KR20000069664A - 안정한 액체 인터페론 제제 - Google Patents
안정한 액체 인터페론 제제 Download PDFInfo
- Publication number
- KR20000069664A KR20000069664A KR1019997005701A KR19997005701A KR20000069664A KR 20000069664 A KR20000069664 A KR 20000069664A KR 1019997005701 A KR1019997005701 A KR 1019997005701A KR 19997005701 A KR19997005701 A KR 19997005701A KR 20000069664 A KR20000069664 A KR 20000069664A
- Authority
- KR
- South Korea
- Prior art keywords
- interferon
- liquid composition
- beta
- liquid
- buffer
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 116
- 102000014150 Interferons Human genes 0.000 title claims abstract description 113
- 108010050904 Interferons Proteins 0.000 title claims abstract description 113
- 229940079322 interferon Drugs 0.000 title claims abstract description 101
- 239000007788 liquid Substances 0.000 title claims abstract description 81
- 238000009472 formulation Methods 0.000 title claims abstract description 42
- 102000003996 Interferon-beta Human genes 0.000 claims abstract description 107
- 108090000467 Interferon-beta Proteins 0.000 claims abstract description 107
- 229960001388 interferon-beta Drugs 0.000 claims abstract description 103
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 49
- 238000000034 method Methods 0.000 claims abstract description 46
- 150000001413 amino acids Chemical class 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 239000003381 stabilizer Substances 0.000 claims abstract description 25
- 239000004471 Glycine Substances 0.000 claims abstract description 24
- 239000004475 Arginine Substances 0.000 claims abstract description 22
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000000463 material Substances 0.000 claims abstract description 21
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims abstract description 13
- 230000002378 acidificating effect Effects 0.000 claims abstract description 9
- 238000007911 parenteral administration Methods 0.000 claims abstract description 6
- 230000000087 stabilizing effect Effects 0.000 claims abstract description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 86
- 239000000872 buffer Substances 0.000 claims description 69
- 235000018102 proteins Nutrition 0.000 claims description 48
- 108090000623 proteins and genes Proteins 0.000 claims description 48
- 102000004169 proteins and genes Human genes 0.000 claims description 48
- 239000011780 sodium chloride Substances 0.000 claims description 41
- 239000012669 liquid formulation Substances 0.000 claims description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 33
- 229940024606 amino acid Drugs 0.000 claims description 30
- 235000001014 amino acid Nutrition 0.000 claims description 30
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 28
- 239000001301 oxygen Substances 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 28
- 238000003860 storage Methods 0.000 claims description 25
- 229960003121 arginine Drugs 0.000 claims description 21
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical group OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 16
- 229960003589 arginine hydrochloride Drugs 0.000 claims description 16
- 229920001296 polysiloxane Polymers 0.000 claims description 16
- 230000000840 anti-viral effect Effects 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 15
- -1 polytetrafluoroethylene Polymers 0.000 claims description 15
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 12
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 11
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 11
- 210000004369 blood Anatomy 0.000 claims description 10
- 239000008280 blood Substances 0.000 claims description 10
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 9
- 229920001993 poloxamer 188 Polymers 0.000 claims description 9
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 8
- 235000011054 acetic acid Nutrition 0.000 claims description 8
- 229960002989 glutamic acid Drugs 0.000 claims description 8
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 8
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 8
- 229960002449 glycine Drugs 0.000 claims description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000008363 phosphate buffer Substances 0.000 claims description 6
- 239000007853 buffer solution Substances 0.000 claims description 5
- 238000004108 freeze drying Methods 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 150000007524 organic acids Chemical group 0.000 claims description 3
- 235000006408 oxalic acid Nutrition 0.000 claims description 3
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 239000000853 adhesive Substances 0.000 claims description 2
- 230000001070 adhesive effect Effects 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 239000000174 gluconic acid Substances 0.000 claims description 2
- 235000012208 gluconic acid Nutrition 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- 235000011087 fumaric acid Nutrition 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 abstract description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 34
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 26
- 239000000523 sample Substances 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 229910019142 PO4 Inorganic materials 0.000 description 18
- 235000021317 phosphate Nutrition 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 17
- 239000010452 phosphate Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 238000001262 western blot Methods 0.000 description 17
- 241000894007 species Species 0.000 description 16
- 238000011282 treatment Methods 0.000 description 14
- 229910052786 argon Inorganic materials 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- 239000007924 injection Substances 0.000 description 13
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 13
- 238000003556 assay Methods 0.000 description 12
- 229940047124 interferons Drugs 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000011521 glass Substances 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 10
- 230000008859 change Effects 0.000 description 10
- 229920006235 chlorinated polyethylene elastomer Polymers 0.000 description 10
- 230000006240 deamidation Effects 0.000 description 10
- 238000001155 isoelectric focusing Methods 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 238000011084 recovery Methods 0.000 description 10
- 235000017281 sodium acetate Nutrition 0.000 description 10
- 238000002835 absorbance Methods 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 8
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 description 8
- 229930195725 Mannitol Natural products 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 8
- 241000700605 Viruses Species 0.000 description 8
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- 239000000594 mannitol Substances 0.000 description 8
- 235000010355 mannitol Nutrition 0.000 description 8
- 201000006417 multiple sclerosis Diseases 0.000 description 8
- 239000001632 sodium acetate Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 108010005716 Interferon beta-1a Proteins 0.000 description 7
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 7
- 229930006000 Sucrose Natural products 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000011261 inert gas Substances 0.000 description 7
- 229960004461 interferon beta-1a Drugs 0.000 description 7
- 229960003646 lysine Drugs 0.000 description 7
- 235000011121 sodium hydroxide Nutrition 0.000 description 7
- 239000005720 sucrose Substances 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 239000004472 Lysine Substances 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- 229920002684 Sepharose Polymers 0.000 description 6
- 238000004007 reversed phase HPLC Methods 0.000 description 6
- 239000001488 sodium phosphate Substances 0.000 description 6
- 229910000162 sodium phosphate Inorganic materials 0.000 description 6
- 235000011008 sodium phosphates Nutrition 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 5
- 150000001720 carbohydrates Chemical class 0.000 description 5
- 235000014633 carbohydrates Nutrition 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000007918 intramuscular administration Methods 0.000 description 5
- 238000012510 peptide mapping method Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 239000008215 water for injection Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000000740 bleeding effect Effects 0.000 description 4
- 239000013522 chelant Substances 0.000 description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 238000002093 isoelectric focusing polyacrylamide gel electrophoresis Methods 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000001502 gel electrophoresis Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 229960001855 mannitol Drugs 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 3
- 238000001542 size-exclusion chromatography Methods 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 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 description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
- 229940074404 sodium succinate Drugs 0.000 description 3
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010022095 Injection Site reaction Diseases 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 238000004061 bleaching Methods 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 229960004926 chlorobutanol Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000009295 crossflow filtration Methods 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
- 235000019800 disodium phosphate Nutrition 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000012931 lyophilized formulation Substances 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 239000005518 polymer electrolyte Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 239000012898 sample dilution Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- MSXHSNHNTORCAW-GGLLEASOSA-M sodium;(2s,3s,4s,5r,6s)-3,4,5,6-tetrahydroxyoxane-2-carboxylate Chemical compound [Na+].O[C@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O MSXHSNHNTORCAW-GGLLEASOSA-M 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000011146 sterile filtration Methods 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 231100000041 toxicology testing Toxicity 0.000 description 2
- 238000002834 transmittance Methods 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- SXFBQAMLJMDXOD-UHFFFAOYSA-N (+)-hydrogentartrate bitartrate salt Chemical compound OC(=O)C(O)C(O)C(O)=O.OC(=O)C(O)C(O)C(O)=O SXFBQAMLJMDXOD-UHFFFAOYSA-N 0.000 description 1
- FKGOBIRUPLSGQT-BUOKYLHBSA-N (e)-but-2-enedioic acid;sodium Chemical compound [Na].OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O FKGOBIRUPLSGQT-BUOKYLHBSA-N 0.000 description 1
- VXXVUHAXJHEYFH-SEPHDYHBSA-N (e)-but-2-enedioic acid;sodium Chemical compound [Na].[Na].OC(=O)\C=C\C(O)=O VXXVUHAXJHEYFH-SEPHDYHBSA-N 0.000 description 1
- GHQFLMULNSGOAR-UHFFFAOYSA-N 2,3-dihydroxybutanedioic acid;sodium Chemical compound [Na].OC(=O)C(O)C(O)C(O)=O GHQFLMULNSGOAR-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- KWTQSFXGGICVPE-WCCKRBBISA-N Arginine hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCCN=C(N)N KWTQSFXGGICVPE-WCCKRBBISA-N 0.000 description 1
- 238000012371 Aseptic Filling Methods 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 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
- 241000699802 Cricetulus griseus Species 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 102000036509 GTP Cyclohydrolase Human genes 0.000 description 1
- 108010023555 GTP Cyclohydrolase Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 108010090665 Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase Proteins 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 108010030544 Peptidyl-Lys metalloendopeptidase Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 238000011190 asparagine deamidation Methods 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037237 body shape Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000000136 cloud-point extraction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000013078 crystal Substances 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
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000011188 deamidation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- IRXRGVFLQOSHOH-UHFFFAOYSA-L dipotassium;oxalate Chemical compound [K+].[K+].[O-]C(=O)C([O-])=O IRXRGVFLQOSHOH-UHFFFAOYSA-L 0.000 description 1
- WGFMTHGYKYEDHF-UHFFFAOYSA-L disodium 2-hydroxy-2-oxoacetate Chemical compound [Na+].[Na+].OC(=O)C(O)=O.[O-]C(=O)C([O-])=O WGFMTHGYKYEDHF-UHFFFAOYSA-L 0.000 description 1
- MYSDBRXBYJKGLB-WOGKQDBSSA-L disodium;(e)-but-2-enedioate;(e)-but-2-enedioic acid Chemical compound [Na+].[Na+].OC(=O)\C=C\C(O)=O.[O-]C(=O)\C=C\C([O-])=O MYSDBRXBYJKGLB-WOGKQDBSSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012537 formulation buffer Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 229940010629 glycine / sodium chloride Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000009215 host defense mechanism Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000013101 initial test Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 239000002973 irritant agent Substances 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 238000002356 laser light scattering Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000008012 organic excipient Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 239000004224 potassium gluconate Substances 0.000 description 1
- 229960003189 potassium gluconate Drugs 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010850 salt effect Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- 239000000176 sodium gluconate Substances 0.000 description 1
- 229940005574 sodium gluconate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- LLVQEXSQFBTIRD-UHFFFAOYSA-M sodium;2,3,4-trihydroxy-4-oxobutanoate;hydrate Chemical compound O.[Na+].OC(=O)C(O)C(O)C([O-])=O LLVQEXSQFBTIRD-UHFFFAOYSA-M 0.000 description 1
- KMPHTYSTEHXSTL-UHFFFAOYSA-M sodium;2-hydroxypropanoate;2-hydroxypropanoic acid Chemical compound [Na+].CC(O)C(O)=O.CC(O)C([O-])=O KMPHTYSTEHXSTL-UHFFFAOYSA-M 0.000 description 1
- VDZDAHYKYRVHJR-UHFFFAOYSA-M sodium;2-hydroxypropanoate;hydrate Chemical compound [OH-].[Na+].CC(O)C(O)=O VDZDAHYKYRVHJR-UHFFFAOYSA-M 0.000 description 1
- OESFSXYRSCBAQJ-UHFFFAOYSA-M sodium;3-carboxy-3,5-dihydroxy-5-oxopentanoate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC([O-])=O OESFSXYRSCBAQJ-UHFFFAOYSA-M 0.000 description 1
- DGPIGKCOQYBCJH-UHFFFAOYSA-M sodium;acetic acid;hydroxide Chemical compound O.[Na+].CC([O-])=O DGPIGKCOQYBCJH-UHFFFAOYSA-M 0.000 description 1
- JISIBLCXFLGVJX-UHFFFAOYSA-M sodium;butanedioic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)CCC(O)=O JISIBLCXFLGVJX-UHFFFAOYSA-M 0.000 description 1
- KIJIBEBWNNLSKE-UHFFFAOYSA-M sodium;oxalic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)C(O)=O KIJIBEBWNNLSKE-UHFFFAOYSA-M 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008646 thermal stress Effects 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
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 1
- 239000011123 type I (borosilicate glass) Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/215—IFN-beta
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Virology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Communicable Diseases (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Gastroenterology & Hepatology (AREA)
- Psychiatry (AREA)
- Zoology (AREA)
- Hospice & Palliative Care (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Dermatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3435396P | 1996-12-24 | 1996-12-24 | |
| US60/034353 | 1996-12-24 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020077010020A Division KR101042660B1 (ko) | 1996-12-24 | 1997-12-23 | 안정한 액체 인터페론 제제 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20000069664A true KR20000069664A (ko) | 2000-11-25 |
Family
ID=21875893
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019997005701A Ceased KR20000069664A (ko) | 1996-12-24 | 1997-12-23 | 안정한 액체 인터페론 제제 |
| KR1020077010020A Expired - Lifetime KR101042660B1 (ko) | 1996-12-24 | 1997-12-23 | 안정한 액체 인터페론 제제 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020077010020A Expired - Lifetime KR101042660B1 (ko) | 1996-12-24 | 1997-12-23 | 안정한 액체 인터페론 제제 |
Country Status (27)
| Country | Link |
|---|---|
| EP (1) | EP0948358B2 (https=) |
| JP (5) | JP4878664B2 (https=) |
| KR (2) | KR20000069664A (https=) |
| CN (2) | CN1733296B (https=) |
| AT (1) | ATE270899T1 (https=) |
| AU (1) | AU738362B2 (https=) |
| BG (2) | BG65171B1 (https=) |
| BR (1) | BR9714434A (https=) |
| CA (1) | CA2275890C (https=) |
| CZ (1) | CZ300636B6 (https=) |
| DE (1) | DE69729880T3 (https=) |
| DK (1) | DK0948358T4 (https=) |
| EA (1) | EA002754B1 (https=) |
| EE (2) | EE04266B1 (https=) |
| ES (1) | ES2224290T5 (https=) |
| HU (1) | HU224222B1 (https=) |
| IL (1) | IL130524A (https=) |
| IS (1) | IS2070B (https=) |
| MX (1) | MX337876B (https=) |
| NO (1) | NO327844B1 (https=) |
| NZ (2) | NZ336548A (https=) |
| PL (1) | PL193447B1 (https=) |
| PT (1) | PT948358E (https=) |
| SI (1) | SI0948358T2 (https=) |
| SK (1) | SK284989B6 (https=) |
| TR (1) | TR199901968T2 (https=) |
| WO (1) | WO1998028007A1 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101238148B1 (ko) * | 2005-01-12 | 2013-03-04 | 바이오겐 아이덱 엠에이 인코포레이티드 | 인터페론 베타의 전달 방법 |
| WO2021010638A1 (ko) * | 2019-07-18 | 2021-01-21 | 에이비온 주식회사 | 2당화된 인터페론-베타 단백질의 정제 방법 |
Families Citing this family (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4878664B2 (ja) * | 1996-12-24 | 2012-02-15 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | 安定な液体インターフェロン処方物 |
| US20030190307A1 (en) | 1996-12-24 | 2003-10-09 | Biogen, Inc. | Stable liquid interferon formulations |
| CA2304808C (en) * | 1997-09-23 | 2011-03-22 | Michael Tschope | Liquid interferon-.beta. formulations |
| KR100767473B1 (ko) * | 1999-05-31 | 2007-10-17 | 미쯔비시 가가꾸 가부시끼가이샤 | 간실질세포 증식인자 동결건조 제제 |
| US6887462B2 (en) | 2001-04-09 | 2005-05-03 | Chiron Corporation | HSA-free formulations of interferon-beta |
| AR034749A1 (es) * | 2001-07-09 | 2004-03-17 | Schering Ag | Formulaciones de interferon beta humano |
| AU2002351756A1 (en) | 2001-12-21 | 2003-07-15 | Novo Nordisk Health Care Ag | Liquid composition of factor vii polypeptides |
| EP1475098B1 (en) * | 2002-01-18 | 2015-08-05 | Asahi Kasei Pharma Corporation | High-concentration preparation of soluble thrombomodulin |
| PT1517698E (pt) | 2002-06-21 | 2014-11-19 | Novo Nordisk Healthcare Ag | Composições sólidas estabilizadas de polipéptidos do fator viia |
| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| US7897734B2 (en) | 2003-03-26 | 2011-03-01 | Novo Nordisk Healthcare Ag | Method for the production of proteins |
| TWI272948B (en) | 2003-05-01 | 2007-02-11 | Ares Trading Sa | HSA-free stabilized interferon liquid formulations |
| AR044302A1 (es) * | 2003-05-13 | 2005-09-07 | Ares Trading Sa | Formulaciones con proteinas liquidas estabilizadas en recipientes farmaceuticos |
| KR20060015574A (ko) | 2003-05-23 | 2006-02-17 | 노보 노르디스크 헬스 케어 악티엔게젤샤프트 | 용액 중 단백질 안정화 |
| CN1318087C (zh) * | 2003-06-06 | 2007-05-30 | 北京三诺佳邑生物技术有限责任公司 | 去白蛋白神经生长因子制剂 |
| ES2574581T3 (es) | 2003-08-14 | 2016-06-20 | Novo Nordisk Health Care Ag | Composición farmacéutica líquida acuosa de polipéptidos de tipo Factor VII |
| BRPI0416042A (pt) * | 2003-11-13 | 2007-01-02 | Alza Corp | composição e aparelho para suprimento transdérmico |
| EP1532983A1 (en) * | 2003-11-18 | 2005-05-25 | ZLB Bioplasma AG | Immunoglobulin preparations having increased stability |
| RU2373953C2 (ru) | 2003-12-19 | 2009-11-27 | Ново Нордиск Хелс Кеа Аг | Стабилизированная композиция, содержащая полипептид фактора vii |
| EP1750750B1 (en) * | 2004-06-01 | 2012-02-01 | Ares Trading S.A. | Method of stabilizing proteins |
| CN101022822B (zh) * | 2004-08-24 | 2012-06-27 | 第一三共株式会社 | 生理学活性肽的液体制剂 |
| DE102004054054A1 (de) | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
| PT1809662E (pt) * | 2004-11-10 | 2009-02-26 | Novartis Vaccines & Diagnostic | Interferão beta desamidado |
| CA2593112A1 (en) * | 2005-01-21 | 2006-07-27 | Alza Corporation | Therapeutic peptide formulations for coating microneedles with improved stability containing at least one counterion |
| EP1899462B1 (en) | 2005-07-02 | 2011-03-09 | Arecor Limited | Stable aqueous systems comprising proteins |
| DE102005035891A1 (de) | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
| PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
| KR101452915B1 (ko) | 2006-05-04 | 2014-10-21 | 베링거 인겔하임 인터내셔날 게엠베하 | 다형태 |
| PT2868315T (pt) * | 2007-12-04 | 2017-09-04 | Remedy Pharmaceuticals Inc | Formulações melhoradas e métodos para liofilização e liofilizados assim produzidos |
| BRPI0821029A2 (pt) | 2007-12-20 | 2015-06-16 | Merck Serono Sa | Fomulações de peg-interferon-beta |
| PE20091730A1 (es) | 2008-04-03 | 2009-12-10 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
| WO2009133408A2 (en) | 2008-05-01 | 2009-11-05 | Arecor Limited | Protein formulation |
| EP2328607A1 (en) | 2008-07-16 | 2011-06-08 | Arecor Limited | Stable formulation of a therapeutic protein |
| KR20190016601A (ko) | 2008-08-06 | 2019-02-18 | 베링거 인겔하임 인터내셔날 게엠베하 | 메트포르민 요법이 부적합한 환자에서의 당뇨병 치료 |
| UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
| CA2736421A1 (en) | 2008-09-10 | 2010-03-18 | Boehringer Ingelheim International Gmbh | Combination therapy for the treatment of diabetes and related conditions |
| DE102008051574A1 (de) | 2008-10-14 | 2010-04-15 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Verfahren zur Herstellung von Interferon-beta und deren Varianten |
| US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
| JP2012512848A (ja) | 2008-12-23 | 2012-06-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 有機化合物の塩の形態 |
| TW201036975A (en) | 2009-01-07 | 2010-10-16 | Boehringer Ingelheim Int | Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy |
| DE102009032179A1 (de) | 2009-07-07 | 2011-01-13 | Biogenerix Ag | Verfahren zur Reinigung von Interferon beta |
| KR20240090632A (ko) | 2009-11-27 | 2024-06-21 | 베링거 인겔하임 인터내셔날 게엠베하 | 리나글립틴과 같은 ｄｐｐ－ｉｖ 억제제를 사용한 유전자형 검사된 당뇨병 환자의 치료 |
| DK2531218T3 (en) | 2010-02-04 | 2019-04-01 | Csl Behring Ag | immunoglobulin |
| EP2361636A1 (en) | 2010-02-26 | 2011-08-31 | CSL Behring AG | Immunoglobulin preparation and storage system for an immunoglobulin preparation |
| DE102010011430A1 (de) * | 2010-03-15 | 2011-09-15 | Kurt Koch | Verfahren für den Bau des Nullenergiehauses in Schalenbauweise durch Ausschäumen aller Wände, Decken und Bedachung |
| CA3070513C (en) | 2010-05-05 | 2023-01-03 | Boehringer Ingelheim International Gmbh | A dpp-4 inhibitor for use in treatment of skin-alterations or necrosis |
| KR20130093012A (ko) | 2010-06-24 | 2013-08-21 | 베링거 인겔하임 인터내셔날 게엠베하 | 당뇨병 요법 |
| AR083878A1 (es) | 2010-11-15 | 2013-03-27 | Boehringer Ingelheim Int | Terapia antidiabetica vasoprotectora y cardioprotectora, linagliptina, metodo de tratamiento |
| EP2649993B1 (en) | 2010-12-09 | 2017-04-05 | Maruishi Pharmaceutical Co., Ltd. | Stabilizer of acetaminophen |
| AU2012229104B2 (en) | 2011-03-15 | 2017-03-16 | Biogen Ma Inc. | Method for reducing flu-like symptoms associated with intramuscular administration of interferon using a fast titration escalating dosing regimen |
| DK2731947T3 (en) | 2011-07-15 | 2019-04-23 | Boehringer Ingelheim Int | SUBSTITUTED DIMERIC QUINAZOLINE DERIVATIVE, PREPARATION AND USE thereof IN PHARMACEUTICAL COMPOSITIONS FOR TREATMENT OF TYPE I AND TYPE II DIABETES |
| US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
| JP2015515480A (ja) * | 2012-04-19 | 2015-05-28 | シー・アール・バード・インコーポレーテッドＣ Ｒ Ｂａｒｄ Ｉｎｃｏｒｐｏｒａｔｅｄ | エチレンオキシド滅菌下のｐＨ安定性が改善された注入液 |
| WO2013171167A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes related disorders and/or nephrotic syndrome |
| WO2013171166A1 (en) | 2012-05-14 | 2013-11-21 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp-4 inhibitor for use in the treatment of sirs and/or sepsis |
| WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
| ITMI20120913A1 (it) * | 2012-05-28 | 2013-11-29 | Nicoletta Maxia | Uso della n-acetil-5-metossitriptamina o suoi analoghi per favorire il meccanismo di impianto dell' embrione, e relative composizioni e mezzi di coltura |
| CN103143000B (zh) * | 2013-03-07 | 2014-11-05 | 安徽安科生物工程（集团）股份有限公司 | 一种重组人干扰素α2b制剂 |
| EP3110449B1 (en) | 2014-02-28 | 2023-06-28 | Boehringer Ingelheim International GmbH | Medical use of a dpp-4 inhibitor |
| JP2014208669A (ja) * | 2014-06-17 | 2014-11-06 | 株式会社スリー・ディー・マトリックス | タンパク質の凝集抑制剤 |
| ES2825704T3 (es) | 2014-12-03 | 2021-05-17 | Csl Behring Ag | Producto farmacéutico con mayor estabilidad que comprende inmunoglobulinas |
| EP4233840A3 (en) | 2016-06-10 | 2023-10-18 | Boehringer Ingelheim International GmbH | Combinations of linagliptin and metformin |
| KR101943160B1 (ko) * | 2016-10-06 | 2019-01-30 | 에이비온 주식회사 | 인터페론 베타 변이체의 안정화 제제 |
| IL272773B2 (en) | 2017-08-22 | 2024-06-01 | Biogen Ma Inc | Pharmaceutical preparations containing anti-amyloid cell antibodies |
| CN110714051B (zh) * | 2019-11-20 | 2023-04-07 | 迈克生物股份有限公司 | 蛋白c活性测定试剂盒 |
| MX2022013662A (es) * | 2020-04-29 | 2023-02-01 | Abion Inc | Variante del interferon-beta humano con doble mutacion y metodo para mejorar la estabilidad de la variante del interferon-beta humano. |
| WO2022207655A1 (en) * | 2021-03-30 | 2022-10-06 | Schott Schweiz Ag | System for low-temperature storage of a pharmaceutical composition, liquid composition, method and uses |
| CN114177273B (zh) * | 2021-11-29 | 2024-05-28 | 苏州人本药业有限公司 | 一种含有神经毒素的液体制剂及其制备方法 |
| AU2022426492A1 (en) * | 2021-12-27 | 2024-07-18 | Enalare Therapeutics Inc. | Respiratory stimulant parenteral formulations |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57175125A (en) * | 1981-04-20 | 1982-10-28 | Wakunaga Yakuhin Kk | Preparation of beta-interferon |
| DE3262575D1 (en) * | 1981-12-23 | 1985-04-18 | Schering Corp | Stabilised interferon formulations and their preparation |
| JPS60243028A (ja) * | 1984-04-28 | 1985-12-03 | Kyowa Hakko Kogyo Co Ltd | インタ−フエロンの可溶化方法 |
| JPS63196268A (ja) * | 1987-02-10 | 1988-08-15 | Kanegafuchi Chem Ind Co Ltd | 無血清培地で継代増殖可能な形質転換細胞、その育種方法およびその細胞による蛋白質の生産方法 |
| EP0284249A1 (en) * | 1987-03-13 | 1988-09-28 | Interferon Sciences, Inc. | Lyophilized lymphokine composition |
| DE3729863A1 (de) * | 1987-09-05 | 1989-03-16 | Boehringer Mannheim Gmbh | Stabilisierte erythropoietin-lyophilisate |
| US4895716A (en) * | 1987-06-09 | 1990-01-23 | Biogen, Inc. | Stabilized formulations of gamma interferons |
| JPH02124832A (ja) * | 1988-07-08 | 1990-05-14 | Toray Ind Inc | インターヘェロンβ組成物 |
| DE3939346A1 (de) * | 1989-11-29 | 1991-06-06 | Behringwerke Ag | Arzneimitel zur subkutanen oder intramuskulaeren applikation enthaltend polypeptide |
| IL109350A (en) * | 1993-05-12 | 2001-01-28 | Genentech Inc | Stable liquid compositions of gamma interferon |
| TW249202B (https=) * | 1993-08-13 | 1995-06-11 | Ciba Gerigy Corp | |
| US5545723A (en) * | 1994-03-15 | 1996-08-13 | Biogen Inc. | Muteins of IFN-β |
| EP0752880A4 (en) * | 1994-04-08 | 2000-08-09 | Brigham & Womens Hospital | TREATMENT OF AUTOIMMUNE DISEASES BY ORAL TOLERATION AND / OR INTERFERON OF TYPE I |
| IT1272252B (it) * | 1994-05-16 | 1997-06-16 | Applied Research Systems | Formulazioni liquide di interferone beta |
| TW426523B (en) * | 1995-04-06 | 2001-03-21 | Hoffmann La Roche | Interferon solution |
| JP4878664B2 (ja) * | 1996-12-24 | 2012-02-15 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | 安定な液体インターフェロン処方物 |
-
1997
- 1997-12-23 JP JP52905698A patent/JP4878664B2/ja not_active Expired - Fee Related
- 1997-12-23 EE EEP200300127A patent/EE04266B1/xx unknown
- 1997-12-23 EP EP97952621A patent/EP0948358B2/en not_active Expired - Lifetime
- 1997-12-23 DE DE69729880T patent/DE69729880T3/de not_active Expired - Lifetime
- 1997-12-23 ES ES97952621T patent/ES2224290T5/es not_active Expired - Lifetime
- 1997-12-23 CN CN2005100915177A patent/CN1733296B/zh not_active Expired - Lifetime
- 1997-12-23 PL PL97334365A patent/PL193447B1/pl unknown
- 1997-12-23 AT AT97952621T patent/ATE270899T1/de active
- 1997-12-23 SK SK858-99A patent/SK284989B6/sk not_active IP Right Cessation
- 1997-12-23 KR KR1019997005701A patent/KR20000069664A/ko not_active Ceased
- 1997-12-23 CA CA2275890A patent/CA2275890C/en not_active Expired - Lifetime
- 1997-12-23 DK DK97952621.7T patent/DK0948358T4/da active
- 1997-12-23 CN CNB971814996A patent/CN1222315C/zh not_active Expired - Lifetime
- 1997-12-23 HU HU0000829A patent/HU224222B1/hu active IP Right Grant
- 1997-12-23 IL IL13052497A patent/IL130524A/xx not_active IP Right Cessation
- 1997-12-23 AU AU56191/98A patent/AU738362B2/en not_active Expired
- 1997-12-23 TR TR1999/01968T patent/TR199901968T2/xx unknown
- 1997-12-23 EE EEP199900313A patent/EE04223B1/xx unknown
- 1997-12-23 SI SI9730670T patent/SI0948358T2/sl unknown
- 1997-12-23 BR BR9714434-7A patent/BR9714434A/pt active Search and Examination
- 1997-12-23 WO PCT/US1997/023817 patent/WO1998028007A1/en not_active Ceased
- 1997-12-23 PT PT97952621T patent/PT948358E/pt unknown
- 1997-12-23 EA EA199900597A patent/EA002754B1/ru not_active IP Right Cessation
- 1997-12-23 KR KR1020077010020A patent/KR101042660B1/ko not_active Expired - Lifetime
- 1997-12-23 NZ NZ336548A patent/NZ336548A/en not_active IP Right Cessation
- 1997-12-23 CZ CZ0228299A patent/CZ300636B6/cs not_active IP Right Cessation
-
1999
- 1999-06-21 IS IS5087A patent/IS2070B/xx unknown
- 1999-06-23 NO NO993121A patent/NO327844B1/no not_active IP Right Cessation
- 1999-06-23 MX MX2012000515A patent/MX337876B/es unknown
- 1999-07-19 BG BG103594A patent/BG65171B1/bg unknown
- 1999-07-19 BG BG109523A patent/BG65418B1/bg unknown
-
2001
- 2001-07-05 NZ NZ512792A patent/NZ512792A/xx not_active IP Right Cessation
-
2007
- 2007-05-18 JP JP2007133540A patent/JP2007204501A/ja not_active Withdrawn
-
2011
- 2011-01-07 JP JP2011002557A patent/JP5851695B2/ja not_active Expired - Lifetime
- 2011-10-04 JP JP2011220534A patent/JP2012006979A/ja not_active Withdrawn
-
2014
- 2014-02-25 JP JP2014033581A patent/JP2014098029A/ja not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101238148B1 (ko) * | 2005-01-12 | 2013-03-04 | 바이오겐 아이덱 엠에이 인코포레이티드 | 인터페론 베타의 전달 방법 |
| WO2021010638A1 (ko) * | 2019-07-18 | 2021-01-21 | 에이비온 주식회사 | 2당화된 인터페론-베타 단백질의 정제 방법 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101042660B1 (ko) | 안정한 액체 인터페론 제제 | |
| US9522174B2 (en) | Stable liquid interferon beta formulations | |
| US7731948B2 (en) | Stabilized interferon liquid formulations | |
| US20170360891A1 (en) | Stable, Benzyl Alcohol-free Aqueous Solution Formulations Containing Alpha-type Interferon | |
| HK1025040B (en) | Stable liquid interferon formulations | |
| MXPA99005977A (en) | Stable liquid interferon formulations | |
| HK1092048B (en) | Stable liquid interferon formulations |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 19990622 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20021223 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20041130 Patent event code: PE09021S01D |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20050707 Patent event code: PE09021S01D |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20051229 Patent event code: PE09021S01D |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20060718 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20070130 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20060718 Comment text: Notification of reason for refusal Patent event code: PE06011S01I Patent event date: 20051229 Comment text: Notification of reason for refusal Patent event code: PE06011S01I Patent event date: 20050707 Comment text: Notification of reason for refusal Patent event code: PE06011S01I Patent event date: 20041130 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |
|
| A107 | Divisional application of patent | ||
| J201 | Request for trial against refusal decision | ||
| PA0104 | Divisional application for international application |
Comment text: Divisional Application for International Patent Patent event code: PA01041R01D Patent event date: 20070502 |
|
| PJ0201 | Trial against decision of rejection |
Patent event date: 20070502 Comment text: Request for Trial against Decision on Refusal Patent event code: PJ02012R01D Patent event date: 20070130 Comment text: Decision to Refuse Application Patent event code: PJ02011S01I Appeal kind category: Appeal against decision to decline refusal Decision date: 20071123 Appeal identifier: 2007101004676 Request date: 20070502 |
|
| J301 | Trial decision |
Free format text: TRIAL DECISION FOR APPEAL AGAINST DECISION TO DECLINE REFUSAL REQUESTED 20070502 Effective date: 20071123 |
|
| PJ1301 | Trial decision |
Patent event code: PJ13011S01D Patent event date: 20071123 Comment text: Trial Decision on Objection to Decision on Refusal Appeal kind category: Appeal against decision to decline refusal Request date: 20070502 Decision date: 20071123 Appeal identifier: 2007101004676 |
|
| PC1202 | Submission of document of withdrawal before decision of registration |
Comment text: [Withdrawal of Procedure relating to Patent, etc.] Withdrawal (Abandonment) Patent event code: PC12021R01D Patent event date: 20071228 |
|
| WITB | Written withdrawal of application |