MX2015003007A - Formulaciones acuosas estables de adalimumab. - Google Patents
Formulaciones acuosas estables de adalimumab.Info
- Publication number
- MX2015003007A MX2015003007A MX2015003007A MX2015003007A MX2015003007A MX 2015003007 A MX2015003007 A MX 2015003007A MX 2015003007 A MX2015003007 A MX 2015003007A MX 2015003007 A MX2015003007 A MX 2015003007A MX 2015003007 A MX2015003007 A MX 2015003007A
- Authority
- MX
- Mexico
- Prior art keywords
- composition
- regulator
- concentration
- adalimumab
- stabilizer
- Prior art date
Links
- 229960002964 adalimumab Drugs 0.000 title claims abstract description 224
- 239000013011 aqueous formulation Substances 0.000 title description 5
- 239000000203 mixture Substances 0.000 claims abstract description 676
- 238000000034 method Methods 0.000 claims abstract description 45
- 230000007774 longterm Effects 0.000 claims abstract description 26
- 238000009472 formulation Methods 0.000 claims description 261
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 145
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 140
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 133
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 120
- 239000003381 stabilizer Substances 0.000 claims description 120
- 229910019142 PO4 Inorganic materials 0.000 claims description 119
- 239000010452 phosphate Substances 0.000 claims description 119
- 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 claims description 104
- 229930195725 Mannitol Natural products 0.000 claims description 104
- 239000000594 mannitol Substances 0.000 claims description 104
- 235000010355 mannitol Nutrition 0.000 claims description 104
- 239000008194 pharmaceutical composition Substances 0.000 claims description 99
- 229920005862 polyol Polymers 0.000 claims description 95
- 150000003077 polyols Chemical class 0.000 claims description 95
- 239000004094 surface-active agent Substances 0.000 claims description 87
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 80
- 239000011780 sodium chloride Substances 0.000 claims description 70
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 67
- 239000004475 Arginine Substances 0.000 claims description 60
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 60
- 239000004471 Glycine Substances 0.000 claims description 57
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 57
- 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 claims description 52
- 239000000600 sorbitol Substances 0.000 claims description 52
- 235000010356 sorbitol Nutrition 0.000 claims description 52
- 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 claims description 51
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 47
- 229920000053 polysorbate 80 Polymers 0.000 claims description 47
- 229940068968 polysorbate 80 Drugs 0.000 claims description 47
- 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 claims description 42
- 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 claims description 42
- 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 claims description 42
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 40
- 229920000136 polysorbate Polymers 0.000 claims description 37
- 229950008882 polysorbate Drugs 0.000 claims description 33
- 230000006641 stabilisation Effects 0.000 claims description 26
- 238000011105 stabilization Methods 0.000 claims description 26
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 14
- 229920001983 poloxamer Polymers 0.000 claims description 11
- 229960000502 poloxamer Drugs 0.000 claims description 9
- 230000001747 exhibiting effect Effects 0.000 claims description 3
- 238000003860 storage Methods 0.000 abstract description 21
- 238000004519 manufacturing process Methods 0.000 abstract 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 70
- 230000000694 effects Effects 0.000 description 70
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 57
- 235000001014 amino acid Nutrition 0.000 description 49
- 150000001413 amino acids Chemical class 0.000 description 49
- 229940024606 amino acid Drugs 0.000 description 48
- 108090000623 proteins and genes Proteins 0.000 description 45
- 102000004169 proteins and genes Human genes 0.000 description 45
- 235000018102 proteins Nutrition 0.000 description 44
- 239000000178 monomer Substances 0.000 description 41
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 35
- 238000001542 size-exclusion chromatography Methods 0.000 description 35
- 229940095064 tartrate Drugs 0.000 description 35
- 150000003839 salts Chemical class 0.000 description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 32
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 31
- 229910021645 metal ion Inorganic materials 0.000 description 31
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 31
- 229930182817 methionine Natural products 0.000 description 27
- 229940048921 humira Drugs 0.000 description 26
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 25
- 238000004007 reversed phase HPLC Methods 0.000 description 25
- 150000005846 sugar alcohols Chemical class 0.000 description 24
- 239000000523 sample Substances 0.000 description 23
- 230000004044 response Effects 0.000 description 20
- 238000000533 capillary isoelectric focusing Methods 0.000 description 19
- 208000035475 disorder Diseases 0.000 description 19
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 18
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 16
- 235000004279 alanine Nutrition 0.000 description 16
- 230000007423 decrease Effects 0.000 description 16
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 14
- 238000002347 injection Methods 0.000 description 14
- 239000007924 injection Substances 0.000 description 14
- 239000011159 matrix material Substances 0.000 description 14
- 239000000546 pharmaceutical excipient Substances 0.000 description 14
- 201000010099 disease Diseases 0.000 description 13
- 229930195712 glutamate Natural products 0.000 description 13
- 230000001105 regulatory effect Effects 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 12
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 12
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 12
- 238000007792 addition Methods 0.000 description 12
- 239000011575 calcium Substances 0.000 description 12
- 229910052791 calcium Inorganic materials 0.000 description 12
- 239000011777 magnesium Substances 0.000 description 12
- 229910052749 magnesium Inorganic materials 0.000 description 12
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 12
- 229910052725 zinc Inorganic materials 0.000 description 12
- 239000011701 zinc Substances 0.000 description 12
- 241000124008 Mammalia Species 0.000 description 11
- 238000013368 capillary electrophoresis sodium dodecyl sulfate analysis Methods 0.000 description 11
- 238000013461 design Methods 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- 239000008181 tonicity modifier Substances 0.000 description 11
- 230000000368 destabilizing effect Effects 0.000 description 10
- 229960000106 biosimilars Drugs 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 238000000502 dialysis Methods 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 235000000346 sugar Nutrition 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000000087 stabilizing effect Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229930006000 Sucrose Natural products 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 230000015556 catabolic process Effects 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 229920001993 poloxamer 188 Polymers 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- 238000010200 validation analysis Methods 0.000 description 6
- 229910001868 water Inorganic materials 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 5
- 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 5
- 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 5
- 238000013019 agitation Methods 0.000 description 5
- 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 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 102100039250 Essential MCU regulator, mitochondrial Human genes 0.000 description 4
- 101000813097 Homo sapiens Essential MCU regulator, mitochondrial Proteins 0.000 description 4
- 101000596041 Homo sapiens Plastin-1 Proteins 0.000 description 4
- 102100035181 Plastin-1 Human genes 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000006172 buffering agent Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- -1 additions Chemical class 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 3
- 102000057041 human TNF Human genes 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012669 liquid formulation Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 229940068977 polysorbate 20 Drugs 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 150000008163 sugars Chemical class 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
- 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 2
- 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 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
- 206010006895 Cachexia Diseases 0.000 description 2
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 101100289061 Drosophila melanogaster lili gene Proteins 0.000 description 2
- 201000009273 Endometriosis Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000005176 Hepatitis C Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 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 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 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 2
- RSPISYXLHRIGJD-UHFFFAOYSA-N OOOO Chemical compound OOOO RSPISYXLHRIGJD-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 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 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000002790 cross-validation Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000013016 damping Methods 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 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
- 230000006872 improvement Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000013178 mathematical model Methods 0.000 description 2
- 238000000491 multivariate analysis Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000006174 pH buffer Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229940068965 polysorbates Drugs 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 239000012460 protein solution Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000008646 thermal stress Effects 0.000 description 2
- 239000012929 tonicity agent Substances 0.000 description 2
- 230000000699 topical effect Effects 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
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- 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 1
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-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
- 241000894006 Bacteria Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 101710112164 Cytochrome b6-f complex subunit 4 Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- JLXVRFDTDUGQEE-YFKPBYRVSA-N Gly-Arg Chemical compound NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N JLXVRFDTDUGQEE-YFKPBYRVSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 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
- 101000596046 Homo sapiens Plastin-2 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 102100035182 Plastin-2 Human genes 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
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 102100038968 WAP four-disulfide core domain protein 1 Human genes 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 201000005008 bacterial sepsis Diseases 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 235000009120 camo Nutrition 0.000 description 1
- 244000213578 camo Species 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000012569 chemometric method Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000011098 chromatofocusing Methods 0.000 description 1
- 239000012539 chromatography resin Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000009260 cross reactivity 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
- 230000007812 deficiency Effects 0.000 description 1
- 230000000593 degrading effect Effects 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
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000012520 frozen sample Substances 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 238000001502 gel electrophoresis 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
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 239000007972 injectable composition 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
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane 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
- 150000001455 metallic ions Chemical class 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000009022 nonlinear effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 238000010238 partial least squares regression Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 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
- 229940111202 pepsin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000008180 pharmaceutical surfactant Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940101027 polysorbate 40 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
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000029219 regulation of pH Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 230000007017 scission Effects 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
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000012496 stress study Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003890 succinate salts Chemical group 0.000 description 1
- 125000000185 sucrose group Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 230000003442 weekly effect Effects 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
Classifications
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
-
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- 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
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
-
- 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]
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/241—Tumor Necrosis Factors
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- 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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/542—Mucosal route oral/gastrointestinal
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Biochemistry (AREA)
- Cardiology (AREA)
- Biophysics (AREA)
- Heart & Thoracic Surgery (AREA)
- Genetics & Genomics (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Inorganic Chemistry (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Communicable Diseases (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261698138P | 2012-09-07 | 2012-09-07 | |
| US201361769581P | 2013-02-26 | 2013-02-26 | |
| US201361770421P | 2013-02-28 | 2013-02-28 | |
| PCT/US2013/058618 WO2014039903A2 (en) | 2012-09-07 | 2013-09-06 | Stable aqueous formulations of adalimumab |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2015003007A true MX2015003007A (es) | 2015-06-05 |
Family
ID=50237778
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2015003007A MX2015003007A (es) | 2012-09-07 | 2013-09-06 | Formulaciones acuosas estables de adalimumab. |
Country Status (31)
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040033228A1 (en) | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
| US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
| US9062106B2 (en) | 2011-04-27 | 2015-06-23 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
| WO2013164837A1 (en) * | 2012-03-07 | 2013-11-07 | Cadila Healthcare Limited | Pharmaceutical formulations of tnf-alpha antibodies |
| US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
| WO2013158273A1 (en) | 2012-04-20 | 2013-10-24 | Abbvie Inc. | Methods to modulate c-terminal lysine variant distribution |
| US9334319B2 (en) | 2012-04-20 | 2016-05-10 | Abbvie Inc. | Low acidic species compositions |
| WO2013176754A1 (en) | 2012-05-24 | 2013-11-28 | Abbvie Inc. | Novel purification of antibodies using hydrophobic interaction chromatography |
| US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
| CN104768576A (zh) | 2012-09-07 | 2015-07-08 | 科荣生生物科学公司 | 稳定的阿达木单抗水性制剂 |
| BR112015017619A2 (pt) * | 2013-01-24 | 2017-11-21 | Glaxosmithkline Ip Dev Ltd | formulação líquida, uso de uma formulação, e, kit |
| CA2905010A1 (en) | 2013-03-12 | 2014-09-18 | Abbvie Inc. | Human antibodies that bind human tnf-alpha and methods of preparing the same |
| US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
| US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
| EP3052640A2 (en) | 2013-10-04 | 2016-08-10 | AbbVie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
| MX374124B (es) | 2013-10-16 | 2025-03-05 | Outlook Therapeutics Inc | Formulaciones de tampón para la estabilidad de anticuerpo mejorada. |
| US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
| US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
| WO2015073884A2 (en) | 2013-11-15 | 2015-05-21 | Abbvie, Inc. | Glycoengineered binding protein compositions |
| WO2015151115A1 (en) | 2014-04-02 | 2015-10-08 | Intas Pharmaceuticals Limited | Liquid pharmaceutical composition of adalimumab |
| EP2946766B1 (en) * | 2014-05-23 | 2016-03-02 | Ares Trading S.A. | Liquid pharmaceutical composition |
| EP2946765B1 (en) * | 2014-05-23 | 2016-08-31 | Ares Trading S.A. | Liquid pharmaceutical composition |
| ES2607489T3 (es) * | 2014-05-23 | 2017-03-31 | Ares Trading S.A. | Composición farmacéutica líquida |
| US20170189528A1 (en) * | 2014-06-10 | 2017-07-06 | Meiji Seika Pharma Co., Ltd. | Stable aqueous adalimumab formulation |
| US9821059B2 (en) * | 2014-10-17 | 2017-11-21 | Alteogen Inc. | Composition for stabilizing protein and pharmaceutical formulation comprising the same |
| HUP1400510A1 (hu) | 2014-10-28 | 2016-05-30 | Richter Gedeon Nyrt | Gyógyászati TNFalfa ellenes antitest készítmény |
| EP3247718B1 (en) | 2015-01-21 | 2021-09-01 | Outlook Therapeutics, Inc. | Modulation of charge variants in a monoclonal antibody composition |
| WO2016120413A1 (en) * | 2015-01-28 | 2016-08-04 | Mabxience S.A. | Pharmaceutical formulations for anti-tnf-alpha antibodies |
| EP3053572A1 (en) * | 2015-02-06 | 2016-08-10 | Ares Trading S.A. | Liquid pharmaceutical composition |
| US20180008707A1 (en) * | 2015-02-13 | 2018-01-11 | Sanofi | Stable liquid formulation for monoclonal antibodies |
| WO2016162819A1 (en) | 2015-04-07 | 2016-10-13 | Lupin Limited | Stable aqueous pharmaceutical composition of anti-tnf alpha antibody |
| US11229702B1 (en) | 2015-10-28 | 2022-01-25 | Coherus Biosciences, Inc. | High concentration formulations of adalimumab |
| US11583584B1 (en) * | 2015-10-28 | 2023-02-21 | Coherus Biosciences, Inc. | Stable protein compositions and methods of their use |
| BR112018014123A2 (pt) * | 2016-01-12 | 2018-12-11 | Dr. Reddy's Laboratories Limited | formulação farmacêutica aquosa estável. |
| WO2017136433A1 (en) * | 2016-02-03 | 2017-08-10 | Oncobiologics, Inc. | Buffer formulations for enhanced antibody stability |
| KR20180116359A (ko) * | 2016-02-23 | 2018-10-24 | 세센 바이오, 아이엔씨. | 인터루킨-6의 길항제 제제 및 이의 용도 |
| EP3443346B1 (en) * | 2016-04-13 | 2023-08-30 | Medimmune, LLC | Use of amino acids as stabilizing compounds in pharmaceutical compositions containing high concentrations of protein-based therapeutic agents |
| WO2017184880A1 (en) * | 2016-04-20 | 2017-10-26 | Coherus Biosciences, Inc. | A method of filling a container with no headspace |
| US20180043020A1 (en) * | 2016-04-20 | 2018-02-15 | Coherus Biosciences, Inc. | Method of reducing immunogenicity of drug products |
| PT3479819T (pt) | 2016-06-30 | 2024-04-15 | Celltrion Inc | Preparação farmacêutica líquida estável |
| WO2018080196A2 (ko) * | 2016-10-28 | 2018-05-03 | (주)셀트리온 | 안정한 약제학적 제제 |
| EP3824906A1 (en) * | 2016-12-21 | 2021-05-26 | Amgen Inc. | Anti-tnf alpha antibody formulations |
| US11608357B2 (en) | 2018-08-28 | 2023-03-21 | Arecor Limited | Stabilized antibody protein solutions |
| EP3372242A1 (en) * | 2017-03-06 | 2018-09-12 | Ares Trading S.A. | Liquid pharmaceutical composition |
| EP3372241A1 (en) | 2017-03-06 | 2018-09-12 | Ares Trading S.A. | Liquid pharmaceutical composition |
| MY197202A (en) * | 2017-03-16 | 2023-05-31 | Lg Chemical Ltd | A liquid formulation of anti-tnf alpha antibody |
| WO2018184693A1 (en) * | 2017-04-07 | 2018-10-11 | Ares Trading S.A. | Liquid pharmaceutical composition |
| WO2018184692A1 (en) * | 2017-04-07 | 2018-10-11 | Ares Trading S.A. | Liquid pharmaceutical composition |
| CN111201042B (zh) * | 2017-09-19 | 2024-05-10 | 里珍纳龙药品有限公司 | 减少粒子形成的方法以及由其形成的组合物 |
| CN111491664A (zh) * | 2017-09-20 | 2020-08-04 | 阿尔沃科技Hf公司 | 阿达木单抗的药物制剂 |
| MX421763B (es) | 2018-03-29 | 2025-03-14 | Airway Therapeutics Inc | Metodos y composiciones que comprenden proteina d tensoactiva (sp-d) |
| WO2020145789A1 (ko) * | 2019-01-11 | 2020-07-16 | 삼성바이오에피스 주식회사 | 항체를 포함하는 약학적 조성물, 이를 포함하는 디바이스, 및 이의 용도 |
| JOP20210229A1 (ar) * | 2019-02-18 | 2023-01-30 | Lilly Co Eli | صيغة جسم مضاد علاجي |
| US20230203147A1 (en) * | 2019-03-18 | 2023-06-29 | Alvotech Hf | Aqueous formulations of tnf-alpha antibodies in high concentrations |
| AU2020337093B2 (en) * | 2019-08-30 | 2025-02-27 | Kashiv Biosciences, Llc | Novel formulation of highly concentrated pharmacologically active antibody |
| CU20190104A7 (es) * | 2019-12-17 | 2021-08-06 | Ct Inmunologia Molecular | Formulación estable del anticuerpo nimotuzumab |
| US20230151102A1 (en) * | 2020-01-13 | 2023-05-18 | Aptevo Research And Development Llc | Methods and compositions for preventing adsorption of therapeutic proteins to drug delivery system components |
| WO2021164717A1 (zh) * | 2020-02-20 | 2021-08-26 | 百奥泰生物制药股份有限公司 | 抗TNF-α的抗体制剂及其制备方法和用途 |
| WO2021182874A1 (ko) * | 2020-03-13 | 2021-09-16 | 삼성바이오에피스 주식회사 | 안정성이 증진된 액상 약제학적 조성물 |
| EP4142792A4 (en) | 2020-05-01 | 2024-11-27 | Kashiv Biosciences, LLC | An improved process of purification of protein |
| WO2021234584A1 (en) * | 2020-05-21 | 2021-11-25 | Shilpa Biologicals Private Limited | Pharmaceutical compositions comprising adalimumab |
| RU2745814C1 (ru) * | 2020-06-05 | 2021-04-01 | Закрытое Акционерное Общество "Биокад" | Водная фармацевтическая композиция левилимаба и ее применение |
| US20240158498A1 (en) * | 2021-03-03 | 2024-05-16 | Allakos Inc. | Anti-siglec-8 antibody formulations |
| US20240366757A1 (en) * | 2021-09-07 | 2024-11-07 | Dr. Reddy’S Laboratories Limited | Formulations of immune check point inhibitors or like |
| EP4400116A4 (en) * | 2021-09-16 | 2025-09-24 | Aprogen Inc | PHARMACEUTICAL COMPOSITION CONTAINING AN ANTI-TNF ALPHA ANTIBODY |
| CN114788809B (zh) * | 2022-01-25 | 2023-04-14 | 江苏广承药业有限公司 | 一种氯雷他定液体制剂 |
| WO2023183898A1 (en) * | 2022-03-24 | 2023-09-28 | Arch Oncology, Inc. | Formulations for anti-cd47 antibodies |
| WO2025038671A2 (en) * | 2023-08-15 | 2025-02-20 | Amgen Inc. | Acidic buffered intravenous solution stabilizers for use in methods of treatment |
Family Cites Families (83)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4597966A (en) * | 1985-01-09 | 1986-07-01 | Ortho Diagnostic Systems, Inc. | Histidine stabilized immunoglobulin and method of preparation |
| US5104651A (en) | 1988-12-16 | 1992-04-14 | Amgen Inc. | Stabilized hydrophobic protein formulations of g-csf |
| US5945098A (en) | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
| CN1138541C (zh) | 1994-08-08 | 2004-02-18 | 德彪药品股份有限公司 | 一种药学上稳定的奥沙利铂制剂 |
| ATE306930T1 (de) | 1994-08-12 | 2005-11-15 | Immunomedics Inc | Für b-zell-lymphom und leukämiezellen spezifische immunkonjugate und humane antikörper |
| US6171576B1 (en) | 1995-11-03 | 2001-01-09 | Organix Inc. | Dopamine transporter imaging agent |
| US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
| WO1997029131A1 (en) | 1996-02-09 | 1997-08-14 | Basf Aktiengesellschaft | HUMAN ANTIBODIES THAT BIND HUMAN TNF$g(a) |
| GB9610992D0 (en) | 1996-05-24 | 1996-07-31 | Glaxo Group Ltd | Concentrated antibody preparation |
| JP2000516594A (ja) | 1996-07-26 | 2000-12-12 | スミスクライン・ビーチャム・コーポレイション | 免疫細胞介在全身性疾患の改良された治療法 |
| EP0852951A1 (de) * | 1996-11-19 | 1998-07-15 | Roche Diagnostics GmbH | Stabile lyophilisierte pharmazeutische Zubereitungen von mono- oder polyklonalen Antikörpern |
| CA2635352C (en) * | 1997-06-13 | 2012-09-11 | Genentech, Inc. | Stabilized antibody formulation |
| 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 |
| US6171686B1 (en) | 1997-10-03 | 2001-01-09 | Marine Environmental Solutions, L.L.C. | Synthetic aquatic structure |
| DE59804785D1 (de) | 1997-11-22 | 2002-08-22 | Roche Diagnostics Gmbh | Verbessertes Verfahren zur Stabilisierung von Proteinen |
| AU2444899A (en) | 1998-01-22 | 1999-08-09 | Astrazeneca Ab | Pharmaceutical formulation comprising an antibody and a citrate buffer |
| US6436897B2 (en) | 1998-06-01 | 2002-08-20 | Celtrix Pharmaceuticals, Inc. | Pharmaceutical formulations for IGF/IGFBP |
| DK2270044T3 (en) | 1998-06-09 | 2015-01-26 | Csl Behring Ag | Liquid immunoglobulin G (IgG) product |
| TR200102715T2 (tr) | 1999-03-25 | 2002-09-23 | Knoll Gmbh | Beşeri IL-12'yi bağlayan beşeri antikorlar ve bunları üretmek için yöntemler. |
| DE60039598D1 (de) | 1999-04-09 | 2008-09-04 | Ortho Mcneil Pharm Inc | Pharmazeutische zusammensetzungen von erythropoietin |
| AUPQ026799A0 (en) | 1999-05-10 | 1999-06-03 | Csl Limited | Method of increasing protein stability by removing immunoglobulin aggregates |
| WO2001047554A1 (fr) * | 1999-12-28 | 2001-07-05 | Chugai Seiyaku Kabushiki Kaisha | Compositions d'anticorps stables et preparations pour injection |
| EP1336410A4 (en) | 2000-08-04 | 2005-10-12 | Chugai Pharmaceutical Co Ltd | PROTEIN INJECTION PREPARATIONS |
| UA81743C2 (uk) | 2000-08-07 | 2008-02-11 | Центокор, Инк. | МОНОКЛОНАЛЬНЕ АНТИТІЛО ЛЮДИНИ, ЩО СПЕЦИФІЧНО ЗВ'ЯЗУЄТЬСЯ З ФАКТОРОМ НЕКРОЗУ ПУХЛИН АЛЬФА (ФНПα), ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЙОГО МІСТИТЬ, ТА СПОСІБ ЛІКУВАННЯ РЕВМАТОЇДНОГО АРТРИТУ |
| JP5485489B2 (ja) | 2000-08-11 | 2014-05-07 | 中外製薬株式会社 | 抗体含有安定化製剤 |
| EP1324776B2 (en) | 2000-10-12 | 2018-03-21 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
| GB0113179D0 (en) | 2001-05-31 | 2001-07-25 | Novartis Ag | Organic compounds |
| CA2385745C (en) | 2001-06-08 | 2015-02-17 | Abbott Laboratories (Bermuda) Ltd. | Methods of administering anti-tnf.alpha. antibodies |
| TR201809008T4 (tr) | 2001-06-26 | 2018-07-23 | Amgen Fremont Inc | Opgl ye karşi antikorlar. |
| US20030138417A1 (en) * | 2001-11-08 | 2003-07-24 | Kaisheva Elizabet A. | Stable liquid pharmaceutical formulation of IgG antibodies |
| ES2311094T3 (es) | 2002-02-27 | 2009-02-01 | Immunex Corporation | Composicion estabilizada de tnfr-fc que comprende arginina. |
| US20030206898A1 (en) | 2002-04-26 | 2003-11-06 | Steven Fischkoff | Use of anti-TNFalpha antibodies and another drug |
| US20040022792A1 (en) | 2002-06-17 | 2004-02-05 | Ralph Klinke | Method of stabilizing proteins at low pH |
| US20060165733A1 (en) | 2002-07-09 | 2006-07-27 | Michael Betz | Liquid formulations with high concentration of hunan growth hormone (hgh) comprising phenol |
| US20040033228A1 (en) * | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
| JP4500683B2 (ja) | 2002-11-01 | 2010-07-14 | バイエル・ヘルスケア・エルエルシー | 巨大分子濃縮方法 |
| FR2853551B1 (fr) | 2003-04-09 | 2006-08-04 | Lab Francais Du Fractionnement | Formulation stabilisante pour compositions d'immunoglobulines g sous forme liquide et sous forme lyophilisee |
| JPWO2005063291A1 (ja) * | 2003-12-25 | 2007-07-19 | 麒麟麦酒株式会社 | 抗体を含有する安定な水性医薬製剤 |
| WO2006022599A1 (en) | 2004-08-27 | 2006-03-02 | Marian Metke | Production method for exfoliated graphite, equipment for its production, exfoliated graphite and means of its use |
| MX2007015476A (es) * | 2005-06-14 | 2008-02-25 | Amgen Inc | Formulaciones de proteina autoamortiguadoras. |
| PT1962886E (pt) | 2005-12-20 | 2014-01-07 | Bristol Myers Squibb Co | Formulações de proteína estáveis |
| WO2007092772A2 (en) | 2006-02-03 | 2007-08-16 | Medimmune, Inc. | Protein formulations |
| TW200833357A (en) | 2006-10-20 | 2008-08-16 | Amgen Inc | Stable polypeptide formulations |
| JP5456658B2 (ja) * | 2007-03-30 | 2014-04-02 | メディミューン，エルエルシー | 抗体製剤 |
| MX2009011408A (es) | 2007-05-02 | 2009-11-05 | Hoffmann La Roche | Metodo para estabilizar una proteina. |
| WO2009015345A1 (en) | 2007-07-25 | 2009-01-29 | Amgen Inc. | Pharmaceutical compositions comprising fc fusion proteins |
| US20090151807A1 (en) | 2007-08-07 | 2009-06-18 | Davis Chanda Janese | Container Insert for Zero Headspace |
| US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
| US20130195888A1 (en) | 2007-11-30 | 2013-08-01 | Abbvie | Ultrafiltration and diafiltration formulation methods for protein processing |
| TW200938221A (en) * | 2007-11-30 | 2009-09-16 | Abbott Lab | Protein formulations and methods of making same |
| WO2009073805A2 (en) | 2007-12-04 | 2009-06-11 | Verdezyne, Inc. | Aglycosylated therapeutic antibodies and therapeutic antibody-encoding nucleotide sequences |
| PE20091174A1 (es) * | 2007-12-27 | 2009-08-03 | Chugai Pharmaceutical Co Ltd | Formulacion liquida con contenido de alta concentracion de anticuerpo |
| NZ601913A (en) * | 2008-01-15 | 2014-02-28 | Abbott Gmbh & Co Kg | Powdered protein compositions and methods of making same |
| EP2350127B1 (en) * | 2008-10-20 | 2015-01-28 | AbbVie Inc. | Isolation and purification of antibodies using protein a affinity chromatography |
| CN104398471A (zh) | 2008-11-28 | 2015-03-11 | Abbvie公司 | 稳定的抗体组合物和用于稳定其的方法 |
| CA2744510A1 (en) | 2008-12-09 | 2010-06-17 | F.Hoffmann-La Roche Ag | Method for obtaining an excipient-free antibody solution |
| CN104490767A (zh) | 2009-05-04 | 2015-04-08 | 艾伯维生物技术有限公司 | 人抗TNF-α抗体的稳定高蛋白质浓度制剂 |
| KR101333276B1 (ko) | 2009-11-20 | 2013-11-27 | 센트로 데 인무노로지아 몰레큘라 | 항체의 제제 |
| BR112012013148A2 (pt) * | 2009-12-29 | 2017-03-21 | F Hoffmann - La Roche Ag | formulação farmacêutica e uso |
| JP5937523B2 (ja) * | 2010-03-01 | 2016-06-22 | サイトダイン インコーポレイテッドＣｙｔｏＤｙｎ， Ｉｎｃ． | 濃縮されたタンパク質製剤およびその使用 |
| EP2568960B1 (en) | 2010-05-10 | 2018-06-06 | Intas Pharmaceuticals Ltd. | Liquid formulation of polypeptides containing an fc domain of an immunoglobulin |
| FR2961107B1 (fr) | 2010-06-15 | 2012-07-27 | Lab Francais Du Fractionnement | Composition d'immunoglobulines humaines stabilisee |
| CH703405B1 (de) | 2010-07-05 | 2014-05-15 | Melexis Tessenderlo Nv | Magnetischer Winkelsensor. |
| US9505829B2 (en) * | 2010-08-19 | 2016-11-29 | Zoetis Belgium S.A. | Anti-NGF antibodies and their use |
| JP2013544762A (ja) * | 2010-09-17 | 2013-12-19 | バクスター、インターナショナル、インコーポレイテッド | 弱酸性〜中性のｐＨにおける、塩化ナトリウムを有する水性製剤を介した免疫グロブリンおよび他のタンパク質の安定化 |
| TWI606840B (zh) * | 2010-11-11 | 2017-12-01 | 艾伯維生物技術有限責任公司 | 具有增進高濃度之抗-ＴＮＦα抗體之液體調配物 |
| EP2471554A1 (en) | 2010-12-28 | 2012-07-04 | Hexal AG | Pharmaceutical formulation comprising a biopharmaceutical drug |
| EP2699265B1 (en) | 2011-04-20 | 2019-10-16 | Sandoz AG | STABLE PHARMACEUTICAL LIQUID FORMULATIONS OF THE FUSION PROTEIN TNFR:Fc |
| CN103547315A (zh) | 2011-05-19 | 2014-01-29 | 诺华股份有限公司 | 用于治疗腺样囊性癌的4-氨基-5-氟-3-[6-(4-甲基哌嗪-1-基)-1h-苯并咪唑-2-基]-1h-喹啉-2-酮 |
| UY34105A (es) | 2011-06-03 | 2012-07-31 | Lg Life Sciences Ltd | Formulación líquida estable de etanercept |
| EA026226B1 (ru) | 2011-07-01 | 2017-03-31 | Байоджен Айдек Ма Инк. | Не содержащие аргинина композиции слитого fc-полипептида и способы их применения |
| GB201112429D0 (en) | 2011-07-19 | 2011-08-31 | Glaxo Group Ltd | Antigen-binding proteins with increased FcRn binding |
| BR112014010186A2 (pt) | 2011-10-28 | 2017-05-02 | Integritybio Inc | formulação farmacêutica estável, kit, composição farmacêutica, método para preparar uma formulação farmacêutica, e, método para tratar um humano ou animal |
| WO2013096835A1 (en) | 2011-12-23 | 2013-06-27 | Abbvie Inc. | Stable protein formulations |
| WO2013164837A1 (en) | 2012-03-07 | 2013-11-07 | Cadila Healthcare Limited | Pharmaceutical formulations of tnf-alpha antibodies |
| EP2863951A1 (en) | 2012-06-12 | 2015-04-29 | Boehringer Ingelheim International GmbH | Pharmaceutical formulation for a therapeutic antibody |
| US20150102042A1 (en) | 2012-07-10 | 2015-04-16 | Gary Matsch | Air Purging Lid |
| CN104768576A (zh) | 2012-09-07 | 2015-07-08 | 科荣生生物科学公司 | 稳定的阿达木单抗水性制剂 |
| WO2014099636A1 (en) | 2012-12-18 | 2014-06-26 | Merck Sharp & Dohme Corp. | Liquid formulations for an anti-tnf alpha antibody |
| CN102988984B (zh) | 2012-12-21 | 2015-05-20 | 嘉和生物药业有限公司 | 增强稳定性的抗TNF-α人单克隆抗体的含水药物制剂 |
| EP2996621B1 (en) | 2013-05-13 | 2018-06-20 | EndoChoice, Inc. | An endoscope tip position visual indicator and heat management system |
| US9681695B2 (en) | 2013-07-31 | 2017-06-20 | Sport Maska Inc. | Helmet with chin cup |
-
2013
- 2013-09-06 CN CN201380058126.8A patent/CN104768576A/zh active Pending
- 2013-09-06 HR HRP20200434TT patent/HRP20200434T1/hr unknown
- 2013-09-06 US US14/020,733 patent/US20140186361A1/en not_active Abandoned
- 2013-09-06 EP EP13835291.9A patent/EP2892550B1/en active Active
- 2013-09-06 SM SM20200147T patent/SMT202000147T1/it unknown
- 2013-09-06 CA CA2884182A patent/CA2884182C/en active Active
- 2013-09-06 ES ES13835291T patent/ES2784861T3/es active Active
- 2013-09-06 SI SI201331693T patent/SI2892550T1/sl unknown
- 2013-09-06 PL PL13835291T patent/PL2892550T3/pl unknown
- 2013-09-06 LT LTEP13835291.9T patent/LT2892550T/lt unknown
- 2013-09-06 KR KR1020157008873A patent/KR102238677B1/ko not_active Expired - Fee Related
- 2013-09-06 PE PE2019002434A patent/PE20191815A1/es unknown
- 2013-09-06 EA EA201791717A patent/EA201791717A1/ru unknown
- 2013-09-06 TW TW102132360A patent/TWI698253B/zh not_active IP Right Cessation
- 2013-09-06 DK DK13835291.9T patent/DK2892550T3/da active
- 2013-09-06 SG SG11201501715QA patent/SG11201501715QA/en unknown
- 2013-09-06 AR ARP130103178A patent/AR092470A1/es not_active Application Discontinuation
- 2013-09-06 EA EA201590518A patent/EA029215B1/ru unknown
- 2013-09-06 PT PT138352919T patent/PT2892550T/pt unknown
- 2013-09-06 BR BR112015004984A patent/BR112015004984A2/pt active Search and Examination
- 2013-09-06 WO PCT/US2013/058618 patent/WO2014039903A2/en not_active Ceased
- 2013-09-06 MX MX2015003007A patent/MX2015003007A/es unknown
- 2013-09-06 CA CA3153799A patent/CA3153799A1/en active Pending
- 2013-09-06 JP JP2015531261A patent/JP6463268B2/ja not_active Expired - Fee Related
- 2013-09-06 TW TW109103597A patent/TW202042841A/zh unknown
- 2013-09-06 EP EP19216514.0A patent/EP3701968A1/en not_active Withdrawn
- 2013-09-06 RS RS20200310A patent/RS60226B1/sr unknown
- 2013-09-06 HU HUE13835291A patent/HUE049282T2/hu unknown
- 2013-09-06 SG SG10201705668XA patent/SG10201705668XA/en unknown
- 2013-09-06 PE PE2015000306A patent/PE20150964A1/es not_active Application Discontinuation
- 2013-09-06 AU AU2013312300A patent/AU2013312300A1/en not_active Abandoned
- 2013-09-06 KR KR1020227004460A patent/KR20220025196A/ko not_active Ceased
- 2013-09-06 KR KR1020217010005A patent/KR102362829B1/ko not_active Expired - Fee Related
-
2014
- 2014-02-26 UY UY0001035351A patent/UY35351A/es not_active Application Discontinuation
-
2015
- 2015-03-05 IL IL237583A patent/IL237583B/en active IP Right Review Request
- 2015-03-06 DO DO2015000051A patent/DOP2015000051A/es unknown
- 2015-03-06 CL CL2015000574A patent/CL2015000574A1/es unknown
- 2015-03-10 US US14/643,844 patent/US9340611B2/en not_active Expired - Fee Related
- 2015-03-18 US US14/661,938 patent/US9382317B2/en not_active Expired - Fee Related
- 2015-03-18 US US14/661,899 patent/US9346880B2/en not_active Expired - Fee Related
- 2015-03-18 US US14/661,849 patent/US9782479B2/en not_active Expired - Fee Related
- 2015-03-18 US US14/661,288 patent/US9340612B2/en not_active Expired - Fee Related
- 2015-04-06 EC ECIEPI201513227A patent/ECSP15013227A/es unknown
- 2015-10-09 US US14/879,847 patent/US9724414B2/en not_active Expired - Fee Related
- 2015-10-09 US US14/879,885 patent/US9808525B2/en not_active Expired - Fee Related
-
2016
- 2016-05-16 US US15/155,982 patent/US9789185B2/en not_active Expired - Fee Related
- 2016-05-16 US US15/155,832 patent/US9682145B2/en not_active Expired - Fee Related
- 2016-05-16 US US15/155,925 patent/US9707293B2/en active Active
- 2016-05-23 US US15/162,140 patent/US9757454B2/en not_active Expired - Fee Related
- 2016-06-27 US US15/193,454 patent/US9782480B2/en not_active Expired - Fee Related
- 2016-06-27 US US15/193,387 patent/US9731008B2/en not_active Expired - Fee Related
- 2016-06-27 US US15/193,486 patent/US9724415B2/en not_active Expired - Fee Related
- 2016-06-27 US US15/193,345 patent/US9770507B2/en not_active Expired - Fee Related
- 2016-06-27 US US15/193,523 patent/US9731009B2/en not_active Expired - Fee Related
- 2016-06-27 US US15/193,415 patent/US9737600B2/en not_active Expired - Fee Related
- 2016-11-23 US US15/360,678 patent/US9861695B2/en active Active
-
2017
- 2017-07-18 US US15/653,228 patent/US10780163B2/en active Active
- 2017-08-15 US US15/677,857 patent/US10786566B2/en active Active
- 2017-10-05 US US15/726,165 patent/US10159732B2/en active Active
- 2017-10-05 US US15/726,195 patent/US10207000B2/en active Active
- 2017-10-05 US US15/726,215 patent/US10159733B2/en active Active
- 2017-10-10 US US15/729,295 patent/US10286072B2/en active Active
- 2017-10-10 US US15/729,243 patent/US10286071B2/en active Active
- 2017-10-11 US US15/730,425 patent/US20180028656A1/en not_active Abandoned
- 2017-10-11 US US15/730,399 patent/US20180028655A1/en not_active Abandoned
- 2017-10-11 US US15/730,445 patent/US20180028657A1/en not_active Abandoned
- 2017-10-31 US US15/799,851 patent/US10155039B2/en active Active
-
2018
- 2018-01-09 US US15/866,154 patent/US10195275B2/en active Active
- 2018-06-29 US US16/023,161 patent/US10799585B2/en active Active
- 2018-06-29 US US16/023,046 patent/US10772959B2/en active Active
- 2018-06-29 US US16/023,205 patent/US10688183B2/en not_active Expired - Fee Related
- 2018-06-29 US US16/023,152 patent/US10772960B2/en active Active
- 2018-07-26 AU AU2018208699A patent/AU2018208699A1/en not_active Abandoned
- 2018-11-01 US US16/178,137 patent/US10722579B2/en not_active Expired - Fee Related
- 2018-11-01 US US16/178,164 patent/US10716852B2/en not_active Expired - Fee Related
- 2018-11-01 US US16/178,319 patent/US10716854B2/en not_active Expired - Fee Related
- 2018-11-01 US US16/178,309 patent/US10716853B2/en not_active Expired - Fee Related
- 2018-12-27 JP JP2018244382A patent/JP6783845B2/ja not_active Expired - Fee Related
-
2020
- 2020-03-18 CY CY20201100247T patent/CY1123407T1/el unknown
- 2020-05-01 AU AU2020202912A patent/AU2020202912A1/en not_active Abandoned
- 2020-09-29 IL IL277652A patent/IL277652B2/en unknown
- 2020-10-21 JP JP2020176477A patent/JP2021020930A/ja not_active Ceased
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10722579B2 (en) | Stable aqueous formulations of adalimumab |