JP2021006544A - ヒト化抗C1s抗体及びその使用方法 - Google Patents
ヒト化抗C1s抗体及びその使用方法 Download PDFInfo
- Publication number
- JP2021006544A JP2021006544A JP2020161908A JP2020161908A JP2021006544A JP 2021006544 A JP2021006544 A JP 2021006544A JP 2020161908 A JP2020161908 A JP 2020161908A JP 2020161908 A JP2020161908 A JP 2020161908A JP 2021006544 A JP2021006544 A JP 2021006544A
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- present disclosure
- amino acid
- humanized anti
- complement
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title abstract description 73
- 230000000295 complement effect Effects 0.000 abstract description 129
- 239000000203 mixture Substances 0.000 abstract description 59
- 210000000056 organ Anatomy 0.000 abstract description 36
- 150000007523 nucleic acids Chemical class 0.000 abstract description 23
- 108020004707 nucleic acids Proteins 0.000 abstract description 22
- 102000039446 nucleic acids Human genes 0.000 abstract description 22
- 238000003776 cleavage reaction Methods 0.000 abstract description 10
- 230000007017 scission Effects 0.000 abstract description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 abstract description 8
- 239000012530 fluid Substances 0.000 abstract description 6
- 150000001413 amino acids Chemical group 0.000 description 253
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 184
- 229940024606 amino acid Drugs 0.000 description 161
- 235000001014 amino acid Nutrition 0.000 description 161
- 230000001404 mediated effect Effects 0.000 description 106
- 201000010099 disease Diseases 0.000 description 94
- 208000035475 disorder Diseases 0.000 description 89
- 210000004027 cell Anatomy 0.000 description 75
- 230000024203 complement activation Effects 0.000 description 55
- 210000001519 tissue Anatomy 0.000 description 53
- 239000008194 pharmaceutical composition Substances 0.000 description 51
- 241000282414 Homo sapiens Species 0.000 description 48
- 210000001124 body fluid Anatomy 0.000 description 44
- 239000010839 body fluid Substances 0.000 description 44
- 230000000694 effects Effects 0.000 description 44
- 238000011282 treatment Methods 0.000 description 44
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 39
- 239000007857 degradation product Substances 0.000 description 39
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 37
- 238000007920 subcutaneous administration Methods 0.000 description 35
- 230000003247 decreasing effect Effects 0.000 description 34
- 238000001990 intravenous administration Methods 0.000 description 34
- 230000027455 binding Effects 0.000 description 33
- 102000016917 Complement C1 Human genes 0.000 description 32
- 108010028774 Complement C1 Proteins 0.000 description 32
- 239000012071 phase Substances 0.000 description 29
- 241001465754 Metazoa Species 0.000 description 26
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 24
- 239000000427 antigen Substances 0.000 description 23
- 108091007433 antigens Proteins 0.000 description 23
- 102000036639 antigens Human genes 0.000 description 23
- 241000124008 Mammalia Species 0.000 description 22
- 230000007423 decrease Effects 0.000 description 21
- 229960002885 histidine Drugs 0.000 description 21
- 108060003951 Immunoglobulin Proteins 0.000 description 20
- 229920001213 Polysorbate 20 Polymers 0.000 description 20
- 102000018358 immunoglobulin Human genes 0.000 description 20
- 239000002773 nucleotide Substances 0.000 description 20
- 125000003729 nucleotide group Chemical group 0.000 description 20
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 20
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 20
- 238000009472 formulation Methods 0.000 description 19
- 239000000546 pharmaceutical excipient Substances 0.000 description 19
- 210000002966 serum Anatomy 0.000 description 19
- 238000007918 intramuscular administration Methods 0.000 description 18
- 238000007913 intrathecal administration Methods 0.000 description 18
- 208000024891 symptom Diseases 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 230000003285 pharmacodynamic effect Effects 0.000 description 16
- 239000013598 vector Substances 0.000 description 16
- 239000003981 vehicle Substances 0.000 description 16
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 15
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 15
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 15
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 15
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 15
- 230000037361 pathway Effects 0.000 description 15
- 230000008021 deposition Effects 0.000 description 14
- 230000008595 infiltration Effects 0.000 description 14
- 238000001764 infiltration Methods 0.000 description 14
- 210000002381 plasma Anatomy 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 229920001184 polypeptide Polymers 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 12
- 238000002648 combination therapy Methods 0.000 description 12
- 239000012634 fragment Substances 0.000 description 12
- 239000012669 liquid formulation Substances 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 238000009097 single-agent therapy Methods 0.000 description 12
- 235000002639 sodium chloride Nutrition 0.000 description 12
- 238000012384 transportation and delivery Methods 0.000 description 12
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 11
- 230000037396 body weight Effects 0.000 description 11
- 239000000872 buffer Substances 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 230000001105 regulatory effect Effects 0.000 description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 10
- 230000000735 allogeneic effect Effects 0.000 description 10
- 238000013270 controlled release Methods 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 9
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 9
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 9
- 229930006000 Sucrose Natural products 0.000 description 9
- 239000003755 preservative agent Substances 0.000 description 9
- 239000005720 sucrose Substances 0.000 description 9
- 239000004094 surface-active agent Substances 0.000 description 9
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 8
- 208000023275 Autoimmune disease Diseases 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 206010052779 Transplant rejections Diseases 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 230000002496 gastric effect Effects 0.000 description 8
- 230000006872 improvement Effects 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 239000007951 isotonicity adjuster Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000004770 neurodegeneration Effects 0.000 description 8
- 208000015122 neurodegenerative disease Diseases 0.000 description 8
- -1 rioprotectants Substances 0.000 description 8
- 239000003381 stabilizer Substances 0.000 description 8
- 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 7
- 241000282693 Cercopithecidae Species 0.000 description 7
- 241000282567 Macaca fascicularis Species 0.000 description 7
- 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 7
- 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 7
- 230000003628 erosive effect Effects 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 210000002540 macrophage Anatomy 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 206010047115 Vasculitis Diseases 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 230000004154 complement system Effects 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 208000026278 immune system disease Diseases 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 5
- 241000251468 Actinopterygii Species 0.000 description 5
- 206010012289 Dementia Diseases 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 241000235648 Pichia Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000002391 anti-complement effect Effects 0.000 description 5
- 108010008730 anticomplement Proteins 0.000 description 5
- 230000003920 cognitive function Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 201000003278 cryoglobulinemia Diseases 0.000 description 5
- 230000009089 cytolysis Effects 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 230000036470 plasma concentration Effects 0.000 description 5
- 230000009870 specific binding Effects 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 206010063837 Reperfusion injury Diseases 0.000 description 4
- 108010034634 Repressor Proteins Proteins 0.000 description 4
- 102000009661 Repressor Proteins Human genes 0.000 description 4
- 208000003441 Transfusion reaction Diseases 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 230000008499 blood brain barrier function Effects 0.000 description 4
- 210000001218 blood-brain barrier Anatomy 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 208000010877 cognitive disease Diseases 0.000 description 4
- 239000008121 dextrose Substances 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 230000007277 glial cell activation Effects 0.000 description 4
- 229940072221 immunoglobulins Drugs 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 208000027866 inflammatory disease Diseases 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 239000012931 lyophilized formulation Substances 0.000 description 4
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 208000019838 Blood disease Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 208000019707 Cryoglobulinemic vasculitis Diseases 0.000 description 3
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- 125000002707 L-tryptophyl group Chemical group [H]C1=C([H])C([H])=C2C(C([C@](N([H])[H])(C(=O)[*])[H])([H])[H])=C([H])N([H])C2=C1[H] 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 210000005013 brain tissue Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 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
- 239000008120 corn starch Substances 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 239000003405 delayed action preparation Substances 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 238000002651 drug therapy Methods 0.000 description 3
- 210000003038 endothelium Anatomy 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000000925 erythroid effect Effects 0.000 description 3
- 208000030533 eye disease Diseases 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 229960002989 glutamic acid Drugs 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 208000014951 hematologic disease Diseases 0.000 description 3
- 208000018706 hematopoietic system disease Diseases 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 3
- 208000017169 kidney disease Diseases 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 210000002850 nasal mucosa Anatomy 0.000 description 3
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 3
- 210000004498 neuroglial cell Anatomy 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 229920001983 poloxamer Polymers 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- 210000005253 yeast cell Anatomy 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- FQVLRGLGWNWPSS-BXBUPLCLSA-N (4r,7s,10s,13s,16r)-16-acetamido-13-(1h-imidazol-5-ylmethyl)-10-methyl-6,9,12,15-tetraoxo-7-propan-2-yl-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carboxamide Chemical compound N1C(=O)[C@@H](NC(C)=O)CSSC[C@@H](C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@@H]1CC1=CN=CN1 FQVLRGLGWNWPSS-BXBUPLCLSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- 102100034035 Alcohol dehydrogenase 1A Human genes 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 108010078015 Complement C3b Proteins 0.000 description 2
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 206010012305 Demyelination Diseases 0.000 description 2
- 206010014950 Eosinophilia Diseases 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000223218 Fusarium Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 101000892220 Geobacillus thermodenitrificans (strain NG80-2) Long-chain-alcohol dehydrogenase 1 Proteins 0.000 description 2
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 101000780443 Homo sapiens Alcohol dehydrogenase 1A Proteins 0.000 description 2
- 208000028622 Immune thrombocytopenia Diseases 0.000 description 2
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 2
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 108090000951 RNA polymerase sigma 70 Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 241000235070 Saccharomyces Species 0.000 description 2
- 102000012479 Serine Proteases Human genes 0.000 description 2
- 108010022999 Serine Proteases Proteins 0.000 description 2
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 150000005215 alkyl ethers Chemical class 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000013011 aqueous formulation Substances 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000020411 cell activation Effects 0.000 description 2
- 230000006727 cell loss Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000006999 cognitive decline Effects 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000010437 erythropoiesis Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000013265 extended release Methods 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000007917 intracranial administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 229960003136 leucine Drugs 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 235000006109 methionine Nutrition 0.000 description 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 208000001488 molybdenum cofactor deficiency Diseases 0.000 description 2
- 208000005264 motor neuron disease Diseases 0.000 description 2
- 201000008383 nephritis Diseases 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 229920002113 octoxynol Polymers 0.000 description 2
- 210000004248 oligodendroglia Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 229920001993 poloxamer 188 Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 201000008171 proliferative glomerulonephritis Diseases 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 150000003839 salts Chemical group 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000012929 tonicity agent Substances 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 1
- XGWFJBFNAQHLEF-UHFFFAOYSA-N 9-anthroic acid Chemical compound C1=CC=C2C(C(=O)O)=C(C=CC=C3)C3=CC2=C1 XGWFJBFNAQHLEF-UHFFFAOYSA-N 0.000 description 1
- 102100036826 Aldehyde oxidase Human genes 0.000 description 1
- 102100034044 All-trans-retinol dehydrogenase [NAD(+)] ADH1B Human genes 0.000 description 1
- 101710193111 All-trans-retinol dehydrogenase [NAD(+)] ADH4 Proteins 0.000 description 1
- 102100034452 Alternative prion protein Human genes 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 101100490659 Arabidopsis thaliana AGP17 gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 241000351920 Aspergillus nidulans Species 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 240000006439 Aspergillus oryzae Species 0.000 description 1
- 235000002247 Aspergillus oryzae Nutrition 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000017309 Autoimmune hemolytic anemia, warm type Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 241000151861 Barnettozyma salicaria Species 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 229920002799 BoPET Polymers 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282817 Bovidae Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000023635 C1q nephropathy Diseases 0.000 description 1
- 101150085381 CDC19 gene Proteins 0.000 description 1
- 101100327917 Caenorhabditis elegans chup-1 gene Proteins 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 229920002284 Cellulose triacetate Polymers 0.000 description 1
- 241000195597 Chlamydomonas reinhardtii Species 0.000 description 1
- 241001674013 Chrysosporium lucknowense Species 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 108010078095 Complement C2a Proteins 0.000 description 1
- 102100033777 Complement C4-B Human genes 0.000 description 1
- 108010077762 Complement C4b Proteins 0.000 description 1
- 206010010996 Corneal degeneration Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 108010091326 Cryoglobulins Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 206010066182 Delayed haemolytic transfusion reaction Diseases 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- 208000004332 Evans syndrome Diseases 0.000 description 1
- 201000003675 Evans' syndrome Diseases 0.000 description 1
- 108010008177 Fd immunoglobulins Proteins 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 241000567178 Fusarium venenatum Species 0.000 description 1
- 101150094690 GAL1 gene Proteins 0.000 description 1
- 101150038242 GAL10 gene Proteins 0.000 description 1
- 102100028501 Galanin peptides Human genes 0.000 description 1
- 102100024637 Galectin-10 Human genes 0.000 description 1
- 102100039555 Galectin-7 Human genes 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 101150009006 HIS3 gene Proteins 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 1
- 101000934958 Homo sapiens Complement C1s subcomponent Proteins 0.000 description 1
- 101100121078 Homo sapiens GAL gene Proteins 0.000 description 1
- 101000608772 Homo sapiens Galectin-7 Proteins 0.000 description 1
- 101001074571 Homo sapiens PIN2/TERF1-interacting telomerase inhibitor 1 Proteins 0.000 description 1
- 101001073025 Homo sapiens Peroxisomal targeting signal 1 receptor Proteins 0.000 description 1
- 101000579123 Homo sapiens Phosphoglycerate kinase 1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 101100273566 Humulus lupulus CCL10 gene Proteins 0.000 description 1
- 206010063725 Idiopathic pneumonia syndrome Diseases 0.000 description 1
- 208000024781 Immune Complex disease Diseases 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
- 208000011200 Kawasaki disease Diseases 0.000 description 1
- 241000235649 Kluyveromyces Species 0.000 description 1
- 241001138401 Kluyveromyces lactis Species 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- 235000019454 L-leucine Nutrition 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 240000000759 Lepidium meyenii Species 0.000 description 1
- 235000000421 Lepidium meyenii Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 101150068888 MET3 gene Proteins 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 208000017256 Mixed-type autoimmune hemolytic anemia Diseases 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 101000969137 Mus musculus Metallothionein-1 Proteins 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 241000713883 Myeloproliferative sarcoma virus Species 0.000 description 1
- 239000005041 Mylar™ Substances 0.000 description 1
- 241000588650 Neisseria meningitidis Species 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 241000221961 Neurospora crassa Species 0.000 description 1
- 101100234604 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) ace-8 gene Proteins 0.000 description 1
- 101100022915 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cys-11 gene Proteins 0.000 description 1
- 101100049938 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) exr-1 gene Proteins 0.000 description 1
- 208000010577 Niemann-Pick disease type C Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000320412 Ogataea angusta Species 0.000 description 1
- 241001452677 Ogataea methanolica Species 0.000 description 1
- 241000489470 Ogataea trehalophila Species 0.000 description 1
- 241000826199 Ogataea wickerhamii Species 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000283898 Ovis Species 0.000 description 1
- KJWZYMMLVHIVSU-IYCNHOCDSA-N PGK1 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](CCCCCCC(O)=O)C(=O)CC1=O KJWZYMMLVHIVSU-IYCNHOCDSA-N 0.000 description 1
- 101150012394 PHO5 gene Proteins 0.000 description 1
- 102100036257 PIN2/TERF1-interacting telomerase inhibitor 1 Human genes 0.000 description 1
- 101150093629 PYK1 gene Proteins 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 241000530350 Phaffomyces opuntiae Species 0.000 description 1
- 241000529953 Phaffomyces thermotolerans Species 0.000 description 1
- 102100028251 Phosphoglycerate kinase 1 Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000235062 Pichia membranifaciens Species 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 101100394989 Rhodopseudomonas palustris (strain ATCC BAA-98 / CGA009) hisI gene Proteins 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 101100434411 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) ADH1 gene Proteins 0.000 description 1
- 101100386089 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) MET17 gene Proteins 0.000 description 1
- 101100406813 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) pagC gene Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 101100022918 Schizosaccharomyces pombe (strain 972 / ATCC 24843) sua1 gene Proteins 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 101710142113 Serine protease inhibitor A3K Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 108010079723 Shiga Toxin Proteins 0.000 description 1
- 241000713896 Spleen necrosis virus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 206010043540 Thromboangiitis obliterans Diseases 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 208000002474 Tinea Diseases 0.000 description 1
- 241000130764 Tinea Species 0.000 description 1
- 241000499912 Trichoderma reesei Species 0.000 description 1
- 206010044688 Trisomy 21 Diseases 0.000 description 1
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010063661 Vascular encephalopathy Diseases 0.000 description 1
- 208000035868 Vascular inflammations Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000370136 Wickerhamomyces pijperi Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 101150102866 adc1 gene Proteins 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 201000004781 bullous keratopathy Diseases 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 208000017004 dementia pugilistica Diseases 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000009459 flexible packaging Methods 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- DWYMPOCYEZONEA-UHFFFAOYSA-L fluoridophosphate Chemical compound [O-]P([O-])(F)=O DWYMPOCYEZONEA-UHFFFAOYSA-L 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000012817 gel-diffusion technique Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 230000007387 gliosis Effects 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 101150118163 h gene Proteins 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 208000024326 hypersensitivity reaction type III disease Diseases 0.000 description 1
- 239000000819 hypertonic solution Substances 0.000 description 1
- 239000000815 hypotonic solution Substances 0.000 description 1
- 208000007915 ichthyosis prematurity syndrome Diseases 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 238000001802 infusion 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
- 238000005342 ion exchange Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 235000012902 lepidium meyenii Nutrition 0.000 description 1
- 239000003509 long acting drug Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 208000027061 mild cognitive impairment Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
- 206010065579 multifocal motor neuropathy Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000036473 myasthenia Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229940037525 nasal preparations Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000307 polymer substrate Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229940051841 polyoxyethylene ether Drugs 0.000 description 1
- 229920000056 polyoxyethylene ether Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920005606 polypropylene copolymer Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000001003 psychopharmacologic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 101150101384 rat1 gene Proteins 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000008362 succinate buffer Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 208000025883 type III hypersensitivity disease Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 208000035603 warm type autoimmune hemolytic anemia Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21106—Hepsin (3.4.21.106)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Transplantation (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
本出願は、2015年4月6日出願の米国特許仮出願第62/143,636号明細書、及び2015年8月4日出願の第62/200,997号明細書の利益を主張し、これらの出願全体が参照によって本明細書に組み込まれる。
補体系は、免疫応答の周知のエフェクター機構であり、病原体及びその他の有害な作用物質に対する保護だけでなく、損傷からの回復もまた提供する。補体経路は、典型的には不活性形態で体内に存在する多数のタンパク質を含む。古典的補体経路は、C1複合体と称される補体第1成分の活性化によって誘発され、この複合体はC1q、C1r、及びC1sタンパク質からなる。免疫複合体またはその他の活性化因子にC1が結合すると、C1s成分、すなわちフルオロリン酸ジイソプロピル(DFP)感受性セリンプロテアーゼが、補体成分C4及びC2を切断し、古典的補体経路の活性化を開始させる。古典的補体経路は、多くの疾患及び障害に関与すると思われる。
「抗体」及び「免疫グロブリン」という用語は、あらゆるアイソタイプの抗体または免疫グロブリン、抗原への特異的結合を保持する抗体の断片、例えば、これらに限定されないがFab、Fv、scFv、及びFd断片を含み、キメラ抗体、ヒト化抗体、一本鎖抗体(scAb)、単一ドメイン抗体(dAb)、単一ドメイン重鎖抗体、単一ドメイン軽鎖抗体、二重特異性抗体、多重特異性抗体、ならびに抗体の抗原−結合(本明細書では抗原結合とも称される)部分及び非抗体タンパク質を含む融合タンパク質を含む。抗体は、例えば、放射性同位体、検出可能な生成物を生成する酵素、蛍光タンパク質などで検出可能なように標識され得る。抗体は、その他の部分、例えば、特異的結合対のメンバーなど、例えば、ビオチン(ビオチン−アビジン特異的結合対のメンバー)などにさらに複合化され得る。抗体は固体支持体にも結合され得、支持体はポリスチレンプレートまたはポリスチレンビーズなどを含むが、これらに限定されない。また、この用語は、抗原への特異的結合を保持するFab’、Fv、F(ab’)2、及びまたはその他の抗体断片、ならびにモノクローナル抗体も包含する。本明細書で使用される場合、モノクローナル抗体は、同一細胞、すなわち、その全てが細胞複製の反復によって単一細胞から産生された細胞の群により産生される抗体である。すなわち、細胞のクローンは、単一の抗体種のみを産生する。モノクローナル抗体は、ハイブリドーマ作製技術を使用して産生され得るが、当業者に既知のその他の産生方法も使用され得る(例えば、抗体ファージディスプレイライブラリーから誘導される抗体)。抗体は、一価または二価であり得る。抗体はIgモノマーであり得、これは4つのポリペプチド鎖、すなわちジスルフィド結合によって連結された2本の重鎖及び2本の軽鎖からなる「Y字型」分子である。
al.、欧州特許第0,120,694(B1)号明細書;Neuberger,M.S.et al.、WO86/01533;Neuberger,M.S.et al.、欧州特許第0,194,276(B1)号明細書;Winter、米国特許第5,225,539号明細書;Winter、欧州特許第0,239,400(B1)号明細書;Padlan,E.A.et al.、欧州特許出願第0,519,596(A1)号明細書を参照のこと。また、一本鎖抗体に関しては、Ladner et al.、米国特許第4,946,778号明細書;Huston、米国特許第5,476,786号明細書;及びBird,R.E.et al.,Science,242:423−426(1988))も参照のこと。
Res.,19(9):2471−2476(1991);及びLewis,A.P.and J.S.Crowe,Gene,101:297−302(1991)を参照のこと)。これらの方法またはその他の好適な方法を使用して、バリアントもまた容易に作製され得る。例えば、クローン化可変領域が突然変異誘発され得、所望の特異性を有するバリアントをコードする配列が選択され得る(例えば、ファージライブラリーから;例えば、Krebber et al.、米国特許第5,514,548号明細書;1993年4月1日公開のHoogenboom et al.,WO93/06213)を参照のこと)。
Eng.8(10):1057−1062(1995));ドメイン抗体(dAb;Holt et al.(2003)Trends Biotechnol.21:484);一本鎖抗体分子;ならびに抗体断片から形成される多重特異性抗体が挙げられる。抗体のパパイン消化により、「Fab」断片と呼ばれる、各々が単一の抗原−結合部位を有する2つの同一抗原−結合断片、及びその名称が容易に結晶化する能力を反映している残りの「Fc」断片が作製される。ペプシン処理により、2つの抗原結合部位を有し、依然として抗原を架橋することができるF(ab’)2断片が生じる。
1991に従って定義された。
本開示は、補体C1sタンパク質と結合するヒト化抗体(すなわち、ヒト化抗補体C1s抗体、本明細書においては「ヒト化抗C1s抗体」、「ヒト化C1s抗体」、及び「本願の抗体」とも称される)ならびにこのような抗体をコードするヌクレオチド配列を含む核酸を提供する。本開示はまた、本開示のヒト化抗C1s抗体を含む組成物を提供する。本開示は、本開示の抗体、核酸、及び組成物を作製する方法及び使用する方法を提供する。本開示は、補体媒介性疾患または障害を処置する方法を提供し、本開示のヒト化抗C1s抗体を投与することを含む。
本開示は、ヒト化抗補体C1s抗体及びこのような抗体を含む医薬組成物を提供する。補体C1sは、補体カスケードの上流に存在するような魅力的な標的であり、基質特異性の範囲が狭い。いくつかの場合には、C1sの活性型と特異的に結合する抗体に関心があり、例えば、この抗体はC1sの不活性型とは実質的に結合しない。
Institutes of Health,Bethesda,Md.,1987 and 1991)によって定義される通りである。代替的構造定義が、Chothia
et al.,J.Mol.Biol.196:901(1987);Nature 342:878(1989);及びJ.Mol.Biol.186:651(1989)(総じて「Chothia」と称される)によって提案されている。上記Kabatによって定義されるようなフレームワーク残基が、上記Chothiaによって定義されるような構造的ループ残基を構成する場合、マウス抗体中に存在するアミノ酸が、ヒト化抗体への置換のために選択され得る。「CDR領域に隣接する」残基は、ヒト化免疫グロブリン鎖の一次配列中におけるCDRのうち1つ以上に直接隣接する位置のアミノ酸残基、例えば、Kabatによって定義されるようなCDR、またはChothiaによって定義されるようなCDR(例えば、Chothia and Lesk JMB 196:901(1987)を参照のこと)に直接隣接する位置のアミノ酸残基を含む。これらのアミノ酸は特に、CDR中のアミノ酸と相互作用する可能性があり、それらがアクセプターから選択される場合、ドナーCDRを変形させて親和性を減少させる可能性がある。さらに、隣接アミノ酸は、抗原と直接相互作用し得(Amit et al.,Science,233:747(1986))、これらのアミノ酸をドナーから選択することは、元の抗体における親和性を提供する抗原接触部位を全て保持するのに望ましいことであり得る。
本開示は、本開示のヒト化抗C1s抗体をコードするヌクレオチド配列を含む核酸を提供する。いくつかの場合には、本開示の核酸は、本開示のヒト化抗C1s抗体のVH領域をコードするヌクレオチド配列を含む。いくつかの場合には、本開示の核酸は、本開示のヒト化抗C1s抗体のVL領域をコードするヌクレオチド配列を含む。いくつかの場合には、本開示の核酸は、本開示のヒト化抗C1s抗体のVH領域及びVL領域をコードするヌクレオチド配列を含む。
al.,Gene Ther 6:515 524,1999;Li and Davidson,PNAS 92:7700 7704,1995;Sakamoto et al.,H Gene Ther 5:1088 1097,1999;WO94/12649、WO93/03769;WO93/19191;WO94/28938;WO95/11984及びWO95/00655を参照のこと);アデノ随伴ウイルス(例えば、Ali et al.,Hum Gene Ther 9:81 86,1998,Flannery et al.,PNAS 94:6916 6921,1997;Bennett et al.,Invest Opthalmol Vis Sci 38:2857 2863,1997;Jomary et al.,Gene Ther
4:683 690,1997,Rolling et al.,Hum Gene Ther 10:641 648,1999;Ali et al.,Hum Mol Genet 5:591 594,1996;WO93/09239のSrivastava、Samulski et al.,J.Vir.(1989)63:3822−3828;Mendelson et al.,Virol.(1988)166:154−165;及びFlotte et al.,PNAS(1993)90:10613−10617を参照のこと);SV40;単純ヘルペスウイルスに基づくウイルスベクター;レトロウイルスベクター(例えば、マウス白血病ウイルス、脾臓壊死ウイルス、ならびにレトロウイルス、例えば、ラウス肉腫ウイルス、ハーベイ肉腫ウイルス、トリ白血病ウイルス、ヒト免疫不全ウイルス(例えば、Miyoshi et al.,PNAS 94:10319 23,1997;Takahashi et al.,J Virol
73:7812 7816,1999を参照のこと)、骨髄増殖性肉腫ウイルス、及び乳房腫瘍ウイルスなどに由来するベクター)などが挙げられるが、これらに限定されない。
本開示は、本願の核酸で遺伝子組換えされる単離された遺伝子組換え宿主細胞(例えば、インビトロ細胞)を提供する。いくつかの実施形態では、本願の単離された遺伝子組換え宿主細胞は、本願の抗体を産生し得る。このような細胞は、「組換え細胞」または「遺伝子組換え宿主細胞」と称される。本開示の遺伝子組換え宿主細胞は、本開示のヒト化抗C1s抗体をコードするヌクレオチド配列を含む核酸を含む。
本開示は、本開示のヒト化抗C1s抗体を含む医薬組成物を含む、組成物を提供する。一般に、医薬組成物は、本明細書では製剤とも称されて、有効量の本開示のヒト化抗C1s抗体を含む。「有効量」は、所望の結果、例えば、補体媒介性疾患または障害と関連する有害症状の減少、補体媒介性疾患または障害の症状の改善、補体媒介性疾患または障害の緩徐進行などをもたらすのに十分な投与量を意味する。一般に、所望の結果は、対照と比較した場合に、補体媒介性疾患または障害の症状を少なくとも減少させることである。いくつかの実施形態では、本開示のヒト化抗C1s抗体は、抗体が血液脳関門を通過できるように製剤化かつ/または改変される。いくつかの実施形態では、本開示のヒト化抗C1s抗体は、血液脳関門を回避するような手法で送達される。いくつかの実施形態では、本開示のヒト化抗C1s抗体は、血液脳関門の通過を容易にする薬剤と共に製剤化される。いくつかの実施形態では、本開示のヒト化抗C1s抗体は、血液脳関門の通過を促進する化合物に、直接またはリンカーを介して融合される。
本願の方法では、本開示のヒト化抗C1s抗体は、所望の治療効果または診断効果をもたらすことができる任意の簡便な手段を使用して宿主に投与され得る。したがって、薬剤は、治療的投与のために様々な製剤中に組み込まれ得る。より具体的には、本開示のヒト化抗C1s抗体は、適切な薬学的に許容される担体、薬学的に許容される希釈剤、またはその他の薬学的に許容される賦形剤と組み合わせることにより医薬組成物へと製剤化され得、固体、半固体、液体または気体形態の調製物、例えば、錠剤、カプセル剤、散剤、顆粒剤、軟膏剤、液剤、坐剤、注射剤、吸入剤及びエアロゾル剤などへと製剤化され得る。いくつかの実施形態では、医薬組成物は、本開示のヒト化抗C1s抗体及び薬学的に許容される賦形剤を含む。
好適な投与量は、様々な臨床因子に基づいて、主治医またはその他の資格のある医療関係者により決定され得る。医療技術分野においては周知の通り、任意の1人の患者に対する投与量は、患者の身体サイズ、体表面積、年齢、投与される特定の化合物、患者の性別、投与時間、及び投与経路、全身の健康状態、ならびに同時に投与されているその他の薬物を含む、多くの因子に依存する。本願の抗体は、1用量あたり1ng/kg体重〜20mg/kg体重、例えば、0.1mg/kg体重〜10mg/kg体重、例えば、0.5mg/kg体重〜5mg/kg体重の量で投与され得るが;特に上述した因子を考慮すると、この例示的な範囲を下回る、または上回る用量が想定される。レジメンが持続注入である場合、その量はまた、毎分1μg〜10mg/キログラム体重の範囲内であり得る。
本願の抗体は、インビボ及びエクスビボの方法に加えて、全身投与経路及び局所投与経路を含む、薬物送達に好適な任意の利用可能な方法及び経路を使用して個体に投与される。
本開示は、補体媒介性疾患または障害を処置する方法を提供する。本方法は一般に、有効量の本開示のヒト化抗C1s抗体、またはこのような抗体を含む医薬組成物を、それを必要とする個体に投与することを含む。いくつかの場合には、本願の抗C1s抗体の投与により、個体の細胞、組織、体液、または器官における補体C1sの活性が調節されて、補体媒介性疾患または障害が処置される。本開示は、個体における補体成分C4の活性化を阻害する方法を提供し、本方法は、個体に有効量の本開示のヒト化抗C1s抗体またはこのような抗体を含む医薬組成物を投与することを含む。本開示は、個体における補体C1s活性を阻害する方法を提供し、本方法は、個体に有効量の本開示のヒト化抗C1s抗体またはこのような抗体を含む医薬組成物を投与することを含む。本開示は、個体における(例えば、個体の体液、組織、または器官における)補体成分分解産物のレベルを減少させる方法を提供し、本方法は、個体に有効量の本開示のヒト化抗C1s抗体またはこのような抗体を含む医薬組成物を投与することを含む。
TNT005のヒト化バリアントを生成した。ヒト化バリアント1〜5の重鎖VHドメインのアミノ酸配列;ヒト化バリアントの重鎖VHドメインをコードするヌクレオチド配列もまた提供する。ヒト化バリアント1、2、及び5の軽鎖VLドメインのアミノ酸配列、ならびにヒト化バリアントの軽鎖VLドメインをコードするヌクレオチド配列を図6〜図8に示す。TNT005のアミノ酸配列(VL配列番号:7;VH配列番号:8)と比較したアミノ酸差異を表2及び表3(それぞれ図9及び図10)にまとめる。
G−グリシン(Gly)
P−プロリン(Pro)
A−アラニン(Ala)
V−バリン(Val)
L−ロイシン(Leu)
I−イソロイシン(Ile)
M−メチオニン(Met)
C−システイン(Cys)
F−フェニルアラニン(Phe)
Y−チロシン(Tyr)
W−トリプトファン(Trp)
H−ヒスチジン(His)
K−リジン(Lys)
R−アルギニン(Arg)
Q−グルタミン(Gln)
N−アスパラギン(Asn)
E−グルタミン酸(Glu)
D−アスパラギン酸(Asp)
S−セリン(Ser)
T−トレオニン(Thr)
ヒト化TNT005バリアントの結合特性を表4及び表5(それぞれ図11及び図12)に提供する。様々なヒト化TNT005バリアントと活性化C1sとの相対的結合親和性を表4(第1データ列)に提供し、これを図11中に提示する。
ヒト化TNT005の薬物動態(PK)及び薬力学的(PD)特性を評価するために、ヒト化TNT005の単回投与及び反復投与試験を、カニクイザル(Macaca fascicularis)において実施した。さらに、様々な投与経路によるヒト化TNT005のバイオアベイラビリティを比較するために、ヒト化TNT005バリアントを血管内(IV)注射または皮下(SC)注射のいずれかにより投与した。ヒト化TNT005の投与後、血漿及び血清試料を指定の時点で採取し、ヒト化TNT005の循環濃度(PK)を決定して、ヒト化TNT005による古典的補体経路の阻害(PD)を評価した。
フェーズ1 薬物動態及び薬力学
フェーズ1においてヒト化TNT005の薬物動態プロファイルを評価するために、表7で指定した時点で採取した血漿試料を希釈し、ELISAを実行してヒト化TNT005血漿濃度を定量化した。簡潔に述べると、希釈した血漿試料を活性化C1sでプレコートした96ウェルプレートに添加した。血漿試料をインキュベートし、続いて洗浄した後、ヒトIgGに特異的な西洋ワサビペルオキシダーゼ複合化検出抗体を添加し、C1s結合ヒト化TNT005を検出した。最後に、3,3’,5,5’−テトラメチルベンジジン(TMB)基質を添加し、比色反応を開始させて分光光度計上で読み取った。血漿試料と並行して実行したヒト化TNT005の標準曲線から補間することにより、ヒト化TNT005血漿濃度を全ての試料について決定した。試験のフェーズ1における薬物動態分析結果を、図14(1〜43日目)及び図15(32〜43日目)に示す。IV投与後、ヒト化TNT005の血漿PKプロファイルは、典型的に高いCmaxに続いて用量依存的なクリアランスを示した。SC投与は、より緩やかな吸収相をもたらし、結果としてCmaxは全体的により低く、対応したIV用量コホートと比較して遅かった。45mg/kgのIV及びSC用量群におけるヒト化TNT005クリアランス速度は、72時間から試験の終了まで同等であった。
フェーズ2におけるヒト化TNT005薬物動態及び薬力学を、フェーズ1に記載したものと同じ手法でアッセイした。試験のフェーズ2における薬物動態及び薬力学分析の結果を図17に示す。低用量ヒト化TNT005(4mg/kg)のSC投与は、投与から最初の24時間以内に緩やかな吸収相をもたらした(図17、赤色プロット、右側y軸)。血漿ヒト化TNT005濃度の上昇に伴い、血清古典的経路活性は減少した(図17、青色プロット、左側y軸)。毎日4mg/kgで反復投与すると、血漿ヒト化TNT005の漸増をもたらし、血清古典的経路活性を7日目までに投与前レベルの10%までさらに減少させた(すなわち、−90%の古典的経路阻害)。
特定の実施形態では、例えば以下の項目が提供される。
(項目1)
補体成分C1sと特異的に結合するヒト化抗体であって、前記抗体が、
a)アミノ酸配列:(Q/E)VQL(V/Q)QSGAE(V/L)KKPGASVK(L/V)SC(T/A)ASGFNIKDDYIHWV(K/R)QAPGQGLEWIGRIDPADGHTKYAPKFQVK(V/A)TITADTST(S/N)TAY(L/M)(E/Q)LSSL(R/T)SEDTAVYYCARYGYGREVFDYWGQGTTVTVSS(配列番号:26)を含むVH領域と;
b)アミノ酸配列:DIVLTQSPDSLAVSLGERATISCKASQSVDYDGDSYMNWYQQK(T/P)GQPPK(I/L)LIYDASNLESGIPARFSGSGSGTDFTLTISSLE(E/P)EDFA(I/V)YYCQQSNEDPWTFGGGTKVEIK(配列番号:27)を含むVL領域と
を含む、前記ヒト化抗体。
(項目2)
a)配列番号:10を含むVH領域と;
b)配列番号:20を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目3)
a)配列番号:10を含むVH領域と;
b)配列番号:22を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目4)
a)配列番号:10を含むVH領域と;
b)配列番号:24を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目5)
a)配列番号:12を含むVH領域と;
b)配列番号:20を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目6)
a)配列番号:12を含むVH領域と;
b)配列番号:22を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目7)
a)配列番号:12を含むVH領域と;
b)配列番号:24を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目8)
a)配列番号:14を含むVH領域と;
b)配列番号:20を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目9)
a)配列番号:14を含むVH領域と;
b)配列番号:22を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目10)
a)配列番号:14を含むVH領域と;
b)配列番号:24を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目11)
a)配列番号:16を含むVH領域と;
b)配列番号:20を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目12)
a)配列番号:16を含むVH領域と;
b)配列番号:22を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目13)
a)配列番号:16を含むVH領域と;
b)配列番号:24を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目14)
a)配列番号:18を含むVH領域と;
b)配列番号:20を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目15)
a)配列番号:18を含むVH領域と;
b)配列番号:22を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目16)
a)配列番号:18を含むVH領域と;
b)配列番号:24を含むVL領域と
を含む、項目1に記載のヒト化抗体。
(項目17)
前記ヒト化抗体が、Fab断片、F(ab’)2断片、scFv、及びFvからなる群から選択される、項目1〜16のいずれか1項に記載のヒト化抗体。
(項目18)
前記ヒト化抗体が、アイソタイプIgG1、IgG2、IgG3、またはIgG4の重鎖定常領域を含む、項目1〜16のいずれか1項に記載のヒト化抗体。
(項目19)
a)項目1〜18のいずれか1項に記載の前記ヒト化抗体と;
b)薬学的に許容される賦形剤と
を含む、組成物。
(項目20)
前記組成物が、等張化剤、懸濁化剤、乳化剤、安定剤、防腐剤、リオプロテクタント、界面活性剤、及び糖のうち1種以上を含む、項目19に記載の組成物。
(項目21)
項目19または項目20に記載の前記組成物を含む、容器。
(項目22)
前記容器が滅菌である、項目21に記載の容器。
(項目23)
前記容器が、バイアル、ボトル、またはシリンジである、項目21または項目22に記載の容器。
(項目24)
個体における補体成分分解産物レベルの減少方法であって、前記個体に項目1〜18のいずれか1項に記載の前記抗体、または項目19もしくは20に記載の前記組成物を、C1sを阻害し、かつ前記分解産物の前記レベルを減少させるのに効果的な量で投与することを含む、前記方法。
(項目25)
前記補体成分分解産物が、C4分解産物である、項目24に記載の方法。
(項目26)
前記補体成分分解産物が、C2分解産物である、項目25に記載の方法。
(項目27)
前記補体成分分解産物が、C3分解産物である、項目25に記載の方法。
(項目28)
前記個体がヒトである、項目24〜27のいずれか1項に記載の方法。
(項目29)
前記投与が静脈内投与である、項目24〜28のいずれか1項に記載の方法。
(項目30)
前記投与が筋肉内投与である、項目24〜28のいずれか1項に記載の方法。
(項目31)
前記投与が髄腔内投与である、項目24〜28のいずれか1項に記載の方法。
(項目32)
前記投与が皮下投与である、項目24〜28のいずれか1項に記載の方法。
(項目33)
前記減少が、補体媒介性障害を処置するのに効果的である、項目24〜28のいずれか1項に記載の方法。
(項目34)
前記補体媒介性障害が、同種免疫障害である、項目33に記載の方法。
(項目35)
前記補体媒介性障害が、自己免疫障害である、項目33に記載の方法。
(項目36)
個体における補体成分のC1s媒介性切断の阻害方法であって、前記個体に項目1〜18のいずれか1項に記載の前記抗体、または項目19もしくは20に記載の前記組成物を、補体成分のC1s媒介性切断を阻害するのに効果的な量で投与することを含む、前記方法。
(項目37)
個体における補体媒介性疾患または障害の処置方法であって、前記個体に項目1〜18のいずれか1項に記載の前記抗体、または項目19もしくは20に記載の前記組成物を、前記補体媒介性疾患または障害を処置するのに効果的な量で投与することを含む、前記方法。
Claims (1)
- 本明細書に記載の発明。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022034295A JP2022078221A (ja) | 2015-04-06 | 2022-03-07 | ヒト化抗C1s抗体及びその使用方法 |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562143636P | 2015-04-06 | 2015-04-06 | |
US62/143,636 | 2015-04-06 | ||
US201562200997P | 2015-08-04 | 2015-08-04 | |
US62/200,997 | 2015-08-04 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018503727A Division JP7005483B2 (ja) | 2015-04-06 | 2016-04-05 | ヒト化抗C1s抗体及びその使用方法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022034295A Division JP2022078221A (ja) | 2015-04-06 | 2022-03-07 | ヒト化抗C1s抗体及びその使用方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021006544A true JP2021006544A (ja) | 2021-01-21 |
JP7153696B2 JP7153696B2 (ja) | 2022-10-14 |
Family
ID=57073330
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018503727A Active JP7005483B2 (ja) | 2015-04-06 | 2016-04-05 | ヒト化抗C1s抗体及びその使用方法 |
JP2020161908A Active JP7153696B2 (ja) | 2015-04-06 | 2020-09-28 | ヒト化抗C1s抗体及びその使用方法 |
JP2022034295A Pending JP2022078221A (ja) | 2015-04-06 | 2022-03-07 | ヒト化抗C1s抗体及びその使用方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018503727A Active JP7005483B2 (ja) | 2015-04-06 | 2016-04-05 | ヒト化抗C1s抗体及びその使用方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022034295A Pending JP2022078221A (ja) | 2015-04-06 | 2022-03-07 | ヒト化抗C1s抗体及びその使用方法 |
Country Status (27)
Country | Link |
---|---|
US (3) | US10729767B2 (ja) |
EP (2) | EP3280440B1 (ja) |
JP (3) | JP7005483B2 (ja) |
KR (1) | KR20180006379A (ja) |
CN (2) | CN117285634A (ja) |
AU (2) | AU2016246452B2 (ja) |
BR (1) | BR112017021289A2 (ja) |
CA (1) | CA2981321A1 (ja) |
CL (1) | CL2017002514A1 (ja) |
CO (1) | CO2017011238A2 (ja) |
DK (1) | DK3280440T3 (ja) |
EA (1) | EA201792080A1 (ja) |
ES (1) | ES2938359T3 (ja) |
FI (1) | FI3280440T3 (ja) |
HK (2) | HK1250930A1 (ja) |
HR (1) | HRP20230093T1 (ja) |
HU (1) | HUE061076T2 (ja) |
IL (2) | IL298180A (ja) |
LT (1) | LT3280440T (ja) |
MX (2) | MX2017012834A (ja) |
PH (1) | PH12017501815A1 (ja) |
PL (1) | PL3280440T3 (ja) |
PT (1) | PT3280440T (ja) |
RS (1) | RS63956B1 (ja) |
SG (2) | SG10201909180SA (ja) |
SI (1) | SI3280440T1 (ja) |
WO (1) | WO2016164358A1 (ja) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014030750A1 (ja) | 2012-08-24 | 2014-02-27 | 中外製薬株式会社 | マウスFcγRII特異的Fc抗体 |
CA3124553A1 (en) | 2012-10-25 | 2014-05-01 | Bioverativ Usa Inc. | Anti-complement c1s antibodies and uses thereof |
CN104884088B (zh) | 2012-11-02 | 2018-06-15 | 美国比奥维拉迪维股份有限公司 | 抗补体C1s抗体和其用途 |
CA2908350C (en) | 2013-04-02 | 2023-08-08 | Futa Mimoto | Fc region variant |
SI3280440T1 (sl) | 2015-04-06 | 2023-03-31 | Bioverativ Usa Inc. | Humanizirana protitelesa proti C1S in načini uporabe |
JP7069138B2 (ja) * | 2016-10-12 | 2022-05-17 | バイオベラティブ・ユーエスエイ・インコーポレイテッド | 抗C1s抗体およびその使用方法 |
BR112020018357A2 (pt) * | 2018-04-13 | 2020-12-29 | Chugai Seiyaku Kabushiki Kaisha | Anticorpos de componente anticomplemento e métodos de uso |
KR20230044312A (ko) | 2020-08-06 | 2023-04-03 | 바이오버라티브 유에스에이 인코포레이티드 | 보체 매개된 질환을 갖는 대상체의 염증성 시토카인 및 피로 |
EP4313296A1 (en) | 2021-03-31 | 2024-02-07 | Bioverativ USA Inc. | Reducing surgery-associated hemolysis in cold agglutinin disease patients |
EP4337332A2 (en) | 2021-07-13 | 2024-03-20 | Mabwell Therapeutics Inc. | Anti-c1s antibodies and uses thereof |
WO2023245048A1 (en) | 2022-06-15 | 2023-12-21 | Bioverativ Usa Inc. | Anti-complement c1s antibody formulation |
US20240025978A1 (en) | 2022-06-24 | 2024-01-25 | Bioverativ Usa Inc. | Methods for treating complement-mediated diseases |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014066744A2 (en) * | 2012-10-25 | 2014-05-01 | True North Therapeutics, Inc. | Anti-complement c1s antibodies and uses thereof |
Family Cites Families (100)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
JPS60192263A (ja) | 1984-03-13 | 1985-09-30 | Teijin Ltd | 免疫複合体測定用標準物質及びそれを用いた免疫複合体の測定法 |
GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
AU612370B2 (en) | 1987-05-21 | 1991-07-11 | Micromet Ag | Targeted multifunctional proteins |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
WO1993003769A1 (en) | 1991-08-20 | 1993-03-04 | THE UNITED STATES OF AMERICA, represented by THE SECRETARY, DEPARTEMENT OF HEALTH AND HUMAN SERVICES | Adenovirus mediated transfer of genes to the gastrointestinal tract |
DK0605522T3 (da) | 1991-09-23 | 2000-01-17 | Medical Res Council | Fremgangsmåde til fremstilling af humaniserede antistoffer |
US5252479A (en) | 1991-11-08 | 1993-10-12 | Research Corporation Technologies, Inc. | Safe vector for gene therapy |
JPH07501451A (ja) | 1991-11-25 | 1995-02-16 | エンゾン・インコーポレイテッド | 多価抗原結合タンパク質 |
FR2688514A1 (fr) | 1992-03-16 | 1993-09-17 | Centre Nat Rech Scient | Adenovirus recombinants defectifs exprimant des cytokines et medicaments antitumoraux les contenant. |
WO1994012649A2 (en) | 1992-12-03 | 1994-06-09 | Genzyme Corporation | Gene therapy for cystic fibrosis |
DE614989T1 (de) | 1993-02-17 | 1995-09-28 | Morphosys Proteinoptimierung | Verfahren für in vivo Selektion von Ligandenbindende Proteine. |
WO1995000655A1 (en) | 1993-06-24 | 1995-01-05 | Mc Master University | Adenovirus vectors for gene therapy |
DE69429816T2 (de) | 1993-09-01 | 2002-09-19 | Sanquin Bloedvoorziening | C1-Esterasehemmer zur Verringerung von Myokardschäden bei akutem Herzinfarkt |
EP1637608B1 (en) | 1993-10-25 | 2009-07-22 | CANJI, Inc. | Recombinant adenoviral vector and methods of use |
SG119177A1 (en) | 1994-12-09 | 2006-02-28 | Imp College Innovations Ltd | Identification of genes |
US6969601B2 (en) | 1997-04-03 | 2005-11-29 | Jensenius Jens Chr | MASP-2, a complement-fixing enzyme, and uses for it |
US6080849A (en) | 1997-09-10 | 2000-06-27 | Vion Pharmaceuticals, Inc. | Genetically modified tumor-targeted bacteria with reduced virulence |
AU3998400A (en) | 1999-02-09 | 2000-08-29 | 3-Dimensional Pharmaceuticals, Inc. | Methods of treating c1s-mediated diseases and conditions, and compounds and compositions therefor |
AU4369000A (en) | 1999-04-26 | 2000-11-10 | Duke University | Inhibition of complement action |
AU6929100A (en) | 1999-08-23 | 2001-03-19 | Biocrystal Limited | Methods and compositions for immunotherapy of b cell involvement in promotion ofa disease condition comprising multiple sclerosis |
JP2003521914A (ja) | 2000-01-31 | 2003-07-22 | ファーミング インテレクチュアル プロパティー ベー.フェー. | トランスジェニック哺乳動物の乳汁に産生されるc1インヒビター |
AU2001249410A1 (en) | 2000-03-23 | 2001-10-03 | Tanox, Inc. | Anti-c2/c2a inhibitors of complement activation |
US7071299B2 (en) | 2000-06-21 | 2006-07-04 | Zymogenetics, Inc. | Peptide and polypeptide inhibitors of complement C1s |
GB0105924D0 (en) | 2001-03-09 | 2001-04-25 | Microscience Ltd | Promoter |
CA2454562A1 (en) | 2001-07-26 | 2003-02-06 | Alexion Pharmaceuticals, Inc. | Method of improving cognitive function |
US20080206242A1 (en) | 2002-03-01 | 2008-08-28 | Xencor, Inc. | Method of treatment of th2-mediated conditions using optimized anti-cd30 antibodies |
SE0202880D0 (sv) | 2002-07-26 | 2002-09-30 | Wieslab Ab | Complement system deficiency assay |
US7666627B2 (en) | 2002-08-08 | 2010-02-23 | Targetex Kft. | Folded recombinant catalytic fragments of multidomain serine proteases, preparation and uses thereof |
US20050271660A1 (en) | 2002-09-06 | 2005-12-08 | Alexion Pharmaceuticals, Inc. | Nebulization of monoclonal antibodies for treating pulmonary diseases |
EP1545611B1 (en) | 2002-09-06 | 2016-11-09 | Alexion Pharmaceuticals, Inc. | Method of treatment of asthma using antibodies to complement component c5 |
US7361339B2 (en) | 2003-01-09 | 2008-04-22 | Alexion Pharmaceuticals, Inc. | Methods for reducing morality associated with acute myocardial infarction |
CA2524534C (en) | 2003-05-15 | 2012-12-11 | Sek Chung Fung | Methods and compositions for the prevention and treatment of sepsis |
US7482376B2 (en) | 2003-07-03 | 2009-01-27 | 3-Dimensional Pharmaceuticals, Inc. | Conjugated complement cascade inhibitors |
WO2005014849A2 (en) | 2003-07-03 | 2005-02-17 | Euro-Celtique, S.A. | Genes associated with responses to neuropathic pain |
WO2005025509A2 (en) | 2003-09-11 | 2005-03-24 | Board Of Regents, The University Of Texas System | Methods and materials for treating autoimmune diseases and conditions |
US8501705B2 (en) | 2003-09-11 | 2013-08-06 | The Board Of Regents Of The University Of Texas System | Methods and materials for treating autoimmune and/or complement mediated diseases and conditions |
US20080075712A1 (en) | 2003-10-14 | 2008-03-27 | Kunihiro Hattori | Double Specific Antibodies Substituting For Functional Proteins |
JP2007512846A (ja) * | 2003-12-04 | 2007-05-24 | ゼンコー・インコーポレイテッド | 増加した宿主ストリング含有量を有する変異体タンパク質の生成方法およびその組成物 |
US7803931B2 (en) | 2004-02-12 | 2010-09-28 | Archemix Corp. | Aptamer therapeutics useful in the treatment of complement-related disorders |
KR100891620B1 (ko) | 2004-04-13 | 2009-04-02 | 에프. 호프만-라 로슈 아게 | 항-p-셀렉틴 항체 |
US8840893B2 (en) | 2004-06-10 | 2014-09-23 | Omeros Corporation | Methods for treating conditions associated with MASP-2 dependent complement activation |
US20060018896A1 (en) | 2004-06-10 | 2006-01-26 | University Of Leicester | Methods for treating conditions associated with lectin-dependent complement activation |
EP2382991A1 (en) | 2004-06-10 | 2011-11-02 | Omeros Corporation | Methods for treating conditions associated with MASP-2 dependent complement activation |
US7919094B2 (en) | 2004-06-10 | 2011-04-05 | Omeros Corporation | Methods for treating conditions associated with MASP-2 dependent complement activation |
US8367805B2 (en) | 2004-11-12 | 2013-02-05 | Xencor, Inc. | Fc variants with altered binding to FcRn |
AU2005313971B2 (en) | 2004-12-08 | 2011-10-13 | Immunomedics, Inc. | Methods and compositions for immunotherapy and detection of inflammatory and immune-dysregulatory disease, infectious disease, pathologic angiogenesis and cancer |
KR20080002832A (ko) | 2005-03-16 | 2008-01-04 | 얀센 파마슈티카 엔.브이. | 보체 매개성 질병 및 이상을 치료하기 위한 신규한 티오펜설폭시민 |
EP2529746A1 (en) | 2005-06-06 | 2012-12-05 | Girish J. Kotwal | Methods for treatment or prophylaxis of reperfusion injury |
US20070093443A1 (en) | 2005-10-21 | 2007-04-26 | Madison Edwin L | Modified proteases that inhibit complement activation |
US9480658B2 (en) | 2005-12-09 | 2016-11-01 | The Board Of Trustees Of The Leland Stanford Junior University | Modulation of synaptic maintenance |
WO2007070375A2 (en) | 2005-12-09 | 2007-06-21 | The Board Of Trustees Of The Leland Stanford Junior University | Modulation of synaptic maintenance |
AU2006327989B2 (en) | 2005-12-21 | 2012-06-07 | Pharming Intellectual Property Bv | Use of C1 inhibitor for the prevention of ischemia-reperfusion injury |
FR2897868B1 (fr) | 2006-02-24 | 2012-08-31 | Lab Francais Du Fractionnement | Anticorps anti-idiotypiques neutralisant l'activite inhibitrice d'un anticorps inhibiteur dirige contre le domaine c1 du facteur viii. |
US20090269356A1 (en) | 2006-03-08 | 2009-10-29 | David Epstein | Complement Binding Aptamers and Anti-C5 Agents Useful in the Treatment of Ocular Disorders |
CA2662480C (en) | 2006-09-05 | 2016-11-08 | Alexion Pharmaceuticals, Inc. | Methods and compositions for the treatment of antibody mediated neuropathies |
LT3028716T (lt) | 2006-10-10 | 2020-12-10 | Regenesance B.V. | Komplemento slopinimas nervų regeneracijos pagerinimui |
WO2008074227A1 (en) | 2006-12-19 | 2008-06-26 | Versitech Limited | Synthetic ion channels |
EP2148691B1 (en) | 2007-02-05 | 2015-05-20 | Apellis Pharmaceuticals, Inc. | Compstatin analogues for use in the treatment of inflammatory conditions of the respiratory system |
US8192742B2 (en) | 2007-03-23 | 2012-06-05 | NovelMed Therapeutics | Method of inhibiting complement activation with human anti-factor C3 antibodies and use thereof |
ATE543835T1 (de) | 2007-07-16 | 2012-02-15 | Genentech Inc | Anti-cd79b-antikörper und immunkonjugate und anwendungsverfahren |
WO2009035786A1 (en) | 2007-08-03 | 2009-03-19 | Genentech, Inc. | Humanized anti-fgf19 antagonists and methods using same |
US20110190221A1 (en) | 2008-03-28 | 2011-08-04 | Apellis Ag | Modulation and repletion/enhancement of the complement system for treatment of trauma |
AU2009239437B2 (en) | 2008-04-25 | 2014-11-13 | University Of Washington | Levels of BCMA protein expression on B cells and use in diagnostic methods |
US20090324585A1 (en) | 2008-06-12 | 2009-12-31 | The Trustees of the Leland Standford Junior University | Complement inhibitory agents as therapeutics in posttraumatic and degenerative arthritis |
AU2009313203B2 (en) | 2008-11-10 | 2015-08-27 | Alexion Pharmaceuticals, Inc. | Methods and compositions for treating complement-associated disorders |
BRPI0923199B8 (pt) | 2008-12-01 | 2021-07-27 | Univ Leland Stanford Junior | método para determinar a presença de anticorpos de fixação de complemento |
US8401799B2 (en) | 2008-12-05 | 2013-03-19 | Lpath, Inc. | Antibody design using anti-lipid antibody crystal structures |
CN102597005A (zh) | 2009-06-23 | 2012-07-18 | 阿雷克森制药公司 | 与补体蛋白质结合的双特异性抗体 |
TW201117824A (en) | 2009-10-12 | 2011-06-01 | Amgen Inc | Use of IL-17 receptor a antigen binding proteins |
PT2488203T (pt) | 2009-10-16 | 2017-03-10 | Univ Leicester | Métodos para tratamento de coagulação intravascular disseminada através da inibição da activação do complemento dependente de masp-2 |
WO2011102342A1 (ja) | 2010-02-16 | 2011-08-25 | 国立大学法人京都工芸繊維大学 | 抗体固定化担体、抗体固定化担体の製造方法および当該抗体固定化担体の利用 |
US8999340B2 (en) | 2010-03-01 | 2015-04-07 | Alexion Pharmaceuticals, Inc. | Methods for treating multiorgan, systemic degos' disease with a complement inhibitor |
AU2011245117B2 (en) | 2010-04-30 | 2015-03-12 | Alexion Pharmaceuticals, Inc. | Anti-C5a antibodies and methods for using the antibodies |
CN103003697A (zh) | 2010-05-17 | 2013-03-27 | 得克萨斯系统大学董事会 | 来自动物的单克隆抗体的快速分离 |
US9421240B2 (en) | 2010-06-22 | 2016-08-23 | Apellis Pharmaceuticals, Inc. | Compstatin analogs for treatment of neuropathic pain |
MX2012014975A (es) | 2010-06-22 | 2013-03-12 | Univ Colorado Regents | Anticuerpos al fragmento c3d de componente 3 de complemento. |
UY33578A (es) | 2010-08-31 | 2012-03-30 | Sanofi Sa | PÉPTIDO O COMPLEJO PEPTÍDICO QUE SE UNE A INTEGRINA a(ALFA) Y MÉTODOS Y USOS QUE IMPLICAN A LOS MISMOS |
TW201241008A (en) | 2010-10-01 | 2012-10-16 | Alexion Pharma Inc | Polypeptides that bind to human complement component C5 |
US8865164B2 (en) | 2010-11-02 | 2014-10-21 | Kypha, Inc. | Detecting complement activation |
PL3156420T3 (pl) | 2010-12-06 | 2019-08-30 | Seattle Genetics, Inc. | Humanizowane przeciwciała przeciw liv-1 i ich stosowanie w leczeniu raka |
JP5937197B2 (ja) | 2011-04-08 | 2016-06-22 | ユニバーシティー オブ レスター | Masp−2依存性補体活性化に関連した状態を治療するための方法 |
DK2704743T3 (en) | 2011-05-04 | 2020-05-25 | Omeros Corp | Compositions for inhibiting masp-2 dependent complement acitivation |
US9289467B2 (en) | 2011-08-10 | 2016-03-22 | Case Western Reserve University | Compositions and methods for treating bone conditions |
CN104080474B (zh) | 2011-12-22 | 2016-04-27 | 德国杰特贝林生物制品有限公司 | C1-抑制剂在治疗中枢神经系统继发性水肿中的应用 |
JP6081699B2 (ja) | 2011-12-28 | 2017-02-15 | 雅史 溝上 | Il−28bの分析方法 |
CN104884088B (zh) | 2012-11-02 | 2018-06-15 | 美国比奥维拉迪维股份有限公司 | 抗补体C1s抗体和其用途 |
RU2663349C2 (ru) | 2013-01-31 | 2018-08-03 | СЕУЛ НЭШНЛ ЮНИВЕРСИТИ Ар энд ДиБи ФАУНДЕЙШН | Антитело против с5 и способ предупреждения и лечения обусловленных комплементом заболеваний |
EP4252769A3 (en) | 2013-07-09 | 2023-11-29 | Annexon, Inc. | Anti-complement factor c1q antibodies and uses thereof |
WO2015084999A1 (en) | 2013-12-06 | 2015-06-11 | True North Therapeutics, Inc. | Complement component biomarker assays |
SI3280440T1 (sl) | 2015-04-06 | 2023-03-31 | Bioverativ Usa Inc. | Humanizirana protitelesa proti C1S in načini uporabe |
BR112017027578A2 (pt) | 2015-06-26 | 2018-08-28 | Bioverativ Usa Inc | métodos de tratamento de distúrbios autoimunes e aloimunes |
JP7069138B2 (ja) | 2016-10-12 | 2022-05-17 | バイオベラティブ・ユーエスエイ・インコーポレイテッド | 抗C1s抗体およびその使用方法 |
SG11201907583TA (en) | 2017-03-14 | 2019-09-27 | Bioverativ Usa Inc | Methods for treating complement-mediated diseases and disorders |
-
2016
- 2016-04-05 SI SI201631662T patent/SI3280440T1/sl unknown
- 2016-04-05 BR BR112017021289A patent/BR112017021289A2/pt active Search and Examination
- 2016-04-05 HR HRP20230093TT patent/HRP20230093T1/hr unknown
- 2016-04-05 SG SG10201909180S patent/SG10201909180SA/en unknown
- 2016-04-05 FI FIEP16777134.4T patent/FI3280440T3/fi active
- 2016-04-05 JP JP2018503727A patent/JP7005483B2/ja active Active
- 2016-04-05 RS RS20230104A patent/RS63956B1/sr unknown
- 2016-04-05 HU HUE16777134A patent/HUE061076T2/hu unknown
- 2016-04-05 CN CN202311019350.8A patent/CN117285634A/zh active Pending
- 2016-04-05 EP EP16777134.4A patent/EP3280440B1/en active Active
- 2016-04-05 CN CN201680032952.9A patent/CN108348598B/zh active Active
- 2016-04-05 LT LTEPPCT/US2016/026038T patent/LT3280440T/lt unknown
- 2016-04-05 IL IL298180A patent/IL298180A/en unknown
- 2016-04-05 US US15/564,904 patent/US10729767B2/en active Active
- 2016-04-05 MX MX2017012834A patent/MX2017012834A/es unknown
- 2016-04-05 SG SG11201707886WA patent/SG11201707886WA/en unknown
- 2016-04-05 KR KR1020177032117A patent/KR20180006379A/ko not_active Application Discontinuation
- 2016-04-05 EA EA201792080A patent/EA201792080A1/ru unknown
- 2016-04-05 IL IL254670A patent/IL254670B2/en unknown
- 2016-04-05 AU AU2016246452A patent/AU2016246452B2/en active Active
- 2016-04-05 EP EP22207626.7A patent/EP4212175A1/en active Pending
- 2016-04-05 PT PT167771344T patent/PT3280440T/pt unknown
- 2016-04-05 CA CA2981321A patent/CA2981321A1/en active Pending
- 2016-04-05 PL PL16777134.4T patent/PL3280440T3/pl unknown
- 2016-04-05 DK DK16777134.4T patent/DK3280440T3/da active
- 2016-04-05 ES ES16777134T patent/ES2938359T3/es active Active
- 2016-04-05 WO PCT/US2016/026038 patent/WO2016164358A1/en active Application Filing
-
2017
- 2017-10-03 PH PH12017501815A patent/PH12017501815A1/en unknown
- 2017-10-05 CL CL2017002514A patent/CL2017002514A1/es unknown
- 2017-10-05 MX MX2022001085A patent/MX2022001085A/es unknown
- 2017-10-31 CO CONC2017/0011238A patent/CO2017011238A2/es unknown
-
2018
- 2018-08-14 HK HK18110393.2A patent/HK1250930A1/zh unknown
-
2019
- 2019-01-30 HK HK19101609.0A patent/HK1259251A1/zh unknown
-
2020
- 2020-06-11 US US16/898,908 patent/US11246926B2/en active Active
- 2020-09-28 JP JP2020161908A patent/JP7153696B2/ja active Active
-
2022
- 2022-03-07 JP JP2022034295A patent/JP2022078221A/ja active Pending
- 2022-05-30 AU AU2022203679A patent/AU2022203679A1/en active Pending
- 2022-08-10 US US17/818,885 patent/US20230218753A1/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014066744A2 (en) * | 2012-10-25 | 2014-05-01 | True North Therapeutics, Inc. | Anti-complement c1s antibodies and uses thereof |
Non-Patent Citations (2)
Title |
---|
ANTIBODY ENGINEERING, vol. vol.1, p.319-339, JPN6021006112, 2010, ISSN: 0004782463 * |
BLOOD, vol. 123, no. 26, JPN6020014467, 2014, pages 4015 - 4022, ISSN: 0004782464 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7210629B2 (ja) | 抗補体C1s抗体とそれらの用途 | |
JP7005483B2 (ja) | ヒト化抗C1s抗体及びその使用方法 | |
JP7326393B2 (ja) | 抗補体Bb因子抗体及びその使用 | |
CN110300520B (zh) | 抗C1s抗体及其使用方法 | |
KR102673420B1 (ko) | 항-보체 인자 bb 항체 및 이의 용도 | |
KR20240096672A (ko) | 항-보체 인자 bb 항체 및 이의 용도 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200928 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210907 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20211124 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220307 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220527 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220829 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20220909 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20221003 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7153696 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |