JP2009503105A - 免疫複合体製剤 - Google Patents
免疫複合体製剤 Download PDFInfo
- Publication number
- JP2009503105A JP2009503105A JP2008525189A JP2008525189A JP2009503105A JP 2009503105 A JP2009503105 A JP 2009503105A JP 2008525189 A JP2008525189 A JP 2008525189A JP 2008525189 A JP2008525189 A JP 2008525189A JP 2009503105 A JP2009503105 A JP 2009503105A
- Authority
- JP
- Japan
- Prior art keywords
- formulation
- polysorbate
- sucrose
- histidine
- glycine
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 143
- 238000009472 formulation Methods 0.000 claims abstract description 99
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 83
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 51
- 229930006000 Sucrose Natural products 0.000 claims abstract description 47
- 239000005720 sucrose Substances 0.000 claims abstract description 47
- 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 abstract description 44
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims abstract description 42
- 239000004471 Glycine Substances 0.000 claims abstract description 40
- 229940127121 immunoconjugate Drugs 0.000 claims abstract description 38
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 36
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 35
- 229920001213 Polysorbate 20 Polymers 0.000 claims abstract description 26
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims abstract description 26
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims abstract description 26
- 239000011780 sodium chloride Substances 0.000 claims abstract description 25
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims abstract description 24
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 24
- 229940068977 polysorbate 20 Drugs 0.000 claims abstract description 24
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 24
- 229940068968 polysorbate 80 Drugs 0.000 claims abstract description 24
- 239000007864 aqueous solution Substances 0.000 claims abstract description 18
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 14
- 150000001413 amino acids Chemical class 0.000 claims abstract description 13
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 13
- 235000011187 glycerol Nutrition 0.000 claims abstract description 12
- 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 abstract description 11
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims abstract description 11
- 229930195725 Mannitol Natural products 0.000 claims abstract description 11
- 239000000594 mannitol Substances 0.000 claims abstract description 11
- 235000010355 mannitol Nutrition 0.000 claims abstract description 11
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 10
- 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 claims abstract description 8
- 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 claims abstract description 8
- 239000008103 glucose Substances 0.000 claims abstract description 7
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229960004793 sucrose Drugs 0.000 claims abstract description 4
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical compound C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 claims description 22
- 229940127089 cytotoxic agent Drugs 0.000 claims description 15
- 239000002254 cytotoxic agent Substances 0.000 claims description 15
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 15
- 229940123237 Taxane Drugs 0.000 claims description 13
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 7
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 6
- 229960000575 trastuzumab Drugs 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 5
- 239000001116 FEMA 4028 Substances 0.000 claims description 5
- 239000008118 PEG 6000 Substances 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims description 5
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 5
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 5
- 229960004853 betadex Drugs 0.000 claims description 5
- 229960004641 rituximab Drugs 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- 239000002245 particle Substances 0.000 abstract description 33
- 210000004027 cell Anatomy 0.000 description 54
- 125000004432 carbon atom Chemical group C* 0.000 description 38
- 125000005647 linker group Chemical group 0.000 description 38
- 125000003342 alkenyl group Chemical group 0.000 description 33
- 239000003814 drug Substances 0.000 description 31
- 238000000034 method Methods 0.000 description 30
- 239000000427 antigen Substances 0.000 description 28
- 102000036639 antigens Human genes 0.000 description 27
- 235000002639 sodium chloride Nutrition 0.000 description 27
- 108091007433 antigens Proteins 0.000 description 26
- 150000001875 compounds Chemical class 0.000 description 26
- 229940079593 drug Drugs 0.000 description 26
- -1 immunoconjugates Chemical class 0.000 description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 18
- 206010028980 Neoplasm Diseases 0.000 description 16
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 15
- 239000000945 filler Substances 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 14
- 201000011510 cancer Diseases 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 239000008194 pharmaceutical composition Substances 0.000 description 13
- 238000003860 storage Methods 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 229960005558 mertansine Drugs 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 11
- 230000027455 binding Effects 0.000 description 11
- 239000012634 fragment Substances 0.000 description 10
- 239000001509 sodium citrate Substances 0.000 description 10
- 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 10
- QWPXBEHQFHACTK-KZVYIGENSA-N (10e,12e)-86-chloro-12,14,4-trihydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-15,16-dihydro-14h-7-aza-1(6,4)-oxazina-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-6-one Chemical compound CN1C(=O)CC(O)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 QWPXBEHQFHACTK-KZVYIGENSA-N 0.000 description 9
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 9
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 9
- 239000011230 binding agent Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 210000004408 hybridoma Anatomy 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 239000006172 buffering agent Substances 0.000 description 8
- 239000003431 cross linking reagent Substances 0.000 description 8
- 229920000136 polysorbate Polymers 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 231100000433 cytotoxic Toxicity 0.000 description 7
- 230000001472 cytotoxic effect Effects 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 125000003107 substituted aryl group Chemical group 0.000 description 7
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 6
- 210000003719 b-lymphocyte Anatomy 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- ANZJBCHSOXCCRQ-FKUXLPTCSA-N mertansine Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)[C@@H](C)[C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(=O)CCS)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 ANZJBCHSOXCCRQ-FKUXLPTCSA-N 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- QWPXBEHQFHACTK-UHFFFAOYSA-N Maytansinol Natural products CN1C(=O)CC(O)C2(C)OC2C(C)C(OC(=O)N2)CC2(O)C(OC)C=CC=C(C)CC2=CC(OC)=C(Cl)C1=C2 QWPXBEHQFHACTK-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 241001529936 Murinae Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 5
- 229950008882 polysorbate Drugs 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 229930126263 Maytansine Natural products 0.000 description 4
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 125000002228 disulfide group Chemical group 0.000 description 4
- AMRJKAQTDDKMCE-UHFFFAOYSA-N dolastatin Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)C)C(OC)CC(=O)N1CCCC1C(OC)C(C)C(=O)NC(C=1SC=CN=1)CC1=CC=CC=C1 AMRJKAQTDDKMCE-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000008176 lyophilized powder Substances 0.000 description 4
- WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 4
- 235000019833 protease Nutrition 0.000 description 4
- 229940074404 sodium succinate Drugs 0.000 description 4
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 150000003573 thiols Chemical class 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- GTBCXYYVWHFQRS-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(pyridin-2-yldisulfanyl)pentanoate Chemical compound C=1C=CC=NC=1SSC(C)CCC(=O)ON1C(=O)CCC1=O GTBCXYYVWHFQRS-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 108090000371 Esterases Proteins 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 241000187747 Streptomyces Species 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 230000002152 alkylating effect Effects 0.000 description 3
- 230000001588 bifunctional effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000003636 chemical group Chemical group 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 229960003668 docetaxel Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012669 liquid formulation Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 229940068965 polysorbates Drugs 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000008362 succinate buffer Substances 0.000 description 3
- 125000000185 sucrose group Chemical group 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 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 2
- NKUZQMZWTZAPSN-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-bromoacetate Chemical compound BrCC(=O)ON1C(=O)CCC1=O NKUZQMZWTZAPSN-UHFFFAOYSA-N 0.000 description 2
- VRDGQQTWSGDXCU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-iodoacetate Chemical compound ICC(=O)ON1C(=O)CCC1=O VRDGQQTWSGDXCU-UHFFFAOYSA-N 0.000 description 2
- LLXVXPPXELIDGQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)benzoate Chemical compound C=1C=CC(N2C(C=CC2=O)=O)=CC=1C(=O)ON1C(=O)CCC1=O LLXVXPPXELIDGQ-UHFFFAOYSA-N 0.000 description 2
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 2
- WGMMKWFUXPMTRW-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[(2-bromoacetyl)amino]propanoate Chemical compound BrCC(=O)NCCC(=O)ON1C(=O)CCC1=O WGMMKWFUXPMTRW-UHFFFAOYSA-N 0.000 description 2
- PVGATNRYUYNBHO-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(2,5-dioxopyrrol-1-yl)butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O PVGATNRYUYNBHO-UHFFFAOYSA-N 0.000 description 2
- PMJWDPGOWBRILU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCC(C=C1)=CC=C1N1C(=O)C=CC1=O PMJWDPGOWBRILU-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 241000189662 Calla Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 230000004568 DNA-binding Effects 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 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
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 102000003729 Neprilysin Human genes 0.000 description 2
- 108090000028 Neprilysin Proteins 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 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 2
- DGBBXVWXOHSLTG-UMDRASRXSA-N ansamitocin p 2 Chemical compound C([C@@H]([C@@]1(O[C@H]1[C@@H]1C)C)OC(=O)CC)C(=O)N(C)C(C(=C(OC)C=2)Cl)=CC=2C\C(C)=C\C=C\[C@@H](OC)[C@]2(O)NC(=O)O[C@H]1C2 DGBBXVWXOHSLTG-UMDRASRXSA-N 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000007813 chromatographic assay Methods 0.000 description 2
- 230000000536 complexating effect Effects 0.000 description 2
- 239000000562 conjugate Substances 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000017858 demethylation Effects 0.000 description 2
- 238000010520 demethylation reaction Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229930188854 dolastatin Natural products 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 125000005179 haloacetyl group Chemical group 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 2
- 239000012931 lyophilized formulation Substances 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 229920001542 oligosaccharide Polymers 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 239000012905 visible particle Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- TYKASZBHFXBROF-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-(2,5-dioxopyrrol-1-yl)acetate Chemical compound O=C1CCC(=O)N1OC(=O)CN1C(=O)C=CC1=O TYKASZBHFXBROF-UHFFFAOYSA-N 0.000 description 1
- JSHOVKSMJRQOGY-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(pyridin-2-yldisulfanyl)butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCSSC1=CC=CC=N1 JSHOVKSMJRQOGY-UHFFFAOYSA-N 0.000 description 1
- IHVODYOQUSEYJJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]amino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)C(CC1)CCC1CN1C(=O)C=CC1=O IHVODYOQUSEYJJ-UHFFFAOYSA-N 0.000 description 1
- DLKUYSQUHXBYPB-NSSHGSRYSA-N (2s,4r)-4-[[2-[(1r,3r)-1-acetyloxy-4-methyl-3-[3-methylbutanoyloxymethyl-[(2s,3s)-3-methyl-2-[[(2r)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-(4-methylphenyl)pentanoic acid Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC(C)C)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC(C)=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C DLKUYSQUHXBYPB-NSSHGSRYSA-N 0.000 description 1
- OJQSISYVGFJJBY-UHFFFAOYSA-N 1-(4-isocyanatophenyl)pyrrole-2,5-dione Chemical compound C1=CC(N=C=O)=CC=C1N1C(=O)C=CC1=O OJQSISYVGFJJBY-UHFFFAOYSA-N 0.000 description 1
- OWDQCSBZQVISPN-UHFFFAOYSA-N 2-[(2,5-dioxopyrrolidin-1-yl)amino]-4-(2-iodoacetyl)benzoic acid Chemical compound OC(=O)C1=CC=C(C(=O)CI)C=C1NN1C(=O)CCC1=O OWDQCSBZQVISPN-UHFFFAOYSA-N 0.000 description 1
- HBEDKBRARKFPIC-UHFFFAOYSA-N 6-(2,5-dioxopyrrol-1-yl)hexanoic acid;1-hydroxypyrrolidine-2,5-dione Chemical compound ON1C(=O)CCC1=O.OC(=O)CCCCCN1C(=O)C=CC1=O HBEDKBRARKFPIC-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- DGBBXVWXOHSLTG-UHFFFAOYSA-N Ansamitocin P2 Natural products CC1C2OC2(C)C(OC(=O)CC)CC(=O)N(C)C(C(=C(OC)C=2)Cl)=CC=2CC(C)=CC=CC(OC)C2(O)NC(=O)OC1C2 DGBBXVWXOHSLTG-UHFFFAOYSA-N 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 0 C[C@@](C(OC(CC(N(C)c(cc(CC(C)=CC=CC(*)C(C1)(N2)O)cc3OC)c3Cl)=O)C3(C)OC3C(C)C1OC2=O)=O)N(C)C(*)=O Chemical compound C[C@@](C(OC(CC(N(C)c(cc(CC(C)=CC=CC(*)C(C1)(N2)O)cc3OC)c3Cl)=O)C3(C)OC3C(C)C1OC2=O)=O)N(C)C(*)=O 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 101100421450 Drosophila melanogaster Shark gene Proteins 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- 101710181478 Envelope glycoprotein GP350 Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101001099381 Homo sapiens Peroxisomal biogenesis factor 19 Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 240000001427 Mallotus nudiflorus Species 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 241000187654 Nocardia Species 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 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
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102100038883 Peroxisomal biogenesis factor 19 Human genes 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 108010029180 Sialic Acid Binding Ig-like Lectin 3 Proteins 0.000 description 1
- 102000001555 Sialic Acid Binding Ig-like Lectin 3 Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 102000004584 Somatomedin Receptors Human genes 0.000 description 1
- 108010017622 Somatomedin Receptors Proteins 0.000 description 1
- 231100000632 Spindle poison Toxicity 0.000 description 1
- 241000133426 Streptomyces zelensis Species 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 101000980463 Treponema pallidum (strain Nichols) Chaperonin GroEL Proteins 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 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
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 239000000611 antibody drug conjugate Substances 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 229940049595 antibody-drug conjugate Drugs 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 239000013602 bacteriophage vector Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229950002903 bivatuzumab Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 1
- 229930195731 calicheamicin Natural products 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 102000008395 cell adhesion mediator activity proteins Human genes 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
- 229960001270 d- tartaric acid Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000006240 deamidation Effects 0.000 description 1
- 238000006298 dechlorination reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 125000005414 dithiopyridyl group Chemical group 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229960005501 duocarmycin Drugs 0.000 description 1
- 229930184221 duocarmycin Natural products 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 239000012537 formulation buffer Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 238000013415 human tumor xenograft model Methods 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000011147 magnesium chloride Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 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
- 210000004962 mammalian cell Anatomy 0.000 description 1
- SVVGCFZPFZGWRG-OTKBOCOUSA-N maytansinoid dm4 Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)C(C)(C)[C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(=O)CCC(C)(C)S)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 SVVGCFZPFZGWRG-OTKBOCOUSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- 229960003151 mercaptamine Drugs 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 210000004412 neuroendocrine cell Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920000889 poly(m-phenylene isophthalamide) Polymers 0.000 description 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- ZCOSUVZGFDGWFV-UHFFFAOYSA-N pyrrolo[2,3-e]indole Chemical compound C1=CC2=NC=CC2=C2N=CC=C21 ZCOSUVZGFDGWFV-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229950008684 sibrotuzumab Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- RCINICONZNJXQF-XAZOAEDWSA-N taxol® Chemical compound O([C@@H]1[C@@]2(CC(C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3(C21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-XAZOAEDWSA-N 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 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
- 229930184737 tubulysin Natural products 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
-
- 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
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6863—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from stomach or intestines cancer cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61K47/26—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
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
Abstract
Description
[02]本発明は、抗体、および1つまたは数個の共有結合により連結された薬剤の分子、で構成される医薬化合物である、免疫複合体(immunoconjugate)の安定な製剤の調製のための方法に関する。
[03]免疫複合体は、癌およびその他の状態の治療のための、非常に強力かつ特異的な物質として開発されている。免疫複合体は、標的細胞抗原、例えば腫瘍細胞抗原、を特異的に認識する抗体、および1つまたは数個の共有結合により連結された薬剤の分子、特に細胞毒性薬剤、例えばメイタンシノイド、タキサン、またはCC−1065類似体、から構成される。そのような免疫複合体に対して使用されるもう1つの名称は、抗体−薬剤複合体である。免疫複合体は、循環血中では不活性であるが、標的細胞表面に結合すると、細胞により内部に取り込まれる。まだ完全には理解されていないメカニズムにより、薬剤はその後抗体からはずれ、それらの薬理学的効果を発することができる。
[10]本発明は、免疫複合体の医薬組成物中の粒子および凝集体の形成は、ある種の賦形剤を使用することにより阻害することができる、という発見に基づく。この新規製剤は、医薬化合物のより高い安定性および実質的により長い有効期間をもたらし、患者の安全性の保証を提供する。
[14]本発明は、粒子および/または凝集体が実質的に存在しない、そして長期間の保存にわたり、また輸送中も粒子および/または凝集体が実質的に存在しないままである、免疫複合体の安定な医薬組成物を提供する。本発明は、免疫複合体の医薬組成物中の粒子および凝集体の形成が、ある種の賦形剤を使用することにより阻害することができる、という発見に基づく。新規製剤は、医薬化合物のより高い安定性および実質的により長い有効期間をもたらし、患者の安全性の保証を提供する。
およびDS6を含む。前立腺癌細胞はまた、細胞結合物質として抗前立腺特異膜抗原(PSMA)、例えばJ591を使用することにより、免疫複合体を用いて標的に向かわせることができる(例えばLiu et al., Cancer Res., 57: 3629-3634 (1997)を参照のこと)。さらにHer2抗原を発現する癌細胞、例えば乳癌、前立腺癌および卵巣癌の細胞は、抗体トラスツツマブを使用して標的に向かわせることができる。インスリン様増殖因子受容体に結合する抗−IGF−IR抗体もまた、免疫複合体において使用することができる。
ここでR1およびR2は、各々独立して1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、好ましくはCH3もしくはC2H5、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、フェニル、置換されたフェニル、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、そしてここでR2はまた、Hであることもでき、
ここでA、B、Dは3−10の炭素原子を有するシクロアルキルもしくはシクロアルケニル、シンプルなアリールもしくは置換されたアリール、または複素環式芳香族、もしくはヘテロシクロアルキルのラジカルであり、
ここでR3、R4、R5、R6、R7、R8、R9、R10、R11、およびR12は各々独立して、H、1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、好ましくはCH3もしくはC2H5、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、フェニル、置換されたフェニル、または複素環式芳香族、もしくはヘテロシクロアルキルのラジカルであり、
ここでl、m、n、p、q、r、s、u、およびtは、各々独立してゼロ、または1から5の整数であるが、ただしl、m、n、p、q、r、s、u、およびtの少なくとも2つは、いずれの時にも同時にゼロではなく、そして
ここでZはH、SRまたはCORであり、ここでRは、1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、シンプルなアリールもしくは置換されたアリール、または複素環式芳香族、もしくはヘテロシクロアルキルのラジカルである。
ここでR1およびR2は、各々独立してH、1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、好ましくはCH3もしくはC2H5、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、フェニル、置換されたフェニル、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、
ここでR3、R4、R5、R6、R7、およびR8はおのおの独立して、H、1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、好ましくはCH3もしくはC2H5、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、フェニル、置換されたフェニル、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、
ここでl、m、およびnは、各々独立して1から5の整数であり、そして加えてnはゼロであることができ、
ここでZはH、SRまたはCORであり、ここでRは、1から10の炭素原子を有する直鎖もしくは分枝鎖のアルキルもしくはアルケニル、3から10の炭素原子を有する環式のアルキルもしくはアルケニル、またはシンプルなアリールもしくは置換されたアリール、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、そして
ここでMayは、C−3、C−14ヒドロキシメチル、C−15ヒドロキシ、またはC−20デスメチルに側鎖を持つメイタンシノイドを表す。
ここでR1およびR2は、各々独立してH、1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、好ましくはCH3もしくはC2H5、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、フェニル、置換されたフェニル、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、ここでR3、R4、R5、R6、R7、およびR8はおのおの独立して、H、1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、好ましくはCH3もしくはC2H5、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、フェニル、置換されたフェニル、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、
ここでl、m、およびnは、各々独立して1から5の整数であり、そして加えてnはゼロであることができ、そして
ここでZはH、SRまたは−CORであり、ここでRは、メチル、1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、またはシンプルなアリールもしくは置換されたアリール、または複素環式芳香族ラジカルもしくはヘテロシクロアルキルのラジカルである。
ここでR1およびR2は、各々独立して1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、好ましくはCH3もしくはC2H5、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、フェニル、置換されたフェニル、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、そしてここでR2はまた、Hであることもでき、
ここでR3、R4、R5、R6、R7、およびR8はおのおの独立して、H、1から10の炭素原子を有する直鎖環式のアルキルもしくはアルケニル、好ましくはCH3もしくはC2H5、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、フェニル、置換されたフェニル、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、
ここでl、m、およびnは、各々独立して1から5の整数であり、そして加えてnはゼロであることができ、
ここでZ2はSRまたはCORであり、ここでRは、1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、またはシンプルなアリールもしくは置換されたアリール、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、そして
ここでMayは、メイタンシノイドである。
ここでR1およびR2は、各々独立して、H、1から10の炭素原子を有する直鎖もしくは分枝鎖のアルキルもしくはアルケニル、好ましくはCH3もしくはC2H5、3から10の炭素原子を有する環式のアルキルもしくはアルケニル、フェニル、置換されたフェニル、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、ここでA、B、およびDは、各々独立して3から10の炭素原子を有するシクロアルキルもしくはシクロアルケニル、シンプルなアリールもしくは置換されたアリール、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、
ここでR3、R4、R5、R6、R7、R8、R9、R10、R11、およびR12は、各々独立してH、1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、好ましくはCH3もしくはC2H5、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、フェニル、置換されたフェニル、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルであり、
ここでl、m、n、p、q、r、s、tおよびuは、各々独立してゼロ、または1から5の整数であるが、ただしl、m、n、p、q、r、s、t、およびuの少なくとも2つは、いずれの時にも同時にゼロではなく、そして
ここでZ2はSRまたは−CORであり、ここでRは、1から10の炭素原子を有する直鎖のアルキルもしくはアルケニル、3から10の炭素原子を有する分枝鎖もしくは環式のアルキルもしくはアルケニル、シンプルなアリールもしくは置換されたアリール、または複素環式芳香族もしくはヘテロシクロアルキルのラジカルである。
[107]この実施例は、製剤化したMAb−DM1複合体サンプルの視覚的外観における、以下の製剤の賦形剤の効果を示す。
[109]この実施例は、複合体の凝集に関して、huN901−SPP−DM1の安定性におけるアミノ酸の効果を示す。
[112]この実施例は、複合体の凝集体の点から、huMy9−6−SPDB−DM4の安定性におけるヒスチジンの効果を示す。
(1)10mM クエン酸ナトリウム、135mM NaCl、pH5.5
(2)150mM ヒスチジン/ヒスチジン塩化物、pH5.5
中に5.0mg/mLにて製剤化した。
[116]この実施例は、複合体の凝集体に関して、huC242−SPDB−DM4の安定性における、緩衝化剤、糖質およびアミノ酸の効果を示す。
(1)10mM クエン酸ナトリウム、135mM NaCl、pH5.5
(2)10mM クエン酸ナトリウム、5% ショ糖、130mM グリシン、0.1%ポリソルベート80、pH5.5
(3)10mM ヒスチジン/ヒスチジン塩化物、5% ショ糖、130mM グリシン、pH5.5
中に5.0mg/mL。
[120]この実施例は、huN901−SPP−DM1複合体の凝集体の含有量における、グリシンと共にまたは含まずにショ糖を含有する様々な製剤の効果を示す。
(2)10mM クエン酸ナトリウム、60mM NaCl、5% ショ糖、pH5.5
(3)10mM クエン酸ナトリウム、60mM NaCl、0.01% ポリソルベート20、5% ショ糖、pH5.5
(4)10mM リン酸ナトリウム、140mM NaCl、pH6.5
(5)10mM コハク酸ナトリウム、0.25M グリシン、0.01% ポリソルベート20、0.5% ショ糖、pH5.5
[122]25℃で保存したサンプルを、3、6および12ヶ月の時点で凝集体の含有量について検査した。
[124]この実施例は、撹拌により誘発される粒子の形成における、ポリソルベート80の効果を示す。このストレスの状態(撹拌)は、静的保存(実施例1で検討している)の間に遭遇するストレスとは反対に、液体の複合体を輸送し取り扱う間に遭遇する擬似的ストレスと期待される。
(2)10mM ヒスチジン、5% ショ糖、130mM グリシン、pH5.5
(3)10mM ヒスチジン、5% ショ糖、130mM グリシン、0.1% ポリソルベート80、pH5.5
(4)10mM ヒスチジン、1% ショ糖、250mM グリシン、pH5.5
(5)10mM ヒスチジン、1% ショ糖、250mM グリシン、0.1% ポリソルベート80、pH5.5
(6)10mM ヒスチジン、280mM グリシン、pH5.5
(7)10mM ヒスチジン、280mM グリシン、0.1% ポリソルベート80、pH5.5
(8)10mM ヒスチジン、10% ショ糖、pH5.5
(9)10mM ヒスチジン、10% ショ糖、0.1% ポリソルベート80、pH5.5
[126]48時間震盪後、すべてのバイアルを目視により検討した。ポリソルベート80を含有したもの(組成3、5、7および9)は透明のままだったが、ポリソルベート80を含有しなかったもの(組成1、2、4、6および8)はすべて濁っていた。これらのデータは、液体複合体の輸送および取り扱いの間に遭遇すると思われるような、撹拌による粒子を低減する上での、ポリソルベート80の有益な効果を実証する。
Claims (21)
- 以下:
(a)免疫複合体;ならびに
(b)ショ糖、ポリソルベート20、ポリソルベート80、シクロデキストリン、ブドウ糖、グリセロール、ポリエチレングリコール、マンニトール、塩化ナトリウム、およびアミノ酸、から成る群より選択される1つまたはそれより多くの賦形剤、
を包含する免疫複合体製剤であって、
製剤が、pH4.5から7.6を有する緩衝化水溶液である、前記免疫複合体製剤。 - 製剤が、以下:
(i)0.1−12% ショ糖、
(ii)0.005−1.0% ポリソルベート20、
(iii)0.5−2% ベータ−シクロデキストリン、
(iv)2−8% グリセロール、
(v)1−5% PEG6000、
(vi)2−8% マンニトール、
(vii)0.005−1.0% ポリソルベート80、
(viii)5−20mM ヒスチジン、
(ix)100−300mM グリシン、および
(x)50−300mM 塩化ナトリウム、
から成る群より選択される1つまたはそれより多くの賦形剤を包含する、請求項1に記載の製剤。 - 製剤が、以下:
(i)5−10% ショ糖、
(ii)0.005−0.2% ポリソルベート20、
(iii)0.5−1% ベータ−シクロデキストリン、
(iv)2−5% グリセロール、
(v)2−3% PEG6000、
(vi)3−5% マンニトール、
(vii)0.005−0.2% ポリソルベート80、
(viii)10−15mM ヒスチジン、
(ix)130−250mM グリシン、および
(x)100−200mM 塩化ナトリウム
から成る群より選択される1つまたはそれより多くの賦形剤を包含する、請求項2に記載の製剤。 - 緩衝化水溶液が、ヒスチジン、コハク酸塩、クエン酸塩、リン酸塩、および酢酸塩の1つまたはそれより多く含有する、請求項1に記載の製剤。
- pHが5.0から7.0である、請求項4に記載の製剤。
- pHが5.0から6.0である、請求項5に記載の製剤。
- 免疫複合体が、huMy9−6、huC242、huN901、DS6、トラスツツマブ、ビバツツマブ、シブロツツマブ、およびリツキシマブ、から成る群より選択されるヒト化抗体を包含する、請求項1に記載の製剤。
- 免疫複合体が、メイタンシノイド、タキサン、およびCC−1065、から成る群より選択される細胞毒性薬剤を包含する、請求項1に記載の製剤。
- 以下:
(a)免疫複合体;ならびに
(b)ヒスチジン、ショ糖、グリシン、および塩化ナトリウム、から成る群より選択される、1つまたはそれより多くの賦形剤、
を包含する免疫複合体製剤であって、
製剤が、pH4.5から7.6を有する緩衝化水溶液である、前記免疫複合体製剤。 - 製剤が、5−200mM ヒスチジン、100−200mM グリシン、および2−8% ショ糖、より選択される1つまたはそれより多くの賦形剤を包含する、請求項9に記載の製剤。
- 賦形剤が、5−100mM ヒスチジン、または100−150mM グリシンである、請求項10に記載の製剤。
- 製剤が、2−8% ショ糖、および100−150mM グリシンを含有する、請求項9に記載の製剤。
- 製剤が、10mM ヒスチジン、5% ショ糖、および130mM グリシンを含有する、請求項12に記載の製剤。
- 緩衝化水溶液が、ヒスチジン、コハク酸塩、クエン酸塩、リン酸塩、および酢酸塩の1つまたはそれより多く含有する、請求項9に記載の製剤。
- pHが5.0から7.0である、請求項14に記載の製剤。
- pHが5.0から6.0である、請求項14に記載の製剤。
- ポリソルベート20および/またはポリソルベート80をさらに包含する、請求項9に記載の製剤。
- 免疫複合体が、huMy9−6、huC242、huN901、DS6、トラスツツマブ、ビバツツマブ、シブロツツマブ、およびリツキシマブ、から成る群より選択されるヒト化抗体を包含する、請求項9に記載の製剤。
- 免疫複合体が、メイタンシノイド、タキサン、およびCC−1065、から成る群より選択される細胞毒性薬剤を包含する、請求項9に記載の製剤。
- 本質的には、以下:
(a)0.5−10mg/mlの濃度のhuN901−DM1免疫複合体;
(b)5−15mM ヒスチジン、および/または5−15mM コハク酸塩;
(c)0.1−10% ショ糖、および/または100−300mM グリシン;
(d)0.005−0.2% ポリソルベート80、および/または0.005−0.2% ポリソルベート20、
から成る免疫複合体製剤であって、製剤が、pH5−6を有する緩衝化水溶液である、前記免疫複合体製剤。 - 本質的には、以下:
(a)0.5−10mg/mlの濃度のhuC242−DM4免疫複合体;
(b)5−15mM ヒスチジン;
(c)0.1−10% ショ糖、および/または100−300mM グリシン;
(d)0.005−0.2% ポリソルベート80、および/または0.005−0.2% ポリソルベート20、
から成る免疫複合体製剤であって、製剤が、pH5−6を有する緩衝化水溶液である、前記免疫複合体製剤。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US70490205P | 2005-08-03 | 2005-08-03 | |
US70716205P | 2005-08-11 | 2005-08-11 | |
US74645606P | 2006-05-04 | 2006-05-04 | |
US74645406P | 2006-05-04 | 2006-05-04 | |
PCT/US2006/030295 WO2007019232A2 (en) | 2005-08-03 | 2006-08-02 | Immunoconjugate formulations |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012138483A Division JP2012211163A (ja) | 2005-08-03 | 2012-06-20 | 免疫複合体製剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009503105A true JP2009503105A (ja) | 2009-01-29 |
JP2009503105A5 JP2009503105A5 (ja) | 2011-11-17 |
Family
ID=37727890
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008525189A Pending JP2009503105A (ja) | 2005-08-03 | 2006-08-02 | 免疫複合体製剤 |
JP2012138483A Withdrawn JP2012211163A (ja) | 2005-08-03 | 2012-06-20 | 免疫複合体製剤 |
JP2015157269A Expired - Fee Related JP6389446B2 (ja) | 2005-08-03 | 2015-08-07 | 免疫複合体製剤 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012138483A Withdrawn JP2012211163A (ja) | 2005-08-03 | 2012-06-20 | 免疫複合体製剤 |
JP2015157269A Expired - Fee Related JP6389446B2 (ja) | 2005-08-03 | 2015-08-07 | 免疫複合体製剤 |
Country Status (14)
Country | Link |
---|---|
US (1) | US9114179B2 (ja) |
EP (1) | EP1917030A4 (ja) |
JP (3) | JP2009503105A (ja) |
KR (1) | KR101566393B1 (ja) |
AU (1) | AU2006278573A1 (ja) |
BR (1) | BRPI0614100A2 (ja) |
CA (1) | CA2615122A1 (ja) |
EA (1) | EA014513B1 (ja) |
EC (1) | ECSP088159A (ja) |
IL (1) | IL188733A (ja) |
MX (1) | MX336033B (ja) |
NO (1) | NO20080612L (ja) |
NZ (3) | NZ599176A (ja) |
WO (1) | WO2007019232A2 (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013527832A (ja) * | 2010-03-22 | 2013-07-04 | ジェネンテック, インコーポレイテッド | タンパク質含有製剤の安定化に有用な組成物及び方法 |
JP2016534062A (ja) * | 2013-10-25 | 2016-11-04 | バイエル ファーマ アクチエンゲゼルシャフト | 新規な安定製剤 |
JP2016539118A (ja) * | 2013-11-21 | 2016-12-15 | ゲンマブ エー/エス | 抗体−薬物コンジュゲート凍結乾燥製剤 |
JP2017071631A (ja) * | 2010-09-17 | 2017-04-13 | バクスアルタ ゲーエムベーハー | 弱酸性〜中性のpHにおける、ヒスチジンを有する水性製剤を介した免疫グロブリンの安定化 |
Families Citing this family (95)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7138262B1 (en) | 2000-08-18 | 2006-11-21 | Shire Human Genetic Therapies, Inc. | High mannose proteins and methods of making high mannose proteins |
DK2163256T3 (en) | 2001-05-11 | 2015-12-07 | Ludwig Inst For Cancer Res Ltd | Specific binding proteins and use thereof |
US20100056762A1 (en) | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses thereof |
US20160279239A1 (en) | 2011-05-02 | 2016-09-29 | Immunomedics, Inc. | Subcutaneous administration of anti-cd74 antibody for systemic lupus erythematosus and autoimmune disease |
US20110166319A1 (en) * | 2005-02-11 | 2011-07-07 | Immunogen, Inc. | Process for preparing purified drug conjugates |
US20160355591A1 (en) | 2011-05-02 | 2016-12-08 | Immunomedics, Inc. | Subcutaneous anti-hla-dr monoclonal antibody for treatment of hematologic malignancies |
EP1928503B1 (en) | 2005-08-24 | 2012-10-03 | ImmunoGen, Inc. | Process for preparing maytansinoid antibody conjugates |
AU2007285763B2 (en) | 2006-08-18 | 2011-12-15 | Armagen Technologies, Inc. | Agents for blood-brain barrier delivery |
US7767206B2 (en) | 2006-10-02 | 2010-08-03 | Amgen Inc. | Neutralizing determinants of IL-17 Receptor A and antibodies that bind thereto |
CN104013956B (zh) * | 2007-01-25 | 2018-12-18 | 达娜-法勃肿瘤研究所公司 | 抗egfr抗体在治疗egfr突变体介导的疾病中的用途 |
MX2009009782A (es) * | 2007-03-15 | 2010-09-10 | Ludwig Inst Cancer Res | Metodo de tratamiento que utiliza anticuerpos egfr e inhibidores de src y formulaciones relacionadas. |
EP2182980A4 (en) | 2007-07-27 | 2012-04-18 | Armagen Technologies Inc | METHOD AND COMPOSITIONS FOR INCREASED ALPHA IDURONIDASE ACTIVITY IN THE CNS |
EP2188311B1 (en) | 2007-08-14 | 2016-10-05 | Ludwig Institute for Cancer Research Ltd. | Monoclonal antibody 175 targeting the egf receptor and derivatives and uses thereof |
US8883146B2 (en) | 2007-11-30 | 2014-11-11 | Abbvie Inc. | Protein formulations and methods of making same |
PE20091174A1 (es) | 2007-12-27 | 2009-08-03 | Chugai Pharmaceutical Co Ltd | Formulacion liquida con contenido de alta concentracion de anticuerpo |
US8454960B2 (en) | 2008-01-03 | 2013-06-04 | The Scripps Research Institute | Multispecific antibody targeting and multivalency through modular recognition domains |
US8574577B2 (en) | 2008-01-03 | 2013-11-05 | The Scripps Research Institute | VEGF antibodies comprising modular recognition domains |
US8557243B2 (en) | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | EFGR antibodies comprising modular recognition domains |
US8557242B2 (en) | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | ERBB2 antibodies comprising modular recognition domains |
MX2010007357A (es) | 2008-01-03 | 2011-03-03 | The Scripps Res Institute Star | Puesta de anti-cuerpos en objetivo mediante un dominio de reconocimiento modular. |
WO2010005726A2 (en) | 2008-06-16 | 2010-01-14 | Bind Biosciences Inc. | Therapeutic polymeric nanoparticles with mtor inhibitors and methods of making and using same |
CN104997732A (zh) * | 2008-06-16 | 2015-10-28 | 佰恩德治疗股份有限公司 | 载药的聚合物纳米微粒及其制备和使用方法 |
JP2012501966A (ja) | 2008-06-16 | 2012-01-26 | バインド バイオサイエンシズ インコーポレイテッド | ビンカアルカロイド含有治療用ポリマーナノ粒子並びにその製造方法及び使用方法 |
PE20120169A1 (es) * | 2008-11-17 | 2012-02-29 | Genentech Inc | Metodo y formulacion para reducir la agregacion de una macromolecula bajo condiciones fisiologicas |
WO2010062896A1 (en) * | 2008-11-28 | 2010-06-03 | Abbott Laboratories | Stable antibody compositions and methods for stabilizing same |
WO2010068866A2 (en) * | 2008-12-12 | 2010-06-17 | Bind Biosciences | Therapeutic particles suitable for parenteral administration and methods of making and using same |
US20100216804A1 (en) | 2008-12-15 | 2010-08-26 | Zale Stephen E | Long Circulating Nanoparticles for Sustained Release of Therapeutic Agents |
WO2010081004A1 (en) | 2009-01-09 | 2010-07-15 | Seattle Genetics, Inc. | Weekly dosing regimens for anti-cd30 vc-pab-mmae antibody drug-conjugates |
EP2408474B1 (en) | 2009-03-18 | 2019-06-26 | Armagen, Inc. | Compositions and methods for blood-brain barrier delivery of igg-decoy receptor fusion proteins |
UY32560A (es) | 2009-04-29 | 2010-11-30 | Bayer Schering Pharma Ag | Inmunoconjugados de antimesotelina y usos de los mismos |
CA2760185A1 (en) * | 2009-05-04 | 2010-11-11 | Abbott Biotechnology Ltd. | Stable high protein concentration formulations of human anti-tnf-alpha antibodies |
BRPI1012301A2 (pt) | 2009-05-29 | 2015-09-22 | Cydex Pharmaceuticals Inc | composições de melfalano injetáveis compreendendo um derivado de ciclodextrina e métodos de preparar e usar o mesmo |
US11020363B2 (en) | 2009-05-29 | 2021-06-01 | Cydex Pharmaceuticals, Inc. | Injectable nitrogen mustard compositions comprising a cyclodextrin derivative and methods of making and using the same |
PT2437790T (pt) | 2009-06-03 | 2019-06-04 | Immunogen Inc | Métodos de conjugação |
PL3354277T3 (pl) | 2009-07-28 | 2021-12-13 | Takeda Pharmaceutical Company Limited | Kompozycje i sposoby leczenia choroby gauchera |
US20110076232A1 (en) * | 2009-09-29 | 2011-03-31 | Ludwig Institute For Cancer Research | Specific binding proteins and uses thereof |
SI2485761T1 (sl) | 2009-10-09 | 2019-05-31 | Armagen, Inc. | Postopki in sestavki za povečanje aktivnosti iduronat-2-sulfataze v CŽS |
DK2509634T3 (en) | 2009-12-11 | 2019-04-23 | Pfizer | Stable formulations for lyophilization of therapeutic particles |
JP5965844B2 (ja) | 2009-12-15 | 2016-08-10 | バインド セラピューティックス インコーポレイテッド | 高いガラス転移温度または高分子量のコポリマーを有する治療用ポリマーナノ粒子組成物 |
UA112288C2 (uk) | 2010-01-15 | 2016-08-25 | Кірін-Емджен, Інк. | Склад антитіла, що специфічно зв'язує рецептор а іl-17, і терапевтичні режими |
JP5841072B2 (ja) | 2010-02-10 | 2016-01-06 | イミュノジェン・インコーポレーテッド | Cd20抗体およびその使用 |
CN110835373A (zh) | 2010-03-01 | 2020-02-25 | 拜耳医药保健有限公司 | 针对组织因子途径抑制剂(tfpi)的优化的单克隆抗体 |
WO2012009705A1 (en) | 2010-07-15 | 2012-01-19 | Zyngenia, Inc. | Ang-2 binding complexes and uses thereof |
JP5919606B2 (ja) | 2010-11-11 | 2016-05-18 | アッヴィ バイオテクノロジー リミテッド | 改良型高濃度抗tnfアルファ抗体液体製剤 |
EP2672982B1 (en) * | 2011-02-09 | 2019-09-04 | The Scripps Research Institute | Ghrelin mimetic polypeptide hapten immunoconjugates having improved solubility and immunogenicity and methods of use thereof |
EP2500035A1 (en) * | 2011-03-15 | 2012-09-19 | Icon Genetics GmbH | Pharmaceutical formulation containing immunglobulin |
TR201902180T4 (tr) | 2011-03-29 | 2019-03-21 | Immunogen Inc | Tek adimli bi̇r i̇şlem i̇le maytansi̇noi̇d anti̇kor konjugatlarinin hazirlanmasi |
KR20190116563A (ko) | 2011-03-31 | 2019-10-14 | 머크 샤프 앤드 돔 코포레이션 | 인간 프로그램화된 사멸 수용체 pd-1에 대한 항체의 안정한 제제 및 관련된 치료 |
JP6024025B2 (ja) | 2011-05-02 | 2016-11-09 | イミューノメディクス、インコーポレイテッドImmunomedics, Inc. | 少容量投与用のアロタイプ選択抗体の限外濾過濃縮 |
CN106432506A (zh) | 2011-05-24 | 2017-02-22 | 泽恩格尼亚股份有限公司 | 多价和单价多特异性复合物及其用途 |
PE20141151A1 (es) | 2011-09-22 | 2014-09-25 | Amgen Inc | Proteinas de union al antigeno cd27l |
WO2013081706A1 (en) | 2011-12-02 | 2013-06-06 | Armagen Technologies, Inc. | Methods and compositions for increasing arylsulfatase a activity in the cns |
AR091069A1 (es) | 2012-05-18 | 2014-12-30 | Amgen Inc | Proteinas de union a antigeno dirigidas contra el receptor st2 |
US9592297B2 (en) | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
TR201909389T4 (tr) | 2012-09-17 | 2019-07-22 | Pfizer | Terapötik nanopartikülleri hazırlamaya yönelik proses. |
WO2014055877A1 (en) | 2012-10-04 | 2014-04-10 | Immunogen, Inc. | Use of a pvdf membrane to purify cell-binding agent cytotoxic agent conjugates |
US9353150B2 (en) | 2012-12-04 | 2016-05-31 | Massachusetts Institute Of Technology | Substituted pyrazino[1′,2′:1 ,5]pyrrolo[2,3-b]-indole-1,4-diones for cancer treatment |
TW201425336A (zh) | 2012-12-07 | 2014-07-01 | Amgen Inc | Bcma抗原結合蛋白質 |
ES2728936T3 (es) | 2013-01-25 | 2019-10-29 | Amgen Inc | Anticuerpos dirigidos contra CDH19 para melanoma |
CA2901575C (en) | 2013-03-13 | 2022-08-30 | Seattle Genetics, Inc. | Cyclodextrin and antibody-drug conjugate formulations |
EA201890895A1 (ru) | 2013-03-15 | 2019-02-28 | Зинджения, Инк. | Мультивалентные и моновалентные мультиспецифические комплексы и их применение |
PT3004167T (pt) | 2013-05-30 | 2018-11-13 | Kiniksa Pharmaceuticals Ltd | Proteínas de ligação ao antigénio do recetor da oncostatina m |
TW201605896A (zh) | 2013-08-30 | 2016-02-16 | 安美基股份有限公司 | Gitr抗原結合蛋白 |
BR112016021130A2 (pt) | 2014-03-14 | 2017-08-15 | Pfizer | Nanopartículas terapêuticas, composição farmacêutica compreendendo as referidas nanopartículas, processo para a preparação e uso das mesmas |
JP2015209384A (ja) * | 2014-04-24 | 2015-11-24 | ミレニアム ファーマシューティカルズ, インコーポレイテッドMillennium Pharmaceuticals, Inc. | 医薬製剤 |
US10538589B2 (en) | 2015-01-14 | 2020-01-21 | Armagen Inc. | Methods and compositions for increasing N-acetylglucosaminidase (NAGLU) activity in the CNS using a fusion antibody comprising an anti-human insulin receptor antibody and NAGLU |
WO2016180941A1 (en) * | 2015-05-13 | 2016-11-17 | Sanofi | Liquid compositions for anti-cd19 antibody-drug conjugates |
CN114853873A (zh) | 2015-06-11 | 2022-08-05 | 格纳西尼有限公司 | 经修饰的白细胞介素-7蛋白及其用途 |
AU2016332900C1 (en) | 2015-09-29 | 2024-02-01 | Amgen Inc. | ASGR inhibitors |
KR102386735B1 (ko) * | 2015-11-06 | 2022-04-14 | 주식회사 제넥신 | 변형된 인터루킨-7 융합 단백질의 제형 |
FI3380525T3 (fi) * | 2015-11-25 | 2024-01-30 | Immunogen Inc | Lääkeformulaatioita ja niiden käyttömenetelmiä |
WO2017095140A1 (ko) | 2015-12-04 | 2017-06-08 | 주식회사 제넥신 | 면역글로불린 fc가 융합된 인터루킨-7 융합 단백질을 포함하는 인플루엔자 바이러스 감염의 예방 또는 치료용 약학적 조성물 |
WO2017095191A1 (ko) | 2015-12-04 | 2017-06-08 | 주식회사 제넥신 | 면역글로불린 fc가 융합된 인터루킨-7 융합 단백질을 포함하는 사람 파필로마바이러스 유래 질환의 예방 또는 치료용 약학적 조성물 |
CN115400220A (zh) | 2015-12-30 | 2022-11-29 | 豪夫迈·罗氏有限公司 | 减少聚山梨酯降解的制剂 |
JP2019505520A (ja) | 2016-01-13 | 2019-02-28 | ゲンマブ エー/エス | 抗体およびその薬物コンジュゲートの製剤 |
US10918627B2 (en) | 2016-05-11 | 2021-02-16 | Massachusetts Institute Of Technology | Convergent and enantioselective total synthesis of Communesin analogs |
WO2018092885A1 (ja) | 2016-11-18 | 2018-05-24 | アステラス製薬株式会社 | 新規な抗ヒトMUC1抗体Fabフラグメント |
WO2018158716A1 (en) * | 2017-03-02 | 2018-09-07 | Cadila Healthcare Limited | Novel protein drug conjugate formulation |
CA3044082A1 (en) | 2017-04-03 | 2018-10-11 | Immunomedics, Inc. | Subcutaneous administration of antibody-drug conjugates for cancer therapy |
JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
WO2018204374A1 (en) | 2017-05-02 | 2018-11-08 | Merck Sharp & Dohme Corp. | Formulations of anti-lag3 antibodies and co-formulations of anti-lag3 antibodies and anti-pd-1 antibodies |
US11932650B2 (en) | 2017-05-11 | 2024-03-19 | Massachusetts Institute Of Technology | Potent agelastatin derivatives as modulators for cancer invasion and metastasis |
TWI795415B (zh) | 2017-07-07 | 2023-03-11 | 日商安斯泰來製藥股份有限公司 | 新穎的抗人類CEACAM5抗體Fab片段 |
US20210128741A1 (en) * | 2017-08-23 | 2021-05-06 | Daiichi Sankyo Company, Limited | Antibody-drug conjugate preparation and lyophilization for same |
CN111051330A (zh) | 2017-08-31 | 2020-04-21 | 第一三共株式会社 | 抗体-药物缀合物的改进制备方法 |
US10640508B2 (en) | 2017-10-13 | 2020-05-05 | Massachusetts Institute Of Technology | Diazene directed modular synthesis of compounds with quaternary carbon centers |
GB201719447D0 (en) | 2017-11-23 | 2018-01-10 | Ucb Biopharma Sprl | Pharmaceutical composition |
PE20201503A1 (es) * | 2018-04-13 | 2020-12-29 | Genentech Inc | Formulaciones de inmunoconjugado anti-cd79b estables |
EP3865154A4 (en) * | 2018-10-10 | 2022-11-09 | Astellas Pharma Inc. | PHARMACEUTICAL COMPOSITION CONTAINING ANTIBODY FAB FRAGMENT COMPLEX AT LABELED ANTI-HUMAN SITE |
KR20210114989A (ko) | 2019-02-18 | 2021-09-24 | 일라이 릴리 앤드 캄파니 | 치료 항체 제제 |
AU2020259492A1 (en) * | 2019-04-18 | 2021-11-11 | Momenta Pharmaceuticals, Inc. | Sialylated glycoproteins |
WO2020234114A1 (en) | 2019-05-21 | 2020-11-26 | Bayer Aktiengesellschaft | A novel stable high concentration formulation for anetumab ravtansine |
WO2020247054A1 (en) | 2019-06-05 | 2020-12-10 | Massachusetts Institute Of Technology | Compounds, conjugates, and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines and uses thereof |
CN111879930A (zh) * | 2020-08-04 | 2020-11-03 | 上海艾瑞德生物科技有限公司 | 肌酸激酶同工酶mb检测试剂盒及其制备方法 |
BR112023002346A2 (pt) * | 2020-08-07 | 2023-05-02 | Fortis Therapeutics Inc | Imunoconjugados direcionados a cd46 e métodos de uso dos mesmos |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002013860A1 (fr) * | 2000-08-11 | 2002-02-21 | Chugai Seiyaku Kabushiki Kaisha | Preparations stabilisees contenant un anticorps |
US20040241174A1 (en) * | 2003-05-14 | 2004-12-02 | Immunogen, Inc. | Drug conjugate composition |
JP2004538287A (ja) * | 2001-07-25 | 2004-12-24 | プロテイン デザイン ラブス インコーポレイティド | IgG抗体の安定な凍結乾燥医薬製剤 |
JP2005508981A (ja) * | 2001-11-08 | 2005-04-07 | プロテイン デザイン ラブス インコーポレイティド | Igg抗体の安定な液体医薬製剤 |
Family Cites Families (59)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3890238A (en) * | 1972-12-21 | 1975-06-17 | Basf Wyandotte Corp | Water solubility of polyoxyalkylene polymers |
US3896111A (en) | 1973-02-20 | 1975-07-22 | Research Corp | Ansa macrolides |
US4151042A (en) | 1977-03-31 | 1979-04-24 | Takeda Chemical Industries, Ltd. | Method for producing maytansinol and its derivatives |
US4563304A (en) | 1981-02-27 | 1986-01-07 | Pharmacia Fine Chemicals Ab | Pyridine compounds modifying proteins, polypeptides or polysaccharides |
US4597966A (en) * | 1985-01-09 | 1986-07-01 | Ortho Diagnostic Systems, Inc. | Histidine stabilized immunoglobulin and method of preparation |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5196193A (en) | 1989-10-31 | 1993-03-23 | Ophidian Pharmaceuticals, Inc. | Antivenoms and methods for making antivenoms |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
EP0546073B1 (en) | 1990-08-29 | 1997-09-10 | GenPharm International, Inc. | production and use of transgenic non-human animals capable of producing heterologous antibodies |
ES2149768T3 (es) | 1992-03-25 | 2000-11-16 | Immunogen Inc | Conjugados de agentes enlazantes de celulas derivados de cc-1065. |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
IL111748A0 (en) | 1993-12-03 | 1995-01-24 | Zeneca Ltd | Proteins |
US6265150B1 (en) | 1995-06-07 | 2001-07-24 | Becton Dickinson & Company | Phage antibodies |
US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
RU2497500C2 (ru) * | 1995-07-27 | 2013-11-10 | Джинентех, Инк | Стабильная изотоническая лиофилизированная протеиновая композиция |
US5714352A (en) | 1996-03-20 | 1998-02-03 | Xenotech Incorporated | Directed switch-mediated DNA recombination |
US6306393B1 (en) | 1997-03-24 | 2001-10-23 | Immunomedics, Inc. | Immunotherapy of B-cell malignancies using anti-CD22 antibodies |
ATE230277T1 (de) * | 1997-06-13 | 2003-01-15 | Genentech Inc | Stabilisierte antikörperformulierung |
US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
WO2000002587A1 (en) | 1998-07-13 | 2000-01-20 | Board Of Regents, The University Of Texas System | Cancer treatment methods using therapeutic conjugates that bind to aminophospholipids |
EP1191944A2 (en) | 1999-06-25 | 2002-04-03 | Genentech, Inc. | METHODS OF TREATMENT USING ANTI-ErbB ANTIBODY-MAYTANSINOID CONJUGATES |
CN100540651C (zh) | 1999-09-22 | 2009-09-16 | 钟渊化学工业株式会社 | 新的面包酵母和含有该酵母的面团 |
EP2266607A3 (en) | 1999-10-01 | 2011-04-20 | Immunogen, Inc. | Immunoconjugates for treating cancer |
US6824780B1 (en) | 1999-10-29 | 2004-11-30 | Genentech, Inc. | Anti-tumor antibody compositions and methods of use |
IL149116A0 (en) | 1999-10-29 | 2002-11-10 | Genentech Inc | Anti-prostate stem cell antigen (psca) antibody compositions and methods of use |
US20020028178A1 (en) | 2000-07-12 | 2002-03-07 | Nabil Hanna | Treatment of B cell malignancies using combination of B cell depleting antibody and immune modulating antibody related applications |
AU765588C (en) | 1999-11-24 | 2004-12-16 | Immunogen, Inc. | Cytotoxic agents comprising taxanes and their therapeutic use |
PT1242438E (pt) | 1999-12-29 | 2007-02-28 | Immunogen Inc | Agentes citotóxicos compreendendo dixorrubicinas e daunorrubicinas modificadas e seu uso terapêutico |
CA2398136A1 (en) | 2000-02-08 | 2001-08-16 | The Penn State Research Foundation | Immunotherapy using interleukin 13 receptor subunit alpha 2 |
US7097840B2 (en) * | 2000-03-16 | 2006-08-29 | Genentech, Inc. | Methods of treatment using anti-ErbB antibody-maytansinoid conjugates |
MXPA03000190A (es) | 2000-06-26 | 2004-09-13 | Rxkinetix Inc | Composicion para el suministro del factor de crecimiento hamtopoyetico. |
US6596503B1 (en) | 2000-08-18 | 2003-07-22 | East Carolina University | Monoclonal antibody DS6, tumor-associated antigen CA6, and methods of use thereof |
US6333410B1 (en) | 2000-08-18 | 2001-12-25 | Immunogen, Inc. | Process for the preparation and purification of thiol-containing maytansinoids |
JP2005503109A (ja) | 2001-01-29 | 2005-02-03 | アイデック ファーマスーティカルズ コーポレイション | 修飾抗体と使用方法 |
CA2446806A1 (en) | 2001-05-11 | 2002-11-21 | Board Of Regents, The University Of Texas System | Anti-cd26 monoclonal antibodies as therapy for diseases associated with cells expressing cd26 |
US6441163B1 (en) | 2001-05-31 | 2002-08-27 | Immunogen, Inc. | Methods for preparation of cytotoxic conjugates of maytansinoids and cell binding agents |
US6716821B2 (en) | 2001-12-21 | 2004-04-06 | Immunogen Inc. | Cytotoxic agents bearing a reactive polyethylene glycol moiety, cytotoxic conjugates comprising polyethylene glycol linking groups, and methods of making and using the same |
NZ533657A (en) | 2002-01-03 | 2008-01-31 | Smithkline Beecham Corp | Methods for the preparation of immunoconjugates, in particular maytansinoids conjugated to a monoclonal antibody |
US6756397B2 (en) | 2002-04-05 | 2004-06-29 | Immunogen, Inc. | Prodrugs of CC-1065 analogs |
US6596757B1 (en) | 2002-05-14 | 2003-07-22 | Immunogen Inc. | Cytotoxic agents comprising polyethylene glycol-containing taxanes and their therapeutic use |
WO2003099320A1 (en) * | 2002-05-24 | 2003-12-04 | Zensun (Shanghai) Sci-Tech.Ltd | Neuregulin based methods and compositions for treating viral myocarditis and dilated cardiomyopathy |
US6982253B2 (en) * | 2002-06-05 | 2006-01-03 | Supergen, Inc. | Liquid formulation of decitabine and use of the same |
US7132100B2 (en) * | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
CN1671741A (zh) * | 2002-06-21 | 2005-09-21 | 拜奥根Idec公司 | 浓缩抗体的缓冲剂制剂及其使用方法 |
JP2005532395A (ja) * | 2002-07-02 | 2005-10-27 | スミスクライン・ビーチャム・コーポレイション | 新規な安定処方 |
US20040126379A1 (en) * | 2002-08-21 | 2004-07-01 | Boehringer Ingelheim International Gmbh | Compositions and methods for treating cancer using cytotoxic CD44 antibody immunoconjugates and chemotherapeutic agents |
EP1391213A1 (en) * | 2002-08-21 | 2004-02-25 | Boehringer Ingelheim International GmbH | Compositions and methods for treating cancer using maytansinoid CD44 antibody immunoconjugates and chemotherapeutic agents |
AU2003276844A1 (en) | 2002-08-28 | 2004-03-19 | Pharmacia Corporation | Formulations of modified antibodies and methods of making the same |
JP2006514954A (ja) | 2002-12-31 | 2006-05-18 | ネクター セラピューティクス | 抗体含有粒子及び組成物 |
WO2004066957A2 (en) | 2003-01-30 | 2004-08-12 | Medimmune, Inc. | ANTI-INTEGRIN ανβ3 ANTIBODY FORMULATIONS AND USES THEREOF |
KR101357443B1 (ko) | 2003-02-25 | 2014-02-06 | 메디뮨 엘엘씨 | 인플루엔자 백신 조성물의 제조 방법 |
GB0317509D0 (en) * | 2003-07-25 | 2003-08-27 | Pfizer Ltd | Nicotinamide derivatives useful as PDE4 inhibitors |
US7404957B2 (en) * | 2003-08-29 | 2008-07-29 | Aerovance, Inc. | Modified IL-4 mutein receptor antagonists |
TW200517114A (en) * | 2003-10-15 | 2005-06-01 | Combinatorx Inc | Methods and reagents for the treatment of immunoinflammatory disorders |
WO2005065709A2 (de) | 2003-12-24 | 2005-07-21 | Boehringer Ingelheim International Gmbh | Gefriergetrocknete formulierung von antikörperkonjugaten |
DE10361599A1 (de) | 2003-12-24 | 2005-07-28 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Flüssigformulierung von Antikörperkonjugaten |
-
2006
- 2006-08-02 NZ NZ59917606A patent/NZ599176A/en unknown
- 2006-08-02 MX MX2008001492A patent/MX336033B/es unknown
- 2006-08-02 AU AU2006278573A patent/AU2006278573A1/en not_active Abandoned
- 2006-08-02 EP EP06800717A patent/EP1917030A4/en not_active Withdrawn
- 2006-08-02 BR BRPI0614100-5A patent/BRPI0614100A2/pt not_active Application Discontinuation
- 2006-08-02 NZ NZ564843A patent/NZ564843A/en not_active IP Right Cessation
- 2006-08-02 EA EA200800233A patent/EA014513B1/ru unknown
- 2006-08-02 WO PCT/US2006/030295 patent/WO2007019232A2/en active Application Filing
- 2006-08-02 KR KR1020087002609A patent/KR101566393B1/ko active IP Right Grant
- 2006-08-02 CA CA 2615122 patent/CA2615122A1/en not_active Abandoned
- 2006-08-02 NZ NZ623901A patent/NZ623901A/en unknown
- 2006-08-02 JP JP2008525189A patent/JP2009503105A/ja active Pending
- 2006-08-03 US US11/498,139 patent/US9114179B2/en not_active Expired - Fee Related
-
2008
- 2008-01-13 IL IL188733A patent/IL188733A/en not_active IP Right Cessation
- 2008-02-01 NO NO20080612A patent/NO20080612L/no not_active Application Discontinuation
- 2008-02-06 EC ECSP088159 patent/ECSP088159A/es unknown
-
2012
- 2012-06-20 JP JP2012138483A patent/JP2012211163A/ja not_active Withdrawn
-
2015
- 2015-08-07 JP JP2015157269A patent/JP6389446B2/ja not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002013860A1 (fr) * | 2000-08-11 | 2002-02-21 | Chugai Seiyaku Kabushiki Kaisha | Preparations stabilisees contenant un anticorps |
JP2004538287A (ja) * | 2001-07-25 | 2004-12-24 | プロテイン デザイン ラブス インコーポレイティド | IgG抗体の安定な凍結乾燥医薬製剤 |
JP2005508981A (ja) * | 2001-11-08 | 2005-04-07 | プロテイン デザイン ラブス インコーポレイティド | Igg抗体の安定な液体医薬製剤 |
US20040241174A1 (en) * | 2003-05-14 | 2004-12-02 | Immunogen, Inc. | Drug conjugate composition |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013527832A (ja) * | 2010-03-22 | 2013-07-04 | ジェネンテック, インコーポレイテッド | タンパク質含有製剤の安定化に有用な組成物及び方法 |
JP2016193909A (ja) * | 2010-03-22 | 2016-11-17 | ジェネンテック, インコーポレイテッド | タンパク質含有製剤の安定化に有用な組成物及び方法 |
US9662395B2 (en) | 2010-03-22 | 2017-05-30 | Genentech, Inc. | Compositions and methods useful for stabilizing protein-containing formulations |
JP2017071631A (ja) * | 2010-09-17 | 2017-04-13 | バクスアルタ ゲーエムベーハー | 弱酸性〜中性のpHにおける、ヒスチジンを有する水性製剤を介した免疫グロブリンの安定化 |
JP2016534062A (ja) * | 2013-10-25 | 2016-11-04 | バイエル ファーマ アクチエンゲゼルシャフト | 新規な安定製剤 |
JP2016539118A (ja) * | 2013-11-21 | 2016-12-15 | ゲンマブ エー/エス | 抗体−薬物コンジュゲート凍結乾燥製剤 |
JP2019163319A (ja) * | 2013-11-21 | 2019-09-26 | ゲンマブ エー/エス | 抗体−薬物コンジュゲート凍結乾燥製剤 |
JP2021119199A (ja) * | 2013-11-21 | 2021-08-12 | ゲンマブ エー/エス | 抗体−薬物コンジュゲート凍結乾燥製剤 |
JP7162695B2 (ja) | 2013-11-21 | 2022-10-28 | ジェンマブ エー/エス | 抗体-薬物コンジュゲート凍結乾燥製剤 |
Also Published As
Publication number | Publication date |
---|---|
JP6389446B2 (ja) | 2018-09-12 |
EP1917030A2 (en) | 2008-05-07 |
KR101566393B1 (ko) | 2015-11-05 |
MX336033B (es) | 2016-01-07 |
JP2012211163A (ja) | 2012-11-01 |
WO2007019232A2 (en) | 2007-02-15 |
MX2008001492A (es) | 2008-04-04 |
CA2615122A1 (en) | 2007-02-15 |
AU2006278573A1 (en) | 2007-02-15 |
WO2007019232A3 (en) | 2007-06-28 |
NZ599176A (en) | 2014-04-30 |
EP1917030A4 (en) | 2011-03-09 |
NZ623901A (en) | 2015-10-30 |
IL188733A (en) | 2015-05-31 |
US20070031402A1 (en) | 2007-02-08 |
ECSP088159A (es) | 2008-03-26 |
US9114179B2 (en) | 2015-08-25 |
EA014513B1 (ru) | 2010-12-30 |
NO20080612L (no) | 2008-04-30 |
KR20080033324A (ko) | 2008-04-16 |
BRPI0614100A2 (pt) | 2011-03-09 |
JP2016020359A (ja) | 2016-02-04 |
NZ564843A (en) | 2012-05-25 |
EA200800233A1 (ru) | 2008-08-29 |
IL188733A0 (en) | 2008-08-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6389446B2 (ja) | 免疫複合体製剤 | |
AU2016216585B2 (en) | Drug conjugate composition | |
EP1853322B1 (en) | Process for preparing maytansinoid antibody conjugates | |
AU2006283726B2 (en) | Process for preparing maytansinoid antibody conjugates | |
AU2006236489B2 (en) | Elimination of heterogeneous or mixed cell population in tumors | |
AU2004282491C1 (en) | Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates | |
US20160045616A1 (en) | Process for preparing purified drug conjugates | |
US20100092495A1 (en) | Potent cell-binding agent drug conjugates | |
CN101237881B (zh) | 免疫偶联物剂型 | |
AU2012211479B2 (en) | Immunoconjugate formulations | |
AU2012227185B2 (en) | Process for preparing maytansinoid antibody conjugates |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090616 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090616 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20110913 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110930 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111220 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120123 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120130 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120620 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20121101 |