423 erythropoietin Drugs 0.000 claims description 11
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical group OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 230000007423 decrease Effects 0.000 claims description 4
- 230000003907 kidney function Effects 0.000 claims description 4
- 239000002773 nucleotide Substances 0.000 claims description 4
- 125000003729 nucleotide group Chemical group 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 3
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 230000003039 myelosuppressive effect Effects 0.000 claims description 3
- 229920000136 polysorbate Polymers 0.000 claims description 3
- 230000002335 preservative effect Effects 0.000 claims description 3
- 239000001509 sodium citrate Substances 0.000 claims description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 3
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 239000003443 antiviral agent Substances 0.000 claims description 2
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 2
- 230000000973 chemotherapeutic effect Effects 0.000 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 229950008882 polysorbate Drugs 0.000 claims description 2
- 108091029865 Exogenous DNA Proteins 0.000 claims 1
- 239000007853 buffer solution Substances 0.000 claims 1
- 239000001488 sodium phosphate Substances 0.000 claims 1
- 229910000162 sodium phosphate Inorganic materials 0.000 claims 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 description 35
- 210000004027 cell Anatomy 0.000 description 30
- 238000001990 intravenous administration Methods 0.000 description 28
- 210000002966 serum Anatomy 0.000 description 26
- 230000000694 effects Effects 0.000 description 23
- 238000003752 polymerase chain reaction Methods 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 238000002474 experimental method Methods 0.000 description 20
- 108090000765 processed proteins & peptides Proteins 0.000 description 20
- 230000003442 weekly effect Effects 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 108020004414 DNA Proteins 0.000 description 18
- 235000001014 amino acid Nutrition 0.000 description 18
- 241000700159 Rattus Species 0.000 description 17
- 229940024606 amino acid Drugs 0.000 description 15
- 238000006467 substitution reaction Methods 0.000 description 15
- 230000004071 biological effect Effects 0.000 description 14
- 238000001727 in vivo Methods 0.000 description 14
- 230000036515 potency Effects 0.000 description 14
- 102000001708 Protein Isoforms Human genes 0.000 description 13
- 108010029485 Protein Isoforms Proteins 0.000 description 13
- 238000007912 intraperitoneal administration Methods 0.000 description 13
- 241000282472 Canis lupus familiaris Species 0.000 description 12
- 238000007792 addition Methods 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 208000020832 chronic kidney disease Diseases 0.000 description 10
- 231100000673 dose–response relationship Toxicity 0.000 description 10
- 230000003389 potentiating effect Effects 0.000 description 10
- 230000002441 reversible effect Effects 0.000 description 10
- 239000007989 BIS-Tris Propane buffer Substances 0.000 description 9
- HHKZCCWKTZRCCL-UHFFFAOYSA-N bis-tris propane Chemical compound OCC(CO)(CO)NCCCNC(CO)(CO)CO HHKZCCWKTZRCCL-UHFFFAOYSA-N 0.000 description 9
- 150000001720 carbohydrates Chemical group 0.000 description 9
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 210000003743 erythrocyte Anatomy 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 125000005629 sialic acid group Chemical group 0.000 description 8
- 238000001356 surgical procedure Methods 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 125000000539 amino acid group Chemical group 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
- 230000010437 erythropoiesis Effects 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 231100000350 mutagenesis Toxicity 0.000 description 7
- 238000002703 mutagenesis Methods 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 231100000219 mutagenic Toxicity 0.000 description 6
- 230000003505 mutagenic effect Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- 230000004988 N-glycosylation Effects 0.000 description 5
- 108091006629 SLC13A2 Proteins 0.000 description 5
- 230000004075 alteration Effects 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 239000007928 intraperitoneal injection Substances 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 241000282412 Homo Species 0.000 description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- 108010071390 Serum Albumin Proteins 0.000 description 4
- 102000007562 Serum Albumin Human genes 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 108010050848 glycylleucine Proteins 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 101100519158 Arabidopsis thaliana PCR2 gene Proteins 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 108010074604 Epoetin Alfa Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 229930182816 L-glutamine Natural products 0.000 description 3
- 101150102573 PCR1 gene Proteins 0.000 description 3
- 108010022394 Threonine synthase Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000012911 assay medium Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000003636 conditioned culture medium Substances 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 102000004419 dihydrofolate reductase Human genes 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 229940089118 epogen Drugs 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 230000037230 mobility Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 150000002482 oligosaccharides Polymers 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 230000000581 polycythemic effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 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 3
- 229960002555 zidovudine Drugs 0.000 description 3
- RJUHZPRQRQLCFL-IMJSIDKUSA-N Asn-Asn Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(O)=O RJUHZPRQRQLCFL-IMJSIDKUSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- FPFOYSCDUWTZBF-IHPCNDPISA-N Leu-Trp-Leu Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H]([NH3+])CC(C)C)C(=O)N[C@@H](CC(C)C)C([O-])=O)=CNC2=C1 FPFOYSCDUWTZBF-IHPCNDPISA-N 0.000 description 2
- SEQKRHFRPICQDD-UHFFFAOYSA-N N-tris(hydroxymethyl)methylglycine Chemical compound OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 2
- 230000004989 O-glycosylation Effects 0.000 description 2
- 239000012564 Q sepharose fast flow resin Substances 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 238000000246 agarose gel electrophoresis Methods 0.000 description 2
- 238000005349 anion exchange Methods 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229910001868 water Inorganic materials 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- RVLOMLVNNBWRSR-KNIFDHDWSA-N (2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O RVLOMLVNNBWRSR-KNIFDHDWSA-N 0.000 description 1
- IPDRTIBDOPMMIQ-VAOFZXAKSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)-2-methyloxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@]1(C)O[C@H](CO)[C@@H](O)C1 IPDRTIBDOPMMIQ-VAOFZXAKSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- NKDFYOWSKOHCCO-YPVLXUMRSA-N 20-hydroxyecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@](C)(O)[C@H](O)CCC(C)(O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 NKDFYOWSKOHCCO-YPVLXUMRSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- JYEBJTDTPNKQJG-FXQIFTODSA-N Ala-Asn-Met Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCSC)C(=O)O)N JYEBJTDTPNKQJG-FXQIFTODSA-N 0.000 description 1
- IXTPACPAXIOCRG-ACZMJKKPSA-N Ala-Glu-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N IXTPACPAXIOCRG-ACZMJKKPSA-N 0.000 description 1
- SOBIAADAMRHGKH-CIUDSAMLSA-N Ala-Leu-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O SOBIAADAMRHGKH-CIUDSAMLSA-N 0.000 description 1
- PEIBBAXIKUAYGN-UBHSHLNASA-N Ala-Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 PEIBBAXIKUAYGN-UBHSHLNASA-N 0.000 description 1
- WPWUFUBLGADILS-WDSKDSINSA-N Ala-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WPWUFUBLGADILS-WDSKDSINSA-N 0.000 description 1
- YJHKTAMKPGFJCT-NRPADANISA-N Ala-Val-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O YJHKTAMKPGFJCT-NRPADANISA-N 0.000 description 1
- 208000030760 Anaemia of chronic disease Diseases 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- IASNWHAGGYTEKX-IUCAKERBSA-N Arg-Arg-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(O)=O IASNWHAGGYTEKX-IUCAKERBSA-N 0.000 description 1
- JSLGXODUIAFWCF-WDSKDSINSA-N Arg-Asn Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(O)=O JSLGXODUIAFWCF-WDSKDSINSA-N 0.000 description 1
- OZNSCVPYWZRQPY-CIUDSAMLSA-N Arg-Asp-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O OZNSCVPYWZRQPY-CIUDSAMLSA-N 0.000 description 1
- OOIMKQRCPJBGPD-XUXIUFHCSA-N Arg-Ile-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O OOIMKQRCPJBGPD-XUXIUFHCSA-N 0.000 description 1
- CLICCYPMVFGUOF-IHRRRGAJSA-N Arg-Lys-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O CLICCYPMVFGUOF-IHRRRGAJSA-N 0.000 description 1
- KMFPQTITXUKJOV-DCAQKATOSA-N Arg-Ser-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O KMFPQTITXUKJOV-DCAQKATOSA-N 0.000 description 1
- UZSQXCMNUPKLCC-FJXKBIBVSA-N Arg-Thr-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O UZSQXCMNUPKLCC-FJXKBIBVSA-N 0.000 description 1
- ZJBUILVYSXQNSW-YTWAJWBKSA-N Arg-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ZJBUILVYSXQNSW-YTWAJWBKSA-N 0.000 description 1
- AEZCCDMZZJOGII-DCAQKATOSA-N Asn-Met-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O AEZCCDMZZJOGII-DCAQKATOSA-N 0.000 description 1
- FANQWNCPNFEPGZ-WHFBIAKZSA-N Asp-Asp-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O FANQWNCPNFEPGZ-WHFBIAKZSA-N 0.000 description 1
- JSNWZMFSLIWAHS-HJGDQZAQSA-N Asp-Thr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O JSNWZMFSLIWAHS-HJGDQZAQSA-N 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 101100228196 Caenorhabditis elegans gly-4 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- JEKIARHEWURQRJ-BZSNNMDCSA-N Cys-Phe-Tyr Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)NC(=O)[C@H](CS)N JEKIARHEWURQRJ-BZSNNMDCSA-N 0.000 description 1
- YNJBLTDKTMKEET-ZLUOBGJFSA-N Cys-Ser-Ser Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O YNJBLTDKTMKEET-ZLUOBGJFSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- UTKICHUQEQBDGC-ACZMJKKPSA-N Glu-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N UTKICHUQEQBDGC-ACZMJKKPSA-N 0.000 description 1
- PCBBLFVHTYNQGG-LAEOZQHASA-N Glu-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)N PCBBLFVHTYNQGG-LAEOZQHASA-N 0.000 description 1
- YBTCBQBIJKGSJP-BQBZGAKWSA-N Glu-Pro Chemical compound OC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O YBTCBQBIJKGSJP-BQBZGAKWSA-N 0.000 description 1
- QXPRJQPCFXMCIY-NKWVEPMBSA-N Gly-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN QXPRJQPCFXMCIY-NKWVEPMBSA-N 0.000 description 1
- LCRDMSSAKLTKBU-ZDLURKLDSA-N Gly-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN LCRDMSSAKLTKBU-ZDLURKLDSA-N 0.000 description 1
- GWCJMBNBFYBQCV-XPUUQOCRSA-N Gly-Val-Ala Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O GWCJMBNBFYBQCV-XPUUQOCRSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- MWWOPNQSBXEUHO-ULQDDVLXSA-N His-Arg-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CN=CN1 MWWOPNQSBXEUHO-ULQDDVLXSA-N 0.000 description 1
- YTKOTXRIWQHSAZ-GUBZILKMSA-N His-Glu-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N YTKOTXRIWQHSAZ-GUBZILKMSA-N 0.000 description 1
- LNCFUHAPNTYMJB-IUCAKERBSA-N His-Pro Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CN=CN1 LNCFUHAPNTYMJB-IUCAKERBSA-N 0.000 description 1
- YOTNPRLPIPHQSB-XUXIUFHCSA-N Ile-Arg-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOTNPRLPIPHQSB-XUXIUFHCSA-N 0.000 description 1
- AXNGDPAKKCEKGY-QPHKQPEJSA-N Ile-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N AXNGDPAKKCEKGY-QPHKQPEJSA-N 0.000 description 1
- XLXPYSDGMXTTNQ-DKIMLUQUSA-N Ile-Phe-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(O)=O XLXPYSDGMXTTNQ-DKIMLUQUSA-N 0.000 description 1
- XLXPYSDGMXTTNQ-UHFFFAOYSA-N Ile-Phe-Leu Natural products CCC(C)C(N)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=CC=C1 XLXPYSDGMXTTNQ-UHFFFAOYSA-N 0.000 description 1
- 239000007760 Iscove's Modified Dulbecco's Medium Substances 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- UGTHTQWIQKEDEH-BQBZGAKWSA-N L-alanyl-L-prolylglycine zwitterion Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UGTHTQWIQKEDEH-BQBZGAKWSA-N 0.000 description 1
- BQSLGJHIAGOZCD-CIUDSAMLSA-N Leu-Ala-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O BQSLGJHIAGOZCD-CIUDSAMLSA-N 0.000 description 1
- MYGQXVYRZMKRDB-SRVKXCTJSA-N Leu-Asp-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN MYGQXVYRZMKRDB-SRVKXCTJSA-N 0.000 description 1
- FAELBUXXFQLUAX-AJNGGQMLSA-N Leu-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C FAELBUXXFQLUAX-AJNGGQMLSA-N 0.000 description 1
- RXGLHDWAZQECBI-SRVKXCTJSA-N Leu-Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O RXGLHDWAZQECBI-SRVKXCTJSA-N 0.000 description 1
- IEWBEPKLKUXQBU-VOAKCMCISA-N Leu-Leu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IEWBEPKLKUXQBU-VOAKCMCISA-N 0.000 description 1
- 206010024291 Leukaemias acute myeloid Diseases 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- UWKNTTJNVSYXPC-CIUDSAMLSA-N Lys-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN UWKNTTJNVSYXPC-CIUDSAMLSA-N 0.000 description 1
- XIZQPFCRXLUNMK-BZSNNMDCSA-N Lys-Leu-Phe Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCCCN)N XIZQPFCRXLUNMK-BZSNNMDCSA-N 0.000 description 1
- VKCPHIOZDWUFSW-ONGXEEELSA-N Lys-Val-Gly Chemical compound OC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN VKCPHIOZDWUFSW-ONGXEEELSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- BMHIFARYXOJDLD-WPRPVWTQSA-N Met-Gly-Val Chemical compound [H]N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O BMHIFARYXOJDLD-WPRPVWTQSA-N 0.000 description 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- 241001460678 Napo <wasp> Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- DMEYUTSDVRCWRS-ULQDDVLXSA-N Phe-Lys-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 DMEYUTSDVRCWRS-ULQDDVLXSA-N 0.000 description 1
- ONPFOYPPPOHMNH-UVBJJODRSA-N Pro-Ala-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@@H]3CCCN3 ONPFOYPPPOHMNH-UVBJJODRSA-N 0.000 description 1
- VCYJKOLZYPYGJV-AVGNSLFASA-N Pro-Arg-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O VCYJKOLZYPYGJV-AVGNSLFASA-N 0.000 description 1
- QXNSKJLSLYCTMT-FXQIFTODSA-N Pro-Cys-Asp Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O QXNSKJLSLYCTMT-FXQIFTODSA-N 0.000 description 1
- HAEGAELAYWSUNC-WPRPVWTQSA-N Pro-Gly-Val Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HAEGAELAYWSUNC-WPRPVWTQSA-N 0.000 description 1
- SVXXJYJCRNKDDE-AVGNSLFASA-N Pro-Pro-His Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NCCC1)C1=CN=CN1 SVXXJYJCRNKDDE-AVGNSLFASA-N 0.000 description 1
- VGFFUEVZKRNRHT-ULQDDVLXSA-N Pro-Trp-Glu Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CCC(=O)O)C(=O)O VGFFUEVZKRNRHT-ULQDDVLXSA-N 0.000 description 1
- KHRLUIPIMIQFGT-AVGNSLFASA-N Pro-Val-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHRLUIPIMIQFGT-AVGNSLFASA-N 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 239000012614 Q-Sepharose Substances 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- SMIDBHKWSYUBRZ-ACZMJKKPSA-N Ser-Glu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O SMIDBHKWSYUBRZ-ACZMJKKPSA-N 0.000 description 1
- SQBLRDDJTUJDMV-ACZMJKKPSA-N Ser-Glu-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O SQBLRDDJTUJDMV-ACZMJKKPSA-N 0.000 description 1
- LRZLZIUXQBIWTB-KATARQTJSA-N Ser-Lys-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LRZLZIUXQBIWTB-KATARQTJSA-N 0.000 description 1
- ADJDNJCSPNFFPI-FXQIFTODSA-N Ser-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO ADJDNJCSPNFFPI-FXQIFTODSA-N 0.000 description 1
- YEDSOSIKVUMIJE-DCAQKATOSA-N Ser-Val-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O YEDSOSIKVUMIJE-DCAQKATOSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 241000890661 Sudra Species 0.000 description 1
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 1
- MQCPGOZXFSYJPS-KZVJFYERSA-N Thr-Ala-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O MQCPGOZXFSYJPS-KZVJFYERSA-N 0.000 description 1
- XOWKUMFHEZLKLT-CIQUZCHMSA-N Thr-Ile-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O XOWKUMFHEZLKLT-CIQUZCHMSA-N 0.000 description 1
- AHERARIZBPOMNU-KATARQTJSA-N Thr-Ser-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O AHERARIZBPOMNU-KATARQTJSA-N 0.000 description 1
- ZMYCLHFLHRVOEA-HEIBUPTGSA-N Thr-Thr-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ZMYCLHFLHRVOEA-HEIBUPTGSA-N 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 108010001244 Tli polymerase Proteins 0.000 description 1
- 239000007997 Tricine buffer Substances 0.000 description 1
- VYQQQIRHIFALGE-UWJYBYFXSA-N Tyr-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 VYQQQIRHIFALGE-UWJYBYFXSA-N 0.000 description 1
- ZZDYJFVIKVSUFA-WLTAIBSBSA-N Tyr-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O ZZDYJFVIKVSUFA-WLTAIBSBSA-N 0.000 description 1
- RMRFSFXLFWWAJZ-HJOGWXRNSA-N Tyr-Tyr-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 RMRFSFXLFWWAJZ-HJOGWXRNSA-N 0.000 description 1
- 108010018161 UlTma DNA polymerase Proteins 0.000 description 1
- REJBPZVUHYNMEN-LSJOCFKGSA-N Val-Ala-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N REJBPZVUHYNMEN-LSJOCFKGSA-N 0.000 description 1
- UEHRGZCNLSWGHK-DLOVCJGASA-N Val-Glu-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UEHRGZCNLSWGHK-DLOVCJGASA-N 0.000 description 1
- MIKHIIQMRFYVOR-RCWTZXSCSA-N Val-Pro-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C(C)C)N)O MIKHIIQMRFYVOR-RCWTZXSCSA-N 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
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 1
- 108010047495 alanylglycine Proteins 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- 208000022400 anemia due to chronic disease Diseases 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 108010068380 arginylarginine Proteins 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 238000007630 basic procedure Methods 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- -1 carrier Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 108010060199 cysteinylproline Proteins 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 201000000523 end stage renal failure Diseases 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 210000003013 erythroid precursor cell Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 108010008237 glutamyl-valyl-glycine Proteins 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 108010085325 histidylproline Proteins 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 108010082795 phenylalanyl-arginyl-arginine Proteins 0.000 description 1
- 108010083476 phenylalanyltryptophan Proteins 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000003156 radioimmunoprecipitation Methods 0.000 description 1
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 108010080629 tryptophan-leucine Proteins 0.000 description 1
- 108010078580 tyrosylleucine Proteins 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/505—Erythropoietin [EPO]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1816—Erythropoietin [EPO]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17829298A | 1998-10-23 | 1998-10-23 | |
| US09/178292 | 1998-10-23 | ||
| PCT/US1999/024435 WO2000024893A2 (en) | 1998-10-23 | 1999-10-18 | Methods and compositions for the prevention and treatment of anemia |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU1124100A AU1124100A (en) | 2000-05-15 |
| AU774989B2 true AU774989B2 (en) | 2004-07-15 |
Family
ID=22651968
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU11241/00A Ceased AU774989B2 (en) | 1998-10-23 | 1999-10-18 | Methods and compositions for the prevention and treatment of anemia |
Country Status (19)
| Country | Link |
|---|---|
| EP (2) | EP1123313B2 (enExample) |
| JP (2) | JP4809977B2 (enExample) |
| KR (1) | KR20010075661A (enExample) |
| CN (2) | CN101703760A (enExample) |
| AR (1) | AR020848A1 (enExample) |
| AT (2) | ATE477270T1 (enExample) |
| AU (1) | AU774989B2 (enExample) |
| CA (1) | CA2345882C (enExample) |
| CY (2) | CY1107584T1 (enExample) |
| DE (2) | DE69935345T3 (enExample) |
| DK (2) | DK1123313T3 (enExample) |
| ES (2) | ES2283139T5 (enExample) |
| HK (1) | HK1040944B (enExample) |
| HU (1) | HU228492B1 (enExample) |
| IL (2) | IL142334A (enExample) |
| PT (2) | PT1813624E (enExample) |
| SI (2) | SI1123313T1 (enExample) |
| TW (1) | TWI234583B (enExample) |
| WO (1) | WO2000024893A2 (enExample) |
Families Citing this family (130)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7217689B1 (en) | 1989-10-13 | 2007-05-15 | Amgen Inc. | Glycosylation analogs of erythropoietin |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| AU719482B2 (en) | 1996-03-14 | 2000-05-11 | Genentech Inc. | Uses of GDNF and GDNF receptor |
| ES2590912T3 (es) | 1997-12-08 | 2016-11-24 | Merck Patent Gmbh | Proteínas de fusión heterodiméricas útiles para inmunoterapia dirigida y estimulación general del sistema inmunitario |
| US7304150B1 (en) | 1998-10-23 | 2007-12-04 | Amgen Inc. | Methods and compositions for the prevention and treatment of anemia |
| US6555343B1 (en) | 1999-05-07 | 2003-04-29 | Genentech Inc. | Chimpanzee erythropoietin (CHEPO) polypeptides and nucleic acids encoding the same |
| MXPA01011264A (es) * | 1999-05-07 | 2002-07-02 | Genentech Inc | Nuevos polipeptidos de eritropoyetina de chimpance (chepo) y aciodos nucleicos que codifican los mismos. |
| US6831060B2 (en) | 1999-05-07 | 2004-12-14 | Genentech, Inc. | Chimpanzee erythropoietin (CHEPO) polypeptides and nucleic acids encoding the same |
| US7067110B1 (en) | 1999-07-21 | 2006-06-27 | Emd Lexigen Research Center Corp. | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
| AU778611B2 (en) | 1999-08-09 | 2004-12-16 | Merck Patent Gmbh | Multiple cytokine-antibody complexes |
| CA2391080A1 (en) | 1999-11-12 | 2001-05-25 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Erythropoietin forms with improved properties |
| ATE336514T1 (de) | 2000-02-11 | 2006-09-15 | Merck Patent Gmbh | Steigerung der zirkulierenden halbwertzeit von auf antikörpern basierenden fusionsproteinen |
| CA2405550A1 (en) | 2000-04-12 | 2001-10-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AU2001255516B2 (en) * | 2000-04-21 | 2007-01-18 | Amgen Inc. | Methods and compositions for the prevention and treatment of anemia |
| CZ304855B6 (cs) | 2000-05-15 | 2014-12-10 | F. Hoffmann-La Roche Ag | Kapalná farmaceutická kompozice obsahující pegylovaný lidský erythropoetin, způsob její přípravy, léčivo pro léčení chorob korelujících s anemií při chronickém renálním selhání a zařízení s jejím obsahem |
| ATE368475T1 (de) | 2000-06-29 | 2007-08-15 | Emd Lexigen Res Ct Corp | Steigerung von durch antikörper-zytokin- fusionsproteine mediierten immunantworten durch eine kombinierte behandlung mit mitteln zur erhöhung der immunzytokinaufnahme |
| US7078376B1 (en) | 2000-08-11 | 2006-07-18 | Baxter Healthcare S.A. | Therapeutic methods for treating subjects with a recombinant erythropoietin having high activity and reduced side effects |
| US7087224B2 (en) * | 2000-10-31 | 2006-08-08 | Amgen Inc. | Method of treating anemia by administering IL-1ra |
| BR0207854A (pt) | 2001-03-07 | 2004-08-24 | Merck Patent Gmbh | Tecnologia de expressão para proteìnas contendo uma porção de anticorpo de isotipo hìbrido |
| WO2002079415A2 (en) | 2001-03-30 | 2002-10-10 | Lexigen Pharmaceuticals Corp. | Reducing the immunogenicity of fusion proteins |
| DK1383785T3 (da) | 2001-05-03 | 2011-05-23 | Merck Patent Gmbh | Rekombinant tumorspecifikt antistof og anvendelse deraf |
| PT1454138E (pt) | 2001-12-04 | 2012-03-28 | Merck Patent Gmbh | Imunocitoquinas com seletividade modulada |
| AU2002364586A1 (en) | 2001-12-21 | 2003-07-30 | Delta Biotechnology Limited | Albumin fusion proteins |
| CA2491567A1 (en) * | 2002-07-01 | 2004-01-08 | The Kenneth S. Warren Institute, Inc. | Recombinant tissue protective cytokines and encoding nucleic acids thereof for protection, restoration, and enhancement of responsive cells, tissues, and organs |
| WO2004009627A1 (en) * | 2002-07-19 | 2004-01-29 | Cangene Corporation | Pegylated erythropoietic compounds |
| DK1572748T3 (da) | 2002-12-17 | 2010-08-23 | Merck Patent Gmbh | Humaniseret antistof (H14.18) af muse-14.18-antistof der binder til GD2 og dets fusionsprotein med IL-2 |
| CA2513213C (en) | 2003-01-22 | 2013-07-30 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| AU2004242928B2 (en) | 2003-05-30 | 2011-03-10 | Gemin X Pharmaceuticals Canada Inc. | Triheterocyclic compounds, compositions, and methods for treating cancer or viral diseases |
| KR20060124656A (ko) | 2003-12-31 | 2006-12-05 | 메르크 파텐트 게엠베하 | 개선된 약물동태를 가지는 Ｆｃ-에리스로포이에틴 융합단백질 |
| TWI376234B (en) | 2005-02-01 | 2012-11-11 | Msd Oss Bv | Conjugates of a polypeptide and an oligosaccharide |
| AU2006250885A1 (en) * | 2005-05-24 | 2006-11-30 | Avesthagen Limited | A recombinant method for production of an erythropoiesis stimulating protein |
| EP2495308A1 (en) | 2005-12-08 | 2012-09-05 | Amgen Inc. | Improved production of glycoproteins using manganese |
| CA2630782C (en) | 2005-12-08 | 2015-02-03 | Amgen Inc. | Improved host cells and culture methods |
| AU2007275638B2 (en) | 2006-07-21 | 2014-01-16 | Amgen Inc. | Method of detecting and/ or measuring hepcidin in a sample |
| CA2701032C (en) | 2007-09-27 | 2021-01-26 | Amgen Inc. | Pharmaceutical formulations |
| EP3381445B1 (en) | 2007-11-15 | 2023-10-25 | Amgen Inc. | Aqueous formulation of antibody stablised by antioxidants for parenteral administration |
| CA2711826C (en) | 2008-01-25 | 2018-02-27 | Amgen Inc. | Ferroportin antibodies and methods of use |
| EP2816059A1 (en) | 2008-05-01 | 2014-12-24 | Amgen, Inc | Anti-hepcidin antibodies and methods of use |
| CN101323630B (zh) * | 2008-07-25 | 2013-06-05 | 中国科学院上海有机化学研究所 | 一种过渡金属络合物、合成方法及其用途 |
| EP2349332B1 (en) | 2008-11-13 | 2019-10-23 | The General Hospital Corporation | Methods and compositions for regulating iron homeostasis by modulation bmp-6 |
| EP2456871B1 (en) | 2009-07-24 | 2016-09-07 | Dr. Reddy's Laboratories, Ltd. | Production of erythropoiesis stimulating protein using metal ions |
| CA2777226A1 (en) | 2009-10-12 | 2011-04-21 | Pfizer Inc. | Cancer treatment |
| AU2010310457B2 (en) | 2009-10-23 | 2015-07-02 | Amgen Inc. | Vial adapter and system |
| KR102513760B1 (ko) | 2010-06-07 | 2023-03-27 | 암젠 인크 | 약물 전달 장치 |
| EP2691065B1 (en) | 2011-03-31 | 2017-03-01 | Amgen Inc. | Vial adapter and system |
| CA3019531A1 (en) | 2011-04-19 | 2012-10-26 | Pfizer Inc. | Combinations of anti-4-1bb antibodies and adcc-inducing antibodies for the treatment of cancer |
| CA2833748C (en) | 2011-04-20 | 2019-07-16 | Amgen Inc. | Autoinjector apparatus |
| EP3335747B1 (en) | 2011-10-14 | 2021-04-07 | Amgen Inc. | Injector and method of assembly |
| EP3072548B1 (en) | 2012-11-21 | 2019-03-06 | Amgen, Inc | Drug delivery device |
| CN111617347B (zh) | 2013-03-15 | 2023-09-29 | 安进公司 | 身体轮廓可调适的自动注射器装置 |
| US10492990B2 (en) | 2013-03-15 | 2019-12-03 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
| JP6336564B2 (ja) | 2013-03-15 | 2018-06-06 | アムゲン・インコーポレーテッド | 薬物カセット、自動注入器、および自動注入器システム |
| DK2968503T3 (en) | 2013-03-15 | 2018-12-03 | Intrinsic Lifesciences Llc | ANTI-HEPCIDIN ANTIBODIES AND APPLICATIONS THEREOF |
| EP2976117B1 (en) | 2013-03-22 | 2020-12-30 | Amgen Inc. | Injector and method of assembly |
| WO2015061389A1 (en) | 2013-10-24 | 2015-04-30 | Amgen Inc. | Drug delivery system with temperature-sensitive control |
| SG11201602876WA (en) | 2013-10-24 | 2016-05-30 | Amgen Inc | Injector and method of assembly |
| US10994112B2 (en) | 2014-02-05 | 2021-05-04 | Amgen Inc. | Drug delivery system with electromagnetic field generator |
| SG10201811702TA (en) | 2014-05-07 | 2019-01-30 | Amgen Inc | Autoinjector with shock reducing elements |
| MX387194B (es) | 2014-06-03 | 2025-03-18 | Amgen Inc | Sistemas y metodos para procesar de manera remota datos recolectados por un dispositivo de suministro de farmaco. |
| EP3197915A4 (en) | 2014-09-22 | 2018-12-19 | Intrinsic Lifesciences LLC | Humanized anti-hepcidin antibodies and uses thereof |
| EP3943135B1 (en) | 2014-10-14 | 2025-09-24 | Amgen Inc. | Drug injection device with visual and audible indicators |
| EP3689394A1 (en) | 2014-12-19 | 2020-08-05 | Amgen Inc. | Drug delivery device with live button or user interface field |
| US10799630B2 (en) | 2014-12-19 | 2020-10-13 | Amgen Inc. | Drug delivery device with proximity sensor |
| CA2972757A1 (en) | 2014-12-31 | 2016-07-07 | Arthur M. Krieg | Combination tumor immunotherapy |
| ES2748750T3 (es) | 2015-02-17 | 2020-03-17 | Amgen Inc | Dispositivo de administración de fármacos con sujeción asistida por vacío y/o realimentación |
| US11806509B2 (en) | 2015-02-27 | 2023-11-07 | Amgen Inc. | Drug delivery device having a needle guard mechanism with a turnable threshold of resistance to needle guard movement |
| WO2017039786A1 (en) | 2015-09-02 | 2017-03-09 | Amgen Inc. | Syringe assembly adapter for a syringe |
| US11351308B2 (en) | 2015-12-09 | 2022-06-07 | Amgen Inc. | Auto-injector with signaling cap |
| US11154661B2 (en) | 2016-01-06 | 2021-10-26 | Amgen Inc. | Auto-injector with signaling electronics |
| EP3429663B1 (en) | 2016-03-15 | 2020-07-15 | Amgen Inc. | Reducing probability of glass breakage in drug delivery devices |
| US11541168B2 (en) | 2016-04-29 | 2023-01-03 | Amgen Inc. | Drug delivery device with messaging label |
| US11389588B2 (en) | 2016-05-02 | 2022-07-19 | Amgen Inc. | Syringe adapter and guide for filling an on-body injector |
| JP7309363B2 (ja) | 2016-05-13 | 2023-07-18 | アムジエン・インコーポレーテツド | バイアル・スリーブ組立体 |
| US11238150B2 (en) | 2016-05-16 | 2022-02-01 | Amgen Inc. | Data encryption in medical devices with limited computational capability |
| WO2017209899A1 (en) | 2016-06-03 | 2017-12-07 | Amgen Inc. | Impact testing apparatuses and methods for drug delivery devices |
| EP3478342B1 (en) | 2016-07-01 | 2025-03-12 | Amgen Inc. | Drug delivery device having minimized risk of component fracture upon impact events |
| WO2018034784A1 (en) | 2016-08-17 | 2018-02-22 | Amgen Inc. | Drug delivery device with placement detection |
| US11202818B2 (en) | 2016-09-14 | 2021-12-21 | President And Fellows Of Harvard College | Methods and compositions for modulating erythropoiesis |
| US20200261643A1 (en) | 2016-10-25 | 2020-08-20 | Amgen Inc. | On-body injector |
| MX2019008432A (es) | 2017-01-17 | 2019-11-18 | Amgen Inc | Dispositivos de inyeccion y metodos relacionados de uso y ensamblaje. |
| MX2019009755A (es) | 2017-02-17 | 2019-10-07 | Amgen Inc | Mecanismo de insercion para dispositivo de suministro de farmacos. |
| US11752258B2 (en) | 2017-02-17 | 2023-09-12 | Amgen Inc. | Drug delivery device with sterile fluid flowpath and related method of assembly |
| WO2018165143A1 (en) | 2017-03-06 | 2018-09-13 | Amgen Inc. | Drug delivery device with activation prevention feature |
| WO2018164829A1 (en) | 2017-03-07 | 2018-09-13 | Amgen Inc. | Needle insertion by overpressure |
| IL268386B2 (en) | 2017-03-09 | 2023-11-01 | Amgen Inc | Insertion mechanism for a drug delivery device |
| JP2020511499A (ja) | 2017-03-20 | 2020-04-16 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 赤血球生成刺激タンパク質のインビトロでの糖鎖改変のための方法 |
| PL3600491T3 (pl) | 2017-03-28 | 2024-03-04 | Amgen Inc. | Układ i sposób montażu trzonu tłoka i strzykawki |
| EP3634546A1 (en) | 2017-06-08 | 2020-04-15 | Amgen Inc. | Torque driven drug delivery device |
| WO2018226515A1 (en) | 2017-06-08 | 2018-12-13 | Amgen Inc. | Syringe assembly for a drug delivery device and method of assembly |
| WO2018236619A1 (en) | 2017-06-22 | 2018-12-27 | Amgen Inc. | Device activation impact/shock reduction |
| JP7475860B2 (ja) | 2017-06-23 | 2024-04-30 | アムジエン・インコーポレーテツド | スイッチアセンブリにより起動されるキャップを含む電子薬物送達デバイス |
| EP3651832B1 (en) | 2017-07-14 | 2023-12-13 | Amgen Inc. | Needle insertion-retraction system having dual torsion spring system |
| US11672733B2 (en) | 2017-07-21 | 2023-06-13 | Amgen Inc. | Gas permeable sealing member for drug container and methods of assembly |
| JP2020528296A (ja) | 2017-07-25 | 2020-09-24 | アムジエン・インコーポレーテツド | ギヤモジュールを有する薬物送達デバイス及び関連する組立方法 |
| JP7242562B2 (ja) | 2017-07-25 | 2023-03-20 | アムジエン・インコーポレーテツド | 容器アクセスシステムを有する薬物送達デバイス及び関連する組立方法 |
| US12318593B2 (en) | 2017-08-09 | 2025-06-03 | Amgen Inc. | Hydraulic-pneumatic pressurized chamber drug delivery system |
| EP3668567A1 (en) | 2017-08-18 | 2020-06-24 | Amgen Inc. | Wearable injector with sterile adhesive patch |
| US11103636B2 (en) | 2017-08-22 | 2021-08-31 | Amgen Inc. | Needle insertion mechanism for drug delivery device |
| US11759565B2 (en) | 2017-10-04 | 2023-09-19 | Amgen Inc. | Flow adapter for drug delivery device |
| EP3691716B1 (en) | 2017-10-06 | 2023-11-29 | Amgen Inc. | Drug delivery device with interlock assembly and related method of assembly |
| IL273323B2 (en) | 2017-10-09 | 2024-10-01 | Amgen Inc | Drug delivery device with drive assembly and related assembly method |
| US11826480B2 (en) | 2017-11-03 | 2023-11-28 | Amgen Inc. | Systems and approaches for sterilizing a drug delivery device |
| MA50569A (fr) | 2017-11-06 | 2020-09-16 | Amgen Inc | Ensembles de remplissage-finition et procédés associés |
| MA50553A (fr) | 2017-11-06 | 2020-09-16 | Amgen Inc | Dispositif d'administration de médicament avec détection de positionnement et de débit |
| SG11202002966QA (en) | 2017-11-10 | 2020-05-28 | Amgen Inc | Plungers for drug delivery devices |
| AU2018368340B2 (en) | 2017-11-16 | 2024-03-07 | Amgen Inc. | Door latch mechanism for drug delivery device |
| JP7747438B2 (ja) | 2017-11-16 | 2025-10-01 | アムジエン・インコーポレーテツド | 失速及び終点検出を有するオートインジェクタ |
| EP3752194A4 (en) | 2018-02-13 | 2022-03-16 | Checkmate Pharmaceuticals, Inc. | COMPOSITIONS AND METHODS FOR TUMOR IMMUNOTHERAPY |
| EP3775218A1 (en) | 2018-04-09 | 2021-02-17 | Checkmate Pharmaceuticals | Packaging oligonucleotides into virus-like particles |
| US10835685B2 (en) | 2018-05-30 | 2020-11-17 | Amgen Inc. | Thermal spring release mechanism for a drug delivery device |
| US11083840B2 (en) | 2018-06-01 | 2021-08-10 | Amgen Inc. | Modular fluid path assemblies for drug delivery devices |
| WO2020023336A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with grip portion |
| EP3826701A1 (en) | 2018-07-24 | 2021-06-02 | Amgen Inc. | Delivery devices for administering drugs |
| MX2021000749A (es) | 2018-07-24 | 2021-03-29 | Amgen Inc | Dispositivos de suministro para administrar farmacos. |
| WO2020023220A1 (en) | 2018-07-24 | 2020-01-30 | Amgen Inc. | Hybrid drug delivery devices with tacky skin attachment portion and related method of preparation |
| WO2020028009A1 (en) | 2018-07-31 | 2020-02-06 | Amgen Inc. | Fluid path assembly for a drug delivery device |
| JP2022500095A (ja) | 2018-09-24 | 2022-01-04 | アムジエン・インコーポレーテツド | インターベンション投薬システム及び方法 |
| IL281469B2 (en) | 2018-09-28 | 2024-08-01 | Amgen Inc | Muscle wire escapement activation assembly for a drug delivery device |
| EP3860685A1 (en) | 2018-10-02 | 2021-08-11 | Amgen Inc. | Injection systems for drug delivery with internal force transmission |
| US12151089B2 (en) | 2018-10-05 | 2024-11-26 | Amgen Inc. | Drug delivery device having dose indicator |
| MA53912A (fr) | 2018-10-15 | 2022-01-19 | Amgen Inc | Dispositif d'administration de médicament comprenant un mécanisme d'amortissement |
| SG11202101824VA (en) | 2018-10-15 | 2021-03-30 | Amgen Inc | Platform assembly process for drug delivery device |
| AU2019370159B2 (en) | 2018-11-01 | 2025-05-29 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
| EP3873566B1 (en) | 2018-11-01 | 2024-11-27 | Amgen Inc. | Drug delivery devices with partial drug delivery member retraction |
| TWI831847B (zh) | 2018-11-01 | 2024-02-11 | 美商安進公司 | 部分針頭縮回之藥物遞送裝置及其操作方法 |
| US20220160972A1 (en) | 2019-04-24 | 2022-05-26 | Amgen Inc. | Syringe sterilization verification assemblies and methods |
| JP7608439B2 (ja) | 2019-08-23 | 2025-01-06 | アムジエン・インコーポレーテツド | 構成可能な針シールド係合構成要素を備えた薬物送達デバイス及び関連方法 |
| US20240208680A1 (en) | 2021-05-21 | 2024-06-27 | Amgen Inc. | Method of optimizing a filling recipe for a drug container |
| WO2023209074A1 (en) | 2022-04-28 | 2023-11-02 | Institut National de la Santé et de la Recherche Médicale | Methods of restoring erythropoiesis in patients suffering from a sf3b1 mutant myelodysplastic syndrome by correcting coasy mis-splicing |
| EP4612312A1 (en) | 2022-11-02 | 2025-09-10 | F. Hoffmann-La Roche AG | Method for producing glycoprotein compositions |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995005465A1 (en) * | 1993-08-17 | 1995-02-23 | Amgen Inc. | Erythropoietin analogs |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4954437A (en) * | 1986-09-15 | 1990-09-04 | Integrated Genetics, Inc. | Cell encoding recombinant human erythropoietin |
| KR100221066B1 (ko) * | 1989-10-13 | 1999-10-01 | 스튜어트 엘.왓트 | 에리트로포이에틴 유사체와 그를 포함하는 제약학적 조성물 |
| US5716644A (en) * | 1992-06-11 | 1998-02-10 | Alkermes, Inc. | Composition for sustained release of non-aggregated erythropoietin |
| US5541458A (en) * | 1994-11-14 | 1996-07-30 | Hewlett-Packard Company | Power supply for timed residual power after turn off |
| DE19535571A1 (de) * | 1995-09-14 | 1997-03-20 | Boehringer Mannheim Gmbh | Pharmazeutische Kombinationspräparate und deren Verwendung zur Behandlung von Hämodialysepatienten |
| PT902085E (pt) * | 1997-09-01 | 2004-02-27 | Aventis Pharma Gmbh | Eritropoietina humana recombinante com perfil de glicosilacao vantajoso |
-
1999
- 1999-10-18 JP JP2000578445A patent/JP4809977B2/ja not_active Expired - Fee Related
- 1999-10-18 AT AT07004087T patent/ATE477270T1/de active
- 1999-10-18 CN CN200910151885A patent/CN101703760A/zh active Pending
- 1999-10-18 CN CN998146978A patent/CN1346369B/zh not_active Expired - Fee Related
- 1999-10-18 DE DE69935345.9T patent/DE69935345T3/de not_active Expired - Lifetime
- 1999-10-18 WO PCT/US1999/024435 patent/WO2000024893A2/en not_active Ceased
- 1999-10-18 PT PT07004087T patent/PT1813624E/pt unknown
- 1999-10-18 HU HU0103920A patent/HU228492B1/hu not_active IP Right Cessation
- 1999-10-18 CA CA2345882A patent/CA2345882C/en not_active Expired - Fee Related
- 1999-10-18 DE DE69942680T patent/DE69942680D1/de not_active Expired - Lifetime
- 1999-10-18 PT PT99955046T patent/PT1123313E/pt unknown
- 1999-10-18 ES ES99955046.0T patent/ES2283139T5/es not_active Expired - Lifetime
- 1999-10-18 AR ARP990105261A patent/AR020848A1/es unknown
- 1999-10-18 DK DK99955046T patent/DK1123313T3/da active
- 1999-10-18 ES ES07004087T patent/ES2347884T3/es not_active Expired - Lifetime
- 1999-10-18 AU AU11241/00A patent/AU774989B2/en not_active Ceased
- 1999-10-18 DK DK07004087.8T patent/DK1813624T3/da active
- 1999-10-18 EP EP99955046.0A patent/EP1123313B2/en not_active Expired - Lifetime
- 1999-10-18 EP EP07004087A patent/EP1813624B1/en not_active Expired - Lifetime
- 1999-10-18 SI SI9930955T patent/SI1123313T1/sl unknown
- 1999-10-18 SI SI9931049T patent/SI1813624T1/sl unknown
- 1999-10-18 AT AT99955046T patent/ATE355303T1/de active
- 1999-10-18 HK HK02101019.3A patent/HK1040944B/en not_active IP Right Cessation
- 1999-10-18 KR KR1020017005047A patent/KR20010075661A/ko not_active Ceased
- 1999-10-22 TW TW088118320A patent/TWI234583B/zh not_active IP Right Cessation
-
2001
- 2001-03-29 IL IL142334A patent/IL142334A/en not_active IP Right Cessation
-
2007
- 2007-03-07 CY CY20071100322T patent/CY1107584T1/el unknown
-
2009
- 2009-01-21 IL IL196645A patent/IL196645A/en not_active IP Right Cessation
-
2010
- 2010-06-07 JP JP2010130046A patent/JP5558213B2/ja not_active Expired - Fee Related
- 2010-09-27 CY CY20101100863T patent/CY1110801T1/el unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995005465A1 (en) * | 1993-08-17 | 1995-02-23 | Amgen Inc. | Erythropoietin analogs |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU774989B2 (en) | Methods and compositions for the prevention and treatment of anemia | |
| US7977311B2 (en) | Methods and compositions for the prevention and treatment of anemia | |
| EP1274728B1 (en) | Methods and compositions for the prevention and treatment of anemia | |
| AU2001255516A1 (en) | Methods and compositions for the prevention and treatment of anemia | |
| AU697453B2 (en) | Erythropoietin analog compositions and methods | |
| HK1127275A (en) | Methods and compositions for the prevention and treatment of anemia | |
| MXPA01003867A (en) | Methods and compositions for the prevention and treatment of anemia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |