JP2019533679A - 医薬製剤及びその製造方法 - Google Patents
医薬製剤及びその製造方法 Download PDFInfo
- Publication number
- JP2019533679A JP2019533679A JP2019520794A JP2019520794A JP2019533679A JP 2019533679 A JP2019533679 A JP 2019533679A JP 2019520794 A JP2019520794 A JP 2019520794A JP 2019520794 A JP2019520794 A JP 2019520794A JP 2019533679 A JP2019533679 A JP 2019533679A
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- etanercept
- nacl
- formulation
- arginine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 10
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 239000000203 mixture Substances 0.000 claims abstract description 180
- 238000009472 formulation Methods 0.000 claims abstract description 169
- 108010008165 Etanercept Proteins 0.000 claims abstract description 138
- 229960000403 etanercept Drugs 0.000 claims abstract description 129
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 127
- 238000000034 method Methods 0.000 claims abstract description 60
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 148
- 239000011780 sodium chloride Substances 0.000 claims description 74
- 239000000872 buffer Substances 0.000 claims description 67
- 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 claims description 58
- 229930006000 Sucrose Natural products 0.000 claims description 58
- 239000005720 sucrose Substances 0.000 claims description 58
- 239000000243 solution Substances 0.000 claims description 53
- 238000003860 storage Methods 0.000 claims description 42
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 32
- 239000004475 Arginine Substances 0.000 claims description 30
- 235000009697 arginine Nutrition 0.000 claims description 30
- 229960003121 arginine Drugs 0.000 claims description 30
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 27
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 27
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 27
- 229940068977 polysorbate 20 Drugs 0.000 claims description 26
- 229930064664 L-arginine Natural products 0.000 claims description 23
- 235000014852 L-arginine Nutrition 0.000 claims description 23
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 22
- 238000004191 hydrophobic interaction chromatography Methods 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 8
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 6
- 238000001542 size-exclusion chromatography Methods 0.000 claims description 6
- KWTQSFXGGICVPE-UHFFFAOYSA-N 2-amino-5-(diaminomethylideneamino)pentanoic acid;hydron;chloride Chemical group Cl.OC(=O)C(N)CCCN=C(N)N KWTQSFXGGICVPE-UHFFFAOYSA-N 0.000 claims description 5
- 238000011026 diafiltration Methods 0.000 claims description 5
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 4
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 4
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 4
- 229940127557 pharmaceutical product Drugs 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 239000013011 aqueous formulation Substances 0.000 claims description 3
- 229940126534 drug product Drugs 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 229940090047 auto-injector Drugs 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 claims 1
- 239000007853 buffer solution Substances 0.000 abstract description 3
- 235000018102 proteins Nutrition 0.000 description 26
- 102000004169 proteins and genes Human genes 0.000 description 26
- 108090000623 proteins and genes Proteins 0.000 description 26
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 24
- 238000002347 injection Methods 0.000 description 20
- 239000007924 injection Substances 0.000 description 20
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 18
- 239000000463 material Substances 0.000 description 18
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 239000008363 phosphate buffer Substances 0.000 description 17
- 239000008186 active pharmaceutical agent Substances 0.000 description 16
- 239000011521 glass Substances 0.000 description 15
- 239000007858 starting material Substances 0.000 description 13
- 238000000502 dialysis Methods 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 230000007774 longterm Effects 0.000 description 11
- 239000004094 surface-active agent Substances 0.000 description 11
- 229910019142 PO4 Inorganic materials 0.000 description 10
- 239000002245 particle Substances 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 10
- 239000010452 phosphate Substances 0.000 description 10
- 230000002776 aggregation Effects 0.000 description 9
- 238000004220 aggregation Methods 0.000 description 9
- 229940073621 enbrel Drugs 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 229910001220 stainless steel Inorganic materials 0.000 description 9
- 239000010935 stainless steel Substances 0.000 description 9
- 235000019445 benzyl alcohol Nutrition 0.000 description 8
- 229920000136 polysorbate Polymers 0.000 description 8
- 239000012906 subvisible particle Substances 0.000 description 8
- 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 7
- 229930195725 Mannitol Natural products 0.000 description 7
- 239000006172 buffering agent Substances 0.000 description 7
- 230000003139 buffering effect Effects 0.000 description 7
- 239000000594 mannitol Substances 0.000 description 7
- 235000010355 mannitol Nutrition 0.000 description 7
- 229920003023 plastic Polymers 0.000 description 7
- 229950008882 polysorbate Drugs 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 101001018259 Homo sapiens Microtubule-associated serine/threonine-protein kinase 1 Proteins 0.000 description 6
- 101000693728 Homo sapiens S-acyl fatty acid synthase thioesterase, medium chain Proteins 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 102100025541 S-acyl fatty acid synthase thioesterase, medium chain Human genes 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 229940088679 drug related substance Drugs 0.000 description 6
- 239000012669 liquid formulation Substances 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 229940068196 placebo Drugs 0.000 description 6
- 239000000902 placebo Substances 0.000 description 6
- 229920002545 silicone oil Polymers 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000013628 high molecular weight specie Substances 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 239000011550 stock solution Substances 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 5
- MYPRUMQOPMOOSZ-UHFFFAOYSA-N 1-(diaminomethylidene)-3-(3-sulfamoylphenyl)urea;hydrochloride Chemical compound Cl.NC(N)=NC(=O)NC1=CC=CC(S(N)(=O)=O)=C1 MYPRUMQOPMOOSZ-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000011067 equilibration Methods 0.000 description 4
- 239000012537 formulation buffer Substances 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 235000014304 histidine Nutrition 0.000 description 4
- 230000003204 osmotic effect Effects 0.000 description 4
- 239000013618 particulate matter Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000001488 sodium phosphate Substances 0.000 description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical group [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 4
- KWTQSFXGGICVPE-WCCKRBBISA-N Arginine hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCCN=C(N)N KWTQSFXGGICVPE-WCCKRBBISA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- -1 amino acid Chemical class 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 229920001993 poloxamer 188 Polymers 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 229940068968 polysorbate 80 Drugs 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000010977 unit operation Methods 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 241000219492 Quercus Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 238000011021 bench scale process Methods 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000012466 permeate Substances 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 229940044519 poloxamer 188 Drugs 0.000 description 2
- 229920001992 poloxamer 407 Polymers 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 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 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 238000013060 ultrafiltration and diafiltration Methods 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 108010010803 Gelatin 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
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 206010022095 Injection Site reaction Diseases 0.000 description 1
- 206010022086 Injection site pain Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 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
- BVHLGVCQOALMSV-JEDNCBNOSA-N L-lysine hydrochloride Chemical compound Cl.NCCCC[C@H](N)C(O)=O BVHLGVCQOALMSV-JEDNCBNOSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920000805 Polyaspartic acid Polymers 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 210000003815 abdominal wall Anatomy 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- XTIMETPJOMYPHC-UHFFFAOYSA-M beryllium monohydroxide Chemical compound O[Be] XTIMETPJOMYPHC-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001351 cycling effect Effects 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
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000000385 dialysis solution Substances 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 239000013022 formulation composition Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001641 gel filtration chromatography Methods 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
- 229960002449 glycine Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000013627 low molecular weight specie Substances 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 229960005337 lysine hydrochloride Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 238000012434 mixed-mode chromatography Methods 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000001139 pH measurement Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229940044476 poloxamer 407 Drugs 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
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
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/1793—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39591—Stabilisation, fragmentation
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
- C07K14/7151—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for tumor necrosis factor [TNF], for lymphotoxin [LT]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/32—Fusion polypeptide fusions with soluble part of a cell surface receptor, "decoy receptors"
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本願は2016年10月21日に出願された米国仮特許出願第62/411,458号の利益を主張するものであり、その全体が参照により本明細書に組み込まれる。
下記の実施例は、製剤がpHを所望の範囲に維持することができるかどうかを、当業者がどのようにして決定することができるかを説明する。基本的には、医薬組成物は試験容器(ガラスバイアル、ガラスシリンジ、プラスチックシリンジ、ステンレス鋼製容器、又は医薬組成物に適した任意の様式の滅菌デバイスであり得る)中で製剤化して保存し、pHを時間0で評価し、その後、必要に応じて、示された時間で評価する。通常、試験条件は医薬組成物の貯蔵の必要性を予測し、それらの条件に重点を置くであろう。例えば、本発明の製剤は、制御された室温(CRT)下で、少なくとも2週間、少なくとも4週間、少なくとも8週間、少なくとも12週間、及び少なくとも24週間、所望のpHを維持することができる。CRTはUSPによって定義され、20℃〜25℃(68°F〜77°F)の通常の慣用の作業環境を包含し;25℃以下であると計算される平均動力学的温度をもたらし;かつ、薬局、病院、及び倉庫で経験される15℃〜30℃(59°F〜86°F)の間の偏位を許可する、サーモスタットで維持された温度を有する。
本発明はまた、緩衝液を除去し、かつpHを標的範囲に維持するための、エタネルセプト医薬組成物を製剤化する方法であって、標的範囲の緩衝製剤形態にエタネルセプトを製剤化する工程と、緩衝製剤を、その標的範囲内の、又は標的範囲のすぐ下の非緩衝製剤に交換する工程と、得られたエタネルセプトの医薬製剤を回収する工程とを含む方法を提供する。下に例示する好ましい実施形態では、本方法は、緩衝液を除去し、かつpHを6.0〜6.6に維持するための、エタネルセプト医薬組成物を製剤化する方法であって、エタネルセプト製剤をpH6.0〜6.6で緩衝製剤形態に製剤化する工程と、緩衝製剤をpH5.6〜6.5の非緩衝製剤に交換する工程と、得られた医薬製剤を回収する工程とを含む方法を提供する。pHを6.1〜6.5に維持するエタネルセプトの非緩衝組成物を得るには、出発の緩衝エタネルセプト製剤と非緩衝製剤の両方のpHの調整を確実に行うことが重要である。例えば、出発の緩衝エタネルセプト製剤がpH7.2である場合、それは、HClなどの強酸で6.1〜6.5の範囲内に調整されるであろう。同様に、交換に使用される非緩衝製剤は、pH5.6〜6.5に滴定されるべきである。交換用に使用される非緩衝製剤は、緩衝剤を有しないので、滴定の間、注意を払うべきである。
この実施例は50mg/mLのエタネルセプトに対するpH及び緩衝液の影響を実証し、リン酸緩衝液を添加しない高濃度(100mg/mL)溶液の安定性を評価する。以下の製剤を試験した。
この試験は、単施設、無作為化、一重盲検、クロスオーバーデザインであり、これには48人の健康な男性及び女性が6種の溶液の単回SC注射を受けた。
いくつかの新しい製剤候補中のエタネルセプトの安定性を観察するために、50mg/mLで長期研究を行った。4℃、25℃及び40℃で貯蔵した後、SE−HPLC、HIC HPLC、dSEC HPLC、及び粒子状物質(HIAC)を使用して、1mLのステークガラス針シリンジ(staked glass needle syringe)中の1mL充填物について安定性を評価した。重量オスモル濃度及びタンパク質濃度を時刻ゼロでのみ試験し、pHは、pHドリフトがないことを確認するために、時刻ゼロ及び12週間の貯蔵後に試験した。研究の結果、試験した製剤は、40℃の加速温度で12週後に、また2〜8℃の推奨貯蔵及び25℃の加速温度で24週後に、現在の市販製剤との類似性を維持していることが示された。
3種の新しい製剤候補中のエタネルセプトの安定性を観察するために、50mg/mLで凍結/融解のサイクル研究を行った。現在市販の製剤PASS(25mMのリン酸緩衝液、25mMのL−アルギニン、100mMのNaCl、1%のスクロース)と比較した製剤は、SAST_100NaCl(25mMのL−アルギニン、100mMのNaCl、1%のスクロース、0.010%のポリソルベート20)、SAS_120NaCl(25mMのL−アルギニン、120mMのNaCl、1%のスクロース)、及びSAST_120NaCl(25 mMのL−アルギニン、120 mMのNaCl、1%のスクロース 0.010%のポリソルベート20)であった。55mLステンレス鋼製凍結容器中で、−30℃〜4℃のサイクルを行った場合の凝集に対する安定性を、SE−HPLCを用いて凍結/融解サイクル5回まで評価した。
これらの実施例の目的は、TMS(トリス、マンニトール、スクロース)中のエタネルセプトの異なる調製物を試験製剤(L−アルギニン、スクロース、NaCl)中に透析し、最終pHを標的pHと比較することであった。
結果の要約を下記の表17に示す。
はじめに:この研究後に選択された製剤溶液は、SAS(120mMの塩化ナトリウム、25mMのL−アルギニン、1%のスクロース、pH6.3)と名付けられ、リン酸緩衝液は添加されていない。前の実施例で、pH7.56の試料中のエタネルセプトから出発する場合、透析するか、又はUF/DFを使用するかでは、標的pH6.3の達成は困難であると示されたことから、SAS製剤への交換の異なる方法が必要であった。異なる最終UF/DF出発材料を利用した以下の2つの方法を評価した:1)出発材料としてカラム3(AEX)中間体プール、及び2)出発材料としてPASS製剤緩衝液(PASS DS中間体プール)中のEnbrel原薬。それぞれの方法は以下に記載され、50g/LのSAS製剤化エタネルセプトを製造するための、最終UF/DF単位操作工程の開発を、SAS製剤溶液の調製、最終UF/DFの負荷調整及び処理を含めて要約する。
調整したAEX中間体プールは、制御された室温(CRT)で52.6時間まで保管することができる。保管中のプールのpHを図8に示す。
AEX中間体プールを出発材料として使用して生成された最終UF/DF SASプールは、CRTで96.3時間まで保管することができる。保管中のpH及び導電率を図9A及びBに示す。96.3時間の保管中、pH及び導電率は許容範囲内に留まる。
この中間体プールは既に目標pH(6.3)にあるので、SAS溶液によるUF/DF処理の前に、このPASSプールを調整する必要はない。プールの状態はEnbrel PASS DSから変えられなかったので、この中間体プールではプール保管研究を実施しなかった。プールは25℃で96時間まで保管することができる。
PASS DS中間体プールを出発材料として生成された、最終UF/DF SASプールは、CRTで96.3時間まで保管することができる。保管中のpH及び導電率を図9A及びBに示す。96.3時間の保管中、pH及び導電率は許容範囲内に留まる。
SAS製剤溶液は、CRTで28日間まで保管することができる。pH及び導電率を図10A及びBに示す。非常に小さなヘッドスペースを有する小規模ステンレス鋼製安定性チャンバ内で42日間保管した場合、SAS製剤溶液はpHを5.6〜6.5内に維持することが示された。35日目及び42日目の時点で沈殿が観察された。21日目の時点の測定値5.09は、その後の時点では提案された許容基準内にあるという事実によって、外れ値のようである。
この実施例の目的は、40℃、75mg/mLでエタネルセプト安定性に対するアルギニン、スクロース又は塩化ナトリウムの増加した濃度が凝集に与える影響を決定することである。リン酸緩衝液を添加せずに、等張製剤を維持するために、これらの賦形剤の濃度をそれぞれ増加させた。さらに、ヒスチジンを、リン酸塩置換用緩衝液として評価した。試験した製剤を表22に要約する。
SAS製剤中、ポリソルベート20が、0、0.005、0.01及び0.015%の場合に、50mg/mLのエタネルセプトの安定性を観察するために長期研究を行った。さらに、100mg/mLの、エタネルセプトのSAST高濃度製剤を試験した。4℃、25℃及び40℃で貯蔵後、SE−HPLC、dSEC HPLC、及びの粒子状物質(HIAC)を使用して、1mLのステークガラス針シリンジ中の1mL充填物について安定性を評価した。時刻ゼロでのみ、重量オスモル濃度、pH、及びタンパク質濃度を試験した。試験の結果は、試験した50mg/mL製剤が、推奨される2〜8℃、ならびに25℃及び40℃の加速温度で24週間後に、現在の市販製剤との類似性を維持したことが示された。100mg/mLのSAST製剤は、pH及びサブビジブル粒子に関して50mg/mL製剤と同等の挙動を示した;SECによる凝集レベルの差異はタンパク質濃度に起因すると考えられた。
COPプラスチック製の、シリコーン油を含まないプレフィルドシリンジシステム中における、50mg/mLエタネルセプトのPASS及びSAS製剤中のエタネルセプト安定性を、ガラス製のシリコーン処理したプレフィルドシリンジと比較して観察するために、長期研究を行った。4℃、25℃及び40℃で貯蔵後、SE−HPLC、pH、及びの粒子状物質(HIAC)を使用して、各種シリンジシステム中の1mL充填物について安定性を評価した。時刻ゼロでのみ、タンパク質濃度を試験した。
Claims (42)
- 75mM〜150mMのNaCl、5mM〜100mMのアルギニン、0.5%〜2%(w/v)スクロース、及び40mg/mL〜100mg/mLのエタネルセプトを含む医薬組成物であって、前記医薬組成物は、2.0mM未満の全追加緩衝剤を含み、かつ前記組成物のpHは、6.1〜6.5である、医薬組成物。
- 1.5mM未満の全追加緩衝剤を含む、請求項1に記載の医薬組成物。
- 1.0mM未満の全追加緩衝剤を含む、請求項2に記載の医薬組成物。
- 0.5mM未満の全追加緩衝剤を含む、請求項2に記載の医薬組成物。
- 0.25mM未満の全追加緩衝剤を含む、請求項2に記載の医薬組成物。
- 0.1mM以下の全追加緩衝剤を含む、請求項2に記載の医薬組成物。
- 前記アルギニンは、L−アルギニンである、請求項1に記載の医薬組成物。
- 前記L−アルギニンは、L−アルギニン塩酸塩である、請求項7に記載の医薬組成物。
- 前記L−アルギニンは、L−アルギニン塩基である、請求項7に記載の医薬組成物。
- 制御された室温(CRT)で2週間保存されたとき、6.1〜6.5のpHを維持する、請求項1に記載の医薬組成物。
- 制御された室温(CRT)で2週間保存されたとき、約6.2〜約6.3のpHを維持する、請求項10に記載の医薬組成物。
- 約25℃で保存されたとき、少なくとも2週間は5.8〜6.7のpHを維持し、サイズ排除クロマトグラフィーを使用して評価すると、前記全エタネルセプトの6%未満が高分子量形態で凝集する、請求項1に記載の医薬組成物。
- 約25℃での前記貯蔵の間、少なくとも2週間は、約6.1〜約6.5のpHを維持する、請求項1に記載の医薬組成物。
- 約25℃での前記貯蔵の間、少なくとも2週間は、約6.2〜約6.4のpHを維持する、請求項1に記載の医薬組成物。
- 約25℃で2週間の貯蔵後、疎水性相互作用クロマトグラフィーを用いて評価すると、前記エタネルセプトの全量の28%未満がミスフォールド形態である、請求項1に記載の医薬組成物。
- 約180〜約420ミリ重量モル浸透圧の重量オスモル濃度を有する、請求項1に記載の医薬組成物。
- 約250〜約350ミリ重量モル浸透圧の重量オスモル濃度を有する、請求項16に記載の医薬組成物。
- 約290〜約310ミリ重量モル浸透圧の重量オスモル濃度を有する、請求項17に記載の医薬組成物。
- 約300〜約310ミリ重量モル浸透圧の重量オスモル濃度を有する、請求項18に記載の医薬組成物。
- 約50mg/mLのエタネルセプト、約120mMのNaCl、約25mMのL−アルギニン塩酸塩、約1%(w/v)のスクロース及び水から実質的になる、請求項1に記載の医薬組成物。
- 約50mg/mLのエタネルセプト、約120mMのNaCl、約25mMのL−アルギニン塩酸塩、約1%(w/v)のスクロース及び水からなる、請求項1に記載の医薬組成物。
- ポリソルベート20をさらに含む、請求項1に記載の医薬組成物。
- 前記ポリソルベート20の濃度(w/v)は、約0.001%〜約0.1%である、請求項22に記載の医薬組成物。
- 前記ポリソルベート20の濃度(w/v)は約0.005%、約0.01%又は約0.015%である、請求項23に記載の医薬組成物。
- 追加の緩衝剤を含まず、6.1〜6.5のpHを有するエタネルセプト医薬組成物の製造方法であって、追加の緩衝剤を含むエタネルセプト製剤を、追加の緩衝剤を含まない溶液に交換する工程を含み、得られる医薬組成物は40mg/mL〜100mg/mLのエタネルセプトを含み、前記追加の緩衝剤を含むエタネルセプト製剤及び前記追加の緩衝剤を含まない溶液は、それぞれ6.1〜6.5のpHを有する、方法。
- 前記交換工程は透析ろ過を使用する、請求項25に記載の方法。
- 前記追加の緩衝剤を含まない溶液は、等張である、請求項25に記載の方法。
- 前記追加の緩衝剤を含まない溶液は、スクロース、アルギニン及びNaClを含有する、請求項25に記載の方法。
- 前記追加の緩衝剤を含まない溶液は、75mM〜150mMのNaCl、5mM〜100mMのアルギニン及び0.5%〜2%(w/v)のスクロースを含有する、請求項28に記載の方法。
- 前記追加の緩衝剤を含まない溶液は、約120mMのNaCl、約25mMのアルギニン、約1%のスクロース、及び水から実質的になる、請求項28に記載の方法。
- 前記医薬組成物をろ過する工程をさらに含む、請求項25に記載の方法。
- 前記医薬組成物を薬剤製品形態へと等分する工程をさらに含む、請求項25に記載の方法。
- 前記追加の緩衝剤を含むエタネルセプト製剤は、75mM〜150mMのNaClを含み、前記追加の緩衝剤を含まない溶液は、75mM〜150mMのNaClを含み、前記医薬組成物は、75mM〜150mMのNaClを含み、前記方法はNaCl除去工程を含まない、請求項25に記載の方法。
- 前記追加の緩衝剤を含むエタネルセプト製剤は、約120mMのNaClを含み、前記追加の緩衝剤を含まない溶液は、約120mMのNaClを含み、前記医薬組成物は約120mMのNaClを含む、請求項33に記載の方法。
- 塩除去工程を含まない、請求項25に記載の方法。
- 75mM〜150mMのNaCl、5mM〜100mMのアルギニン、0.5%〜2%(w/v)スクロース、及び40mg/mL〜100mg/mLのエタネルセプトを含む医薬組成物であって、2.0mM未満の全追加緩衝剤を含み、前記組成物のpHは、6.1〜6.5であり、前記医薬組成物は請求項25に記載の方法を使用して製造される医薬組成物。
- 薬剤製品形態の請求項1に記載の医薬組成物と、保存及び使用のための説明書とを含むキット。
- 請求項1に記載の医薬組成物を含有する単一用量容器。
- バイアル、シリンジ、又は自己注射器である、請求項38に記載の単一用量容器。
- 50.0mg/mLのエタネルセプト、120mMの塩化ナトリウム、25mMのL−アルギニン塩酸塩及び1.0%(w/v)のスクロースからなる水性製剤を含む、請求項38に記載の単一用量容器。
- 単一用量容器の調製方法であって、約単一用量の請求項1に記載の医薬組成物を、無菌条件下で前記単一用量容器に充填する工程を含む方法。
- 関節リウマチ、乾癬性関節炎、強直性脊椎炎、又は乾癬を有する患者の治療方法であって、前記患者に請求項1に記載の医薬製剤を投与することを含む方法。
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2021080160A JP7402195B2 (ja) | 2016-10-21 | 2021-05-11 | 医薬製剤及びその製造方法 |
JP2023180119A JP2024010026A (ja) | 2016-10-21 | 2023-10-19 | 医薬製剤及びその製造方法 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662411458P | 2016-10-21 | 2016-10-21 | |
US62/411,458 | 2016-10-21 | ||
PCT/US2017/057472 WO2018075818A1 (en) | 2016-10-21 | 2017-10-19 | Pharmaceutical formulations and methods of making the same |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021080160A Division JP7402195B2 (ja) | 2016-10-21 | 2021-05-11 | 医薬製剤及びその製造方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2019533679A true JP2019533679A (ja) | 2019-11-21 |
JP2019533679A5 JP2019533679A5 (ja) | 2020-12-10 |
JP6884858B2 JP6884858B2 (ja) | 2021-06-09 |
Family
ID=61971152
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019520794A Active JP6884858B2 (ja) | 2016-10-21 | 2017-10-19 | 医薬製剤及びその製造方法 |
JP2021080160A Active JP7402195B2 (ja) | 2016-10-21 | 2021-05-11 | 医薬製剤及びその製造方法 |
JP2023180119A Pending JP2024010026A (ja) | 2016-10-21 | 2023-10-19 | 医薬製剤及びその製造方法 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021080160A Active JP7402195B2 (ja) | 2016-10-21 | 2021-05-11 | 医薬製剤及びその製造方法 |
JP2023180119A Pending JP2024010026A (ja) | 2016-10-21 | 2023-10-19 | 医薬製剤及びその製造方法 |
Country Status (14)
Country | Link |
---|---|
US (4) | US20180110856A1 (ja) |
EP (1) | EP3528787A4 (ja) |
JP (3) | JP6884858B2 (ja) |
KR (2) | KR102413592B1 (ja) |
CN (2) | CN109982685B (ja) |
AU (1) | AU2017345490B2 (ja) |
BR (1) | BR112019007858A2 (ja) |
CA (1) | CA3040899A1 (ja) |
CL (1) | CL2019001053A1 (ja) |
EA (1) | EA201990998A1 (ja) |
IL (1) | IL266132B (ja) |
MX (1) | MX2019004580A (ja) |
SG (1) | SG11201903521XA (ja) |
WO (1) | WO2018075818A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2021120393A (ja) * | 2016-10-21 | 2021-08-19 | アムジエン・インコーポレーテツド | 医薬製剤及びその製造方法 |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EA012801B1 (ru) | 2005-06-14 | 2009-12-30 | Эмджен Инк. | Самобуферирующиеся композиции белков |
GB201911461D0 (en) * | 2019-08-09 | 2019-09-25 | Arecor Ltd | Novel composition |
TW202200615A (zh) | 2020-03-12 | 2022-01-01 | 美商安進公司 | 用於治療和預防患者的crs之方法 |
US11777543B2 (en) | 2020-05-12 | 2023-10-03 | Nec Corporation | Distortion compensation apparatus and distortion compensation method |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014530864A (ja) * | 2011-10-18 | 2014-11-20 | コヒラス・バイオサイエンシズ・インコーポレイテッド | 糖およびポリオールの組合せによって安定化されたエタネルセプト製剤 |
JP2015525763A (ja) * | 2012-07-09 | 2015-09-07 | コヒラス・バイオサイエンシズ・インコーポレイテッド | 肉眼不可視粒子の著しい低減を示すエタネルセプト製剤 |
WO2016102328A1 (en) * | 2014-12-22 | 2016-06-30 | Ares Trading S.A. | Liquid pharmaceutical composition |
Family Cites Families (153)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2837168A1 (de) | 1978-08-25 | 1980-03-06 | Blutspendedienst Dt Rote Kreuz | Verfahren zur herstellung einer fuer die intravenoese anwendung geeigneten immunglobulinloesung |
US4362661A (en) | 1979-08-09 | 1982-12-07 | Teijin Limited | Immunoglobulin composition having a high monomer content, and process for production thereof |
US4360457A (en) | 1979-08-30 | 1982-11-23 | Teijin Limited | S-Sulfonated immunoglobulin composition having a high monomer content and a process for production thereof |
US4374763A (en) | 1979-09-17 | 1983-02-22 | Morishita Pharmaceutical Co., Ltd. | Method for producing gamma-globulin for use in intravenous administration and method for producing a pharmaceutical preparation thereof |
US4396608A (en) | 1981-08-24 | 1983-08-02 | Cutter Laboratories | Intravenously injectable immune serum globulin |
US5702699A (en) | 1982-09-23 | 1997-12-30 | Cetus Corporation | Process for the recovery of lipophilic proteins |
US4681713A (en) | 1984-03-15 | 1987-07-21 | Toyo Boseki Kabushiki Kaisha | Method of making a hollow fiber membrane for dialysis |
US4597966A (en) | 1985-01-09 | 1986-07-01 | Ortho Diagnostic Systems, Inc. | Histidine stabilized immunoglobulin and method of preparation |
US6673347B1 (en) | 1986-04-30 | 2004-01-06 | Gryphon Therapeutics | Polypeptide and protein derivatives and process for their preparation |
GB8628104D0 (en) | 1986-11-25 | 1986-12-31 | Connaught Lab | Pasteurization of immunoglobin solutions |
DE3640513A1 (de) | 1986-11-27 | 1988-06-09 | Biotest Pharma Gmbh | Verfahren zur herstellung eines virussicheren, lagerstabilen und intravenoes vertraeglichen immunglobulin-g-praeparates |
JP2547556B2 (ja) | 1987-02-06 | 1996-10-23 | 株式会社 ミドリ十字 | r−グロブリンの液状製剤 |
WO1990005183A1 (en) | 1988-10-31 | 1990-05-17 | Immunex Corporation | Interleukin-4 receptors |
US5395760A (en) | 1989-09-05 | 1995-03-07 | Immunex Corporation | DNA encoding tumor necrosis factor-α and -β receptors |
EP1132471A3 (de) | 1989-09-12 | 2001-11-28 | F. Hoffmann-La Roche Ag | TNF-bindende Proteine |
DE3939346A1 (de) | 1989-11-29 | 1991-06-06 | Behringwerke Ag | Arzneimitel zur subkutanen oder intramuskulaeren applikation enthaltend polypeptide |
US5177194A (en) | 1990-02-01 | 1993-01-05 | Baxter International, Inc. | Process for purifying immune serum globulins |
US5945098A (en) | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
GB9017002D0 (en) | 1990-08-02 | 1990-09-19 | Health Lab Service Board | Improved method for the purification of erwina l-asparaginase |
JP3179538B2 (ja) | 1990-12-11 | 2001-06-25 | ノバルティス アクチエンゲゼルシャフト | 安定なヒトカルシトニンの水性溶液 |
US5110910A (en) | 1991-03-25 | 1992-05-05 | Miles Inc. | Virucidal euglobulin precipitation |
US5256571A (en) | 1991-05-01 | 1993-10-26 | Cytyc Corporation | Cell preservative solution |
WO1993013133A1 (en) | 1991-12-20 | 1993-07-08 | Yamanouchi Pharmaceutical Co., Ltd. | HUMAN TYPE ANTIBODY REACTIVE WITH GPIIb/IIIa |
US6004555A (en) | 1992-03-05 | 1999-12-21 | Board Of Regents, The University Of Texas System | Methods for the specific coagulation of vasculature |
US5298410A (en) | 1993-02-25 | 1994-03-29 | Sterling Winthrop Inc. | Lyophilized formulation of polyethylene oxide modified proteins with increased shelf-life |
US5484892A (en) | 1993-05-21 | 1996-01-16 | Dana-Farber Cancer Institute, Inc. | Monoclonal antibodies that block ligand binding to the CD22 receptor in mature B cells |
DE4344824C1 (de) | 1993-12-28 | 1995-08-31 | Immuno Ag | Hochkonzentriertes Immunglobulin-Präparat und Verfahren zu seiner Herstellung |
GB9401448D0 (en) | 1994-01-26 | 1994-03-23 | Ciba Geigy Ag | Stable dry powders |
US5580856A (en) | 1994-07-15 | 1996-12-03 | Prestrelski; Steven J. | Formulation of a reconstituted protein, and method and kit for the production thereof |
IL114909A (en) | 1994-08-12 | 1999-10-28 | Immunomedics Inc | Immunoconjugates and humanized antibodies specific for b-cell lymphoma and leukemia cells |
US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
CN101712720A (zh) | 1996-02-09 | 2010-05-26 | 艾博特生物技术有限公司 | 结合人TNFα的人抗体 |
TW518219B (en) | 1996-04-26 | 2003-01-21 | Chugai Pharmaceutical Co Ltd | Erythropoietin solution preparation |
GB9610992D0 (en) | 1996-05-24 | 1996-07-31 | Glaxo Group Ltd | Concentrated antibody preparation |
TW555765B (en) | 1996-07-09 | 2003-10-01 | Amgen Inc | Low molecular weight soluble tumor necrosis factor type-I and type-II proteins |
CA2261291A1 (en) | 1996-07-18 | 1998-01-29 | Csl Limited | Pasteurization of immunoglobulin solutions |
TW491855B (en) | 1996-08-07 | 2002-06-21 | Csl Ltd | Purification of immunoglobulins |
EP0852951A1 (de) | 1996-11-19 | 1998-07-15 | Roche Diagnostics GmbH | Stabile lyophilisierte pharmazeutische Zubereitungen von mono- oder polyklonalen Antikörpern |
US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
US5886154A (en) | 1997-06-20 | 1999-03-23 | Lebing; Wytold R. | Chromatographic method for high yield purification and viral inactivation of antibodies |
JP3679406B2 (ja) | 1998-05-20 | 2005-08-03 | 協和醗酵工業株式会社 | 遺伝子組換え抗体 |
US6436897B2 (en) | 1998-06-01 | 2002-08-20 | Celtrix Pharmaceuticals, Inc. | Pharmaceutical formulations for IGF/IGFBP |
JP4685238B2 (ja) | 1998-06-09 | 2011-05-18 | ツエー・エス・エル・ベーリング・アクチエンゲゼルシヤフト | 静脈投与用免疫グロブリン及び他の免疫グロブリン生成物の製造法 |
US6610206B1 (en) | 1998-10-20 | 2003-08-26 | Advanced Renal Technologies | Buffered compositions for dialysis |
IL127127A0 (en) | 1998-11-18 | 1999-09-22 | Peptor Ltd | Small functional units of antibody heavy chain variable regions |
US7294481B1 (en) | 1999-01-05 | 2007-11-13 | Immunex Corporation | Method for producing recombinant proteins |
EP2332976B1 (en) | 1999-02-03 | 2014-04-02 | Amgen, Inc | Novel polypeptides involved in immune response |
DK1165119T3 (da) | 1999-04-08 | 2003-12-15 | Genentech Inc | Sammensætning baseret på modsat ladede polypeptider |
DK1181036T3 (da) | 1999-04-09 | 2008-11-24 | Ortho Mcneil Pharm Inc | Farmaceutiske sammensætninger af erythropoietin |
US20040220103A1 (en) | 1999-04-19 | 2004-11-04 | Immunex Corporation | Soluble tumor necrosis factor receptor treatment of medical disorders |
US20010021380A1 (en) | 1999-04-19 | 2001-09-13 | Pluenneke John D. | Soluble tumor necrosis factor receptor treatment of medical disorders |
CA2366785C (en) | 1999-04-19 | 2012-02-07 | Immunex Corporation | Soluble tumor necrosis factor receptor treatment of medical disorders |
EP1220682B1 (en) | 1999-10-04 | 2006-11-22 | Novartis Vaccines and Diagnostics, Inc. | Stabilized liquid polypeptide-containing pharmaceutical compositions |
NZ519222A (en) | 1999-12-14 | 2004-04-30 | Genentech Inc | TNF-alpha antagonists and LFA-1 antagonist for treating LFA-1 or TNF-alpha mediated disorder |
AU2262501A (en) | 1999-12-16 | 2001-06-25 | Amgen, Inc. | Tnfr/opg-like molecules and uses thereof |
JP2003522155A (ja) | 2000-02-10 | 2003-07-22 | ワイス | 細胞損傷または細胞死を治療または阻害する方法 |
ES2267593T3 (es) | 2000-02-16 | 2007-03-16 | Genentech, Inc. | Anticuerpos anti-april y celulas hibridomas. |
US20050209447A1 (en) | 2000-07-25 | 2005-09-22 | Takashi Ito | Process for producing recombinant protein |
JP5490972B2 (ja) | 2000-08-04 | 2014-05-14 | 中外製薬株式会社 | タンパク質注射製剤 |
WO2002013860A1 (fr) | 2000-08-11 | 2002-02-21 | Chugai Seiyaku Kabushiki Kaisha | Preparations stabilisees contenant un anticorps |
AU2002213441B2 (en) | 2000-10-12 | 2006-10-26 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
MXPA03005327A (es) | 2000-12-14 | 2004-12-03 | Fujisawa Pharmaceutical Co | Anticuerpos anti-cd28 silenciados y el uso de estos. |
US6693173B2 (en) | 2000-12-26 | 2004-02-17 | Alpha Therapeutic Corporation | Method to remove citrate and aluminum from proteins |
WO2002053596A2 (en) | 2001-01-05 | 2002-07-11 | Pfizer Inc. | Antibodies to insulin-like growth factor i receptor |
ES2184594B1 (es) | 2001-01-17 | 2004-01-01 | Probitas Pharma Sa | Procedimiento para la produccion de gammaglobulina g humana inactivada de virus. |
CZ20032208A3 (cs) | 2001-02-23 | 2004-01-14 | Immunex Corporation | Zvýšený výtěžek aktivních proteinů |
GB0113179D0 (en) | 2001-05-31 | 2001-07-25 | Novartis Ag | Organic compounds |
JP2004521474A (ja) | 2001-06-25 | 2004-07-15 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | 高圧ガス放電ランプおよび高圧ガス放電ランプの製造方法 |
CN1547486A (zh) | 2001-06-26 | 2004-11-17 | 抗opgl抗体 | |
WO2004081026A2 (en) | 2003-06-30 | 2004-09-23 | Domantis Limited | Polypeptides |
US7153507B2 (en) * | 2001-08-23 | 2006-12-26 | Genmab A/S | Human antibodies specific for interleukin 15 (IL-15) |
US7247304B2 (en) | 2001-08-23 | 2007-07-24 | Genmab A/S | Methods of treating using anti-IL-15 antibodies |
WO2003024388A2 (en) | 2001-09-20 | 2003-03-27 | Cornell Research Foundation, Inc. | Methods and compositions for treating and preventing skin disorders using binding agents specific for psma |
EP1441589B1 (en) | 2001-11-08 | 2012-05-09 | Abbott Biotherapeutics Corp. | Stable liquid pharmaceutical formulation of igg antibodies |
AU2002359495A1 (en) | 2001-11-30 | 2003-06-17 | Centocor, Inc. | Anti-tnf antibodies, compositions, methods and uses |
US7122641B2 (en) | 2001-12-21 | 2006-10-17 | Immunex Corporation | Methods for purifying protein |
JP4364645B2 (ja) | 2002-02-14 | 2009-11-18 | 中外製薬株式会社 | 抗体含有溶液製剤 |
EP1476120B1 (en) | 2002-02-21 | 2010-09-29 | Duke University | Treatment methods using anti-cd22 antibodies |
SI1478394T1 (sl) | 2002-02-27 | 2008-12-31 | Immunex Corp | STABILIZIRAN TNFR-Fc SESTAVEK Z ARGININOM |
MXPA04009381A (es) | 2002-03-27 | 2005-01-25 | Immunex Corp | Metodos para incrementar la produccion de polipeptidos. |
EP1494714A4 (en) | 2002-04-05 | 2008-03-05 | Amgen Inc | HUMAN ANTI-OPGL NEUTRALIZING ANTIBODIES AS SELECTIVE OPGL PATH HEMMER |
DK1501369T3 (en) | 2002-04-26 | 2015-09-28 | Genentech Inc | Non-affinity purification of proteins |
US20030206898A1 (en) | 2002-04-26 | 2003-11-06 | Steven Fischkoff | Use of anti-TNFalpha antibodies and another drug |
GB0210121D0 (en) | 2002-05-02 | 2002-06-12 | Celltech R&D Ltd | Biological products |
CA2490423A1 (en) | 2002-06-21 | 2003-12-31 | Biogen Idec Inc. | Buffered formulations for concentrating antibodies and methods of use thereof |
KR20050042466A (ko) | 2002-07-19 | 2005-05-09 | 애보트 바이오테크놀로지 리미티드 | TNFα 관련 질환의 치료 |
US20040033228A1 (en) | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
US7674885B2 (en) | 2002-11-01 | 2010-03-09 | Bayer Healthcare Llc | Process for concentration of macromolecules |
US20040086532A1 (en) | 2002-11-05 | 2004-05-06 | Allergan, Inc., | Botulinum toxin formulations for oral administration |
NZ541253A (en) | 2002-12-20 | 2010-03-26 | Amgen Inc | Peptide binding agents which inhibit myostatin |
EP1603948A1 (en) | 2003-03-14 | 2005-12-14 | Pharmacia Corporation | Antibodies to igf-i receptor for the treatment of cancers |
ZA200507757B (en) | 2003-04-04 | 2007-01-31 | Genentech Inc | High concentration antibody and protein formulations |
JP4850709B2 (ja) | 2003-05-14 | 2012-01-11 | ダニスコ・ユーエス・インコーポレーテッド | 反復配列タンパク質ポリマーを使用する、活性剤の制御放出 |
US7354578B2 (en) | 2003-06-06 | 2008-04-08 | Regeneron Pharmaceuticals, Inc. | Method of tumor regression with VEGF inhibitors |
ATE548388T1 (de) | 2003-11-07 | 2012-03-15 | Immunex Corp | An den interleukin-4-rezeptor bindende antikörper |
EP1532983A1 (en) | 2003-11-18 | 2005-05-25 | ZLB Bioplasma AG | Immunoglobulin preparations having increased stability |
CN1953768B (zh) | 2004-02-12 | 2010-10-13 | 默克专利有限公司 | 抗-egfr抗体的高浓缩液体制剂 |
US20070292346A1 (en) | 2004-03-25 | 2007-12-20 | Rong Fan | Lng105 Antibody Composition and Methods of Use, and Use of Lng105 to Assess Lung Cancer Risk |
CN103393601A (zh) | 2004-05-12 | 2013-11-20 | 巴克斯特国际公司 | 含有蛋白并在高浓度蛋白下显示可注射性的微球体 |
WO2006003999A1 (ja) | 2004-07-05 | 2006-01-12 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | ヒト抗ヒトb7rp-1抗体およびその抗体フラグメント |
US7648742B2 (en) * | 2004-07-29 | 2010-01-19 | Merck Patent Gmbh | Difluorosubstituted heterocyclic compounds and the use thereof in the form of components in liquid crystalline media |
TW200621282A (en) | 2004-08-13 | 2006-07-01 | Wyeth Corp | Stabilizing formulations |
US7300773B2 (en) | 2004-08-27 | 2007-11-27 | Wyeth Research Ireland Limited | Production of TNFR-Ig |
CA2581208A1 (en) | 2004-08-30 | 2006-03-09 | Lonza Biologics Plc. | Affinity- plus ion exchange- chromatography for purifying antibodies |
US20060051347A1 (en) | 2004-09-09 | 2006-03-09 | Winter Charles M | Process for concentration of antibodies and therapeutic products thereof |
WO2006064373A2 (en) | 2004-12-16 | 2006-06-22 | Genzyme Polyclonals S.A.S. | Methods of purifying immunologlobulins |
JP4498939B2 (ja) | 2005-02-01 | 2010-07-07 | 東京応化工業株式会社 | ポジ型レジスト組成物およびレジストパターン形成方法 |
US8597709B2 (en) | 2005-04-12 | 2013-12-03 | Inovobiologic Inc. | Dietary supplement and methods of use |
EA012801B1 (ru) | 2005-06-14 | 2009-12-30 | Эмджен Инк. | Самобуферирующиеся композиции белков |
US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
US20070049732A1 (en) | 2005-09-01 | 2007-03-01 | Zurlo Eugene J | Ultra-high yield intravenous immune globulin preparation |
US8877281B2 (en) | 2005-09-21 | 2014-11-04 | Burcon Nutrascience (Mb) Corp. | Preparation of canola protein isolate involving isoelectric precipitation |
US8067350B2 (en) | 2005-12-15 | 2011-11-29 | Kimberly-Clark Worldwide, Inc. | Color changing cleansing composition |
US20070202051A1 (en) | 2006-02-10 | 2007-08-30 | Pari Gmbh | Aerosols for sinunasal drug delivery |
CA2649538C (en) | 2006-04-21 | 2014-06-03 | Yatin Gokarn | Buffering agents for biopharmaceutical formulations |
JP5290152B2 (ja) | 2006-04-21 | 2013-09-18 | ノバルティス アーゲー | 拮抗剤抗cd40抗体薬学的組成物 |
EP2059523A2 (en) | 2006-09-15 | 2009-05-20 | Barofold, Inc. | High pressure treatment of proteins for reduced immunogenicity |
CA2667655A1 (en) | 2006-10-27 | 2008-05-15 | Abbott Biotechnology Ltd. | Crystalline anti-htnfalpha antibodies |
CA2790018C (en) | 2006-12-21 | 2015-02-03 | Amgen Inc. | Formulations |
US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
CA2904458C (en) | 2007-11-30 | 2017-07-25 | Wolfgang Fraunhofer | Protein formulations and methods of making same |
US20110060290A1 (en) * | 2008-02-07 | 2011-03-10 | Amgen Inc. | Stabilized protein compositions |
EP2276527B1 (en) | 2008-05-20 | 2018-02-28 | Avant Medical Corp. | Autoinjector system |
US8177749B2 (en) | 2008-05-20 | 2012-05-15 | Avant Medical Corp. | Cassette for a hidden injection needle |
US8052645B2 (en) | 2008-07-23 | 2011-11-08 | Avant Medical Corp. | System and method for an injection using a syringe needle |
CN102159204B (zh) * | 2008-09-19 | 2015-04-01 | 辉瑞公司 | 稳定的液体抗体制剂 |
MX345226B (es) * | 2008-10-29 | 2017-01-20 | Ablynx Nv | Formulaciones de moleculas de union a antigeno de dominio sencillo. |
RU2011140498A (ru) | 2009-03-06 | 2013-04-20 | Дженентек, Инк. | Препарат антител |
US20110070227A1 (en) | 2009-09-18 | 2011-03-24 | Anna-Marie Novotney-Barry | Treatment of Autoimmune and Inflammatory Diseases |
MX344727B (es) | 2010-11-11 | 2017-01-05 | Abbvie Biotechnology Ltd | Formulaciones liquidas de anticuerpos anti-tnf-alfa de alta concentracion mejoradas. |
US9173999B2 (en) * | 2011-01-26 | 2015-11-03 | Kaleo, Inc. | Devices and methods for delivering medicaments from a multi-chamber container |
CA2833427C (en) * | 2011-04-20 | 2019-09-24 | Sandoz Ag | Stable pharmaceutical liquid formulations of the fusion protein tnfr:fc |
LT2699293T (lt) | 2011-04-20 | 2019-04-25 | Amgen Inc. | Automatinio purškimo prietaisas |
UY34105A (es) * | 2011-06-03 | 2012-07-31 | Lg Life Sciences Ltd | Formulación líquida estable de etanercept |
KR102061355B1 (ko) | 2011-07-01 | 2019-12-31 | 바이오젠 엠에이 인코포레이티드 | 아르기닌-없는 tnfr : fc-융합 폴리펩티드 조성물 및 이용 방법 |
WO2013186230A1 (en) * | 2012-06-12 | 2013-12-19 | Boehringer Ingelheim International Gmbh | Pharmaceutical formulation for a therapeutic antibody |
EP2869871B1 (en) | 2012-07-05 | 2021-03-17 | UNL Holdings LLC | Automatic injectors for injectable cartridges and drive control mechanisms therefor |
IN2015KN00452A (ja) * | 2012-09-11 | 2015-07-17 | Coherus Biosciences Inc | |
US10058589B2 (en) | 2012-10-26 | 2018-08-28 | Lupin Limited | Stable pharmaceutical composition of Etanercept in a phosphate citrate buffer with glycine as an anti-aggregating agent |
EP2919812A4 (en) | 2012-11-19 | 2016-05-18 | Merck Sharp & Dohme | Liquid formulations for TNFR: FC fusion proteins |
WO2014084508A1 (ko) * | 2012-11-27 | 2014-06-05 | (주)알테오젠 | 단백질과 Fc 도메인을 융합한 융합 단백질의 안정화용 조성물 |
US9452138B2 (en) | 2012-12-28 | 2016-09-27 | Abbott Cardiovascular Systems Inc. | Delivery of biologic therapeutics |
TWI639449B (zh) | 2013-03-15 | 2018-11-01 | 美商安美基公司 | 用於注射器之匣盒 |
CA2904725C (en) | 2013-03-15 | 2022-04-12 | Amgen Inc. | Drug cassette, autoinjector, and autoinjector system |
JP2016518386A (ja) * | 2013-05-02 | 2016-06-23 | マブキシェンス エス.アー. | TNFR:Fc融合ポリペプチドの代替配合物 |
KR20210041101A (ko) * | 2013-10-24 | 2021-04-14 | 아스트라제네카 아베 | 안정한 수성 항체 제제 |
KR101712245B1 (ko) * | 2013-11-29 | 2017-03-06 | 아레스 트레이딩 에스.에이. | TNFR 및 면역글로블린 Fc 영역을 포함하는 융합 단백질을 포함하는 액상 제제 |
ES2733298T3 (es) | 2014-07-18 | 2019-11-28 | Sandoz Ag | Cuantificación de TNFR2:Fc plegado erróneamente |
EP3733228B1 (en) | 2014-08-28 | 2024-03-06 | UNL Holdings LLC | Sensor systems for drug delivery devices |
CN107106769A (zh) | 2014-08-28 | 2017-08-29 | 尤尼特拉克特注射器控股有限公司 | 用于药物递送装置的皮肤传感器 |
EP3268042A4 (en) | 2015-03-13 | 2018-08-01 | Samsung Bioepis Co., Ltd. | Anti-tnf-alpha polypeptide composition and use thereof |
US9763976B1 (en) | 2016-08-02 | 2017-09-19 | Zo Skin Health, Inc. | Composition and method for treating skin conditions |
EP3528787A4 (en) | 2016-10-21 | 2020-05-06 | Amgen Inc. | PHARMACEUTICAL FORMULATIONS AND PROCESSES FOR THEIR PREPARATION |
-
2017
- 2017-10-19 EP EP17862991.1A patent/EP3528787A4/en active Pending
- 2017-10-19 KR KR1020217042112A patent/KR102413592B1/ko active IP Right Grant
- 2017-10-19 BR BR112019007858A patent/BR112019007858A2/pt active Search and Examination
- 2017-10-19 JP JP2019520794A patent/JP6884858B2/ja active Active
- 2017-10-19 AU AU2017345490A patent/AU2017345490B2/en active Active
- 2017-10-19 US US15/788,762 patent/US20180110856A1/en not_active Abandoned
- 2017-10-19 SG SG11201903521XA patent/SG11201903521XA/en unknown
- 2017-10-19 CN CN201780072322.9A patent/CN109982685B/zh active Active
- 2017-10-19 MX MX2019004580A patent/MX2019004580A/es unknown
- 2017-10-19 WO PCT/US2017/057472 patent/WO2018075818A1/en active Application Filing
- 2017-10-19 KR KR1020197014130A patent/KR102446838B1/ko active IP Right Grant
- 2017-10-19 CA CA3040899A patent/CA3040899A1/en not_active Abandoned
- 2017-10-19 CN CN202210152416.XA patent/CN114917185B/zh active Active
- 2017-10-19 EA EA201990998A patent/EA201990998A1/ru unknown
-
2018
- 2018-04-20 US US15/958,261 patent/US10307483B2/en active Active
- 2018-09-27 US US16/144,120 patent/US11491223B2/en active Active
-
2019
- 2019-04-17 CL CL2019001053A patent/CL2019001053A1/es unknown
- 2019-04-18 IL IL266132A patent/IL266132B/en unknown
-
2021
- 2021-05-11 JP JP2021080160A patent/JP7402195B2/ja active Active
-
2022
- 2022-09-16 US US17/933,055 patent/US20230080571A1/en active Pending
-
2023
- 2023-10-19 JP JP2023180119A patent/JP2024010026A/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014530864A (ja) * | 2011-10-18 | 2014-11-20 | コヒラス・バイオサイエンシズ・インコーポレイテッド | 糖およびポリオールの組合せによって安定化されたエタネルセプト製剤 |
JP2015525763A (ja) * | 2012-07-09 | 2015-09-07 | コヒラス・バイオサイエンシズ・インコーポレイテッド | 肉眼不可視粒子の著しい低減を示すエタネルセプト製剤 |
WO2016102328A1 (en) * | 2014-12-22 | 2016-06-30 | Ares Trading S.A. | Liquid pharmaceutical composition |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2021120393A (ja) * | 2016-10-21 | 2021-08-19 | アムジエン・インコーポレーテツド | 医薬製剤及びその製造方法 |
JP7402195B2 (ja) | 2016-10-21 | 2023-12-20 | アムジエン・インコーポレーテツド | 医薬製剤及びその製造方法 |
Also Published As
Publication number | Publication date |
---|---|
SG11201903521XA (en) | 2019-05-30 |
AU2017345490B2 (en) | 2022-07-07 |
EP3528787A4 (en) | 2020-05-06 |
CN109982685A (zh) | 2019-07-05 |
IL266132A (en) | 2019-06-30 |
EP3528787A1 (en) | 2019-08-28 |
MX2019004580A (es) | 2019-08-12 |
AU2017345490A1 (en) | 2019-05-09 |
JP2024010026A (ja) | 2024-01-23 |
CN109982685B (zh) | 2022-03-11 |
KR20210158878A (ko) | 2021-12-31 |
US20180110856A1 (en) | 2018-04-26 |
CA3040899A1 (en) | 2018-04-26 |
US20190022217A1 (en) | 2019-01-24 |
JP7402195B2 (ja) | 2023-12-20 |
CL2019001053A1 (es) | 2019-08-02 |
WO2018075818A1 (en) | 2018-04-26 |
IL266132B (en) | 2021-12-01 |
JP2021120393A (ja) | 2021-08-19 |
JP6884858B2 (ja) | 2021-06-09 |
US20180256718A1 (en) | 2018-09-13 |
CN114917185B (zh) | 2023-11-14 |
KR102446838B1 (ko) | 2022-09-26 |
EA201990998A1 (ru) | 2019-11-29 |
BR112019007858A2 (pt) | 2019-07-02 |
US11491223B2 (en) | 2022-11-08 |
CN114917185A (zh) | 2022-08-19 |
KR102413592B1 (ko) | 2022-06-27 |
KR20190071760A (ko) | 2019-06-24 |
US10307483B2 (en) | 2019-06-04 |
US20230080571A1 (en) | 2023-03-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2020244614B2 (en) | Stable protein solution formulation containing high concentration of an anti-VEGF antibody | |
JP7402195B2 (ja) | 医薬製剤及びその製造方法 | |
EP2714009B1 (en) | Stable liquid formulation of etanercept | |
AU2013255413B2 (en) | Pharmaceutical formulations of TNF-alpha antibodies | |
JP6220788B2 (ja) | 塩化ナトリウムによって安定化されたエタネルセプト製剤 | |
EP2726090B1 (en) | Arginine - free tnfr : fc- fusion polypeptide compositions | |
BRPI0620316A2 (pt) | formulações de proteìnas com viscosidades reduzida e seus usos | |
WO2017104778A1 (ja) | 抗ヒトtslp受容体抗体含有医薬組成物 | |
US11945859B2 (en) | Protein solution formulation containing high concentration of an anti-VEGF antibody | |
EP3236990A1 (en) | Liquid pharmaceutical composition | |
EA041785B1 (ru) | Фармацевтическая композиция и способ ее получения | |
JP2022546400A (ja) | 高濃度の薬理学的に活性な抗体の新規製剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201014 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20201014 |
|
A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20201014 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201027 |
|
A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20201030 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20201124 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210219 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20210413 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210512 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6884858 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |